Age-specific Associations between Estradiol, Cortico-Amygdalar Structural Covariance, Verbal and Spatial Skills.

Estradiol is known to play an important role in the developing human brain, but little is known on the entire network of potential regions which might be affected and on how these effects may vary from childhood to early adulthood, which in turn can explain sexually differentiated behaviors. Here we examined the relationship between estradiol, cortico-amygdalar structural covariance, and cognitive or behavioral measures typically showing sex differences (verbal/spatial skills, anxious-depressed symptomatology) in 152 children and adolescents (6-22 years old). Cortico-amygdalar structural covariance shifted from positive to negative across the age range. Estradiol was found to diminish the impact of age on cortico-amygdalar covariance for the pre-supplementary motor area/frontal eye field and retrosplenial cortex (across the age range), and for the posterior cingulate cortex (in older children). Moreover, the influence of estradiol on age-related cortico-amygdalar networks was associated with higher word identification and spatial working memory (across the age range), as well as higher reading comprehension (in older children), but did not impact anxious-depressed symptoms. There were no significant sex effects on any of the above relationships. These findings confirm the importance of developmental timing on estradiol-related effects and hint at the non-sexually dimorphic role of estradiol-related cortico-amygdalar structural networks in aspects of cognition distinct from emotional processes. This article is protected by copyright. All rights reserved.