Etiologies underlying sex differences in Autism Spectrum Disorders

@article{Schaafsma2014EtiologiesUS,
  title={Etiologies underlying sex differences in Autism Spectrum Disorders},
  author={Sara M. Schaafsma and Donald W. Pfaff},
  journal={Frontiers in Neuroendocrinology},
  year={2014},
  volume={35},
  pages={255-271}
}
The male predominance of Autism Spectrum Disorders (ASD) is one of the best-known, and at the same time, one of the least understood characteristics of these disorders. In this paper we review genetic, epigenetic, hormonal, and environmental mechanisms underlying this male preponderance. Sex-specific effects of Y-linked genes (including SRY expression leading to testicular development), balanced and skewed X-inactivation, genes that escape X-inactivation, parent-of-origin allelic imprinting… 
View on Elsevier
doi.org
128 Citations
Highly Influential Citations
8
Background Citations
42
Results Citations
1

128 Citations

Citation Type

Citation Type

Sex-specific gene–environment interactions underlying ASD-like behaviors
TLDR
It was found that LPS-induced maternal immune activation caused male-specific deficits in certain social responses in the contactin-associated protein-like 2 mouse model for ASD, providing proof-of-principle that genetic and environmental factors interact to cause sex-specific effects that may help explain the male bias in ASD incidence.
Sex Differences in Autism Spectrum Disorder: a Review
TLDR
Current findings and theories that contribute to male preponderance of neurodevelopmental disorders, with a focus on autism are reviewed, and the possibilities of female underdiagnosis and a multi-hit hypothesis are discussed.
Incidence and Characteristics of ASD
Autism spectrum disorder (ASD) is a class of neurodevelopmental disorders that affects males more frequently than females. Numerous genetic and environmental risk factors have been suggested to…
The epigenetics of autism
TLDR
The key epigenetic mechanisms, such as DNA methylation and histone modifications, as potential contributors to the etiopathogenesis of ASCs are discussed.
Endocrine Insights into the Pathophysiology of Autism Spectrum Disorder
TLDR
Emerging evidence suggests that the placenta may be particularly important as a mediator of the actions of environmental and endocrine risk factors on the developing brain, with the male being particularly sensitive to these effects.
Sex/gender differences in neurology and psychiatry: Autism.
TLDR
It is concluded that current research points toward coexisting quantitative and qualitative sex/gender-modulation effects in autism across multiple neurobiological aspects, and that future research should use big data approaches and new stratification methods to decompose sex- and gender-related heterogeneity in autism and work toward personalized, sex/ gender-informed intervention and support for autistic people.
Genes and sex hormones interaction in neurodevelopmental disorders
TLDR
Findings suggest that modulation of sex steroid-related pathways may represent an innovative approach for neurodevelopmental disorders of well-established genetic origin, and much effort is now expected to unravel the potential therapeutic efficacy of drugs targeting sex hormones-related signaling pathways.
Biological factors underlying sex differences in neurological disorders.
TLDR
Better understanding of regulation and function of SRY in the male brain could provide entirely novel and important insights into genetic factors involved in the susceptibility of men to neurological disorders, as well as development of novel sex-specific therapies.
Investigation of sex differences in the expression of RORA and its transcriptional targets in the brain as a potential contributor to the sex bias in autism
TLDR
It is suggested that disruption of Rora/RORA expression may have a greater impact on males, since sex differences in the correlation of R ORA and target gene expression indicate that RORA-deficient males may experience greater dysregulation of genes relevant to ASD in certain brain regions during development.
The Genetic and Epigenetic Basis Involved in the Pathophysiology of ASD: Therapeutic Implications
TLDR
The current literature regarding the epigenetic changes involved in ASD is reviewed, including their possible mechanisms of action such as oxidative stress, altered fatty acid metabolism, mitochondrial dysfunction, DNA methylation and histone methylation (via the one‐carbon metabolism cycle), histone variants, and ATP‐dependent chromatin remodeling.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 276 REFERENCES
Autism in association with Turner syndrome: Genetic implications for male vulnerability to pervasive developmental disorders
Genetic factors play a substantial part in the aetiology of autism, although no satisfactory model has been proposed that could account for the excess of male phenotypes. We present five cases of…
Possible association between the androgen receptor gene and autism spectrum disorder
TLDR
The results lend some support for an influence of the studied polymorphisms on the susceptibility for autism, but argue against the possibility that mutations in the AR gene are common in subjects with this condition.
The epidemiology of autism spectrum disorders.
TLDR
Future epidemiologic research should focus on expanding population-based descriptive data on ASDs, exploring candidate risk factors in large well-designed studies incorporating both genetic and environmental exposure data and addressing possible etiologic heterogeneity in studies that can stratify case groups and consider alternate endophenotypes.
Evidence for sex-specific risk alleles in autism spectrum disorder.
TLDR
The results suggest that sexual dichotomy is an important factor in the genetics of autism; the same strategy can be used to explore this possibility in other complex disorders that exhibit significant sex biases.
Genes related to sex steroids, neural growth, and social–emotional behavior are associated with autistic traits, empathy, and Asperger syndrome
TLDR
A study of common genetic variation in candidate genes associated with autistic traits and Asperger syndrome (AS), and the first candidate‐gene association study of AS and of autistic traits.
Disruption at the PTCHD1 Locus on Xp22.11 in Autism Spectrum Disorder and Intellectual Disability
TLDR
Genetic analysis in thousands of patients and control subjects suggests that the PTCHD1 gene may be part of the Hedgehog signaling pathway, which is important in embryonic development, and suggests that this locus is involved in ~1% of individuals with ASD and intellectual disability.
Traits of ADHD and autism in girls with a twin brother: a Mendelian randomization study
TLDR
It is found that female twins with a twin brother scored significantly lower in parent-reported traits of ADHD and ASD than those with a twins sister, indicating that a twinbrother reduces traits of attention-deficit/hyperactivity disorder and ASD in females.
Why Are Autism Spectrum Conditions More Prevalent in Males?
TLDR
Some of the evidence relating to the EMB theory of ASC is described and how typical sex differences in brain structure may be relevant to ASC is considered, as these theories are not mutually exclusive and ASC is multi-factorial.
Opinion: Sex, Gender and the Diagnosis of Autism - A Biosocial View of the Male Preponderance.
  • Sylvie Goldman
  • Psychology, Medicine
    Research in autism spectrum disorders
  • 2013
TLDR
The goal of this article is to draw attention to the role of gender-based socialization practices and behavioral expectations during the clinical evaluation, together with gender-biased standardized instruments used to support the diagnosis of ASD, to contribute to the higher prevalence of males with ASD.
Genetic and Immunologic Considerations in Autism
TLDR
This review summarizes advances in the molecular genetics of autism, as well as recently emerging concerns addressing the disease incidence and triggering factors, and discusses evidence of similar phenomena in autism.
...
1
2
3
4
5
...