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Cereb Cortex. 2018 Apr 1;28(4):1272-1281. doi: 10.1093/cercor/bhx040.

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

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Department of Psychology, University of Toronto, Toronto M5S 3G3, Canada.
Rotman Research Institute, Baycrest, Toronto M6A 2E1, Canada.
Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto M5T 1R8, Canada.
Department of Psychiatry, University of Toronto, Toronto M5T 1R8, Canada.
Montreal Neurological Institute, McGill University, Montréal H3A 2B4, Canada.
ECOBES, Cégep de Jonquière, Jonquière G7X 7W2, Canada.
University of Quebec in Chicoutimi, Chicoutimi G7H 2B1, Canada.
Department of Radiology and Hotchkiss Brain Institute, University of Calgary, Calgary T2N 4N1, Canada.
The Hospital for Sick Children, University of Toronto, Toronto M5G 1X8, Canada.
Child Mind Institute, New York, NY 10022, USA.


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 (R2 = 0.46) and females (R2 = 0.30) and AR in males only (R2 = 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: R2 = 0.64; females: R2 = 0.58) but not high (males: R2 = 0.0045; females: R2 = 0.15) levels of AR mRNA expression. These results suggest that glucocorticoid and androgen receptors contribute to cortical maturation during adolescence.

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