Introduction. Pathophysiology of Depression: The Emerging Role of Substance P

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In recent years, antagonism of the substance P (SP)-neurokinin-1 (NK1) receptor pathway has emerged as a novel approach to treatment of depression and associated anxiety. The following supplement, based on the symposium held on May 18, 2002, at the annual meeting of the Society of Biological Psychiatry in Philadelphia, Pennsylvania, provides an overview of our current understanding of the biology of the SP-NK1 receptor pathway, its role in affective behavior, and clinical experience with SP (NK1 receptor) antagonists (SPAs) in the management of depression.

In the first article, Patrick W. Mantyh, Ph.D., J.D. (University of Minnesota), describes the expression of SP and NK1 receptors in the brain and spinal cord and briefly reviews the results of preliminary studies involving selective pharmacologic inactivation of NK1 receptor-expressing neurons in various regions of the brain using cytotoxic SP-saporin (SAP) complexes.’ ‹