Federal Grant Award Summary

The National Institute of Mental Health (NIMH) awarded a $728,751 Project Grant to the University of Pittsburgh under the Mental Health Research Grants program (CFDA 93.242) for the period April 1, 2026 through March 31, 2031. This research project investigates the neural mechanisms underlying antidepressant placebo effects in patients with major depressive disorder (MDD). The study employs theta burst stimulation (TBS) to examine the causal roles of the salience network (SN) and default mode network (DMN) in mediating antidepressant expectancy and mood regulation. The research involves a two-by-three factorial design with 200 MDD patients randomized to three counter-balanced TBS conditions (intermittent, continuous, and sham) targeting either the SN or DMN, with measurements of trial-by-trial expectancy, mood ratings, and neural encoding of expectancies and mood reward signals.

This project addresses a critical gap in antidepressant treatment efficacy, where first-line medications demonstrate modest efficacy (~50%) alongside high placebo response rates (~40%) that contribute to antidepressant trial failures. The research builds on prior findings demonstrating that antidepressant expectancies encoded in the SN trigger mood changes through an expectancy-mood feedback loop and that enhanced functional connectivity between the SN and DMN predicts long-term placebo effects. Products delivered through this award include experimental data, computational models of antidepressant placebo mechanisms, peer-reviewed publications, and evidence to inform more effective treatment strategies for the estimated 21 million U.S. adults experiencing MDD annually.