Document Detail


Antidepressants normalize the default mode network in patients with dysthymia.
MedLine Citation:
PMID:  23389382     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
IMPORTANCE: The default mode network (DMN) is a collection of brain regions that reliably deactivate during goal-directed behaviors and is more active during a baseline, or so-called resting, condition. Coherence of neural activity, or functional connectivity, within the brain's DMN is increased in major depressive disorder relative to healthy control (HC) subjects; however, whether similar abnormalities are present in persons with dysthymic disorder (DD) is unknown. Moreover, the effect of antidepressant medications on DMN connectivity in patients with DD is also unknown.
OBJECTIVE: To use resting-state functional-connectivity magnetic resonance imaging (MRI) to study (1) the functional connectivity of the DMN in subjects with DD vs HC participants and (2) the effects of antidepressant therapy on DMN connectivity.
DESIGN: After collecting baseline MRI scans from subjects with DD and HC participants, we enrolled the participants with DD into a 10-week prospective, double-blind, placebo-controlled trial of duloxetine and collected MRI scans again at the conclusion of the study. Enrollment occurred between 2007 and 2011.
SETTING: University research institute.
PARTICIPANTS: Volunteer sample of 41 subjects with DD and 25 HC participants aged 18 to 53 years. Control subjects were group matched to patients with DD by age and sex.
MAIN OUTCOME MEASURES: We used resting-state functional-connectivity MRI to measure the functional connectivity of the brain's DMN in persons with DD compared with HC subjects, and we examined the effects of treatment with duloxetine vs placebo on DMN connectivity.
RESULTS: Of the 41 subjects with DD, 32 completed the clinical trial and MRI scans, along with the 25 HC participants. At baseline, we found that the coherence of neural activity within the brain's DMN was greater in persons with DD compared with HC subjects. Following a 10-week clinical trial, we found that treatment with duloxetine, but not placebo, normalized DMN connectivity.
CONCLUSIONS AND RELEVANCE: The baseline imaging findings are consistent with those found in patients with major depressive disorder and suggest that increased connectivity within the DMN may be important in the pathophysiology of both acute and chronic manifestations of depressive illness. The normalization of DMN connectivity following antidepressant treatment suggests an important causal pathway through which antidepressants may reduce depression.
Authors:
Jonathan Posner; David J Hellerstein; Inbal Gat; Anna Mechling; Kristin Klahr; Zhishun Wang; Patrick J McGrath; Jonathan W Stewart; Bradley S Peterson
Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  JAMA psychiatry     Volume:  70     ISSN:  2168-6238     ISO Abbreviation:  JAMA Psychiatry     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-04     Completed Date:  2013-05-31     Revised Date:  2014-02-27    
Medline Journal Info:
Nlm Unique ID:  101589550     Medline TA:  JAMA Psychiatry     Country:  United States    
Other Details:
Languages:  eng     Pagination:  373-82     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Adult
Antidepressive Agents / pharmacology,  therapeutic use*
Brain / drug effects*,  physiopathology
Case-Control Studies
Double-Blind Method
Dysthymic Disorder / drug therapy*,  physiopathology
Female
Functional Neuroimaging
Humans
Magnetic Resonance Imaging
Male
Nerve Net / drug effects,  physiopathology
Thiophenes / pharmacology,  therapeutic use*
Grant Support
ID/Acronym/Agency:
K02-74677//PHS HHS; K23 MH091249/MH/NIMH NIH HHS; K23-MH091249/MH/NIMH NIH HHS
Chemical
Reg. No./Substance:
0/Antidepressive Agents; 0/Thiophenes; O5TNM5N07U/duloxetine
Comments/Corrections

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