Familial morbid risk for severe psychiatric disorders increases in bipolar patients with dosage of sert alleles 484 and Stin2.10

In the present study, specific familial morbidity risks (FMR) were calculated in relation to variability in the HTR2A gene (four polymorphisms analyzed), the HTR2C gene (one polymorphism), the COMT gene (two polymorphisms), and the SERT gene (two polymorphisms). The sample consisted of 88 patients diagnosed with bipolar affective disorder (DSM-III-R). Family history was determined on the basis of a structural personal interview (FH-RDC) with a mean of 2.22 healthy first degree relatives of each proband. FMR were calculated by the method of Ströngren using age of onset distributions derived from the study of Takei et al. [1992] to define period of risk. No differences were found in the distribution of FMR values according to allele or genotype variability in the HTR2A, HTR2C, and COMT genes. However, our results revealed a dose-response effect between number of 484 alleles (5-HTTLPR polymorphism, SERT gene) and Stin2.10 alleles (VNTR, SERT gene) and FMR for severe affective disorders (major depression and bipolar disorder). Thus, subjects without 484 alleles (homozygous for the 528 variant) had an FMR for severe affective disorders (SAD) of 2.9%; heterozygous (with one 484 allele) had an FMR for SAD of 8.1%; and 484 homozygous (carriers of two 484 alleles) had an FMR for SAD of 10.2% (Spearman's P < 0.01). The same trend was observed for the Stin2.10 allele (VNTR): FMR for SAD were 4.4% in noncarriers of allele STin2.10; 8.9% in heterozygous; and 15.4% in Stin2.10 homozygous (Spearman's P < 0.01). Our findings are in agreement with an involvement of the serotonin transporter gene in the origin of bipolar disorder, at least in the subgroup of patients with a clear familial prevalence of SAD.