JAMA Psychiatry: Dynamic Feedback Between Antidepressant Placebo Expectancies and Mood

Marta Peciña, MD, PhD (Associate Professor of Psychiatry), conducts research focused on the mechanisms of antidepressant treatment response, and uses placebos to investigate how expectancies and learning mechanisms impact mood improvement. In a recent paper published in JAMA Psychiatry, Dr. Peciña and investigators including Alex Dombrovski, MD (Pittsburgh Foundation Endowed Professor in Brain and Mind Research and Associate Professor of Psychiatry), from Pitt Psychiatry, investigated what makes antidepressant placebo effects persist over time. 

The scientists studied the association between mood dynamics and antidepressant placebo effects, looking at neural encoding of placebo expectancies and learning signals. Study participants, individuals diagnosed with major depressive disorder, participated in an experimental manipulation including an antidepressant placebo functional magnetic resonance imaging (fMRI) task. The team manipulated antidepressant expectancies using purported fast-acting antidepressant infusions and presented ostensible physiological evidence of mood improvement via sham neurofeedback.

Findings from the study revealed that antidepressant expectancies, perceived in the sensory cortex and dorsal attention network, are encoded in the salience network. Expectancies are then maintained through the formation of expectancy-mood loop dynamics explained by models of reinforcement learning that combined biased learning from placebo cues (infusions) and combined sensory evidence of antidepressant effects (sham neurofeedback) and momentary mood.

“Our results suggest that, in the absence of true biological effects, antidepressant placebos, encoded in the salience network, trigger sporadic mood responses that further enhance expectancies through the formation of expectancy-mood loops, which contributes to our understanding of the persistence of this effect,” said Dr. Peciña, the study’s corresponding author.

Dynamic Feedback Between Antidepressant Placebo Expectancies and Mood
Peciña M, Chen J, Karp JF, Dombrovski AY.

JAMA Psychiatry. Published online March 1, 2023. doi:10.1001/jamapsychiatry.2023.0010