Sex/gender differences and autism: setting the scene for future research.

OBJECTIVE: The relationship between sex/gender differences and autism has attracted a variety of research ranging from clinical and neurobiological to etiological, stimulated by the male bias in autism prevalence. Findings are complex and do not always relate to each other in a straightforward manner. Distinct but interlinked questions on the relationship between sex/gender differences and autism remain underaddressed. To better understand the implications from existing research and to help design future studies, we propose a 4-level conceptual framework to clarify the embedded themes. METHOD: We searched PubMed for publications before September 2014 using search terms "'sex OR gender OR females' AND autism." A total of 1,906 articles were screened for relevance, along with publications identified via additional literature reviews, resulting in 329 articles that were reviewed. RESULTS: Level 1, "Nosological and diagnostic challenges," concerns the question, "How should autism be defined and diagnosed in males and females?" Level 2, "Sex/gender-independent and sex/gender-dependent characteristics," addresses the question, "What are the similarities and differences between males and females with autism?" Level 3, "General models of etiology: liability and threshold," asks the question, "How is the liability for developing autism linked to sex/gender?" Level 4, "Specific etiological-developmental mechanisms," focuses on the question, "What etiological-developmental mechanisms of autism are implicated by sex/gender and/or sexual/gender differentiation?" CONCLUSIONS: Using this conceptual framework, findings can be more clearly summarized, and the implications of the links between findings from different levels can become clearer. Based on this 4-level framework, we suggest future research directions, methodology, and specific topics in sex/gender differences and autism.Dr. Lai has received grant or research support from the William Binks Autism Neuroscience Fellowship, the European Autism Interventions— A Multicentre Study for Developing New Medications (EU-AIMS), and Wolfson College, Cambridge University. Dr. Lombardo has received grant or research support from the British Academy, the Wellcome Trust, and Jesus College, Cambridge University. Dr. Auyeung has received grant or research support from the Wellcome Trust. Dr. Chakrabarti has received grant or research support from the UK Medical Research Council. Dr. Baron-Cohen has received grant or research support from the Wellcome Trust, the EU-AIMS, the UK Medical Research Council, and the Autism Research Trust.This is the final published version. It first appeared at http://www.sciencedirect.com/science/article/pii/S0890856714007254#