Youth (including both childhood and adolescence) is a period when the brain undergoes dramatic remodeling and is also a time when neuropsychiatric conditions often emerge. Many of these illnesses have substantial sex differences in prevalence, suggesting that sex differences in brain development may underlie differential risk for psychiatric symptoms between males and females. Substantial evidence documents sex differences in brain structure and function in adults, and accumulating data suggests that these sex differences may be present or emerge during development. Here we review the evidence for sex differences in brain structure, white matter organization, and perfusion during development. We then use these normative differences as a framework to understand sex differences in brain development associated with psychopathology. In particular, we focus on sex differences in the brain as they relate to anxiety, depression, psychosis, and attention-deficit/hyperactivity symptoms. Finally, we highlight existing limitations, gaps in knowledge, and fertile avenues for future research.
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This work was supported by a Research Supplement to Promote Diversity in Health-Related Research and NIMH grants (grant numbers: R01MH107703 to TDS; R01MH113550 to TDS) and by the Lifespan Brain Institute at the Children’s Hospital of Philadelphia and Penn Medicine. Support was also provided by a NARSAD Young Investigator Award (ANK), as well as a Building Interdisciplinary Research Careers in Women’s Health (BIRCWH) grant (K12 HD085848) and Penn PROMOTES Research on Sex and Gender in Health grant at the University of Pennsylvania (ANK). This research was funded in part by the Intramural Research Program of the NIMH (Clinical trial reg. no. NCT00001246, clinicaltrials.gov; NIH Annual Report Number, ZIA MH002794, Protocol ID 89-M-0006).
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Journal of Molecular Neuroscience (2019)