Differential effects of 5-HTTLPR genotypes on inhibition of negative emotional information following acute stress exposure and Tryptophan challenge

Previous data suggest that a polymorphism at the serotonin (5-HT) transporter gene (5-HTTLPR) may influence stress resilience and stress-related depression symptoms due to interactions between brain 5-HT dysfunction and stress exposure. Although attentional bias for emotional information has been reliably observed in depression, the interaction between 5-HT transporter-linked promoter region (5-HTTLPR), brain 5-HT vulnerability, and acute stress on affective information processing has not yet been investigated. This study examines the effects of tryptophan (TRP) augmentation (indicating 5-HT manipulation) on inhibition of negative emotional information under stress in mainly female S'/S'-vs L'/L'-allele carriers. A total of 15 female homozygotic short-allele 5-HTTLPR (S'/S' S/S, S/L(G), L(G)/L(G)) and 13 female homozygotic long-allele 5-HTTLPR (L'/L' L(A)/L(A)) subjects were tested for mood and inhibition of emotional information in a double-blind, placebo-controlled design before and after stress exposure following TRP manipulation. Stress exposure significantly impaired inhibition of negative affective information only in S'/S' carriers, whereas L'/L' carriers even showed increased inhibition of negative information. The S'/S' allele 5-HTTLPR genotype increases cognitive-attentional bias for negative emotional information under acute stress. As this bias is an important component of depression, this may be a mediating mechanism making S'/S'-allele carriers more vulnerability for stress-induced depression symptoms. Moreover, current data suggest that L'/L'-allele genotypes are more resilient, even increasing cognitive emotional (inhibitory) control after stress. Neuropsychopharmacology (2011) 36, 819-826; doi:10.1038/npp.2010.221; published online 8 December 2010Previous data suggest that a polymorphism at the serotonin (5-HT) transporter gene (5-HTTLPR) may influence stress resilience and stress-related depression symptoms due to interactions between brain 5-HT dysfunction and stress exposure. Although attentional bias for emotional information has been reliably observed in depression, the interaction between 5-HT transporter-linked promoter region (5-HTTLPR), brain 5-HT vulnerability, and acute stress on affective information processing has not yet been investigated. This study examines the effects of tryptophan (TRP) augmentation (indicating 5-HT manipulation) on inhibition of negative emotional information under stress in mainly female S'/S'-vs L'/L'-allele carriers. A total of 15 female homozygotic short-allele 5-HTTLPR (S'/S' S/S, S/L(G), L(G)/L(G)) and 13 female homozygotic long-allele 5-HTTLPR (L'/L' L(A)/L(A)) subjects were tested for mood and inhibition of emotional information in a double-blind, placebo-controlled design before and after stress exposure following TRP manipulation. Stress exposure significantly impaired inhibition of negative affective information only in S'/S' carriers, whereas L'/L' carriers even showed increased inhibition of negative information. The S'/S' allele 5-HTTLPR genotype increases cognitive-attentional bias for negative emotional information under acute stress. As this bias is an important component of depression, this may be a mediating mechanism making S'/S'-allele carriers more vulnerability for stress-induced depression symptoms. Moreover, current data suggest that L'/L'-allele genotypes are more resilient, even increasing cognitive emotional (inhibitory) control after stress. Neuropsychopharmacology (2011) 36, 819-826; doi:10.1038/npp.2010.221; published online 8 December 2010A