Inter-Regional Variations in Gene Expression and Age-Related Cortical Thinning in the Adolescent Brain

Age-related decreases in cortical thickness observed during adolescence may be related to fluctuations in sex and stress hormones. We examine this possibility by relating inter-regional variations in age-related cortical thinning (data from the Saguenay Youth Study) to inter-regional variations in expression levels of relevant genes (data from the Allen Human Brain Atlas); we focus on genes coding for glucocorticoid receptor (NR3C1), androgen receptor (AR), progesterone receptor (PGR), and estrogen receptors (ESR1 and ESR2). Across 34 cortical regions (Desikan-Killiany parcellation), age-related cortical thinning varied as a function of mRNA expression levels of NR3C1 in males (R-2 = 0.46) and females (R-2 = 0.30) and AR in males only (R-2 = 0.25). Cortical thinning did not vary as a function of expression levels of PGR, ESR1, or ESR2 in either sex; this might be due to the observed low consistency of expression profiles of these 3 genes across donors. Inter-regional levels of the NR3C1 and AR expression interacted with each other vis-a-vis cortical thinning: age-related cortical thinning varied as a function of NR3C1 mRNA expression in brain regions with low (males: R-2 = 0.64; females: R-2 = 0.58) but not high (males: R-2 = 0.0045; females: R-2 = 0.15) levels of AR mRNA expression. These results suggest that glucocorticoid and androgen receptors contribute to cortical maturation during adolescence.