Differential expression of disrupted-in-schizophrenia (DISC1) in bipolar disorder.

BACKGROUND: The disruption of the disrupted-in-schizophrenia (DISC1) gene segregates with major mental illnesses in a Scottish family. Association of DISC1 with schizophrenia has been reported in several ethnic groups, and now recently with mood disorder. METHODS: A family-based association study of DISC1 and bipolar disorder (BP) in 57 bipolar pedigrees was conducted. Then, we examined possible association of bipolar disorder with DISC1 mRNA expression in human lymphoblasts. We also studied the correlation of several clinical features with the levels of DISC1 mRNA expression. RESULTS: Haplotype analysis identified one haplotype (HP1) that was overtransmitted to the BP phenotype (p = .01) and a second haplotype that was undertransmitted (HP2). There was a gender influence in the transmission distortion, with overtransmission of HP1 to affected females (p = .004). A significant decrease in DISC1 mRNA expression was observed in lymphoblasts from affected HP1 group compared to those from unaffected subjects with the HP2 (p = .006). Further, a higher number of manic symptoms correlated with lower levels of DISC1 expression (p = .008). CONCLUSIONS: These results suggest that decreased mRNA levels of DISC1 expression, associating with the risk haplotype, may be implicated in the pathophysiology of bipolar disorder.