Exploring the effects of ketamine on mood, error-related negativity, and error related positivity in adults with treatment resistant depression

Shiba Esfand, BA

McLean Hospital – Research Assistant

Scientific Abstract


Ketamine has displayed robust antidepressant effects in individuals with treatment resistant depression (TRD) 24-hours following an infusion. Despite this clinical benefit, the precise mechanisms of action of ketamine are not fully understood. In addition to experiencing low mood, previous research suggests individuals with depression display deficits in error and response monitoring. This can be measured via the error related negativity (ERN) and the error related positivity (Pe), which are event related potential components that occur after committing an error. The current study aimed to examine the impact of ketamine on response monitoring and  measures of depression in individuals with TRD.


Participants with TRD (n=7) and healthy control participants (n=24) completed two test sessions, 48-hours apart. In between sessions, participants with TRD received 0.5mg of ketamine intravenously. During each session, participants completed a version of the Eriksen Flanker task, used to probe the ERN, while 96-channel EEG was recorded. Participants also completed the Beck Depression Inventory, BDI-II, and the Snaith Hamilton Pleasure Scale, SHAPS, to examine changes in mood following ketamine. We assessed differences in self-reported mood and ERN in participants with TRD pre and post ketamine treatment.


After receiving ketamine, TRD subjects displayed no significant difference in ERN, t(5)= -0.36, p=.739 and no improvement in BDI (Z=-1.52, p= .128) and SHAPS (Z=-0.52,p=.6) scores. Additionally, a trend for larger Pe at post vs. pre-infusion emerged t(5)=-2.71, p=.054, with 80% of TRD subjects showing an increase in Pe after ketamine. Healthy controls also displayed no difference in ERN, BDI, and SHAPS between sessions (all p’s > .05). Data collection is ongoing thus results should be interpreted cautiously due to small sample size of TRD subjects.


The proposed research will shed light on the mechanisms underlying ketamine treatment for TRD. Additionally, results could identify specific biomarkers of depression that could help identify individuals who might preferentially benefit from ketamine treatment.

Live Zoom Session – March 9th

research Areas


Shiba M. Esfand, BA, Jason N. Scott, jr.,BA, Samantha R. Linton, PhD, Rachel Lobien, BA, Steven J. Lamontagne, PhD, Shuang Li, MD, Brian W. Boyle, MD, Paula S. Bolton, CNP, Courtney G. Miller, RN, Robert C. Meisner, MD, Diego A. Pizzagalli, PhD

Principal Investigator

Diego A. Pizzagalli, PhD