Neurobiology of bipolar disorders: a review of genetic components, signaling pathways, biochemical changes, and neuroimaging findings

Abstract

Bipolar disorder (BD) is a chronic mental illness characterized by changes in mood that alternate between mania and hypomania or between depression and mixed states, often associated with functional impairment. Although effective pharmacological and non-pharmacological treatments are available, several patients with BD remain symptomatic. The advance in the understanding of the neurobiology underlying BD could help in the identification of new therapeutic targets as well as biomarkers for early detection, prognosis, and response to treatment in BD. In this review, we discuss genetic, epigenetic, molecular, physiological and neuroimaging findings associated with the neurobiology of BD. Despite the advances in the pathophysiological knowledge of BD, the diagnosis and management of the disease are still essentially clinical. Given the complexity of the brain and the close relationship between environmental exposure and brain function, initiatives that incorporate genetic, epigenetic, molecular, physiological, clinical, environmental data, and brain imaging are necessary to produce information that can be translated into prevention and better outcomes for patients with BD.

Treatment-resistant bipolar depression: concepts and challenges for novel interventions

“…Genetic, biochemical, bioenergetic, inflammatory, and brain activity and connectivity dysfunction have been reported as associated with BD. 11,12 These dysfunctional biological processes can help identify effective treatment interventions. [11][12][13][14] However, the neurobiology could be even harder to disentangle when dealing with specific clinical characteristics and mood states, such as treatment-resistant depression.…”

Concepts of Neuroinflammation and Their Relationship With Impaired Mitochondrial Functions in Bipolar Disorder

“…All of these elements are involved in the chronic stress response, which demonstrates their close relationship with the immune system, where all of them causes a decrease in the capacity for neuronal repair, and mitochondrial transport to synaptic regions via the cytoskeleton with further neuronal dysfunction and death (Mizisin and Weerasuriya, 2011 ; Lacroix, 2019 ). There is compelling evidence that BD arises through alterations in the synapses and critical circuit functions, rather than an imbalance of specific neurotransmitters mediating affective and cognitive functions (Martinowich et al, 2009 ; Scaini et al, 2020 ). Furthermore, prolonged metabolic dysregulation, deficient neurotrophin (NT) signaling, oxidative stress, and neuroinflammation, which may contribute to the increased frequency and severity of manic and depressive episodes, as well as other sequelae with age (Heneka et al, 2010 ; Kim et al, 2020 ).…”

Insufficient consumption of micronutrients and common mental disorders in Brazilian adolescents

“…Anxiety and depression are affected by several genetic, hormonal, immunological, biochemical, neurodegenerative and nutritional factors 3 . More and more research shows the relationship between diet quality and mental disorders 4 .…”