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It is prone to posttranslational changes such as misassembly and aggregation but the significance of such transformations for human mental illness has remained unclear. We aimed to demonstrate the occurrence of DISC1 protein aggregates in patients with first\u2010episode psychosis (FEP).<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>Cerebrospinal fluid samples of patients with FEP (<jats:italic>n<\/jats:italic>\u2009=\u200950) and matched healthy controls (HCs; <jats:italic>n<\/jats:italic>\u2009=\u200947) were measured by the highly sensitive surface\u2010based fluorescence intensity distribution analysis technology that enables single aggregate detection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We demonstrate that DISC1 protein aggregates are increased in cerebrospinal fluid samples of patients with FEP versus HCs. The concentration was in the low femtomolar range. No correlations were found with specific symptom levels, but the difference was particularly significant in the subset of patients with the diagnoses schizophrenia, unspecified (DSM\u2010IV 295.9) or schizoaffective disorder (DSM\u2010IV 295.70) at 18\u2010month follow\u2010up. DISC1 protein aggregate levels did not significantly change within the 18\u2010month observation interval and were on average higher for individuals carrying the major DISC1 rs821577 allele, before correction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The occurrence of protein aggregates <jats:italic>in vivo<\/jats:italic> in patients with psychotic disorders has not been previously reported. It underscores the significance of posttranslational modifications of proteins both as pathogenetic mechanisms and as potential diagnostic markers in these disorders.<\/jats:p><\/jats:sec>","DOI":"10.1111\/pcn.13594","type":"journal-article","created":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T14:34:36Z","timestamp":1693924476000},"page":"665-671","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Disrupted\u2010in\u2010schizophrenia 1 protein aggregates in cerebrospinal fluid are elevated in patients with first\u2010episode psychosis"],"prefix":"10.1111","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1506-3675","authenticated-orcid":false,"given":"Marlene","family":"Pils","sequence":"first","affiliation":[{"name":"Institute of Biological Information Processing (Structural Biochemistry: IBI\u20107) Forschungszentrum J\u00fclich  J\u00fclich Germany"},{"name":"attyloid GmbH  D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Rutsch","sequence":"additional","affiliation":[{"name":"Department of Neuropathology Heinrich Heine University of D\u00fcsseldorf  D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feride","family":"Eren","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00f6ran","family":"Engberg","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fredrik","family":"Piehl","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience Karolinska Institutet  Stockholm Sweden"},{"name":"Department of Neurology Karolinska University Hospital  Stockholm 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