Although selective serotonin reuptake inhibitors (SSRIs) are the first-line pharmacological treatment for depression and anxiety, many patients continue to experience persistent symptoms, and the psychological mechanisms underlying this variability remain poorly understood. In my lecture, I will argue that reinforcement sensitivity, defined as stable differences in responsiveness to positive and negative feedback, offers a behaviorally grounded framework for explaining why residual symptom patterns differ across individuals.
I will present data from over 3,000 participants taking citalopram, fluoxetine, or sertraline. Participants completed standardized measures of anxiety and depression as well as experimental tasks assessing sensitivity to reinforcement and were classified into four phenotypes (P−N−, P+N+, P−N+, P+N−).
Although all participants taking SSRIs displayed elevated levels of residual anxiety and depressive-like symptoms relative to controls, the pattern of symptom change depended systematically on reinforcement sensitivity phenotype. Thus, despite overall elevated symptom levels, specific symptoms improved selectively in particular phenotype–drug combinations.
Insomnia decreased primarily in individuals with low sensitivity to both positive and negative feedback (P−N−) taking citalopram or fluoxetine, whereas sertraline was associated with improved sleep mainly in individuals sensitive to both kinds of feedback (P+N+). Genitourinary symptoms were selectively alleviated in P−N− and P−N+ individuals taking citalopram, but were reduced only in P+N− participants taking fluoxetine or sertraline. Dose-dependent effects were also observed.
I will discuss how these findings support reinforcement sensitivity as a meaningful psychological construct for characterizing residual psychopathology and underscore the value of behavioral phenotyping for advancing psychologically informed precision psychiatry. Supported: Polish National Science Centre (2021/43/B/HS6/02007)

Authors:
Rafal Rygula, Maj Institute of Pharmacology Polish Academy of Sciences, Poland
Michal Piksa, Maj Institute of Pharmacology Polish Academy of Sciences, Poland
Agata Cieslik-Starkiewicz, Maj Institute of Pharmacology Polish Academy of Sciences, Poland

About the Presenter(s)
Professor Rafal Rygula is a University Associate Professor/Senior Lecturer at Maj Institute of Pharmacology Polish Academy of Sciences in Poland

See this presentation on the full schedule – Thursday Schedule

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