The neuroprogressive nature of bipolar disorder: Mechanisms and implications

Abstract Bipolar disorder (BD) is a mental disorder characterized by alternate episodes of depression and mania. Although the etiology of BD is not clearly understood, the interaction between genetic predisposition and environmental influences, for example, stressful life events, and comorbid somatoprogression, that is, presence of metabolic disorders, have been associated with the onset and sustenance of neuropathological processes in BD. Dysregulated neurotransmission and monoamine metabolism, activation of inflammatory, oxidative and nitrosative stress pathways, mitochondrial dysfunction, decrease in neurotrophin levels, and impaired hypothalamic-pituitary-adrenal axis activity has been reported during BD. The wide-ranging implications of BD pose a multitude of questions to our scientific community and make it imperative to devise better management strategies to halt the neuroprogression of BD. Antidepressants, mood stabilizers, and atypical antipsychotics in combination with cognitive behavioral therapy and psychosocial support are effective treatment of the acute phase of BD and the prevention of relapse; however, the overall efficacy of the currently available therapeutic strategy is far from satisfactory, especially for patients in advanced stages of BD, and may result in treatment resistance over a period of time. Personalized treatments may be required to control the neuroprogression of BD.