{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T09:40:22Z","timestamp":1792575622562,"version":"4.5.0"},"reference-count":25,"publisher":"Cambridge University Press (CUP)","license":[{"start":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:00:00Z","timestamp":1792540800000},"content-version":"unspecified","delay-in-days":293,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:00:00Z","timestamp":1792540800000},"content-version":"tdm","delay-in-days":293,"URL":"https:\/\/www.cambridge.org\/tdm\/tdmrep-policy.json"}],"funder":[{"DOI":"10.13039\/501100000241","name":"Physicians' Services Incorporated Foundation","doi-asserted-by":"publisher","award":["20-24"],"award-info":[{"award-number":["20-24"]}],"id":[{"id":"10.13039\/501100000241","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["Psychol. Med."],"published-print":{"date-parts":[[2026]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"S0033291726106412_sec1\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Explore\/exploit decision-making is a crucial component of motivated behavior. Explore\/exploit behaviors are related to disparate cognitive and reward-related functions and have been implicated in multiple neuropsychiatric conditions, including major depressive disorder (MDD). Several mediators of explore\/exploit decision-making have been proposed; metabolic mechanisms have been theorized to potentially affect its underlying processes. Here, we examined the effects of a GLP-1 receptor agonist (GLP-1RA), semaglutide, on explore\/exploit behavior in patients with MDD, using a four-armed restless bandit task.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0033291726106412_sec2\" sec-type=\"methods\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this secondary analysis of a randomized clinical trial, 72 participants with MDD were randomized either to oral semaglutide (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a035) or placebo (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a037), and completed the bandit task at baseline and following 16\u00a0weeks of treatment. Explore\/exploit decision-making was assessed using computational modeling of choice behavior, with a trial-by-trial reinforcement-learning model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0033291726106412_sec3\" sec-type=\"results\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Treatment with semaglutide resulted in increased exploitation (i.e. choosing the option with the highest expected reward) (Average Treatment Effect [ATE]\u00a0=\u00a00.0242,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.001), directed exploration (i.e. exploring a choice with higher uncertainty) (ATE\u00a0=\u00a00.0619,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.013), and perseveration (i.e. the value-independent tendency to repeat the previous action) (ATE\u00a0=\u00a00.3017,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.013). These effects were moderated by, but ultimately independent of, baseline characteristics and weight loss during the trial.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0033291726106412_sec4\" sec-type=\"conclusions\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Treatment with semaglutide modulated explore\/exploit behaviors in patients with MDD. These results highlight the role of metabolic mechanisms in decision-making processes in MDD and expand knowledge of the potential neuropsychiatric effects of GLP-1RAs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1017\/s0033291726106412","type":"journal-article","created":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T08:46:28Z","timestamp":1792572388000},"update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":0,"title":["Semaglutide modulates explore\/exploit decision-making in major depressive disorder: A randomized clinical trial"],"prefix":"10.1017","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-3627-3443","authenticated-orcid":false,"given":"Ziyuan","family":"Zhang","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03dbr7087","id-type":"ROR","asserted-by":"publisher"}],"name":"University of 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The Author(s), 2026. Published by Cambridge University Press","name":"copyright","label":"Copyright","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}},{"value":"This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http:\/\/creativecommons.org\/licenses\/by\/4.0), which permits unrestricted re-use, distribution and reproduction, provided the original article is properly cited.","name":"license","label":"License","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}},{"value":"This content has been made available to all.","name":"free","label":"Free to read"}],"article-number":"e344"}}