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Typical Male Brain Anatomy Associated With Higher Probability of Autism Spectrum Disorder

Summary: A new study reports neurotypical male brain anatomy is associated with a higher risk of ASD, and biological females with more typical male brain anatomy are three times more likely to be diagnosed with ASD.

Source: JAMA Network.

A study of high-functioning adults with autism spectrum disorder (ASD) suggests that characteristically male brain anatomy was associated with increased probability of ASD, according to a new article published online by JAMA Psychiatry.

ASD is a neurodevelopmental condition that is more common in males then females. Christine Ecker, Ph.D., of Goethe University, Frankfurt, Germany, and coauthors examined the probability of ASD as a function of sex-related variation in brain anatomy.

The study included 98 right-handed, high-functioning adults with ASD and 98 neurotypical adults (ages 18 to 42 years) for comparison. Imaging and statistical analysis were used to assess ASD probability. The study based its analysis on cortical thickness in the brain because that can vary between males and females and be altered in people with ASD, according to the article.

The authors report characteristically male anatomy of the brain was associated with a higher probability of risk for ASD than characteristically female brain anatomy. For example, biological females with more typical male brain anatomy were about three times more likely to have ASD than biological females with characteristically female brain anatomy, according to the study.

Image shows different areas higlighted in a 'typical' male and female brain.

Predictive maps (ie, w × CT) associated with low and high probability of ASD in female individuals (A) and male individuals (B). Low ASD probability maps were computed across all male individuals (or female individuals) with predictive probabilities lower than 0.5 (ie, biological male individuals or female individuals falling into the category of phenotypic female individuals). High ASD probability maps were computed across all male individuals (or female individuals) with predictive probabilities larger than 0.5 (ie, biological male individuals or female individuals falling into the category of phenotypic male individuals). At each vertex, the color scale thus indicates the product of the weight vector w and cortical thickness (CT), averaged across all individuals within the 4 probability groups. The probability of ASD was determined as the number of male individuals (or female individuals) with ASD relative to the total number of individuals within predictive probability bins. NeuroscienceNews.com image is credited to Ecker et al./JAMA Psychiatry.

The authors note limitations of their findings, including the need for future research to examine possible causes. The study findings also must be replicated in other subgroups on the autism spectrum. “Our study demonstrates that normative sex-related phenotypic diversity in brain structure affects the prevalence of ASD in addition to biological sex alone, with male neuroanatomical characteristics carrying a higher intrinsic risk for ASD than female characteristics,” the article concludes.

About this autism research article

Source: Christine Ecker, Ph.D – JAMA Network
Image Source: NeuroscienceNews.com image is credited to Ecker et al./JAMA Psychiatry..
Original Research: Full open access research for “Association Between the Probability of Autism Spectrum Disorder and Normative Sex-Related Phenotypic Diversity in Brain Structure” by Christine Ecker, PhD; Derek S. Andrews, MSc; Christina M. Gudbrandsen, MSc; Andre F. Marquand, PhD; Cedric E. Ginestet, PhD; Eileen M. Daly, PhD; Clodagh M. Murphy, PhD; Meng-Chuan Lai, PhD; Michael V. Lombardo, PhD; Amber N. V. Ruigrok, PhD; Edward T. Bullmore, PhD, FRCPsych; John Suckling, PhD; Steven C. R. Williams, PhD; Simon Baron-Cohen, PhD; Michael C. Craig, PhD; Declan G. M. Murphy, FRCPsych; for the Medical Research Council Autism Imaging Multicentre Study (MRC AIMS) Consortium in JAMA Psychiatry. Published online February 8 2017 doi:10.1001/jamapsychiatry.2016.3990

Cite This NeuroscienceNews.com Article
JAMA Network “Typical Male Brain Anatomy Associated With Higher Probability of Autism Spectrum Disorder.” NeuroscienceNews. NeuroscienceNews, 8 February 2017.
<http://neurosciencenews.com/male-brain-asd-6078/>.
JAMA Network (2017, February 8). Typical Male Brain Anatomy Associated With Higher Probability of Autism Spectrum Disorder. NeuroscienceNew. Retrieved February 8, 2017 from http://neurosciencenews.com/male-brain-asd-6078/
JAMA Network “Typical Male Brain Anatomy Associated With Higher Probability of Autism Spectrum Disorder.” http://neurosciencenews.com/male-brain-asd-6078/ (accessed February 8, 2017).

