Genetic and Biological Predispositions

Bipolar disorder unquestionably runs in families. Concordance rates between identical twins average 57% and between fraternal twins, 14% (Alda, 1997). The family pedigrees of bipolar probands are characterized by increased rates of bipolar disorder, unipolar disorder, and alcoholism. At least 20% of the first-degree relatives of bipolar patients have major affective disorders (Gershon, 1990). Although several gene loci have been identified, there is a particularly promising set of findings linking bipolar disorder to loci on the long arm of chromosome 18. This linkage is strongest among families of bipolar patients who are co-morbid for Panic Disorder (MacKinnon et al., 1998). There is also growing evidence that a variant in the serotonin transporter gene, which might lead to instabilities in the regulation of serotonin within the CNS, may be related to the onset of bipolar disorder (Collier et al., 1996).

Bipolar disorder is presumed to involve imbalances in the activity of neurotransmitter (e.g., dopamine, serotonin) and neurohormonal (e.g., glucorticoid) systems. A recent theory of dysfunction in the activity of signal-transducing guanine nucleotide-binding proteins (G-proteins) is gaining credibility. Bipolar patients have higher platelet levels of stimulatory G-protein subunits than do normal comparison subjects, even when patients are examined in the remitted state (Mitchell et al., 1997). Lithium carbonate— the primary medication used in treating bipolar disorder— has been found to reduce G-protein function in animals (Avissar, Schreiber, Danon, & Belmaker, 1988) and in normal humans (Risby et al., 1991). Other research has focused on the protein kinase C signaling cascade, a mediator of signals within cells when receptors are stimulated by neurotransmitters. Drugs used to treat bipolar disorder, including lithium carbonate and divalproex sodium, reduce activity of the protein kinase C signaling cascade (Manji, 2001).

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Understanding And Treating Bipolar Disorders

Understanding And Treating Bipolar Disorders

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