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Record W4416452510 · doi:10.1101/2025.11.19.25340633

Elevated plasma neurofilament light chain protein in alcohol use, anorexia nervosa, mania, psychosis and other acute psychiatric disorder presentations

2025· preprint· W4416452510 on OpenAlexaff
Dhamidhu Eratne, Matthew Kang, Charles B. Malpas, Samantha M. Loi, Alexander Santillo, Henrik Zetterberg, Naveen Thomas, Ian Everall, Chad Bousman, Christos Pantelis, K R Patel, Jeffrey M. Smith, Michael Christie, Cherie Chiang, Dennis Velakoulis

Bibliographic record

VenuemedRxiv · 2025
Typepreprint
Language
FieldHealth Professions
TopicDysphagia Assessment and Management
Canadian institutionsUniversity of Calgary
FundersNational Health and Medical Research CouncilMedical Research CouncilHORIZON EUROPE Framework ProgrammeHjärnfondenUniversity College LondonNational Institute for Health and Care ResearchEU Joint Programme – Neurodegenerative Disease ResearchAlzheimer's AssociationUK Dementia Research InstituteVetenskapsrådetAustralian GovernmentCure Alzheimer's FundEuropean CommissionFamiljen Erling-Perssons StiftelseStiftelsen för Gamla TjänarinnorAlzheimer's Drug Discovery Foundation
KeywordsPsychosisGlial fibrillary acidic proteinAnorexiaDepression (economics)AlcoholLithium (medication)Schizophrenia (object-oriented programming)Alcohol use disorderNeurofilament

Abstract

fetched live from OpenAlex

Abstract Objective To investigate plasma neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) levels across a range of acute psychiatric disorder presentations, and to determine whether elevations are specific to certain diagnoses. Methods We analysed biobanked lithium heparin plasma samples from 121 patients with acute psychiatric presentations (including mania, psychosis, alcohol use disorder, anorexia nervosa, depression, and adjustment disorder), and 59 healthy controls. NfL and GFAP were measured using Simoa assays. Group differences were compared via bootstrapped general linear models adjusted for age, sex, and weight. Results Among 180 participants, adjusted NfL was significantly elevated compared with controls in alcohol use disorder (β=1.32, p=0.002), anorexia nervosa (β=0.86, p<0.001), mania (β=0.44, p=0.015), and psychosis (β=0.34, p=0.034), but not in depression or adjustment disorder. Unadjusted NfL was highest in alcohol use disorder (mean 43 pg/mL) and anorexia nervosa (20 pg/mL) versus controls (9 pg/mL). Adjusted GFAP was elevated only in alcohol use disorder (β=1.01, p=0.024). Conclusions Plasma NfL and GFAP are not uniformly elevated across psychiatric disorders, but show a disorder-specific pattern, with the largest elevations in alcohol use disorder and anorexia nervosa and more modest elevations in mania and psychosis. These findings support nuanced, biologically grounded, diagnosis- and stage-specific interpretation of these biomarkers in psychiatry, and caution against interpreting a single elevated value as evidence of neurodegeneration. Because some acute psychiatric presentations show elevations approaching the neurodegenerative range, control-derived reference ranges may be insufficient when distinguishing neurodegeneration from primary psychiatric disorders, supporting the need for diagnosis- and state-specific reference data.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.003
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.010

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.003
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.001
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0030.000

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 head0.040
GPT teacher head0.372
Teacher spread0.332 · 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 source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
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".

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Citations1
Published2025
Admission routes1
Has abstractyes

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