12 - 7 Schizophrenia Spectrum and Other Psychotic Disor

01 - 7.1 Schizophrenia
7.1 Schizophrenia
Schizophrenia Spectrum and Other
Psychotic Disorders
7.1 Schizophrenia
Although schizophrenia is discussed as if it is a single disease, it probably comprises a
group of disorders with heterogeneous etiologies, and it includes patients whose clinical
presentations, treatment response, and courses of illness vary. Signs and symptoms are
variable and include changes in perception, emotion, cognition, thinking, and behavior.
The expression of these manifestations varies across patients and over time, but the
effect of the illness is always severe and is usually long lasting. The disorder usually
begins before age 25 years, persists throughout life, and affects persons of all social
classes. Both patients and their families often suffer from poor care and social ostracism
because of widespread ignorance about the disorder. Schizophrenia is one of the most
common of the serious mental disorders, but its essential nature remains to be clarified;
thus, it is sometimes referred to as a syndrome, as the group of schizophrenias, or as in
the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), the
schizophrenia spectrum. Clinicians should appreciate that the diagnosis of schizophrenia
is based entirely on the psychiatric history and mental status examination. There is no
laboratory test for schizophrenia.
HISTORY
Written descriptions of symptoms commonly observed today in patients with
schizophrenia are found throughout history. Early Greek physicians described delusions
of grandeur, paranoia, and deterioration in cognitive functions and personality. It was
not until the 19th century, however, that schizophrenia emerged as a medical condition
worthy of study and treatment. Two major figures in psychiatry and neurology who
studied the disorder were Emil Kraepelin (1856–1926) and Eugene Bleuler (1857–1939).
Earlier, Benedict Morel (1809–1873), a French psychiatrist, had used the term démence
précoce to describe deteriorated patients whose illnesses began in adolescence.
Emil Kraepelin
Kraepelin (Fig. 7.1-1) translated Morel’s démence précoce into dementia precox, a term
that emphasized the change in cognition (dementia) and early onset (precox) of the
disorder. Patients with dementia precox were described as having a long-term
deteriorating course and the clinical symptoms of hallucinations and delusions.
Kraepelin distinguished these patients from those who underwent distinct episodes of
illness alternating with periods of normal functioning, which he classified as having
manic-depressive
psychosis.
Another
separate
condition
called
paranoia
was
characterized by persistent persecutory delusions. These patients lacked the
deteriorating course of dementia precox and the intermittent symptoms of manicdepressive psychosis.
FIGURE 7.1-1
Emil Kraepelin, 1856–1926. (Courtesy of National Library of Medicine, Bethesda, MD.)
Eugene Bleuler
Bleuler (Fig. 7.1-2) coined the term schizophrenia, which replaced dementia precox in the
literature. He chose the term to express the presence of schisms among thought,
emotion, and behavior in patients with the disorder. Bleuler stressed that, unlike
Kraepelin’s concept of dementia precox, schizophrenia need not have a deteriorating
course. This term is often misconstrued, especially by lay people, to mean split
personality. Split personality, called dissociative identity disorder, differs completely
from schizophrenia (see Chapter 12).
FIGURE 7.1-2
Eugene Bleuler, 1857–1939. (Courtesy of National Library of Medicine, Bethesda, MD.)
The Four As.
Bleuler identified specific fundamental (or primary) symptoms of
schizophrenia to develop his theory about the internal mental schisms of patients. These
symptoms included associational disturbances of thought, especially looseness, affective
disturbances, autism, and ambivalence, summarized as the four As: associations, affect,
autism, and ambivalence. Bleuler also identified accessory (secondary) symptoms, which
included the symptoms that Kraepelin saw as major indicators of dementia precox:
hallucinations and delusions.
Other Theorists
Ernst Kretschmer (1888–1926).
Kretschmer compiled data to support the idea
that schizophrenia occurred more often among persons with asthenic (i.e., slender,
lightly muscled physiques), athletic, or dysplastic body types rather than among persons
with pyknic (i.e., short, stocky physiques) body types. He thought the latter were more
likely to incur bipolar disorders. His observations may seem strange, but they are not
inconsistent with a superficial impression of the body types in many persons with
schizophrenia.
Kurt Schneider (1887–1967).
Schneider contributed a description of first-rank
symptoms, which, he stressed, were not specific for schizophrenia and were not to be
rigidly applied but were useful for making diagnoses. He emphasized that in patients
who showed no first-rank symptoms, the disorder could be diagnosed exclusively on the
basis of second-rank symptoms and an otherwise typical clinical appearance. Clinicians
frequently ignore his warnings and sometimes see the absence of first-rank symptoms
during a single interview as evidence that a person does not have schizophrenia.
Karl Jaspers (1883–1969).
Jaspers, a psychiatrist and philosopher, played a
major role in developing existential psychoanalysis. He was interested in the
phenomenology of mental illness and the subjective feelings of patients with mental
illness. His work paved the way toward trying to understand the psychological meaning
of schizophrenic signs and symptoms such as delusions and hallucinations.
Adolf Meyer (1866–1950).
Meyer, the founder of psychobiology, saw
schizophrenia as a reaction to life stresses. It was a maladaptation that was
understandable in terms of the patient’s life experiences. Meyer’s view was represented
in the nomenclature of the 1950s, which referred to the schizophrenic reaction. In later
editions of DSM, the term reaction was dropped.
EPIDEMIOLOGY
In the United States, the lifetime prevalence of schizophrenia is about 1 percent, which
means that about one person in 100 will develop schizophrenia during their lifetime.
The Epidemiologic Catchment Area study sponsored by the National Institute of Mental
Health reported a lifetime prevalence of 0.6 to 1.9 percent. In the United States, about
0.05 percent of the total population is treated for schizophrenia in any single year, and
only about half of all patients with schizophrenia obtain treatment, despite the severity
of the disorder.
Gender and Age
Schizophrenia is equally prevalent in men and women. The two genders differ, however,
in the onset and course of illness. Onset is earlier in men than in women. More than half
of all male schizophrenia patients, but only one-third of all female schizophrenia
patients, are first admitted to a psychiatric hospital before age 25 years. The peak ages
of onset are 10 to 25 years for men and 25 to 35 years for women. Unlike men, women
display a bimodal age distribution, with a second peak occurring in middle age.
Approximately 3 to 10 percent of women with schizophrenia present with disease onset
after age 40 years. About 90 percent of patients in treatment for schizophrenia are
between 15 and 55 years old. Onset of schizophrenia before age 10 years or after age 60
years is extremely rare. Some studies have indicated that men are more likely to be
impaired by negative symptoms (described later) than are women and that women are
more likely to have better social functioning than are men before disease onset. In
general, the outcome for female schizophrenia patients is better than that for male
schizophrenia patients. When onset occurs after age 45 years, the disorder is
characterized as late-onset schizophrenia.
Reproductive Factors
The use of psychopharmacological drugs, the open-door policies in hospitals, the
deinstitutionalization in state hospitals, and the emphasis on rehabilitation and
community-based care for patients have all led to an increase in the marriage and
fertility rates among persons with schizophrenia. Because of these factors, the number of
children born to parents with schizophrenia is continually increasing. The fertility rate
for persons with schizophrenia is close to that for the general population. First-degree
biological relatives of persons with schizophrenia have a ten times greater risk for
developing the disease than the general population.
Medical Illness
Persons with schizophrenia have a higher mortality rate from accidents and natural
causes than the general population. Institution- or treatment-related variables do not
explain the increased mortality rate, but the higher rate may be related to the fact that
the diagnosis and treatment of medical and surgical conditions in schizophrenia patients
can be clinical challenges. Several studies have shown that up to 80 percent of all
schizophrenia patients have significant concurrent medical illnesses and that up to 50
percent of these conditions may be undiagnosed.
Infection and Birth Season
Persons who develop schizophrenia are more likely to have been born in the winter and
early spring and less likely to have been born in late spring and summer. In the
Northern Hemisphere, including the United States, persons with schizophrenia are more
often born in the months from January to April. In the Southern Hemisphere, persons
with schizophrenia are more often born in the months from July to September. Seasonspecific risk factors, such as a virus or a seasonal change in diet, may be operative.
Another hypothesis is that persons with a genetic predisposition for schizophrenia have
a decreased biological advantage to survive season-specific insults.
Studies have pointed to gestational and birth complications, exposure to influenza
epidemics, maternal starvation during pregnancy, Rhesus factor incompatibility, and an
excess of winter births in the etiology of schizophrenia. The nature of these factors
suggests a neurodevelopmental pathological process in schizophrenia, but the exact
pathophysiological mechanism associated with these risk factors is not known.
Epidemiological data show a high incidence of schizophrenia after prenatal exposure
to influenza during several epidemics of the disease. Some studies show that the
frequency of schizophrenia is increased after exposure to influenza—which occurs in the
winter—during the second trimester of pregnancy. Other data supporting a viral
hypothesis are an increased number of physical anomalies at birth, an increased rate of
pregnancy and birth complications, seasonality of birth consistent with viral infection,
geographical clusters of adult cases, and seasonality of hospitalizations.
Viral theories stem from the fact that several specific viral theories have the power to
explain the particular localization of pathology necessary to account for a range of
manifestations in schizophrenia without overt febrile encephalitis.
Substance Abuse
Substance abuse is common in schizophrenia. The lifetime prevalence of any drug abuse
(other than tobacco) is often greater than 50 percent. For all drugs of abuse (other than
tobacco), abuse is associated with poorer function. In one population-based study, the
lifetime prevalence of alcohol within schizophrenia was 40 percent. Alcohol abuse
increases risk of hospitalization and, in some patients, may increase psychotic
symptoms. People with schizophrenia have an increased prevalence of abuse of common
street drugs. There has been particular interest in the association between cannabis and
schizophrenia. Those reporting high levels of cannabis use (more than 50 occasions)
were at sixfold increased risk of schizophrenia compared with nonusers. The use of
amphetamines, cocaine, and similar drugs should raise particular concern because of
their marked ability to increase psychotic symptoms.
Nicotine.
Up to 90 percent of schizophrenia patients may be dependent on nicotine.
Apart from smoking-associated mortality, nicotine decreases the blood concentrations of
some antipsychotics. There are suggestions that the increased prevalence in smoking is
due, at least in part, to brain abnormalities in nicotinic receptors. A specific
polymorphism in a nicotinic receptor has been linked to a genetic risk for schizophrenia.
Nicotine administration appears to improve some cognitive impairments and
parkinsonism in schizophrenia, possibly because of nicotine-dependent activation of
dopamine neurons. Recent studies have also demonstrated that nicotine may decrease
positive symptoms such as hallucinations in schizophrenia patients by its effect on
nicotine receptors in the brain that reduce the perception of outside stimuli, especially
noise. In that sense, smoking is a form of self-medication.
Population Density
The prevalence of schizophrenia has been correlated with local population density in
cities with populations of more than 1 million people. The correlation is weaker in cities
of 100,000 to 500,000 people and is absent in cities with fewer than 10,000 people. The
effect of population density is consistent with the observation that the incidence of
schizophrenia in children of either one or two parents with schizophrenia is twice as
high in cities as in rural communities. These observations suggest that social stressors in
urban settings may affect the development of schizophrenia in persons at risk.
Socioeconomic and Cultural Factors
Economics.
Because schizophrenia begins early in life; causes significant and longlasting impairments; makes heavy demands for hospital care; and requires ongoing
clinical care, rehabilitation, and support services, the financial cost of the illness in the
United States is estimated to exceed that of all cancers combined. Patients with a
diagnosis of schizophrenia are reported to account for 15 to 45 percent of homeless
Americans.
Hospitalization.
The development of effective antipsychotic drugs and changes in
political and popular attitudes toward the treatment and the rights of persons who are
mentally ill have dramatically changed the patterns of hospitalization for schizophrenia
patients since the mid-1950s. Even with antipsychotic medication, however, the
probability of readmission within 2 years after discharge from the first hospitalization is
about 40 to 60 percent. Patients with schizophrenia occupy about 50 percent of all
mental hospital beds and account for about 16 percent of all psychiatric patients who
receive any treatment.
ETIOLOGY
Genetic Factors
There is a genetic contribution to some, perhaps all, forms of schizophrenia, and a high
proportion of the variance in liability to schizophrenia is due to additive genetic effects.
For example, schizophrenia and schizophrenia-related disorders (e.g., schizotypal
personality disorder) occur at an increased rate among the biological relatives of
patients with schizophrenia. The likelihood of a person having schizophrenia is
correlated with the closeness of the relationship to an affected relative (e.g., first- or
second-degree relative). In the case of monozygotic twins who have identical genetic
endowment, there is an approximately 50 percent concordance rate for schizophrenia.
This rate is four to five times the concordance rate in dizygotic twins or the rate of
occurrence found in other first-degree relatives (i.e., siblings, parents, or offspring). The
role of genetic factors is further reflected in the drop-off in the occurrence of
schizophrenia among second- and third-degree relatives, in whom one would
hypothesize a decreased genetic loading. The finding of a higher rate of schizophrenia
among the biological relatives of an adopted-away person who develops schizophrenia,
compared with the adoptive, nonbiological relatives who rear the patient, provides
further support to the genetic contribution in the etiology of schizophrenia.
Nevertheless, the monozygotic twin data clearly demonstrate the fact that individuals
who are genetically vulnerable to schizophrenia do not inevitably develop
schizophrenia; other factors (e.g., environment) must be involved in determining a
schizophrenia outcome. If a vulnerability-liability model of schizophrenia is correct in its
postulation of an environmental influence, then other biological or psychosocial
environment factors may prevent or cause schizophrenia in the genetically vulnerable
individual.
Some data indicate that the age of the father has a correlation with the development
of schizophrenia. In studies of schizophrenia patients with no history of illness in either
the maternal or paternal line, it was found that those born from fathers older than the
age of 60 years were vulnerable to developing the disorder. Presumably,
spermatogenesis in older men is subject to greater epigenetic damage than in younger
men.
The modes of genetic transmission in schizophrenia are unknown, but several genes appear to make a contribution to
schizophrenia vulnerability. Linkage and association genetic studies have provided strong evidence for nine linkage sites:
1q, 5q, 6p, 6q, 8p, 10p, 13q, 15q, and 22q. Further analyses of these chromosomal sites have led to the identification of
specific candidate genes, and the best current candidates are α-7 nicotinic receptor, DISC 1, GRM 3, COMT, NRG 1, RGS 4,
and G 72. Recently, mutations of the genes dystrobrevin (DTNBP1) and neureglin 1 have been found to be associated with
negative features of schizophrenia.
Biochemical Factors
Dopamine Hypothesis.
The simplest formulation of the dopamine hypothesis of
schizophrenia posits that schizophrenia results from too much dopaminergic activity.
The theory evolved from two observations. First, the efficacy and the potency of many
antipsychotic drugs (i.e., the dopamine receptor antagonists [DRAs]) are correlated with
their ability to act as antagonists of the dopamine type 2 (D2) receptor. Second, drugs
that increase dopaminergic activity, notably cocaine and amphetamine, are
psychotomimetic. The basic theory does not elaborate on whether the dopaminergic
hyperactivity is due to too much release of dopamine, too many dopamine receptors,
hypersensitivity of the dopamine receptors to dopamine, or a combination of these
mechanisms. Which dopamine tracts in the brain are involved is also not specified in the
theory, although the mesocortical and mesolimbic tracts are most often implicated. The
dopaminergic neurons in these tracts project from their cell bodies in the midbrain to
dopaminoceptive neurons in the limbic system and the cerebral cortex.
Excessive dopamine release in patients with schizophrenia has been linked to the
severity of positive psychotic symptoms. Position emission tomography studies of
dopamine receptors document an increase in D2 receptors in the caudate nucleus of
drug-free patients with schizophrenia. There have also been reports of increased
dopamine concentration in the amygdala, decreased density of the dopamine
transporter, and increased numbers of dopamine type 4 receptors in the entorhinal
cortex.
Serotonin.
Current hypotheses posit serotonin excess as a cause of both positive and
negative symptoms in schizophrenia. The robust serotonin antagonist activity of
clozapine and other second-generation antipsychotics coupled with the effectiveness of
clozapine to decrease positive symptoms in chronic patients has contributed to the
validity of this proposition.
Norepinephrine.
Anhedonia—the impaired capacity for emotional gratification
and the decreased ability to experience pleasure—has long been noted to be a
prominent feature of schizophrenia. A selective neuronal degeneration within the
norepinephrine reward neural system could account for this aspect of schizophrenic
symptomatology. However, biochemical and pharmacological data bearing on this
proposal are inconclusive.
GABA.
The inhibitory amino acid neurotransmitter γ-aminobutyric acid (GABA) has
been implicated in the pathophysiology of schizophrenia based on the finding that some
patients with schizophrenia have a loss of GABAergic neurons in the hippocampus.
GABA has a regulatory effect on dopamine activity, and the loss of inhibitory GABAergic
neurons could lead to the hyperactivity of dopaminergic neurons.
Neuropeptides.
Neuropeptides, such as substance P and neurotensin, are localized
with the catecholamine and indolamine neurotransmitters and influence the action of
these neurotransmitters. Alteration in neuropeptide mechanisms could facilitate, inhibit,
or otherwise alter the pattern of firing these neuronal systems.
Glutamate.
Glutamate has been implicated because ingestion of phencyclidine, a
glutamate antagonist, produces an acute syndrome similar to schizophrenia. The
hypotheses proposed about glutamate include those of hyperactivity, hypoactivity, and
glutamate-induced neurotoxicity.
Acetylcholine and Nicotine.
Postmortem studies in schizophrenia have
demonstrated decreased muscarinic and nicotinic receptors in the caudate-putamen,
hippocampus, and selected regions of the prefrontal cortex. These receptors play a role
in the regulation of neurotransmitter systems involved in cognition, which is impaired
in schizophrenia.
Neuropathology
In the 19th century, neuropathologists failed to find a neuropathological basis for
schizophrenia, and thus they classified schizophrenia as a functional disorder. By the end
of the 20th century, however, researchers had made significant strides in revealing a
potential neuropathological basis for schizophrenia, primarily in the limbic system and
the basal ganglia, including neuropathological or neurochemical abnormalities in the
cerebral cortex, the thalamus, and the brainstem. The loss of brain volume widely
reported in schizophrenic brains appears to result from reduced density of the axons,
dendrites, and synapses that mediate associative functions of the brain. Synaptic density
is highest at age 1 year and then is pared down to adult values in early adolescence.
One theory, based in part on the observation that patients often develop schizophrenic
symptoms during adolescence, holds that schizophrenia results from excessive pruning of
synapses during this phase of development.
Cerebral Ventricles.
Computed tomography (CT) scans of patients with
schizophrenia have consistently shown lateral and third ventricular enlargement and
some reduction in cortical volume. Reduced volumes of cortical gray matter have been
demonstrated during the earliest stages of the disease. Several investigators have
attempted to determine whether the abnormalities detected by CT are progressive or
static. Some studies have concluded that the lesions observed on CT scan are present at
the onset of the illness and do not progress. Other studies, however, have concluded that
the pathological process visualized on CT scan continues to progress during the illness.
Thus, whether an active pathological process is continuing to evolve in schizophrenia
patients is still uncertain.
Reduced Symmetry.
There is a reduced symmetry in several brain areas in
schizophrenia, including the temporal, frontal, and occipital lobes. This reduced
symmetry is believed by some investigators to originate during fetal life and to be
indicative of a disruption in brain lateralization during neurodevelopment.
Limbic System.
Because of its role in controlling emotions, the limbic system has
been hypothesized to be involved in the pathophysiology of schizophrenia. Studies of
postmortem brain samples from schizophrenia patients have shown a decrease in the
size of the region, including the amygdala, the hippocampus, and the parahippocampal
gyrus. This neuropathological finding agrees with the observation made by magnetic
resonance imaging studies of patients with schizophrenia. The hippocampus is not only
smaller in size in schizophrenia but is also functionally abnormal as indicated by
disturbances in glutamate transmission. Disorganization of the neurons within the
hippocampus has also been seen in brain tissue sections of schizophrenia patients
compared with healthy control participants without schizophrenia.
Prefrontal Cortex.
There is considerable evidence from postmortem brain studies
that supports anatomical abnormalities in the prefrontal cortex in schizophrenia.
Functional deficits in the prefrontal brain imaging region have also been demonstrated.
It has long been noted that several symptoms of schizophrenia mimic those found in
persons with prefrontal lobotomies or frontal lobe syndromes.
Thalamus.
Some studies of the thalamus show evidence of volume shrinkage or
neuronal loss, in particular subnuclei. The medial dorsal nucleus of the thalamus, which
has reciprocal connections with the prefrontal cortex, has been reported to contain a
reduced number of neurons. The total number of neurons, oligodendrocytes, and
astrocytes is reduced by 30 to 45 percent in schizophrenia patients. This putative finding
does not appear to be due to the effects of antipsychotic drugs because the volume of the
thalamus is similar in size between patients with schizophrenia treated chronically with
medication and neuroleptic-naive subjects.
Basal Ganglia and Cerebellum.
The basal ganglia and cerebellum have been of
theoretical interest in schizophrenia for at least two reasons. First, many patients with
schizophrenia show odd movements, even in the absence of medication-induced
movement disorders (e.g., tardive dyskinesia). The odd movements can include an
awkward gait, facial grimacing, and stereotypies. Because the basal ganglia and
cerebellum are involved in the control of movement, disease in these areas is implicated
in the pathophysiology of schizophrenia. Second, the movement disorders involving the
basal ganglia (e.g., Huntington’s disease, Parkinson’s disease) are the ones most
commonly associated with psychosis. Neuropathological studies of the basal ganglia
have produced variable and inconclusive reports about cell loss or the reduction of
volume of the globus pallidus and the substantia nigra. Studies have also shown an
increase in the number of D2 receptors in the caudate, the putamen, and the nucleus
accumbens. The question remains, however, whether the increase is secondary to the
patient having received antipsychotic medications. Some investigators have begun to
study the serotonergic system in the basal ganglia; a role for serotonin in psychotic
disorder is suggested by the clinical usefulness of antipsychotic drugs that are serotonin
antagonists (e.g., clozapine, risperidone).
Neural Circuits
There has been a gradual evolution from conceptualizing schizophrenia as a disorder
that involves discrete areas of the brain to a perspective that views schizophrenia as a
disorder of brain neural circuits. For example, as mentioned previously, the basal
ganglia and cerebellum are reciprocally connected to the frontal lobes, and the
abnormalities in frontal lobe function seen in some brain imaging studies may be due to
disease in either area rather than in the frontal lobes themselves. It is also hypothesized
that an early developmental lesion of the dopaminergic tracts to the prefrontal cortex
results in the disturbance of prefrontal and limbic system function and leads to the
positive and negative symptoms and cognitive impairments observed in patients with
schizophrenia.
Of particular interest in the context of neural circuit hypotheses linking the prefrontal
cortex and limbic system are studies demonstrating a relationship between hippocampal
morphological abnormalities and disturbances in prefrontal cortex metabolism or
function (or both). Data from functional and structural imaging studies in humans
suggest that whereas dysfunction of the anterior cingulate basal ganglia thalamocortical
circuit underlies the production of positive psychotic symptoms, dysfunction of the
dorsolateral prefrontal circuit underlies the production of primary, enduring, negative
or deficit symptoms. There is a neural basis for cognitive functions that is impaired in
patients with schizophrenia. The observation of the relationship among impaired
working memory performance, disrupted prefrontal neuronal integrity, altered
prefrontal, cingulate, and inferior parietal cortex, and altered hippocampal blood flow
provides strong support for disruption of the normal working memory neural circuit in
patients with schizophrenia. The involvement of this circuit, at least for auditory
hallucinations, has been documented in a number of functional imaging studies that
contrast hallucinating and nonhallucinating patients.
Brain Metabolism
Studies using magnetic resonance spectroscopy, a technique that measures the
concentration of specific molecules in the brain, found that patients with schizophrenia
had lower levels of phosphomonoester and inorganic phosphate and higher levels of
phosphodiester than a control group. Furthermore, concentrations of N-acetyl aspartate,
a marker of neurons, were lower in the hippocampus and frontal lobes of patients with
schizophrenia.
Applied Electrophysiology
Electroencephalographic studies indicate that many schizophrenia patients have
abnormal records, increased sensitivity to activation procedures (e.g., frequent spike
activity after sleep deprivation), decreased alpha activity, increased theta and delta
activity, possibly more epileptiform activity than usual, and possibly more left-sided
abnormalities than usual. Schizophrenia patients also exhibit an inability to filter out
irrelevant sounds and are extremely sensitive to background noise. The flooding of
sound that results makes concentration difficult and may be a factor in the production of
auditory hallucinations. This sound sensitivity may be associated with a genetic defect.
Complex Partial Epilepsy.
Schizophrenia-like psychoses have been reported to
occur more frequently than expected in patients with complex partial seizures,
especially seizures involving the temporal lobes. Factors associated with the
development of psychosis in these patients include a left-sided seizure focus, medial
temporal location of the lesion, and an early onset of seizures. The first-rank symptoms
described by Schneider may be similar to symptoms of patients with complex partial
epilepsy and may reflect the presence of a temporal lobe disorder when seen in patients
with schizophrenia.
Evoked Potentials.
A large number of abnormalities in evoked potential among
patients with schizophrenia has been described. The P300 has been most studied and is
defined as a large, positive evoked-potential wave that occurs about 300 milliseconds
after a sensory stimulus is detected. The major source of the P300 wave may be located
in the limbic system structures of the medial temporal lobes. In patients with
schizophrenia, the P300 has been reported to be statistically smaller than in comparison
groups. Abnormalities in the P300 wave have also been reported to be more common in
children who, because they have affected parents, are at high risk for schizophrenia.
