Evaluation of serum GDNF, TIMP4, and tPA levels in generalized anxiety disorder: a case–control study

Abstract

Background: Generalized anxiety disorder (GAD) is a psychological condition marked by persistent, overwhelming concern and intensified anxiety reactions that surpass situational stimuli, profoundly impacting social, vocational, and daily activities. Emerging evidence indicates that altered levels of cytokines and other biomarkers may contribute to mental disorders; however, knowledge on GDNF, TIMP4, and tPA with GAD remains ambiguous, limited, and inconsistent. The objective of this study was to evaluate their association with the pathophysiology of GAD. Methods: This case–control study enrolled 101 GAD patients from the National Institute of Mental Health Hospital in Dhaka and 101 healthy controls from several sites across Dhaka city. The participants were assessed by a qualified psychiatrist according to DSM-5 criteria. To determine the severity of GAD symptoms, the GAD-7 scale was employed. Serum levels of GDNF, TIMP4, and tPA were quantified by ELISA methods. Results: We found elevated serum GDNF levels in patients compared to control subjects. This increment demonstrated a significantly positive correlation with the patients' GAD severity. The ROC analysis of serum GDNF levels revealed diagnostic efficacy, with a sensitivity of 79.2% and a specificity of 74.7%. Furthermore, patients with GAD showed reduced serum TIMP4 levels than controls. This reduction exhibited a significantly negative correlation with the severity of GAD in patients. The ROC analysis of serum TIMP4 levels indicated diagnostic performance, with sensitivity and specificity of 75.2% and 78.2%, respectively. Additionally, a significant negative correlation was observed between serum GDNF and TIMP4 levels. However, we noted no such changes in serum tPA levels in GAD. Conclusions: The current study demonstrates the altered serum GDNF and TIMP4 levels may be associated with the pathophysiology of GAD. The findings emphasize the potential of GDNF and TIMP4 for risk evaluation and therapeutic response for GAD. © The Author(s) 2026.