Evidence map›Paper›PMID 40098476›Full record

ArticlePsychological medicine2025

Integrating causal discovery and clinically-relevant insights to explore directional relationships between autistic features, sex at birth, and cognitive abilities.

Angela Tseng, Sunday M Francis, Eric Rawls, Christine Conelea, Nicola M Grissom, Erich Kummerfeld, Sisi Ma, Suma Jacob

Erratum issuedAbstract read
In one paragraph

Article in Psychological medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Angela TsengDivision of Child & Adolescent Psychiatry, Semel Institute of Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA, USA.
Sunday M FrancisDepartment of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis, MN, USA.
Eric RawlsDepartment of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis, MN, USA.
Christine ConeleaDepartment of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis, MN, USA.
Nicola M GrissomDepartment of Psychology, University of Minnesota, Minneapolis, MN, USA.
Erich KummerfeldInstitute for Health Informatics, University of Minnesota, Minneapolis, MN, USA.
Sisi MaInstitute for Health Informatics, University of Minnesota, Minneapolis, MN, USA.
Suma JacobDivision of Child & Adolescent Psychiatry, Semel Institute of Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA, USA.ORCID 0000-0001-7434-7398

Funding

Non-invasive Neuromodulation Unit (NNU)ZIAMH002955 · NIMH · NATIONAL INSTITUTE OF MENTAL HEALTH · PI ZARATE, CARLOS · 2016 to 2025
$40.3M
University of Minnesota Clinical and Translational Science Institute (UMN CTSI)UL1TR002494 · NCATS · UNIVERSITY OF MINNESOTA · PI BLAZAR, BRUCE R, WEISDORF, DANIEL J · 2018 to 2022
$34.9M
Parsing early emerging heterogeneity related to autism spectrum disorderR01MH115046 · NIMH · UNIVERSITY OF MINNESOTA · PI ELISON, JED THOMAS, JACOB, SUMA · 2019 to 2023
$3.8M
Sex-biased impacts of 16p11.2 variants on reward-guided choiceR01MH123661 · NIMH · UNIVERSITY OF MINNESOTA · PI GRISSOM, NICOLA · 2020 to 2024
$2.5M
Using Computation to Achieve Breakthroughs in NeuroscienceT32MH115886 · NIMH · UNIVERSITY OF MINNESOTA · PI REDISH, A DAVID · 2018 to 2022
$1.7M
Clinical and Translational Science Institute, University of Minnesota TL1R002493Intramural NIH HHS ZIA MH002955NCATS NIH HHS UL1 TR002494NIMH NIH HHS R01 MH115046NIMH NIH HHS R01 MH123661NIMH NIH HHS T32 MH115886
6 · The paper itself

Abstract

backgroundAccess to "big data" is a boon for researchers, fostering collaboration and resource-sharing to accelerate advancements across fields. Yet, disentangling complex datasets has been hindered by methodological limitations, calling for alternative, interdisciplinary approaches to parse manifold multi-directional pathways between clinical features, particularly for highly heterogeneous autism spectrum disorder (ASD). Despite a long history of male-bias in ASD prevalence, no consensus has been reached regarding mechanisms underlying sex-related discrepancies.

methodsApplying a novel network-theory-based approach, we extracted data-driven, clinically-relevant insights from a well-characterized sample (http://sfari.org/simons-simplex-collection) of autistic males (N = 2175, Age = 8.9 ± 3.5 years) and females (N = 334, Age = 9.2 ± 3.7 years). Expert clinical review of exploratory factor analysis (EFA) results yielded factors of interest in sensory, social, and restricted and repetitive behavior domains. To offset inherent confounds of sample imbalance, we identified a comparison subgroup of males (N = 331) matched to females (by age, IQ). We applied data-driven causal discovery analysis (CDA) using Greedy Fast Causal Inference (GFCI) on three groups (all females, all males, matched males). Structural equation modeling (SEM) extracted measures of model-fit and effect sizes for causal relationships between sex, age-at-enrollment, and IQ on EFA-determined factors.

resultsWe identified potential targets for intervention at nodes with mediating or indirect effects. For example, in the female and matched male groups, analyses suggest mitigating RRB domain behaviors may lead to downstream reductions in oppositional and self-injurious behaviors.

conclusionsOur investigation unveiled sex-specific directional relationships that inform our understanding of differing needs and outcomes associated with biological sex in autism and may serve to further development of targeted interventions.

Indexed as

Autism Spectrum DisorderCognitionAdolescentChildFemaleHumansMaleSex FactorsAutismCausal Discovery AnalysisCognitiveRestricted and Repetitive Behaviors (RRBs)Sex Differences

Identifiers

PMID40098476
PMCPMC12080652

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.