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320. Investigating the Role of Serotonin in Stressor Controllability and Mental Effort Allocation
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320. Investigating the Role of Serotonin in Stressor Controllability and Mental Effort Allocation

Debbie Yee, Tony El Nemer, Steven Rasmussen and Amitai Shenhav
Biological psychiatry (1969), Vol.99(10 Supplement), pp.S237-S237
05/15/2026
DOI: 10.1016/j.biopsych.2026.03.554

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Abstract

Background Exposure to sustained and uncontrollable stressors plays a significant role in the onset and longitudinal course of many neuropsychiatric disorders. However, few computational frameworks mechanistically capture how humans exert mental effort under sustained stress. We developed a novel Stressor Controllability and Cognitive Control model which predicts that controllability shapes how individuals allocate mental effort and experience negative affect. Establishing a theoretical model of stress-control interactions is foundational for providing insight into how serotonin-based drug treatments (e.g., SSRIs) impact therapeutic response. Methods Healthy volunteers (n=49) performed a self-paced rule-guided rotation task (e.g. correct responses are based on stimulus color and orientation) across task conditions varying the controllability, contingency, and predictability of mild electric shocks. Participants rated their subjective experiences after each experimental condition (e.g., stress, frustration). We are currently conducting a within-subjects placebo-controlled SSRI study, where participants (n=40 of targeted 50) are administered a single dose of 20 mg escitalopram or placebo and perform the same task in both conditions. Results Across both studies, participants were slowest and more accurate when avoiding controllable shocks delivered for a mistake compared to the other conditions (p <.001). They reported the highest stress and frustration when experiencing uncontrollable and unpredictable shocks, and the least stress and frustration for avoidable shocks (p’s <.001). Conclusions Participants exerted distinct adaptive control strategies for working to escape from or avoid controllable shocks, with greater perceived control when they could avoid controllable shocks. Additionally, predictability is crucial for differentiating the affective experience of uncontrollable stressors on cognitive control allocation.

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