Antidepressants Normalize the Default Mode Network in Patients With Dysthymia

New York State Psychiatric Institute, New York, New York, United States
JAMA Psychiatry (Impact Factor: 12.01). 02/2013; 70(4):1-10. DOI: 10.1001/jamapsychiatry.2013.455
Source: PubMed


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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Available from: David J Hellerstein, Feb 14, 2014
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    • "This problem could potentially be avoided by including placebo treatment groups, although this is often not possible because of ethical considerations. Alternatively, this could be addressed, as shown by a recent study,164 by integrating neuroimaging protocols into future clinical trials. Comparisons of predictive biomarkers for multiple treatments also might allow markers that are specific to individual treatments to be distinguished from those that are predictive of general improvement. "
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    • "The ROIs were derived from the LFPN (centered on the MNI coordinate of the cluster peaks, and with a radius of 4 mm) (Figure 1). Prior connectivity studies have employed similar approaches to the investigation of the default mode network (DMN) (Dosenbach et al., 2007; Fair et al., 2008; Posner et al., 2013). The LFPN ROIs and their coordinates are delineated in Table 1. "
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    • "Reflecting the growing concern regarding the impact of participant motion in resting state MRI studies (Power et al., 2012; Satterthwaite et al., 2012; Van Dijk et al., 2012), we undertook several measures to ensure our final results were not confounded by motion. First, during individual subject analyses, any TR with motion greater than 1.5 mm was removed; the selection of this threshold was informed by results from Posner et al. (2013). Second , we designated motion in the x, y, and z directions and roll, pitch, and yaw, generated during individual alignment and registration , as regressors of no interest during preprocessing, prior to blurring. "
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