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Genetic polymorphism of CYP2C19 and subcortical variability in the human adult brain

View ORCID ProfileJulia C. Stingl, View ORCID ProfileCatharina Scholl, View ORCID ProfileJulia E. Bosch, View ORCID ProfileRoberto Viviani
doi: https://doi.org/10.1101/2020.12.18.423183
Julia C. Stingl
1Institute of Clinical Pharmacology, University Hospital of RWTH Aachen, Aachen, Germany
2Research Division, Federal Institute for Drugs and Medical Devices, Bonn, Germany
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Catharina Scholl
2Research Division, Federal Institute for Drugs and Medical Devices, Bonn, Germany
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Julia E. Bosch
3Psychiatry and Psychotherapy Clinic III, University of Ulm, Germany
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Roberto Viviani
4Institute of Psychology, University of Innsbruck, Austria
3Psychiatry and Psychotherapy Clinic III, University of Ulm, Germany
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  • For correspondence: roberto.viviani@uibk.ac.at
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Abstract

Pharmacogenetic studies have shown involvement of cytochrome P450 enzymes in the metabolism of psychotropic drugs. However, expression and activity on endogenous substrates in the brain may underlie a constitutive role of these enzymes beyond drug metabolism. CYP2C19, which is expressed in the human fetal brain during neurodevelopment, shows affinity for endogenous compounds including monoaminergic neurotransmitters, steroid hormones, and endocannabinoids. In this study (N=608), we looked at the genetic polymorphism of CYP2C19 and its potential associations with structural phenotypes of subcortical brain volume with structural imaging. Using two independent volume estimation techniques, we found converging evidence for a positive association between CYP2C19 activity scores, as inferred from the genotype, and basal ganglia and hippocampal volume. This association was present only in female individuals, raising the possibility that effects on brain morphology may arise through a mechanism involving the metabolism of estrogen steroids.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted August 17, 2021.
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Genetic polymorphism of CYP2C19 and subcortical variability in the human adult brain
Julia C. Stingl, Catharina Scholl, Julia E. Bosch, Roberto Viviani
bioRxiv 2020.12.18.423183; doi: https://doi.org/10.1101/2020.12.18.423183
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Genetic polymorphism of CYP2C19 and subcortical variability in the human adult brain
Julia C. Stingl, Catharina Scholl, Julia E. Bosch, Roberto Viviani
bioRxiv 2020.12.18.423183; doi: https://doi.org/10.1101/2020.12.18.423183

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