Association of serotonin system-related genes with homicidal behavior and criminal aggression in a prison population of Pakistani Origin

The serotonin transporter (SLC6A4), 5-HT2A (HTR2A) and 5-HT2B (HTR2B) recepter genes, express proteins that are important regulators of serotonin reuptake and signaling, and thereby may contribute to the pathogenesis of aggressive criminal behavior. 370 sentenced murderers in Pakistani prisons and 359 men without any history of violence or criminal delinquency were genotyped for six candidate polymorphisms in SLC6A4, HTR2A and HTR2B genes. An association of higher expressing L/L and L-A/L-A variants of the 5-HTTLPR polymorphism was observed with homicidal behavior (bi-allelic: OR=1.29, p=0.016, tri-allelic: OR=1.32, p=0.015) and in the murderer group only with response to verbal abuse (OR=2.11, p=0.015), but not with other measures of self-reported aggression. L/L and L-A/L-A genotypes of the 5-HTTLPR polymorphism were associated with higher aggression scores on STAX1 scale of aggression compared to lower expressing genotypes (S/S, S/L-G, L-G/L-G) in prison inmates. No associations were apparent for other serotonergic gene polymorphisms analyzed. Using the Braineac and GTEx databases, we demonstrated significant eQTL based functional effects for rs25531 in HTTLPR and other serotonergic polymorphisms analyzed in different brain regions and peripheral tissues. In conclusion, these findings implicate SLC6A4* HTTLPR as a major genetic determinant associated with criminal aggression. Future studies are needed to replicate this finding and establish the biologic intermediate phenotypes mediating this relationship.

Automated summary

The study identified an association between the serotonin transporter gene SLC6A4 HTTLPR polymorphism and criminal aggression in Pakistani prisoners, with the L/L and L-A/L-A genotypes being linked to higher aggression scores. Functional effects were demonstrated for the rs25531 polymorphism in HTTLPR and other serotonergic polymorphisms in different brain regions and peripheral tissues. Further research is needed to replicate and understand the biological mechanisms underlying this relationship.