Share this article on:

Ketamine-Associated Brain Changes: A Review of the Neuroimaging Literature

Ionescu, Dawn F. MD; Felicione, Julia M. BA; Gosai, Aishwarya BA; Cusin, Cristina MD; Shin, Philip BS; Shapero, Benjamin G. PhD; Deckersbach, Thilo PhD

doi: 10.1097/HRP.0000000000000179
Review: PDF Only

Major depressive disorder (MDD) is one of the most prevalent conditions in psychiatry. Patients who do not respond to traditional monoaminergic antidepressant treatments have an especially difficult-to-treat type of MDD termed treatment-resistant depression. Subanesthetic doses of ketamine—a glutamatergic modulator—have shown great promise for rapidly treating patients with the most severe forms of depression. As such, ketamine represents a promising probe for understanding the pathophysiology of depression and treatment response. Through neuroimaging, ketamine’s mechanism may be elucidated in humans. Here, we review 47 articles of ketamine’s effects as revealed by neuroimaging studies. Some important brain areas emerge, especially the subgenual anterior cingulate cortex. Furthermore, ketamine may decrease the ability to self-monitor, may increase emotional blunting, and may increase activity in reward processing. Further studies are needed, however, to elucidate ketamine’s mechanism of antidepressant action.

From Harvard Medical School (Drs. Ionescu, Cusin, Shapero, and Deckersbach); Department of Psychiatry, Massachusetts General Hospital, Boston, MA (all); Athinoula A. Martinos Center for Biomedical Imaging, Boston, MA (Dr. Deckersbach).

Supported by National Institute of Mental Health grant nos. K23-MH107776 (Dr. Ionescu) and R01MH102279 (Dr. Cusin); Brain and Behavior Research Foundation (NARSAD Young Investigator Award) (Dr. Ionescu); MGH Executive Committee on Research (Dr. Ionescu); Louis V. Gerstner Family Foundation (Dr. Shapero); Depressive and Bipolar Disorder Alternative Treatment Foundation, International OCD Association, and Tourette Syndrome Association (Dr. Deckersbach).

Original manuscript received 5 March 2017; revised manuscript received 20 July 2017, accepted for publication 23 August 2017.

Correspondence: Cristina Cusin, MD, Department of Psychiatry, Massachusetts General Hospital, Depression Clinical and Research Program, 1 Bowdoin Square, Floor 6, Boston, MA 02114. Email:

© 2018 President and Fellows of Harvard College