Association between serotonin transporter gene promoter polymorphism (5HTTLPR) and behavioral responses to tryptophan depletion in healthy women with and without family history of depression.

نویسندگان

  • Alexander Neumeister
  • Anastasios Konstantinidis
  • Juergen Stastny
  • Markus J Schwarz
  • Oliver Vitouch
  • Matthaus Willeit
  • Nicole Praschak-Rieder
  • Johanna Zach
  • Martina de Zwaan
  • Brigitta Bondy
  • Manfred Ackenheil
  • Siegfried Kasper
چکیده

BACKGROUND Evidence suggests that serotonin transporter gene promoter polymorphism (5HTTLPR)-dependent low transcriptional activity of the human serotonin transporter gene may be a genetic susceptibility factor for depression. We studied the behavioral responses to tryptophan depletion (TD) in healthy women with and without a first-degree family history of depression and examined the relationship to 5HTTLPR alleles. METHODS Twenty-four healthy women with a negative family history of depression and 21 women with a positive family history of depression were genotyped for the polymorphism of the 5HTTLPR and then entered a double-blind, placebo-controlled, randomized crossover TD study. The effects of these interventions were assessed with measures of depression and plasma tryptophan levels. RESULTS The TD induced a robust decrease of plasma tryptophan levels in all women irrespective of family history of depression or 5HTTLPR genotypes. The s/s genotype of the 5HTTLPR was associated with an increased risk of developing depressive symptoms during TD irrespective of family history. In contrast, individuals with the l/l genotype did not develop depressive symptoms, irrespective of family history. Finally, s/l subjects without family history showed a mood response that was intermediate between the s/s and l/l subjects, while s/l subjects with a family history of depression showed the same depressiogenic effect of TD as seen in the s/s subjects. CONCLUSIONS The results of the present study suggest that the s-allele of the 5HTTLPR and a positive family history of depression are additive risk factors for the development of depression during TD.

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عنوان ژورنال:
  • Archives of general psychiatry

دوره 59 7  شماره 

صفحات  -

تاریخ انتشار 2002