Chapter

The Handbook of Neuropsychiatric Biomarkers, Endophenotypes and Genes

pp 171-189

Retinoic Acid Signalling in Neuropsychiatric Disease: Possible Markers and Treatment Agents

  • Sarah J. BaileyAffiliated withDepartment of Pharmacy and Pharmacology, University of Bath
  • , Peter J. McCafferyAffiliated withUniversity of Aberdeen, Institute of Medical Sciences

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Retinoic acid is the transcriptionally active product of vitamin A, potentially controlling expression of several hundred genes through activation of specific nuclear receptors. The retinoic acid receptors (RARs) are expressed through much of the adult brain; in contrast the ligand for these receptors is much more restricted in its extent of expression. Non-liganded RARs likely control function through transcriptional repression whereas ligand activated receptors probably regulate more restricted functions including neuroplasticity and neurogenesis. Deregulation of retinoic acid signalling through application of excess levels of this ligand have been associated with depression while genetic and anatomical evidence has linked retinoic acid with the neurodevelopmental hypothesis of schizophrenia and autism. The RARs frequently act in conjunction with the second class of retinoid receptors, the retinoid X receptors (RXRs). These RXRs heterodimerize with other classes of nuclear receptors, including the thyroid hormone receptor which, like those for retinoic acid, are associated with schizophrenia and depression. It is possible that drugs that act on RXRs may be particularly effective in psychiatric disease by acting simultaneously on several nuclear receptor signalling pathways.

Keywords

Depression schizophrenia autism RXR nuclear receptor retinoic acid vitamin A serotonin hippocampus neurogenesis dopamine receptor epigenetic