Chapter 1 - Novel therapeutic approaches targeting oxidative stress in mood disorders

Abstract

Mood disorders, such as major depressive disorder (MDD) and bipolar disorder (BD), have been treated with a wide range of pharmacological therapies, including but not restricted to antidepressants, mood stabilizers, and second-generation antipsychotics. Current gold standard interventions primarily target numerous monoaminergic brain systems, to prompt relief of depressive symptoms. However, these interventions provide symptomatic relief in only ~ 50% of patients. To address these limitations, there has been a greater emphasis on understanding the role of neuronal oxidative stress and its subsequent impact on the pathology of various mood disorders. Numerous sources have been identified within neurons of the central nervous system (CNS) that contribute significantly to both reactive oxygen species (ROS) and reactive nitrogen species (RNS) accumulation within the brain. The aerobic mitochondrial process of oxidative phosphorylation and various neuronal enzymes are indirectly associated with the production of common ROS and RNS. Numerous anatomical and physiological properties promote a greater susceptibility to neuronal ROS-inflicted subcellular damage, interrupting the functional and structural integrity of cells across the CNS. The association of mood disorder pathology with increased oxidative stress markers has prompted interventional strategies that reduce the cellular REDOX state and ensures that an adequate balance of ROS is maintained within the neuron. Whether the ROS will have a detrimental or beneficial effect on the neuron is heavily reliant upon the activity of several key enzymes associated with ROS homeostasis. Though the individual sources of neuronal ROS can be targeted, antioxidant systems are critical in moderating ROS accumulation. Thus, the exploration of antioxidants as adjunctive therapy for mood disorders provides a promising mechanism for targeting neuronal oxidative stress and increasing symptomatic relief across patients.