Systemic inflammation has been thought to play a considerable part in psychiatric disorders. However, the causal relationships between systemic inflammation and psychiatric disorders and the directions of the causal effects remain elusive and need further investigation. By leveraging the summary statistics of genome-wide association studies, the standard inverse variance weighted method was applied to assess the causal associations among 41 systemic inflammatory regulators and 7 major psychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD), anorexia nervosa (AN), autism spectrum disorder (ASD), bipolar disorder (BIP), major depression disorder (MDD), obsessive-compulsive disorder (OCD), and schizophrenia (SCZ), within a two-sample bidirectional Mendelian randomization analysis. Additionally, the weighted median test and the Mendelian randomization pleiotropy residual sum and outlier test were conducted for sensitivity analyses. The results suggested a total of 15 unique systemic inflammatory regulators might be causally associated with disease risk, including 2 for ADHD, 4 for AN, 2 for ASD, 2 for MDD, 2 for OCD, and 5 for SCZ. Among them, the genetically predicted concentration of basic fibroblast growth factor was significantly related to AN at the Bonferroni-corrected threshold (Odds ratio = 0.403, 95% confidence interval = (0.261, 0.622), P = 4.03 × 10). Furthermore, the concentrations of 9 systemic inflammatory regulators might be influenced by neuropsychiatric disorders, including 2 by ADHD, 2 by BIP, 3 by MDD, and 2 by SCZ, and the causal effects of ASD, AN, and OCD need to be further assessed when more significant genetic variants are identified in the future. Overall, this study provides additional insights into the relationships between systemic inflammation and psychiatric disorders and may provide new clues regarding the aetiology, diagnosis and treatment of psychiatric disorders. -5
