The association of specific polymorphisms in the serotonergic system with aggressive, impulsive and suicidal behaviour

[摘要] English: Suicidal behaviour and the consequences thereof are a major global issue and need to be researched in order to promote a better understanding of this maladaptive behaviour. However, understanding the aetiology of suicidal behaviour is important, but difficult, as it is multifactorial and complex. Although there is a growing body of research pertaining to suicidal behaviour, there is a lack of research on the genetic contribution towards an endophenotype for suicidal behaviour in South Africa.Due to the complex nature of suicidal behaviour, it was suggested that the use of an endophenotype would contribute to the possible intervention in this maladaptive behaviour. It has been suggested that some people were genetically predisposed to suicidal behaviour, and more importantly, the tendency to act on suicidal thoughts, and that this genetic vulnerability, underlain by the serotonergic system, might possibly be linked to inherited personality traits such as impulsiveness and aggression. Impulsiveness and aggression have therefore been suggested as possible endophenotypes of suicidal behaviour. Variation in the chosen genetic markers of the serotonergic system may modify the endophenotype of impulsivity and aggression, and in turn, influence the phenotype, suicidal behaviour.The aim of the research was to determine if impulsivity and aggression can act as a potential endophenotype for suicidal behaviour, and therefore, firstly, to determine whether aggression and impulsivity, as personal variables, are associated with suicidal behaviour, and secondly, to investigate the possible association of candidate polymorphisms (HTR1A rs6295, HTR1B rs6296, HTR2A rs6311 and SLC6A4 HTTLPR) of the serotonergic system to impulsivity, aggression and attempted suicide. Genes can thus be studied as a contributing factor and not the only factor that influence suicidal behaviour.A cohort of 25 research participants with a previous suicide attempt were recruited and matched to 25 healthy controls. All participants completed the BIS-11, RPQ, and BPAQ as quantifiable measures. Participants were also genotyped for HTR1A (rs6295), HTR1B (rs6296), HTR2A (rs6311) and SLC6A4 HTTLPR. The results for this study indicated that the suicide attempters scored significantly higher than the control group in all the questionnaires for aggression and impulsivity. This led to the conclusion that impulsivity and aggression is positively associated with suicidal behaviour. However, with regards to the molecular genetic analysis, only the HTR2A gene variant, rs6311, showed a significant difference between the suicide attempters and controls, with the A allele being more frequent in the suicide attempters (p = 0.0066). The suicide attempters were the only group that presented with the X allele for SLC6A4 HTTLPR and further studies are needed to replicate this finding. Interesting trends were observed regarding the other genetic variants, but no significant results were obtained. For HTR1A rs6295, the homozygous GG genotype conferred the highest risk for impulsive and aggressive behaviours in suicide attempters. The G allele for HTR2A rs6311, together with the S allele for HTTLPR, also seemed to increase impulsive and aggressive traits. In the case of HTTLPR, this finding was valid irrespective of the presence of suicidal behaviour. Overall, the results provide support for the use of behavioural measures of impulsivity and aggression as an endophenotype for suicidal behaviour. Some support was also found for the use of impulsive aggression as a single construct with regards to suicidal behaviour.The combination of psychology and genetic results are among the first ever reported for suicide attempters in South Africa. Despite the limited size of the study, perhaps due to the sensitivity of the construct under investigation, this study nevertheless adds significant value to the body of research pertaining to the under-studied topic of suicidal behaviour in South Africa. This study can improve phenotyping that will ultimately benefit South-African individuals.

[发布机构] University of the Free State