{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T17:15:32Z","timestamp":1767892532544,"version":"3.49.0"},"reference-count":54,"publisher":"Royal College of Psychiatrists","issue":"3","license":[{"start":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T00:00:00Z","timestamp":1733356800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/www.cambridge.org\/core\/terms"}],"funder":[{"DOI":"10.13039\/501100003554","name":"Lundbeck Foundation","doi-asserted-by":"publisher","award":["R279-2018-1145"],"award-info":[{"award-number":["R279-2018-1145"]}],"id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["Br J Psychiatry"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:sec id=\"S0007125024001430_sec_a1\"><jats:title>Background<\/jats:title><jats:p>Using [<jats:sup>18<\/jats:sup>F]altanserin, a serotonin 2A receptor (5-HT<jats:sub>2A<\/jats:sub>R) antagonist Positron Emission Tomography (PET) tracer, a positive association between cortical 5-HT<jats:sub>2A<\/jats:sub>R binding and the inward-directed facets of neuroticism has been demonstrated in healthy individuals. Psilocybin, a 5-HT<jats:sub>2A<\/jats:sub>R agonist, shows promise for the treatment of depression, reducing neuroticism and mood symptoms potentially via hypothalamic-pituitary-adrenal (HPA) modulation. 5-HT<jats:sub>2A<\/jats:sub>R and neuroticism are both modulated by HPA axis function.<\/jats:p><\/jats:sec><jats:sec id=\"S0007125024001430_sec_a2\"><jats:title>Aims<\/jats:title><jats:p>In this study, we examined whether the association between 5-HT<jats:sub>2A<\/jats:sub>R binding and the inward facets of neuroticism can be replicated in an independent healthy cohort using the new 5-HT<jats:sub>2A<\/jats:sub>R agonist tracer [<jats:sup>11<\/jats:sup>C]Cimbi-36, and if their association is moderated by cortisol awakening response (CAR), an index of HPA axis function. If so, this could advance mechanistic insights into interventions that target the 5-HT<jats:sub>2A<\/jats:sub>R and reduce neuroticism.<\/jats:p><\/jats:sec><jats:sec id=\"S0007125024001430_sec_a3\" sec-type=\"methods\"><jats:title>Method<\/jats:title><jats:p>Eighty healthy volunteers underwent [<jats:sup>11<\/jats:sup>C]Cimbi-36 PET scans and completed the NEO personality inventory (NEO-PI-R) for the assessment of neuroticism. Salivary samples were available for determination of CAR in 70 of the participants. Using linear latent variable models, we evaluated the association between 5-HT<jats:sub>2A<\/jats:sub>R binding and inward facets of neuroticism, namely depression, anxiety, self-consciousness and vulnerability to stress, and whether CAR moderated this association.<\/jats:p><\/jats:sec><jats:sec id=\"S0007125024001430_sec_a4\" sec-type=\"results\"><jats:title>Results<\/jats:title><jats:p>The study confirms the positive association between 5-HT<jats:sub>2A<\/jats:sub>R binding and the inward facets of neuroticism (<jats:italic>\u03b2<\/jats:italic> = 0.01, 95% CI = [0.0005: 0.02], <jats:italic>P<\/jats:italic> = 0.04), and this association is independent of CAR (<jats:italic>P<\/jats:italic> = 0.33).<\/jats:p><\/jats:sec><jats:sec id=\"S0007125024001430_sec_a5\" sec-type=\"conclusions\"><jats:title>Conclusions<\/jats:title><jats:p>The findings prompt consideration of whether novel interventions such as psilocybin that actively targets 5-HT<jats:sub>2A<\/jats:sub>R and causes changes in personality could be particularly beneficial if implemented as a targeted approach based on neuroticism profiles.<\/jats:p><\/jats:sec>","DOI":"10.1192\/bjp.2024.143","type":"journal-article","created":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T07:34:31Z","timestamp":1733384071000},"page":"137-143","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":4,"title":["Consistent evidence that brain serotonin 2A receptor binding is positively associated with personality-based risk markers of depression"],"prefix":"10.1192","volume":"226","author":[{"given":"Emma 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