The neurobiology of bipolar disorder: focus on signal transduction pathways and the regulation of gene expression

Can J Psychiatry. 2002 Mar;47(2):135-48. doi: 10.1177/070674370204700203.


Objective: This article presents an overview of signal transduction pathways and reviews the research undertaken to study these systems in clinically relevant samples from patients with bipolar disorder (BD).

Method: We reviewed the published findings from studies of postmortem brain tissue and blood samples from patients with BD.

Results: Although the exact biochemical abnormalities have yet to be identified, the presented findings strongly suggest that BD may be due, at least in part, to abnormalities in signal transduction mechanisms. In particular, altered levels or function, or both, of G-protein alpha subunits and effector molecules such as protein kinase A (PKA) and protein kinase C (PKC) have consistently been associated with BD both in peripheral cells and in postmortem brain tissue, while more recent studies implicate disruption in novel second-messenger cascades, such as the ERK/MAPK pathway.

Conclusions: Despite the difficulties inherent in biochemical studies of clinically relevant tissue samples, numerous investigations have illuminated the signal transduction mechanisms in patients with BD. These studies also suggest that BD may be due to the interaction of many abnormalities. In this context, novel techniques enabling the study of gene expression promise to assist in untangling these complex interactions, through visualizing the end result of these changes at the level of gene transcription.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Bipolar Disorder / genetics
  • Bipolar Disorder / physiopathology*
  • Bipolar Disorder / psychology
  • Brain / physiopathology
  • Cyclic AMP-Dependent Protein Kinases / genetics
  • Cyclic AMP-Dependent Protein Kinases / physiology
  • Gene Expression Regulation / physiology*
  • Heterotrimeric GTP-Binding Proteins / genetics
  • Heterotrimeric GTP-Binding Proteins / physiology
  • Humans
  • Protein Kinase C / genetics
  • Protein Kinase C / physiology
  • Signal Transduction / genetics
  • Signal Transduction / physiology*


  • Cyclic AMP-Dependent Protein Kinases
  • Protein Kinase C
  • Heterotrimeric GTP-Binding Proteins