Brain-Volume Increase With Sustained Remission in Patients With Treatment-Resistant Unipolar Depression

Objective: Previous magnetic resonance imaging (MRI) studies have demonstrated brain-volume reductions in unipolar major depressive disorder (MDD). It is not clear whether these atrophic changes can be stabilized with antidepressant treatment and/or reversed with remission. The objective of this study was to prospectively examine brain-volume changes in patients with treatment-resistant depression, comparing those who achieved sustained remission with those who did not remit.

Method: This prospective observational cohort study investigated the roles of clinical responsiveness and antidepressant treatment in lessening brain atrophy in depression. Data were collected between October 2004 and December 2008. Baseline MRI scans were obtained from 28 outpatients with treatment-resistant MDD (diagnosed according to DSM-IV criteria) who were recruited from the Mood Disorders Research Unit at the Royal Ottawa Mental Health Centre, Ottawa, Ontario, Canada. Twenty-seven patients underwent follow-up scanning after either 6 months of sustained remission (Montgomery-Asberg Depression Rating Scale score ≤ 12) or 12 months of failure to remit. Longitudinal whole-brain and voxel-based gray- and white-matter volume changes were estimated.

Results: Twelve patients (mean age at baseline = 47.5 years) achieved sustained 6-month remission. In contrast to nonremitters (n = 15; mean age at baseline = 44.3 years), remitted patients demonstrated a significant mean increase in whole-brain volume during follow-up F^1,27 = 9.51, P = .005). Within-subject voxel-based morphometry analyses identified increased gray-matter volume in remitters in the right orbitofrontal cortex (t¹¹ = 7.61, P = .006) and the right inferior temporal gyrus (t¹¹ = 6.65, P = .004). Nonremitters showed decreased white-matter volume in the left anterior limb of the internal capsule (t¹³ = 3.86, P = .04).

Conclusions: Given that remitters exhibited a mean increase in brain volume while nonremitters lost volume, pharmacotherapy in the absence of sustained remission is most likely insufficient to elicit brain-volume increase in MDD. The findings suggest that clinical remission rather than pharmacotherapy may be the key factor involved in driving volumetric recovery in treatment-resistant depression.

J Clin Psychiatry 2012; 73(5): 625-631

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