Signal Transduction Abnormalities in Schizophrenia: the cAMP System

Understanding the neurochemistry of schizophrenia involves the study not only of neurotransmitters and their receptors, but also of the signal transduction systems that translate their actions into neural activity. Of particular interest is the signal transduction system involving the second messenger cyclic adenosine monophosphate (cAMP), as all dopamine receptors are either positively or negatively coupled to this system. Studies in blood platelets, cerebrospinal fluid, or postmortem brains of patients with schizophrenia demonstrate abnormalities of stimulated cAMP production. Neuroleptic administration in animal models results in altered cAMP metabolism in a pattern opposite to that seen in schizophrenic patients. These studies suggest that abnormal signal transduction may be involved in the pathogenesis of schizophrenia and that the normalization of this defect may be one mechanism of action of neuroleptic drugs. Psychopharmacology Bulletin. 2002;36(4):92-105