Signaling pathways in schizophrenia: emerging targets and therapeutic strategies

• Published in: Trends in pharmacological sciences (Regular ed.) Vol. 31; no. 8; pp. 381 - 390
• Main Authors: Karam, Caline S, Ballon, Jacob S, Bivens, Nancy M, Freyberg, Zachary, Girgis, Ragy R, Lizardi-Ortiz, José E, Markx, Sander, Lieberman, Jeffrey A, Javitch, Jonathan A
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-08-2010
• Subjects: Advanced Basic Science; Animals; Antipsychotic Agents - pharmacology; Dopamine D2 Receptor Antagonists; Drug Delivery Systems; Drug Design; Humans; Schizophrenia - drug therapy; Schizophrenia - genetics; Schizophrenia - physiopathology; Signal Transduction - drug effects
• ISSN: 0165-6147; 1873-3735
• DOI: 10.1016/j.tips.2010.05.004

Dopamine D2 receptor antagonism is a unifying property of all antipsychotic drugs in use for schizophrenia. While often effective at ameliorating psychosis, these drugs are largely ineffective at treating negative and cognitive symptoms. Increasing attention is being focused on the complex genetics of the illness and the signaling pathways implicated in its pathophysiology. We review targeted approaches for pharmacotherapy involving the glutamatergic, GABAergic and cholinergic pathways. We also describe several of the major genetic findings that identify signaling pathways representing potential targets for novel pharmacological intervention. These include genes in the 22q11 locus, DISC1, Neuregulin 1/ErbB4, and components of the Akt/GSK-3 pathway.