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Record W4416762761 · doi:10.1016/j.bbih.2025.101144

Immune and metabolic disturbance as a function of genetic risk and phase of illness in major depression

2025· article· en· W4416762761 on OpenAlexfundno aff
David M. Howard, Lachlan Gilchrist, Petroula Proitsi, Elisabeth Paul, Markus Heilig, Robin Kämpe, J. Paul Hamilton

Bibliographic record

VenueBrain Behavior & Immunity - Health · 2025
Typearticle
Languageen
FieldNeuroscience
TopicTryptophan and brain disorders
Canadian institutionsnot available
FundersMedicinska ForskningsrådetWellcome TrustMedical Research CouncilOffice of Research and DevelopmentHealth Services Research and DevelopmentRegion ÖstergötlandAlberta Law Foundation
KeywordsDepression (economics)Major depressive disorderConfoundingImmune systemRisk factorAntidepressantEpidemiologyImmune DysfunctionInflammation

Abstract

Immune and metabolic factors are important in the pathophysiology of major depressive disorder (MDD) but we know little about how these factors manifest in relation to the status of depressive illness-from genetic risk for MDD, to a depressive episode, to depression in remission. Using genetic, diagnostic, biometric, and blood-bioassay data from the UK Biobank, we examined measures of pro-inflammatory signaling (C-reactive protein) and metabolic dysfunction (metabolic syndrome symptomatology) in females (N = 37,806) and males (N = 17,946) as a function of polygenic load for MDD (high versus low) interacting with depression status (never depressed, currently depressed, or depression in remission). We examined socioeconomic status (SES) as an exploratory factor in this design. Groups were matched for several confounders using a propensity-matching algorithm (females: n = 6301 per group for N = 37,806; n = 2991 per group for N = 17,946). In females we found increased inflammation and metabolic dysfunction in the higher-versus-lower PRS quartile, in those below-versus-above the median SES, and in those suffering currently from depression relative to their remitted depressed and healthy counterparts. This association remained when considering only non-psychotropic-medicated persons. Nonetheless, we also saw in both male and female samples that measures of immunological and metabolic dysfunction increased with increasing anti-depressant medication load. We discuss these findings in terms of the epidemiological significance of immune and metabolic functioning in depression and their paradoxical relation with antidepressant treatment.

Stored with the screening record, where it is evidence for the labels above.

How this classification was reachedexpand

The three-model screen

all 5,600 screened works →

All three models called this out of scope.

stratum: fund_new · design weight: 1678.90 (the sample is stratified; any rate computed without the weight is wrong)
Claude Opus 4.8OUT
genre: empirical
about Canada: no
confidence: high

Biobank study of inflammation and metabolic dysfunction in major depression.

GPT-5.6 (high)OUT
genre: empirical
about Canada: no
confidence: high

The study examines biological and clinical features of depression rather than research itself.

Grok 4.5OUT
genre: empirical
about Canada: no
confidence: high

Clinical epidemiology of inflammation and metabolism in depression, not research methods.

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)0.002
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 score0.002
Threshold uncertainty score0.000

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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 head0.020
GPT teacher head0.322
Teacher spread0.302 · 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".

Quick stats

Citations0
Published2025
Admission routes1
Has abstractyes

Explore more

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