Corticosteroids and Regional Variations in Thickness of the Human Cerebral Cortex across the Lifespan

Nadine Parker, Didac Vidal-Pineiro, Leon French, Jean Shin, Hieab H.H. Adams, Henry Brodaty, Simon R. Cox, Ian J. Deary, Anders M. Fjell, Stefan Frenzel, Hans Grabe, Norbert Hosten, Mohammad Arfan Ikram, Jiyang Jiang, Maria J. Knol, Bernard Mazoyer, Aniket Mishra, Perminder S. Sachdev, Giovanni Salum, Claudia L. SatizabalHelena Schmidt, Reinhold Schmidt, Sudha Seshadri, Gunter Schumann, Henry Völzke, Kristine B. Walhovd, Wei Wen, Katharina Wittfeld, Qiong Yang, Stephanie Debette, Zdenka Pausova, Tomáš Paus

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


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.

Original languageEnglish
Pages (from-to)575-586
Number of pages12
JournalCerebral Cortex
Issue number2
StatePublished - 21 Mar 2020
Externally publishedYes


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