Bi-directional causal association between 17 neurosurgical diseases and three emotional disorders: perspective from Mendelian randomization analysis

Background Although numerous studies have reported correlations between emotional disorders and neurosurgical conditions, their causal relationships is not convincing. Therefore, we seek to comprehensively investigate the connection between the two using bidirectional Mendelian randomization studies. Methods The GWAS aggregated data encompassed 17 types of neurosurgical diseases (including cerebrovascular diseases, functional disorders, central nervous system neoplasms, spinal and spinal cord diseases, and other brain conditions) and 3 emotional disorders (anxiety, mania, and depression), sourced from IEU and FINNGEN. The primary analysis method applied was inverse variance-weighted (IVW) analysis, supplemented by MR-Egger and weighted median methods to ensure robust estimates. A series of sensitivity analyses, including Cochran’s Q test, MR-Egger regression, and leave-one-out analysis, were conducted to detect pleiotropy or heterogeneity. Results IVW estimates indicated that trigeminal neuralgia significantly associated with the risk of mania (p=0.002, odds ratio [OR]=1.008, 95 % confidence interval [CI] = 1.003 to 1.014), a higher genetic predisposition to congenital malformations of nervous system may reduce the development of depression (p=0.002, OR= 0.996; 95 %CI = 0.992 to 0.998) and the causal effect of depression on transient ischemic attack (IVW, P=0.004, odds ratio (p=0.004, OR = 4.141; 95 %CI = 1.560 to 10.988). The results of comprehensive sensitivity analyses were consistent with the main causality estimate. No pleiotropy and heterogeneity were detected in our MR study. Conclusions Our large-scaled MR analysis indicated that trigeminal neuralgia and congenital malformations of the nervous system predispose patients to emotional disorders, while depression, in particular, increases vulnerability to transient ischemic stroke.