Sex differences in pre-diagnosis concerns for children later diagnosed with autism spectrum disorder

Hiller, Rachel; Young, Robyn L.; Weber, Nathan

doi:10.1177/1362361314568899

Cited by 118 publications

(127 citation statements)

References 18 publications

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“…(31) This could explain the observation in some studies that the ratio of boys to girls is about 4 at younger ages, but rises closer to 2 in late childhood and beyond. (45–47) …”

Section: Discussionmentioning

confidence: 99%

Girls and Boys Born before 28 Weeks Gestation: Risks of Cognitive, Behavioral, and Neurologic Outcomes at Age 10 Years

Kuban

Joseph

O’Shea

et al. 2016

The Journal of Pediatrics

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Objectives To compare the prevalence of cognitive, neurological, and behavioral outcomes at 10 years of age in 428 girls and 446 boys who were born extremely preterm (EP). Study design 889 of 966 eligible children previously enrolled in the multi-center Extremely Low Gestational Age Newborns (ELGAN) Study from 2002–2004 were evaluated at 10 years of age. Children underwent a neuropsychological battery and testing for autism spectrum disorder (ASD), and parents reported on their child’s behavior, development, and seizures. Results 28% of boys and 21% of girls exhibited moderate to severe impairment on summary measures of cognitive abilities. Boys had a higher prevalence of impairment than girls in nearly all measures of cognition, were more than twice as likely to have microcephaly (15% in boys, 8% in girls), and require more often assistive devices to ambulate (6% in boys, 4% in girls). In contrast, boys and girls had comparable risk for a history of seizure (identified in 10% of the cohort) or epilepsy (identified in 7% of the cohort). The boy-to-girl ratio of ASD (9% in boys, 5% in girls) was lower than expected compared with the overall US autism population. Conclusion In this contemporary cohort of children born extremely premature and evaluated at school age, boys had higher prevalence of cognitive, neurological, and behavioral deficits than girls. The ratio of boys to girls among those with ASD deserves further study as does the perinatal environmental- genetic interactions that might contribute to male preponderance of deficits in this high-risk sample.

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“…(31) This could explain the observation in some studies that the ratio of boys to girls is about 4 at younger ages, but rises closer to 2 in late childhood and beyond. (45–47) …”

Section: Discussionmentioning

confidence: 99%

Girls and Boys Born before 28 Weeks Gestation: Risks of Cognitive, Behavioral, and Neurologic Outcomes at Age 10 Years

Kuban

Joseph

O’Shea

et al. 2016

The Journal of Pediatrics

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“…In other words, the early signs of autism presented by females might be different from that of males, hence the diagnosis may vary even when controlling for certain variables such as IQ or age. This has been demonstrated in a study where early signs of autism before diagnosis were obtained from caregivers and compared between males and females who later went on to be diagnosed with autism (Hiller et al 2015). It was found that there are sex differences in several “core” autistic symptoms early on, in that females were more likely to engage in mimicking in social settings as well as displaying a stronger desire to interact with peers, which is in contrast to males who displayed social isolation.…”

Section: Sex Differences In Brain Disorders (Human Clinical Studies)mentioning

confidence: 97%

Sex differences in neurodevelopmental and neurodegenerative disorders: Focus on microglial function and neuroinflammation during development

Hanamsagar

Bilbo

2016

The Journal of Steroid Biochemistry and Molecular Biology

307

208

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Several neurological conditions are associated with sex differences in prevalence or outcome. For example, autism predominantly affects boys, depression is more common in women, Parkinson's disease more common in men, and Multiple sclerosis in women. In the case of stroke, women have a less favorable outcome and suffer from a more precipitous drop in health status compared to men. As a result, treatment of such diseases is difficult and yields variable results. Despite this, sex is rarely considered when making treatment decisions. The mechanisms underlying sex differences in disease progression are not well understood, however a strong link exists between different inflammation states of men and women and their propensity to develop certain diseases. As neuroinflammation is an important component of pathophysiology in many neurological conditions, it can be speculated that any changes in the state of inflammation in the brain during normal development can potentially lead to an increase in susceptibility to neurological and neurodegenerative diseases. Microglia play a crucial role in onset and modulation of inflammation and thus sex differences in microglial function could explain, at least in part, differences observed in susceptibilities and outcomes of neurological disorders in men and women. Understanding the mechanisms behind sex differences could help develop more targeted therapy with higher success rate, especially in diseases where sex differences are most prominent.

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“…The application of this rote knowledge of social behavior may effectively hide an innate lack of skill in certain interactions, but the frequently monumental effort required to do this often goes unnoticed. In fact, though autistic females may have similar trouble with social communication as autistic boys do early in life, females may have greater social motivation and desire to be liked and engaged with her peers [62, 63]; this motivation may be what drives high functioning females in particular to camouflage their difficulties. It is unclear to what extent this desire and ability to compensate for social challenges by rote learning and performance of normative behaviors may be truly compensatory or protective against diagnosis in females, versus an exhausting and distressing burden for affected females to bear.…”

Section: Introductionmentioning

confidence: 99%

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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Sex differences in pre-diagnosis concerns for children later diagnosed with autism spectrum disorder

Cited by 118 publications

References 18 publications

Girls and Boys Born before 28 Weeks Gestation: Risks of Cognitive, Behavioral, and Neurologic Outcomes at Age 10 Years

Girls and Boys Born before 28 Weeks Gestation: Risks of Cognitive, Behavioral, and Neurologic Outcomes at Age 10 Years

Sex differences in neurodevelopmental and neurodegenerative disorders: Focus on microglial function and neuroinflammation during development

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

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