Dysfunction of the cholinergic muscarinic receptors and bipolar disorder

Andrew Stuart Gibbons

Research output: Contribution to journalArticleResearchpeer-review


The underlying molecular cause of bipolar disorder remains poorly understood. Observations of increased symptoms of depression in individuals following prolonged exposure to anticholinesterase insecticides led to the proposal that the manic and depressive symptoms of bipolar disorder result from imbalances in the cholinergic and adrenergic neurotransmitter systems - a hypothesis that has been supported by subsequent pharmacological studies, which have highlighted the involvement of the muscarinic receptor family of cholinergic receptors. Candidate gene studies that have looked for polymorphisms within the muscarinic receptor gene sequences have failed to provide conclusive evidence of mutations in the gene sequence associated with the incidence of bipolar disorder. However, recent studies using radioligands that selectively bind to specific muscarinic receptors have reported deficits in the expression of cholinergic receptor muscarinic-2 (CHRM2) and CHRM3 proteins in subjects with bipolar disorder, significantly advancing our understanding of which receptors are affected in the disorder, while providing evidence against proposed common causes of bipolar disorder and other psychiatric disorders, such as major depression and schizophrenia. Regional variations in the expression of CHRM2 and CHRM3 implicate their involvement in aspects of mood, cognition and decision-making that are commonly affected in bipolar disorder. The growing realisation of the role CHRM2 plays in inflammatory responses may also offer insight into the activation of pro-inflammatory cytokine networks that has been reported in individuals with bipolar disorder.

Original languageEnglish
Pages (from-to)97-100
Number of pages4
JournalEuropean Psychiatric Review
Issue number2
Publication statusPublished - Dec 2011
Externally publishedYes


  • Bipolar disorder
  • Cholinergic system
  • Depression
  • Mood disorders
  • Muscarinic receptors

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