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.