Photobiomodulation as a Therapeutic Strategy for Major Depressive Disorder: Mechanisms and Prospects

Background: Depression is a prevalent mental disorder characterized by mental suffering and emotional distress. Its pathogenesis involves the concurrent action of multiple factors, including genetic predisposition, stress exposure, hypothalamic-pituitary-adrenal axis dysregulation, imbalances in neurotransmitters and their receptors, inflammatory responses, and mitochondrial malfunction. Photobiomodulation (PBM), a noninvasive therapeutic approach, has shown potential in treating mood disorders such as depression and has emerged as a promising intervention for various pathologies; however, unified standards for PBM irradiation parameters (e.g., based on species, gender, age) are currently lacking. Objective: This review aims to introduce the potential mechanisms underlying depression and summarize the latest pre-clinical and clinical progress of PBM in the treatment of this mood disorder. Materials and Methods: As a narrative review, this work synthesizes and analyzes existing literature on the pathological mechanisms of depression and the application of PBM in depression treatment. Results Polytherapy with PBM targeting multiple biological pathways exerts beneficial effects on depression. Specifically, PBM enhances mitochondrial function in the brain, promotes neurogenesis and synaptogenesis, regulates neurotransmitter homeostasis, and provides neuroprotection through anti-inflammatory and antioxidant actions, while simultaneously supplying energy to brain tissues. Additionally, the curative effect of PBM is found to be associated with multiple factors, including irradiation parameters, species, gender, and age, highlighting the lack of unified parameter standards in current research. Conclusions: PBM exhibits therapeutic potential for depression by modulating key pathological pathways (e.g., mitochondrial function, neurogenesis, inflammation). The latest pre-clinical and clinical evidence supports its role as a promising noninvasive intervention. However, the establishment of unified PBM irradiation parameters is essential for standardizing its clinical application in depression treatment. Future research should focus on optimizing parameter standards to enhance the efficacy and reproducibility of PBM therapy.