Whether the characteristics of the P300 represent a state or a trait phenomenon remains
controversial. Other evoked potentials reported to be abnormal in patients with
schizophrenia are the N100 and the contingent negative variation. The N100 is a
negative wave that occurs about 100 milliseconds after a stimulus, and the contingent
negative variation is a slowly developing, negative-voltage shift following the
presentation of a sensory stimulus that is a warning for an upcoming stimulus. The
evoked-potential data have been interpreted as indicating that although patients with
schizophrenia are unusually sensitive to a sensory stimulus (larger early evoked
potentials), they compensate for the increased sensitivity by blunting the processing of
information at higher cortical levels (indicated by smaller late evoked potentials).
Eye Movement Dysfunction
The inability to follow a moving visual target accurately is the defining basis for the
disorders of smooth visual pursuit and disinhibition of saccadic eye movements seen in
patients with schizophrenia. Eye movement dysfunction may be a trait marker for
schizophrenia; it is independent of drug treatment and clinical state and is also seen in
first-degree relatives of probands with schizophrenia. Various studies have reported
abnormal eye movements in 50 to 85 percent of patients with schizophrenia compared
with about 25 percent in psychiatric patients without schizophrenia and fewer than 10
percent in nonpsychiatrically ill control participant.
Psychoneuroimmunology
Several immunological abnormalities have been associated with patients who have
schizophrenia. The abnormalities include decreased T-cell interleukin-2 production,
reduced number and responsiveness of peripheral lymphocytes, abnormal cellular and
humoral reactivity to neurons, and the presence of brain-directed (antibrain) antibodies.
The data can be interpreted variously as representing the effects of a neurotoxic virus or
of an endogenous autoimmune disorder. Most carefully conducted investigations that
have searched for evidence of neurotoxic viral infections in schizophrenia have had
negative results, although epidemiological data show a high incidence of schizophrenia
after prenatal exposure to influenza during several epidemics of the disease. Other data
supporting a viral hypothesis are an increased number of physical anomalies at birth,
an increased rate of pregnancy and birth complications, seasonality of birth consistent
with viral infection, geographical clusters of adult cases, and seasonality of
hospitalizations. Nonetheless, the inability to detect genetic evidence of viral infection
reduces the significance of all circumstantial data. The possibility of autoimmune brain
antibodies has some data to support it; the pathophysiological process, if it exists,
however, probably explains only a subset of the population with schizophrenia.
Psychoneuroendocrinology
Many reports describe neuroendocrine differences between groups of patients with
schizophrenia and groups of control subjects. For example, results of the
dexamethasone-suppression test have been reported to be abnormal in various
subgroups of patients with schizophrenia, although the practical or predictive value of
the test in schizophrenia has been questioned. One carefully done report, however, has
correlated persistent nonsuppression on the dexamethasone-suppression test in
schizophrenia with a poor long-term outcome.
Some data suggest decreased concentrations of luteinizing hormone or folliclestimulating hormone, perhaps correlated with age of onset and length of illness. Two
additional reported abnormalities may be correlated with the presence of negative
symptoms: a blunted release of prolactin and growth hormone on gonadotropinreleasing hormone or thyrotropin-releasing hormone stimulation and a blunted release
of growth hormone on apomorphine stimulation.
PSYCHOSOCIAL AND PSYCHOANALYTIC THEORIES
If schizophrenia is a disease of the brain, it is likely to parallel diseases of other organs
(e.g., myocardial infarctions, diabetes) whose courses are affected by psychosocial
stress. Thus, clinicians should consider both psychosocial and biological factors affecting
schizophrenia.
The disorder affects individual patients, each of whom has a unique psychological
makeup. Although many psychodynamic theories about the pathogenesis of
schizophrenia seem outdated, perceptive clinical observations can help contemporary
clinicians understand how the disease may affect a patient’s psyche.
Psychoanalytic Theories.
Sigmund Freud postulated that schizophrenia resulted
from developmental fixations early in life. These fixations produce defects in ego
development, and he postulated that such defects contributed to the symptoms of
schizophrenia. Ego disintegration in schizophrenia represents a return to the time when
the ego was not yet developed or had just begun to be established. Because the ego
affects the interpretation of reality and the control of inner drives, such as sex and
aggression, these ego functions are impaired. Thus, intrapsychic conflict arising from the
early fixations and the ego defect, which may have resulted from poor early object
relations, fuel the psychotic symptoms.
As described by Margaret Mahler, there are distortions in the reciprocal relationship between the infant and the mother.
The child is unable to separate from, and progress beyond, the closeness and complete dependence that characterize the
mother–child relationship in the oral phase of development. As a result, the person’s identity never becomes secure.
Paul Federn hypothesized that the defect in ego functions permits intense hostility and aggression to distort the mother–
infant relationship, which leads to eventual personality disorganization and vulnerability to stress. The onset of symptoms
during adolescence occurs when teenagers need a strong ego to function independently, to separate from the parents, to
identify tasks, to control increased internal drives, and to cope with intense external stimulation.
Harry Stack Sullivan viewed schizophrenia as a disturbance in interpersonal relatedness. The patient’s massive anxiety
creates a sense of unrelatedness that is transformed into parataxic distortions, which are usually, but not always,
persecutory. To Sullivan, schizophrenia is an adaptive method used to avoid panic, terror, and disintegration of the sense
of self. The source of pathological anxiety results from cumulative experiential traumas during development.
Psychoanalytic theory also postulates that the various symptoms of schizophrenia have symbolic meaning for
individual patients. For example, fantasies of the world coming to an end may indicate a perception that a person’s internal
world has broken down. Feelings of inferiority are replaced by delusions of grandeur and omnipotence. Hallucinations may
be substitutes for a patient’s inability to deal with objective reality and may represent inner wishes or fears. Delusions,
similar to hallucinations, are regressive, restitutive attempts to create a new reality or to express hidden fears or impulses
(Fig. 7.1-3).
Regardless of the theoretical model, all psychodynamic approaches are founded on the
premise that psychotic symptoms have meaning in schizophrenia. Patients, for example,
may become grandiose after an injury to their self-esteem. Similarly, all theories
recognize that human relatedness may be terrifying for persons with schizophrenia.
Although research on the efficacy of psychotherapy with schizophrenia shows mixed
results, concerned persons who offer compassion and a sanctuary in the confusing world
of schizophrenia must be a cornerstone of any overall treatment plan. Long-term followup studies show that some patients who bury psychotic episodes probably do not benefit
from exploratory psychotherapy, but those who are able to integrate the psychotic
experience into their lives may benefit from some insight-oriented approaches. There is
renewed interest in the use of long-term individual psychotherapy in the treatment of
schizophrenia, especially when combined with medication.
FIGURE 7.1-3
This patient wore suits too large for him in the delusional belief that he would appear
taller to others. (Courtesy of Emil Kraepelin, M.D.)
Learning Theories.
According to learning theorists, children who later have
schizophrenia learn irrational reactions and ways of thinking by imitating parents who
have their own significant emotional problems. In learning theory, the poor
interpersonal relationships of persons with schizophrenia develop because of poor
models for learning during childhood.
Family Dynamics
In a study of British 4-year-old children, those who had a poor mother–child relationship
had a sixfold increase in the risk of developing schizophrenia, and offspring from
schizophrenic mothers who were adopted away at birth were more likely to develop the
illness if they were reared in adverse circumstances compared with those raised in
loving homes by stable adoptive parents. Nevertheless, no well-controlled evidence
indicates that a specific family pattern plays a causative role in the development of
schizophrenia. Some patients with schizophrenia do come from dysfunctional families,
just as do many nonpsychiatrically ill persons. It is important, however, not to overlook
pathological family behavior that can significantly increase the emotional stress with
which a vulnerable patient with schizophrenia must cope.
Double Bind.
The double-bind concept was formulated by Gregory Bateson and
Donald Jackson to describe a hypothetical family in which children receive conflicting
parental messages about their behavior, attitudes, and feelings. In Bateson’s hypothesis,
children withdraw into a psychotic state to escape the unsolvable confusion of the
double bind. Unfortunately, the family studies that were conducted to validate the
theory were seriously flawed methodologically. The theory has value only as a
descriptive pattern, not as a causal explanation of schizophrenia. An example of a
double bind is a parent who tells a child to provide cookies for his or her friends and
then chastises the child for giving away too many cookies to playmates.
Schisms and Skewed Families.
Theodore Lidz described two abnormal patterns
of family behavior. In one family type, with a prominent schism between the parents,
one parent is overly close to a child of the opposite gender. In the other family type, a
skewed relationship between a child and one parent involves a power struggle between
the parents and the resulting dominance of one parent. These dynamics stress the
tenuous adaptive capacity of the person with schizophrenia.
Pseudomutual and Pseudohostile Families.
As described by Lyman Wynne,
some families suppress emotional expression by consistently using pseudomutual or
pseudohostile verbal communication. In such families, a unique verbal communication
develops, and when a child leaves home and must relate to other persons, problems may
arise. The child’s verbal communication may be incomprehensible to outsiders.
Expressed Emotion.
Parents or other caregivers may behave with overt criticism,
hostility, and overinvolvement toward a person with schizophrenia. Many studies have
indicated that in families with high levels of expressed emotion, the relapse rate for
schizophrenia is high. The assessment of expressed emotion involves analyzing both
what is said and the manner in which it is said.
DIAGNOSIS
The DSM-5 diagnostic criteria include course specifiers (i.e., prognosis) that offer
clinicians several options and describe actual clinical situations (Table 7.1-1). The
presence of hallucinations or delusions is not necessary for a diagnosis of schizophrenia;
the patient’s disorder is diagnosed as schizophrenia when the patient exhibits two of the
symptoms listed in symptoms 1 through 5 of Criterion A in Table 7.1-1 (e.g.,
disorganized speech). Criterion B requires that impaired functioning, although not
deteriorations, be present during the active phase of the illness. Symptoms must persist
for at least 6 months, and a diagnosis of schizoaffective disorder or mood disorder must
be absent.
Table 7.1-1
DSM-5 Diagnostic Criteria for Schizophrenia
Subtypes
Five subtypes of schizophrenia have been described based predominantly on clinical
presentation: paranoid, disorganized, catatonic, undifferentiated, and residual. DSM-5
no longer uses these subtypes but they are listed in the 10th revision of the International
Statistical Classification of Diseases and Related Health Problems (ICD-10). They are
included in this text because the authors believe them to be of clinical significance and
they are still used by most clinicians in the United States and around the world to
describe the phenomenology of schizophrenia.
Paranoid Type.
The paranoid type of schizophrenia is characterized by
preoccupation with one or more delusions or frequent auditory hallucinations.
Classically, the paranoid type of schizophrenia is characterized mainly by the presence
of delusions of persecution or grandeur (Fig. 7.1-4). Patients with paranoid
schizophrenia usually have their first episode of illness at an older age than do patients
with catatonic or disorganized schizophrenia. Patients in whom schizophrenia occurs in
the late 20s or 30s have usually established a social life that may help them through
their illness, and the ego resources of paranoid patients tend to be greater than those of
patients with catatonic and disorganized schizophrenia. Patients with the paranoid type
of schizophrenia show less regression of their mental faculties, emotional responses, and
behavior than do patients with other types of schizophrenia.
FIGURE 7.1-4
This patient had an artificial eye that he believed had special powers when removed
from the socket. (Courtesy of Emil Kraepelin, M.D.)
Patients with paranoid schizophrenia are typically tense, suspicious, guarded,
reserved, and sometimes hostile or aggressive, but they can occasionally conduct
themselves adequately in social situations. Their intelligence in areas not invaded by
their psychosis tends to remain intact.
Disorganized Type.
The disorganized type of schizophrenia is characterized by a
marked regression to primitive, disinhibited, and unorganized behavior and by the
absence of symptoms that meet the criteria for the catatonic type. The onset of this
subtype is generally early, occurring before age 25 years. Disorganized patients are
usually active but in an aimless, nonconstructive manner. Their thought disorder is
pronounced, and their contact with reality is poor. Their personal appearance is
disheveled, and their social behavior and their emotional responses are inappropriate.
They often burst into laughter without any apparent reason. Incongruous grinning and
grimacing are common in these patients, whose behavior is best described as silly or
fatuous.
Patient AB, a 32-year-old woman, began to lose weight and became careless about
her work, which deteriorated in quality and quantity. She believed that other women
at her place of employment were circulating slanderous stories concerning her and
complained that a young man employed in the same plant had put his arm around her
and insulted her. Her family demanded that the charge be investigated, which showed
not only that the charge was without foundation but also that the man in question had
not spoken to her for months. One day she returned home from work, and as she
entered the house, she laughed loudly, watched her sister-in-law suspiciously, refused
to answer questions, and at the sight of her brother began to cry. She refused to go to
the bathroom, saying that a man was looking in the windows at her. She ate no food,
and the next day she declared that her sisters were “bad women,” that everyone was
talking about her, and that someone had been having sexual relations with her, and
although she could not see him, he was “always around.”
The patient was admitted to a public psychiatric hospital. As she entered the
admitting office, she laughed loudly and repeatedly screamed in a loud tone, “She
cannot stay here; she’s got to go home!” She grimaced and performed various
stereotyped movements of her hands. When seen on the ward an hour later, she paid
no attention to questions, although she talked to herself in a childish tone. She moved
about constantly, walked on her toes in a dancing manner, pointed aimlessly about,
and put out her tongue and sucked her lips in the manner of an infant. At times she
moaned and cried like a child but shed no tears. As the months passed, she remained
silly, childish, preoccupied, and inaccessible, grimacing, gesturing, pointing at objects
in a stereotyped way, and usually chattering to herself in a peculiar high-pitched
voice, with little of what she said being understood. Her condition continued to
deteriorate, she remained unkempt, and she presented a picture of extreme
introversion and regression, with no interest either in the activities of the institution
or in her relatives who visited her. (Adapted from case of Arthur P. Noyes, M.D., and
Lawrence C. Kolb, M.D.)
Catatonic Type.
The catatonic type of schizophrenia, which was common several
decades ago, has become rare in Europe and North America. The classic feature of the
catatonic type is a marked disturbance in motor function; this disturbance may involve
stupor, negativism, rigidity, excitement, or posturing. Sometimes the patient shows a
rapid alteration between extremes of excitement and stupor. Associated features include
stereotypies, mannerisms, and waxy flexibility. Mutism is particularly common. During
catatonic excitement, patients need careful supervision to prevent them from hurting
themselves or others. Medical care may be needed because of malnutrition, exhaustion,
hyperpyrexia, or self-inflicted injury.
AC, age 32 years, was admitted to the hospital. On arrival, he was noted to be an
asthenic, poorly nourished man with dilated pupils, hyperactive tendon reflexes, and
a pulse rate of 120 beats/min. He showed many mannerisms, laid down on the floor,
pulled at his foot, made undirected violent striking movements, struck attendants,
grimaced, assumed rigid and strange postures, refused to speak, and appeared to be
having auditory hallucinations. When seen later in the day, he was found to be in a
stuporous state. His face was without expression, he was mute and rigid, and he paid
no attention to those about him or to their questions. His eyes were closed, and his
eyelids could be separated only with effort. There was no response to pinpricks or
other painful stimuli.
He gradually became accessible, and when asked concerning himself, he referred to
his stuporous period as sleep and maintained that he had no recollection of any
events occurring during it. He said, “I didn’t know anything. Everything seemed to be
dark as far as my mind is concerned. Then I began to see a little light, like the shape
of a star. Then my head got through the star gradually. I saw more and more light
until I saw everything in a perfect form a few days ago.” He explained his mutism by
saying that he had been afraid he would “say the wrong thing” and that he “didn’t
know exactly what to talk about.” From his obviously inadequate emotional response
and his statement that he was “a scientist and an inventor of the most extraordinary
genius of the 20th century,” it was plain that he was still far from well. (Adapted from
case of Arthur P. Noyes, M.D., and Lawrence C. Kolb, M.D.)
Undifferentiated Type.
Frequently, patients who clearly have schizophrenia
cannot be easily fit into one type or another. These patients are classified as having
schizophrenia of the undifferentiated type.
Residual Type.
The residual type of schizophrenia is characterized by continuing
evidence of the schizophrenic disturbance in the absence of a complete set of active
symptoms or of sufficient symptoms to meet the diagnosis of another type of
schizophrenia. Emotional blunting, social withdrawal, eccentric behavior, illogical
thinking, and mild loosening of associations commonly appear in the residual type.
When delusions or hallucinations occur, they are neither prominent nor accompanied by
strong affect.
Other Subtypes
The subtyping of schizophrenia has had a long history; other subtyping schemes appear
in the literature, especially literature from countries other than the United States.
Bouffée Délirante (Acute Delusional Psychosis).
This French diagnostic
concept differs from a diagnosis of schizophrenia primarily on the basis of a symptom
duration of less than 3 months. The diagnosis is similar to the DSM-5 diagnosis of
schizophreniform disorder. French clinicians report that about 40 percent of patients
with a diagnosis of bouffée délirante progress in their illness and are eventually classified
as having schizophrenia.
Latent.
The concept of latent schizophrenia was developed during a time when
theorists conceived of the disorder in broad diagnostic terms. Currently, patients must be
very mentally ill to warrant a diagnosis of schizophrenia, but with a broad diagnostic
concept of schizophrenia, the condition of patients who would not currently be thought
of as severely ill could have received a diagnosis of schizophrenia. Latent schizophrenia,
for example, was often the diagnosis used for what are now called borderline, schizoid,
and schizotypal personality disorders. These patients may occasionally show peculiar
behaviors or thought disorders but do not consistently manifest psychotic symptoms. In
the past, the syndrome was also termed borderline schizophrenia.
Oneiroid.
The oneiroid state refers to a dream-like state in which patients may be
deeply perplexed and not fully oriented in time and place. The term oneiroid
schizophrenia has been used for patients who are engaged in their hallucinatory
experiences to the exclusion of involvement in the real world. When an oneiroid state is
present, clinicians should be particularly careful to examine patients for medical or
neurological causes of the symptoms.
After a 20-year-old female college student had recovered from her schizophrenic
breakdown, she wrote the following description of her experiences during the oneiroid
phase:
This is how I remember it. The road has changed. It is twisted and it used to be
straight. Nothing is constant—all is in motion. The trees are moving. They do not
remain at rest. How is it my mother does not bump into the trees that are moving? I
follow my mother. I am afraid, but I follow. I have to share my strange thoughts with
someone. We are sitting on a bench. The bench seems low. It, too, has moved. “The
bench is low,” I say. “Yes,” says my mother. “This isn’t how it used to be. How come
there are no people around? There are usually lots of people and it is Sunday and
there are no people. This is strange.” All these strange questions irritate my mother
who then says she must be going soon. While I continue thinking I’m in a kind of
nowhere....
There are no days; no nights; sometimes it is darker than other times—that’s all. It
is never quite black, just dark gray. There is no such thing as time—there is only
eternity. There is no such thing as death—nor heaven and hell—there is only a
timeless—hateful—spaceless—worsening of things. You can never go forward; you
must always regress into this horrific mess....
The outside was moving rather swiftly, everything seemed topsy-turvy—things were
flying about. It was very strange. I wanted to get back to the quiet very badly but
when I got back I couldn’t remember where anything was (e.g., the bathroom)....
(Courtesy of Heinz E. Lehmann, M.D.)
Paraphrenia.
The term paraphrenia is sometimes used as a synonym for paranoid
schizophrenia or for either a progressively deteriorating course of illness or the presence
of a well-systemized delusional system. The multiple meanings of the term render it
ineffectual in communicating information.
Pseudoneurotic Schizophrenia.
Occasionally, patients who initially have such
symptoms as anxiety, phobias, obsessions, and compulsions later reveal symptoms of
thought disorder and psychosis. These patients are characterized by symptoms of
pananxiety, panphobia, panambivalence, and sometimes chaotic sexuality. Unlike
persons with anxiety disorders, pseudoneurotic patients have free-floating anxiety that
rarely subsides. In clinical descriptions, the patients seldom become overtly and severely
psychotic. This condition is currently diagnosed as borderline personality disorder.
Simple Deteriorative Disorder (Simple Schizophrenia).
Simple
deteriorative disorder is characterized by a gradual, insidious loss of drive and ambition.
Patients with the disorder are usually not overtly psychotic and do not experience
persistent hallucinations or delusions. Their primary symptom is withdrawal from social
and work-related situations. The syndrome must be differentiated from depression, a
phobia, a dementia, or an exacerbation of personality traits. Clinicians should be sure
that patients truly meet the diagnostic criteria for schizophrenia before making the
diagnosis.
An unmarried man, 27 years old, was brought to the mental hospital because he had
on several occasions become violent toward his father. For a few weeks, he had
hallucinations and heard voices. The voices eventually ceased, but he then adopted a
strange way of life. He would sit up all night, sleep all day, and become very angry
when his father tried to get him out of bed. He did not shave or wash for weeks,
smoked continuously, ate very irregularly, and drank enormous quantities of tea.
In the hospital, he adjusted rapidly to the new environment and was found to be
generally cooperative. He showed no marked abnormalities of mental state or
behavior, except for his lack of concern for just about anything. He kept to himself as
much as possible and conversed little with patients or staff. His personal hygiene had
to be supervised by the nursing staff; otherwise, he would quickly become dirty and
untidy.
Six years after his admission to the hospital, he is described as shiftless and careless,
sullen and unreasonable. He lies on a couch all day long. Although many efforts have
been made to get the patient to accept therapeutic work assignments, he refuses to
consider any kind of regular occupation. In the summer, he wanders about the
hospital grounds or lies under a tree. In the winter, he wanders through the tunnels
connecting the various hospital buildings and is often seen stretched out for hours
under the warm pipes that carry the steam through the tunnels. (Courtesy of Heinz
E. Lehmann, M.D.)
Postpsychotic Depressive Disorder of Schizophrenia.
After an acute
schizophrenia episode, some patients become depressed. The symptoms of postpsychotic
depressive disorder of schizophrenia can closely resemble the symptoms of the residual
phase of schizophrenia and the adverse effects of commonly used antipsychotic
medications. The diagnosis should not be made if they are substance induced or part of a
mood disorder due to a general medical condition. These depressive states occur in up to
25 percent of patients with schizophrenia and are associated with an increased risk of
suicide.
Early-Onset Schizophrenia.
A small minority of patients manifest schizophrenia
in childhood. Such children may at first present diagnostic problems, particularly with
differentiation from mental retardation and autistic disorder. Recent studies have
established that the diagnosis of childhood schizophrenia may be based on the same
symptoms used for adult schizophrenia. Its onset is usually insidious, its course tends to
be chronic, and the prognosis is mostly unfavorable.
Late-Onset Schizophrenia.
Late-onset schizophrenia is clinically
indistinguishable from schizophrenia but has an onset after age 45 years. This condition
tends to appear more frequently in women and tends to be characterized by a
predominance of paranoid symptoms. The prognosis is favorable, and these patients
usually do well on antipsychotic medication.
Deficit Schizophrenia.
In the 1980s, criteria were promulgated for a subtype of
schizophrenia characterized by enduring, idiopathic negative symptoms. These patients
were said to exhibit the deficit syndrome. This group of patients is now said to have
deficit schizophrenia (see the criteria for that putative disease diagnosis in Table 7.1-2).
Patients with schizophrenia with positive symptoms are said to have nondeficit
schizophrenia. The symptoms used to define deficit schizophrenia are strongly
interrelated, although various combinations of the six negative symptoms in the criteria
can be found.
Table 7.1-2
Diagnostic Criteria for Deficit Schizophrenia
Deficit patients have a more severe course of illness than nondeficit patients, with a higher prevalence of abnormal
involuntary movements before administration of antipsychotic drugs and poorer social function before the onset of
psychotic symptoms. The onset of the first psychotic episode is more often insidious, and these patients show less longterm recovery of function than do nondeficit patients. Deficit patients are also less likely to marry than are other patients
with schizophrenia. However, despite their poorer level of function and greater social isolation, both of which should
increase a patient’s stress and, therefore, the risk of serious depression, deficit patients appear to have a decreased risk of
major depression and probably have a decreased risk of suicide as well.
The risk factors of deficit patients differ from those of nondeficit patients; whereas
deficit schizophrenia is associated with an excess of summer births, nondeficit patients
have an excess of winter births. Deficit schizophrenia may also be associated with a
greater familial risk of schizophrenia and of mild, deficit-like features in the
nonpsychotic relatives of deficit probands. Within a family with multiple affected
siblings, the deficit–nondeficit categorization tends to be uniform. The deficit group also
has a higher prevalence of men. The psychopathology of deficit patients impacts
treatment; their lack of motivation, lack of distress, greater cognitive impairment, and
asocial nature undermine the efficacy of psychosocial interventions, as well as their
adherence to medication regimens. Their cognitive impairment, which is greater than
that of nondeficit subjects, also contributes to this lack of efficacy.
PSYCHOLOGICAL TESTING. Patients with schizophrenia generally perform poorly on a wide
range of neuropsychological tests. Vigilance, memory, and concept formation are most
affected and consistent with pathological involvement in the frontotemporal cortex.
Objective measures of neuropsychological performance, such as the Halstead-Reitan
battery and the Luria-Nebraska battery, often give abnormal findings, such as bilateral
frontal and temporal lobe dysfunction, including impairments in attention, retention
time, and problem-solving ability. Motor ability is also impaired, possibly related to
brain asymmetry.
INTELLIGENCE TESTS. When groups of patients with schizophrenia are compared with
groups of psychiatric patients without schizophrenia or with the general population, the
schizophrenia patients tend to score lower on intelligence tests. Statistically, the
evidence suggests that low intelligence is often present at the onset, and intelligence
may continue to deteriorate with the progression of the disorder.
PROJECTIVE AND PERSONALITY TESTS. Projective tests, such as the Rorschach test and the
Thematic Apperception Test, may indicate bizarre ideation. Personality inventories,
such as the Minnesota Multiphasic Personality Inventory, often give abnormal results in
schizophrenia, but the contribution to diagnosis and treatment planning is minimal.
CLINICAL FEATURES
A discussion of the clinical signs and symptoms of schizophrenia raises three key issues.
