Association between serotonin transporter gene promoter polymorphism (5HTTLPR) and behavioral responses to tryptophan depletion in healthy women with and without family history of depression.
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.
Neumeister
Alexander
A
National Institutes of Health, NIMH, Mood and Anxiety Disorders Program, Bethesda, MD 20892-2670. neumeisa@intra.nimh.nih.gov
Konstantinidis
Anastasios
A
Stastny
Juergen
J
Schwarz
Markus J
MJ
Vitouch
Oliver
O
Willeit
Matthaus
M
Praschak-Rieder
Nicole
N
Zach
Johanna
J
de Zwaan
Martina
M
Bondy
Brigitta
B
Ackenheil
Manfred
M
Kasper
Siegfried
S
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*
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