Therapeutic Interventions to Mitigate Mitochondrial Dysfunction and Oxidative Stress–Induced Damage in Patients with Bipolar Disorder

Abstract

Bipolar disorder (BD) is characterized by mood changes, including recurrent manic, hypomanic, and depressive episodes, which may involve mixed symptoms. Despite the progress in neurobiological research, the pathophysiology of BD has not been extensively described to date. Progress in the understanding of the neurobiology driving BD could help facilitate the discovery of therapeutic targets and biomarkers for its early detection. Oxidative stress (OS), which damages biomolecules and causes mitochondrial and dopamine system dysfunctions, is a persistent finding in patients with BD. Inflammation and immune dysfunction might also play a role in BD pathophysiology. Specific nutrient supplements (nutraceuticals) may target neurobiological pathways suggested to be perturbed in BD, such as inflammation, mitochondrial dysfunction, and OS. Consequently, nutraceuticals may be used in the adjunctive treatment of BD. This paper summarizes the possible roles of OS, mitochondrial dysfunction, and immune system dysregulation in the onset of BD. It then discusses OS-mitigating strategies that may serve as therapeutic interventions for BD. It also analyzes the relationship between diet and BD as well as the use of nutritional interventions in the treatment of BD. In addition, it addresses the use of lithium therapy; novel antipsychotic agents, including clozapine, olanzapine, risperidone, cariprazine, and quetiapine; and anti-inflammatory agents to treat BD. Furthermore, it reviews the efficacy of the most used therapies for BD, such as cognitive–behavioral therapy, bright light therapy, imagery-focused cognitive therapy, and electroconvulsive therapy. A better understanding of the roles of OS, mitochondrial dysfunction, and inflammation in the pathogenesis of bipolar disorder, along with a stronger elucidation of the therapeutic functions of antioxidants, antipsychotics, anti-inflammatory agents, lithium therapy, and light therapies, may lead to improved strategies for the treatment and prevention of bipolar disorder.

Nutritional interventions for the prevention and treatment of neurological disorders such as anxiety, bipolar disorder, depression, epilepsy, multiple sclerosis, and schizophrenia

“…Patients with BD have been found to have altered levels of PUFAs [130][131][132]; an analysis of six studies involving a total of 118 patients with BD-I and 147 healthy controls found erythrocyte DHA and EPA levels to be decreased in patients with BD-I [131]. Supplementation with omega-3 PUFAs has been proposed to be bene icial for many diseases including dementia, cancer, hypertension, diabetes, arthritis, arteriosclerosis and autoimmune disease and evidence supporting the use of ω3 PUFAs in managing BD is particularly promising [133].…”

Advances in the pathophysiology of bipolar disorder

“…New treatments for BD are being studied, and most target disparate effector systems, mainly related to molecular targets in neuroplasticity, neurotrophic factors, inflammation, stress, mitochondrial function, and related metabolic pathways [46][47][48]. Clinical trials have demonstrated the efficacy of adjunctive inflammatory modulation with celecoxib in treatment-resistant bipolar depression, showing that add-on celecoxib reduces treatment resistance and enhances antidepressant response in patients with treatment-resistant bipolar depression [49,50].…”

The Role of Diet as a Modulator of the Inflammatory Process in the Neurological Diseases

“…Additionally, a randomized controlled trial found that a dietary supplement containing omega-3 fatty acids, vitamins, and minerals improved symptoms and quality of life in patients with BD, possibly by correcting nutrient deficiencies and reducing oxidative stress [ 192 ]. Furthermore, a review of the literature suggests that a Mediterranean-style diet, which is high in fruits, vegetables, whole grains, legumes, nuts, and olive oil, may be associated with a lower risk of BD and improve mood in patients with BD, possibly due to its anti-inflammatory and antioxidant properties [ 193 ].…”