Differential effects of 5-HTTLPR genotypes on mood, memory, and attention bias following acute tryptophan depletion and stress exposure

Abstract

Rationale Polymorphisms of the serotonin transporter gene (5-HTTLPR) may be associated with increased vulnerability to acute tryptophan depletion (ATD) and depression vulnerability especially following stressful life events. Objective The aim of the present study was to investigate the effects of ATD in subjects with different 5-HTTLPR profiles before and after stress exposure on affective and cognitive-attentional changes. Materials and methods Eighteen subjects with homozygotic short alleles (S′/S′) and 17 subjects with homozygotic long alleles (L′/L′) of the 5-HTTLPR participated in a double-blind, placebo-controlled, crossover design to measure the effects of ATD on mood, memory, and attention before and after acute stress exposure. Results ATD lowered mood in all subjects independent of genotype. In S′/S′ genotypes, mild acute stress increased depressive mood and in L′/L′ genotypes increased feelings of vigor. Furthermore, S′/S′ genotypes differed from L′/L′ genotypes on measures of attention independent of treatment and memory following ATD. Conclusions Polymorphisms of the 5-HTTLPR differentially affect responses to mild stress and ATD, suggesting greater vulnerability of S′/S′ carriers to serotonergic manipulations and supporting increased depression vulnerability.

Effects of acute psychosocial stress exposure on endocrine and affective reactivity in college students differing in the 5-HTTLPR genotype and trait neuroticism

“…Four studies reported a main effect of the 5-HTTLPR genotype (Gotlib et al 2008;Dougherty et al 2010;Mueller et al 2010;Way and Taylor 2010), whereas four studies did not find a main effect of the same genotype (Alexander et al 2009;Firk and Markus 2009;Markus and Firk 2009;Wust et al 2009). These conflicting results might be explained by methodological differences between the studies, such as inconsistencies in the nature of the stress task, the use of different study populations, and discrepancies in the timing of salivary cortisol sampling.…”

Cognitive effects of genetic variation in monoamine neurotransmitter systems: A population‐based study of COMT , MAOA , and 5HTTLPR

“…We can therefore definitively say that there is no evidence for cognitive effects of 5HTTLPR on these measures of working memory, response inhibition, or IQ in healthy children. It remains plausible, however, that genetic effects on cognition are seen in circumstances in which the serotonergic status quo has been disrupted, for example, by stress, tryptophan depletion [Roiser et al, 2007; Firk and Markus, 2009[ or in neuropsychiatric disorders [Beevers et al, 2007; da Rocha et al, 2008[. Some apparently conflicting results may therefore have arisen because cognitive differences between genotypes appear exaggerated in circumstances of serotonergic perturbation, where normal mechanisms of compensation for genetic variation are disturbed.…”

“…MAOA genotype has been reported to significantly affect IQ among healthy Chinese women [Yu et al, 2005[ and children with autism [Yirmiya et al, 2002; Cohen et al, 2003[ but with conflicting directions of effect. Reports regarding cognitive effects of the 5HTTLPR polymorphism have been predominantly negative for standard neuropsychological measures such as IQ, response inhibition, and sustained attention [Fallgatter et al, 1999; Clark et al, 2005; Payton et al, 2005; Roiser et al, 2007; Strobel et al, 2007; da Rocha et al, 2008; Borg et al, 2009[, though there are now multiple reports of associations with risk-taking, decision-making, and attentional biases [Beevers et al, 2007; Homberg et al, 2008; da Rocha et al, 2008; Crisan et al, 2009; Firk and Markus, 2009; Fox et al, 2009; Roiser et al, 2009[.…”

Serotonin, genetic variability, behaviour, and psychiatric disorders - a review

“…A study performed on healthy women exposed to tryptophan depletion showed reduction in mood compared to controls, but this effect was shown to be moderated by genotype in the 5HTTLPR. A stress-inducing task caused a significant increase in depressive symptoms and reduced sense of vigour among carriers of the low-functioning variant of 5HTTLPR in response to tryptophan depletion, whereas the opposite effect was observed for carriers of the high-functioning variant (70). These results are in line with the observations that the low-functioning variant of 5HTTLPR has been associated with increased amygdala reactivity and reduced stress-coping (71).…”