The Role of Serotonergic Gene Methylation in Regulating Anxiety-Related Personality Traits in Chimpanzees

SIMPLE SUMMARY: Serotonin is a neurotransmitter known to regulate psychological health (depression, anxiety) and personality in humans. External factors such as early life stress or medication use can impact the serotonin system, for example, through epigenetic modification of the genes that code for its different components. While human studies are currently exploring the effects of serotonergic methylation, an example of epigenetic modification, primate studies are largely lacking. In this study, we investigated to what extent personality traits in captive chimpanzees are associated with methylation levels of two genes that play a major role in serotonin transmission: the gene coding for its receptor subtype 1A (HTR1A) and the gene coding for its transporter (SLC6A4). Using a methylation array identical to human studies, we show that methylation levels are associated with variation in four chimpanzee personality traits linked with a reduction in anxiety and aggression and increase in prosocial and explorative behavior. Different from human studies, early atypical social rearing conditions only had a minor impact on methylation. The results from this study highlight evolutionarily conserved methylation sites that can be targeted in future hypothesis-driven studies across species. ABSTRACT: While low serotonergic activity is often associated with psychological disorders such as depression, anxiety, mood, and personality disorders, variations in serotonin also contribute to normal personality differences. In this study, we investigated the role of blood DNA methylation levels at individual CpG sites of two key serotonergic genes (serotonin receptor gene 1A, HTR1A; serotonin transporter gene, SLC6A4) in predicting the personalities of captive chimpanzees. We found associations between methylation at 9/48 CpG sites with four personality dimensions: Dominance, Reactivity/Dependability, Agreeableness, and Openness. Directionality of effects were CpG location-dependent and confirmed a role of serotonergic methylation in reducing anxiety (Dominance) and aggression-related personality (Reactivity/Undependability) while simultaneously promoting prosocial (Agreeableness) and exploratory personalities (Openness). Although early-life adversity has been shown to impact serotonergic methylation patterns in other species, here, atypical early social rearing experiences only had a modest impact on CpG methylation levels in this chimpanzee sample. The precise environmental factors impacting serotonergic methylation in chimpanzees remain to be identified. Nevertheless, our study suggests a role in shaping natural variation in animal personalities. The results of this study offer a basis for future hypothesis-driven testing in additional populations and species to better understand the impact of ecology and evolution on complex behavioral traits.