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.