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Record W4366290800 · doi:10.1101/2023.04.17.23288687

Disrupted-in-schizophrenia 1 (DISC1) protein aggregates in cerebrospinal fluid are elevated in first-episode psychosis patients

2023· preprint· en· W4366290800 on OpenAlexfundno aff
Marlene Pils, Julia Rutsch, Feride Eren, Göran Engberg, Fredrik Piehl, Simon Červenka, Carl M. Sellgren, Svenja V. Trossbach, Dieter Willbold, Sophie Erhardt, Oliver Bannach, Carsten Korth

Bibliographic record

VenuemedRxiv · 2023
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicPhosphodiesterase function and regulation
Canadian institutionsnot available
FundersVetenskapsrådetStockholms Läns LandstingDeutsche ForschungsgemeinschaftWeston Brain InstituteKarolinska InstitutetALS AssociationAlzheimer's AssociationForschungszentrum JülichMichael J. Fox Foundation for Parkinson's Research
KeywordsSchizophrenia (object-oriented programming)Schizoaffective disorderPsychosisDISC1Cerebrospinal fluidClinical significanceInternal medicinePsychiatryMedicinePsychologyNeuroscienceChemistryGeneBiochemistry

Abstract

fetched live from OpenAlex

Abstract The Disrupted-in-schizophrenia 1 (DISC1) protein is a key regulator at the intersection of 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. Here we demonstrate that DISC1 protein aggregates are increased in CSF samples of patients with first episode psychosis (n=50) compared to healthy controls (n=47), as measured by the highly sensitive surface-based fluorescence intensity distribution analysis technology that enables single aggregate detection. The concentration was in the low femtomolar range. No correlations were found to 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. 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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.015
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.015
GPT teacher head0.252
Teacher spread0.236 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2023
Admission routes1
Has abstractyes

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