Interaction between 5-HTTLPR genotype and cognitive stress vulnerability on sleep quality: effects of sub-chronic tryptophan administration

Int J Neuropsychopharmacol. 2015 Feb 2;18(3):pyu057. doi: 10.1093/ijnp/pyu057.

Abstract

Background: Abundant evidence suggests that allelic variation in the serotonin transporter-linked polymorphic region (5-HTTLPR) influences susceptibility to stress and its affective consequences due to brain serotonergic vulnerability. Based on recent assumptions, the present study examined whether the 5-HTTLPR genotype may also interact with a vulnerability to chronic stress experience (conceptualized by trait neuroticism) in order to influence sleep quality and, additionally, whether this is influenced by brain serotonergic manipulations.

Methods: In a well-balanced experimental design, homozygous S-allele (n = 57) and L-allele (n = 54) genotypes with high and low chronic stress vulnerability (neuroticism) were first assessed for general past sleep quality during a month before onset of the experiment. Then subjects were assessed for sleep quality following 7 days of tryptophan (3.0g/day) or placebo intake.

Results: Although high neuroticism was significantly related to a higher frequency of stressful life events and daily hassles, it did not interact with the 5-HTTLPR genotype on general past sleep quality. However, as expected, a 7 day period of tryptophan administration was exclusively associated with better sleep quality scores in the S'/S' genotype with high trait neuroticism.

Conclusions: Current findings suggest that 5-HTTLPR does not directly interact with stress vulnerability in order to influence sleep quality. Instead, based on current and previous findings, it is suggested that the S'/S' 5-HTTLPR genotype promotes the risk for stress-related sleep disturbances because of an increased susceptibility to the depressogenic consequences of stress. Accordingly, by way of reducing depressive symptomatology, tryptophan augmentation may particularly improve sleep quality in stress-vulnerable individuals carrying the 5-HTTLPR S-allele.

Keywords: 5-HTTLPR; depression; sleep; stress; tryptophan.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Analysis of Variance
  • Antidepressive Agents, Second-Generation / administration & dosage*
  • Anxiety Disorders* / diet therapy
  • Anxiety Disorders* / genetics
  • Anxiety Disorders* / psychology
  • Double-Blind Method
  • Female
  • Genotype
  • Humans
  • Life Change Events*
  • Male
  • Neuroticism
  • Personality Inventory
  • Psychiatric Status Rating Scales
  • Serotonin Plasma Membrane Transport Proteins / genetics*
  • Sleep Wake Disorders / etiology*
  • Sleep Wake Disorders / genetics
  • Tryptophan / administration & dosage*
  • Young Adult

Substances

  • Antidepressive Agents, Second-Generation
  • Serotonin Plasma Membrane Transport Proteins
  • Tryptophan