{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T04:51:55Z","timestamp":1791435115863,"version":"4.3.3"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"European Community\u2019s Seventh Framework Programme","award":["HEALTH-F2-2010-241909"],"award-info":[{"award-number":["HEALTH-F2-2010-241909"]}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CIBER -Consorcio Centro de Investigaci\u00f3n Biom\u00e9dica en Red-","award":["CB\/07\/09\/0023"],"award-info":[{"award-number":["CB\/07\/09\/0023"]}],"id":[{"id":"https:\/\/ror.org\/02g87qh62","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Madrid Regional Government","award":["S2022\/BMD-7216 AGES 3-CM"],"award-info":[{"award-number":["S2022\/BMD-7216 AGES 3-CM"]}]},{"name":"European Union Seventh Framework Program","id":[{"id":"https:\/\/ror.org\/019w4f821","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Innovative Medicines Initiative 2 Joint Undertaking: Project PRISM-2","award":["101034377"],"award-info":[{"award-number":["101034377"]}],"id":[{"id":"https:\/\/ror.org\/019af4n30","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Project AIMS-2-TRIALS","award":["777394"],"award-info":[{"award-number":["777394"]}]},{"name":"Project COllaborative Network for European Clinical Trials For Children \u201cc4c\u201d","award":["777389"],"award-info":[{"award-number":["777389"]}]},{"name":"National Institute of Mental Health of the National Institutes of Health","award":["1U01MH124639-01"],"award-info":[{"award-number":["1U01MH124639-01"]}]},{"name":"National Institute of Mental Health of the National Institutes of Health","award":["5P50MH115846-03"],"award-info":[{"award-number":["5P50MH115846-03"]}]},{"name":"National Institute of Mental Health of the National Institutes of Health","award":["1R01MH128971-01A1"],"award-info":[{"award-number":["1R01MH128971-01A1"]}]},{"name":"Fundaci\u00f3n Familia Alonso, and Fundaci\u00f3n Alicia Koplowitz","id":[{"id":"https:\/\/ror.org\/036jhs482","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Prolonged childhood and adolescent loneliness (CAL) may mark an early socio-emotional vulnerability relevant to psychosis and interact with genetic liability. We examined whether CAL increases odds of first-episode psychosis (FEP), relates to diagnostic subtype and functioning, and interacts with polygenic risk scores (PGS) for schizophrenia (SCZ), bipolar disorder (BIP), and major depression (MDD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study Methods<\/jats:title>\n                    <jats:p>We analyzed 2565 participants (1084 FEP, 1481 controls) from European Gene\u2013Environment Interactions in Schizophrenia (EU-GEI) study. CAL was assessed retrospectively before age 12 (LNL12) and at 12-16\u00a0years (LNL12-16). Functioning was rated with a modified Global Assessment of Functioning (GAF). Genome-wide PGS for SCZ, BIP, and MDD were calculated using polygenic risk score\u2013continuous shrinkage. Mixed-effects logistic and linear regression models tested associations of CAL with FEP, subtype, and functioning, including sex-stratified analyses. Additive gene\u2013environment interaction was examined using dichotomized PGS and the Relative Excess Risk due to Interaction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study Results<\/jats:title>\n                    <jats:p>Both LNL12 (OR\u2009=\u20092.90, 95% CI, 2.30-3.66) and LNL12-16 (OR\u2009=\u20092.34, 95% CI, 1.94-2.84) were associated with FEP, independent of premorbid social isolation. CAL increased FEP odds in both sexes. LNL12-16, but not LNL12, was associated with affective versus non-affective psychosis (OR\u2009=\u20091.37, 95% CI, 1.02-1.83), more clearly in females (OR\u2009=\u20091.79, 95% CI, 1.16-2.77). CAL was also associated with poorer functioning, with 3-4-point lower GAF Disability scores. Significant additive interactions were observed between LNL12-16 and SCZ-PGS, and between LNL12 and MDD-PGS, although the latter did not replicate in European-ancestry sensitivity analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Prolonged CAL is linked to higher risk of FEP, preferentially affective psychosis in females, poorer functioning, and developmental potentiation of polygenic liability.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/schbul\/sbag107","type":"journal-article","created":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T11:43:40Z","timestamp":1779882220000},"source":"Crossref","is-referenced-by-count":0,"title":["Prolonged Childhood and Adolescent Loneliness in First-Episode Psychosis: Synergistic Polygenic Effects and Functional Outcomes"],"prefix":"10.1093","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1467-7341","authenticated-orcid":false,"given":"\u00c1lvaro","family":"Andreu-Bernabeu","sequence":"first","affiliation":[{"name":"Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Mara\u00f1\u00f3n, Instituto de Investigaci\u00f3n Sanitaria Gregorio Mara\u00f1\u00f3n (IiSGM) , Madrid ,","place":["Spain"]},{"name":"Biomedical Research Networking Centre in Mental Health (CIBERSAM) ,","place":["Spain"]},{"name":"School of Medicine, Universidad Complutense de Madrid , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Gonz\u00e1lez-Pe\u00f1as","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Mara\u00f1\u00f3n, Instituto de Investigaci\u00f3n Sanitaria Gregorio Mara\u00f1\u00f3n (IiSGM) , Madrid ,","place":["Spain"]},{"name":"Biomedical Research Networking Centre in Mental Health (CIBERSAM) ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8748-6717","authenticated-orcid":false,"given":"Miguel","family":"Bernardo","sequence":"additional","affiliation":[{"name":"Barcelona Cl\u00ednic Schizophrenia Unit, Hospital Cl\u00ednic de Barcelona , Barcelona ,","place":["Spain"]},{"name":"Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer , Barcelona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Amoretti","sequence":"additional","affiliation":[{"name":"Psychiatry, Mental Health and Addictions Group, Vall d'Hebron Research Institute (VHIR), Instituto de Investigaci\u00f3n Sanitaria Acreditado Instituto de Investigaci\u00f3n - Hospital Universitario Vall d'Hebron (IR-HUVH), Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Salud Mental, Instituto de Salud Carlos III , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio","family":"Bobes","sequence":"additional","affiliation":[{"name":"Biomedical Research Networking Centre in Mental Health (CIBERSAM) ,","place":["Spain"]},{"name":"Department of Psychiatry, School of Medicine, University of Oviedo , Oviedo ,","place":["Spain"]},{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA) , Oviedo ,","place":["Spain"]},{"name":"Mental Health Services of Principado de Asturias (SESPA) , Oviedo ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Arrojo","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Instituto de Investigaci\u00f3n Sanitaria, Complejo Hospitalario Universitario de Santiago de Compostela , Santiago de Compostela ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara","family":"Parellada","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Mara\u00f1\u00f3n, Instituto de Investigaci\u00f3n Sanitaria Gregorio Mara\u00f1\u00f3n (IiSGM) , Madrid ,","place":["Spain"]},{"name":"Biomedical Research Networking Centre in Mental Health (CIBERSAM) ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"O'Donovan","sequence":"additional","affiliation":[{"name":"Cardiff University Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University , Cardiff ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jim","family":"van Os","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, UMC Utrecht Brain Centre, University Medical Centre Utrecht, Utrecht University , Utrecht ,","place":["The Netherlands"]},{"name":"Department of Translational Neuroscience, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University , Utrecht ,","place":["The Netherlands"]},{"name":"GGNet Mental Health , Apeldoorn ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart P F","family":"Rutten","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neuropsychology, Mental Health and Neuroscience Research Institute, Maastricht University Medical Centre , Maastricht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin M","family":"Murray","sequence":"additional","affiliation":[{"name":"Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King\u2019s College 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