Updated meta-analysis of circulating glial cell line-derived neurotrophic factor levels in major depressive disorder: Clarifying case-control differences and treatment effects.

BACKGROUND

Major depressive disorder (MDD) is a significant cause of disability, and glial cell line-derived neurotrophic factor (GDNF) plays a crucial role in its mechanisms. Previous findings on circulating GDNF levels in MDD have been inconsistent. This meta-analysis aims to clarify the relationship between GDNF levels in circulation and MDD by quantifying case-control differences and evaluating the impact of treatment on GDNF modulation.

METHODS

A meta-analytic review was conducted involving 21 case-control studies with 2524 participants, including 1262 MDD patients and 1262 healthy controls, along with two intervention studies comprising 355 participants. GDNF levels were compared between the two groups, assessing pre- and post-treatment changes. A random-effects model was used to accommodate high heterogeneity, and meta-regression and subgroup analyses examined the influence of moderators such as age, sex ratio, depression severity, and methodological factors.

RESULTS

GDNF levels were significantly lower in MDD patients compared to healthy controls (d = -0.78, p = 0.001), with high heterogeneity but no significant publication bias. GDNF reductions were most pronounced in treated patients, those with severe depression (HDRS >19), and older patients. Serum GDNF levels were considerably lower in MDD patients, while plasma levels showed no significant difference. Meta-regression identified the female sex ratio as a significant moderator of GDNF levels. Therapeutic interventions significantly increased GDNF levels (d = 0.23, p = 0.035) with low heterogeneity.

CONCLUSION

Circulating GDNF levels are decreased in MDD patients, and increased by treatment. These findings support GDNF's capability as both a biomarker and therapeutic target for MDD.