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

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.