# 45 - Molecular associations (Schizophrenia and Bip

# Molecular associations (Schizophrenia and Bipolar disorder)

© SPMM Course 
Other implicated chromosomes – 
 
Chr 18 - nearly 4 loci, affective disorders in general;? parent of origin effect) 
 
Chr 21q - both in scz and BPAD. 
 
An X-chromosomal locus to BPAD has been suggested on the basis of the cosegregation of BPAD in some 
families with color blindness, the glucose-6-phosphate dehydrogenase deficiency, and the coagulation 
factor IX deficiency. In an extended Finnish pedigree, Xq24-q27.1 was demonstrated to segregate with 
bipolar disorder. 
 
Low activity allele in COMT gene may be associated with rapid cycling. 
 
Serotonin transporter gene (hSERT) and 5HT2A gene may be associated with modest statistical 
significance in Seasonal Affective Disorder. 
 
 
Unipolar depression (MDD) 
 Age-adjusted risk of MDD to first-degree relatives: 5-30%, relative risk 1.1-4.0. MZ Twin concordance 
for MDD: 40%. DZ Twin concordance for MDD: 11%. Heritability: Unclear (~20-80%); meta-analysis 
reports 31-42%. (Data from NCHPEG Empric Risk Data: Retrieved from www.nchpeg.org ) 
 Early onset and recurrent episodes likely increase risks to first-degree relatives. Recurrence risks for 
unipolar depression could be 50 percent or higher for probands with early-onset and recurrent 
episodes. While the definition of “early onset” is not entirely clear, research suggests that family 
members of probands who had onset before age 25-30 years have the highest risk; relatives of 
probands with onset between ages 25-40 years have an intermediate risk; and relatives of probands 
with onset after age 40 years have a risk that is only slightly increased over the population risk 
Schizoaffective disorder 
 The risk to first-degree relatives for ANY psychiatric disorder is higher in SA disorder than any other 
psychiatric disorder. The extent of heritability is unclear, although likely in the range of schizophrenia. 
 Relatives have a higher rate of schizoaffective illness, schizophrenia and bipolar disorder. 
 The rate of bipolar disorder is high if proband has a schizoaffective-manic presentation. The rate of 
schizophrenia is high if proband has schizoaffective-depressive presentation. In depressive subtype no 
elevation in bipolar risk has been noted in a large cohort (Andreasen 1987). 
 
 
Molecular associations (Schizophrenia and Bipolar disorder) 
 G72: The function of G72 (also sometimes referred to as DAOA) may be to, oxidize serine, a potent 
activator of glutamate transmission via a modulatory site on the NMDA (n-methyl-d-aspartate) 
receptor. Inadequate DAOA function might be hypothesized to lead to problems in modulating the 
glutamate signal in areas of the brain such as the prefrontal cortex. A new suggestion is that the major 
role of G72 may be in maintaining neuronal structure. 
 Brain-Derived Neurotrophic Factor (BDNF): Several studies have shown that antidepressant 
administration is associated with increased central BDNF levels in experimental animals, and 
administration of BDNF itself has been associated with the antidepressant-like activity. Depression has 
Shared genes – BPAD and Schizophrenia 
DAO & BDNF – seen more in mood disorders than schizophrenia 
DISC 1 & NRG – shared with schizophrenia; seen in schizoaffective disorder 
Dysbindin – seen more in schizophrenia than mood disorders 
CREB1 (chr2) – unipolar depression