First, no clinical sign or symptom is pathognomonic for schizophrenia; every sign or
symptom seen in schizophrenia occurs in other psychiatric and neurological disorders.
This observation is contrary to the often-heard clinical opinion that certain signs and
symptoms are diagnostic of schizophrenia. Therefore, a patient’s history is essential for
the diagnosis of schizophrenia; clinicians cannot diagnose schizophrenia simply by
results of a mental status examination, which may vary. Second, a patient’s symptoms
change with time. For example, a patient may have intermittent hallucinations and a
varying ability to perform adequately in social situations, or significant symptoms of a
mood disorder may come and go during the course of schizophrenia. Third, clinicians
must take into account the patient’s educational level, intellectual ability, and cultural
and subcultural membership. An impaired ability to understand abstract concepts, for
example, may reflect either the patient’s education or his or her intelligence. Religious
organizations and cults may have customs that seem strange to outsiders but are normal
to those within the cultural setting.
Premorbid Signs and Symptoms
In theoretical formulations of the course of schizophrenia, premorbid signs and
symptoms appear before the prodromal phase of the illness. The differentiation implies
that premorbid signs and symptoms exist before the disease process evidences itself and
that the prodromal signs and symptoms are parts of the evolving disorder. In the
typical, but not invariable, premorbid history of schizophrenia, patients had schizoid or
schizotypal personalities characterized as quiet, passive, and introverted; as children,
they had few friends. Preschizophrenic adolescents may have no close friends and no
dates and may avoid team sports. They may enjoy watching movies and television,
listening to music, or playing computer games to the exclusion of social activities. Some
adolescent patients may show a sudden onset of obsessive-compulsive behavior as part
of the prodromal picture.
The validity of the prodromal signs and symptoms, almost invariably recognized after
the diagnosis of schizophrenia has been made, is uncertain; after schizophrenia is
diagnosed, the retrospective remembrance of early signs and symptoms is affected.
Nevertheless, although the first hospitalization is often believed to mark the beginning
of the disorder, signs and symptoms have often been present for months or even years.
The signs may have started with complaints about somatic symptoms, such as headache,
back and muscle pain, weakness, and digestive problems. The initial diagnosis may be
malingering, chronic fatigue syndrome, or somatization disorder. Family and friends
may eventually notice that the person has changed and is no longer functioning well in
occupational, social, and personal activities. During this stage, a patient may begin to
develop an interest in abstract ideas, philosophy, and the occult or religious questions
(Fig. 7.1-5). Additional prodromal signs and symptoms can include markedly peculiar
behavior, abnormal affect, unusual speech, bizarre ideas, and strange perceptual
experiences.
FIGURE 7.1-5
Schizophrenia patient schema. This illustrates his fragmented, abstract, and overly
inclusive thinking and preoccupation with religious ideologies and mathematical proofs.
(Courtesy of Heinz E. Lehmann.)
Mental Status Examination
General Description.
The appearance of a patient with schizophrenia can range
from that of a completely disheveled, screaming, agitated person to an obsessively
groomed, completely silent, and immobile person. Between these two poles, patients
may be talkative and may exhibit bizarre postures. Their behavior may become agitated
or violent, apparently in an unprovoked manner, but usually in response to
hallucinations. In contrast, in catatonic stupor, often referred to as catatonia, patients
seem completely lifeless and may exhibit such signs as muteness, negativism, and
automatic obedience. Waxy flexibility, once a common sign in catatonia, has become
rare, as has manneristic behavior. A person with a less extreme subtype of catatonia
may show marked social withdrawal and egocentricity, a lack of spontaneous speech or
movement, and an absence of goal-directed behavior. Patients with catatonia may sit
immobile and speechless in their chairs, respond to questions with only short answers,
and move only when directed to move. Other obvious behavior may include odd
clumsiness or stiffness in body movements, signs now seen as possibly indicating a
disease process in the basal ganglia. Patients with schizophrenia are often poorly
groomed, fail to bathe, and dress much too warmly for the prevailing temperatures.
Other odd behaviors include tics; stereotypies; mannerisms; and, occasionally,
echopraxia, in which patients imitate the posture or the behavior of the examiner.
PRECOX FEELING. Some experienced clinicians report a precox feeling, an intuitive
experience of their inability to establish an emotional rapport with a patient. Although
the experience is common, no data indicate that it is a valid or reliable criterion in the
diagnosis of schizophrenia.
Mood, Feelings, and Affect
Two
common
affective
symptoms
in
schizophrenia
are
reduced
emotional
responsiveness, sometimes severe enough to warrant the label of anhedonia, and overly
active and inappropriate emotions such as extremes of rage, happiness, and anxiety. A
flat or blunted affect can be a symptom of the illness itself, of the parkinsonian adverse
effects of antipsychotic medications, or of depression, and differentiating these
symptoms can be a clinical challenge. Overly emotional patients may describe exultant
feelings of omnipotence, religious ecstasy, terror at the disintegration of their souls, or
paralyzing anxiety about the destruction of the universe. Other feeling tones include
perplexity, a sense of isolation, overwhelming ambivalence, and depression.
Perceptual Disturbances
HALLUCINATIONS. Any of the five senses may be affected by hallucinatory experiences in
patients with schizophrenia. The most common hallucinations, however, are auditory,
with voices that are often threatening, obscene, accusatory, or insulting. Two or more
voices may converse among themselves, or a voice may comment on the patient’s life or
behavior. Visual hallucinations are common (Fig. 7.1-6), but tactile, olfactory, and
gustatory hallucinations are unusual; their presence should prompt the clinician to
consider the possibility of an underlying medical or neurological disorder that is causing
the entire syndrome.
FIGURE 7.1-6
A symbolic representation of the strange perceptions of the schizophrenia patient.
(Courtesy of Arthur Tress.)
A 48-year-old man, who had been diagnosed with schizophrenia while in the army
at age 21 years, led an isolated and often frightened existence, living alone and
supported by disability payments. Although he would confirm that he had chronic
auditory hallucinations, he was never comfortable with discussing the content of these
hallucinations, and a review of records showed this was a long-term pattern for the
patient. Otherwise the patient had good rapport with his psychiatrist and was
enthusiastic about the possibility of participating in a study of a novel antipsychotic
agent. During the informed consent procedure, the patient asked about the possibility
that the new medication might decrease his chronic auditory hallucinations. When it
was acknowledged that any response was possible, including decreases in his
hallucinations, the patient broke off the discussion abruptly and left the office. At a
later visit, he reported that his most reliable pleasure in life was nightly discussions of
gossip with hallucinations of voices he believed belonged to 17th- century French
courtiers, and the chance that he might lose these conversations and the
companionship they offered was too frightening for him to consider. (Adapted from
Stephen Lewis, M.D., P. Rodrigo Escalona, M.D., and Samuel J. Keith, M.D.)
Cenesthetic Hallucinations.
Cenesthetic hallucinations are unfounded sensations of
altered states in bodily organs. Examples of cenesthetic hallucinations include a burning
sensation in the brain, a pushing sensation in the blood vessels, and a cutting sensation
in the bone marrow. Bodily distortions may also occur.
ILLUSIONS. As differentiated from hallucinations, whereas illusions are distortions of real
images or sensations, hallucinations are not based on real images or sensations.
Illusions can occur in schizophrenia patients during active phases, but they can also
occur during the prodromal phases and during periods of remission. Whenever illusions
or hallucinations occur, clinicians should consider the possibility of a substance-related
cause for the symptoms, even when patients have already received a diagnosis of
schizophrenia.
Thought.
Disorders of thought are the most difficult symptoms for many clinicians
and students to understand, but they may be the core symptoms of schizophrenia.
Dividing the disorders of thought into disorders of thought content, form of thought, and
thought process is one way to clarify them.
THOUGHT CONTENT. Disorders of thought content reflect the patient’s ideas, beliefs, and
interpretations of stimuli. Delusions, the most obvious example of a disorder of thought
content, are varied in schizophrenia and may assume persecutory, grandiose, religious,
or somatic forms.
Patients may believe that an outside entity controls their thoughts or behavior or,
conversely, that they control outside events in an extraordinary fashion (such as causing
the sun to rise and set or by preventing earthquakes). Patients may have an intense and
consuming preoccupation with esoteric, abstract, symbolic, psychological, or
philosophical ideas. Patients may also worry about allegedly life-threatening but bizarre
and implausible somatic conditions, such as the presence of aliens inside the patient’s
testicles affecting his ability to father children.
The phrase loss of ego boundaries describes the lack of a clear sense of where the
patient’s own body, mind, and influence end and where those of other animate and
inanimate objects begin. For example, patients may think that other persons, the
television, or the newspapers are referring to them (ideas of reference). Other symptoms
of the loss of ego boundaries include the sense that the patient has physically fused with
an outside object (e.g., a tree or another person) or that the patient has disintegrated
and fused with the entire universe (cosmic identity). With such a state of mind, some
patients with schizophrenia doubt their gender or their sexual orientation. These
symptoms should not be confused with transvestism, transsexuality, or other gender
identity problems.
FORM OF THOUGHT. Disorders of the form of thought are objectively observable in
patients’ spoken and written language (Fig. 7.1-7). The disorders include looseness of
associations, derailment, incoherence, tangentiality, circumstantiality, neologisms,
echolalia, verbigeration, word salad, and mutism. Although looseness of associations
was once described as pathognomonic for schizophrenia, the symptom is frequently seen
in mania. Distinguishing between looseness of associations and tangentiality can be
difficult for even the most experienced clinicians.
FIGURE 7.1-7
Sample of noncommunicative writing by a patient with chronic paranoid schizophrenia.
This letter, written to the patient’s psychiatrist, illustrates manneristic writing,
verbigeration, and neologisms.
The following sample is taken from a memo typed by a secretary with schizophrenia
who was still able to work part time in an office. Note her preoccupation with the mind,
the Trinity, and other esoteric matters. Also note that peculiar restructuring of concepts
by hyphenating the words germ-any (the patient had a distinct fear of germs) and infer-
no (inferring that there will be no salvation). The “chain reaction” is a reference to
atomic piles.
Mental health is the Blessed Trinity, and as man cannot be without God, it is futile to deny His Son. For the Creation
understand germ-any in Voice New Order, not lie of chained reaction, spawning mark in temple Cain with Babel grave’n
image to wanton V day “Israel.”
Lucifer fell Jew prostitute and lambeth walks by roam to sex ritual, in Bible six million of the Babylon woman, infer-no
Salvation.
The one common factor in the thought process above is a preoccupation with invisible
forces, radiation, witchcraft, religion, philosophy, and psychology and a leaning toward
the esoteric, the abstract, and the symbolic. Consequently, the thinking of a person with
schizophrenia is characterized simultaneously by both an overly concrete and an overly
symbolic nature.
THOUGHT PROCESS. Disorders in thought process concern the way ideas and languages
are formulated. The examiner infers a disorder from what and how the patient speaks,
writes, or draws. The examiner may also assess the patient’s thought process by
observing his or her behavior, especially in carrying out discrete tasks (e.g., in
occupational therapy). Disorders of thought process include flight of ideas, thought
blocking, impaired attention, poverty of thought content, poor abstraction abilities,
perseveration, idiosyncratic associations (e.g., identical predicates, clang associations),
overinclusion, and circumstantiality. Thought control, in which outside forces are
controlling what the patient thinks or feels, is common, as is thought broadcasting, in
which patients think others can read their minds or that their thoughts are broadcast
through television sets or radios.
Impulsiveness, Violence, Suicide, and Homicide.
Patients with
schizophrenia may be agitated and have little impulse control when ill. They may also
have decreased social sensitivity and appear to be impulsive when, for example, they
grab another patient’s cigarettes, change television channels abruptly, or throw food on
the floor. Some apparently impulsive behavior, including suicide and homicide attempts,
may be in response to hallucinations commanding the patient to act.
VIOLENCE. Violent behavior (excluding homicide) is common among untreated
schizophrenia patients. Delusions of a persecutory nature, previous episodes of violence,
and neurological deficits are risk factors for violent or impulsive behavior. Management
includes appropriate antipsychotic medication. Emergency treatment consists of
restraints and seclusion. Acute sedation with lorazepam (Ativan), 1 to 2 mg
intramuscularly, repeated every hour as needed, may be necessary to prevent the
patient from harming others. If a clinician feels fearful in the presence of a
schizophrenia patient, it should be taken as an internal clue that the patient may be on
the verge of acting out violently. In such cases, the interview should be terminated or be
conducted with an attendant at the ready.
SUICIDE. Suicide is the single leading cause of premature death among people with
schizophrenia. Suicide attempts are made by 20 to 50 percent of the patients, with longterm rates of suicide estimated to be 10 to 13 percent. According to DSM-5
approximately 5 to 6 percent of schizophrenic patients die by suicide, but this is
probably an underestimation. Often, suicide in schizophrenia seems to occur “out of the
blue,” without prior warnings or expressions of verbal intent. The most important factor
is the presence of a major depressive episode. Epidemiological studies indicate that up
to 80 percent of schizophrenia patients may have a major depressive episode at some
time in their lives. Some data suggest that those patients with the best prognosis (few
negative symptoms, preservation of capacity to experience affects, better abstract
thinking) can paradoxically also be at highest risk for suicide. The profile of the patient
at greatest risk is a young man who once had high expectations, declined from a higher
level of functioning, realizes that his dreams are not likely to come true, and has lost
faith in the effectiveness of treatment. Other possible contributors to the high rate of
suicide include command hallucinations and drug abuse. Two-thirds or more of
schizophrenic patients who commit suicide have seen an apparently unsuspecting
clinician within 72 hours of death. A large pharmacological study suggests that
clozapine (Clozaril) may have particular efficacy in reducing suicidal ideation in
schizophrenia patients with prior hospitalizations for suicidality. Adjunctive
antidepressant medications have been shown to be effective in alleviating co-occurring
major depression in schizophrenia.
The following is an example of an unpredictable suicide in a patient with
schizophrenia who had been responding to psychiatric treatment:
The patient had been an autistic child and did not speak until he was 7 years old.
He had responded well to psychiatric treatment, and at age 13 his IQ was reported as
122. At age 17 he became violent toward his parents, shaved all his hair off, and
made such statements as, “I like bank robbers knocking people unconscious” and “I
think tough gangs are funny because they beat down people.” While saying this, he
laughed loudly. He was admitted to a mental hospital, where he responded with
definite improvement to pharmacotherapy and psychotherapy, and he went home
regularly for weekends.
He left various notes on his desk before committing suicide. Among these notes was
an eight-page list giving 211 “inexcusable mistakes throughout my life.” Each one was
dated, for example, “1952, 2nd of November: throwing up in my friend’s house on a
shoe-box. 1953, 17th August: accidentally wearing a watch that wasn’t water-proof in
the bath-tub. 1956, 23rd of September: slamming back-door of Meteor after getting
in.”
He then proceeded in his notes to give “the causes of the mistakes:” “Montreal
having a mountain; I have a receding hair-line; my height since I was nine years old;
Canada having two languages....” He also wrote: “My feelings of tension since 1962 is
getting worse most of the time. I planned the date of my death without the slightest
trace of emotion....”
The boy hanged himself at age 18 in the family garage. An experienced psychiatrist
who had repeatedly interviewed him noted no signs of depression only a week before.
(Courtesy of Heinz E. Lehmann, M.D.)
HOMICIDE. Despite the sensational attention that the news media provides when a
patient with schizophrenia murders someone, the available data indicate that these
patients are no more likely to commit homicide than is a member of the general
population. When a patient with schizophrenia does commit homicide, it may be for
unpredictable or bizarre reasons based on hallucinations or delusions. Possible
predictors of homicidal activity are a history of previous violence, dangerous behavior
while hospitalized, and hallucinations or delusions involving such violence.
Sensorium and Cognition
Orientation.
Patients with schizophrenia are usually oriented to person, time, and
place. The lack of such orientation should prompt clinicians to investigate the possibility
of a medical or neurological brain disorder. Some patients with schizophrenia may give
incorrect or bizarre answers to questions about orientation, for example, “I am Christ;
this is heaven; and it is AD 35.”
Memory.
Memory, as tested in the mental status examination, is usually intact, but
there can be minor cognitive deficiencies. It may not be possible, however, to get the
patient to attend closely enough to the memory tests for the ability to be assessed
adequately.
Cognitive Impairment.
An important development in the understanding of the
psychopathology of schizophrenia is an appreciation of the importance of cognitive
impairment in the disorder. In outpatients, cognitive impairment is a better predictor of
level of function than is the severity of psychotic symptoms. Patients with schizophrenia
typically exhibit subtle cognitive dysfunction in the domains of attention, executive
function, working memory, and episodic memory. Although a substantial percentage of
patients have normal intelligence quotients, it is possible that every person who has
schizophrenia has cognitive dysfunction compared with what he or she would be able to
do without the disorder. Although these impairments cannot function as diagnostic tools,
they are strongly related to the functional outcome of the illness and, for that reason,
have clinical value as prognostic variables, as well as for treatment planning.
The cognitive impairment seems already to be present when patients have their first
episode and appears largely to remain stable over the course of early illness. (There
may be a small subgroup of patients who have a true dementia in late life that is not
due to other cognitive disorders, such as Alzheimer’s disease.) Cognitive impairments are
also present in attenuated forms in nonpsychotic relatives of schizophrenia patients.
The
cognitive
impairments
of
schizophrenia
have
become
the
target
of
pharmacological and psychosocial treatment trials. It is likely that effective treatments
will become widely available within a few years, and these are likely to lead to an
improvement in the quality of life and level of functioning of people with schizophrenia.
Judgment and Insight.
Classically, patients with schizophrenia are described as
having poor insight into the nature and the severity of their disorder. The so-called lack
of insight is associated with poor compliance with treatment. When examining
schizophrenia patients, clinicians should carefully define various aspects of insight, such
as awareness of symptoms, trouble getting along with people, and the reasons for these
problems. Such information can be clinically useful in tailoring a treatment strategy and
theoretically useful in postulating what areas of the brain contribute to the observed
lack of insight (e.g., the parietal lobes).
Reliability.
A patient with schizophrenia is no less reliable than any other
psychiatric patient. The nature of the disorder, however, requires the examiner to verify
important information through additional sources.
Somatic Comorbidity
Neurological Findings.
Localizing and nonlocalizing neurological signs (also
known as hard and soft signs, respectively) have been reported to be more common in
patients with schizophrenia than in other psychiatric patients. Nonlocalizing signs
include dysdiadochokinesia, astereognosis, primitive reflexes, and diminished dexterity.
The presence of neurological signs and symptoms correlates with increased severity of
illness, affective blunting, and a poor prognosis. Other abnormal neurological signs
include tics, stereotypies, grimacing, impaired fine motor skills, abnormal motor tone,
and abnormal movements. One study has found that only about 25 percent of patients
with schizophrenia are aware of their own abnormal involuntary movements and that
the lack of awareness is correlated with a lack of insight about the primary psychiatric
disorder and the duration of illness.
Eye Examination.
In addition to the disorder of smooth ocular pursuit (saccadic
movement), patients with schizophrenia have an elevated blink rate. The elevated blink
rate is believed to reflect hyperdopaminergic activity. In primates, blinking can be
increased by dopamine agonists and reduced by dopamine antagonists.
Speech.
Although the disorders of speech in schizophrenia (e.g., looseness of
associations) are classically considered to indicate a thought disorder, they may also
indicate a forme fruste of aphasia, perhaps implicating the dominant parietal lobe. The
inability of schizophrenia patients to perceive the prosody of speech or to inflect their
own speech can be seen as a neurological symptom of a disorder in the nondominant
parietal lobe. Other parietal lobe–like symptoms in schizophrenia include the inability
to carry out tasks (i.e., apraxia), right–left disorientation, and lack of concern about the
disorder.
Other Comorbidity
Obesity.
Patients with schizophrenia appear to be more obese, with higher body
mass indexes (BMIs) than age- and gender-matched cohorts in the general population.
This is due, at least in part, to the effect of many antipsychotic medications, as well as
poor nutritional balance and decreased motor activity. This weight gain, in turn,
contributes to an increased risk of cardiovascular morbidity and mortality, an increased
risk of diabetes, and other obesity-related conditions such as hyperlipidemia and
obstructive sleep apnea.
Diabetes Mellitus.
Schizophrenia is associated with an increased risk of type II
diabetes mellitus. This is probably due, in part, to the association with obesity noted
previously, but there is also evidence that some antipsychotic medications cause diabetes
through a direct mechanism.
Cardiovascular Disease.
Many antipsychotic medications have direct effects on
cardiac electrophysiology. In addition, obesity; increased rates of smoking, diabetes,
hyperlipidemia; and a sedentary lifestyle all independently increase the risk of
cardiovascular morbidity and mortality.
HIV.
Patients with schizophrenia appear to have a risk of HIV infection that is 1.5 to
2 times that of the general population. This association is thought to be due to increased
risk behaviors, such as unprotected sex, multiple partners, and increased drug use.
Chronic Obstructive Pulmonary Disease.
Rates of chronic obstructive
pulmonary disease are reportedly increased in schizophrenia compared with the general
population. The increased prevalence of smoking is an obvious contributor to this
problem and may be the only cause.
Rheumatoid Arthritis.
Patients with schizophrenia have approximately one-third
the risk of rheumatoid arthritis that is found in the general population. This inverse
association has been replicated several times, the significance of which is unknown.
DIFFERENTIAL DIAGNOSIS
Secondary Psychotic Disorders
A wide range of nonpsychiatric medical conditions and a variety of substances can
induce symptoms of psychosis and catatonia (Table 7.1-3). The most appropriate
diagnosis for such psychosis or catatonia is psychotic disorder due to a general medical
condition, catatonic disorder due to a general medical condition, or substance-induced
psychotic disorder.
Table 7.1-3
Differential Diagnosis of Schizophrenia-Like Symptoms
When evaluating a patient with psychotic symptoms, clinicians should follow the
general guidelines for assessing nonpsychiatric conditions. First, clinicians should
aggressively pursue an undiagnosed nonpsychiatric medical condition when a patient
exhibits any unusual or rare symptoms or any variation in the level of consciousness.
Second, clinicians should attempt to obtain a complete family history, including a
history of medical, neurological, and psychiatric disorders. Third, clinicians should
consider the possibility of a nonpsychiatric medical condition, even in patients with
previous diagnoses of schizophrenia. A patient with schizophrenia is just as likely to
have a brain tumor that produces psychotic symptoms as is a patient without
schizophrenia.
Other Psychotic Disorders
The psychotic symptoms of schizophrenia can be identical with those of
schizophreniform disorder, brief psychotic disorder, schizoaffective disorder, and
delusional disorders. Schizophreniform disorder differs from schizophrenia in that the
symptoms have a duration of at least 1 month but less than 6 months. Brief psychotic
disorder is the appropriate diagnosis when the symptoms have lasted at least 1 day but
less than 1 month and when the patient has not returned to the premorbid state of
functioning within that time. There may also be a precipitating traumatic event. When a
manic or depressive syndrome develops concurrently with the major symptoms of
schizophrenia, schizoaffective disorder is the appropriate diagnosis. Nonbizarre delusions
present for at least 1 month without other symptoms of schizophrenia or a mood
disorder warrant the diagnosis of delusional disorder.
Mood Disorders
A patient with a major depressive episode may present with delusions and
hallucinations, whether the patient has unipolar or bipolar mood disorder. Delusions
seen with psychotic depression are typically mood congruent and involve themes such as
guilt, self-depreciation, deserved punishment, and incurable illnesses. In mood disorders,
psychotic symptoms resolve completely with the resolution of depression. A depressive
episode that is this severe may also result in loss of functioning, decline in self-care, and
social isolation, but these are secondary to the depressive symptoms and should not be
confused with the negative symptoms of schizophrenia.
A full-blown manic episode often presents with delusions and sometimes
hallucinations. Delusions in mania are most often mood congruent and typically involve
grandiose themes. The flight of ideas seen in mania may, at times, be confused with the
thought disorder of schizophrenia. Special attention during mental status examination of
a patient with a flight of ideas is required to note whether the associative links between
topics are conserved, although the conversation is difficult for the observer to follow
because of the patient’s accelerated rate of thinking.
Personality Disorders
Various personality disorders may have some features of schizophrenia. Schizotypal,
schizoid, and borderline personality disorders are the personality disorders with the
most similar symptoms. Severe obsessive-compulsive personality disorder may mask an
underlying schizophrenic process. Personality disorders, unlike schizophrenia, have mild
symptoms and a history of occurring throughout a patient’s life; they also lack an
identifiable date of onset.
Malingering and Factitious Disorders
For a patient who imitates the symptoms of schizophrenia but does not actually have the
disorder, either malingering or factitious disorder may be an appropriate diagnosis.
Persons have faked schizophrenic symptoms and have been admitted into and treated at
psychiatric hospitals. The condition of patients who are completely in control of their
symptom production may qualify for a diagnosis of malingering; such patients usually
have some obvious financial or legal reason to want to be considered mentally ill. The
condition of patients who are less in control of their falsification of psychotic symptoms
may qualify for a diagnosis of factitious disorder. Some patients with schizophrenia,
however, may falsely complain of an exacerbation of psychotic symptoms to obtain
increased assistance benefits or to gain admission to a hospital.
COURSE AND PROGNOSIS
Course
A premorbid pattern of symptoms may be the first evidence of illness, although the
importance
of
the
symptoms
is
usually
recognized
only
retrospectively.
Characteristically, the symptoms begin in adolescence and are followed by the
development of prodromal symptoms in days to a few months. Social or environmental
changes, such as going away to college, using a substance, or a relative’s death, may
precipitate the disturbing symptoms, and the prodromal syndrome may last a year or
more before the onset of overt psychotic symptoms.
The classic course of schizophrenia is one of exacerbations and remissions. After the
first psychotic episode, a patient gradually recovers and may then function relatively
normally for a long time. Patients usually relapse, however, and the pattern of illness
during the first 5 years after the diagnosis generally indicates the patient’s course.
