Increased Serum TNF-α Levels Are Associated With Generalized Anxiety Disorder: A Case-Control Study.

Background and Aims: Generalized anxiety disorder (GAD) is a mental health disorder that affects many people in all aspects of their lives. It is characterized by persistent and excessive worry that the affected person finds difficult to control. The actual pathophysiology and mechanisms underlying GAD are still elusive. However, cytokines and cell signaling proteins are hypothesized to contribute to the pathogenesis of anxiety. The present study aimed to understand the association of tumor necrosis factor-α (TNF-α) in the pathophysiology of GAD. Methods: This case-control study recruited 43 GAD patients and 26 healthy controls (HCs) matched by age, sex, and other demographic factors. A clinical psychiatrist diagnosed patients and evaluated controls according to DSM-5 criteria. The GAD-7 scale was used to measure the severity of GAD symptoms. Serum TNF-α levels were measured using enzyme-linked immunosorbent assay (ELISA), and appropriate statistical methods were applied to find the associations among the analyzed parameters. Results: The results showed that TNF-α levels in GAD patients were significantly elevated than in HCs. The increased TNF-α levels were positively correlated with the severity of GAD symptoms. Moreover, the ROC curve reveals the AUC, sensitivity, and specificity as 0.888 (95% CI: 0.810-0.966), 84.6%, and 83.3%, respectively, at a cut-off value of 50.86 pg/ml. These results suggest a potential role of TNF-α in the pathophysiology and development of GAD. Conclusion: These findings indicate the role of cytokine dysregulation in GAD pathogenesis. This research advances the understanding of the immune system's association with GAD. However, as this was a cross-sectional case-control study, TNF-α should at present be regarded as a candidate biomarker that needs validation in larger and longer-term studies before it can be used clinically.