Major depressive disorder (MDD) is associated with various biochemical changes that contribute to chronic inflammation and the buildup of reactive oxygen species (ROS) in the body. One of the key alterations observed in MDD is the depletion of glutathione (GSH). This decrease in GSH results from impaired cysteine uptake, reduced glutathione peroxidase (GPx) activity, and mitochondrial dysfunction. In the human body, GSH is a vital intracellular antioxidant responsible for metabolizing ROS and modulating immune responses. This paper summarizes current literature on how GSH depletion associated with MDD disrupts key immunoregulatory functions, specifically as it applies to the immune response to Mycobacterium tuberculosis (M. tb). Research has shown that this disruption leads to increased oxidative stress and a weakened host immune response. Effective control of M. tb depends on balanced ROS activity and GSH-dependent macrophage function. Reduced GSH compromises these processes by limiting the ability of immune cells to function normally. Therefore, individuals with MDD-associated GSH depletion are at risk of developing severe tuberculosis (TB). Understanding this connection has important clinical and public health implications, particularly in regions where TB is endemic and depression is underdiagnosed. Integrating mental health assessment and considering antioxidant supportive strategies may improve TB management, especially in high-burden settings. Emerging evidence suggests that increasing levels of GSH through adjunct treatment with N-acetylcysteine or liposomal GSH may improve both depressive symptoms and the antimicrobial immune response. Despite this supporting research, further exploration is needed to clarify their therapeutic potential in individuals with comorbid MDD and TB.
Anjum et al. (Thu,) studied this question.