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The cognitive metabolomic signatures in schizophrenia spectrum disorders: A systematic review

2025· review· en· W4414483012 on OpenAlexafffund
Kristoffer Panganiban, Emily C. C. Smith, Nicolette Stogios, Sri Mahavir Agarwal, Kristen M. Ward, Margaret Hahn

Bibliographic record

VenuePsychiatry Research · 2025
Typereview
Languageen
FieldNeuroscience
TopicTryptophan and brain disorders
Canadian institutionsUniversity of TorontoCentre for Addiction and Mental Health
FundersBanting and Best Diabetes Centre, University of TorontoCanadian Institutes of Health ResearchPhysicians' Services Incorporated FoundationDanish Diabetes AcademyDepartment of Psychiatry, University of TorontoCentre for Addiction and Mental Health FoundationUniversity of TorontoWeston Brain Institute
KeywordsCognitionSchizophrenia (object-oriented programming)MetabolomicsGlutamate receptorCognitive impairmentGlutamineEnergy metabolismLipid metabolism

Abstract

fetched live from OpenAlex

BACKGROUND: Understanding the metabolome, the metabolite profile within biological samples, can provide insight into the mechanisms and processes underlying schizophrenia spectrum disorders (SSDs). Given that cognitive impairments are a core symptom domain of SSDs, investigating metabolomic alterations and their associations with cognitive impairments may help uncover pathways and mechanisms, with the potential to provide future treatments. Currently, there are no systematic reviews exploring the associations between cognition and metabolomic signatures. Therefore, the objective of this systematic review is to identify and examine these associations. METHOD: A systematic database search was conducted in Ovid MEDLINE, EMBASE and Scopus for studies related to the following three conceptual domains: "schizophrenia spectrum disorders", "metabolomics", and "cognition." Studies with a case-control component and/or association analyses were included in the review. Risk of bias assessments were conducted using the appropriate Johanna Briggs Institute Critical Appraisal Tool. RESULTS: Nine studies met inclusions for this review. Within these studies, 44 metabolites were identified as being dysregulated in cognitively impaired individuals with SSDs as compared to cognitively normal patients; 38 metabolites were downregulated while 6 were upregulated. The most frequently dysregulated classes of metabolites were carboxylic acids and derivatives, organooxygen compounds, and fatty acyls. For the association analyses, a mixture of positive and negative associations was found between cognition and metabolites, and the metabolite classes mainly dysregulated were glycerophospholipids, glycerolipids and fatty acyls. CONCLUSION: The identified metabolites may impact pathways related to inflammation, glutamate and glutamine metabolism, and lipid metabolism which may have an influence on cognition impairment in SSDs.

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)0.002
metaresearch head score (Gemma)0.006
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Systematic review · Consensus signal: Systematic review
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.005
Threshold uncertainty score0.013

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.006
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0050.005
Bibliometrics0.0040.005
Science and technology studies0.0000.000
Scholarly communication0.0020.001
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0040.000

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 head0.060
GPT teacher head0.410
Teacher spread0.350 · 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 designSystematic review
Domainnot available
GenreReview

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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Citations0
Published2025
Admission routes2
Has abstractno

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