title: Imaging sex/gender and autism in the brain: Etiological implications.
abstract: The male preponderance in autism prevalence has brought together the disparate topics of sex/gender and autism research. Two directions of neuroimaging studies on the relationships between sex/gender and autism may inform male-specific risk mechanisms and female-specific protective mechanisms of autism. First, we review how sex/gender moderates autism-related brain changes and how this informs general models of autism etiology. Better-powered human neuroimaging studies suggest that the brain characteristics of autism are qualitatively, rather than simply quantitatively, different between males and females. However, age and comorbidities might substantially moderate the pattern of differences. Second, we review how the relationship between autism-related brain changes (separately in males and females) and normative brain sex/gender differences informs specific etiological-developmental mechanisms. Both human and animal studies converge to indicate that the brain characteristics of autism are partly associated with normative brain sex/gender differences, suggesting convergence or overlap between the mechanisms leading to and modifying the development of autism and the mechanisms underlying sex differentiation and/or gender socialization. Future animal work needs to investigate sex differences in rodent mutants modeling autism-relevant genes and environmental exposures. Future human work needs to address the substantial phenotypic and etiological heterogeneity of autism and to focus on longitudinal neuroimaging studies (from early development) on the developmental trajectories of sex/gender-differential neural characteristics of autism. Combining animal and human work links up the causal chain from etiological factors, brain and physical development, to phenotypes. These together help delineate the different roles of sex and gender in relation to risk vs. protective mechanisms. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Child and Youth Mental Health Collaborative at the Centre for Addiction and Mental Health and the Hospital for Sick Children, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.|Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.|Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
authors.forename: Meng-Chuan
authors.initials: MC
authors.lastname: Lai
authors.affiliation: Mouse Imaging Centre, Hospital for Sick Children, Toronto, Ontario, Canada.|Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Jason P
authors.initials: JP
authors.lastname: Lerch
authors.affiliation: Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.|New York University Child Study Center, New York, New York, USA.
authors.forename: Dorothea L
authors.initials: DL
authors.lastname: Floris
authors.affiliation: Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Amber N V
authors.initials: AN
authors.lastname: Ruigrok
authors.affiliation: Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Alexa
authors.initials: A
authors.lastname: Pohl
authors.affiliation: Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.|Department of Psychology and Center of Applied Neuroscience, University of Cyprus, Nicosia, Cyprus.
authors.forename: Michael V
authors.initials: MV
authors.lastname: Lombardo
authors.affiliation: Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.|CLASS Clinic, Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, United Kingdom.
authors.forename: Simon
authors.initials: S
authors.lastname: Baron-Cohen
mesh_terms: D000375:Aging; D001321:Autistic Disorder / Q000000981:diagnostic imaging* / Q000209:etiology*; D001921:Brain / Q000000981:diagnostic imaging* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D059906:Neuroimaging; D012727:Sex Characteristics
keywords: animal model; autism; brain; etiology; gender; neuroimaging; sex