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Sex is a biological variable that contributes to individual variability in brain structure and behavior. Neuroimaging studies of population‐based samples have identified normative differences in brain structure between males and females, many of which are exacerbated in psychiatric and neurological conditions. Still, sex differences in MRI outcomes are understudied, particularly in clinical samples with known sex differences in disease risk, prevalence, and expression of clinical symptoms. Here we review the existing literature on sex differences in adult brain structure in normative samples and in 14 distinct psychiatric and neurological disorders. We discuss commonalities and sources of variance in study designs, analysis procedures, disease subtype effects, and the impact of these factors on MRI interpretation. Lastly, we identify key problems in the neuroimaging literature on sex differences and offer potential recommendations to address current barriers and optimize rigor and reproducibility. In particular, we emphasize the importance of large‐scale neuroimaging initiatives such as the Enhancing NeuroImaging Genetics through Meta‐Analyses consortium, the UK Biobank, Human Connectome Project, and others to provide unprecedented power to evaluate sex‐specific phenotypes in major brain diseases. [ABSTRACT FROM AUTHOR]

Secondhand smoke exposure is a major public health risk that is especially harmful to the developing brain, but it is unclear if early exposure affects brain structure during middle age and older adulthood. Here we analyzed brain MRI data from the UK Biobank in a population-based sample of individuals (ages 44-80) who were exposed (n = 2510) or unexposed (n = 6079) to smoking around birth. We used robust statistical models, including quantile regressions, to test the effect of perinatal smoke exposure (PSE) on cortical surface area (SA), thickness, and subcortical volumes. We hypothesized that PSE would be associated with cortical disruption in primary sensory areas compared to unexposed (PSE-) adults. After adjusting for multiple comparisons, SA was significantly lower in the pericalcarine (PCAL), inferior parietal (IPL), and regions of the temporal and frontal cortex of PSE+ adults; these abnormalities were associated with increased risk for several diseases, including circulatory and endocrine conditions. Sensitivity analyses conducted in a hold-out group of healthy participants (exposed, n = 109, unexposed, n = 315) replicated the effect of PSE on SA in the PCAL and IPL. Collectively our results show a negative, long term effect of PSE on sensory cortices that may increase risk for disease later in life., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)