Second messenger imbalance hypothesis of schizophrenia

Prostaglandins Leukot Essent Fatty Acids. 1992 May;46(1):33-8. doi: 10.1016/0952-3278(92)90056-o.


Based on the results of studies on intracellular signaling in platelets of schizophrenics, an imbalance of the second messenger system is proposed: Diacylglycerol (DG), which activates protein kinase C (PKC), was increased, while adenylate cyclase (AC)-cAMP function was decreased. It is proposed that the increased DG/PKC function may entail a decrease in inositol 1,4,5-trisphosphate (IP3)/Ca2+ function and lowering of phosphoinositide turnover. If such a pathological intracellular signaling takes place in the brain, it may cause a distorted balance of protein activation via phosphorylation in neurons, resulting in some of the deficits of schizophrenia. Neuroleptics have been reported to antagonize the above-mentioned pathological processes of intracellular signaling. The imbalance hypothesis of the DG/PKC pathway and AC-cAMP pathway is not inconsistent with the dopamine hypothesis of schizophrenia, because dopamine receptor stimulation is indirectly related to reduction in IP3/Ca2+ function and lowering of phosphoinositide metabolism.

Publication types

  • Review

MeSH terms

  • Antipsychotic Agents / pharmacology
  • Blood Platelets / metabolism
  • Calcium / metabolism
  • Cyclic AMP / metabolism
  • Diglycerides / metabolism*
  • Humans
  • Inositol 1,4,5-Trisphosphate / biosynthesis
  • Models, Neurological*
  • Nerve Tissue Proteins / metabolism
  • Phosphatidylinositols / metabolism*
  • Phosphorylation
  • Protein Kinase C / metabolism*
  • Protein Processing, Post-Translational
  • Receptors, Dopamine / metabolism
  • Schizophrenia / metabolism*
  • Second Messenger Systems* / drug effects
  • Synaptic Transmission


  • 1,2-diacylglycerol
  • Antipsychotic Agents
  • Diglycerides
  • Nerve Tissue Proteins
  • Phosphatidylinositols
  • Receptors, Dopamine
  • Inositol 1,4,5-Trisphosphate
  • Cyclic AMP
  • Protein Kinase C
  • Calcium