title: Association between serotonin transporter gene promoter polymorphism (5HTTLPR) and behavioral responses to tryptophan depletion in healthy women with and without family history of depression.
abstract: 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.
authors.affiliation: National Institutes of Health, NIMH, Mood and Anxiety Disorders Program, Bethesda, MD 20892-2670. neumeisa@intra.nimh.nih.gov
authors.forename: Alexander
authors.initials: A
authors.lastname: Neumeister
authors.forename: Anastasios
authors.initials: A
authors.lastname: Konstantinidis
authors.forename: Juergen
authors.initials: J
authors.lastname: Stastny
authors.forename: Markus J
authors.initials: MJ
authors.lastname: Schwarz
authors.forename: Oliver
authors.initials: O
authors.lastname: Vitouch
authors.forename: Matthaus
authors.initials: M
authors.lastname: Willeit
authors.forename: Nicole
authors.initials: N
authors.lastname: Praschak-Rieder
authors.forename: Johanna
authors.initials: J
authors.lastname: Zach
authors.forename: Martina
authors.initials: M
authors.lastname: de Zwaan
authors.forename: Brigitta
authors.initials: B
authors.lastname: Bondy
authors.forename: Manfred
authors.initials: M
authors.lastname: Ackenheil
authors.forename: Siegfried
authors.initials: S
authors.lastname: Kasper
mesh_terms: D000328:Adult; D002352:Carrier Proteins / Q000235:genetics; D003866:Depressive Disorder / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology*; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D010919:Placebos; D011110:Polymorphism, Genetic / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D012307:Risk Factors; D012701:Serotonin / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D050486:Serotonin Plasma Membrane Transport Proteins; D014364:Tryptophan / Q000097:blood / Q000172:deficiency* / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D010919:Placebos; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D014364:Tryptophan