Further deterioration in the patient’s baseline functioning follows each relapse of the
psychosis. This failure to return to baseline functioning after each relapse is the major
distinction between schizophrenia and the mood disorders. Sometimes a clinically
observable postpsychotic depression follows a psychotic episode, and the schizophrenia
patient’s vulnerability to stress is usually lifelong. Positive symptoms tend to become
less severe with time, but the socially debilitating negative or deficit symptoms may
increase in severity. Although about one-third of all schizophrenia patients have some
marginal or integrated social existence, most have lives characterized by aimlessness;
inactivity; frequent hospitalizations; and, in urban settings, homelessness and poverty.
Prognosis
Several studies have shown that over the 5- to 10-year period after the first psychiatric
hospitalization for schizophrenia, only about 10 to 20 percent of patients can be
described as having a good outcome. More than 50 percent of patients can be described
as having a poor outcome, with repeated hospitalizations, exacerbations of symptoms,
episodes of major mood disorders, and suicide attempts. Despite these glum figures,
schizophrenia does not always run a deteriorating course, and several factors have been
associated with a good prognosis (Table 7.1-4).
Table 7.1-4
Features Weighting Toward Good to Poor Prognosis in Schizophrenia
Reported remission rates range from 10 to 60 percent, and a reasonable estimate is
that 20 to 30 percent of all schizophrenia patients are able to lead somewhat normal
lives. About 20 to 30 percent of patients continue to experience moderate symptoms,
and 40 to 60 percent of patients remain significantly impaired by their disorder for their
entire lives. Patients with schizophrenia do much poorer than patients with mood
disorders, although 20 to 25 percent of mood disorder patients are also severely
disturbed at long-term follow-up.
TREATMENT
Although antipsychotic medications are the mainstay of the treatment for schizophrenia,
research has found that psychosocial interventions, including psychotherapy, can
augment the clinical improvement. Just as pharmacological agents are used to treat
presumed chemical imbalances, nonpharmacological strategies must treat nonbiological
issues. The complexity of schizophrenia usually renders any single therapeutic approach
inadequate to deal with the multifaceted disorder. Psychosocial modalities should be
integrated into the drug treatment regimen and should support it. Patients with
schizophrenia benefit more from the combined use of antipsychotic drugs and
psychosocial treatment than from either treatment used alone.
Hospitalization
Hospitalization is indicated for diagnostic purposes; for stabilization of medications; for
patients’ safety because of suicidal or homicidal ideation; and for grossly disorganized or
inappropriate behavior, including the inability to take care of basic needs such as food,
clothing, and shelter. Establishing an effective association between patients and
community support systems is also a primary goal of hospitalization.
Short stays of 4 to 6 weeks are just as effective as long-term hospitalizations, and
hospital settings with active behavioral approaches produce better results than do
custodial institutions. Hospital treatment plans should be oriented toward practical
issues of self-care, quality of life, employment, and social relationships. During
hospitalization, patients should be coordinated with aftercare facilities, including their
family homes, foster families, board-and-care homes, and halfway houses. Day care
centers and home visits by therapists or nurses can help patients remain out of the
hospital for long periods and can improve the quality of their daily lives.
Pharmacotherapy
The introduction of chlorpromazine (Thorazine) in 1952 may be the most important
single contribution to the treatment of a psychiatric illness. Henri Laborit, a surgeon in
Paris, noticed that administering chlorpromazine to patients before surgery resulted in
an unusual state in which they seemed less anxious regarding the procedure.
Chlorpromazine was subsequently shown to be effective at reducing hallucinations and
delusions, as well as excitement. It was also noted that it caused side effects that
appeared similar to parkinsonism.
Antipsychotics diminish psychotic symptom expression and reduce relapse rates.
Approximately 70 percent of patients treated with any antipsychotic achieve remission.
The drugs used to treat schizophrenia have a wide variety of pharmacological
properties, but all share the capacity to antagonize postsynaptic dopamine receptors in
the brain. Antipsychotics can be categorized into two main groups: the older
conventional antipsychotics, which have also been called first-generation antipsychotics or
dopamine receptor antagonists, and the newer drugs, which have been called secondgeneration antipsychotics or serotonin dopamine antagonists (SDAs).
Clozapine (Clozaril), the first effective antipsychotic with negligible extrapyramidal
side effects, was discovered in 1958 and first studied during the 1960s. However, in
1976, it was noted that clozapine was associated with a substantial risk of
agranulocytosis. This property resulted in delays in the introduction of clozapine. In
1990, clozapine finally became available in the United States, but its use was restricted
to patients who responded poorly to other agents.
PHASES OF TREATMENT IN SCHIZOPHRENIA
Treatment of Acute Psychosis
Acute psychotic symptoms require immediate attention. Treatment during the acute
phase focuses on alleviating the most severe psychotic symptoms. This phase usually
lasts from 4 to 8 weeks. Acute schizophrenia is typically associated with severe
agitation, which can result from such symptoms as frightening delusions, hallucinations,
or suspiciousness, or from other causes (including stimulant abuse). Patients with
akathisia can appear agitated when they experience a subjective feeling of motor
restlessness. Differentiating akathisia from psychotic agitation can be difficult,
particularly when patients are incapable of describing their internal experience. If
patients are receiving an agent associated with extrapyramidal side effects, usually a
first-generation antipsychotic, a trial with an anticholinergic anti-Parkinson medication,
benzodiazepine, or propranolol (Inderal) may be helpful in making the discrimination.
Clinicians have a number of options for managing agitation that results from
psychosis. Antipsychotics and benzodiazepines can result in relatively rapid calming of
patients. With highly agitated patients, intramuscular administration of antipsychotics
produces a more rapid effect. An advantage of an antipsychotic is that a single
intramuscular injection of haloperidol (Haldol), fluphenazine (Prolixin, Permitil),
olanzapine (Zyprexa), or ziprasidone (Geodon) will often result in calming effect
without excessive sedation. Low-potency antipsychotics are often associated with
sedation and postural hypotension, particularly when they are administered
intramuscularly. Intramuscular ziprasidone and olanzapine are similar to their oral
counterparts in not causing substantial extrapyramidal side effects during acute
treatment. This can be an important advantage over haloperidol or fluphenazine, which
can cause frightening dystonias or akathisia in some patients. A rapidly dissolving oral
formulation of olanzapine (Zydis) may also be helpful as an alternative to an
intramuscular injection.
Benzodiazepines are also effective for agitation during acute psychosis. Lorazepam
(Ativan) has the advantage of reliable absorption when it is administered either orally
or intramuscularly. The use of benzodiazepines may also reduce the amount of
antipsychotic that is needed to control psychotic patients.
Treatment During Stabilization and Maintenance Phase
In the stable or maintenance phase, the illness is in a relative stage of remission. The
goals during this phase are to prevent psychotic relapse and to assist patients in
improving their level of functioning. As newer medications have been introduced with a
substantively reduced risk of tardive dyskinesia, one of the major concerns about longterm treatment has been diminished. During this phase, patients are usually in a relative
state of remission with only minimal psychotic symptoms. Stable patients who are
maintained on an antipsychotic have a much lower relapse rate than patients who have
their medications discontinued. Data suggest that 16 to 23 percent of patients receiving
treatment will experience a relapse within 1 year, and 53 to 72 percent will relapse
without medications. Even patients who have had only one episode have a four in five
chance of relapsing at least once over the following 5 years. Stopping medication
increases this risk fivefold. Although published guidelines do not make definitive
recommendations about the duration of maintenance treatment after the first episode,
recent data suggest that 1 or 2 years might not be adequate. This is a particular concern
when patients have achieved good employment status or are involved in educational
programs because they have a lot to lose if they experience another psychotic
decompensation.
It is generally recommended that multiepisode patients receive maintenance
treatment for at least 5 years, and many experts recommend pharmacotherapy on an
indefinite basis.
Noncompliance.
Noncompliance with long-term antipsychotic treatment is very
high. An estimated 40 to 50 percent of patients become noncompliant within 1 or 2
years. Compliance increases when long-acting medication is used instead of oral
medication.
When beginning long-acting drugs, some oral supplementation is necessary while
peak plasma levels are being achieved. Fluphenazine and haloperidol have been
formulated as long-acting injectables. Long-acting forms of risperidone, paliperidone,
aripiprazole, and olanzapine are also available.
There are a number of advantages to using long-acting injectable medication.
Clinicians know immediately when noncompliance occurs and have some time to
initiate appropriate interventions before the medication effect dissipates; there is less
day-to-day variability in blood levels, making it easier to establish a minimum effective
dose; and finally, many patients prefer it to having to remember dosage schedules of
daily oral preparations.
STRATEGIES FOR POOR RESPONDERS
When patients with acute schizophrenia are administered an antipsychotic medication,
approximately 60 percent will improve to the extent that they will achieve a complete
remission or experience only mild symptoms; the remaining 40 percent of patients will
improve but still demonstrate variable levels of positive symptoms that are resistant to
the medications. Rather than categorizing patients into responders and nonresponders,
it is more accurate to consider the degree to which the illness is improved by medication.
Some resistant patients are so severely ill that they require chronic institutionalization.
Others respond to an antipsychotic with substantial suppression of their psychotic
symptoms but demonstrate persistent symptoms, such as hallucinations or delusions.
Before considering a patient a poor responder to a particular drug, it is important to
assure that they received an adequate trial of the medication. A 4- to 6-week trial on an
adequate dose of an antipsychotic represents a reasonable trial for most patients.
Patients who demonstrate even a mild amount of improvement during this period may
continue to improve at a steady rate for 3 to 6 months. It may be helpful to confirm that
the patient is receiving an adequate amount of the drug by monitoring the plasma
concentration. This information is available for a number of antipsychotics, including
haloperidol, clozapine, fluphenazine, trifluoperazine (Stelazine), and perphenazine
(Trilafon). A very low plasma concentration may indicate that the patient has been
noncompliant or, more commonly, only partially compliant. It may also suggest that the
patient is a rapid metabolizer of the antipsychotic or that the drug is not being
adequately absorbed. Under these conditions, raising the dose may be helpful. If the
level is relatively high, clinicians should consider whether side effects may be interfering
with therapeutic response.
If the patient is responding poorly, one may increase the dose above the usual
therapeutic level; however, higher doses are not usually associated with greater
improvement than conventional doses. Changing to another drug is preferable to
titrating to a high dose.
If a patient has responded poorly to a conventional DRA, it is unlikely that this
individual will do well on another DRA. Changing to an SDA is more likely to be helpful.
Clozapine is effective for patients who respond poorly to DRAs. Double-blind studies comparing clozapine with other
antipsychotics indicated that clozapine had the clearest advantage over conventional drugs in patients with the most severe
psychotic symptoms, as well as in those who had previously responded poorly to other antipsychotics. When clozapine
was compared with chlorpromazine in a severely psychotic group of individuals who had failed in trials with at least
three antipsychotics, clozapine was significantly more effective in nearly every dimension of psychopathology, including
both positive symptoms and negative symptoms.
MANAGING SIDE EFFECTS
Patients frequently experience side effects of an antipsychotic before they experience
clinical improvement. Whereas a clinical response may be delayed for days or weeks
after drugs are started, side effects may begin almost immediately. For low-potency
drugs, these side effects are likely to include sedation, postural hypotension, and
anticholinergic effects, whereas high-potency drugs are likely to cause extrapyramidal
side effects.
Extrapyramidal Side Effects
Clinicians have a number of alternatives for treating extrapyramidal side effects. These
include reducing the dose of the antipsychotic (which is most commonly a DRA), adding
an anti-Parkinson medication, and changing the patient to an SDA that is less likely to
cause extrapyramidal side effects. The most effective anti-Parkinson medications are the
anticholinergic anti-Parkinson drugs. However, these medications have their own side
effects, including dry mouth; constipation; blurred vision; and, often, memory loss. Also,
these medications are often only partially effective, leaving patients with substantial
amounts of lingering extrapyramidal side effects. Centrally acting β-blockers, such as
propranolol, are also often effective for treating akathisia. Most patients respond to
dosages between 30 and 90 mg per day.
If conventional antipsychotics are being prescribed, clinicians may consider
prescribing prophylactic anti-Parkinson medications for patients who are likely to
experience disturbing extrapyramidal side effects. These include patients who have a
history of extrapyramidal side effect sensitivity and those who are being treated with
relatively high doses of high-potency drugs. Prophylactic anti-Parkinson medications
may also be indicated when high-potency drugs are prescribed for young men who tend
to have an increased vulnerability for developing dystonias. Again, these patients
should be candidates for newer drugs.
Some individuals are highly sensitive to extrapyramidal side effects at the dose that is
necessary to control their psychosis. For many of these patients, medication side effects
may seem worse than the illness itself. These patients should be treated routinely with
an SDA because these agents result in substantially fewer extrapyramidal side effects
than the DRAs. However, these highly sensitive individuals may even experience
extrapyramidal side effects on an SDA. Risperidone may cause extrapyramidal side
effects even at low doses—for example, 0.5 mg—but the severity and risk are increased
at higher doses—for example, more than 6 mg. Olanzapine and ziprasidone are also
associated with dose-related parkinsonism and akathisia.
Tardive Dyskinesia
About 20 to 30 percent of patients on long-term treatment with a conventional DRA will
exhibit symptoms of tardive dyskinesia. About 3 to 5 percent of young patients receiving
a DRA develop tardive dyskinesia each year. The risk in elderly patients is much higher.
Although seriously disabling dyskinesia is uncommon, it can affect walking, breathing,
eating, and talking when it occurs. Individuals who are more sensitive to acute
extrapyramidal side effects appear to be more vulnerable to developing tardive
dyskinesia. Patients with comorbid cognitive or mood disorders may also be more
vulnerable to tardive dyskinesia than those with only schizophrenia.
The onset of the abnormal movements usually occurs either while the patient is
receiving an antipsychotic or within 4 weeks of discontinuing an oral antipsychotic or 8
weeks after the withdrawal of a depot antipsychotic. There is a slightly lower risk of
tardive dyskinesia with new-generation drugs. However, the risk of tardive dyskinesia is
not absent with the SDAs.
Recommendations for preventing and managing tardive dyskinesia include (1) using
the lowest effective dose of antipsychotic; (2) prescribing cautiously with children,
elderly patients, and patients with mood disorders; (3) examining patients on a regular
basis for evidence of tardive dyskinesia; (4) considering alternatives to the antipsychotic
being used and considering dosage reduction when tardive dyskinesia is diagnosed; and
(5) considering a number of options if the tardive dyskinesia worsens, including
discontinuing the antipsychotic or switching to a different drug. Clozapine has been
shown to be effective in reducing severe tardive dyskinesia or tardive dystonia.
Other Side Effects
Sedation and postural hypotension can be important side effects for patients who are
being treated with low-potency DRAs, such as perphenazine. These effects are often
most severe during the initial dosing with these medications. As a result, patients treated
with these medications—particularly clozapine—may require weeks to reach a
therapeutic dose. Although most patients develop tolerance to sedation and postural
hypotension, sedation may continue to be a problem. In these patients, daytime
drowsiness may interfere with a patient’s attempts to return to community life.
All DRAs, as well as SDAs, elevate prolactin levels, which can result in galactorrhea
and irregular menses. Long-term elevations in prolactin and the resultant suppression in
gonadotropin-releasing hormone can cause suppression in gonadal hormones. These, in
turn, may have effects on libido and sexual functioning. There is also concern that
elevated prolactin may cause decreases in bone density and lead to osteoporosis. The
concerns about hyperprolactinemia, sexual functioning, and bone density are based on
experiences with prolactin elevations related to tumors and other causes. It is unclear if
these risks are also associated with the lower elevations that occur with prolactinelevating drugs.
Health Monitoring in Patients Receiving Antipsychotics
Because of the effects of the SDAs on insulin metabolism, psychiatrists should monitor a
number of health indicators, including BMI, fasting blood glucose, and lipid profiles.
Patients should be weighed and their BMIs calculated for every visit for 6 months after a
medication change.
Side Effects of Clozapine
Clozapine has a number of side effects that make it a difficult drug to administer. The
most serious is a risk of agranulocytosis. This potentially fatal condition occurs in
approximately 0.3 percent of patients treated with clozapine during the first year of
exposure. Subsequently, the risk is substantially lower. As a result, patients who receive
clozapine in the United States are required to be in a program of weekly blood
monitoring for the first 6 months and biweekly monitoring for the next 6 months. After
1 year of treatment without hematological problems, monitoring can be performed
monthly.
Clozapine is also associated with a higher risk of seizures than other antipsychotics.
The risk reaches nearly 5 percent at doses of more than 600 mg. Patients who develop
seizures with clozapine can usually be managed by reducing the dose and adding an
anticonvulsant, usually valproate (Depakene). Myocarditis has been reported to occur in
approximately five patients per 100,000 patient-years. Other side effects with clozapine
include hypersalivation, sedation, tachycardia, weight gain, diabetes, fever, and
postural hypotension.
OTHER BIOLOGICAL THERAPIES
Electroconvulsive therapy (ECT) has been studied in both acute and chronic
schizophrenia. Studies in recent-onset patients indicate that ECT is about as effective as
antipsychotic medications and more effective than psychotherapy. Other studies suggest
that supplementing antipsychotic medications with ECT is more effective than
antipsychotic medications alone. Antipsychotic medications should be administered
during and after ECT treatment. Although psychosurgery is no longer considered an
appropriate treatment, it is practiced on a limited experimental basis for severe,
intractable cases.
PSYCHOSOCIAL THERAPIES
Psychosocial therapies include a variety of methods to increase social abilities, selfsufficiency, practical skills, and interpersonal communication in schizophrenia patients.
The goal is to enable persons who are severely ill to develop social and vocational skills
for independent living. Such treatment is carried out at many sites, including hospitals,
outpatient clinics, mental health centers, day hospitals, and home or social clubs.
Social Skills Training
Social skills training is sometimes referred to as behavioral skills therapy. Along with
pharmacological therapy, this therapy can be directly supportive and useful to the
patient. In addition to the psychotic symptoms seen in patients with schizophrenia,
other noticeable symptoms involve the way the person relates to others, including poor
eye contact, unusual delays in response, odd facial expressions, lack of spontaneity in
social situations, and inaccurate perception or lack of perception of emotions in other
people. Behavioral skills training addresses these behaviors through the use of
videotapes of others and of the patient, role playing in therapy, and homework
assignments for the specific skills being practiced. Social skills training has been shown
to reduce relapse rates as measured by the need for hospitalization.
Family-Oriented Therapies
Because patients with schizophrenia are often discharged in an only partially remitted
state, a family to which a patient returns can often benefit from a brief but intensive (as
often as daily) course of family therapy. The therapy should focus on the immediate
situation and should include identifying and avoiding potentially troublesome
situations. When problems do emerge with the patient in the family, the aim of the
therapy should be to resolve the problem quickly.
In wanting to help, family members often encourage a relative with schizophrenia to
resume regular activities too quickly, both from ignorance about the disorder and from
denial of its severity. Without being overly discouraging, therapists must help both the
family and the patient understand and learn about schizophrenia and must encourage
discussion of the psychotic episode and the events leading up to it. Ignoring the
psychotic episode, a common occurrence, often increases the shame associated with the
event and does not exploit the freshness of the episode to understand it better. Psychotic
symptoms often frighten family members, and talking openly with the psychiatrist and
with the relative with schizophrenia often eases all parties. Therapists can direct later
family therapy toward long-range application of stress-reducing and coping strategies
and toward the patient’s gradual reintegration into everyday life.
Therapists must control the emotional intensity of family sessions with patients with
schizophrenia. The excessive expression of emotion during a session can damage a
patient’s recovery process and undermine potentially successful future family therapy.
Several studies have shown that family therapy is especially effective in reducing
relapses.
National Alliance on Mental Illness (NAMI).
The NAMI and similar
organizations offer support groups for family members and friends of patients who are
mentally ill and for patients themselves. These organizations offer emotional and
practical advice about obtaining care in the sometimes complex health care delivery
system and are useful sources to which to refer family members. NAMI has also waged a
campaign to destigmatize mental illness and to increase government awareness of the
needs and rights of persons who are mentally ill and their families.
Case Management
Because a variety of professionals with specialized skills, such as psychiatrists, social
workers, and occupational therapists, among others, are involved in a treatment
program, it is helpful to have one person aware of all the forces acting on the patient.
The case manager ensures that their efforts are coordinated and that the patient keeps
appointments and complies with treatment plans; the case manager may make home
visits and even accompany the patient to work. The success of the program depends on
the educational background, training, and competence of the individual case manager,
which vary. Case managers often have too many cases to manage effectively. The
ultimate benefits of the program have yet to be demonstrated.
Assertive Community Treatment
The Assertive Community Treatment (ACT) program was originally developed by
researchers in Madison, Wisconsin, in the 1970s, for the delivery of services for persons
with chronic mental illness. Patients are assigned to one multidisciplinary team (e.g.,
case manager, psychiatrist, nurse, general physicians). The team has a fixed caseload of
patients and delivers all services when and where needed by the patient, 24 hours a
day, 7 days a week. This is mobile and intensive intervention that provides treatment,
rehabilitation, and support activities. These include home delivery of medications,
monitoring of mental and physical health, in vivo social skills, and frequent contact
with family members. There is a high staff-to-patient ratio (1:12). ACT programs can
effectively decrease the risk of rehospitalization for persons with schizophrenia, but they
are labor-intensive and expensive programs to administer.
Group Therapy
Group therapy for persons with schizophrenia generally focuses on real-life plans,
problems, and relationships. Groups may be behaviorally oriented, psychodynamically
or insight oriented, or supportive. Some investigators doubt that dynamic interpretation
and insight therapy are valuable for typical patients with schizophrenia. But group
therapy is effective in reducing social isolation, increasing the sense of cohesiveness,
and improving reality testing for patients with schizophrenia. Groups led in a
supportive manner appear to be most helpful for schizophrenia patients.
Cognitive Behavioral Therapy
Cognitive behavioral therapy has been used in schizophrenia patients to improve
cognitive distortions, reduce distractibility, and correct errors in judgment. There are
reports of ameliorating delusions and hallucinations in some patients using this method.
Patients who might benefit generally have some insight into their illness.
Individual Psychotherapy
Studies of the effects of individual psychotherapy in the treatment of schizophrenia have
provided data that the therapy is helpful and that the effects are additive to those of
pharmacological treatment. In psychotherapy with a schizophrenia patient, developing
a therapeutic relationship that the patient experiences as safe is critical. The therapist’s
reliability, the emotional distance between the therapist and the patient, and the
genuineness of the therapist as interpreted by the patient all affect the therapeutic
experience. Psychotherapy for a schizophrenia patient should be thought of in terms of
decades, rather than sessions, months, or even years.
Some clinicians and researchers have emphasized that the ability of a patient with
schizophrenia to form a therapeutic alliance with a therapist is predictive of the
outcome. Schizophrenia patients who are able to form a good therapeutic alliance are
likely to remain in psychotherapy, to remain compliant with their medications, and to
have good outcomes at 2-year follow-up evaluations.
The relationship between clinicians and patients differs from that encountered in the
treatment of nonpsychotic patients. Establishing a relationship is often difficult. Persons
with schizophrenia are desperately lonely, yet defend against closeness and trust; they
are likely to become suspicious, anxious, or hostile or to regress when someone attempts
to draw close (Fig. 7.1-8). Therapists should scrupulously respect a patient’s distance
and privacy and should demonstrate simple directness, patience, sincerity, and
sensitivity to social conventions in preference to premature informality and the
condescending use of first names. The patient is likely to perceive exaggerated warmth
or professions of friendship as attempts at bribery, manipulation, or exploitation.
FIGURE 7.1-8
Patients with schizophrenia live in a state of chronic anxiety and fear. The environment
is seen as hostile and threatening as symbolized in this illustration. (Courtesy of Arthur
Tress.)
In the context of a professional relationship, however, flexibility is essential in
establishing a working alliance with the patient. A therapist may have meals with the
patient, sit on the floor, go for a walk, eat at a restaurant, accept and give gifts, play
table tennis, remember the patient’s birthday, or just sit silently with the patient. The
major aim is to convey the idea that the therapist is trustworthy, wants to understand
the patient and tries to do so, and has faith in the patient’s potential as a human, no
matter how disturbed, hostile, or bizarre the patient may be at the moment.
Personal Therapy
A flexible type of psychotherapy called personal therapy is a recently developed form of
individual treatment for schizophrenia patients. Its objective is to enhance personal and
social adjustment and to forestall relapse. It is a select method using social skills and
relaxation exercises, psychoeducation, self-reflection, self-awareness, and exploration of
individual vulnerability to stress. The therapist provides a setting that stresses
acceptance and empathy. Patients receiving personal therapy show improvement in
social adjustment (a composite measure that includes work performance, leisure, and
interpersonal relationships) and have a lower relapse rate after 3 years than patients
not receiving personal therapy.
Dialectical Behavior Therapy
This form of therapy, which combines cognitive and behavioral theories in both
individual and group settings, has proved useful in borderline states and may have
benefit in schizophrenia. Emphasis is placed on improving interpersonal skills in the
presence of an active and empathic therapist.
Vocational Therapy
A variety of methods and settings are used to help patients regain old skills or develop
new ones. These include sheltered workshops, job clubs, and part-time or transitional
employment programs. Enabling patients to become gainfully employed is both a means
toward, and a sign of, recovery. Many schizophrenia patients are capable of performing
high-quality work despite their illness. Others may exhibit exceptional skill or even
brilliance in a limited field as a result of some idiosyncratic aspect of their disorder.
Art Therapy
Many schizophrenia patients benefit from art therapy, which provides them with an
outlet for their constant bombardment of imagery. It helps them communicate with
others and share their inner, often frightening world with others.
Cognitive Training
Cognitive training or cognitive remediation is a technique introduced recently for the
treatment of schizophrenia. Utilizing computer generated exercises, neural networks are
influenced in such a way that cognition, including working memory, is improved which
translates into more effective social functioning. The field is in its infancy and further
work and replication of studies is needed; however, it is a technique that is easily
learned and administered and holds great promise.
