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- Title
Molecular mechanisms underlying synergistic effects of SSRI-antipsychotic augmentation in treatment of negative symptoms in schizophrenia.
- Authors
Chertkow, Yael; Weinreb, Orly; Youdim, Moussa B H; Silver, Henry
- Abstract
Negative symptoms in schizophrenia respond poorly to antipsychotics, but may improve when these are augmented with selective serotonin reuptake inhibitors (SSRIs). The molecular mechanisms underlying the augmentation are unclear. Nevertheless, significant progress has been made, pointing to some candidate systems which may be involved in SSRI-antipsychotic synergism. Thus, the enhanced dopamine release by SSRI-antipsychotic treatment is modulated by specific serotonergic receptors and by tyrosine hydroxylase. There are modifications in gamma-aminobutyric acid system via glutamate decarboxylase 67, protein kinase C beta and the receptor for activated C-kinase 1 (Rack1). Some studies indicate the input of transcription and neurotrophic factors as phospho-cyclic adenosine monophosphate response element-binding protein, Fos and fibroblast growth factor-2. Alterations in calcium signaling (neurogranin, regulator of G-protein signaling and Rack1) and in cytokine receptors for interleukin-8 and chemokine have also been reported. While as yet limited in scope, the evidence suggests definable molecular targets which may be implicated in drug development based on SSRI-antipsychotic synergistic actions.
- Publication
Journal of neural transmission (Vienna, Austria : 1996), 2009, Vol 116, Issue 11, p1529
- ISSN
1435-1463
- Publication type
Journal Article
- DOI
10.1007/s00702-009-0255-4