MK4MDD

Genetic/Epigenetic Locus Search Cross Data Search

Study Report

Reference

Citation	Neumeister, 2006 PubMed
Full Info	Neumeister, A., Hu, X.Z., Luckenbaugh, D.A., Schwarz, M., Nugent, A.C., Bonne, O., Herscovitch, P., Goldman, D., Drevets, W.C. and Charney, D.S. (2006) Differential effects of 5-HTTLPR genotypes on the behavioral and neural responses to tryptophan depletion in patients with major depression and controls. Arch Gen Psychiatry, 63, 978-986.

Study

Hypothesis or Background	Tryptophan depletion (TD) is a model used to study the contribution of reduced serotonin transmission to the pathogenesis of major depressive disorder (MDD). Recent studies have not sufficiently addressed the relative contribution of a functional-length triallelic polymorphism in the promoter of the serotonin transporter, 5-HTTLPR, to the behavioral and neural responses to TD in individuals with remitted MDD (rMDD) and controls. OBJECTIVE: To determine the role of 5-HTTLPR on the behavioral and neural responses to TD in medication-free patients with rMDD and individually matched controls.
Sample Information	Twenty-seven medication-free patients with rMDD (18 women and 9 men) and 26 controls (17 women and 9 men).
Method Detail	Participants were stratified according to diagnosis and 5-HTTLPR genotypes and underwent TD on one test day and sham depletion on the other test day in a prospective, double-blind, randomized order. Tryptophan depletion was induced by administration of capsules containing an amino acid mixture without tryptophan. Sham depletion used identical capsules containing lactose. Fludeoxyglucose F 18 positron emission tomography was performed 6 hours after TD. Magnetic resonance images were obtained for each participant. MAIN OUTCOME MEASURES: Quantitative positron emission tomography of regional cerebral metabolic rates for glucose and measures of depression using the Hamilton Depression Rating Scale.
Method Keywords	positron emission tomography (PET); dose administration; genotyping
Result	Behavioral responses to TD are affected by 5-HTTLPR in patients with rMDD and controls. A direct effect of 5-HTTLPR on the regulation of regional cerebral metabolic rates for glucose was identified in patients with rMDD for the amygdala, hippocampus, and subgenual anterior cingulate cortex.
Conclusions	Variations in 5-HTTLPR modulate the sensitivity of patients with rMDD and controls to the behavioral effects of TD. In patients with rMDD, variations in triallelic 5-HTTLPR have a direct effect on regulation of regional cerebral metabolic rates for glucose in a corticolimbic circuit that has been implicated in rMDD.

Relationships reported by Neumeister, 2006

Component A Approved Name (Name in Paper)	Component A Type	Component B Approved Name (Name in Paper)	Component B Type	Statistical Result	Relationship Description	Result Category (Positive/Negative))
MDD	syndrome	Hippocampus (hippocampus)	brain morphology and function		A direct effect of 5-HTTLPR on the regulation of regional cerebral metabolic rates for glucose was identified in patients with rMDD for the amygdala, hippocampus, and subgenual anterior cingulate cortex.	Positive
MDD	syndrome	subgenual anterior cingulate (subgenual anterior cingulate cortex)	brain morphology and function		A direct effect of 5-HTTLPR on the regulation of regional cerebral metabolic rates for glucose was identified in patients with rMDD for the amygdala, hippocampus, and subgenual anterior cingulate cortex.	Positive
MDD	syndrome	Amygdala (amygdala)	brain morphology and function		A direct effect of 5-HTTLPR on the regulation of regional cerebral metabolic rates for glucose was identified in patients with rMDD for the amygdala, hippocampus, and subgenual anterior cingulate cortex.	Positive
MDD	syndrome	SLC6A4 (5-HTTLPR)	gene		A direct effect of 5-HTTLPR on the regulation of regional cerebral metabolic rates for glucose was identified in patients with rMDD for the amygdala, hippocampus, and subgenual anterior cingulate cortex.	Positive
subgenual anterior cingulate (subgenual anterior cingulate cortex)	brain morphology and function	SLC6A4 (5-HTTLPR)	gene		A direct effect of 5-HTTLPR on the regulation of regional cerebral metabolic rates for glucose was identified in patients with rMDD for the amygdala, hippocampus, and subgenual anterior cingulate cortex.	Positive
Hippocampus (hippocampus)	brain morphology and function	SLC6A4 (5-HTTLPR)	gene		A direct effect of 5-HTTLPR on the regulation of regional cerebral metabolic rates for glucose was identified in patients with rMDD for the amygdala, hippocampus, and subgenual anterior cingulate cortex.	Positive
Amygdala (amygdala)	brain morphology and function	SLC6A4 (5-HTTLPR)	gene		A direct effect of 5-HTTLPR on the regulation of regional cerebral metabolic rates for glucose was identified in patients with rMDD for the amygdala, hippocampus, and subgenual anterior cingulate cortex.	Positive