REFERENCES
Beck AT, Rector NA, Stolar N, Grant P. Schizophrenia: Cognitive Theory, Research, and Therapy. New York: Guilford Press;
2009.
Deserno L, Sterzer P, Wüstenberg T, Heinz A, Schlagenhauf F. Reduced prefrontal-parietal effective connectivity and
working memory deficits in schizophrenia. J Neurosci. 2012;32:12.
Diederen KMJ, Neggers SFW, Daalman K, Blom JD, Goekoop R, Kahn RS, Sommer IEC. Deactivation of the
parahippocampal gyrus preceding auditory hallucinations in schizophrenia. Am J Psychiatry. 2010;167:427.
Fisher M, Holland C, Merzenich MM, Vinogradov S. Using neuroplasticity-based auditory training to improve verbal
memory in schizophrenia. Am J Psychiatry. 2009;166:805.
Glick ID, Stekoll AH, Hays S. The role of the family and improvement in treatment maintenance, adherence, and outcome
for schizophrenia. J Clin Psychopharmacology. 2011;31:82.
Hare E, Glahn DC, Dassori A, Raventos H, Nicolini H, Ontiveros A, Medina R, Mendoza R, Jerez A, Muñoz R, Almasy L,
Escamilla MA. Heritability of age of onset of psychosis in schizophrenia. Am J Med Genet Part B. 2010; 153B:298.
Howes OD, Montgomery AJ, Asselin MC, Murray RM, Valli I, Tabraham P, Bramon-Bosch E, Valmaggia L, Johns L, Broome
M, McGuire PK, Grasby PM. Elevated striatal dopamine function linked to prodromal signs of schizophrenia. Arch Gen
Psychiatry. 2009;66:13.
Johnson I, Tabbane K, Dellagi L, Kebir O. Self-perceived cognitive functioning does not correlate with objective measures
of cognition in schizophrenia. Compr Psychiatry. 2011;52(6):688.
Keshavan MS, Vinogradov S, Rumsey J, Sherril J, Wagner A. Cognitive Training in Mental Disorders. Am J Psychiatry. 2014;
171:510–522.
Kring AM, Germans-Gard M, Gard DE. Emotion deficits in schizophrenia: Timing matters. J Abnorm Psychol. 2011;120:79.
Meyer JM, Nasrallah HA, eds. Medical Illness and Schizophrenia. Arlington, VA: American Psychiatric Publishing; 2009.
Remington G, Foussias G, Agid O. Progress in defining optimal treatment outcome in schizophrenia. CNS Drugs. 2010;24:9.
Rosenheck RA, Krystal JH, Lew R, Barnett PG, Fiore L, Valley D, Thwin SS, Vertrees JE, Liang MH. Long-acting risperidone
and oral antipsychotics in unstable schizophrenia. N Engl J Med. 2011;364:842.
Tamminga CA. Schizophrenia and other psychotic disorders: Introduction and overview. In: Sadock BJ, Sadock VA, Ruiz
P, eds. Kaplan & Sadock’s Comprehensive Textbook of Psychiatry. 9th edition. Philadelphia: Lippincott Williams &
Wilkins; 2009:1432.
Van Os J. The dynamic of subthreshold psychopathology: Implications for diagnosis and treatment. Am J Psych.
2013;170:695.
Viron M, Baggett T, Hill M, Freudenreich O. Schizophrenia for primary care providers: How to contribute to the care of a
vulnerable patient population. Am J Med. 2012;125:223.

02 - 7.2 Schizoaffective Disorder
7.2 Schizoaffective Disorder
7.2 Schizoaffective Disorder
Schizoaffective disorder has features of both schizophrenia and mood disorders. In
current diagnostic systems, patients can receive the diagnosis of schizoaffective disorder
if they fit into one of the following six categories: (1) patients with schizophrenia who
have mood symptoms, (2) patients with mood disorder who have symptoms of
schizophrenia, (3) patients with both mood disorder and schizophrenia, (4) patients
with a third psychosis unrelated to schizophrenia and mood disorder, (5) patients whose
disorder is on a continuum between schizophrenia and mood disorder, and (6) patients
with some combination of the above.
George H. Kirby, in 1913, and August Hoch, in 1921, both described patients with mixed features of schizophrenia and
affective (mood) disorders. Because their patients did not have the deteriorating course of dementia precox, Kirby and
Hoch classified them in Emil Kraepelin’s manic-depressive psychosis group.
In 1933, Jacob Kasanin introduced the term schizoaffective disorder to refer to a disorder with symptoms of both
schizophrenia and mood disorders. In patients with the disorder, the onset of symptoms was sudden and often occurred in
adolescence. Patients tended to have a good premorbid level of functioning, and often a specific stressor preceded the onset
of symptoms. The family histories of the patients often included a mood disorder. Because Eugen Bleuler’s broad concept
of schizophrenia had eclipsed Kraepelin’s narrow concept, Kasanin believed that the patients had a type of schizophrenia.
From 1933 to about 1970, patients whose symptoms were similar to those of Kasanin’s patients were variously classified
as having schizoaffective disorder, atypical schizophrenia, good-prognosis schizophrenia, remitting schizophrenia, and
cycloid psychosis—terms that emphasized a relation to schizophrenia.
Around 1970, two sets of data shifted the view of schizoaffective disorder from a schizophrenic illness to a mood
disorder. First, lithium carbonate (Eskalith) was shown to be an effective and specific treatment for both bipolar disorders
and some cases of schizoaffective disorder. Second, the United States–United Kingdom study published in 1968 by John
Cooper and his colleagues showed that the variation in the number of patients classified as schizophrenic in the United
States and in the United Kingdom resulted from an overemphasis in the United States on the presence of psychotic
symptoms as a diagnostic criterion for schizophrenia.
EPIDEMIOLOGY
The lifetime prevalence of schizoaffective disorder is less than 1 percent, possibly in the
range of 0.5 to 0.8 percent. These figures, however, are estimates; various studies of
schizoaffective disorder have used varying diagnostic criteria. In clinical practice, a
preliminary diagnosis of schizoaffective disorder is frequently used when a clinician is
uncertain of the diagnosis.
Gender and Age Differences
Sex differences in the rates of schizoaffective disorder in clinical samples generally
parallel sex differences seen in mood disorders, with approximately equal numbers of
men and women who have the bipolar subtype and are more than twofold female to
male predominance among individuals with the depressed subtype of schizoaffective
disorder. The depressive type of schizoaffective disorder may be more common in older
persons than in younger persons, and the bipolar type may be more common in young
adults than in older adults. The age of onset for women is later than that for men, as in
schizophrenia. Men with schizoaffective disorder are likely to exhibit antisocial behavior
and to have a markedly flat or inappropriate affect.
ETIOLOGY
The cause of schizoaffective disorder is unknown. The disorder may be a type of
schizophrenia, a type of mood disorder, or the simultaneous expression of each.
Schizoaffective disorder may also be a distinct third type of psychosis, one that is
unrelated to either schizophrenia or a mood disorder. The most likely possibility is that
schizoaffective disorder is a heterogeneous group of disorders encompassing all of these
possibilities.
Studies designed to explore the etiology have examined family histories, biological
markers, short-term treatment responses, and long-term outcomes. Most studies have
considered patients with schizoaffective disorder to be a homogeneous group, but recent
studies have examined the bipolar and depressive types of schizoaffective disorder
separately.
Although much of the family and genetic research in schizoaffective disorder is based
on the premise that schizophrenia and the mood disorders are completely separate
entities, some data indicate that they may be genetically related. Studies of the
disrupted in schizophrenia 1 (DISC1) gene, located on chromosome 1q42, suggest its
possible involvement in schizoaffective disorder as well as schizophrenia and bipolar
disorder.
As a group, patients with schizoaffective disorder have a better prognosis than
patients with schizophrenia and a worse prognosis than patients with mood disorders.
Also, as a group, patients with schizoaffective disorder tend to have a nondeteriorating
course and respond better to lithium than do patients with schizophrenia.
Consolidation of Data
A reasonable conclusion from the available data is that patients with schizoaffective
disorder are a heterogeneous group: some have schizophrenia with prominent affective
symptoms, others have a mood disorder with prominent schizophrenic symptoms, and
still others have a distinct clinical syndrome. The hypothesis that patients with
schizoaffective disorder have both schizophrenia and a mood disorder is untenable
because the calculated co-occurrence of the two disorders is much lower than the
incidence of schizoaffective disorder.
DIAGNOSIS AND CLINICAL FEATURES
The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5)
criteria for schizoaffective disorder are provided in Table 7.2-1. The clinician must
accurately diagnose the affective illness, making sure it meets the criteria of either a
manic or a depressive episode but also determining the exact length of each episode (not
always easy or even possible).
Table 7.2-1
DSM-5 Diagnostic Criteria for Schizoaffective Disorder
The length of each episode is critical for two reasons. First, to meet the Criterion B
(psychotic symptoms in the absence of a major mood episode [depressive or manic]), it
is important to know when the affective episode ends and the psychosis continues.
Second, to meet Criterion C, the length of all mood episodes must be combined and
compared with the total length of the illness. If the mood component is present for the
majority (>50 percent) of the total illness, then that criterion is met. As with most
psychiatric diagnoses, schizoaffective disorder should not be used if the symptoms are
caused by substance abuse or a secondary medical condition.
Mr. C was 24 years old with no previous psychiatric history. Pregnancy, birth, early
development, and adjustment through army service as a paramedic were normal.
After discharge from the army, he began to study law but then quit school and
traveled in Asia, where he used cannabis. Family members who saw him during this
time noticed several changes: He insisted on changing his name, he began to isolate
himself, and he believed that he was the heir of the Dali Lama. When he became
aggressive and argumentative, he was brought home and hospitalized. On admission,
he was dressed like a Tibetan monk, with his head shaved. Although oriented to time
and place, he had delusions of grandeur, stating that he was the most clever man on
the planet and was the ancestor of the Messiah. He was also suspicious, arrogant, and
argumentative. On laboratory assessment, he was also found to have hepatitis A. He
was treated with perphenazine 28 mg per day and ultimately discharged to outpatient
treatment. He tried again to attend law school but could not persist for more than a
year before quitting. When his psychiatrist agreed to stop his antipsychotic
medications, he relapsed a month later. His second admission occurred following a
manic episode during which he spent money lavishly, had angry outbursts, was
excessively talkative, was hyperactive, and believed he was the Messiah. He was
treated with haloperidol 5 mg per day and lithium (Eskalith) 1,200 mg. After
discharge and another attempt at law school, he traveled to India. He was brought
home, rehospitalized with another manic episode, and discharged on depot
antipsychotic medications. After being rehospitalized because of extrapyramidal side
effects, he was prescribed olanzapine 20 mg per day and valproic acid (Depakene)
1,000 mg per day. During that hospitalization, his mood seemed more depressed, but
he did not meet the criteria for an episode of major depressive disorder. During the
subsequent 5 years, he remained out of the hospital and had no episodes of mood
disorder. He was careful to avoid using cannabis or other substances. He does not
work but functions well as a husband and father. From time to time he has thoughts
that he might be hurt by other people inflicting injury on his liver, but these thoughts
never last more than a few days.
The first aspect of establishing a differential diagnosis was determining whether the
psychosis was due to a general medical condition or a substance-use disorder. These
possibilities seemed unlikely because hepatitis would rarely be associated with the
development of an acute manic syndrome. Although cannabis use can precipitate
psychosis, the patient’s psychotic symptoms and mood disturbance also occurred in
the absence of substance use. In addition, the patient’s longitudinal course was not
consistent with either a substance-induced disorder or a psychosis due to a general
medical condition. Mr. C’s mood episodes were distinct, but he also had clear
psychotic symptoms in the absence of a mood episode, making schizoaffective
disorder a more appropriate diagnosis than bipolar disorder with psychotic features.
His course also showed a lack of return to his premorbid level of function despite
reasonable control of his symptoms with an antipsychotic and a mood stabilizing
anticonvulsant. The duration of his mood symptoms relative to the total illness
duration was significant and consistent with a diagnosis of schizoaffective disorder.
Mrs. P is a 47-year-old, divorced, unemployed woman who lived alone and who
experienced chronic psychotic symptoms despite treatment with olanzapine 20 mg per
day and citalopram (Celexa) 20 mg per day. She believed that she was getting
messages from God and the police department to go on a mission to fight against
drugs. She also believed that an organized crime group was trying to stop her in this
pursuit. The onset of her illness began at age 20 years when she experienced the first
of several depressive episodes. She also described periods when she felt more
energetic and talkative; had a decreased need for sleep; and was more active,
sometimes cleaning her house throughout the night. About 4 years after the onset of
her symptoms, she began to hear “voices” that became stronger when she was
depressed but were still present and disturbed her even when her mood was euthymic.
About 10 years after her illness began, she developed the belief that policemen were
everywhere and that the neighbors were spying on her. She was hospitalized
voluntarily. Two years later, she had another depressive episode, and the auditory
hallucinations told her she could not live in her apartment. She was tried on lithium,
antidepressants, and antipsychotic medications but continued to be chronically
symptomatic with mood symptoms as well as psychosis.
Mrs. P demonstrates a “classic” presentation of schizoaffective disorder in which
clear depressive and hypomanic episodes are present in combination with continuous
psychotic illness and first-rank symptoms. Her course is typical of many individuals
with schizoaffective disorder.
DIFFERENTIAL DIAGNOSIS
The psychiatric differential diagnosis includes all the possibilities usually considered for
mood disorders and for schizophrenia. In any differential diagnosis of psychotic
disorders, a complete medical workup should be performed to rule out organic causes for
the symptoms. A history of substance use (with or without positive results on a
toxicology screening test) may indicate a substance-induced disorder. Preexisting
medical conditions, their treatment, or both can cause psychotic and mood disorders.
Any suspicion of a neurological abnormality warrants consideration of a brain scan to
rule out anatomical pathology and an electroencephalogram to determine any possible
seizure disorders (e.g., temporal lobe epilepsy). Psychotic disorder caused by seizure
disorder is more common than that seen in the general population. It tends to be
characterized by paranoia, hallucinations, and ideas of reference. Patients with epilepsy
with psychosis are believed to have a better level of function than patients with
schizophrenic spectrum disorders. Better control of the seizures can reduce the psychosis.
COURSE AND PROGNOSIS
Considering the uncertainty and evolving diagnosis of schizoaffective disorder, it is
difficult to determine the long-term course and prognosis. Given the definition of the
diagnosis, patients with schizoaffective disorder might be expected to have a course
similar to an episodic mood disorder, a chronic schizophrenic course, or some
intermediate outcome. It has been presumed that an increasing presence of
schizophrenic symptoms predicted a worse prognosis. After 1 year, patients with
schizoaffective disorder had different outcomes, depending on whether their
predominant symptoms were affective (better prognosis) or schizophrenic (worse
prognosis). One study that followed patients diagnosed with schizoaffective disorder for
8 years found that the outcomes of these patients more closely resembled schizophrenia
than a mood disorder with psychotic features.
TREATMENT
Mood stabilizers are a mainstay of treatment for bipolar disorders and would be
expected to be important in the treatment of patients with schizoaffective disorder. One
study that compared lithium with carbamazepine (Tegretol) found that carbamazepine
was superior for schizoaffective disorder, depressive type, but found no difference in the
two agents for the bipolar type. In practice, however, these medications are used
extensively alone, in combination with each other, or with an antipsychotic agent. In
manic episodes, patients who are schizoaffective should be treated aggressively with
dosages of a mood stabilizer in the middle to high therapeutic blood concentration
range. As the patient enters maintenance phase, the dosage can be reduced to a low to
middle range to avoid adverse effects and potential effects on organ systems (e.g.,
thyroid and kidney) and to improve ease of use and compliance. Laboratory monitoring
of plasma drug concentrations and periodic screening of thyroid, kidney, and
hematological functioning should be performed.
By definition, many patients who are schizoaffective have major depressive episodes.
Treatment with antidepressants mirrors treatment of bipolar depression. Care should be
taken not to precipitate a cycle of rapid switches from depression to mania with the
antidepressant. The choice of antidepressant should take into account previous
antidepressant successes or failures. Selective serotonin reuptake inhibitors (e.g.,
fluoxetine [Prozac] and sertraline [Zoloft]) are often used as first-line agents because
they have less effect on cardiac status and have a favorable overdose profile. Agitated or
insomniac patients, however, may benefit from a tricyclic drug. As in all cases of
intractable mania, the use of ECT should be considered. As mentioned, antipsychotic
agents are important in the treatment of the psychotic symptoms of schizoaffective
disorder.
Psychosocial Treatment
Patients benefit from a combination of family therapy, social skills training, and
cognitive rehabilitation. Because the psychiatric field has had difficulty deciding on the
exact diagnosis and prognosis of schizoaffective disorder, this uncertainty must be
explained to the patient. The range of symptoms can be vast because patients contend
with both ongoing psychosis and varying mood states. It can be very difficult for family

03 - 7.3 Schizophreniform Disorder
7.3 Schizophreniform Disorder
members to keep up with the changing nature and needs of these patients. Medication
regimens can be complicated, with multiple medications from all classes of drugs.
REFERENCES
Bychkov ER, Ahmed MR, Gurevich VV, Benovi JL, Gurevich EV. Reduced expression of G protein-coupled receptor
kinases in schizophrenia but not in schizoaffective disorder. Neurobiol Dis. 2011;44(2):248.
Canuso CM, Lindenmayer JP, Kosik-Gonzalez C, Turkoz I, Carothers J, Bossie CA, Schooler NR. A randomized, doubleblind, placebo-controlled study of 2 dose ranges of paliperidone extended-release in the treatment of subjects with
schizoaffective disorder. J Clin Psychiatry. 2010;71(5):587.
Canuso CM, Schooler N, Carothers J, Turkoz I, Kosik-Gonzalez C, Bossie CA, Walling D, Lindenmayer JP. Paliperidone
extended-release in schizoaffective disorder: A randomized, controlled study comparing a flexible dose with placebo in
patients treated with and without antidepressants and/or mood stabilizers. J Clin Psychopharm. 2010;30(5):487.
Cardno AG, Owen MJ. Genetic relationships between schizophrenia, bipolar disorder, and schizoaffective disorder.
Schizophrenia Bulletin. 2014;40(3), 504–515.
Fochtmann LJ, Mojtabai R, Bromet EJ: Other psychotic disorders. In: Sadock BJ, Sadock VA, Ruiz P, eds. Kaplan &
Sadock’s Comprehensive Textbook of Psychiatry. 9th edition. Philadelphia: Lippincott Williams & Wilkins; 2009:1605.
Glick ID, Mankoski R, Eudicone JM, Marcus RN, Tran QV, Assunção-Talbott S. The efficacy, safety, and tolerability of
aripiprazole for the treatment of schizoaffective disorder: Results from a pooled analysis of a sub-population of subjects
from two randomized, double-blind, placebo-controlled, pivotal trials. J Affect Disord. 2009;115(1–2):18.
Hooper SR, Giuliano AJ, Youngstrom EA, Breiger D, Sikich L, Frazier JA, Findling RL, McClellan J, Hamer RM, Vitiello B,
Lieberman JA. Neurocognition in early-onset schizophrenia and schizoaffective disorders. J Am Acad Child Adolescent
Psychiatry. 2010;49:52.
Kane JM. Performance improvement CME: Schizoaffective disorder. J Clin Psychiatry. 2011;72(7):e23.
Kane JM. Strategies for making an accurate differential diagnosis of schizoaffective disorder. J Clin Psychiatry. 2010;71:4.
Kane JM. The differential diagnosis of schizoaffective disorder. J Clin Psychiatry. 2010;71(12):e33.
Kinnan S, Petty F, Wilson DR. Zolpidem-induced mania in a patient with schizoaffective disorder. Psychosomatics.
2011;52(5):493.
Pandina G, Bilder R, Turkoz I, Alphs L. Identification of clinically meaningful relationships among cognition, functionality,
and symptoms in subjects with schizophrenia or schizoaffective disorder. Schizophrenia research. 2013;143(2–3):312–
318.
Salzer MS, Baron RC, Brusilovskiy E, Lawer LJ, Mandell DS: Access and outcomes for persons with psychotic and affective
disorders receiving vocational rehabilitation services. Psychiatr Serv. 2011;62(7):796.
7.3 Schizophreniform Disorder
The concept of schizophreniform disorder was introduced in 1939 by Gabriel Langfeldt
(1895–1983) to describe a condition with a sudden onset and benign course associated
with mood symptoms and clouding of consciousness. The symptoms of schizophreniform
are similar to those of schizophrenia; however, with schizophreniform disorder, the
symptoms last for at least 1 month but less than 6 months. In contrast, for a patient to
meet the diagnostic criteria for schizophrenia, the symptoms must have been present for
at least 6 months. Patients with schizophreniform disorder return to their baseline level
of functioning after the disorder has resolved.
EPIDEMIOLOGY
Little is known about the incidence, prevalence, and sex ratio of schizophreniform
disorder. The disorder is most common in adolescents and young adults and is less than
half as common as schizophrenia. A fivefold greater rate of schizophreniform disorder
has been found in men than in women. A 1-year prevalence rate of 0.09 percent and a
lifetime prevalence rate of 0.11 percent have been reported.
Several studies have shown that the relatives of patients with schizophreniform
disorder are at high risk of having other psychiatric disorders, but the distribution of the
disorders differs from the distribution seen in the relatives of patients with schizophrenia
and bipolar disorders. Specifically, the relatives of patients with schizophreniform
disorders are more likely to have mood disorders than are the relatives of patients with
schizophrenia. In addition, the relatives of patients with schizophreniform disorder are
more likely to have a diagnosis of a psychotic mood disorder than are the relatives of
patients with bipolar disorders.
ETIOLOGY
The cause of schizophreniform disorder is not known. As Langfeldt noted in 1939,
patients with this diagnostic label are likely to be heterogeneous. In general, whereas
some patients have a disorder similar to schizophrenia, others have a disorder similar to
a mood disorder. Because of the generally good outcome, the disorder probably has
similarities to the episodic nature of mood disorders. Some data, however, indicate a
close relation to schizophrenia.
In support of the relation to mood disorders, several studies have shown that patients
with schizophreniform disorder, as a group, have more affective symptoms (especially
mania) and a better outcome than patients with schizophrenia. Also, the increased
occurrence of mood disorders in the relatives of patients with schizophreniform disorder
indicates a relation to mood disorders. Thus, the biological and epidemiological data are
most consistent with the hypothesis that the current diagnostic category defines a group
of patients, some of whom have a disorder similar to schizophrenia; others have a
disorder resembling a mood disorder.
Brain Imaging
A relative activation deficit in the inferior prefrontal region of the brain while the
patient is performing a region-specific psychological task (the Wisconsin Card Sorting
Test), as reported for patients with schizophrenia, has been reported in patients with
schizophreniform disorder. One study showed the deficit to be limited to the left
hemisphere and found impaired striatal activity suppression limited to the left
hemisphere during the activation procedure. The data can be interpreted to indicate a
physiological similarity between the psychosis of schizophrenia and the psychosis of
schizophreniform disorder. Additional central nervous system factors, as yet
unidentified, may lead to either the long-term course of schizophrenia or the
foreshortened course of schizophreniform disorder.
Although some data indicate that patients with schizophreniform disorder may have
enlarged cerebral ventricles, as determined by computed tomography and magnetic
resonance imaging, other data indicate that, unlike the enlargement seen in
schizophrenia, the ventricular enlargement in schizophreniform disorder is not
correlated with either outcome or other biological measures.
Other Biological Measures
Although brain imaging studies point to a similarity between schizophreniform disorder
and schizophrenia, at least one study of electrodermal activity indicated a difference.
Patients with schizophrenia who were born during the winter and spring months (a
period of high risk for the birth of these patients) had hyporesponsive skin
conductances, but this association was absent in patients with schizophreniform
disorder. The significance and the meaning of this single study are difficult to interpret,
but the results do suggest caution in assuming similarity between patients with
schizophrenia and those with schizophreniform disorder. Data from at least one study of
eye tracking in the two groups also indicate that they may differ in some biological
measures.
DIAGNOSTIC AND CLINICAL FEATURES
The DSM-5 criteria for schizophreniform disorder are listed in Table 7.3-1.
Schizophreniform disorder is an acute psychotic disorder that has a rapid onset and lacks
a long prodromal phase. Although many patients with schizophreniform disorder may
experience functional impairment at the time of an episode, they are unlikely to report
a progressive decline in social and occupational functioning. The initial symptom profile
is the same as that of schizophrenia in that two or more psychotic symptoms
(hallucinations, delusions, disorganized speech and behavior, or negative symptoms)
must be present. Schneiderian first-rank symptoms are frequently observed. Also an
increased likelihood is found of emotional turmoil and confusion, the presence of which
may indicate a good prognosis. Although negative symptoms may be present, they are
relatively uncommon in schizophreniform disorder and are considered poor prognostic
features. In a small series of first-admission patients with schizophreniform, one-fourth
had moderate to severe negative symptoms. Almost all were initially categorized as
having “schizophreniform disorder without good prognostic features,” and 2 years later,
73 percent were rediagnosed with schizophrenia compared with 38 percent of those with
“good prognostic features.”
Table 7.3-1
DSM-5 Diagnostic Criteria for Schizophreniform Disorder
By definition, patients with schizophreniform disorder return to their baseline state
within 6 months. In some instances, the illness is episodic, with more than one episode
occurring after long periods of full remission. If the combined duration of
symptomatology exceeds 6 months, however, then schizophrenia should be considered.
Mr. C, a 28-year-old accountant, was brought to the emergency department by the
police in handcuffs. He was disheveled, and shouted and struggled with the police
officers. It was apparent that he was hearing voices because he would respond to
them with shouts such as, “Shut up! I told you I won’t do it!” However, when
confronted about the voices, he denied hearing anything. Mr. C had a hypervigilant
stare and jumped at the slightest noise. He stated that he must run away quickly
because he knew he would be killed shortly otherwise.
