TY - JOUR
T1 - Corticosteroids and Regional Variations in Thickness of the Human Cerebral Cortex across the Lifespan
AU - Parker, Nadine
AU - Vidal-Pineiro, Didac
AU - French, Leon
AU - Shin, Jean
AU - Adams, Hieab H.H.
AU - Brodaty, Henry
AU - Cox, Simon R.
AU - Deary, Ian J.
AU - Fjell, Anders M.
AU - Frenzel, Stefan
AU - Grabe, Hans
AU - Hosten, Norbert
AU - Ikram, Mohammad Arfan
AU - Jiang, Jiyang
AU - Knol, Maria J.
AU - Mazoyer, Bernard
AU - Mishra, Aniket
AU - Sachdev, Perminder S.
AU - Salum, Giovanni
AU - Satizabal, Claudia L.
AU - Schmidt, Helena
AU - Schmidt, Reinhold
AU - Seshadri, Sudha
AU - Schumann, Gunter
AU - Völzke, Henry
AU - Walhovd, Kristine B.
AU - Wen, Wei
AU - Wittfeld, Katharina
AU - Yang, Qiong
AU - Debette, Stephanie
AU - Pausova, Zdenka
AU - Paus, Tomáš
N1 - Publisher Copyright:
© 2019 The Author(s) 2019. Published by Oxford University Press. All rights reserved.
PY - 2020/3/21
Y1 - 2020/3/21
N2 - Exposures to life stressors accumulate across the lifespan, with possible impact on brain health. Little is known, however, about the mechanisms mediating age-related changes in brain structure. We use a lifespan sample of participants (n = 21 251; 4-97 years) to investigate the relationship between the thickness of cerebral cortex and the expression of the glucocorticoid- and the mineralocorticoid-receptor genes (NR3C1 and NR3C2, respectively), obtained from the Allen Human Brain Atlas. In all participants, cortical thickness correlated negatively with the expression of both NR3C1 and NR3C2 across 34 cortical regions. The magnitude of this correlation varied across the lifespan. From childhood through early adulthood, the profile similarity (between NR3C1/NR3C2 expression and thickness) increased with age. Conversely, both profile similarities decreased with age in late life. These variations do not reflect age-related changes in NR3C1 and NR3C2 expression, as observed in 5 databases of gene expression in the human cerebral cortex (502 donors). Based on the co-expression of NR3C1 (and NR3C2) with genes specific to neural cell types, we determine the potential involvement of microglia, astrocytes, and CA1 pyramidal cells in mediating the relationship between corticosteroid exposure and cortical thickness. Therefore, corticosteroids may influence brain structure to a variable degree throughout life.
AB - Exposures to life stressors accumulate across the lifespan, with possible impact on brain health. Little is known, however, about the mechanisms mediating age-related changes in brain structure. We use a lifespan sample of participants (n = 21 251; 4-97 years) to investigate the relationship between the thickness of cerebral cortex and the expression of the glucocorticoid- and the mineralocorticoid-receptor genes (NR3C1 and NR3C2, respectively), obtained from the Allen Human Brain Atlas. In all participants, cortical thickness correlated negatively with the expression of both NR3C1 and NR3C2 across 34 cortical regions. The magnitude of this correlation varied across the lifespan. From childhood through early adulthood, the profile similarity (between NR3C1/NR3C2 expression and thickness) increased with age. Conversely, both profile similarities decreased with age in late life. These variations do not reflect age-related changes in NR3C1 and NR3C2 expression, as observed in 5 databases of gene expression in the human cerebral cortex (502 donors). Based on the co-expression of NR3C1 (and NR3C2) with genes specific to neural cell types, we determine the potential involvement of microglia, astrocytes, and CA1 pyramidal cells in mediating the relationship between corticosteroid exposure and cortical thickness. Therefore, corticosteroids may influence brain structure to a variable degree throughout life.
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U2 - 10.1093/cercor/bhz108
DO - 10.1093/cercor/bhz108
M3 - Article
C2 - 31240317
AN - SCOPUS:85077459311
SN - 1047-3211
VL - 30
SP - 575
EP - 586
JO - Cerebral Cortex
JF - Cerebral Cortex
IS - 2
ER -