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.
Highlights
Bipolar disorder (BD) is a chronic mental illness characterized by an alternation between mania or hypomania and depression [1,2,3,4]
BD may include underlying mitochondrial dysfunction based on observations of decreased cellular respiration, altered mitochondrial structure, mitochondrial DNA (mtDNA) mutations, and decreased production of proteins involved in respiration [54,87]
BD is becoming increasingly understood as a condition of aberrant neuroplasticity
Summary
Bipolar disorder (BD) is a chronic mental illness characterized by an alternation between mania or hypomania and depression [1,2,3,4]. This review focuses on the roles of ROS and ROS-induced oxidative damage, mitochondrial dysfunction, DNA damage, and DA system dysregulation, and immune dysfunction in the pathophysiology of BD. It presents an overview of potential biomarkers, including lipid peroxidation, thiobarbituric acid reactive substances (TBARSs), and brain-derived neurotrophic factor (BDNF), in patients with BD. Some patients with BD exhibit neuroprogression [65,66,67], which is characterized by progressive changes in neuroanatomy, including decreased hippocampal volume [68], increased lateral ventricle size [69], and decreased cortical thickness [70] These neuroanatomical changes are associated with functional impairment. TThhee ppootteennttiiaallininteteraractcitoionns sbebtewtweeenenBDBD, O, OS,Sm, mitoictohcohnodnridarlidalydsfyusnfcutniocnti,oinm,mimumneudnyesdfuynscfutinonc-, atinotnio,xaindtainotxsi,daanntitds,epanretsidsaenptraegsseanntst,aagnetin-itns,flaanmtim-iantfolarymamgeantotsr,yaangtiepnstysc,haontticipasgyecnhtos,tiacnadgleignhtst,tahnerdapliigehs.t therapies
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