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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-à-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.

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