{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T16:51:38Z","timestamp":1786121498234,"version":"build-2736575974"},"reference-count":91,"publisher":"Cambridge University Press (CUP)","license":[{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"unspecified","delay-in-days":218,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004008","name":"Istituto Superiore di Sanit\u00e0","doi-asserted-by":"publisher","award":["EnviroMood"],"award-info":[{"award-number":["EnviroMood"]}],"id":[{"id":"10.13039\/501100004008","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:p>Psychiatric disorders are complex conditions involving multifactorial, nonlinear causal dynamics, which make effective treatment challenging. To address this complexity, a framework is proposed that distinguishes between types of causality: permissive causality, which pertains to factors affecting the likelihood of an outcome occurring, and instructive causality, which refers to factors shaping the specific features of the outcome. In this framework, when considering an individual as a complex adaptive system, causal processes within the individual are permissive, whereas causal processes outside the individual can be either permissive or instructive in relation to the individual\u2019s global emergent outcomes. Accordingly, when dealing with mental states or complex behaviors, biological substrates \u2013 from genes to brain areas \u2013 operate through permissive causality, shaping a space of possibilities rather than instructing a specific outcome. By contrast, contextual factors \u2013 such as life challenges or subjective appraisal \u2013 can also operate through instructive causality, steering behavior and mental states toward specific trajectories. Therapeutic strategies should harness the synergistic interplay between these types of causality, targeting biological substrates to enable transitions in mental states, and leveraging contextual factors to steer these transitions toward mental well-being. Recognizing such interplay holds promise for developing innovative and effective approaches in precision psychiatry, especially for treatments enhancing plasticity \u2013 which itself operates through permissive causality \u2013 including antidepressants and psychedelics.<\/jats:p>","DOI":"10.1017\/s003329172610467x","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T05:01:53Z","timestamp":1786078913000},"update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":0,"title":["Permissive and instructive causality: integrating biological and environmental factors in mental health"],"prefix":"10.1017","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4484-3598","authenticated-orcid":false,"given":"Igor","family":"Branchi","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02hssy432","id-type":"ROR","asserted-by":"publisher"}],"name":"Istituto Superiore Di Sanita"},{"id":[{"id":"https:\/\/ror.org\/02hssy432","id-type":"ROR","asserted-by":"publisher"}],"name":"Istituto Superiore Di Sanita"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"56","published-online":{"date-parts":[[2026,8,7]]},"reference":[{"key":"S003329172610467X_r41","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-021-00602-9"},{"key":"S003329172610467X_r17","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2022.104678"},{"key":"S003329172610467X_r38","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1176\/ajp.137.5.535","article-title":"The clinical application of the biopsychosocial model","volume":"137","author":"Engel","year":"1980","journal-title":"American Journal of Psychiatry"},{"key":"S003329172610467X_r59","doi-asserted-by":"publisher","DOI":"10.1002\/wps.21072"},{"key":"S003329172610467X_r64","doi-asserted-by":"publisher","DOI":"10.1017\/CBO9780511803161"},{"key":"S003329172610467X_r75","doi-asserted-by":"publisher","DOI":"10.1016\/j.euroneuro.2013.09.010"},{"key":"S003329172610467X_r3","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1820838116"},{"key":"S003329172610467X_r88","first-page":"536","article-title":"Science and complexity","volume":"36","author":"Weaver","year":"1948","journal-title":"American