Editors' ChoiceDepression

Reconnecting the Depressed Brain

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Science Translational Medicine  11 Apr 2012:
Vol. 4, Issue 129, pp. 129ec62
DOI: 10.1126/scitranslmed.3004092

Depression is a leading cause of morbidity and mortality, yet the mechanisms underlying this highly prevalent disorder are still unclear. Moreover, for some individuals with depression available drugs offer only modest improvements in symptoms. For intractable depression that is unresponsive to drugs, electroconvulsive therapy (ECT) has proved beneficial, yet it remains unclear how the brain responds to this intervention. Perrin et al. now shed light on the effects of ECT on brain connectivity in patients with refractory depression and in so doing provide insight into how depression may evolve.

Perrin and colleagues used functional magnetic resonance imaging and a data-driven analytic approach to identify changes in functional connectivity in the brains of nine patients with depression before and after ECT. Researchers found that ECT confers enduring effects on brain functioning in individuals with depression. Specifically, average global functional connectivity was decreased in the left dorsolateral prefrontal cortex after ECT, and this change was accompanied by a substantial improvement in depressive symptoms. The findings reported here add weight to the emerging “hyperconnectivity hypothesis” in depression and support the proposal that increased connectivity may constitute both a biomarker for mood disorders and a potential therapeutic target.

By using in vivo neuroimaging coupled with data-driven analytic techniques, these researchers demonstrate that increased brain activity, which may be a pathological feature of depression, responds to ECT. These findings are, however, limited by the small sample size of the patient cohort and by the fact that all nine individuals continued to use psychotropic medications throughout the study and were exposed to repeated anesthesia (propofol) and a muscle relaxant (suxamethonium) during the course of ECT. Despite these potentially confounding effects on the results, the hope is that research of this kind might continue to advance knowledge about the biological underpinnings of depression and the effects of interventions targeted to aberrant neural circuits.

J. S. Perrin et al., Electroconvulsive therapy reduces frontal cortical connectivity in severe depressive disorder. Proc. Natl. Acad. Sci. U.S.A. 109, 5464–5468 (2012). [Abstract]

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