title: Understanding the molecular mechanisms underlying mood stabilizer treatments in bipolar disorder: Potential involvement of epigenetics.
abstract: Mood stabilizers are a category of medications used in the management of mood disorders. The mood stabilizing properties of lithium were first reported in 1949 by John Cade, and since then it has been considered the first line treatment for bipolar disorder. Despite presenting more differences than similarities, mood stabilizers are all characterized by high variability in response in treated patients. This feature has stimulated a vast body of research on potential predictive markers of clinical response, with promising but often inconclusive findings. Pharmacogenetics of mood stabilizers has provided valuable hints toward the involvement of genes and pathways in modulating response. However, with the exception of lithium, the number of studies is still too sparse to draw definite conclusions. Moreover, the mechanism of action of these drugs has yet to be completely elucidated. A growing body of research has explored the effect of mood stabilizers on a family of molecular players responsible for the regulation of gene expression without interfering with the DNA sequence. These processes belong to the epigenetic machinery and represent the mechanisms through which our biological systems interact with environmental factors, including drug treatments. In this review we focused on findings from preclinical and clinical studies suggesting that mood stabilizers may interfere with epigenetic mechanisms, providing an intriguing perspective that may help us filling the gap between molecular functions and clinical efficacy of mood stabilizers.
authors.affiliation: Department of Biomedical Sciences, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Pisanu
authors.affiliation: Department of Biomedical Sciences, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, Italy.
authors.forename: Eleni Merkouri
authors.initials: EM
authors.lastname: Papadima
authors.affiliation: Department of Biomedical Sciences, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, Italy; Unit of Clinical Pharmacology of the University Hospital of Cagliari, Italy. Electronic address: delzompo@unica.it.
authors.forename: Maria
authors.initials: M
authors.lastname: Del Zompo
authors.affiliation: Department of Biomedical Sciences, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, Italy; Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada. Electronic address: squassina@unica.it.
authors.forename: Alessio
authors.initials: A
authors.lastname: Squassina
mesh_terms: D018692:Antimanic Agents / Q000494:pharmacology*; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000235:genetics* / Q000523:psychology; D002220:Carbamazepine / Q000494:pharmacology; D044127:Epigenesis, Genetic; D057890:Epigenomics; D006801:Humans; D018020:Lithium Compounds / Q000494:pharmacology; D019964:Mood Disorders / Q000188:drug therapy / Q000235:genetics / Q000523:psychology; D014635:Valproic Acid / Q000494:pharmacology
chemical_list: D018692:Antimanic Agents; D018020:Lithium Compounds; D002220:Carbamazepine; D014635:Valproic Acid
keywords: Bipolar disorder; Epigenetics; Mood stabilizers; Pharmacogenetics