Scientist"},{"key":"S003329172610467X_r5","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2022.06.003"},{"key":"S003329172610467X_r65","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(99)00081-0"},{"key":"S003329172610467X_r87","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.13m08855"},{"key":"S003329172610467X_r9","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.48.113006.094711"},{"key":"S003329172610467X_r53","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.05.036"},{"key":"S003329172610467X_r29","doi-asserted-by":"publisher","DOI":"10.1111\/acps.13335"},{"key":"S003329172610467X_r40","doi-asserted-by":"publisher","DOI":"10.1007\/BF00485230"},{"key":"S003329172610467X_r20","doi-asserted-by":"publisher","DOI":"10.1016\/j.euroneuro.2020.12.001"},{"key":"S003329172610467X_r57","doi-asserted-by":"publisher","DOI":"10.31887\/DCNS.2005.7.2\/mmeaney"},{"key":"S003329172610467X_r82","volume-title":"The study of instinct","author":"Tinbergen","year":"1951"},{"key":"S003329172610467X_r56","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2016.263"},{"key":"S003329172610467X_r83","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.163.1.28"},{"key":"S003329172610467X_r37","doi-asserted-by":"publisher","DOI":"10.1111\/j.1467-8721.2008.00571.x"},{"key":"S003329172610467X_r35","article-title":"Treatment expectancies and psilocybin vs Escitalopram for depression","author":"Dutcher","year":"2024","journal-title":"JAMA Psychiatry"},{"key":"S003329172610467X_r74","article-title":"Intranasal oxytocin and physical intimacy for dermatological wound healing and neuroendocrine stress: A randomized clinical trial","author":"Schneider","year":"2025","journal-title":"JAMA Psychiatry"},{"key":"S003329172610467X_r79","doi-asserted-by":"publisher","DOI":"10.1038\/nrc800"},{"key":"S003329172610467X_r25","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2017.35"},{"key":"S003329172610467X_r51","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.60.9.929"},{"key":"S003329172610467X_r76","doi-asserted-by":"publisher","DOI":"10.1016\/S2215-0366(24)00333-X"},{"key":"S003329172610467X_r66","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.20220216"},{"key":"S003329172610467X_r78","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.2021.61"},{"key":"S003329172610467X_r22","doi-asserted-by":"publisher","DOI":"10.1177\/0269881118754710"},{"key":"S003329172610467X_r86","doi-asserted-by":"publisher","DOI":"10.1001\/jama.287.14.1840"},{"key":"S003329172610467X_r15","doi-asserted-by":"publisher","DOI":"10.1016\/j.psyneuen.2010.08.011"},{"key":"S003329172610467X_r14","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2022.2996"},{"key":"S003329172610467X_r32","doi-asserted-by":"publisher","DOI":"10.1038\/s44220-023-00192-z"},{"key":"S003329172610467X_r44","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291701003312"},{"key":"S003329172610467X_r60","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2013.4291"},{"key":"S003329172610467X_r7","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2009.09071016"},{"key":"S003329172610467X_r30","doi-asserted-by":"publisher","DOI":"10.1002\/wps.20701"},{"key":"S003329172610467X_r42","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2008.04.033"},{"key":"S003329172610467X_r72","doi-asserted-by":"publisher","DOI":"10.1353\/pbm.1996.0057"},{"key":"S003329172610467X_r90","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3713"},{"key":"S003329172610467X_r23","doi-asserted-by":"publisher","DOI":"10.1177\/2167702613497473"},{"key":"S003329172610467X_r24","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.164.2.190"},{"key":"S003329172610467X_r77","doi-asserted-by":"publisher","DOI":"10.1002\/gps.4104"},{"key":"S003329172610467X_r13","doi-asserted-by":"publisher","DOI":"10.1002\/wps.20375"},{"key":"S003329172610467X_r45","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2016.130"},{"key":"S003329172610467X_r63","article-title":"Embracing complexity in psychiatry-from reductionistic to systems approaches","author":"Ongur","year":"2024","journal-title":"Lancet Psychiatry"},{"key":"S003329172610467X_r1","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.178.3.192"},{"key":"S003329172610467X_r43","doi-asserted-by":"publisher","DOI":"10.1016\/S2215-0366(19)30217-2"},{"key":"S003329172610467X_r12","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph16183501"},{"key":"S003329172610467X_r47","volume-title":"Hidden order: How adaptation builds complexity","author":"Holland","year":"1995"},{"key":"S003329172610467X_r71","volume-title":"Stanford encyclopedia of philosophy","author":"Ross","year":"2023"},{"key":"S003329172610467X_r73","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2024.0215"},{"key":"S003329172610467X_r52","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0050045"},{"key":"S003329172610467X_r91","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2026.106765"},{"key":"S003329172610467X_r69","doi-asserted-by":"publisher","DOI":"10.1038\/d41586-024-02597-x"},{"key":"S003329172610467X_r70","unstructured":"Ross, L. N. (2019). Explanation in contexts of causal complexity: Lessons from psychiatric genetics. PhilSci Archive. https:\/\/philsci-archive.pitt.edu\/15728\/."