Association between mental disorders and trigeminal neuralgia: a cohort study and Mendelian randomization analysis

Clinical observational evidence suggests a close association between Trigeminal Neuralgia (TN) and Mental disorders (MDs). However, the causal relationship between the two remains unclear. This study aims to observe and analyse the associations between depression, anxiety, insomnia, and TN through clinical research. It also employs Mendelian randomization (MR) analysis to verify the potential genetic correlation between TN and various mental disorders. offering new insights for the diagnosis, prevention, and intervention strategies for TN.

In the cohort study section, clinical data were collected from 154 patients with TN, all of whom were excluded from preoperative use of psychotropic drugs such as carbamazepine. The PHQ-9, GAD-7, and ISI scales were used to assess preoperative symptoms of depression, anxiety, and insomnia. Multivariable linear regression models were used to identify factors associated with questionnaire scores, with model performance evaluated by adjusted R², AIC, BIC, and p-values. Patients with significant positive symptoms preoperatively were followed up one-year after surgery, and non-parametric tests were employed to examine changes in mental disorder symptoms after pain relief. In MR analysis section, the main MR analysis methods include Inverse Variance Weighted (IVW), MR Egger, Weighted Median, Simple Mode, and Weighted Mode. The Benjamini-Hochberg (BH) method was used to adjust the p -values ​​and control the false discovery rate (FDR). Subsequent sensitivity analyses involved Cochran's Q test, MR-Egger regression intercept, MR-pleiotropy residual sum and outlier test (MR-PRESSO).

Multiple linear regression analyses revealed that longer disease duration and greater involvement of trigeminal branches were consistently associated with higher PHQ-9, GAD-7, and ISI scores, while demographic factors and baseline BNI scores showed no significant predictive value. MR analysis indicated that autism (OR = 0.697, 95% CI [0.494-0.982], P = 0.039), schizophrenia (OR = 0.910, 95% CI [0.831-0.997], P = 0.042), and ADHD combined with OCD (OR = 0.175, 95% CI [0.044-0.693], P = 0.013) reduced the risk of TN. Conversely, bipolar disorder (OR = 1.249, 95% CI [1.016-1.535], P = 0.034), depression (OR = 2.375, 95% CI [1.043-5.409], P = 0.039), anxiety (OR = 1.174, 95% CI [1.008-1.368], P = 0.039), and insomnia (OR = 2.036, 95% CI [1.074-3.861], P = 0.029)increased the risk of TN. TN also elevated the risk of anxiety (OR = 1.43, 95% CI [1.04-1.96], P = 0.034), depression (OR = 1.00305, 95% CI [1.00036-1.00549], P = 0.013), and insomnia (OR = 1.00918, 95% CI [1.00236-1.01605], P = 0.008).

Longer disease duration and broader trigeminal nerve involvement were independently associated with increased severity of depressive, anxiety, and insomnia symptoms, highlighting the importance of early clinical intervention in patients with TN. And results of MR analysis provide evidence supporting a causal relationship between MDs and TN. In contrast to the traditional view that pain causes mood changes such as anxiety and depression, a variety of MDs such as anxiety, depression, and insomnia also alter the risk of developing TN.