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- Pils, Marlene (author)
Disrupted-in-schizophrenia 1 (DISC1) protein aggregates in cerebrospinal fluid are elevated in first-episode psychosis patients.
- Article/chapterEnglish2023
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- 2023
- 2023
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- LIBRIS-ID:oai:DiVA.org:uu-511173
- https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-511173URI
- https://doi.org/10.1111/pcn.13594DOI
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- Language:English
- Summary in:English
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- AIM: The Disrupted-in-schizophrenia 1 (DISC1) protein is a key regulator at the intersection of major signaling pathways relevant for adaptive behavior. 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 episode psychosis (FEP).METHOD: Cerebrospinal fluid (CSF) samples of patients with FEP (n = 50) and matched healthy controls (HC; n = 47) were measured by the highly sensitive surface-based fluorescence intensity distribution analysis (sFIDA) technology that enables single aggregate detection.RESULTS: Here we demonstrate that DISC1 protein aggregates are increased in CSF samples of FEP vs. HC. The concentration was in the low femtomolar range. No correlations were found to specific symptom levels, but the difference was particularly significant in the subset of patients receiving the diagnoses "schizophrenia, unspecified" (DSM IV 295.9) or schizoaffective disorder (DSM IV 295.70) at 18-month follow-up. DISC1 protein aggregate levels did not significantly change within the 18 months observation interval, and were in average higher for individuals carrying the major DISC1 rs821577 allele before correction.CONCLUSION: The occurrence of protein aggregates in vivo 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. This article is protected by copyright. All rights reserved.
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- Rutsch, Julia (author)
- Eren, Feride (author)
- Engberg, Göran (author)
- Piehl, Fredrik (author)
- Cervenka, SimonUppsala universitet,Psykiatri(Swepub:uu)simce160 (author)
- Sellgren, Carl (author)
- Troßbach, Svenja (author)
- Willbold, Dieter (author)
- Erhardt, Sophie (author)
- Bannach, Oliver (author)
- Korth, Carsten (author)
- Uppsala universitetPsykiatri (creator_code:org_t)
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- In:Psychiatry and Clinical Neurosciences1323-13161440-1819
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- Sellgren, Carl
- Troßbach, Svenja
- Willbold, Dieter
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- Korth, Carsten
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