Sex differences in the blood–brain barrier: Implications for mental health

Prevalence of mental disorders, including major depressive disorder (MDD), bipolar disorder (BD) and schizophrenia (SZ) are increasing at alarming rates in our societies. Growing evidence points toward major sex differences in these conditions, and high rates of treatment resistance support the need to consider novel biological mechanisms outside of neuronal function to gain mechanistic insights that could lead to innovative therapies. Blood-brain barrier alterations have been reported in MDD, BD and SZ. Here, we provide an overview of sex-specific immune, endocrine, vascular and transcriptional-mediated changes that could affect neurovascular integrity and possibly contribute to the pathogenesis of mental disorders. We also identify pitfalls in current literature and highlight promising vascular biomarkers. Better understanding of how these adaptations can contribute to mental health status is essential not only in the context of MDD, BD and SZ but also cardiovascular diseases and stroke which are associated with higher prevalence of these conditions.