Studies on serotonergic dysfunction in suicide

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We investigated the association of suicide with serotonin transporter promoter region (5HTT-LPR), dopamine receptor promoter region (DRD4), monoamine oxydase A promoter region (MAOA-uVNTR ) and catechol-O-methyltransferase (COMT) which could affect monoamine neurotransmission and might be related to temperament. Gene variants were determined using PCR-based techniques in 163 completed suicides and 169 controls. There were no statistical differences between completed suicides and controls in the genotypes and allelic distribution of 5HTT-LPR, MAOA-uVNTR and DRD4. We found that the genotype distribution of COMT between male suicide completers and malecontrols was significantly different. In addition, the G allele, high-activity allele showed a tendency to occur less frequently in male suicide completers. These results indicate that in male the high COMT activity could play an inhibitory role in suicide. We also investigated possible genetic interactions among these four polymorphisims. Significant interactions were observed in 5HTT-LPR x MAOA-uVNTR and 5HTT-LPR x COMT between male suicide completers and male controls. Further studies are needed to clarify the epistatic effects of these genes.