Mr. C was functioning well until 2 months before hospitalization. He was an
accountant at a prestigious company and had close friends and a live-in girlfriend.
Most people who knew him would describe him as friendly, but he was occasionally
quarrelsome.
When his girlfriend suddenly broke off the relationship and moved out of their
apartment, Mr. C was distressed. However, he was convinced that he could win her
back, so he began to “accidentally” run into her at her job or her new apartment with
flowers and various gifts. When she strongly told him that she wanted nothing more
to do with him and requested that he leave her alone, Mr. C was convinced that she
wanted him dead. He became so preoccupied with this notion that his work began to
suffer. Out of fear for his life, Mr. C took off from work frequently, and when he did
report to work, he was often tardy and did subpar work, making many errors. His
supervisor confronted Mr. C about his behavior, threatening termination if it
continued. Mr. C was embarrassed and resented his supervisor for the confrontation.
He believed that his ex-girlfriend had hired the supervisor to kill him.
His beliefs were confirmed by a voice that would mock him. The voice told him time
and again that he should quit his job, relocate to another city, and forget about his exgirlfriend, but Mr. C refused, believing it would give them “more satisfaction than
they deserved.” He continued working, albeit cautiously, all the while fearing for his
life.
Through it all, Mr. C believed himself to be the lone victim. He would awake
abruptly at night from nightmares but would be able to fall right back to sleep. He
had not lost any weight and had no other vegetative symptoms. His affect alternated
between rage and terror. His mind was unusually alert and active, but he was not
otherwise hyperactive, excessively energetic, or expansive. He did not display any
formal thought disorder.
Mr. C was hospitalized and treated with antipsychotic medication. His symptoms
remitted after several weeks of treatment, and he was well and able to return to work
shortly after discharge.
DIFFERENTIAL DIAGNOSIS
It is important to first differentiate schizophreniform disorder from psychoses that can
arise from medical conditions. This is accomplished by taking a detailed history and
physical examination and, when indicated, performing laboratory tests or imaging
studies. A detailed history of medication use, including over-the-counter medications and
herbal products, is essential because many therapeutic agents can also produce an acute
psychosis. Although it is not always possible to distinguish substance-induced psychosis
from other psychotic disorders cross-sectionally, a rapid onset of psychotic symptoms in
a patient with a significant substance history should raise the suspicion of a substanceinduced psychosis. A detailed substance use history and toxicological screen are also
important for treatment planning in an individual with a new onset of psychosis.
The duration of psychotic symptoms is one factor that distinguishes schizophreniform
disorder from other syndromes. Schizophrenia is diagnosed if the duration of the
prodromal, active, and residual phases lasts for more than 6 months; symptoms that
occur for less than 1 month indicate a brief psychotic disorder. In general, a diagnosis of
brief psychotic disorder does not require that a major stressor be present.
Distinguishing mood disorders with psychotic features from schizophreniform disorder
is sometimes difficult. Furthermore, schizophreniform disorder and schizophrenia can be
highly comorbid with mood and anxiety disorders. Additional confounds are that mood
symptoms, such as loss of interest and pleasure, may be difficult to distinguish from
negative symptoms, avolition, and anhedonia. Some mood symptoms may also be
present during the early course of schizophrenia. A thorough longitudinal history is
important in elucidating the diagnosis because the presence of psychotic symptoms
exclusively during periods of mood disturbance is an indication of a primary mood
disorder.
COURSE AND PROGNOSIS
The course of schizophreniform disorder, for the most part, is defined in the criteria. It is
a psychotic illness lasting more than 1 month and less than 6 months. The real issue is
what happens to persons with this illness over time. Most estimates of progression to
schizophrenia range between 60 and 80 percent. What happens to the other 20 to 40
percent is currently not known. Some will have a second or third episode during which
they will deteriorate into a more chronic condition of schizophrenia. A few, however,
may have only this single episode and then continue on with their lives, which is clearly
the outcome desired by all clinicians and family members, although it is probably a rare
occurrence and should not be held out as likely.
TREATMENT
Hospitalization, which is often necessary in treating patients with schizophreniform
disorder, allows effective assessment, treatment, and supervision of a patient’s behavior.
The psychotic symptoms can usually be treated by a 3- to 6-month course of
antipsychotic drugs (e.g., risperidone). Several studies have shown that patients with
schizophreniform disorder respond to antipsychotic treatment much more rapidly than
patients with schizophrenia. In one study, about 75 percent of patients with
schizophreniform disorder and only 20 percent of the patients with schizophrenia
responded to antipsychotic medications within 8 days. A trial of lithium (Eskalith),
carbamazepine (Tegretol), or valproate (Depakene) may be warranted for treatment
and prophylaxis if a patient has a recurrent episode. Psychotherapy is usually necessary
to help patients integrate the psychotic experience into their understanding of their own
minds and lives. ECT may be indicated for some patients, especially those with marked
catatonic or depressed features.
Finally, most patients with schizophreniform disorder progress to full-blown
schizophrenia despite treatment. In those cases, a course of management consistent with
a chronic illness must be formulated.
REFERENCES
Bobes J, Arango C, Garcia-Garcia M. Rejas J. Prevalence of negative symptoms in outpatients with schizophrenia spectrum
disorders treated with antipsychotics in routine clinical practice: findings from the CLAMORS study. J Clin Psychiatry.
2010;71(3):280.
Boonstra G, van Haren NEM, Schnack HG, Cahn W, Burger H, Boersma M, de Kroon B, Grobbee DE, Hulshoff P, Hilleke E,
Khan RS. Brain volume changes after withdrawal of atypical antipsychotics in patients with first-episode

04 - 7.4 Delusional Disorder and Shared Psychotic
7.4 Delusional Disorder and Shared Psychotic Disorder
schizophrenia. J Clin Psychopharm. 2011;31(2):146.
Derks EM, Fleischhacker WW, Boter H, Peuskens J, Kahn RS. Antipsychotic drug treatment in first-episode psychosis:
Should patients be switched to a different antipsychotic drug after 2, 4, or 6 weeks of nonresponse? J Clin Psychopharm.
2010;30(2):176.
Fochtmann LJ, Mojtabai R, Bromet EJ. Other psychotic disorders. In: Sadock BJ, Sadock VA, Ruiz P, eds. Kaplan &
Sadock’s Comprehensive Textbook of Psychiatry. 9th edition. Philadelphia: Lippincott Williams & Wilkins; 2009:1605.
Goldstein JM, Buka SL, Seidman LJ, Tsuang MT. Specificity of familial transmission of schizophrenia psychosis spectrum
and affective psychoses in the New England family study’s high-risk design. Arch Gen Psychiatry. 2010;67(5):458.
Huang CF, Huang TY, Lin PY. Hypothermia and rhabdomyolysis following olanzapine injection in an adolescent with
schizophreniform disorder. Gen Hosp Psychiatry. 2009;31(4):376.
Kuha AL, Suvisaari J, Perälä J, Eerola M, Saarni SS, Partonen T, Lönnqvist J, Tuulio-Henriksson A. Associations of
anhedonia and cognition in persons with schizophrenia spectrum disorders, their siblings, and controls. J Nerv Ment
Dis. 2011;199:30.
Lambert M, Conus P, Cotton S, Robinson J, McGorry PD, Schimmelmann BG. Prevalence, predictors, and consequences of
long-term refusal of antipsychotic treatment in first-episode psychosis. J Clin Psychopharm. 2010;30(5):565.
Melle I, Røssberg JI, Joa I, Friis S, Haahr U, Johannessen JO, Larsen TK, Opjordsmoen S, Rund BR, Simonsen E, Vaglum P,
McGlashan T. The development of subjective quality of life over the first 2 years in first-episode psychosis. J Nerv Ment
Dis. 2010;198(12):864.
Purdon SE, Waldie B, Woodward ND, Wilman AH, Tibbo PG. Procedural learning in first episode schizophrenia
investigated with functional magnetic resonance imaging. Neuropsychology. 2011;25(2):147.
7.4 Delusional Disorder and Shared Psychotic Disorder
Delusions are false fixed beliefs not in keeping with the culture. They are among the
most interesting of psychiatric symptoms because of the great variety of false beliefs
that can be held by so many people and because they are so difficult to treat. The
diagnosis of delusional disorder is made when a person exhibits nonbizarre delusions of
at least 1 month’s duration that cannot be attributed to other psychiatric disorders.
Nonbizarre means that the delusions must be about situations that can occur in real life,
such as being followed, infected, loved at a distance, and so on; that is, they usually
have to do with phenomena that, although not real, are nonetheless possible. Several
types of delusions may be present and the predominant type is specified when the
diagnosis is made.
EPIDEMIOLOGY
An accurate assessment of the epidemiology of delusional disorder is hampered by the
relative rareness of the disorder, as well as by its changing definitions in recent history.
Moreover, delusional disorder may be underreported because delusional patients rarely
seek psychiatric help unless forced to do so by their families or by the courts. Even with
these limitations, however, the literature does support the contention that delusional
disorder, although uncommon, has a relatively steady rate.
The prevalence of delusional disorder in the United States is currently estimated to be
0.2 to 0.3 percent. Thus, delusional disorder is much rarer than schizophrenia, which has
a prevalence of about 1 percent, and the mood disorders, which have a prevalence of
about 5 percent. The annual incidence of delusional disorder is one to three new cases
per 100,000 persons. The mean age of onset is about 40 years, but the range for age of
onset runs from 18 years of age to the 90s. A slight preponderance of female patients
exists. Men are more likely to develop paranoid delusions than women, who are more
likely to develop delusions of erotomania. Many patients are married and employed,
but some association is seen with recent immigration and low socioeconomic status.
ETIOLOGY
As with all major psychiatric disorders, the cause of delusional disorder is unknown.
Moreover, patients currently classified as having delusional disorder probably have a
heterogeneous group of conditions with delusions as the predominant symptom. The
central concept about the cause of delusional disorder is its distinctness from
schizophrenia and the mood disorders. Delusional disorder is much rarer than either
schizophrenia or mood disorders, with a later onset than schizophrenia and a much less
pronounced female predominance than the mood disorders. The most convincing data
come from family studies that report an increased prevalence of delusional disorder and
related personality traits (e.g., suspiciousness, jealousy, and secretiveness) in the
relatives of delusional disorder probands. Family studies have reported neither an
increased incidence of schizophrenia and mood disorders in the families of delusional
disorder probands nor an increased incidence of delusional disorder in the families of
probands with schizophrenia. Long-term follow-up of patients with delusional disorder
indicates that the diagnosis of delusional disorder is relatively stable, with fewer than
one-fourth of the patients eventually being reclassified as having schizophrenia and
fewer than 10 percent of patients eventually being reclassified as having a mood
disorder. These data indicate that delusional disorder is not simply an early stage in the
development of one or both of these two more common disorders.
Biological Factors
A wide range of nonpsychiatric medical conditions and substances, including clear-cut
biological factors, can cause delusions, but not everyone with a brain tumor, for
example, has delusions. Unique, and not yet understood, factors in a patient’s brain and
personality are likely to be relevant to the specific pathophysiology of delusional
disorder.
The neurological conditions most commonly associated with delusions affect the
limbic system and the basal ganglia. Patients whose delusions are caused by
neurological diseases and who show no intellectual impairment tend to have complex
delusions similar to those in patients with delusional disorder. Conversely, patients with
neurological disorder with intellectual impairments often have simple delusions unlike
those in patients with delusional disorder. Thus, delusional disorder may involve the
limbic system or basal ganglia in patients who have intact cerebral cortical functioning.
Delusional disorder can arise as a normal response to abnormal experiences in the
environment, the peripheral nervous system, or the central nervous system (CNS). Thus,
if patients have erroneous sensory experiences of being followed (e.g., hearing
footsteps), they may come to believe that they are actually being followed. This
hypothesis hinges on the presence of hallucinatory-like experiences that need to be
explained. The presence of such hallucinatory experiences in delusional disorder has not
been proved.
Psychodynamic Factors
Practitioners have a strong clinical impression that many patients with delusional
disorder are socially isolated and have attained less than expected levels of
achievement. Specific psychodynamic theories about the cause and the evolution of
delusional symptoms involve suppositions regarding hypersensitive persons and specific
ego mechanisms, which are reaction formation, projection, and denial.
Freud’s Contributions.
Sigmund Freud believed that delusions, rather than being
symptoms of the disorder, are part of a healing process. In 1896, he described projection
as the main defense mechanism in paranoia. Later, Freud read Memories of My Nervous
Illness, an autobiographical account by Daniel Paul Schreber. Although he never met
Schreber, Freud theorized from his review of the autobiography that unconscious
homosexual tendencies are defended against by denial and projection. According to
classic psychodynamic theory, the dynamics underlying the formation of delusions for a
female patient are the same as for a male patient. Careful studies of patients with
delusions have been unable to corroborate Freud’s theories, although they may be
relevant in individual cases. Overall, no higher incidence of homosexual ideation or
activity is found in patients with delusions than in other groups. Freud’s major
contribution, however, was to demonstrate the role of projection in the formation of
delusional thought.
Paranoid Pseudocommunity.
Norman Cameron described seven situations that
favor the development of delusional disorders: an increased expectation of receiving
sadistic treatment, situations that increase distrust and suspicion, social isolation,
situations that increase envy and jealousy, situations that lower self-esteem, situations
that cause persons to see their own defects in others, and situations that increase the
potential for rumination over probable meanings and motivations. When frustration
from any combination of these conditions exceeds the tolerable limit, persons become
withdrawn and anxious; they realize that something is wrong, seek an explanation for
the problem, and crystallize a delusional system as a solution. Elaboration of the
delusion to include imagined persons and attribution of malevolent motivations to both
real and imagined persons results in the organization of the pseudocommunity—a
perceived community of plotters. This delusional entity hypothetically binds together
projected fears and wishes to justify the patient’s aggression and to provide a tangible
target for the patient’s hostilities.
Other Psychodynamic Factors.
Clinical observations indicate that many, if not
all, paranoid patients experience a lack of trust in relationships. A hypothesis relates
this distrust to a consistently hostile family environment, often with an overcontrolling
mother and a distant or sadistic father. Erik Erikson’s concept of trust versus mistrust in
early development is a useful model to explain the suspiciousness of a paranoid
individual who never went through the healthy experience of having his or her needs
satisfied by what Erikson termed the “outer-providers.” Thus, they have a general
distrust of their environment.
Defense Mechanisms.
Patients with delusional disorder use primarily the defense
mechanisms of reaction formation, denial, and projection. They use reaction formation
as a defense against aggression, dependence needs, and feelings of affection and
transform the need for dependence into staunch independence. Patients use denial to
avoid awareness of painful reality. Consumed with anger and hostility and unable to
face responsibility for the rage, they project their resentment and anger onto others and
use projection to protect themselves from recognizing unacceptable impulses in
themselves.
Other Relevant Factors.
Delusions have been linked to a variety of additional
factors such as social and sensory isolation, socioeconomic deprivation, and personality
disturbance. Deaf and visually impaired individuals and possibly immigrants with
limited ability in a new language may be more vulnerable to delusion formation than
the normal population. Vulnerability is heightened with advanced age. Delusional
disturbance and other paranoid features are common in elderly adults. In short, multiple
risk factors are associated with the formation of delusions, and the source and
pathogenesis of delusional disorders per se have yet to be specified (Table 7.4-1).
Table 7.4-1
Risk Factors Associated with Delusional Disorder
DIAGNOSIS AND CLINICAL FEATURES
The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5)
criteria for delusional disorder are listed in Table 7.4-2.
Table 7.4-2
DSM-5 Diagnostic Criteria for Delusional Disorder
Mental Status
General Description.
Patients are usually well groomed and well dressed, without
evidence of gross disintegration of personality or of daily activities, yet they may seem
eccentric, odd, suspicious, or hostile. They are sometimes litigious and may make this
inclination clear to the examiner. The most remarkable feature of patients with
delusional disorder is that the mental status examination shows them to be quite normal
except for a markedly abnormal delusional system. Patients may attempt to engage
clinicians as allies in their delusions, but a clinician should not pretend to accept the
delusion; this collusion further confounds reality and sets the stage for eventual distrust
between the patient and the therapist.
Mood, Feelings, and Affect.
Patients’ moods are consistent with the content of
their delusions. A patient with grandiose delusions is euphoric; one with persecutory
delusions is suspicious. Whatever the nature of the delusional system, the examiner may
sense some mild depressive qualities.
Perceptual Disturbances.
By definition, patients with delusional disorder do not
have prominent or sustained hallucinations. A few delusional patients have other
hallucinatory experiences—virtually always auditory rather than visual.
Thought.
Disorder of thought content, in the form of delusions, is the key symptom
of the disorder. The delusions are usually systematized and are characterized as being
possible (e.g., delusions of being persecuted, having an unfaithful spouse, being infected
with a virus, or being loved by a famous person). These examples of delusional content
contrast with the bizarre and impossible delusional content in some patients with
schizophrenia. The delusional system itself can be complex or simple. Patients lack other
signs of thought disorder, although some may be verbose, circumstantial, or
idiosyncratic in their speech when they talk about their delusions. Clinicians should not
assume that all unlikely scenarios are delusional; the veracity of a patient’s beliefs
should be checked before deeming their content to be delusional.
Sensorium and Cognition.
ORIENTATION. Patients with delusional disorder usually have no abnormality in
orientation unless they have a specific delusion about a person, place, or time.
MEMORY. Memory and other cognitive processes are intact in patients with delusional
disorder.
Impulse Control.
Clinicians must evaluate patients with delusional disorder for
ideation or plans to act on their delusional material by suicide, homicide, or other
violence. Although the incidence of these behaviors is not known, therapists should not
hesitate to ask patients about their suicidal, homicidal, or other violent plans.
Destructive aggression is most common in patients with a history of violence; if
aggressive feelings existed in the past, therapists should ask patients how they managed
those feelings. If patients cannot control their impulses, hospitalization is probably
necessary. Therapists can sometimes help foster a therapeutic alliance by openly
discussing how hospitalization can help patients gain additional control of their
impulses.
Judgment and Insight.
Patients with delusional disorder have virtually no insight
into their condition and are almost always brought to the hospital by the police, family
members, or employers. Judgment can best be assessed by evaluating the patient’s past,
present, and planned behavior.
Reliability.
Patients with delusional disorder are usually reliable in their
information, except when it impinges on their delusional system.
TYPES
Persecutory Type
The delusion of persecution is a classic symptom of delusional disorder; persecutory-type
and jealousy-type delusions are probably the forms seen most frequently by
psychiatrists. Patients with this subtype are convinced that they are being persecuted or
harmed. The persecutory beliefs are often associated with querulousness, irritability, and
anger, and the individual who acts out his or her anger may at times be assaultive or
even homicidal. At other times, such individuals may become preoccupied with formal
litigation against their perceived persecutors. In contrast to persecutory delusions in
schizophrenia, the clarity, logic, and systematic elaboration of the persecutory theme in
delusional disorder leave a remarkable stamp on this condition. The absence of other
psychopathology, of deterioration in personality, or of deterioration in most areas of
functioning also contrasts with the typical manifestations of schizophrenia.
Mrs. S, 62 years old, was referred to a psychiatrist because of reports of being
unable to sleep. She had previously worked full time taking care of children, and she
played tennis almost every day and managed her household chores. However, she had
now become preoccupied with the idea that her downstairs neighbor was doing a
variety of things to harass her and wanted to get her to move away. At first, Mrs. S
based her belief on certain looks that he gave her and damage done to her mailbox,
but later she felt he might be leaving empty bottles of cleaning solutions in the
basement so she would be overcome by fumes. As a result, the patient was fearful of
falling asleep, convinced that she might be asphyxiated and unable to awaken in time
to get help. She felt somewhat depressed and thought her appetite might be decreased
from the stress of being harassed. However, she had not lost weight and still enjoyed
playing tennis and going out with friends. At one point she considered moving to
another apartment but then decided to fight back. The episode had gone on for 8
months when her daughter persuaded her to have a psychiatric assessment. In the
interview, Mrs. S was pleasant and cooperative. Except for mild depressive symptoms
and the specific delusion about being harassed by her neighbor, her mental status was
normal.
Mrs. S had a past history of depression 30 years before, which followed the death of
a close friend. She saw a counselor for several months and found this helpful, but she
was not treated with medication. For the current episode, she agreed to take
medications, although she believed her neighbor was more in need of treatment than
she was. Her symptoms improved somewhat with risperidone (Risperdal) 2 mg at
bedtime and clonazepam (Klonopin) 0.5 mg every morning and at bedtime.
This patient presented with a single delusion regarding her neighbor that was
within the realm of possibility (i.e., not bizarre). Other areas of her functioning were
normal. Although mild depressive symptoms were present, she did not meet criteria
for major depressive disorder. Her prior symptoms of depression appeared to be
related to a normal bereavement reaction and had not required pharmacotherapy or
hospitalization. Thus, her current presentation is one of delusional disorder,
persecutory type and not major depressive disorder with psychotic features. In terms
of treatment, the ability to create a working alliance with the patient; avoiding the
discussion of the veracity of her delusion; and focusing on her anxiety, depression,
and difficulty falling asleep enabled her psychiatrist to introduce the medications with
beneficial results. (Courtesy of Laura J. Fochtmann, M.D., Ramin Mojtabai, M.D.,
Ph.D., M.P.H., and Evelyn J. Bromet, Ph.D.)
Jealous Type
Delusional disorder with delusions of infidelity has been called conjugal paranoia when it
is limited to the delusion that a spouse has been unfaithful. The eponym Othello
syndrome has been used to describe morbid jealousy that can arise from multiple
concerns. The delusion usually affects men, often those with no prior psychiatric illness.
It may appear suddenly and serve to explain a host of present and past events involving
the spouse’s behavior. The condition is difficult to treat and may diminish only on
separation, divorce, or death of the spouse.
Marked jealousy (usually termed pathological or morbid jealousy) is thus a symptom of
many disorders—including schizophrenia (in which female patients more commonly
display this feature), epilepsy, mood disorders, drug abuse, and alcoholism—for which
treatment is directed at the primary disorder. Jealousy is a powerful emotion; when it
occurs in delusional disorder or as part of another condition, it can be potentially
dangerous and has been associated with violence, notably both suicide and homicide
(Fig. 7.4-1). The forensic aspects of the symptom have been noted repeatedly, especially
its role as a motive for murder. Physical and verbal abuse occur more frequently,
however, than do extreme actions among individuals with this symptom. Caution and
care in deciding how to deal with such presentations are essential not only for diagnosis
but also from the point of view of safety.
FIGURE 7.4-1
A detail from the painting An Allegory with Venus and Cupid by Bronzino depicting a
jealous lover. There is a high risk of homicide when morbid jealousy becomes the
dominant theme in a relationship in which one partner is jealous of the other. That rage
is well-depicted in Bronzino’s painting.
Mr. M was a 51-year-old married white man who lived with his wife in their own
home and who worked full time driving a sanitation truck. Before his hospitalization,
he became concerned that his wife was having an affair. He began to follow her, kept
notes on his observations, and badgered her constantly about this, often waking her
up in the middle of the night to make accusations. Shortly before admission, these
arguments led to physical violence, and he was brought to the hospital by police. In
addition to concerns about his wife’s fidelity, Mr. M reported feelings of depression
over his wife’s “betrayal of [their] marriage vows,” but he noted no changes in sleep,
appetite, or work-related functioning. He was treated with a low dose of an
antipsychotic medication and described being less concerned about his wife’s
behavior. After discharge, he remained on medications and was seen by a psychiatrist
monthly, but 10 years later, he continued to believe that his wife was unfaithful. His
wife noted that he sometimes became upset about the delusion but that he had not
become aggressive or required readmission.
This patient experienced a fixed, encapsulated delusion of jealousy that did not
interfere with his other activities and that showed a partial response to antipsychotic
medications. Although he initially reported feeling somewhat depressed over his wife’s
perceived infidelity, he did not have other symptoms suggestive of a major depressive
episode. (Courtesy of Laura J. Fochtmann, M.D., Ramin Mojtabai, M.D., Ph.D.,
M.P.H., and Evelyn J. Bromet, Ph.D.)
Erotomanic Type
In erotomania, which has also been referred to as de Clérambault syndrome or psychose
passionelle, the patient has the delusional conviction that another person, usually of
higher status, is in love with him or her. Such patients also tend to be solitary,
withdrawn, dependent, and sexually inhibited as well as to have poor levels of social or
occupational functioning. The following operational criteria for the diagnosis of
erotomania
have
been
suggested:
(1)
a
delusional
conviction
of
amorous
communication, (2) object of much higher rank, (3) object being the first to fall in love,
(4) object being the first to make advances, (5) sudden onset (within a 7-day period),
(6) object remains unchanged, (7) patient rationalizes paradoxical behavior of the
object, (8) chronic course, and (9) absence of hallucinations. Besides being the key
symptom in some cases of delusional disorder, it is known to occur in schizophrenia,
mood disorder, and other organic disorders.
Patients with erotomania frequently show certain characteristics: They are generally
unattractive women in low-level jobs who lead withdrawn, lonely lives; they are single
and have few sexual contacts. They select secret lovers who differ substantially from
them. They exhibit what has been called paradoxical conduct, the delusional phenomenon
of interpreting all denials of love, no matter how clear, as secret affirmations of love.
The course may be chronic, recurrent, or brief. Separation from the love object may be
the only satisfactory intervention. Although men are less commonly affected by this
condition than women, they may be more aggressive and possibly violent in their
pursuit of love. Hence, in forensic populations, men with this condition predominate.
The object of aggression may not be the loved individual but companions or protectors
of the love object who are viewed as trying to come between the lovers. The tendency
toward violence among men with erotomania may lead initially to police, rather than
psychiatric, contact. In certain cases, resentment and rage in response to an absence of
reaction from all forms of love communication may sufficiently escalate to put the love
object in danger. So-called stalkers, who continually follow their perceived lovers,
frequently have delusions. Although most stalkers are men, women also stalk, and both
groups have a high potential for violence.
