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

<span class="paragraphSection"><div class="boxTitle">Abstract</div>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 (<span style="font-style:italic;">NR3C1</span>), androgen receptor (<span style="font-style:italic;">AR</span>), progesterone receptor (<span style="font-style:italic;">PGR</span>), and estrogen receptors (<span style="font-style:italic;">ESR1</span> and <span style="font-style:italic;">ESR2</span>). Across 34 cortical regions (Desikan-Killiany parcellation), age-related cortical thinning varied as a function of mRNA expression levels of <span style="font-style:italic;">NR3C1</span> in males (<span style="font-style:italic;">R</span>² = 0.46) and females (<span style="font-style:italic;">R</span>² = 0.30) and <span style="font-style:italic;">AR</span> in males only (<span style="font-style:italic;">R</span>² = 0.25). Cortical thinning did not vary as a function of expression levels of <span style="font-style:italic;">PGR</span>, <span style="font-style:italic;">ESR1</span>, or <span style="font-style:italic;">ESR2</span> 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 <span style="font-style:italic;">NR3C1</span> and <span style="font-style:italic;">AR</span> expression interacted with each other vis-à-vis cortical thinning: age-related cortical thinning varied as a function of <span style="font-style:italic;">NR3C1</span> mRNA expression in brain regions with low (males: <span style="font-style:italic;">R</span>² = 0.64; females: <span style="font-style:italic;">R</span>² = 0.58) but not high (males: <span style="font-style:italic;">R</span>² = 0.0045; females: <span style="font-style:italic;">R</span>² = 0.15) levels of <span style="font-style:italic;">AR</span> mRNA expression. These results suggest that glucocorticoid and androgen receptors contribute to cortical maturation during adolescence.</span>

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