Antidepressants normalize the default mode network in patients with dysthymia.
Author(s): Posner J(1), Hellerstein DJ, Gat I, Mechling A, Klahr K, Wang Z, McGrath PJ,
Stewart JW, Peterson BS.
Affiliation(s): Author information:
(1)Columbia University College of Physicians and Surgeons, and New York State
Psychiatric Institute, New York, New York 10032, USA. posnerj@nyspi.columbia.edu
Publication date & source: 2013, JAMA Psychiatry. , 70(4):373-82
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.
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