Inter-Regional Variations in Gene Expression and Age-Related Cortical Thinning in the Adolescent Brain
Overview
Authors
Affiliations
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.
Sex differences in normative modeling of cortical thickness in cannabis use disorder.
Martin E, Campbell L, Thorn K, Sahlem G, McRae-Clark A, Benitez A Drug Alcohol Depend Rep. 2025; 14:100318.
PMID: 39897590 PMC: 11783377. DOI: 10.1016/j.dadr.2025.100318.
Regional patterns of human cortex development correlate with underlying neurobiology.
Lotter L, Saberi A, Hansen J, Misic B, Paquola C, Barker G Nat Commun. 2024; 15(1):7987.
PMID: 39284858 PMC: 11405413. DOI: 10.1038/s41467-024-52366-7.
Corrigan N, Rokem A, Kuhl P Proc Natl Acad Sci U S A. 2024; 121(38):e2403200121.
PMID: 39250666 PMC: 11420155. DOI: 10.1073/pnas.2403200121.
Moodie J, Harris S, Harris M, Buchanan C, Davies G, Taylor A Hum Brain Mapp. 2024; 45(4):e26641.
PMID: 38488470 PMC: 10941541. DOI: 10.1002/hbm.26641.
Regional patterns of human cortex development correlate with underlying neurobiology.
Lotter L, Saberi A, Hansen J, Misic B, Paquola C, Barker G bioRxiv. 2023; .
PMID: 37205539 PMC: 10187287. DOI: 10.1101/2023.05.05.539537.