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 (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.
Department of Psychology, University of Toronto, Toronto M5S 3G3, Canada.|Rotman Research Institute, Baycrest, Toronto M6A 2E1, Canada.
Angelita Pui-Yee
AP
Wong
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.
Leon
L
French
Montreal Neurological Institute, McGill University, Montréal H3A 2B4, Canada.
Gabriel
G
Leonard
ECOBES, Cégep de Jonquière, Jonquière G7X 7W2, Canada.|University of Quebec in Chicoutimi, Chicoutimi G7H 2B1, Canada.
Michel
M
Perron
Department of Radiology and Hotchkiss Brain Institute, University of Calgary, Calgary T2N 4N1, Canada.
G Bruce
GB
Pike
University of Quebec in Chicoutimi, Chicoutimi G7H 2B1, Canada.
Louis
L
Richer
ECOBES, Cégep de Jonquière, Jonquière G7X 7W2, Canada.|University of Quebec in Chicoutimi, Chicoutimi G7H 2B1, Canada.
Suzanne
S
Veillette
The Hospital for Sick Children, University of Toronto, Toronto M5G 1X8, Canada.
Zdenka
Z
Pausova
Department of Psychology, University of Toronto, Toronto M5S 3G3, Canada.|Rotman Research Institute, Baycrest, Toronto M6A 2E1, Canada.|Department of Psychiatry, University of Toronto, Toronto M5T 1R8, Canada.|Child Mind Institute, New York, NY 10022, USA.
Tomáš
T
Paus
D000293:Adolescent; D000375:Aging / Q000502:physiology*; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000502:physiology*; D002648:Child; D005260:Female; D015870:Gene Expression / Q000502:physiology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism; D012737:Sex Factors; D059467:Transcriptome
C497713:NR3C1 protein, human; D012333:RNA, Messenger; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D011965:Receptors, Glucocorticoid; D011980:Receptors, Progesterone