Understanding vulnerability through variability: a longitudinal twin study linking sex differences in neurodiversity, neurodevelopment and X-linked genetic mechanisms.

Abstract

Background: There are marked sex/gender differences in the prevalence and expression of neurodiversity. Yet, it is unclear how sex/gender related mechanisms may affect differences in expression of symptoms. In the present study we test whether previously reported greater male than female variability in neuroanatomy is related to sex differences in X-linked mechanisms and may explain behavioral and cognitive variation in neurodiversity. Method: The present study included a longitudinal twin study (N=990 twins; 56% monozygotic, 7-14 yo). Results: Greater male than female variability was most pronounced in structure and development of cortical surface area. Twin modeling results support a significant role of X-chromosome expression related to neuroanatomical variation. In addition, normative modeling analysis, showed that deviations in brain anatomy were associated to neurodiverse behavior. Conclusions: These findings together highlight the importance of studying sex and gender linked mechanisms in the brain and mental illness beyond mean group modeling.