Interaction of schizophrenia polygenic risk and cortisol level on pre-adolescent brain structure. (March 2019)

• Record Type: Journal Article
• Authors: Bolhuis, Koen; Tiemeier, Henning; Jansen, Philip R.; Muetzel, Ryan L.; Neumann, Alexander; Hillegers, Manon H.J.; van den Akker, Erica T.L.; van Rossum, Elisabeth F.C.; Jaddoe, Vincent W.V.; Vernooij, Meike W.; White, Tonya; Kushner, Steven A.
• Is Part Of: Psychoneuroendocrinology. Volume 101(2019)
• Page Start: 295
• Page End: 303
• Publication Date: 2019-03
• Subjects: Genetic -- Psychosis -- Gene-environment -- Stress -- Neuroimaging -- Diffusion tensor imaging; Psychoneuroendocrinology -- Periodicals; Endocrinology -- Periodicals; Neurology -- Periodicals; Psychiatry -- Periodicals; Neuropsychoendocrinologie -- Périodiques; 616.8
• DOI: 10.1016/j.psyneuen.2018.12.231
• Languages: English
• ISSNs: 0306-4530

Abstract

Highlights: Bolhuis et al., "Interaction of schizophrenia polygenic risk and cortisol level on pre-adolescent brain structure". Cortisol and schizophrenia PRS do not independently predict child brain structure. After multiple testing correction, no PRS x cortisol interaction was found. GxE interplay affects schizophrenia pathophysiology, novel hypotheses discussed. Abstract: 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 ( P interaction = 0.02) and global white matter microstructure ( P interaction = 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.