Implications of epigenetic modulation for novel treatment approaches in patients with schizophrenia.
Schizophrenia is a heterogeneous and complex mental disorder with high rates of disability, non-recovery, and relapse. The primary pharmacological treatments for schizophrenia are antipsychotics. Notwithstanding the efficacy of antipsychotics in ameliorating positive symptoms and reducing relapse rates, cognitive deficits and negative symptoms are not sufficiently treated with available pharmaceutical agents. Moreover, schizophrenia is associated with consistent, replicable, and clinically significant deficits in cognition. The importance of cognitive deficits in schizophrenia is emphasized by reports indicating that the severity of cognitive deficits is predictive of treatment compliance, adherence, and risk of relapse among first-episode individuals. Taken together, this review highlights epigenetic modulations involving histone deacetylase (HDAC) inhibitors as a potential avenue for novel treatment toward improvements in cognition and functional outcomes in patients with schizophrenia. The combination of epigenetic modulation with pharmacological interventions that engage multiple disparate physiological systems implicated in schizophrenia are discussed, and may represent a more effective strategy in ameliorating cognitive deficits and mitigating symptoms for improved functionality.
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Canada; Institute of Medical Science, University of Toronto, Toronto, Canada.
Danielle S
DS
Cha
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Canada; Institute of Medical Science, University of Toronto, Toronto, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
Paul A
PA
Kudlow
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Canada; Centre for Neuroscience Studies, Queen's University, Kingston Canada.
Anusha
A
Baskaran
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Canada; Interdisciplinary Laboratory of Clinical Neurosciences (LINC), Department of Psychiatry, Universidade Federal de São Paulo, São Paulo, Brazil.
Rodrigo B
RB
Mansur
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Canada; Institute of Medical Science, University of Toronto, Toronto, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Department of Pharmacology, University of Toronto, Toronto, ON, Canada. Electronic address: Roger.McIntyre@uhn.ca.
Roger S
RS
McIntyre
D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D044127:Epigenesis, Genetic / Q000187:drug effects*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics
D014150:Antipsychotic Agents; D056572:Histone Deacetylase Inhibitors
Antipsychotic; Cognition; Epigenetic; Histone acetylase; Histone deacetylase; Histone modification; Schizophrenia; Treatment