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Dissociable cortico-striatal connectivity abnormalities in major depression in response to monetary gains and penalties

Published online by Cambridge University Press:  15 May 2014

R. Admon
Affiliation:
Center for Depression, Anxiety and Stress Research, McLean Hospital/Harvard Medical School Belmont, MA, USA
L. D. Nickerson
Affiliation:
McLean Imaging Center, McLean Hospital/Harvard Medical School Belmont, MA, USA
D. G. Dillon
Affiliation:
Center for Depression, Anxiety and Stress Research, McLean Hospital/Harvard Medical School Belmont, MA, USA
A. J. Holmes
Affiliation:
Department of Psychology, Harvard University, Cambridge, MA, USA Department of Psychiatry, Massachusetts General Hospital/Harvard Medical School Boston, MA, USA
R. Bogdan
Affiliation:
Department of Psychology, Washington University in St Louis, St Louis, MO, USA
P. Kumar
Affiliation:
Center for Depression, Anxiety and Stress Research, McLean Hospital/Harvard Medical School Belmont, MA, USA
D. D. Dougherty
Affiliation:
Department of Psychiatry, Massachusetts General Hospital/Harvard Medical School Boston, MA, USA
D. V. Iosifescu
Affiliation:
Mood and Anxiety Disorders Program, Mount Sinai School of Medicine, New York, NY, USA
D. Mischoulon
Affiliation:
Department of Psychiatry, Massachusetts General Hospital/Harvard Medical School Boston, MA, USA
M. Fava
Affiliation:
Department of Psychiatry, Massachusetts General Hospital/Harvard Medical School Boston, MA, USA
D. A. Pizzagalli*
Affiliation:
Center for Depression, Anxiety and Stress Research, McLean Hospital/Harvard Medical School Belmont, MA, USA McLean Imaging Center, McLean Hospital/Harvard Medical School Belmont, MA, USA
*
*Address for correspondence: D. A. Pizzagalli, Ph.D., Center for Depression, Anxiety and Stress Research, Room 233C, McLean Hospital, 115 Mill Street, Belmont, MA 02478, USA. (Email: [email protected])

Abstract

Background

Individuals with major depressive disorder (MDD) are characterized by maladaptive responses to both positive and negative outcomes, which have been linked to localized abnormal activations in cortical and striatal brain regions. However, the exact neural circuitry implicated in such abnormalities remains largely unexplored.

Method

In this study 26 unmedicated adults with MDD and 29 matched healthy controls (HCs) completed a monetary incentive delay task during functional magnetic resonance imaging (fMRI). Psychophysiological interaction (PPI) analyses probed group differences in connectivity separately in response to positive and negative outcomes (i.e. monetary gains and penalties).

Results

Relative to HCs, MDD subjects displayed decreased connectivity between the caudate and dorsal anterior cingulate cortex (dACC) in response to monetary gains, yet increased connectivity between the caudate and a different, more rostral, dACC subregion in response to monetary penalties. Moreover, exploratory analyses of 14 MDD patients who completed a 12-week, double-blind, placebo-controlled clinical trial after the baseline fMRI scans indicated that a more normative pattern of cortico-striatal connectivity pre-treatment was associated with greater improvement in symptoms 12 weeks later.

Conclusions

These results identify the caudate as a region with dissociable incentive-dependent dACC connectivity abnormalities in MDD, and provide initial evidence that cortico-striatal circuitry may play a role in MDD treatment response. Given the role of cortico-striatal circuitry in encoding action–outcome contingencies, such dysregulated connectivity may relate to the prominent disruptions in goal-directed behavior that characterize MDD.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2014 

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