Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9016299 | Progress in Neuro-Psychopharmacology and Biological Psychiatry | 2005 | 11 Pages |
Abstract
Although antidepressants have been used clinically for more than 50 years, no consensus has been reached concerning their precise molecular mechanism of action. Pharmacogenomics is a powerful tool that can be used to identify genes affected by antidepressants or by other effective therapeutic manipulations. Using this tool, others and we have identified as candidate molecular targets several genes or expressed sequence tags (ESTs) that are induced by chronic antidepressant treatment. In this article, we review antidepressant-elicited changes in gene expression, focusing especially on the remodeling of neuronal circuits that results. This refocusing motivates our hypothesis that this plasticity represents the mechanism for drug efficacy, and thus a causal event for clinical improvement. Defining the roles of these molecules in drug-induced neural plasticity is likely to transform the course of research on the biological basis of antidepressants. Such detailed knowledge will have profound effects on the diagnosis, prevention, and treatment of depression. Consideration of novel biological approaches beyond the “monoamine hypothesis” of depression is expected to evoke paradigm shifts in the future of antidepressant research.
Keywords
CREBsoluble N-ethylmaleimide-sensitive fusion protein attachment protein receptorCSPECTRDATCALALGAP-43SNARENGFBDNFcAMPSALCyclic adenosine monophosphateESTDepressionrepresentational difference analysisSerial analysis of gene expressionExpressed Sequence TagSAGETricyclic antidepressantElectroconvulsive therapyMicroarrayAntidepressantPharmacogenomicsnerve growth factorBrain-derived neurotrophic factorSelective serotonin reuptake inhibitorSSRIHPAcAMP response element binding proteinCysteine string proteinNeural plasticity
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Authors
Mitsuhiko Yamada, Misa Yamada, Teruhiko Higuchi,