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Record W4411678908 · doi:10.1016/j.bbi.2025.06.035

Peripheral leptin receptor gene network modulates the impact of childhood adversity on mental health disorders

2025· article· en· W4411678908 on OpenAlexaff
Randriely Merscher Sobreira de Lima, Bárbara Barth, Danusa Mar Arcego, Euclides José de Mendonça Filho, Sachin Patel, Zihan Wang, Guillaume Elgbeili, Irina Pokhvisneva, Carine Parent, Robert D. Levitan, Michael S. Kobor, Carla Dalmaz, Patrícia Pelufo Silveira

Bibliographic record

VenueBrain Behavior and Immunity · 2025
Typearticle
Languageen
FieldNeuroscience
TopicStress Responses and Cortisol
Canadian institutionsUniversity of British ColumbiaBC Children's HospitalUniversity of TorontoCentre for Addiction and Mental HealthMcGill University Health CentreMcGill UniversityDouglas Mental Health University Institute
Fundersnot available
KeywordsPeripheralLeptinMental healthGenePsychologyReceptorMedicinePsychiatryInternal medicineGeneticsBiologyObesity

Abstract

fetched live from OpenAlex

Psychiatric disorders are highly prevalent and often co-morbid with metabolic syndrome. Exposure to adversity in early life is a risk factor for both metabolic and behavioral problems, modifying leptin metabolism and signaling. Leptin is not only an energy-balance regulator, being also associated with the development of affective disorders. Our objective was to investigate if individual variations in peripheral leptin receptor (LepR) gene network function moderate the effect of childhood adversity on psychopathology. We created expression-based polygenic scores (ePRS) reflecting genetic variations that affect expression of the liver LepR gene network. We investigated the interaction between the LepR-ePRS and early adversity on mental health outcomes, namely anxiety and depression, in childhood (MAVAN) and adolescence (ALSPAC). In both cohorts, there were interaction effects between early adversity exposure and the liver-based LepR-ePRS, in which adversity was associated with depression only in individuals from the high ePRS group. Our findings suggest that exposure to early adversity is associated with mental health problems in children and adolescents. The liver leptin receptor gene network is an important moderator of these effects, and this may be due to individual differences within metabolic and inflammatory pathways represented by this gene network.

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)0.000
metaresearch head score (Gemma)0.000
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: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.008

Distilled classifier scores by category (both heads)

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 integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

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 head0.298
Teacher spread0.284 · 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

Citations1
Published2025
Admission routes1
Has abstractno

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