Bipolar disorder 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. 

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)... 

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. 

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. 

Marx CE, Stevens RD, Shampine LJ, Uzunova V, Trost WT, Butterfield MI et al. Neuroactive steroids are altered in schizophrenia and bipolar disorder relevance to pathophysiology and therapeutics. Neuropsychopharmacology 2006 31 1249-1263. Molina-Hernandez M, Tellez-Alcantara NP, Garcia JP, Lopez JI, Jaramillo MT. Antidepressant-like actions of intra-accumbens infusions of allopregnanolone in ovariectomized wistar rats. Pharmacol. Biochem. Behav. 2005 80 401-409. 

Tolerance to the drug can develop. This is uncommon however, there is increasing evidence that some medications work well in early stages of some biologically based mental illnesses but are not as successful in later phases of the illness. For example, lithium is very effective in early episodes of bipolar disorder but is less effective after a number of episodes. This probably does not represent true "tolerance" but rather a change in the underlying pathophysiology or neurochemical substrate. 

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