Modulating the Mitochondria for Mood Disorders: Emerging Evidence for Transcranial Photobiomodulation in Major Depressive Disorder

Major depressive disorder (MDD) is a leading cause of disability worldwide; however, current treatments have inconsistent remission rates and burdensome side effects. In part, this may be due to the altered neurometabolism in MDD or the inability of current treatments to target mitochondrial function. Human and animal studies suggest key links between mitochondrial function and MDD. Transcranial photobiomodulation (t-PBM) is an innovative therapy for targeting the mitochondria via stimulating Complex IV of the mitochondrial respiratory changing (cytochrome c oxidase) and increasing adenosine triphosphate (ATP) synthesis and cerebral blood flow. In this review, we detail the application of t-PBM in both human and animal models of MDD and summarize the post-treatment changes in depressive symptoms and neurophysiology. Decreases in depression and increases in cerebral blood flow have been shown in clinical studies, while decreased depression behaviors and altered neurophysiology have been shown in pre-clinical studies after t-PBM. Although limited by small sample sizes and heterogeneity across the methods employed (e.g., measures of depression, t-PBM parameters), animal and human studies suggest that t-PBM is promising in its ability to modulate brain activity and reduce MDD symptoms. Large randomized clinical trials and more methodological consistency are needed in future studies to further support the use of t-PBM for MDD symptoms and underlying pathophysiology.