TY - JOUR
T1 - Interaction of schizophrenia polygenic risk and cortisol level on pre-adolescent brain structure
AU - Bolhuis, Koen
AU - Tiemeier, Henning
AU - Jansen, Philip R
AU - Muetzel, Ryan L
AU - Neumann, Alexander
AU - Hillegers, Manon H J
AU - van den Akker, Erica T L
AU - van Rossum, Elisabeth F C
AU - Jaddoe, Vincent W V
AU - Vernooij, Meike W
AU - White, Tonya
AU - Kushner, Steven A
N1 - Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.
PY - 2019/3/1
Y1 - 2019/3/1
N2 - The etiology of schizophrenia is multi-factorial with early neurodevelopmental antecedents, likely to result from a complex interaction of genetic and environmental risk. However, few studies have examined how schizophrenia polygenic risk scores (PRS) are moderated by environmental factors in shaping neurodevelopmental brain structure, prior to the onset of psychotic symptoms. Here, we examined whether hair cortisol, a quantitative metric of chronic stress, moderated the association between genetic risk for schizophrenia and pre-adolescent brain structure. This study was embedded within the Generation R Study, involving pre-adolescents of European ancestry assessed regarding schizophrenia PRS, hair cortisol, and brain imaging (n = 498 structural; n = 526 diffusion tensor imaging). Linear regression was performed to determine the association between schizophrenia PRS, hair cortisol level, and brain imaging outcomes. Although no single measure exceeded the multiple testing threshold, nominally significant interactions were observed for total ventricle volume (Pinteraction = 0.02) and global white matter microstructure (Pinteraction = 0.01) - two of the most well replicated brain structural findings in schizophrenia. These findings provide suggestive evidence for the joint effects of schizophrenia liability and cortisol levels on brain correlates in the pediatric general population. Given the widely replicated finding of ventricular enlargement and lower white matter integrity among schizophrenia patients, our findings generate novel hypotheses for future research on gene-environment interactions affecting the neurodevelopmental pathophysiology of schizophrenia.
AB - The etiology of schizophrenia is multi-factorial with early neurodevelopmental antecedents, likely to result from a complex interaction of genetic and environmental risk. However, few studies have examined how schizophrenia polygenic risk scores (PRS) are moderated by environmental factors in shaping neurodevelopmental brain structure, prior to the onset of psychotic symptoms. Here, we examined whether hair cortisol, a quantitative metric of chronic stress, moderated the association between genetic risk for schizophrenia and pre-adolescent brain structure. This study was embedded within the Generation R Study, involving pre-adolescents of European ancestry assessed regarding schizophrenia PRS, hair cortisol, and brain imaging (n = 498 structural; n = 526 diffusion tensor imaging). Linear regression was performed to determine the association between schizophrenia PRS, hair cortisol level, and brain imaging outcomes. Although no single measure exceeded the multiple testing threshold, nominally significant interactions were observed for total ventricle volume (Pinteraction = 0.02) and global white matter microstructure (Pinteraction = 0.01) - two of the most well replicated brain structural findings in schizophrenia. These findings provide suggestive evidence for the joint effects of schizophrenia liability and cortisol levels on brain correlates in the pediatric general population. Given the widely replicated finding of ventricular enlargement and lower white matter integrity among schizophrenia patients, our findings generate novel hypotheses for future research on gene-environment interactions affecting the neurodevelopmental pathophysiology of schizophrenia.
KW - Brain/physiopathology
KW - Child
KW - Diffusion Tensor Imaging
KW - Female
KW - Gene-Environment Interaction
KW - Gene-environment
KW - Genetic
KW - Genetic Predisposition to Disease
KW - Hair/chemistry
KW - Humans
KW - Hydrocortisone/analysis
KW - Male
KW - Multifactorial Inheritance/genetics
KW - Netherlands
KW - Neuroimaging
KW - Psychosis
KW - Psychotic Disorders/diagnosis
KW - Risk Factors
KW - Schizophrenia/genetics
KW - Stress
KW - White Matter/physiopathology
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UR - https://www.ncbi.nlm.nih.gov/pubmed/30599318
U2 - https://doi.org/10.1016/j.psyneuen.2018.12.231
DO - https://doi.org/10.1016/j.psyneuen.2018.12.231
M3 - Article
C2 - 30599318
SN - 0306-4530
VL - 101
SP - 295
EP - 303
JO - Psychoneuroendocrinology
JF - Psychoneuroendocrinology
ER -