Fig. 3

Sex-related differences in attention deficit hyperactivity disorder and potential influence on blood–brain barrier development. A Attention deficit hyperactivity disorder (ADHD) is more prevalent in men than women at a ratio ranging between 4:1 and 9:1, and sex differences are reported not only in symptomatology but also in symptom severity. B Sex hormones may be implicated in ADHD pathophysiology. Increased circulating estrogen (during pregnancy, for example) has been associated with dampening of symptoms. Moreover, high prenatal testosterone exposure is a risk factor for ADHD. C Motor hyperactivity could represent a compensatory mechanism for low lactate shuttling into the brain via the BBB. D Single nucleotide polymorphisms (SNPs) of two vascular endothelial growth factor (VEGF) receptors, NRP1 and NRP2 interact with birth weight percentile predicting severity of hyperactive-impulsive symptoms. Likewise, sex-specific gene variants of two essential Wnt receptors, LRP5 and LRP6 are reported in children with ADHD, possibly implicating BBB-related alterations in this disorder. Full arrows represent empirical findings and dotted lines represent hypothetical associations. Considering the data available, we postulate that cerebrovascular factors, influenced by sex differences, may contribute to variations in the development and severity of ADHD symptoms, potentially highlighting a novel avenue for understanding and treating ADHD