ReviewNeuron2022
Can the "female protective effect" liability threshold model explain sex differences in autism spectrum disorder?
Review in Neuron, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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.
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.
Who cites it
42 citing papers in PubMed, 55 citations in OpenAlex.
- Homozygous CHD8 mutation intensifies ASD phenotypes and attenuates sex differences.Molecular psychiatry · 2026Article
- Organoid intelligence: a promising paradigm for autism spectrum disorder research.Molecular psychiatry · 2026Review
- The NeuroWES project: lessons learned from comprehensive phenotyping and genetic analysis of neurodevelopmental disorders over a decade.Human genetics · 2026Article
- Sex-Specific Genetic Architecture of ALS: Evidence of a Female Protective Effect?Annals of neurology · 2026Article
- Modeling rare coding variation on chromosome X provides insight into the genetics and differential sex prevalence of autism spectrum disorder.medRxiv : the preprint server for health sciences · 2026Article
- Bazedoxifene reverses sexually dimorphic autistic-like abnormalities in biallelic MDGA1-mutant mice.EMBO molecular medicine · 2026Article
- The inactive X chromosome as a female protector in autism and beyond.Nature genetics · 2026Review
- Mitigating Sex-Related Biases to Elucidate the Autism Phenotype.Biological psychiatry · 2026Review
- Time trends in the male to female ratio for autism incidence: population based, prospectively collected, birth cohort study.BMJ (Clinical research ed.) · 2026Article
- Sex-dependent prediction of autism.Frontiers in genetics · 2026Article
- Sex Differences in the role of Additive Genetic Variants in Autism: A Systematic Review.medRxiv : the preprint server for health sciences · 2025Article
- Valproate-Induced Autism and Sexual Hormone Disturbances: A Literature Review and Hypotheses.Neurochemical research · 2025Review
- Transcriptomic Convergence and the Female Protective Effect in Autism.bioRxiv : the preprint server for biology · 2025Article
- Centrality of Touch Avoidance in Social Touch Experiences in Autism.Journal of autism and developmental disorders · 2025Article
- Social Communication, Repetitive Behaviors and Interests, and Adaptive Behavior in Girls With Autism Spectrum Disorder Without Intellectual Disability.Journal of autism and developmental disorders · 2025Article
- The inactive X chromosome as a female protector in autism and beyond.Research square · 2025Article
- Advancing precision diagnosis in autism: Insights from large-scale genomic studies.Molecules and cells · 2025Review
- Molecular Screening Reveals De Novo Loss-of-FunctionInternational journal of molecular sciences · 2025Article
- Single-cell technology grows up: Leveraging high-resolution omics approaches to understand neurodevelopmental disorders.Current opinion in neurobiology · 2025Review
- DecodingJournal of clinical medicine · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
Male sex is a strong risk factor for autism spectrum disorder (ASD). The leading theory for a "female protective effect" (FPE) envisions males and females have "differing thresholds" under a "liability threshold model" (DT-LTM). Specifically, this model posits that females require either a greater number or larger magnitude of risk factors (i.e., greater liability) to manifest ASD, which is supported by the finding that a greater proportion of females with ASD have highly penetrant genetic mutations. Herein, we derive testable hypotheses from the DT-LTM for ASD, investigating heritability, familial recurrence, correlation between ASD penetrance and sex ratio, population traits, clinical features, the stability of the sex ratio across diagnostic changes, and highlight other key prerequisites. Our findings reveal that several key predictions of the DT-LTM are not supported by current data, requiring us to establish a different conceptual framework for evaluating alternate models that explain sex differences in ASD.
Indexed as
Identifiers
What Socratic holds
Registered trials
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 Socratic graph.