TPH and suicidal behavior: a study in suicide completers

An association between the gene that codes for tryptophan hydroxylase (TPH) -the rate-limiting enzyme in the synthesis of serotonin-and suicidal behavi or has been investigated with some detail in samples of living subjects who attempted suicide. In this study, we investigated TPH and suicide completi on, the most severe form of suicidal behavior. A relatively large sample of suicide completers (n = 101) was genotyped at three TPH loci (two polymorp hisms in the promoter region, A-6526G and G-5806T, and one in intron 7, A21 8C) and compared to psychiatrically normal living controls (n = 129). Altho ugh no significant differences were found between groups for genetic variat ion at single loci, haplotype analysis revealed that one haplotype (6-6526G -5806T 218C) was significantly more frequent among suicide cases than in n ormal controls (chi (2) = 11.30, df = 2, P = 0.0008; OR = 2.0 CI: 1.30-3.6) . Further analyses suggested that this haplotype is particularly more frequ ent among subjects who committed suicide using violent methods. Similar res ults were observed in recent haplotype analyses in suicide attempters, whic h found that the equivalent of haplotype -6526G -5806T 218C was more freque nt in impulsive attempters (Rotondo et al, Mol Psychiatry 1999; 4: 360-368) . Our results replicate in suicide completers previous data observed in sui cide attempters. These and other results continue to point to the substanti al role that the gene that codes for TPH may play in the neurobiology of su icidal behavior.