Bipolar pathophysiology

Explain the pathophysiologic mechanisms underlying bipolar disorder. 

The precise etiology of bipolar disorder is unknown. Thought to be genetically based, bipolar disorder is influenced by a variety of factors that may enhance gene expression. These include trauma, environmental factors, anatomic abnormalities, exposure to chemicals or drugs, and others.3-5 Neurochemical abnormalities in bipolar disorder may be caused by these factors, as discussed further in the pathophysiology section. 

From Fankhauser MP, Freeman MP. Bipolar disorder. In DiPiro JT, Talbert RL, Yee CC, et al, (eds.) Pharmacotherapy A Pathophysiologic Approach. 6th ed. New York McGraw-Hill 2005 1261, with permission. 

Tab. 20.2 Pathophysiology of bipolar disorder constraints for experimental design...

Manji HK. Signaling Cellular insights into the pathophysiology of bipolar disorder. Biol Psych 2000 48 518-530. 

NEUROTRANSMITTER AND NEUROPEPTIDE SYSTEMS ARE IMPLICATED IN THE PATHOPHYSIOLOGY OF BIPOLAR AND MAJOR DEPRESSIVE DISORDERS 889... 

Hahn, C. G. and Friedman, E. Abnormalities in protein kinase C signaling and the pathophysiology of bipolar disorder. Bipolar Disord. 1 81-86,1999. 

Etiology and pathophysiology of bipolar disorder are shown in Table 69-2. 

Etiologic and Pathophysiologic Theories of Bipolar Disorder (Continued)... 

Unipolar and bipolar depressive disorders in children and adolescents are serious conditions. The pathophysiology of these disorders is poorly understood. The new tools available through neuroimaging techniques will help to unravel the neuroanatomical systems involved in the onset and recurrence of these disorders. There is a need for more developmentally informed predinical research and more studies of the normal development of the neural systems implicated in emotional regulation. 

The relevance of these findings for the pathophysiology of mood disorders has not yet been established. A study by L. T. Young et al. (1991) found elevated Ggtt subunit levels in the cerebral cortex of patients with bipolar affective disorder. The significance of this finding is difficult to gauge because corticosteroids, which are elevated in this disorder, were reported to increase this particular G-protein subunit in rat cerebral cortex (Salto et al. 1989). 

The most serious theoretical side effect of inositol treatment could be reversal of therapeutic effects of Li or induction of mania in patients with bipolar disorder. So far, this has not been definitely seen in four patients with bipolar depression who were treated with full 12 g of inositol daily for depression [Levine et al. 1995a] or in 18 Li -treated patients with bipolar disorder who were treated with low-dose inositol for polyuria [Bersudsky et al. 1992] or EEG abnormalities [Barak et al. 1994]. The pathophysiological relationship of inositol reversal of Li side effects and inositol therapeutic efficacy in depression and panic is not clear. 

The study of antidepressant maintenance medications for patients with unipolar MDD has been historically neglected. Such neglect is puzzling. Considering that multiple recurrences may well be the sine qua non for unmedicated patients with manic depression [Coryell and Winokur 1982 NIMH/ NIH Consensus Development Panel 1985 Prien et al. 1984 Suppes et al. 1991 Zis and Goodwin 1979 Zis et al. 1980] and that unipolar illness is pathophysiologically similar to bipolar disorder in many important respects, recurrences could have been presumed to be innate. 

Manji HK, Chen G, Hsiao JK, et al Regulation of signal transduction pathways by mood stabilizing agents implications for the pathophysiology and treatment of bipolar affective disorder, in Bipolar Medications Mechanisms of Action. Edited by Manji HK, Bowden CL, Belmaker RH. Washington, DC, American Psychiatric Press [in press)... 

Bipolar disorder can be divided into primary and secondary types, with the latter developing as a consequence of various medical conditions or substances that can alter brain function or structure. This categorization underscores the view of mania as a syndrome subsequent to various pathophysiologies. 

Bipolar disorder, once known as manic-depressive illness, was conceived of as a psychotic disorder distinct from schizophrenia at the end of the 19th century. Before that both of these disorders were considered part of a continuum. It is ironic that the weight of the evidence today is that there is profound overlap in these disorders. This is not to say that there are no pathophysiologically important differences or that some drug treatments are differentially effective in these disorders. According to DSM-IV, they are separate disease entities while research continues to define the dimensions of these illnesses and their genetic and other biological markers. 

Quiroz et al Emerging experimental therapeutics for bipolar disorder Clues from the molecular pathophysiology. Mol Psychiatry 2004 9 756. [PMID 15136795]... 

Neurogenesis and Neuroenhancement in the Pathophysiology and Treatment of Bipolar Disorder... 

Pathophysiology of the disorder There is no commonly accepted theory about the biological origins of manic depression or bipolar disorder that would explain the actions of any currently used mood stabiliser in disease-centred terms. 

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