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We enrolled 1,000 participants (aged 16\u201340 years) across five Egyptian centers, randomly allocating them to SEI (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009502) or treatment-as-usual (TAU;\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009498). TAU included standard antipsychotic treatment (primarily risperidone or haloperidol), monthly psychiatric follow-ups, and case management without structured psychosocial components. SEI combined monthly family psychoeducation, weekly cognitive-behavioral therapy, and low-dose risperidone (2\u00a0mg\/day) with therapeutic drug monitoring. At 2-year follow-up, 26.3% of participants transitioned to schizophrenia. Transition rates were significantly higher in SIPD (29.1%) than in BPD (20.4%; HR\u2009=\u20091.48,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.008), particularly among those with cannabis-associated SIPD (38.1%). SEI was associated with a 39% reduction in transition risk compared to TAU (HR\u2009=\u20090.61,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.008). Key predictors included neurocognitive deficits (verbal learning OR\u2009=\u20090.79; working memory OR\u2009=\u20090.83), severe positive symptoms (OR\u2009=\u20091.15), and elevated inflammatory markers (CRP OR\u2009=\u20091.39). These findings suggest that SEI may reduce conversion, although causality cannot be definitively established. The study highlights the substantial risk of schizophrenia following a first psychotic episode, especially in the context of substance use. A comprehensive, multi-component early intervention appears effective in reducing transition rates, underscoring the importance of targeted preventive strategies.\n                  <\/jats:p>","DOI":"10.1038\/s41598-025-24785-z","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T11:22:45Z","timestamp":1763464965000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Transition rates to schizophrenia and early intervention effectiveness in substance-induced and brief psychotic disorders: a randomized controlled trial"],"prefix":"10.1038","volume":"15","author":[{"given":"Mohamed","family":"Abouzed","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amgad","family":"Gabr","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamed","family":"Elsheikh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khaled A.","family":"Elag","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamed Y.","family":"Zeid","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mostafa","family":"Barakat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ehab","family":"Elasaly","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nisrin","family":"Elsaadouni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahmoud","family":"Soliman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,11,18]]},"reference":[{"issue":"4","key":"24785_CR1","doi-asserted-by":"publisher","first-page":"e0195687","DOI":"10.1371\/journal.pone.0195687","volume":"13","author":"B Moreno-K\u00fcstner","year":"2018","unstructured":"Moreno-K\u00fcstner, B., Mart\u00edn, C. & Pastor, L. 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