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Record W4416681818 · doi:10.1101/2025.11.10.25339891

As rates of ASD and ADHD rise, genetic contributions fall: Evidence for widening diagnostic criteria

2025· preprint· en· W4416681818 on OpenAlexaff
Sonja LaBianca, Mette Lise Lousdal, Morten Dybdahl Krebs, Ole Kromann Hansen, Kajsa-Lotta LA Georgii Hellberg, Mischa Lundberg, Johanne Østerby Sørensen, Jesper R. Gaadin, Henrik Ohlsson, Anders D. Børglum, Esben Agerbo, Thomas Werge, Clara Albiñana, Bjarni J. Vilhjálmsson, Kenneth S. Kendler, Oleguer Plana‐Ripoll, Andrew J. Schork

Bibliographic record

VenuemedRxiv · 2025
Typepreprint
Languageen
FieldNeuroscience
TopicAutism Spectrum Disorder Research
Canadian institutionsInstitute for Biological Sciences
FundersLundbeckfondenNational Institutes of HealthH. Lundbeck A/SRegion HovedstadenNational Institute of Mental HealthNovo Nordisk
KeywordsMedical diagnosisAutism spectrum disorderAutismGenetic testingGenetic diagnosisPsychiatric diagnosis

Abstract

fetched live from OpenAlex

Importance: The incidence of ADHD and autism spectrum disorder (ASD) has increased markedly over recent decades, raising concerns about the emergence of new risk factors. Current literature typically attributes increased rates to changes in diagnostic practice, stigmatization, and awareness, but critically few studies have explored changes in underlying risk factors. Objective: To assess changes in the genetic risk profile of individuals diagnosed with ASD or ADHD according to year of incident diagnosis. Design: We used the iPSYCH2015 study, a population-based case-cohort with complete ascertainment of incident diagnoses for ASD and ADHD made from 1994 to 2016. Setting: Denmark. Participants: ASD (N=17,071) and ADHD (N=20,111). Exposure: Year of incident diagnosis. Regression models tested changes in the mean genetic risk profile of individuals diagnosed in each consecutive year (1994-2016), adjusting for age, sex, and ancestry. Main Outcomes: We used polygenic scores for psychiatric (ADHD, ASD, depression, bipolar, schizophrenia) and cognitive-behavioral (addiction, educational attainment, IQ, neuroticism, risk-taking) outcomes to capture the genetic risk profiles of diagnosed individuals. Results: A more recent ADHD diagnosis was associated (p<0.001) with less genetic risk for ADHD (β=-0.06 SD per 10 years) and other disorders (ASD, bipolar, schizophrenia). Similarly, a more recent ASD diagnosis was associated with less genetic risk for ASD (β=-0.07) and other disorders/traits (bipolar, schizophrenia, educational attainment). Conclusions and Relevance: Our novel approach suggests that over recent decades diagnostic practice around ADHD and ASD has evolved to capture a different profile of genetic risk. These findings support broadening diagnostic criteria as the explanation for the rise in incidence, with implications for understanding prevalence trends in relation to changes in risk factors and clinical practice. KEY POINTS: Our results suggest that recent increase in ASD and ADHD diagnoses coincide with a broadening of diagnostic criteria.

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)0.032
metaresearch head score (Gemma)0.120
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 score0.043
Threshold uncertainty score0.169

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0320.120
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0040.004
Science and technology studies0.0010.003
Scholarly communication0.0020.003
Open science0.0030.003
Research integrity0.0010.002
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 head0.103
GPT teacher head0.426
Teacher spread0.323 · 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 abstractyes

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