Perseverative behavior under uncertainty is enhanced by tryptophan depletion but diminished with subclinical obsessive–compulsive symptoms
Perseverative behavior under uncertainty is enhanced by tryptophan depletion but diminished with subclinical obsessive–compulsive symptoms
Abstract Serotonin is critically involved in flexible decision-making, yet the preponderance of evidence comes from non-human studies. Many insights about the serotonin’s function have come from the technique of dietary acute tryptophan depletion (ATD). However, it is unclear whether ATD modulates choice behavior during probabilistic reversal learning (PRL), a widely used model of behavioral flexibility with significant translational and clinical value. To determine whether ATD affects latent choice tendencies, we applied computational models of reinforcement learning to PRL data from healthy human volunteers (n = 62; 29 females) who had received either ATD or placebo in a randomized, double-blind, placebo-controlled procedure. A secondary objective was to ascertain how model parameters related to clinically relevant self-report questionnaires. ATD did not affect the updating (“learning rates”) or deployment (“reinforcement sensitivity”) of value representations driving choice. However, ATD increased “stimulus stickiness”, the tendency to choose a previously chosen visual stimulus again, regardless of reinforcement—a pattern seen in stimulant use disorder (SUD). Greater subclinical obsessive–compulsive symptoms were associated with lower stimulus stickiness, a pattern seen in clinically diagnosed obsessive–compulsive disorder (OCD). Low reinforcement sensitivity was instead related to intolerance of uncertainty and symptoms of depression and anxiety. Individuals with higher trait impulsivity showed lower reward and higher punishment learning rates, which parallels findings in SUD. Collectively, these results point to a role for serotonin in compulsive tendencies. They underscore the utility of computational modelling in illuminating the microstructure of behavior, which could point towards new markers of vulnerability to psychopathology.
Kanen Jonathan W.、Christmas David M.、Luo Qiang、Cardinal Rudolf N.、Arntz Fr¨|derique E.、Apergis-Schoute Annemieke M.、Sahakian Barbara J.、Yellowlees Robyn、Robbins Trevor W.
Department of Psychology, University of Cambridge||Behavioural and Clinical Neuroscience Institute, University of CambridgeDepartment of Psychiatry, University of Cambridge||Cambridgeshire and Peterborough NHS Foundation TrustInstitute of Science and Technology for Brain-Inspired Intelligence, Ministry of Education Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Fudan University||State Key Laboratory of Medical Neurobiology and Ministry of Education Frontiers Center for Brain Science, Institutes of Brain Science and Human Phenome Institute, Fudan University||National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan UniversityDepartment of Psychiatry, University of Cambridge||Cambridgeshire and Peterborough NHS Foundation TrustDepartment of Psychology, Leiden UniversityDepartment of Neuroscience, Psychology, and Behaviour, University of LeicesterBehavioural and Clinical Neuroscience Institute, University of Cambridge||Department of Psychiatry, University of CambridgeSection of Eating Disorders, Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King?ˉs College LondonDepartment of Psychology, University of Cambridge||Behavioural and Clinical Neuroscience Institute, University of Cambridge
医学研究方法神经病学、精神病学基础医学
acute tryptophan depletionserotoninprobabilistic reversal learningreinforcement learningcompulsivity
Kanen Jonathan W.,Christmas David M.,Luo Qiang,Cardinal Rudolf N.,Arntz Fr¨|derique E.,Apergis-Schoute Annemieke M.,Sahakian Barbara J.,Yellowlees Robyn,Robbins Trevor W..Perseverative behavior under uncertainty is enhanced by tryptophan depletion but diminished with subclinical obsessive–compulsive symptoms[EB/OL].(2025-03-28)[2025-05-23].https://www.biorxiv.org/content/10.1101/2021.04.05.437619.点此复制
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