Mrs. D was a 32-year-old nurse who was married and had two children. She had
worked in the hospital for 12 years and functioned well in her job. She had previously
believed that one of the hospital’s attending physicians was in love with her. Now she
was referred by her supervisor for a psychiatric evaluation after she had assaulted one
of the residents, claiming he was in love with her. Her current delusion began when
the young physician entered a room where she was lying in bed after cosmetic surgery
and pointed at her. She had not known him before, but at that moment she became
convinced that he was in love with her. She tried to approach him several times by
letter and phone, and although he did not respond, she was convinced that he was
trying to transmit his love through looks he gave her and through the tone of his
voice. She did not report any associated hallucinatory experiences. The resident met
her and denied being in love with her, but she began stalking him, culminating in the
assault and the request for consultation.
Mrs. D initially refused to take any medications. She was treated with
psychotherapy for several months, during which she continued to work and was able
to avoid contact with the resident. The therapist arranged a three-way meeting with
himself, the patient, and the resident. After this meeting, there was a small reduction
in the intensity of Mrs. D’s belief, but she continued to maintain it nonetheless. She
subsequently agreed to take antipsychotic medications and was given perphenazine
16 mg per day, but there was no improvement. The delusion subsided only after the
resident moved to another hospital.
This patient’s presentation demonstrates a number of the features of the erotomanic
type of delusional disorder. In particular, her delusion began abruptly with what she
perceived to be a specific response to her by the resident. Her delusional conviction
that he was in love with her persisted even after being confronted, and she
rationalized his lack of apparent interest in her. The presence of a previous episode
and the poor response to antipsychotic medications are consistent with the often
chronic nature of the disorder, albeit with a different person being the object of her
delusions. The absence of hallucinations and the preservation of her ability to
function suggest a diagnosis of delusional disorder rather than schizophrenia.
(Example provided by S. Fennig and originally published in Fennig S, Fochtmann LJ,
Bromet EJ. Delusional disorder and shared psychotic disorder. In: Sadock BJ, Sadock
VA, eds. Kaplan and Sadock’s Comprehensive Textbook of Psychiatry. 8th edition.
Philadelphia: Lippincott Williams & Wilkins; 2005:1525.)
Somatic Type
Delusional disorder with somatic delusions has been called monosymptomatic
hypochondriacal
psychosis.
The
condition
differs
from
other
conditions
with
hypochondriacal symptoms in the degree of reality impairment. In delusional disorder,
the delusion is fixed, unarguable, and presented intensely because the patient is totally
convinced of the physical nature of the disorder. In contrast, persons with
hypochondriasis often admit that their fear of illness is largely groundless. The content
of the somatic delusion can vary widely from case to case. The three main types are (1)
delusions of infestation (including parasitosis); (2) delusions of dysmorphophobia, such
as of misshapenness, personal ugliness, or exaggerated size of body parts (this category
seems closest to that of body dysmorphic disorder); and (3) delusions of foul body odors
or halitosis. This third category, sometimes referred to as olfactory reference syndrome,
appears somewhat different from the category of delusions of infestation in that
patients with the former have an earlier age of onset (mean, 25 years), male
predominance, single status, and absence of past psychiatric treatment. Otherwise, the
three groups, although individually low in prevalence, appear to overlap.
The onset of symptoms with the somatic type of delusional disorder may be gradual or
sudden. In most patients, the illness is unremitting, although the delusion severity may
fluctuate. Hyperalertness and high anxiety also characterize patients with this subtype.
Some themes recur, such as concerns about infestation in delusional parasitosis,
preoccupation with body features with the dysmorphic delusions, and delusional
concerns about body odor, which are sometimes referred to as bromosis. In delusional
parasitosis, tactile sensory phenomena are often linked to the delusional beliefs.
Patients with the somatic type of delusional disorder rarely present for psychiatric
evaluation, and when they do, it is usually in the context of a psychiatric consultation or
liaison service. Instead, patients generally present to a specific medical specialist for
evaluation. Thus, these individuals are more often encountered by dermatologists,
plastic surgeons, urologists, acquired immune deficiency syndrome (AIDS) specialists,
and sometimes dentists or gastroenterologists.
Ms G. was a 56-year-old homemaker and mother of two who was hospitalized in the
burn unit for wound care and skin grafting after sustaining chemical burns to her
trunk and extremities. Six months before admission, Ms. G had become increasingly
convinced that tiny bugs had burrowed underneath her skin. She tried to rid herself of
them by washing multiple times each day with medicated soap and lindane shampoo.
She also visited several dermatologists and had provided samples of “dead bugs” for
them to examine under the microscope. All told her there was nothing wrong with her
and suggested that her problems were psychiatric in nature. She became increasingly
distressed by the infestation and worried that the bugs might invade her other organs
if not eradicated. Consequently, she decided to asphyxiate the bugs by covering her
body with gasoline and holding it against her skin with plastic wrap. She noted that
her skin became red and felt as though it were burning, but she viewed this as a
positive sign that the bugs were being killed and writhing around as they died.
Several hours after she had applied the gasoline, her daughter came to the house, saw
Ms. G’s condition, and took her to the hospital. When evaluated in the burn unit, Ms.
G spoke openly of her concerns about the bugs and was still unsure whether they were
present or not. At the same time, she recognized that it had been a mistake to try to
kill them with gasoline. She was oriented to person, place, and time and had no other
delusional beliefs or auditory or visual hallucinations. She said her mood was “okay,”
although she was realistically concerned about the extensive treatment that she would
require and the difficult process of recovering from her injury. She reported no
suicidal ideas or intent before admission and had no history of psychiatric treatment.
She also did not report any use of substances except for drinking several beers socially
about twice each month. During her stay in the hospital, she was treated with
haloperidol in doses of up to 5 mg per day with improvement in her delusions.
This patient demonstrates a classic presentation of delusional parasitosis, including
the repeated visits to other physicians, the absolute conviction that an infestation is
present, and the collection of “evidence” to support this belief. The lack of a
significant history of alcohol or substance use suggests that the sensation of bugs
crawling on her skin was not associated with substance intoxication or withdrawal.
She also did not have disorientation or fluctuations in her level of consciousness that
would suggest delirium, other psychotic symptoms that would suggest schizophrenia,
or depressive symptoms that would suggest major depressive disorder with psychotic
features. (Courtesy of Laura J. Fochtmann, M.D., Ramin Mojtabai, M.D., Ph.D.,
M.P.H., and Evelyn J. Bromet, Ph.D.)
Grandiose Type
Delusions of grandeur (megalomania) have been noted for years. They were first
described by Kraepelin.
A 51-year-old man was arrested for disturbing the peace. Police had been called to a
local park to stop him from carving his initials and those of a recently formed
religious cult into various trees surrounding a pond in the park. When confronted, he
had scornfully argued that having been chosen to begin a new town-wide religious
revival, it was necessary for him to publicize his intent in a permanent fashion. The
police were unsuccessful in preventing the man from cutting another tree and arrested
him. Psychiatric examination was ordered at the state hospital, and the patient was
observed there for several weeks. He denied any emotional difficulty and had never
received psychiatric treatment. He had no history of euphoria or mood swings. The
patient was angry about being hospitalized and only gradually permitted the doctor
to interview him. In a few days, however, he was busy preaching to his fellow
patients and letting them know that he had been given a special mandate from God to
bring in new converts through his ability to heal. Eventually, his preoccupation with
special powers diminished, and no other evidence of psychopathology was observed.
The patient was discharged, having received no medication at all. Two months later
he was arrested at a local theater, this time for disrupting the showing of a film that
depicted subjects he believed to be satanic.
Mixed Type
The category mixed type applies to patients with two or more delusional themes. This
diagnosis should be reserved for cases in which no single delusional type predominates.
Unspecified Type
The category unspecified type is reserved for cases in which the predominant delusion
cannot be subtyped within the previous categories. A possible example is certain
delusions of misidentification, for example, Capgras syndrome, named for the French
psychiatrist who described the illusion des sosies, or the illusion of doubles. The delusion
in Capgras syndrome is the belief that a familiar person has been replaced by an
impostor. Others have described variants of the Capgras syndrome, namely, the delusion
that persecutors or familiar persons can assume the guise of strangers (Frégoli’s
phenomenon) and the very rare delusion that familiar persons can change themselves
into other persons at will (intermetamorphosis). Each disorder is not only rare but may
also be associated with schizophrenia, dementia, epilepsy, and other organic disorders.
Reported cases have been predominantly in women, have had associated paranoid
features, and have included feelings of depersonalization or derealization. The delusion
may be short lived, recurrent, or persistent. It is unclear whether delusional disorder can
appear with such a delusion. Certainly, the Frégoli and intermetamorphosis delusions
have bizarre content and are unlikely, but the delusion in Capgras syndrome is a
possible candidate for delusional disorder. The role of hallucination or perceptual
disturbance in this condition needs to be explicated. Cases have appeared after sudden
brain damage.
In the 19th century, the French psychiatrist Jules Cotard described several patients
with a syndrome called délire de négation, sometimes referred to as nihilistic delusional
disorder or Cotard syndrome. Patients with the syndrome complain of having lost not
only possessions, status, and strength but also their heart, blood, and intestines. The
world beyond them is reduced to nothingness. This relatively rare syndrome is usually
considered a precursor to a schizophrenic or depressive episode. With the common use
today of antipsychotic drugs, the syndrome is seen even less frequently than in the past.
SHARED PSYCHOTIC DISORDER
Shared psychotic disorder (also referred to over the years as shared paranoid disorder,
induced psychotic disorder, folie impose, and double insanity) was first described by two
French psychiatrists, Lasegue and Falret, in 1877, who named it folie á deux. In DSM-5,
this disorder is referred to as “Delusional Symptoms in Partner of Individual with
Delusional Disorder,” an unnecessary nomenclature change in the view of most
psychiatrists. It is probably rare, but incidence and prevalence figures are lacking, and
the literature consists almost entirely of case reports.
The disorder is characterized by the transfer of delusions from one person to another.
Both persons are closely associated for a long time and typically live together in relative
social isolation. In its most common form, the individual who first has the delusion (the
primary case) is often chronically ill and typically is the influential member of a close
relationship with a more suggestible person (the secondary case) who also develops the
delusion. The person in the secondary case is frequently less intelligent, more gullible,
more passive, or more lacking in self-esteem than the person in the primary case. If the
pair separates, the secondary person may abandon the delusion, but this outcome is not
seen uniformly. The occurrence of the delusion is attributed to the strong influence of
the more dominant member. Old age, low intelligence, sensory impairment,
cerebrovascular disease, and alcohol abuse are among the factors associated with this
peculiar form of psychotic disorder. A genetic predisposition to idiopathic psychoses has
also been suggested as a possible risk factor.
Other special forms have been reported, such as folie simultanée, in which two persons
become psychotic simultaneously and share the same delusion. Occasionally, more than
two individuals are involved (e.g., folie á trois, quatre, cinq; also folie á famille), but such
cases are especially rare. The most common relationships in shared psychotic disorder
are sister–sister, husband–wife, and mother–child, but other combinations have also
been described. Almost all cases involve members of a single family.
A 52-year-old man was referred by the court for inpatient psychiatric examination,
charged with disturbing the peace. He had been arrested for disrupting a trial,
complaining of harassment by various judges. He had walked into a courtroom,
marched to the bench, and begun to berate the probate judge. While in the hospital,
he related a detailed account of conspiratorial goings-on in the local judiciary. A
target of certain judges, he claimed he had been singled out for a variety of reasons
for many years: he knew what was going on; he had kept records of wrongdoings;
and he understood the significance of the whole matter. He refused to elaborate on
the specific nature of the conspiracy. He had responded to it with frequent letters to
newspapers, the local bar association, and even to a Congressional subcommittee. His
mental state, apart from his story and a mildly depressed mood, was entirely normal.
A family interview revealed that his wife and several grown children shared the
belief in a judicial conspiracy directed against the patient. There was no change in
delusional thinking in the patient or the family after ten days of observation. The
patient refused follow-up.
In this case, protection is provided by others who share the delusion and believe in
the reasonableness of the response; such cases are uncommon, if not rare. (Courtesy
of TC Manschreck, M.D.)
DIFFERENTIAL DIAGNOSIS
Medical Conditions
In making a diagnosis of delusional disorder, the first step is to eliminate medical
disorders as a potential cause of delusions. Many medical conditions can be associated
with the development of delusions (Table 7.4-3), at times accompanying a delirious
state.
Table 7.4-3
Potential Medical Etiologies of Delusional Syndromes
Toxic-metabolic conditions and disorders affecting the limbic system and basal ganglia
are most often associated with the emergence of delusional beliefs. Complex delusions
occur more frequently in patients with subcortical pathology. In Huntington’s disease
and in individuals with idiopathic basal ganglia calcifications, for example, more than
50 percent of patients demonstrated delusions at some point in their illness. After right
cerebral infarction, types of delusions that are more prevalent include anosognosia and
reduplicative paramnesia (i.e., individuals believing they are in different places at the
same time). Capgras syndrome has been observed in a number of medical disorders,
including CNS lesions, vitamin B12 deficiency, hepatic encephalopathy, diabetes, and
hypothyroidism. Focal syndromes have more often involved the right rather than the left
hemisphere. Delusions of infestation, lycanthropy (i.e., the false belief that the patient is
an animal, often a wolf or “werewolf”), heutoscopy (i.e., the false belief that one has a
double), and erotomania have been reported in small numbers of patients with epilepsy,
CNS lesions, or toxic-metabolic disorders.
Delirium, Dementia, and Substance-Related Disorders
Delirium and dementia should be considered in the differential diagnosis of a patient
with delusions. Delirium can be differentiated by the presence of a fluctuating level of
consciousness or impaired cognitive abilities. Delusions early in the course of a
dementing illness, as in dementia of the Alzheimer’s type, can give the appearance of a
delusional disorder; however, neuropsychological testing usually detects cognitive
impairment. Although alcohol abuse is an associated feature for patients with delusional
disorder, delusional disorder should be distinguished from alcohol-induced psychotic
disorder
with
hallucinations.
Intoxication
with
sympathomimetics
(including
amphetamine), marijuana, or L-dopa is likely to result in delusional symptoms.
Other Disorders
The psychiatric differential diagnosis for delusional disorder includes malingering and
factitious disorder with predominantly psychological signs and symptoms. The
nonfactitious disorders in the differential diagnosis are schizophrenia, mood disorders,
obsessive-compulsive disorder, somatoform disorders, and paranoid personality disorder.
Delusional disorder is distinguished from schizophrenia by the absence of other
schizophrenic symptoms and by the nonbizarre quality of the delusions; patients with
delusional disorder also lack the impaired functioning seen in schizophrenia. The
somatic type of delusional disorder may resemble a depressive disorder or a somatoform
disorder. The somatic type of delusional disorder is differentiated from depressive
disorders by the absence of other signs of depression and the lack of a pervasive quality
to the depression. Delusional disorder can be differentiated from somatoform disorders
by the degree to which the somatic belief is held by the patient. Patients with
somatoform disorders allow for the possibility that their disorder does not exist, but
patients with delusional disorder do not doubt its reality. Separating paranoid
personality disorder from delusional disorder requires the sometimes difficult clinical
distinction between extreme suspiciousness and frank delusion. In general, if clinicians
doubt that a symptom is a delusion, the diagnosis of delusional disorder should not be
made.
COURSE AND PROGNOSIS
Some clinicians and some research data indicate that an identifiable psychosocial
stressor often accompanies the onset of delusional disorder. The nature of the stressor,
in fact, may warrant some suspicion or concern. Examples of such stressors are recent
immigration, social conflict with family members or friends, and social isolation. A
sudden onset is generally thought to be more common than an insidious onset. Some
clinicians believe that a person with delusional disorder is likely to have below-average
intelligence and that the premorbid personality of such a person is likely to be
extroverted, dominant, and hypersensitive. The person’s initial suspicions or concerns
gradually become elaborate, consume much of the person’s attention, and finally
become delusional. Persons may begin quarreling with coworkers; may seek protection
from the Federal Bureau of Investigation (FBI) or the police; or may begin visiting many
medical or surgical physicians to seek consultations, lawyers about suits, or police about
delusional suspicions.
As mentioned, delusional disorder is considered a fairly stable diagnosis. About 50
percent of patients have recovered at long-term follow-up, 20 percent show decreased
symptoms, and 30 percent exhibit no change. The following factors correlate with a
good prognosis: high levels of occupational, social, and functional adjustments; female
sex; onset before age 30 years; sudden onset; short duration of illness; and the presence
of precipitating factors. Although reliable data are limited, patients with persecutory,
somatic, and erotic delusions are thought to have a better prognosis than patients with
grandiose and jealous delusions.
TREATMENT
Delusional disorder was generally regarded as resistant to treatment, and interventions
often focused on managing the morbidity of the disorder by reducing the impact of the
delusion on the patient’s (and family’s) life. In recent years, however, the outlook has
become less pessimistic or restricted in planning effective treatment. The goals of
treatment are to establish the diagnosis, to decide on appropriate interventions, and to
manage complications (Table 7.4-4). The success of these goals depends on an effective
and therapeutic doctor–patient relationship, which is far from easy to establish. The
patients do not complain about psychiatric symptoms and often enter treatment against
their will; even psychiatrists may be drawn into their delusional nets.
Table 7.4-4
Diagnosis and Management of Delusional Disorder
In shared psychiatric disorder, the patients must be separated. If hospitalization is
indicated, they should be placed on different units and have no contact. In general, the
healthier of the two will give up the delusional belief (sometimes without any other
therapeutic intervention). The sicker of the two will maintain the false fixed belief.
Psychotherapy
The essential element in effective psychotherapy is to establish a relationship in which
patients begin to trust a therapist. Individual therapy seems to be more effective than
group therapy; insight-oriented, supportive, cognitive, and behavioral therapies are
often effective. Initially, a therapist should neither agree with nor challenge a patient’s
delusions. Although therapists must ask about a delusion to establish its extent,
persistent questioning about it should probably be avoided. Physicians may stimulate
the motivation to receive help by emphasizing a willingness to help patients with their
anxiety or irritability without suggesting that the delusions be treated, but therapists
should not actively support the notion that the delusions are real.
The unwavering reliability of therapists is essential in psychotherapy. Therapists
should be on time and make appointments as regularly as possible, with the goal of
developing a solid and trusting relationship with a patient. Overgratification may
actually increase patients’ hostility and suspiciousness because ultimately they must
realize that not all demands can be met. Therapists can avoid overgratification by not
extending the designated appointment period, by not giving extra appointments unless
absolutely necessary, and by not being lenient about the fee.
Therapists should avoid making disparaging remarks about a patient’s delusions or
ideas but can sympathetically indicate to patients that their preoccupation with their
delusions is both distressing to themselves and interferes with a constructive life. When
patients begin to waver in their delusional beliefs, therapists may increase reality
testing by asking the patients to clarify their concerns.
A useful approach in building a therapeutic alliance is to empathize with the patient’s
internal experience of being overwhelmed by persecution. It may be helpful to make
such comments as, “You must be exhausted, considering what you have been through.”
Without agreeing with every delusional misperception, a therapist can acknowledge
that from the patient’s perspective, such perceptions create much distress. The ultimate
goal is to help patients entertain the possibility of doubt about their perceptions. As they
become less rigid, feelings of weakness and inferiority, associated with some depression,
may surface. When a patient allows feelings of vulnerability to enter into the therapy, a
positive therapeutic alliance has been established, and constructive therapy becomes
possible.
When family members are available, clinicians may decide to involve them in the
treatment plan. Without being delusionally seen as siding with the enemy, a clinician
should attempt to enlist the family as allies in the treatment process. Consequently, both
the patient and the family need to understand that the therapist maintains physician–
patient confidentiality and that communications from relatives are discussed with the
patient. The family may benefit from the therapist’s support and thus may support the
patient.
A good therapeutic outcome depends on a psychiatrist’s ability to respond to the
patient’s mistrust of others and the resulting interpersonal conflicts, frustrations, and
failures. The mark of successful treatment may be a satisfactory social adjustment rather
than abatement of the patient’s delusions.
Hospitalization
Patients with delusional disorder can generally be treated as outpatients, but clinicians
should consider hospitalization for several reasons. First, patients may need a complete
medical and neurological evaluation to determine whether a nonpsychiatric medical
condition is causing the delusional symptoms. Second, patients need an assessment of
their ability to control violent impulses (e.g., to commit suicide or homicide) that may
be related to the delusional material. Third, patients’ behavior about the delusions may
have significantly affected their ability to function within their family or occupational
settings; they may require professional intervention to stabilize social or occupational
relationships.
If a physician is convinced that a patient would receive the best treatment in a
hospital, then the physician should attempt to persuade the patient to accept
hospitalization; failing that, legal commitment may be indicated. If a physician
convinces a patient that hospitalization is inevitable, the patient often voluntarily
enters a hospital to avoid legal commitment.
Pharmacotherapy
In an emergency, severely agitated patients should be given an antipsychotic drug
intramuscularly. Although no adequately conducted clinical trials with large numbers of
patients have been conducted, most clinicians consider antipsychotic drugs the
treatment of choice for delusional disorder. Patients are likely to refuse medication
because they can easily incorporate the administration of drugs into their delusional
systems; physicians should not insist on medication immediately after hospitalization
but, rather, should spend a few days establishing rapport with the patient. Physicians
should explain potential adverse effects to patients, so that they do not later suspect
that the physician lied.
A patient’s history of medication response is the best guide to choosing a drug. A
physician should often start with low doses (e.g., 2 mg of haloperidol [Haldol] or 2 mg
of risperidone [Risperdal]) and increase the dose slowly. If a patient fails to respond to
the drug at a reasonable dosage in a 6-week trial, antipsychotic drugs from other classes
should be tried. Some investigators have indicated that pimozide may be particularly
effective in delusional disorder, especially in patients with somatic delusions. A common
cause of drug failure is noncompliance, which should also be evaluated. Concurrent
psychotherapy facilitates compliance with drug treatment.
If the patient receives no benefit from antipsychotic medication, discontinue use of
the drug. In patients who do respond to antipsychotic drugs, some data indicate that
maintenance doses can be low. Although essentially no studies evaluate the use of
antidepressants, lithium (Eskalith), or anticonvulsants (e.g., carbamazepine [Tegretol]
and valproate [Depakene]) in the treatment of delusional disorder, trials with these
drugs may be warranted in patients who do not respond to antipsychotic drugs. Trials of
these drugs should also be considered when a patient has either the features of a mood
disorder or a family history of mood disorders.
REFERENCES
Bury JE, Bostwick JM. Iatrogenic delusional parasitosis: A case of physician–patient folie a deux. Gen Hosp Psychiatry.
2010;32(2):210.
Christensen RC, Ramos E. The social and treatment consequences of a shared delusional disorder in a homeless family.
Innov Clin Neurosci. 2011;8(4):42.
Edlich RF, Cross CL, Wack CA, Long WB III. Delusions of parasitosis. Am J Emerg Med. 2009;27(8):997.
Fochtmann LJ, Mojtabai R, Bromet EJ. Other psychotic disorders. In: Sadock BJ, Sadock VA, Ruiz P, eds. Kaplan &
Sadock’s Comprehensive Textbook of Psychiatry. 9th edition. Philadelphia: Lippincott Williams & Wilkins; 2009:1605.
Freeman D, Pugh K, Vorontsova N, Antley A, Slater M. Testing the continuum of delusional beliefs: An experimental study
using virtual reality. J Abnorm Psychiatry. 2010;119:83.
Hayashi H, Akahane T, Suzuki H, Sasaki T, Kawakatsu S, Otani K. Successful treatment by paroxetine of delusional
disorder, somatic type, accompanied by severe secondary depression. Clin Neuropharmacology. 2010;33:48.
Mishara AL, Fusar-Poli P. The phenomenology and neurobiology of delusion formation during psychosis onset: Jaspers,
Truman symptoms, and aberrant salience. Schizophrenia Bulletin. 2013;39(2):278–286.
Smith T, Horwath E, Cournos F. Schizophrenia and other psychotic disorders. In: Cutler JS, Marcus ER, eds. Psychiatry.
2nd edition. New York: Oxford University Press; 2010:101.
Szily E, Keri S. Delusion proneness and emotion appraisal in individuals with high psychosis vulnerability. Clin Psychol
Psychother. 2013;20(2):166–170.
7.5 Brief Psychotic Disorder, Other Psychotic Disorders,

05 - 7.5 Brief Psychotic Disorder, Other Psychotic
7.5 Brief Psychotic Disorder, Other Psychotic Disorders, and Catatonia
and Catatonia
BRIEF PSYCHOTIC DISORDER
Brief psychotic disorder is defined as a psychotic condition that involves the sudden
onset of psychotic symptoms, which lasts 1 day or more but less than 1 month.
Remission is full, and the individual returns to the premorbid level of functioning. Brief
psychotic disorder is an acute and transient psychotic syndrome.
History
Brief psychotic disorder has been poorly studied in psychiatry in the United States,
partly because of the frequent changes in diagnostic criteria during the past 15 years.
The diagnosis has been better appreciated and more completely studied in Scandinavia
and other Western European countries than in the United States. Patients with disorders
similar to brief psychotic disorder were previously classified as having reactive,
hysterical, stress, and psychogenic psychoses.
Reactive psychosis was often used as a synonym for good-prognosis schizophrenia, but
a diagnosis of brief psychotic disorder is not meant to imply a relation with
schizophrenia. In 1913, Karl Jaspers described several essential features for the
diagnosis of reactive psychosis, including an identifiable and extremely traumatic
stressor, a close temporal relation between the stressor and the development of the
psychosis, and a generally benign course for the psychotic episode. Jaspers also stated
that the content of the psychosis often reflected the nature of the traumatic experience
and that the development of the psychosis seemed to serve a purpose for the patient,
often as an escape from a traumatic condition.
