ArticleProceedings of the National Academy of Sciences of the United States of America2017
Sex-specific gene-environment interactions underlying ASD-like behaviors.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 2 of them syntheses that pooled it.
What it found
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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.
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Who cites it
67 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Alteration of peripheral cortisol and autism spectrum disorder: A meta-analysis.Frontiers in psychiatry · 2022Pooled it
- Association of Hypertensive Disorders of Pregnancy With Risk of Neurodevelopmental Disorders in Offspring: A Systematic Review and Meta-analysis.JAMA psychiatry · 2018Pooled it
- The impact of probiotic treatment on sex-specific behavioral differences in valproic acid-induced autism animal model.Brain, behavior, & immunity - health · 2026Article
- Cell-type-specific disruption of nucleus accumbens social representations in a mouse model of autism.Neuron · 2026Article
- Association of cumulative early medical events and neurodevelopmental conditions through a common latent factor-A population-based twin study.JCPP advances · 2026Article
- Maternal Stress During Pregnancy Induces Higher Anxiety-Like Behavior in Male Mice Offspring Under Acute Stress by Upregulating CRF/CRFR1 and Driving Time-Specific Activation of the MHb-IPN Circuit.Neuroscience bulletin · 2026Article
- Placental and juvenile immune responses to maternal immune activation are differentially regulated by sex chromosomes and gonads across gestation.Journal of neuroinflammation · 2026Article
- Analysis of Gene, Environment, and Sex Interaction in the Development of Autistic-like Phenotype in Mice.International journal of molecular sciences · 2026Article
- The Convergence of Early-Life Stress and Autism Spectrum Disorder on the Epigenetics of Genes Key to the HPA Axis.Biology · 2025Review
- Sex-Specific Behavioral Features of Juvenile and Adult Haploinsufficient Scn2aGenes, brain, and behavior · 2025Article
- Digestive Neurobiology in Autism: From Enteric and Central Nervous System Interactions to Shared Genetic Pathways.International journal of molecular sciences · 2025Review
- Excess Neonatal Testosterone Causes Male-Specific Social and Fear Memory Deficits in Wild-Type Mice.eNeuro · 2025Article
- Autism Spectrum Disorder: From Experimental Models to Probiotic Application with a Special Focus onNutrients · 2025Review
- Transient CSF1R inhibition ameliorates behavioral deficits in Cntnap2 knockout and valproic acid-exposed mouse models of autism.Journal of neuroinflammation · 2024Article
- The contributions of neonatal inhalation of copper to air pollution-induced neurodevelopmental outcomes in mice.Neurotoxicology · 2024Article
- Sexual dimorphism in the social behaviour of Cntnap2-null mice correlates with disrupted synaptic connectivity and increased microglial activity in the anterior cingulate cortex.Communications biology · 2023Article
- [Association between maternal gestational diabetes mellitus and the risk of autism spectrum disorder in offspring].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2023Article
- Characterizing maternal isolation-induced ultrasonic vocalizations in a gene-environment interaction rat model for autism.Genes, brain, and behavior · 2023Article
- Review
- Sex-Specific Neurodevelopmental Outcomes Among Offspring of Mothers With SARS-CoV-2 Infection During Pregnancy.JAMA network open · 2023Article
7 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The male bias in the incidence of autism spectrum disorders (ASDs) is one of the most notable characteristics of this group of neurodevelopmental disorders. The etiology of this sex bias is far from known, but pivotal for understanding the etiology of ASDs in general. Here we investigate whether a "three-hit" (genetic load × environmental factor × sex) theory of autism may help explain the male predominance. We found that LPS-induced maternal immune activation caused male-specific deficits in certain social responses in the contactin-associated protein-like 2 (Cntnap2) mouse model for ASD. The three "hits" had cumulative effects on ultrasonic vocalizations at postnatal day 3. Hits synergistically affected social recognition in adulthood: only mice exposed to all three hits showed deficits in this aspect of social behavior. In brains of the same mice we found a significant three-way interaction on corticotropin-releasing hormone receptor-1 (Crhr1) gene expression, in the left hippocampus specifically, which co-occurred with epigenetic alterations in histone H3 N-terminal lysine 4 trimethylation (H3K4me3) over the Crhr1 promoter. Although it is highly likely that multiple (synergistic) interactions may be at work, change in the expression of genes in the hypothalamic-pituitary-adrenal/stress system (e.g., Crhr1) is one of them. The data provide proof-of-principle that genetic and environmental factors interact to cause sex-specific effects that may help explain the male bias in ASD incidence.
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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.