Inflammation and Brain Structure in Schizophrenia and Other Neuropsychiatric Disorders: A Mendelian Randomization Study.
Williams JA., Burgess S., Suckling J., Lalousis PA., Batool F., Griffiths SL., Palmer E., Karwath A., Barsky A., Gkoutos GV., Wood S., Barnes NM., David AS., Donohoe G., Neill JC., Deakin B., Khandaker GM., Upthegrove R., PIMS Collaboration None.
IMPORTANCE: Previous in vitro and postmortem research suggests that inflammation may lead to structural brain changes via activation of microglia and/or astrocytic dysfunction in a range of neuropsychiatric disorders. OBJECTIVE: To investigate the relationship between inflammation and changes in brain structures in vivo and to explore a transcriptome-driven functional basis with relevance to mental illness. DESIGN, SETTING, AND PARTICIPANTS: This study used multistage linked analyses, including mendelian randomization (MR), gene expression correlation, and connectivity analyses. A total of 20 688 participants in the UK Biobank, which includes clinical, genomic, and neuroimaging data, and 6 postmortem brains from neurotypical individuals in the Allen Human Brain Atlas (AHBA), including RNA microarray data. Data were extracted in February 2021 and analyzed between March and October 2021. EXPOSURES: Genetic variants regulating levels and activity of circulating interleukin 1 (IL-1), IL-2, IL-6, C-reactive protein (CRP), and brain-derived neurotrophic factor (BDNF) were used as exposures in MR analyses. MAIN OUTCOMES AND MEASURES: Brain imaging measures, including gray matter volume (GMV) and cortical thickness (CT), were used as outcomes. Associations were considered significant at a multiple testing-corrected threshold of P