Abstract

Association Between the Probability of Autism Spectrum Disorder and Normative Sex-Related Phenotypic Diversity in Brain Structure

Importance Autism spectrum disorder (ASD) is 2 to 5 times more common in male individuals than in female individuals. While the male preponderant prevalence of ASD might partially be explained by sex differences in clinical symptoms, etiological models suggest that the biological male phenotype carries a higher intrinsic risk for ASD than the female phenotype. To our knowledge, this hypothesis has never been tested directly, and the neurobiological mechanisms that modulate ASD risk in male individuals and female individuals remain elusive.

Objectives To examine the probability of ASD as a function of normative sex-related phenotypic diversity in brain structure and to identify the patterns of sex-related neuroanatomical variability associated with low or high probability of ASD.

Design, Setting, and Participants This study examined a cross-sectional sample of 98 right-handed, high-functioning adults with ASD and 98 matched neurotypical control individuals aged 18 to 42 years. A multivariate probabilistic classification approach was used to develop a predictive model of biological sex based on cortical thickness measures assessed via magnetic resonance imaging in neurotypical controls. This normative model was subsequently applied to individuals with ASD. The study dates were June 2005 to October 2009, and this analysis was conducted between June 2015 and July 2016.

Main Outcomes and Measures Sample and population ASD probability estimates as a function of normative sex-related diversity in brain structure, as well as neuroanatomical patterns associated with low or high ASD probability in male individuals and female individuals.

Results Among the 98 individuals with ASD, 49 were male and 49 female, with a mean (SD) age of 26.88 (7.18) years. Among the 98 controls, 51 were male and 47 female, with a mean (SD) age of 27.39 (6.44) years. The sample probability of ASD increased significantly with predictive probabilities for the male neuroanatomical brain phenotype. For example, biological female individuals with a more male-typic pattern of brain anatomy were significantly (ie, 3 times) more likely to have ASD than biological female individuals with a characteristically female brain phenotype (P = .72 vs .24, respectively; χ21 = 20.26; P < .001; difference in P values, 0.48; 95% CI, 0.29-0.68). This finding translates to an estimated variability in population prevalence from 0.2% to 1.3%, respectively. Moreover, the patterns of neuroanatomical variability carrying low or high ASD probability were sex specific (eg, in inferior temporal regions, where ASD has different neurobiological underpinnings in male individuals and female individuals).

Conclusions and Relevance These findings highlight the need for considering normative sex-related phenotypic diversity when determining an individual’s risk for ASD and provide important novel insights into the neurobiological mechanisms mediating sex differences in ASD prevalence.

“Association Between the Probability of Autism Spectrum Disorder and Normative Sex-Related Phenotypic Diversity in Brain Structure” by Christine Ecker, PhD; Derek S. Andrews, MSc; Christina M. Gudbrandsen, MSc; Andre F. Marquand, PhD; Cedric E. Ginestet, PhD; Eileen M. Daly, PhD; Clodagh M. Murphy, PhD; Meng-Chuan Lai, PhD; Michael V. Lombardo, PhD; Amber N. V. Ruigrok, PhD; Edward T. Bullmore, PhD, FRCPsych; John Suckling, PhD; Steven C. R. Williams, PhD; Simon Baron-Cohen, PhD; Michael C. Craig, PhD; Declan G. M. Murphy, FRCPsych; for the Medical Research Council Autism Imaging Multicentre Study (MRC AIMS) Consortium in JAMA Psychiatry. Published online February 8 2017 doi:10.1001/jamapsychiatry.2016.3990

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