{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T23:39:54Z","timestamp":1791589194736,"version":"4.3.4"},"reference-count":55,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,5,16]],"date-time":"2021-05-16T00:00:00Z","timestamp":1621123200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Early Intervention Psych"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Early age at schizophrenia onset (EOS) has been associated with a worse clinical course, although previous studies reported substantial heterogeneity. Despite the relevance of the subject, the relationship between the age of onset and treatment resistant schizophrenia (TRS) is less clear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We screened 197 non\u2010affective psychotic patients. Of these, 99 suffered from schizophrenia and were putative TRS and were included in a prospective 4\u2010to\u20108\u2010week trial to assess their response to antipsychotics. According to status (TRS\/nonTRS) and age\u2010at\u2010onset (early: \u226418\u2009years, EOS; adult: &gt;18\u2009years, adult onset schizophrenia [AOS]) patients were subdivided in EOS\u2010TRS, EOS\u2010nonTRS, AOS\u2010TRS, AOS\u2010nonTRS. Multiple clinical variables were measured and compared by analysis of covariance (ANCOVA), using age as a covariate. Two\u2010way analysis of variance (ANOVA) was used to assess whether significant differences were attributable to TRS status or age\u2010at\u2010onset.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The rate of TRS patients was significantly higher in EOS compared to AOS. At the ANCOVA, EOS\u2010TRS had significantly worse clinical, cognitive, and psychosocial outcomes compared to the other groups. Overall, EOS\u2010TRS were more impaired than EOS\u2010nonTRS, while significant differences with AOS\u2010TRS were less consistent, albeit appreciable. Two\u2010way ANOVA demonstrated that, in the majority of the investigated variables, the significant differences among groups were attributable to the TRS status effect rather than to age\u2010at\u2010onset or combined effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These results suggest that refractoriness to antipsychotics may be strongly linked to the early onset of psychotic symptoms, possibly as a result of common neurobiology.<\/jats:p><\/jats:sec>","DOI":"10.1111\/eip.13174","type":"journal-article","created":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T02:54:35Z","timestamp":1621220075000},"page":"352-362","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Relationships between early age at onset of psychotic symptoms and treatment resistant 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