Epidemiology
The exact incidence and prevalence of brief psychotic disorder is not known, but it is
generally considered uncommon. The disorder occurs more often among younger
patients (20s and 30s) than among older patients. Brief psychotic disorder is more
common in women than in men. Such epidemiological patterns are sharply distinct from
those of schizophrenia. Some clinicians indicate that the disorder may be seen most
frequently in patients from low socioeconomic classes and in those who have
experienced disasters or major cultural changes (e.g., immigrants). The age of onset in
industrialized settings may be higher than in developing countries. Persons who have
gone through major psychosocial stressors may be at greater risk for subsequent brief
psychotic disorder.
Comorbidity
The disorder is often seen in patients with personality disorders (most commonly,
histrionic, narcissistic, paranoid, schizotypal, and borderline personality disorders).
Etiology
The cause of brief psychotic disorder is unknown. Patients who have a personality
disorder may have a biological or psychological vulnerability for the development of
psychotic symptoms, particularly those with borderline, schizoid, schizotypal, or
paranoid qualities. Some patients with brief psychotic disorder have a history of
schizophrenia or mood disorders in their families, but this finding is nonconclusive.
Psychodynamic formulations have emphasized the presence of inadequate coping
mechanisms and the possibility of secondary gain for patients with psychotic symptoms.
Additional psychodynamic theories suggest that the psychotic symptoms are a defense
against a prohibited fantasy, the fulfillment of an unattained wish, or an escape from a
stressful psychosocial situation.
Diagnosis
A diagnosis of brief psychotic disorder is appropriate when psychotic symptoms last at
least 1 day but less than 1 month and are not associated with a mood disorder, a
substance-related disorder, or a psychotic disorder caused by a general medical
condition. There are three subtypes of brief psychotic disorder: (1) the presence of a
stressor, (2) the absence of a stressor, and (3) a postpartum onset. As with other acutely
ill psychiatric patients, the history necessary to make the diagnosis may not be
obtainable solely from the patient. Although psychotic symptoms may be obvious,
information about prodromal symptoms, previous episodes of a mood disorder, and a
recent history of ingestion of a psychotomimetic substance may not be available from
the clinical interview alone. In addition, clinicians may not be able to obtain accurate
information about the presence or absence of precipitating stressors. Such information is
usually best and most accurately obtained from a relative or a friend.
Clinical Features
The symptoms of brief psychotic disorder always include at least one major symptom of
psychosis, such as hallucinations, delusions, and disorganized thoughts, usually with an
abrupt onset, but do not always include the entire symptom pattern seen in
schizophrenia. Some clinicians have observed that labile mood, confusion, and impaired
attention may be more common at the onset of brief psychotic disorder than at the onset
of eventually chronic psychotic disorders. Characteristic symptoms in brief psychotic
disorder include emotional volatility, strange or bizarre behavior, screaming or
muteness, and impaired memory of recent events. Some of the symptoms suggest a
diagnosis of delirium and warrant a medical workup, especially to rule out adverse
reactions to drugs.
Scandinavian and other European literature describes several characteristic symptom
patterns in brief psychotic disorder, although these may differ somewhat in Europe and
America. The symptom patterns include acute paranoid reactions and reactive
confusion, excitation, and depression. Some data suggest that, in the United States,
paranoia is often the predominant symptom in the disorder. In French psychiatry,
bouffée délirante is similar to brief psychotic disorder.
Precipitating Stressors.
The clearest examples of precipitating stressors are
major life events that would cause any person significant emotional upset. Such events
include the loss of a close family member or a severe automobile accident. Some
clinicians argue that the severity of the event must be considered in relation to the
patient’s life. This view, although reasonable, may broaden the definition of
precipitating stressor to include events unrelated to the psychotic episode. Others have
argued that the stressor may be a series of modestly stressful events rather than a single
markedly stressful event, but evaluating the amount of stress caused by a sequence of
events calls for an almost impossibly high degree of clinical judgment.
A 20-year-old man was admitted to the psychiatric ward of a hospital shortly after
starting military duty. During the first week after his arrival to the military base, he
thought the other recruits looked at him in a strange way. He watched the people
around him to see whether they were out “to get” him. He heard voices calling his
name several times. He became increasingly suspicious and after another week had to
be admitted for psychiatric evaluation. There he was guarded, scowling, skeptical,
and depressed. He gave the impression of being very shy and inhibited. His psychotic
symptoms disappeared rapidly when he was treated with an antipsychotic drug.
However, he had difficulties in adjusting to hospital light. Transfer to a long-term
medical hospital was considered, but after 3 months, a decision was made to discharge
him to his home. He was subsequently judged unfit to return to military services.
The patient was the eldest of five siblings. His father was an intemperate drinker
who became angry and brutal when drunk. The family was poor, and there were
constant fights between the parents. As a child, the patient was inhibited and fearful
and often ran into the woods when troubled. He had academic difficulties.
When the patient got older, he preferred to spend time alone and disliked being
with people. He occasionally took part in local parties. Although he was never a
heavy drinker, he often got into fights when he had a drink or two.
The patient was reinterviewed by hospital personnel at 4 years, 7 years, and 23
years after his admission. He has had no recurrences of any psychotic symptoms and
has been fully employed since 6 months after he left the hospital. He married, and at
the last follow-up, he had two grown children.
After leaving the hospital, the patient worked for 2 years in a factory. For the past
20 years, he has managed a small business, and it has run well. He has been very
happy at work and in his family life. He has made an effort to overcome his tendency
toward isolation and has several friends.
The patient believes that his natural tendency is to be socially isolated and that his
disorder was connected with the fact that in the military, he was forced to deal with
other people. (Adapted from Laura J. Fochtmann, M.D., Ramin Mojtabai, M.D., Ph.D.,
M.P.H., and Evelyn J. Bromet, Ph.D.)
Differential Diagnosis
Clinicians must not assume that the correct diagnosis for a patient who is briefly
psychotic is brief psychotic disorder, even when a clear precipitating psychosocial factor
is identified. Such a factor may be merely coincidental. If psychotic symptoms are
present longer than 1 month, the diagnoses of schizophreniform disorder, schizoaffective
disorder, schizophrenia, mood disorders with psychotic features, delusional disorder, and
psychotic disorder not otherwise specified must be entertained. If psychotic symptoms of
sudden onset are present for less than 1 month in response to an obvious stressor,
however, the diagnosis of brief psychotic disorder is strongly suggested. Other diagnoses
to consider in the differential diagnosis include factitious disorder with predominantly
psychological signs and symptoms, malingering, psychotic disorder caused by a general
medical condition, and substance-induced psychotic disorder. In factitious disorder,
symptoms are intentionally produced; in malingering, a specific goal is involved in
appearing psychotic (e.g., to gain admission to the hospital); and when associated with
a medical condition or drugs, the cause becomes apparent with proper medical or drug
workups. If the patient admits to using illicit substances, the clinician can make the
assessment of substance intoxication or substance withdrawal without the use of
laboratory testing. Patients with epilepsy or delirium can also show psychotic symptoms
that resemble those seen in brief psychotic disorder. Additional psychiatric disorders to
be considered in the differential diagnosis include dissociative identity disorder and
psychotic episodes associated with borderline and schizotypal personality disorders.
Course and Prognosis
By definition, the course of brief psychotic disorder is less than 1 month. Nonetheless,
the development of such a significant psychiatric disorder may signify a patient’s mental
vulnerability. Approximately half of patients who are first classified as having brief
psychotic disorder later display chronic psychiatric syndromes such as schizophrenia and
mood disorders. Patients with brief psychotic disorder, however, generally have good
prognoses, and European studies have indicated that 50 to 80 percent of all patients
have no further major psychiatric problems.
The length of the acute and residual symptoms is often just a few days. Occasionally,
depressive symptoms follow the resolution of the psychotic symptoms. Suicide is a
concern during both the psychotic phase and the postpsychotic depressive phase. Several
indicators have been associated with a good prognosis. See Table 7.5-1 for a summary of
good prognostic signs in brief psychotic disorder.
Table 7.5-1
Good Prognostic Features for Brief Psychotic Disorder
Treatment
Hospitalization.
A patient who is acutely psychotic may need brief hospitalization
for both evaluation and protection. Evaluation requires close monitoring of symptoms
and assessment of the patient’s level of danger to self and others. In addition, the quiet,
structured setting of a hospital may help patients regain their sense of reality. While
clinicians wait for the setting or the drugs to have their effects, seclusion, physical
restraints, or one-to-one monitoring of the patient may be necessary.
Pharmacotherapy.
The two major classes of drugs to be considered in the
treatment of brief psychotic disorder are the antipsychotic drugs and the
benzodiazepines. When an antipsychotic drug is chosen, a high-potency antipsychotic
drug, such as haloperidol, or a serotonin dopamine agonist such as ziprasidone may be
used. In patients who are at high risk for the development of extrapyramidal adverse
effects (e.g., young men), a serotonin dopamine antagonist drug should be administered
as prophylaxis against medication-induced movement disorder symptoms. Alternatively,
benzodiazepines can be used in the short-term treatment of psychosis. Although
benzodiazepines have limited or no usefulness in the long-term treatment of psychotic
disorders, they can be effective for a short time and are associated with fewer adverse
effects than the antipsychotic drugs. In rare cases, the benzodiazepines are associated
with increased agitation and, more rarely still, with withdrawal seizures, which usually
occur only with the sustained use of high dosages. The use of other drugs in the
treatment of brief psychotic disorder, although reported in case studies, has not been
supported in any large-scale studies. Anxiolytic medications, however, are often useful
during the first 2 to 3 weeks after the resolution of the psychotic episode. Clinicians
should avoid long-term use of any medication in the treatment of the disorder. If
maintenance medication is necessary, a clinician may have to reconsider the diagnosis.
Psychotherapy.
Although hospitalization and pharmacotherapy are likely to
control short-term situations, the difficult part of treatment is the psychological
integration of the experience (and possibly the precipitating trauma, if one was present)
into the lives of the patients and their families. Psychotherapy is of use in providing an
opportunity to discuss the stressors and the psychotic episode. Exploration and
development of coping strategies are the major topics in psychotherapy. Associated
issues include helping patients deal with the loss of self-esteem and to regain selfconfidence. An individualized treatment strategy based on increasing problem-solving
skills while strengthening the ego structure through psychotherapy appears to be the
most efficacious. Family involvement in the treatment process may be crucial to a
successful outcome.
PSYCHOTIC DISORDER NOT OTHERWISE SPECIFIED
Under the umbrella of psychosis not otherwise specified is a variety of clinical
presentations that do not fit within current diagnostic rubrics. It includes psychotic
symptomatology
(i.e.,
delusions,
hallucinations,
disorganized
speech,
grossly
disorganized or catatonic behavior) about which there is inadequate information to
make a specific diagnosis or about which there is contradictory information. It also
includes disorders with psychotic symptoms that do not meet the criteria for any specific
psychotic disorder, such as patients who present to hospital with persistent auditory
hallucinations that are not accompanied by mood disturbances and that are not
pathognomonic for schizophrenia.
Autoscopic Psychosis
Although not included in DSM-5, autoscopic psychosis is of clinical interest. The
characteristic symptom of autoscopic psychosis is a visual hallucination of all or part of
the person’s own body. The hallucinatory perception, which is called a phantom, is
usually colorless and transparent, and because the phantom imitates the person’s
movements, it is perceived as though appearing in a mirror. The phantom tends to
appear suddenly and without warning.
Epidemiology.
Autoscopy is a rare phenomenon. Some persons have an autoscopic
experience only once or a few times; others have the experience more often. Although
the data are limited, sex, age, heredity, and intelligence do not seem to be related to the
occurrence of the syndrome.
Etiology.
The cause of the autoscopic phenomenon is unknown. A biological
hypothesis is that abnormal, episodic activity in areas of the temporoparietal lobes is
involved with the sense of self, perhaps combined with abnormal activity in parts of the
visual cortex. Psychological theories have associated the syndrome with personalities
characterized by imagination; visual sensitivity; and, possibly, narcissistic personality
disorder traits. Such persons may likely experience autoscopic phenomena during
periods of stress.
Course and Prognosis.
The classic descriptions of the phenomenon indicate that,
in most cases, the syndrome is neither progressive nor incapacitating. Affected persons
usually maintain some emotional distance from the phenomenon, an observation that
suggests a specific neuroanatomical lesion. Rarely do the symptoms reflect the onset of
schizophrenia or other psychotic disorders.
Treatment.
Patients usually respond to antianxiety medication. In severe cases,
antipsychotic medications may be needed.
Motility Psychosis
Motility psychosis is not considered an “official” DSM-5 diagnosis but is of clinical
significance. It is probably a variant of brief psychotic disorder. The two forms of
motility psychosis are akinetic and hyperkinetic. The akinetic form of motility psychosis
has a clinical presentation similar to that of catatonic stupor. In contrast to the
catatonic type of schizophrenia, however, akinetic motility psychosis has a rapidly
resolving and favorable course that does not lead to personality deterioration. In its
hyperkinetic form, motility psychosis can resemble manic or catatonic excitement. As
with the akinetic form, the hyperkinetic form usually has a rapidly resolving and
favorable course. Patients may switch from the akinetic to hyperkinetic form rapidly
and may represent a danger to others during the excited phase. Mood is extremely labile
in these patients.
Postpartum Psychosis
Postpartum psychosis (sometimes called puerperal psychosis) is an example of psychotic
disorder not otherwise specified that occurs in women who have recently delivered a
baby; the syndrome is most often characterized by the mother’s depression, delusions,
and thoughts of harming either her infant or herself. For a more detailed discussion see
Section 21.1.
PSYCHOTIC DISORDERS DUE TO A GENERAL MEDICAL CONDITION AND
SUBSTANCE- OR MEDICATION-INDUCED PSYCHOTIC DISORDER
The evaluation of a patient with psychotic disorders requires consideration of the
possibility that the psychotic symptoms result from a general medical condition such as
a brain tumor or the ingestion of a substance such as phencyclidine (PCP) or medication
such as cortisol.
Epidemiology
Relevant epidemiological data about psychotic disorder caused by a general medical
condition and substance-induced psychotic disorder are lacking. The disorders are most
often encountered in patients who abuse alcohol or other substances on a long-term
basis. The delusional syndrome that may accompany complex partial seizures is more
common in women than in men.
Etiology
Physical conditions such as cerebral neoplasms, particularly of the occipital or temporal
areas (Fig. 7.5-1), can cause hallucinations. Sensory deprivation, as in people who are
blind or deaf, can also result in hallucinatory or delusional experiences. Lesions
involving the temporal lobe and other cerebral regions, especially the right hemisphere
and the parietal lobe, are associated with delusions.
FIGURE 7.5-1
Temporal meningioma. (From Rowland LP, Pedley TA. Merritt’s Neurology. 12th edition.
Philadelphia: Lippincott Williams & Wilkins; 2010.)
Psychoactive substances are common causes of psychotic syndromes. The most
commonly involved substances are alcohol, indole hallucinogens, such as lysergic acid
diethylamide (LSD), amphetamine, cocaine, mescaline, PCP, and ketamine. Many other
substances, including steroids and thyroxine, can produce hallucinations.
Diagnosis
Psychotic Disorder Due to a General Medical Condition.
The diagnosis of
psychotic disorder due to a general medical condition is defined by specifying the
predominant symptoms. When the diagnosis is used, the medical condition, along with
the predominant symptoms pattern, should be included in the diagnosis (e.g., psychotic
disorder due to a brain tumor, with delusions). The disorder does not occur exclusively
while a patient is delirious or demented, and the symptoms are not better accounted for
by another mental disorder.
Substance- or Medication-Induced Psychotic Disorder.
The diagnostic
category of substance-induced psychotic disorder is reserved for those with psychotic
symptoms and impaired reality testing caused by substances or medications. People with
substance-induced psychotic symptoms (e.g., hallucinations) but with intact reality
testing should be classified as having a substance-related disorder (e.g., PCP intoxication
with perceptual disturbances). The full diagnosis of substance-induced psychotic disorder
should include the type of substance or medication involved, the stage of substance use
when the disorder began (e.g., during intoxication or withdrawal), and the clinical
phenomena (e.g., hallucinations or delusions). See Table 7.5-2 for the DSM-5 diagnostic
criteria.
Table 7.5-2
DSM-5 Diagnostic Criteria for Substance- or Medication-Induced Psychotic
Disorder
Clinical Features
Hallucinations.
Hallucinations can occur in one or more sensory modalities.
Tactile hallucinations (e.g., a sensation of bugs crawling on the skin) are characteristic
of cocaine use. Auditory hallucinations are usually associated with psychoactive
substance abuse; auditory hallucinations can also occur in persons who are deaf.
Olfactory hallucinations can result from temporal lobe epilepsy; visual hallucinations
can occur in persons who are blind because of cataracts. Hallucinations are either
recurrent or persistent and are experienced in a state of full wakefulness and alertness;
a hallucinating patient shows no significant changes in cognitive functions. Visual
hallucinations often take the form of scenes involving diminutive (lilliputian) human
figures or small animals. Rare musical hallucinations typically feature religious songs.
Patients with psychotic disorder caused by a general medical condition and substanceinduced psychotic disorder may act on their hallucinations. In alcohol-related
hallucinations, threatening, critical, or insulting third-person voices speak about the
patients and may tell them to harm either themselves or others. Such patients are
dangerous and are at significant risk for suicide or homicide. Patients may or may not
believe that the hallucinations are real.
Delusions.
Secondary and substance-induced delusions are usually present in a state
of full wakefulness. Patients experience no change in the level of consciousness,
although mild cognitive impairment may be observed. Patients may appear confused,
disheveled, or eccentric, with tangential or even incoherent speech. Hyperactivity and
apathy may be present, and an associated dysphoric mood is thought to be common.
The delusions can be systematized or fragmentary, with varying content, but
persecutory delusions are the most common.
Differential Diagnosis.
Psychotic disorder due to a general medical condition and
substance- or medication-induced psychotic disorder must be distinguished from delirium
(in which patients have a clouded sensorium), from dementia (in which patients have
major intellectual deficits), and from schizophrenia (in which patients have other
symptoms of thought disorder and impaired functioning). Psychotic disorder due to a
general medical condition and substance-induced psychotic disorder must also be
differentiated from psychotic mood disorders (in which other affective symptoms are
pronounced).
Treatment
Treatment involves identifying the general medical condition or the particular substance
involved. At that point, treatment is directed toward the underlying condition and the
patient’s immediate behavioral control. Hospitalization may be necessary to evaluate
patients completely and to ensure their safety. Antipsychotic agents (e.g., olanzapine
[Zyprexa] or haloperidol) may be necessary for immediate and short-term control of
psychotic or aggressive behavior, although benzodiazepines may also be useful for
controlling agitation and anxiety.
CATATONIC DISORDER
Catatonia is a new diagnostic category in DSM-5 introduced because it can occur over a
broad spectrum of mental disorders, most often in severe psychotic and mood disorders.
It can also be caused by an underlying medical condition or induced by a substance.
Definition
Catatonia is a clinical syndrome characterized by striking behavioral abnormalities that
may include motoric immobility or excitement, profound negativism, or echolalia
(mimicry of speech) or echopraxia (mimicry of movement). A diagnosis of catatonic
disorder due to a general medical condition can be made if there is evidence that the
condition is due to the physiological effects of a general medical condition. The
diagnosis is not made if the catatonia is better explained by a primary mental disorder,
such as schizophrenia or psychotic depression, or if catatonic symptoms occur
exclusively within the course of delirium.
Epidemiology
Catatonia is an uncommon condition mostly seen in advanced primary mood or
psychotic illnesses. Among inpatients with catatonia, 25 to 50 percent are related to
mood disorders (e.g., major depressive episode, recurrent, with catatonic features), and
approximately 10 percent are associated with schizophrenia. The prevalence of
catatonia due to medical conditions of substances is unknown.
Etiology
Medical conditions that can cause catatonia include neurological disorders (e.g.,
nonconvulsive status epilepticus, and head trauma), infections (e.g., encephalitis), and
metabolic
disturbances
(e.g.,
hepatic
encephalopathy,
hyponatremia,
and
hypercalcemia).
Medications that can cause catatonia include corticosteroids, immunosuppressants,
and antipsychotic (i.e., neuroleptic) agents. Catatonic symptoms may be seen in
extreme forms of neuroleptic-induced parkinsonism or neuroleptic malignant syndrome,
a rare, potentially life-threatening disorder associated with fever, autonomic instability,
impaired consciousness, and rigidity.
Diagnosis and Clinical Features
DSM-5 criteria for the diagnosis of catatonic disorder due to a general medical condition
(Table 7.5-3) include behavioral changes characteristic of catatonia, evidence of a
physiological basis for the symptoms, and exclusion of primary mental disorders and
delirium. The diagnosis of catatonia due to a mental disorder is used when the disorder
occurs in a psychiatric rather than another medical condition (Table 7.5-4). In either
case, the signs and symptoms of catatonia are similar; it is the etiology that differs.
Behavioral changes may include motoric immobility or excessive activity, extreme
negativism or mutism, peculiarities of voluntary movement, and echolalia or
echopraxia. Waxy flexibility, a form of artificial posturing often evident on physical
examination, may be present (Fig. 7.5-2). Lethal catatonia is a rare advanced stage of
the disorder that features fever and autonomic instability and may be fatal.
FIGURE 7.5-2
A chronic schizophrenic patient stands in a catatonic position. He maintained this
uncomfortable position for hours. (Courtesy of Emil Kraepelin, M.D.)
Table 7.5-3
DSM-5 Diagnostic Criteria for Catatonic Disorder Due to Another Medical
Condition
Table 7.5-4
DSM-5 Diagnostic Criteria for Catatonia Associated with Another Mental
Disorder
For catatonia secondary to antipsychotic agents, the diagnoses of neuroleptic-induced
parkinsonism and neuroleptic malignant syndrome may be appropriate. For catatonia
due to non-neuroleptic substances, the diagnosis of medication-induced movement
disorder not otherwise specified is available.
Laboratory Examination
There are no pathognomonic laboratory findings in catatonia. The laboratory
evaluation should be used to rule out an underlying medical condition. Appropriate
medical tests may include complete blood counts, electrolytes, brain imaging, and
electroencephalography (if seizures are suspected). In addition, serum creatinine
phosphokinase, white blood cell count, and serum transaminases should be checked
because the results of laboratory tests are elevated in patients with neuroleptic
malignant syndrome.
Differential Diagnosis
Differential diagnoses include hypoactive delirium, end-stage dementia, and akinetic
mutism, as well as catatonia due to a primary psychiatric disorder. It is important to
identify cases of catatonia occurring in the setting of neuroleptic malignant syndrome
because the latter diagnosis can be fatal. Features suggesting neuroleptic malignant
syndrome include autonomic instability and delirium in addition to elevated serum
creatinine phosphokinase, white blood cell count, and serum transaminases.
Course and Treatment
Catatonia impairs a person’s ability to care for himself or herself and therefore requires
hospitalization. In an excited state, the catatonic patient may represent a danger to
others; hence, close supervision is needed. Fluid and nutrient intake must be
maintained, often with intravenous lines or feeding tubes. The catatonic individual must
be assisted with hygiene.
The primary treatment modality is identifying and correcting the underlying medical
or pharmacological cause. Offending substances must be removed or minimized.
Benzodiazepines can provide temporary improvement in symptoms, and their use
may improve patients’ ability to communicate and to care for themselves. ECT is
appropriate for catatonia due to a general medical condition, especially if the catatonia
is life threatening (e.g., inability to eat) or has developed into lethal (malignant)
catatonia. The mechanism behind the efficacy of ECT is unknown.
REFERENCES
Breen R. Psychotic disorders. In: Thornhill JT, ed. NMS Psychiatry. 6th edition. Baltimore: Lippincott Williams & Wilkins:
2011:17.
Correll CU, Smith CW, Auther AM, McLaughlin D, Shah M, Foley C, Olsen R, Lencz T, Kane JM, Cornblatt BA. Predictors of
remission, schizophrenia, and bipolar disorder in adolescents with brief psychotic disorder or psychotic disorder not
otherwise specified considered at very high risk for schizophrenia. J Child Adolesc Pscyhopharmacol. 2008;18:475.
Fochtmann LJ, Mojtabai R, Bromet EJ. Other psychotic disorders. In: Sadock BJ, Sadock VA, Ruiz P, eds. Kaplan &
Sadock’s Comprehensive Textbook of Psychiatry, 9th edition. Philadelphia: Lippincott Williams & Wilkins: 2009: 1605.
Hasija D, Jadapalle SLK, Badr A. Status epilepticus and psychosis of epilepsy. Psych Ann. 2012:42:11.
Hedges DW, Woon FL, Hoppes SP. Caffeine-induced psychosis. CNS Spectr. 2009:14:127.
Jacobson SA. Psychotic disorder due to a general medical condition (secondary psychosis). In: Laboratory Medicine in
Psychiatry and Behavioral Science. Arlington, VA: American Psychiatric Publishing; 2012:554.
Lukens EP, Ogden LP. Psychotic conditions. In: Heller NR, Gitterman A, eds. Mental Health and Social Problems: A Social
Work Perspective. New York: Routledge; 2011:423.
Nykiel SA, Baldessarini RJ, Bower MC, Goodwin J, Salvatore P. Psychosis NOS: Search for diagnostic clarity. Harv Rev
Psychiatry. 2010;18:22.
Pierre JM. Hallucinations in nonpsychotic disorders: Toward a differential diagnosis of “hearing voices.” Harv Rev
Psychiatry. 2010;18:22.
Smith MJ, Thirthalli J, Abdallah AB, Murray RM, Cottler LB. Prevalence of psychotic symptoms in substance users: A
comparison across substances. Comp Psychiatry. 2009:50:245.
Tebartz van Elst L, Klöppel S, Rauer S. Voltage-gated potassium channel/LGI1 antibody-associated encephalopathy may
cause brief psychotic disorder. J Clin Psychiatry. 2011:72:722.