Signaling pathways in schizophrenia: emerging targets and therapeutic strategies.
Dopamine D(2) 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.
Karam
Caline S
CS
Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Ballon
Jacob S
JS
Bivens
Nancy M
NM
Freyberg
Zachary
Z
Girgis
Ragy R
RR
Lizardi-Ortiz
José E
JE
Markx
Sander
S
Lieberman
Jeffrey A
JA
Javitch
Jonathan A
JA
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D016503:Drug Delivery Systems; D015195:Drug Design; D006801:Humans; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D015398:Signal Transduction / Q000187:drug effects
D014150:Antipsychotic Agents; D065127:Dopamine D2 Receptor Antagonists