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Sci. STKE, 4 November 2003
Vol. 2003, Issue 207, p. pe49
Signal Transduction and Genes-to-Behaviors Pathways in Psychiatric Diseases
Husseini K. Manji1*,
Irving I. Gottesman2*, and
Todd D. Gould1*
lLaboratory of Molecular Pathophysiology, Mood and Anxiety Disorders Program, NIMH, Bethesda, MD 20892, USA. 2Department of Psychiatry, University of Minnesota Medical School, Minneapolis, MN 55454, USA.
Although psychiatric diseases are among the most common and destructive of all human illnesses, the molecular and cellular mechanisms underlying their complex origins remain to be elucidated. Dysfunction of critical intracellular signaling pathways is very likely to be involved. This conclusion is based on a number of observations, including the short- and long-term cellular effects of psychiatric drugs; the critical role signaling pathways play in neurotransmitter, neuropeptide, and neurohormone communication; and the fact that signaling pathways are principle regulators of the diverse array of behavioral symptoms experienced by patients. The genomics era has brought to psychiatry an abundance of genetic linkage and candidate gene findings. The difficult task--now under way--is to discern the functional relevance of these results. Recent evidence suggests the involvement of the ubiquitous protein phosphatase 2B (calcineurin), a critical regulator of many signal transduction pathways, as a schizophrenia susceptibility gene. It is likely that genetic findings in severe psychiatric disorders will continue to implicate direct and indirect modulation of critical intracellular signaling pathways.