Polymorphisms in dopaminergic system genes; association with criminal behavior and self-reported aggression in violent prison inmates from Pakistan

Abstract

Genetic factors contribute to antisocial and criminal behavior. Dopamine transporter DAT-1 (SLC6A3) and DRD2 gene for the dopamine-2 receptor are dopaminergic system genes that regulate dopamine reuptake and signaling, and may be part of the pathogenesis of psychiatric disorders including antisocial behaviors and traits. No previous studies have analyzed DAT-1 and DRD2 polymorphisms in convicted murderers, particularly from Indian subcontinent. In this study we investigated the association of 40 bp VNTR polymorphism of DAT-1 and Taq1 variant of DRD2 gene (rs1800479) with criminal behavior and self-reported aggression in 729 subjects, including 370 men in Pakistani prisons convicted of first degree murder(s) and 359 control men without any history of violence or criminal tendency. The 9R allele of DAT-1 VNTR polymorphism was more prevalent in convicted murderers compared with control samples, for either one or two risk alleles (OR = 1.49 and 3.99 respectively, P = 0.003). This potential association of DAT-1 9R allele polymorphism with murderer phenotype was confirmed assuming different genetic models of inheritance. However, no genetic association was found for DRD2 Taq1 polymorphism. In addition, a combined haplotype (9R-A2) of DAT-1 and DRD2 genes was associated with this murderer phenotype. Further, 9R allele of DAT-1 was also associated with response to verbal abuse and parental marital complications, but not with other measures pertinent to self-reported aggression. These results suggest that 9R allele, which may influence levels of intra-synaptic dopamine in the brain, may contribute to criminal tendency in this sample of violent murderers of Pakistani origin. Future studies are needed to replicate this finding in other populations of murderers and see if this finding extends to other forms of violence and lesser degrees of aggression.

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

“…The basic characteristics of the study sample set (including demographic details and parameters pertinent to measures of self-reported aggression) are as described previously 47 and summarized in Supplementary Table S1 . Only male prison inmates were included in this study.…”

“…Ethical approvals, consent and study subjects. The details of consent, subject recruitment and study sample set have been described previously 47 . Briefly, the present study was conducted after obtaining permission and approval from higher police authorities and Institutional Ethics Committee at University of the Punjab, Lahore and all experiments were performed in accordance with latest version of Declaration of Helsinki guidelines.…”

Differential expression of 10 genes in the hypothalamus of two generations of rats selected for a reaction to humans

“…The expression of the Drd2 gene (dopamine D2 receptor) is associated with aggressive behavior, as uncovered in studies on rats (VanErp, Miczek, 2000) and on humans (Qadeer et al, 2017). Given that dopamine (an endogenous ligand [agonist] of D2 receptor), just as serotonin, is involved in the regulation of aggressive behavior, a change in Drd2 expression leads to various pathologies, for example, to increased aggressiveness (VanErp, Miczek, 2000;Miczek et al, 2002;Kim V. et al, 2015;Golden et al, 2019).…”

The Basis For A Neurobiological-Associative Model of Personality and Group Cohesion: The Evolutionary And System Biological Origins Of Social Exclusion, Hierarchy, and Structure

“…Although dopamine receptor binding relative to transporter expression has not yet been investigated for dopamine, the hypothesis of lower transporter activity relating to lower receptor sensitivity is suggested based on evidence from the serotonin system, as evidenced for the 5-HT1A (David et al, 2005) and 5-HT2A (Rioux et al, 1999) serotonin receptors relative to SERT expression. Further, the contribution of dopamine to interpersonal aggression is similar to that of serotonin, with an increased prevalence of low DAT1 (Qadeer et al, 2017) and SERT (Toshchakova et al, 2018) expression in violent criminals relative to the general population and other criminals.…”