title: Antidepressants normalize the default mode network in patients with dysthymia.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  University research institute.
  
  
  METHODS
  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.
  
  
  METHODS
  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
  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: Columbia University College of Physicians and Surgeons, and New York State Psychiatric Institute, New York, New York 10032, USA. posnerj@nyspi.columbia.edu
authors: Jonathan
authors: J
authors: Posner
authors: David J
authors: DJ
authors: Hellerstein
authors: Inbal
authors: I
authors: Gat
authors: Anna
authors: A
authors: Mechling
authors: Kristin
authors: K
authors: Klahr
authors: Zhishun
authors: Z
authors: Wang
authors: Patrick J
authors: PJ
authors: McGrath
authors: Jonathan W
authors: JW
authors: Stewart
authors: Bradley S
authors: BS
authors: Peterson
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D016022:Case-Control Studies; D004311:Double-Blind Method; D000068736:Duloxetine Hydrochloride; D019263:Dysthymic Disorder / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D059907:Functional Neuroimaging; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009415:Nerve Net / Q000187:drug effects / Q000503:physiopathology; D013876:Thiophenes / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000928:Antidepressive Agents; D013876:Thiophenes; D000068736:Duloxetine Hydrochloride
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