Mitochondria-targeted Treatments: The Uncharted Frontier in Psychiatry

Abstract Psychiatric conditions are present in close to 900 million individuals worldwide and contribute substantially to global disability and socioeconomic burden. Although pharmacotherapy, psychotherapy, and neuromodulation approaches have progressed, many patients continue to experience incomplete response and treatment resistance to various therapies, highlighting the need for novel therapeutic approaches. Studies indicate that mitochondrial dysfunction is a key factor in a range of psychiatric disorders, particularly significant for major depressive disorder, bipolar disorder, and psychotic spectrum disorders. Mitochondria direct important cellular pathways such as energy metabolism, oxidative stress regulation, calcium homeostasis, apoptosis, and neuronal plasticity, all of which function in normal brain physiology. If these critical processes are disrupted to some extent, neuronal resilience will be compromised and neuropsychiatric symptomatology will arise. These recent findings have led to research into treatments aimed toward mitochondrial dysfunction, such as mitochondria-specific antioxidants and metabolic cofactors, among other compounds that modulate mitochondrial dynamics and quality control. By combining mitochondrial-targeted interventions with current psychiatric treatment options, promising therapeutic targets can be addressed by addressing underlying cellular factors leading to better outcomes and increasing the applicability of precision-oriented psychiatric medicine.