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