Document Detail


Norepinephrine and serotonin transporter genes: impact on treatment response in depression.
MedLine Citation:
PMID:  20588071     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND/AIMS: The norepinephrine transporter (NET) and serotonin transporter (5-HTT) genes constitute promising candidate genes in major depression. Seven polymorphisms in the promoter, intronic and exonic region of the NET gene, as well as serotonin-transporter-linked promoter region (5-HTTLPR) and 5-HTT rs25531 polymorphisms were analyzed with respect to antidepressant treatment response with particular attention to gender effects and subtypes of melancholic or anxious depression. METHODS: 252 unrelated Caucasian patients (f = 142; m = 110) with major depression were genotyped for NET and 5-HTT polymorphisms. Genotype effects on Hamilton Depression Rating Scale score changes over 6 weeks of antidepressant treatment were analyzed using analysis of covariance with repeated measures. RESULTS: There was no effect of any of the 7 investigated NET, or the two 5-HTT polymorphisms, on the overall treatment response. An additional -/CT insertion/deletion (ins/del) polymorphism (rs58532686), however, was significantly associated with melancholic depression, with a better response in 12 patients carrying the deletion. Stratification for anxious versus nonanxious depression revealed a significantly detrimental effect of the less active 5-HTTLPR S allele (p = 0.007) and 5-HTTLPR/5-HTT rs25531 haplotypes on treatment response in patients with anxious depression. CONCLUSION: The present findings do not support a major impact of the NET and 5-HTT genes on antidepressant treatment response in major depression per se. However, there might be an impact of a -/CT ins/del polymorphism in the enhancer domain of the NET gene on treatment response in melancholic depression, which remains to be functionally investigated in future studies. The observed significant influence of the 5-HTT gene variation on antidepressant treatment in anxious depression points to anxious depression as a potential diagnostic entity of its own, requiring specific diagnostic and therapeutic attention.
Authors:
Anna Baffa; Christa Hohoff; Bernhard T Baune; Carsten Müller-Tidow; Nicola Tidow; Christine Freitag; Peter Zwanzger; Jürgen Deckert; Volker Arolt; Katharina Domschke
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-06-30
Journal Detail:
Title:  Neuropsychobiology     Volume:  62     ISSN:  1423-0224     ISO Abbreviation:  Neuropsychobiology     Publication Date:  2010  
Date Detail:
Created Date:  2010-07-19     Completed Date:  2010-10-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7512895     Medline TA:  Neuropsychobiology     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  121-31     Citation Subset:  IM    
Copyright Information:
Copyright 2010 S. Karger AG, Basel.
Affiliation:
Department of Psychiatry, University of Münster, Münster, Germany.
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MeSH Terms
Descriptor/Qualifier:
Adult
Analysis of Variance
Antidepressive Agents / therapeutic use
DNA Mutational Analysis / methods
Depressive Disorder, Major / drug therapy,  genetics*
European Continental Ancestry Group
Female
Follow-Up Studies
Genotype
Humans
Male
Middle Aged
Norepinephrine Plasma Membrane Transport Proteins / genetics*
Pharmacogenetics*
Polymorphism, Genetic / genetics*
Psychiatric Status Rating Scales
Serotonin Plasma Membrane Transport Proteins / genetics*
Treatment Outcome
Chemical
Reg. No./Substance:
0/Antidepressive Agents; 0/Norepinephrine Plasma Membrane Transport Proteins; 0/Serotonin Plasma Membrane Transport Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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