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DNA Methylation, Prenatal Maternal Stress and the Broad Autism Phenotype in Adolescence: Project Ice Storm

2025· preprint· en· W4411632694 on OpenAlexfundaboutno aff
Lei Cao-Lei, Guillaume Elgbeili, David P. Laplante, Moshe Szyf, Suzanne King

Bibliographic record

VenuePreprints.org · 2025
Typepreprint
Languageen
FieldMedicine
TopicChild Nutrition and Feeding Issues
Canadian institutionsnot available
FundersCanadian Institutes of Health Research
KeywordsDNA methylationPhenotypeAutismEpigeneticsStormPrenatal stressMethylationPsychologyGeneticsDevelopmental psychologyDNABiologyPregnancyGeographyMeteorologyGene

Abstract

fetched live from OpenAlex

Background/Objectives. Prenatal maternal stress (PNMS) predicts risk for autism spectrum disorders (ASD) although the mechanisms are unknown. The aim of this study was to determine the extent to which DNA methylation mediates the effects of PNMS from a natural disaster on autistic-like traits in offspring assessed during adolescence. Methods. Five months following the 1998 ice storm in Quebec, Canada we recruited women who had been pregnant during the crisis and assessed their PNMS: objective hardship, subjective distress, and cognitive appraisal. At age 13, their children provided blood samples for DNA. At ages 15, 16 and 19, the youth self-reported their own autistic-like traits using the Broad Autism Phenotype Questionnaire. Results. Results showed that mothers’ disaster-related objective hardship and their negative cognitive appraisal of the disaster predicted DNA methylation at age 13, which then predicted the severity of their children’s Aloof Personality and Pragmatic Language Deficits, but not Rigid Personality, at ages 15, 16 and 19. Mediation was significant particularly through genes within the PI3K/AKT/mTOR pathway which has been implicated in various neurodevelopmental disorders, including ASD. Interestingly, while greater PNMS predicted more severe ASD traits, the epigenetics effects were for less severe traits. Conclusions. These results suggest that DNA methylation, assessed in early adolescence, may protect against ASD traits at later ages, particularly when there is a mismatch between the prenatal environment (disaster) and the postnatal environment (absence of disaster). The interpretation of these results in the context of fetal programming and the predictive adaptive response are discussed.

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)0.001
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 score0.456
Threshold uncertainty score0.906

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0010.000
Scholarly communication0.0000.000
Open science0.0000.001
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 head0.064
GPT teacher head0.355
Teacher spread0.291 · 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 routes2
Has abstractyes

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