Decreased protein kinase C (PKC) in platelets of pediatric bipolar patients: effect of treatment with mood stabilizing drugs

J Psychiatr Res. 2008 Jan;42(2):106-16. doi: 10.1016/j.jpsychires.2006.11.004. Epub 2007 Jan 8.

Abstract

Pediatric bipolar disorder (PBD) is a major public health concern, however, its neurobiology is poorly understood. We, therefore, studied the role of protein kinase C (PKC) in the pathophysiology of bipolar illness. We determined PKC activity and immunolabeling of various PKC isozymes (i.e., PKC alpha, PKC betaI, PKC betaII, and PKC delta) in the cytosol and membrane fractions of platelets obtained from PBD patients and normal control subjects. PKC activity and PKC isozymes were also determined after 8 weeks of pharmacotherapy of PBD patients (n=16) with mood stabilizers. PKC activity and the protein expression of PKC betaI and betaII, but not PKC alpha or PKC delta, were significantly decreased in both membrane as well as cytosol fractions of platelets obtained from medication-free PBD patients compared with normal control subjects. Eight weeks of pharmacotherapy resulted in significantly increased PKC activity but no significant changes in any of the PKC isozymes in PBD patients. These results indicate that decreases of specific PKC isozymes and decreased PKC activity may be associated with the pathophysiology of PBD and that pharmacotherapy with mood stabilizing drugs results in an increase and normalization of PKC activity along with improvement in clinical symptoms.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Anticonvulsants / therapeutic use*
  • Antimanic Agents / therapeutic use*
  • Antipsychotic Agents / therapeutic use*
  • Bipolar Disorder / drug therapy*
  • Bipolar Disorder / enzymology*
  • Blood Platelets / drug effects*
  • Blood Platelets / enzymology*
  • Child
  • Female
  • Humans
  • Isoenzymes / blood*
  • Lithium Carbonate / therapeutic use
  • Male
  • Protein Kinase C / blood*
  • Psychiatric Status Rating Scales
  • Reference Values
  • Statistics as Topic
  • Treatment Outcome

Substances

  • Anticonvulsants
  • Antimanic Agents
  • Antipsychotic Agents
  • Isoenzymes
  • Lithium Carbonate
  • Protein Kinase C