Journal Article

FZJ-2024-00735

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Disrupted‐in‐schizophrenia 1 protein aggregates in cerebrospinal fluid are elevated in patients with first‐episode psychosis

Pils, M.FZJ* ; Rutsch, J. ; Eren, F. ; Engberg, G. ; Piehl, F. ; Cervenka, S. ; Sellgren, C. ; Troßbach, S. ; Willbold, D.FZJ* ; Erhardt, S. ; Bannach, O. (Corresponding author)FZJ* ; Korth, C. (Corresponding author)

2023
Wiley-Blackwell Oxford [u.a.]

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Please use a persistent id in citations: doi:10.1111/pcn.13594  doi:10.34734/FZJ-2024-00735

Abstract: 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 samples of patients with FEP (n = 50) and matched healthy controls (HCs; n = 47) were measured by the highly sensitive surface-based fluorescence intensity distribution analysis technology that enables single aggregate detection.Results: 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-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-month observation interval and were on 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.

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Contributing Institute(s):

1. Strukturbiochemie (IBI-7)

Research Program(s):

1. 5244 - Information Processing in Neuronal Networks (POF4-524) (POF4-524)

Appears in the scientific report 2023

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Database coverage:
; ; ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DEAL Wiley ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 10 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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