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Record W4226168421 · doi:10.1038/s41380-022-01533-7

Corticolimbic DCC gene co-expression networks as predictors of impulsivity in children

2022· article· en· W4226168421 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueMolecular Psychiatry · 2022
Typearticle
Languageen
FieldEnvironmental Science
TopicHealth, Environment, Cognitive Aging
Canadian institutionsMcGill University Health CentreMcGill UniversityDouglas Mental Health University Institute
FundersNational Institute on Drug AbuseFonds de Recherche du Québec - SantéUniversité de MontréalJewish General HospitalCanadian Institutes of Health ResearchCanadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of CanadaGovernment of CanadaUniversity of BristolU.S. Department of Health and Human ServicesWellcome TrustMcGill UniversityMedical Research CouncilNational Healthcare GroupMcMaster University
KeywordsImpulsivityPsychologyExpression (computer science)Developmental psychologyNeuroscienceClinical psychologyComputer science

Abstract

fetched live from OpenAlex

Inhibitory control deficits are prevalent in multiple neuropsychiatric conditions. The communication- as well as the connectivity- between corticolimbic regions of the brain are fundamental for eliciting inhibitory control behaviors, but early markers of vulnerability to this behavioral trait are yet to be discovered. The gradual maturation of the prefrontal cortex (PFC), in particular of the mesocortical dopamine innervation, mirrors the protracted development of inhibitory control; both are present early in life, but reach full maturation by early adulthood. Evidence suggests the involvement of the Netrin-1/DCC signaling pathway and its associated gene networks in corticolimbic development. Here we investigated whether an expression-based polygenic score (ePRS) based on corticolimbic-specific DCC gene co-expression networks associates with impulsivity-related phenotypes in community samples of children. We found that lower ePRS scores associate with higher measurements of impulsive choice in 6-year-old children tested in the Information Sampling Task and with impulsive action in 6- and 10-year-old children tested in the Stop Signal Task. We also found the ePRS to be a better overall predictor of impulsivity when compared to a conventional PRS score comparable in size to the ePRS (4515 SNPs in our discovery cohort) and derived from the latest GWAS for ADHD. We propose that the corticolimbic DCC-ePRS can serve as a novel type of marker for impulsivity-related phenotypes in children. By adopting a systems biology approach based on gene co-expression networks and genotype-gene expression (rather than genotype-disease) associations, these results further validate our methodology to construct polygenic scores linked to the overall biological function of tissue-specific gene networks.

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.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesInsufficient payload (model declined to judge)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.051
Threshold uncertainty score0.999

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
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 head0.003
GPT teacher head0.222
Teacher spread0.219 · 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