Over the past 15 years, Giedd and colleagues at the NIMH have compiled normative growth curves for the brain. Their work reveals the heterochronous, regionally specific, and sexually dimorphic nature of brain development in which total cerebral volume is reached by age 10.5 in girls and age 14.5 in boys.26
Of particular importance for understanding sex differences in ADHD are the patterns of growth in the frontal lobes and basal ganglia (both known to be anomalous in ADHD). Bush32 found that frontal lobe gray matter volume peaks at around 9.5 years in girls and 10.5 years in boys. The caudate nucleus peaks at 10.5 years in girls and at 14.0 years in boys.
By adulthood, a number of regions of the brain are larger in women than in men (after adjusting for total cerebral volume), including the frontal lobes and hippocampus.33 Given these observations, when considering neuropsychiatric development in boys and girls in whom ADHD is suspected, it may be best to make determinations of “impairment” on the basis of sex-specific comparisons and to consider the different developmental course of ADHD in males and females.
Early neuroimaging studies of ADHD have identified widespread cortical and subcortical volumetric reductions, including delayed cortical maturation, among school-aged children with ADHD.34,35 To date, the generalizability of many published MRI findings in children with ADHD to girls with ADHD has been questioned because most conclusions have been based on samples consisting primarily (or exclusively) of boys, with girls underrepresented in imaging studies of ADHD.19
A recent meta-analysis of neuroimaging studies in ADHD found that only 20% of participants were female and only 50% of the ADHD samples included females.36 More recent brain mapping studies of ADHD suggest a more subtle pattern of neuroanatomic differences among girls that appears to parallel the earlier reduction in externalizing symptoms.
In a study that compared functional frontal lobe subdivisions in boys and girls with ADHD (aged 8 to 12 years), both boys and girls showed reductions in supplementary motor cortex. Conversely, boys (but not girls) showed reductions in dorsolateral prefrontal cortex, while girls (but not boys) showed reduced premotor cortex volumes. In both sexes, the differential reductions were associated with different patterns of executive dysfunction, but boys showed more relative problems with inhibitory control.37
In a study that assessed basal ganglia volume and shape in boys and girls with ADHD (aged 8 to 13 years) and age-matched controls, compared with controls, boys with ADHD showed compression in several regions, including the left anterior and right ventral putamen, the bilateral mid-body of the caudate, and the left dorsolateral and right ventromedial head of the caudate.38 However, no differences were observed in girls with ADHD compared with controls.