5-HTTLPR moderates effects of current life events on neuroticism: Differential susceptibility to environmental influences

Abstract

Research chronicling links between a polymorphism in the serotonin transporter gene (5-HTTLPR) and neuroticism has yielded inconsistent results. One possible explanation for this inconsistency is that any gene-phenotype association is obscured by a gene-X-environment (GXE) interaction. We studied a healthy non-clinical sample (N = 118) to determine whether the 5-HTTLPR interacts with current life events in predicting neuroticism. The differentialsusceptibility hypothesis led to the prediction of such an interaction, reflecting the fact that individuals with short alleles would be affected more by both negative and positive life events than those homozygous for long alleles. Participants completed questionnaires concerning recent life events and neuroticism. The 5-HTTLPR was genotyped using a standard protocol with DNA extracted from oral fluid. For those homozygous for the short allele, more negative life events proved related to greater neuroticism, whereas more positive life events proved related to less neuroticism. No such association emerged in the case of those homozygous for the long allele. Whereas neuroticism is likely to be an especially stable trait in individuals homozygous for the long allele, this may be less so the case for those carrying short alleles.

Genetic modulation of the serotonergic pathway: influence on weight reduction and weight maintenance

“…Both polymorphisms have also been associated with other personality traits and disorders, such as impulsiveness and impaired self-control, both of which are known to lead to elevated body weight and obesity (Terracciano et al 2009). This behavior may also be derive from biochemical alterations in areas of the brain responsible for emotional control (Lung et al 2011;Sookoian et al 2008;Cervilla et al 2006;Zalsman et al 2006;Pluess et al 2010;Fortier et al 2010). Subjects carrying the low activity-related 3R genotype of the MAOA uVNTR polymorphism have been reported to have increased aggressive behavior.…”

“…5-HTTLPR is a 44-bp insertion/deletion polymorphism leading to either a short (S) or long (L) variant (Lesch et al 1993). It has been demonstrated that the S allele is associated with a 40 % decrease in transcriptional activity in vitro Lesch et al 1996;Hranilovic et al 2004) and is associated with anxiety, affective disorder, diabetes and obesity in both human and animal studies (Sookoian et al 2007; Lesch et al 1996;Collier et al 1996;Pluess et al 2010). Furthermore, this polymorphism has also been shown to be associated with nutritional impairment in female patients suffering from bulimia nervosa (Monteleone et al 2006).…”

“…Studies have shown that the low-activity alleles are related to obesity and psychiatric disorders and may therefore influence the ability to reduce and maintain weight reduction in people who are prone to develop obesity (Need et al 2006;York et al 2004;Beach et al 2010). The association of 5R allele with respect to obesity and weight regulation remains unclear (Pluess et al 2010;Collier et al 1996).…”

A Possible Solution to the Etiological Paradox that Ties Anti-Social Personality Disorder to Major Depression

“…That said, it is important to go beyond the naive premise that the increase in vulnerability to major depression represented by the presence of copies of the polymorphic short variation of the SLC6A4 represents a direct effect of the serotonergic hypofunction. Current views of the nature-nurture structure of depression suggest that it is much more appropriately seem as a complex byproduct of an intensification of the vulnerability to a wide range of deleterious personality manifestations, which can be more specifically defined under the concept of neuroticism ( [33,34]; that is, of a personality style linked to negative emotional states and acute conflictive interactions.…”

Variants at serotonin transporter and 2A receptor genes predict cooperative behavior differentially according to presence of punishment

“…A length polymorphism (5-HTTLPR) in the promoter region of the serotonin transporter gene, SLC6A4 [solute carrier family 6 (neurotransmitter transporter, serotonin), member 4, also referred to as 5-HTT], predicts increased observational fear conditioning (9) and amygdala activation in the presence of threatening social cues (10). This polymorphism, as well as a polymorphism in the promoter region of the serotonin 2A receptor gene, HTR2A [5-hydroxytryptamine (serotonin) receptor 2A, G protein-coupled, also referred to as 5-HT 2A ], is also associated with the personality dimension of neuroticism (11,12), increased risk for depression and other psychiatric disorders (13,14), and increased cortisol response to a psychosocial stressor (12,15). Intriguingly, a recent assessment of global variation at SLC6A4 and HTR2A suggests unusual evolutionary histories at these loci in humans (16).…”