Blood cytokines in major depressive disorder in drug-naïve adolescents: A systematic review and meta-analysis.

Background: Major depressive disorder (MDD) is the most common mental health problem worldwide. Increased levels of inflammation are associated with MDD, though this relationship has been suggested to be bidirectional. The first incidence of a depressive episode usually occurs during adolescence. Hence, examining depressed, drug-naïve adolescents is important to understand the role of inflammation in the pathophysiology of MDD. Cytokines might play a crucial role in inflammation associated with MDD. Therefore, this article aims to investigate the changes in the levels of peripheral blood cytokines in adolescents with MDD.

Methods: We conducted a systematic review and meta-analysis to assess the changes in peripheral blood cytokines in drug-naïve adolescents (10-18 years) with MDD. A comprehensive search across four databases was performed to identify original research articles. Studies in which the diagnosis of MDD was set by semi-structured interview were included.

Results: Of 2291 articles, 12 met the inclusion criteria for the review, with seven suitable for meta-analysis & including up to five studies per cytokine. The meta-analysis revealed significant associations between tumor necrosis factor (TNF)-α (n = 222, Hedge's g = 0.51, p <0.01) and MDD in adolescents compared to healthy individuals. However, other blood cytokines, including interleukin (IL)-1β, IL-4, IL-6, IL-8, and interferon (IFN)-γ, did not significantly correlate with MDD in adolescents.

Conclusion: TNF-α was significantly elevated in drug-naïve adolescents with MDD. To further understand the role of TNF-α in MDD, a thorough investigation is required, taking into account the diversity, subtypes, chronicity, and severity of MDD.