title: The neurobiology of bipolar disorder: identifying targets for specific agents and synergies for combination treatment.
abstract: Bipolar disorder (BD) is a chronic psychiatric illness described by severe changes in mood. Extensive research has been carried out to understand the aetiology and pathophysiology of BD. Several hypotheses have been postulated, including alteration in genetic factors, protein expression, calcium signalling, neuropathological alteration, mitochondrial dysfunction and oxidative stress in BD. In the following paper, we will attempt to integrate these data in a manner which is to understand targets of treatment and how they may be, in particular, relevant to combination treatment. In summary, the data suggested that BD might be associated with neuronal and glial cellular impairment in specific brain areas, including the prefrontal cortex. From molecular and genetics: (1) alterations in dopaminergic system, through catechol-O-aminotransferase; (2) decreased expression and polymorphism on brain-derived neurotrophic factor; (3) alterations cyclic-AMP responsive element binding; (4) dysregulation of calcium signalling, including genome-wide finding for voltage-dependent calcium channel α-1 subunit are relevant findings in BD. Future studies are now necessary to understand how these molecular pathways interact and their connection to the complex clinical manifestations observed in BD.
authors: Departments of Psychiatry and Pharmacology,University of Toronto,Toronto,Canada.
authors: Ana C
authors: AC
authors: Andreazza
authors: Departments of Psychiatry and Pharmacology,University of Toronto,Toronto,Canada.
authors: L Trevor
authors: LT
authors: Young
mesh_terms: D000818:Animals; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000503:physiopathology*; D001921:Brain / Q000503:physiopathology*; D004359:Drug Therapy, Combination / Q000379:methods; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology