Genetics of psychiatric disease

Area of Science:

• Psychiatric Genetics
• Molecular Psychiatry
• Genetic Epidemiology

Background:

• Family studies indicate increased risk for bipolar disorder (BIP), recurrent unipolar (RUP), and schizoaffective (SA) disorders among relatives of BIP probands.
• Relatives of schizophrenia (SZ) probands show elevated risk for SZ, SA, and RUP disorders, suggesting overlapping familial risks.
• The observed familial risk overlap points towards a potential shared genetic susceptibility between these psychiatric disorders.

Purpose of the Study:

• To investigate the shared genetic susceptibility between bipolar disorder and schizophrenia.
• To review evidence from genetic linkage and family studies implicating specific genomic regions in these disorders.
• To explore whether current nosological distinctions accurately reflect the underlying genetic relationships.

Main Methods:

• Review of genetic epidemiologic studies examining familial risk patterns for BIP, RUP, SA, and SZ disorders.
• Analysis of genetic linkage studies identifying susceptibility loci for BIP and SZ disorders.
• Comparison of identified genetic loci across studies to detect shared genomic regions.

Main Results:

• Confirmed susceptibility loci for BIP disorder identified on chromosomes 4p16, 12q24, 18p11.2, 18q22, 21q21, 22q11-13, and Xq26.
• Robust evidence for SZ susceptibility loci at 18p11.2 and 22q11-13, regions also implicated in BIP disorder.
• Confirmed SZ vulnerability loci mapped to 6p24, 8p, and 13q32, with strong statistical evidence for a BIP susceptibility locus at 13q32.

Conclusions:

• Both family and molecular genetic studies strongly suggest a shared genetic susceptibility underlying bipolar disorder and schizophrenia.
• The identified overlapping genetic loci challenge the notion that these disorders are entirely distinct entities.
• Current diagnostic classifications may need re-evaluation in light of the accumulating evidence for shared genetic underpinnings.