Chen Xinzhen, Yao Ting, Cai Jinliang, Fu Xihang, Li Huiru, Wu Jing
Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China; Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.
Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China; Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.
Prog Neuropsychopharmacol Biol Psychiatry. 2022 Jun 8;116:110534. doi: 10.1016/j.pnpbp.2022.110534. Epub 2022 Feb 9.
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.
全身炎症被认为在精神疾病中起相当大的作用。然而，全身炎症与精神疾病之间的因果关系以及因果效应的方向仍不明确，需要进一步研究。通过利用全基因组关联研究的汇总统计数据，应用标准逆方差加权法在两样本双向孟德尔随机化分析中评估41种全身炎症调节因子与7种主要精神疾病之间的因果关联，这7种精神疾病包括注意力缺陷多动障碍（ADHD）、神经性厌食症（AN）、自闭症谱系障碍（ASD）、双相情感障碍（BIP）、重度抑郁症（MDD）、强迫症（OCD）和精神分裂症（SCZ）。此外，还进行了加权中位数检验和孟德尔随机化多效性残差和离群值检验以进行敏感性分析。结果表明，共有15种独特的全身炎症调节因子可能与疾病风险存在因果关联，其中2种与ADHD有关，4种与AN有关，2种与ASD有关，2种与MDD有关，2种与OCD有关，5种与SCZ有关。其中，在Bonferroni校正阈值下，基因预测的碱性成纤维细胞生长因子浓度与AN显著相关（优势比 = 0.403，95%置信区间 = (0.261, 0.622)，P = 4.03 × 10）。此外，9种全身炎症调节因子的浓度可能受神经精神疾病影响，其中2种受ADHD影响，2种受BIP影响，3种受MDD影响，2种受SCZ影响，未来当发现更显著的基因变异时，需要进一步评估ASD、AN和OCD的因果效应。总体而言，本研究为全身炎症与精神疾病之间的关系提供了更多见解，并可能为精神疾病的病因、诊断和治疗提供新线索。
