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The Nature of Bipolar Disorder

Husseini K. Manji, MD, FRCPC, and Robert H. Lenox, MD

Published: November 30, 2000

Article Abstract

The underlying pathophysiology of bipolar disorder is a continually evolving complexity of multilayerinteracting and independent systems. The dearth of adequate preclinical or clinical models thatincorporate the various features of the illness, i.e., acute and chronic, recurrent and episodic, and time-courseand treatment-related variables, has made the consistency and interpretation of data difficult.Newer technologies and the availability of structurally and mechanistically distinct pharmacologicagents have expanded opportunities for experimental study. In addition to the well-known neurotransmittersystems that are disrupted in mood disorders, critical guanine nucleotide-binding protein(G protein)-coupled signaling pathways are implicated in modulating mood state. Regulation of geneexpression and identification of factors regulating neuroplasticity and neurotrophic events in the centralnervous system in bipolar disorder are 2 of the more recent approaches contributing to clarificationof the pathophysiology and potential treatment options.

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