Neumeister,A.
Konstantinidis,A.
Stastny,J.
Schwarz,M.J.
Vitouch,O.
Willeit,M.
Praschak-Rieder,N.
Zach,J.
de Zwaan,M.
Bondy,B.
Ackenheil,M.
Kasper,S.

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-con trolled, 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 intermedia e 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.

Neumeister, A., Konstantinidis, A., Stastny, J., Schwarz, M. J., Vitouch, O., Willeit, M., Praschak-Rieder, N., Zach, J., Zwaan, M. d., Bondy, B., Ackenheil, M., & Kasper, S. (2002). Association between serotonin transporter gene promoter polymorphism (5HTTLPR) and behavioral responses to tryptophan depletion in healthy women with and without family history of depression. Archives of General Psychiatry, 59, 613-620.

Publication year	2002
Document type:	Article
Publication status:	Published
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Keywords:	anxiety-related traitsdopamine-d4 receptorface-to-facefunctional polymorphismintravenous tryptophanmajor affective-disorderneutral amino-acidsonset alzheimers-diseaseplasma tryptophantridimensional personality questionnaire