Sex Differences in Autism Spectrum Disorders: Does Sex Moderate the Pathway from Clinical Symptoms to Adaptive Behavior?

Mandic-Maravic, Vanja; Pejovic-Milovancevic, Milica; Mitkovic-Voncina, Marija; Kostić, Milutin; Aleksić-Hil, Olivera; Radosavljev-Kircanski, Jelena; Minčić, Teodora; Lečić-Toševski, Dušica

doi:10.1038/srep10418

Cited by 45 publications

(33 citation statements)

References 32 publications

(59 reference statements)

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Section: Introductionmentioning

confidence: 99%

“…Thus far, studies of very young children have failed to identify sex differences in ASD symptoms among affected individuals [60, 61]. Outside of ASD-specific traits, one such study did also observe higher scores in affected females on the Daily Living Skills Subscale of the Vineland Adaptive Behavior Scales (VABS) [61]. Another study of male and female adults with ASD found no sex differences in retrospective reports of childhood autism traits, in keeping with the pattern above, but sex differences in social communication were apparent in adulthood [62].…”

Section: Introductionmentioning

confidence: 99%

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The role of sex-differential biology in risk for autism spectrum disorder

2016

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Autism spectrum disorder (ASD) is a developmental condition that affects approximately four times as many males as females, a strong sex bias that has not yet been fully explained. Understanding the causes of this biased prevalence may highlight novel avenues for treatment development that could benefit patients with diverse genetic backgrounds, and the expertise of sex differences researchers will be invaluable in this endeavor. In this review, I aim to assess current evidence pertaining to the sex difference in ASD prevalence and to identify outstanding questions and remaining gaps in our understanding of how males come to be more frequently affected and/or diagnosed with ASD. Though males consistently outnumber females in ASD prevalence studies, prevalence estimates generated using different approaches report male/female ratios of variable magnitude that suggest that ascertainment or diagnostic biases may contribute to the male skew in ASD. Here, I present the different methods applied and implications of their findings. Additionally, even as prevalence estimations challenge the degree of male bias in ASD, support is growing for the long-proposed female protective effect model of ASD risk, and I review the relevant results from recurrence rate, quantitative trait, and genetic analyses. Lastly, I describe work investigating several sex-differential biological factors and pathways that may be responsible for females’ protection and/or males’ increased risk predicted by the female protective effect model, including sex steroid hormone exposure and regulation and sex-differential activity of certain neural cell types. However, much future work from both the ASD and sex differences research communities will be required to flesh out our understanding of how these factors act to influence the developing brain and modulate ASD risk.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The role of sex-differential biology in risk for autism spectrum disorder

2016

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“…They also score higher on the “Taste, Smell, and Touch Response and Use” section of the Childhood Autism Rating Scale than boys with high functioning autism (Kumazakia, Muramatsub et al 2015). Finally, they are less likely to be diagnosed with typical autism than their male counterparts (Mandic-Maravic, Pejovic-Milovancevic et al 2015). …”

Section: Sex Differences In Autistic Diagnosis and Phenotypementioning

confidence: 99%

Developmental neurogenetics and multimodal neuroimaging of sex differences in autism

Chen

Horn

2016

Brain Imaging and Behavior

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Examining sex differences in the brain has been contentious but is nonetheless important for advancing mental health for both girls and boys. Unfortunately, females in biomedical research remain underrepresented in most mental health conditions including autism spectrum disorders (ASD), even though equal inclusion of females would improve treatment for girls and yield benefits to boys. This review examines sex differences in the relationship between neuroanatomy and neurogenetics of ASD. Recent findings reveal that girls diagnosed with ASD exhibit more intellectual and behavioral problems compared to their male counterparts, suggesting that girls may be less likely diagnosed in the absence of such problems or that they require a higher mutational load to meet the diagnostic criteria. Thus far, the female biased effect of chromosome 4, 5p15.33, 8p, 9p24.1, 11p12-13, 15q, and Xp22.3 and the male biased effect of 1p31.3, 5q12.3, 7q, 9q33.3, 11q13.4, 13q33.3, 16p11.2, 17q11-21, Xp22.33/Yp11.31, DRD1, NLGN3, MAOA, and SHANK1 deletion have been discovered in ASD. The SNPs of genes such as RYR2, UPP2, and the androgen receptor gene have been shown to have sex-biasing factors in both girls and boys diagnosed with ASD. These sex-related genetic factors may drive sex differences in the neuroanatomy of these girls and boys, including abnormal enlargement in temporal gray and white matter volumes, and atypical reduction in cerebellar gray matter volumes and corpus callosum fibers projecting to the anterior frontal cortex in ASD girls relative to boys. Such factors may also be responsible for the attenuation of brain sexual differentiation in adult men and women with ASD; however, much remains to be uncovered or replicated. Future research should leverage further the association between neuroanatomy and genetics in girls for an integrated and interdisciplinary understanding of ASD.

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“…According to the latest research, the prevalence of autism in children of 8 years of age is 1 in 68 (23.6 in 1000 boys and 5.3 in 1000 girls) (4). The prevalence of ASD is averagely four times higher in boys than in girls, which has been explored in several ways -using biological studies (5), but also exploring sex specific differences in clinical symptoms of ASD (6). Furthermore, recent analyses from 2008 indicate that the prevalence of autism has increased 23% since 2006 (7).…”

Section: Sažetakmentioning

confidence: 99%

Perinatal complications, environmental factors and autism spectrum disorders

Mandic-Maravic¹,

Pejović-Milovančević²,

Gazibara³

et al. 2016

Med podmladak

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Objectives: Autism spectrum disorders (ASD) are characterized by qualitative impairment of social interactions, impairment of verbal and nonverbal communication, as well as restricted interests and repetitive behavior. ASD represent a group of complex psychiatric disorders, with both genetic and environmental factors implicated in their etiology. Recent neuroanatomical and epidemiological studies point out to prenatal and early postnatal genesis of ASD. Aim: In this review, we present recent studies that explored the effect of environmental, prenatal and perinatal risk factors on development of ASD. Also, we point out those factors that have been proven to have the strongest association with ASD, and emphasize a very complex interaction of individual factors that might eventually lead to manifestation of this group of disorders. Conclusion: A precise defining of risk factors might provide more insight not only into etiology of ASD, but might also give us a possibility for early recognition and possible prevention of autism spectrum disorders, especially in susceptible individuals. It is also a first step in defining the basis of the gene-environment interaction mechanism, which might enable the development of an individualized therapeutic approach for this group of disorders.

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Sex Differences in Autism Spectrum Disorders: Does Sex Moderate the Pathway from Clinical Symptoms to Adaptive Behavior?

Cited by 45 publications

References 32 publications

The role of sex-differential biology in risk for autism spectrum disorder

The role of sex-differential biology in risk for autism spectrum disorder

Developmental neurogenetics and multimodal neuroimaging of sex differences in autism

Perinatal complications, environmental factors and autism spectrum disorders

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