Genetics of mood disorders Flashcards
One parent has a mood disorder
-child has risk of 10-25 % for mood disorder
Both parents have a mood disorder
-child’s risk is doubled to 50%
Family history of bipolar
- conveys greater risk for mood disorders
- bipolar disorder in particular
- broad heritability is 85-90%
- sex is not important
lifetime risk of unrelated person to someone with bipolar
- risk of having bipolar 0.5-1.5%
- risk of unipolar 5-10%
1st degree relative of someone with bipolar
- risk of bipolar 5-10%
- risk of unipolar 10-
Monozygotic co-twin of a bipolar person
- risk of bipolar 40-70%
- risk of unipolar 15-25%
BDNF
- brain derived neurotrophic factor
- 11p13
DAO G72/G30
- D aminoacid oxidase
- 13q33
COMT
- catechol-o-methyl transferase
- breakpoint cluster region (BCR) gene
- 22q11
Chromosome 18
- near loci 4
- affective disordres in general
Chromosome 21q
-both in schizophrenia and BPAD
Serotonin transporter gene
- hSERT and 5HT2A gene
- associated with modest statistical significance in seasonal affective disorder
Schizoaffective disorder
- the risk to a first degree relative for any psychiatric disorder is higher in schizoaffective disorder than any other psychiatric disorder
- rate of bipolar is high if the proband has a schizoaffective-manic presentation
- rate of schizophrenia is high if the poband has schizoaffective-depressive presentation
DAO & BDNF
-seen more in mood disorders than schizophrenia
DISC 1 and NRG
- shared with schizophrenia
- seen in schizoaffective disorder
Dysbindin
-seen more in schizophrenia than mood disorders
CREB1 (chr 2)
-unipolar depression
G72
-the function of G72 (aka DAOA) may be to oxidize serine, a potent activator of glutamate transmission via a modulatory site on the NMDA (n-methyl-d aspartate) receptor
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 antidepressant-like activity
Disrupted in Schizophrenia 1
- gene on chromosome 1q
- expressed in multiple brain regions including the hippocampus
5HTT, MAO and COMT
-these three genes have been shown to be associated with BPAD
Dysbindin
- aka dystrobrevin binding protein 1
- involved in the formation of synaptic structures
Neuroregulin
-involved in neuronal migration and the genesis of glial cells and subsequent myelination of neurons by these cells
GRK3
- this is the only candidate identified using animal model studies
- gene participates in down-regulation of G-proetin coupled receptors and is associated with BPAD
