Signaling: Cellular insights into the pathophysiology of bipolar disorder

Clinical studies over the years have provided evidence that monoamine signa ling and hypothalamic-pituitary-adrenal axis disruption are integral to the pathophysiology of bipolar disorder. A full understanding of the pathophys iology from a molecular to a systems level must await the identification of the susceptibility and protective genes driving the underlying neurobiolog y of bipolar disorder. Furthermore, the complexity of the unique biology of this affective disorder, which includes the predisposition to episodic and often progressive mood disturbance, and the dynamic nature of compensatory processes in the brain, coupled with limitations in experimental design, h ave hindered our progress to date. Imaging studies in patient populations h ave provided evidence of a role for anterior cingulate, amygdala, and prefr ontal cortex in the pathophysiology of bipolar disorder. More recent resear ch strategies designed to uncover the molecular mechanisms underlying our p harmacologic treatments and their interaction in the regulation of signal t ransduction as well as more advanced brain imaging studies remain promising approaches. This experimental strategy provides data derived from the phys iologic response of the system in affected individuals and addresses the cr itical dynamic interaction with pharmacologic agents that effectively modif y the clinical expression of the pathophysiology. (C) 2000 Society of Biolo gical Psychiatry.