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

ObjectiveTo 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 methods227 suicide attempters, 686 non-suicidal psychiatric patients, and 420 healthy controls from a homogeneous Spanish Caucasian population were genotyped using standard methods.ResultsThere were no differences in genotype frequencies between the three groups. The −1438A/G [χ2 (df) = 9.80 (2), uncorrected p = 0.007] and IL-1α −889C/T [χ2 (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 (86 bp)n [LRT (df) = 12.21 (4), p = 0.016] in relation to suicide attempt lethality.ConclusionThese 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.

Research highlights
► We examine the role of genes related to low serotonergic activity in suicidality.
► The HTR2A and IL-1α genes are associated with the impulsivity of the suicide attempt.
► High medical lethality of the attempt was associated with the SLC6A4 gene.
► Interaction between the APOE and ILRA genes is related to suicide attempt lethality.
► Impulsivity and lethality of the attempt may be influenced by serotonergic activity.