Impact of Sex and Gonadal Steroids on Neonatal Brain Structure

Abstract

There are numerous reports of sexual dimorphism in brain structure in children and adults, but data on sex differences in infancy are extremely limited. Our primary goal was to identify sex differences in neonatal brain structure. Our secondary goal was to explore whether brain structure was related to androgen exposure or sensitivity. Two hundred and ninety-three neonates (149 males) received high-resolution structural magnetic resonance imaging scans. Sensitivity to androgen was measured using the number of cytosine, adenine, guanine (CAG) triplets in the androgen receptor gene and the ratio of the second to fourth digit, provided a proxy measure of prenatal androgen exposure. There was a significant sex difference in intracranial volume of 5.87%, which was not related to CAG triplets or digit ratios. Tensor-based morphometry identified extensive areas of local sexual dimorphism. Males had larger volumes in medial temporal cortex and rolandic operculum, and females had larger volumes in dorsolateral prefrontal, motor, and visual cortices. Androgen exposure and sensitivity had minor sex-specific effects on local gray matter volume, but did not appear to be the primary determinant of sexual dimorphism at this age. Comparing our study with the existing literature suggests that sex differences in cortical structure vary in a complex and highly dynamic way across the human lifespan.

Gender affects early psychomotor milestones and long‐term neurodevelopment of preterm infants

“…Nevertheless, specific frontal, temporal, and parietal cortex regions, known to be involved in hand gesture imitation (Perkins, Bittar, McGillivray, Cox, & Stokes, ), displayed different activation patterns in male‐biased neurodevelopmental disorders such as autism. Larger volume of the orbitofrontal cortex, involved in social cognition, has been shown in females during childhood and adulthood (Knickmeyer et al, ). Our time‐related evaluation of pointing may be consistent with a faster maturation of social skills in girls that was persistently observed in the long‐term GMDS assessment by personal–social subscale where females showed better outcomes in activities of daily living, level of independence, and social interaction.…”

Imaging structural and functional brain development in early childhood

“…Studies focused on infancy and early childhood are more limited, but indicate that many of these sex differences are present at birth. Male neonate brains are about 6% larger than female brains at birth, and even at this stage there are already several areas that evidence local sexual dimorphism 123 . For example, the medial temporal cortex and rolandic operculum are larger in males, whereas the dorsolateral prefrontal, motor, and visual cortices are larger in females 123 .…”

“…Male neonate brains are about 6% larger than female brains at birth, and even at this stage there are already several areas that evidence local sexual dimorphism 123 . For example, the medial temporal cortex and rolandic operculum are larger in males, whereas the dorsolateral prefrontal, motor, and visual cortices are larger in females 123 . A more recent study with a larger sample size and more stringent statistical thresholds replicated the finding of increased medial temporal cortex in males and also indicated that female neonates have greater grey-matter volumes around the temporal-parietal junction, a crucial brain region for social cognition 124 .…”

Developmental neurogenetics and multimodal neuroimaging of sex differences in autism

“…These findings of atypical regional brain growth in girls with ASD correspond with the fact that these girls show greater signs of many cognitive and behavioral impairments than boys. Given that striking sex differences exist in the typical neonatal, infant, and adolescent brain as well as in brain developmental trajectories (Gilmore, Lin et al 2007, Lenroot, Gogtay et al 2007, Lenroot and Giedd 2010, Giedd, Raznahan et al 2012, Knickmeyer, Wang et al 2014), future longitudinal studies during these developmental periods are needed to confirm whether similar sex differences in ASD neuroanatomy still hold.…”