},{"key":"S003329172610467X_r18","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.16331"},{"key":"S003329172610467X_r89","doi-asserted-by":"publisher","DOI":"10.1093\/0195155270.001.0001"},{"key":"S003329172610467X_r67","doi-asserted-by":"publisher","DOI":"10.1038\/nn1352"},{"key":"S003329172610467X_r81","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000002365"},{"key":"S003329172610467X_r48","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.162.3.433"},{"key":"S003329172610467X_r26","doi-asserted-by":"publisher","DOI":"10.1038\/ncponc1134"},{"key":"S003329172610467X_r16","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2022.104691"},{"key":"S003329172610467X_r28","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1705"},{"key":"S003329172610467X_r62","doi-asserted-by":"publisher","DOI":"10.1037\/abn0000740"},{"key":"S003329172610467X_r19","doi-asserted-by":"publisher","DOI":"10.1192\/j.eurpsy.2025.19"},{"key":"S003329172610467X_r46","doi-asserted-by":"publisher","DOI":"10.1016\/S2215-0366(23)00363-2"},{"key":"S003329172610467X_r55","doi-asserted-by":"publisher","DOI":"10.1126\/science.ads4470"},{"key":"S003329172610467X_r21","doi-asserted-by":"publisher","DOI":"10.1007\/s10539-017-9568-0"},{"key":"S003329172610467X_r34","doi-asserted-by":"publisher","DOI":"10.1002\/wps.21177"},{"key":"S003329172610467X_r36","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.231499798"},{"key":"S003329172610467X_r39","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.88889.3"},{"key":"S003329172610467X_r27","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)60046-5"},{"key":"S003329172610467X_r2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1820"},{"key":"S003329172610467X_r4","doi-asserted-by":"publisher","DOI":"10.1037\/0022-006X.70.5.1129"},{"key":"S003329172610467X_r50","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291708004467"},{"key":"S003329172610467X_r58","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02565-4"},{"key":"S003329172610467X_r31","volume-title":"The origin of species","author":"Darwin","year":"1859"},{"key":"S003329172610467X_r61","doi-asserted-by":"publisher","DOI":"10.1098\/rsfs.2011.0067"},{"key":"S003329172610467X_r49","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2011.182"},{"key":"S003329172610467X_r80","doi-asserted-by":"publisher","DOI":"10.1136\/bmj-2021-067606"},{"key":"S003329172610467X_r85","doi-asserted-by":"publisher","DOI":"10.1038\/s41397-019-0080-6"},{"key":"S003329172610467X_r11","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2020.10.011"},{"key":"S003329172610467X_r6","doi-asserted-by":"publisher","DOI":"10.1002\/bies.201100185"},{"key":"S003329172610467X_r10","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291723002660"},{"key":"S003329172610467X_r33","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2010.03.022"},{"key":"S003329172610467X_r84","doi-asserted-by":"publisher","DOI":"10.1177\/2632077020937690"},{"key":"S003329172610467X_r54","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2021.118829"},{"key":"S003329172610467X_r8","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2009.44"},{"key":"S003329172610467X_r68","doi-asserted-by":"publisher","DOI":"10.2307\/jj.6380610.6"}],"container-title":["Psychological Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S003329172610467X","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T05:01:56Z","timestamp":1786078916000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S003329172610467X\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026]]},"references-count":91,"alternative-id":["S003329172610467X"],"URL":"https:\/\/doi.org\/10.1017\/s003329172610467x","relation":{},"ISSN":["0033-2917","1469-8978"],"issn-type":[{"value":"0033-2917","type":"print"},{"value":"1469-8978","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026]]},"assertion":[{"value":"\u00a9 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":"e253"}}