Skip to main content

Abstract

Objective:

Major depressive disorder is characterized by reduced reward-related striatal activation and dysfunctional reward learning, putatively reflecting decreased dopaminergic signaling. The goal of this study was to test whether a pharmacological challenge designed to facilitate dopaminergic transmission can enhance striatal responses to reward and improve reward learning in depressed individuals.

Method:

In a double-blind placebo-controlled design, 46 unmedicated depressed participants and 43 healthy control participants were randomly assigned to receive either placebo or a single low dose (50 mg) of the D2/D3 receptor antagonist amisulpride, which is believed to increase dopamine signaling through presynaptic autoreceptor blockade. To investigate the effects of increased dopaminergic transmission on reward-related striatal function and behavior, a monetary incentive delay task (in conjunction with functional MRI) and a probabilistic reward learning task were administered at absorption peaks of amisulpride.

Results:

Depressed participants selected previously rewarded stimuli less frequently than did control participants, indicating reduced reward learning, but this effect was not modulated by amisulpride. Relative to depressed participants receiving placebo (and control participants receiving amisulpride), depressed participants receiving amisulpride exhibited increased striatal activation and potentiated corticostriatal functional connectivity between the nucleus accumbens and the midcingulate cortex in response to monetary rewards. Stronger corticostriatal connectivity in response to rewards predicted better reward learning among depressed individuals receiving amisulpride as well as among control participants receiving placebo.

Conclusions:

Acute enhancement of dopaminergic transmission potentiated reward-related striatal activation and corticostriatal functional connectivity in depressed individuals but had no behavioral effects. Taken together, the results suggest that targeted pharmacological treatments may normalize neural correlates of reward processing in depression; despite such acute effects on neural function, behavioral modification may require more chronic exposure. This is consistent with previous reports that antidepressant effects of amisulpride in depression emerged after sustained administration.

Formats available

You can view the full content in the following formats:

Information & Authors

Information

Published In

Go to American Journal of Psychiatry
Go to American Journal of Psychiatry
American Journal of Psychiatry
Pages: 378 - 386
PubMed: 27771973

History

Received: 26 January 2016
Revision received: 15 April 2016
Accepted: 16 August 2016
Published online: 24 October 2016
Published in print: April 01, 2017

Keywords

  1. Antidepressants
  2. Brain Imaging Techniques
  3. Biological Markers
  4. Mood Disorders-Unipolar
  5. Dopamine
  6. Reward

Authors

Details

Roee Admon, Ph.D.
From the Center for Depression, Anxiety, and Stress Research and the McLean Imaging Center, McLean Hospital, Belmont, Mass.; and the Department of Psychiatry, Harvard Medical School, Boston.
Roselinde H. Kaiser, Ph.D.
From the Center for Depression, Anxiety, and Stress Research and the McLean Imaging Center, McLean Hospital, Belmont, Mass.; and the Department of Psychiatry, Harvard Medical School, Boston.
Daniel G. Dillon, Ph.D.
From the Center for Depression, Anxiety, and Stress Research and the McLean Imaging Center, McLean Hospital, Belmont, Mass.; and the Department of Psychiatry, Harvard Medical School, Boston.
Miranda Beltzer, B.S.
From the Center for Depression, Anxiety, and Stress Research and the McLean Imaging Center, McLean Hospital, Belmont, Mass.; and the Department of Psychiatry, Harvard Medical School, Boston.
Franziska Goer, B.S.
From the Center for Depression, Anxiety, and Stress Research and the McLean Imaging Center, McLean Hospital, Belmont, Mass.; and the Department of Psychiatry, Harvard Medical School, Boston.
David P. Olson, M.D., Ph.D.
From the Center for Depression, Anxiety, and Stress Research and the McLean Imaging Center, McLean Hospital, Belmont, Mass.; and the Department of Psychiatry, Harvard Medical School, Boston.
Gordana Vitaliano, M.D.
From the Center for Depression, Anxiety, and Stress Research and the McLean Imaging Center, McLean Hospital, Belmont, Mass.; and the Department of Psychiatry, Harvard Medical School, Boston.
Diego A. Pizzagalli, Ph.D.
From the Center for Depression, Anxiety, and Stress Research and the McLean Imaging Center, McLean Hospital, Belmont, Mass.; and the Department of Psychiatry, Harvard Medical School, Boston.

Notes

Address correspondence to Dr. Pizzagalli ([email protected]).
The first two authors contributed equally.
Presented at the annual Anxiety and Depression Conference of the Anxiety and Depression Association of America, Miami, April 9–12, 2015.

Competing Interests

Dr. Dillon has served as a consultant for Pfizer. Dr. Vitaliano has equity ownership in EXQOR Technologies. Dr. Pizzagalli has received honoraria or consulting fees from Akili Interactive Labs, BlackThorn Therapeutics, Otsuka America Pharmaceutical, and Pfizer. The other authors report no financial relationships with commercial interests.

Funding Information

National Institute of Mental Health10.13039/100000025: 1F32MH106262, K99MH094438, MH068376, MH101521
Supported by NIMH R01 grants MH068376 and MH101521 to Dr. Pizzagalli. Dr. Admon was supported by a Brain and Behavior Research Foundation Young Investigator Award and an Adam Corneel Young Investigator Award. Dr. Kaiser and Dr. Dillon were supported by NIMH grants F32MH106262 and K99MH094438, respectively.

Metrics & Citations

Metrics

Citations

Export Citations

If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download.

For more information or tips please see 'Downloading to a citation manager' in the Help menu.

Format
Citation style
Style
Copy to clipboard

View Options

View options

PDF/EPUB

View PDF/EPUB

Full Text

View Full Text

Get Access

Login options

Already a subscriber? Access your subscription through your login credentials or your institution for full access to this article.

Personal login Institutional Login Open Athens login
Purchase Options

Purchase this article to access the full text.

PPV Articles - American Journal of Psychiatry

PPV Articles - American Journal of Psychiatry

Not a subscriber?

Subscribe Now / Learn More

PsychiatryOnline subscription options offer access to the DSM-5-TR® library, books, journals, CME, and patient resources. This all-in-one virtual library provides psychiatrists and mental health professionals with key resources for diagnosis, treatment, research, and professional development.

Need more help? PsychiatryOnline Customer Service may be reached by emailing [email protected] or by calling 800-368-5777 (in the U.S.) or 703-907-7322 (outside the U.S.).

Media

Figures

Other

Tables

Share

Share

Share article link

Share