Abstract
The serotonin system is thought to play a role in the aetiology of callous-unemotional (CU) traits in children. Previous research identified a functional single nucleotide polymorphism (SNP) from the promoter region of the serotonin 1B receptor gene as being associated with CU traits in boys with antisocial behaviour problems. This research tested the hypothesis that CU traits are associated with reduced methylation of the promoter region of the serotonin 1B receptor gene due to the influence of methylation on gene expression. Participants (N = 117) were boys with antisocial behaviour problems aged 3-16 years referred to University of New South Wales Child Behaviour Research Clinics. Participants volunteered a saliva sample from which the genotype of a SNP from the promoter region of the serotonin 1B receptor gene and the methylation levels of 30 CpG sites from 3 CpG regions surrounding the location of this polymorphism were assayed. Lower levels of serotonin 1B receptor gene methylation were associated with higher levels of CU traits. This relationship, however, was found to be moderated by genotype and carried exclusively by two CpG sites for which levels of methylation were negatively associated with overall methylation levels in this region of the gene. Results provide support to the emerging literature that argues for a genetically-driven system-wide alteration in serotonin function in the aetiology of CU traits. Furthermore, the results suggest that there may be two pathways to CU traits that involve methylation of the serotonin 1B receptor gene; one that is driven by a genotypic risk and another that is associated with risk for generally increased levels of methylation. Future research that aims to replicate and further investigate these results is required.
Highlights
Psychopathy is commonly defined as comprising two factors
Before assessing the relationship between HTR1B methylation and CU traits, we first checked if the previously found association between genotypes of single nucleotide polymorphism (SNP) rs11568817 and CU traits was conserved in this sample which overlapped with the original sample in which this relationship was found
To test whether methylation of HTR1B was a significant predictor of CU traits, an analysis of variance was conducted with CU traits as the dependent variable, Attention Deficit Hyperactivity Disorder (ADHD) severity included as a covariate, and genotype, HTR1B methylation and an HTR1B methylation by genotype interaction variable entered as independent predictors
Summary
Psychopathy is commonly defined as comprising two factors. Factor one concerns features of personality including a lack of empathy and a cold, manipulative interpersonal style. The results from previous research [12] would suggest that increased expression of HTR1B that is associated with the minor allele of rs11568817 could be a causal factor in the aetiology of callous-unemotional traits. This is in opposition to previous research to suggest that decreased expression of HTR1B is associated with increased aggression and impulsivity—both of which are behavioural features of psychopathy. Psychopathy comprises two factors; the first of which concerns features of personality and interpersonal style (CU traits) and the second describes behaviours such as impulsivity and antisocial acts. As promoter methylation generally diminishes gene expression [25], this hypothesis would equate to lower levels of HTR1B methylation being associated with higher levels of CU traits
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