Role of serotonergic-related systems in suicidal behavior: Data from a case-control association study

Objective: To investigate whether functional polymorphisms directly (HTR2A and SLC6A4 genes) or indirectly (IL-1 gene complex, APOE and ACE genes) related with serotonergic neurotransmission were associated with suicidal behavior. Subjects and methods: 227 suicide attempters, 686 non-suicidal psychiatric patients, and 420 healthy controls from a homogeneous Spanish Caucasian population were genotyped using standard methods. Results: There were no differences in genotype frequencies between the three groups. The -1438A/G [- ² (df)=9.80 (2), uncorrected p=0.007] and IL-1- -889C/T [- ² (df)=8.76 (2), uncorrected p=0.013] genotype frequencies between impulsive and planned suicide attempts trended toward being different (not significant after Bonferroni correction). Suicide attempts were more often impulsive in the presence of -1438G/G or IL-1α -889C/T or C/C genotypes. There was interaction between the polymorphism 5-HTTLPR and age [LRT (df)=6.84 (2), p=0.033] and between the polymorphisms APOE and IL-1RA (86bp) _n [LRT (df)=12.21 (4), p=0.016] in relation to suicide attempt lethality. Conclusion: These findings further evidence the complexity of the association between genetics and suicidal behavior, the need to study homogenous forms of the behavior and the relevance of impulsive and aggressive traits as endophenotypes for suicidal behavior.