Research article summary (published 28 Jul 2008):

Serotonin transporter genotype and depressive phenotype determination by discriminant analysis of glucose metabolism under acute tryptophan depletion.

Full Abstract

Acute tryptophan depletion (ATD) putatively results in a transient reduction in central serotonin transmission, and induces depressed mood in some un-medicated subjects with remitted major depressive disorder (MDD). The 5-HT transporter promoter region length polymorphism (5-HTTLPR) has been shown to influence behavioral and metabolic responses to ATD, as well as the risk for developing MDD within the context of stress. The current study investigates the relationships between 5-HTTLPR genotype, neurophysiologic response to ATD, and diagnostic phenotype (healthy control subjects versus MDD subjects differentiated by their depressive response to ATD) using (18)FDG-PET. Un-medicated subjects with remitted MDD and healthy controls were genotyped for the long (l) and short (s) alleles of the 5-HTTLPR polymorphism and categorized into one of three genotypes. On two separate occasions, subjects received either a placebo or an amino acid mixture designed to deplete plasma tryptophan, followed by (18)FDG-PET scanning. Depressive symptoms were rated to determine the diagnostic phenotype. Descriptive and predictive discriminant analyses were performed using brain regional metabolic data to classify according to phenotype and genotype. Overall, 79% of the cases were classified correctly by genotype, and 85% were classified correctly by phenotype. In a leave-one-out cross-validation, 72% of the subjects were classified correctly as carrying an s-allele, and 79% of the subjects were classified correctly by primary diagnosis. The robust nature of the classification results indicates that much of the variance in metabolic response to ATD is accounted for by genotypic and phenotypic category.

Author information

Author/s: Nugent, Allison C (AC); Neumeister, Alexander (A); Goldman, David (D); Herscovitch, Peter (P); Charney, Dennis S (DS); Drevets, Wayne C (WC);

Affiliation: Section on Neuroimaging in Mood and Anxiety Disorders, National Institute of Mental Health, NIH, Bethesda, MD 20892-0940, USA. nugenta(-atsign-)mail.nih.gov

Journal and publication information

Publication Type: Journal Article; Randomized Controlled Trial

Journal: NeuroImage (Neuroimage), published in United States. (Language: eng)

Reference: 2008-Dec; vol 43 (issue 4) : pp 764-74

Dates: Created 2008/11/05; Completed 2009/02/10; Revised 2009/03/04;

PMID: 18718871, status: MEDLINE (last retrieved date: 3/10/2009)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

Adult Brain - metabolism Depression - genetics; metabolism Discriminant Analysis Female Fluorodeoxyglucose F18 - diagnostic use; pharmacokinetics Genetic Predisposition to Disease - genetics Glucose

Humans Male Phenotype Placebo Effect Positron-Emission Tomography - methods Radiopharmaceuticals - diagnostic use; pharmacokinetics Serotonin Plasma Membrane Transport Proteins - genetics; metabolism Tryptophan - deficiency

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: Radiopharmaceuticals (0) ; Serotonin Plasma Membrane Transport Proteins (0) ; Glucose (50-99-7) ; Fluorodeoxyglucose F18 (63503-12-8) ; Tryptophan (73-22-3)

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