Mitochondrial Dysfunction and Clinical Aspects in Psychosis: A Review

Mitochondria are essential organelles responsible for cellular energy production through adenosine triphosphate (ATP) synthesis and play a crucial role in neuronal energy metabolism and redox homeostasis. In psychotic disorders, particularly schizophrenia, growing evidence links impaired neuronal function, neuroplasticity, and neural circuitry to mitochondrial dysfunction and oxidative stress. Mitochondrial abnormalities involve disruptions in brain energy metabolism, including glycolysis, oxidative phosphorylation, and the utilization of lactate as a neuronal energy substrate. Genetic, structural, and functional changes in mitochondria further exacerbate the redox imbalance, leading to excessive production of reactive oxygen species (ROS). Oxidative stress, defined as an imbalance between oxidant formation and antioxidant defense mechanisms, results in damage to lipids, proteins, and deoxyribonucleic acid (DNA) and has been proposed as a core mechanism in the pathophysiology of psychosis. These findings have sparked interest in antioxidant therapy as an adjunct to antipsychotic treatment. Emerging clinical evidence suggests that antioxidant supplementation can improve positive symptoms, negative symptoms, and cognitive deficits in certain patient populations. This review summarizes the current evidence linking mitochondrial dysfunction and oxidative stress to psychosis and critically evaluates the therapeutic potential of antioxidant-based interventions. The aim of this review is to summarize the current evidence on the role of mitochondrial dysfunction and oxidative stress in psychosis and to critically evaluate the therapeutic potential of antioxidant-based interventions.