title: The Role of Norepinephrine and Its α-Adrenergic Receptors in the Pathophysiology and Treatment of Major Depressive Disorder and Schizophrenia: A Systematic Review.
abstract: Norepinephrine (NE) is recognized as having a key role in the pathophysiology of major depressive disorder (MDD) and schizophrenia, although its distinct actionsviaα-adrenergic receptors (α-ARs) are not well defined. We performed a systematic review examining the roles of NE and α-ARs in MDD and schizophrenia. PubMed and ProQuest database searches were performed to identify English language papers published between 2008 and 2015. In total, 2,427 publications (PubMed,n= 669; ProQuest,n= 1,758) were identified. Duplicates, articles deemed not relevant, case studies, reviews, meta-analyses, preclinical reports, or articles on non-target indications were excluded. To limit the review to the most recent data representative of the literature, the review further focused on publications from 2010 to 2015, which were screened independently by all authors. A total of 16 research reports were identified: six clinical trial reports, six genetic studies, two biomarker studies, and two receptor studies. Overall, the studies provided indirect evidence that α-AR activity may play an important role in aberrant regulation of cognition, arousal, and valence systems associated with MDD and schizophrenia. Characterization of the NE pathway in patients may provide clinicians with information for more personalized therapy of these heterogeneous diseases. Current clinical studies do not provide direct evidence to support the role of NE α-ARs in the pathophysiology of MDD and schizophrenia and in the treatment response of patients with these diseases, in particular with relation to specific valence systems. Clinical studies that attempt to define associations between specific receptor binding profiles of psychotropics and particular clinical outcomes are needed.
authors.affiliation: Department of Neuropsychiatry and Behavioral Science, University of South Carolina , Columbia, SC , USA.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Maletic
authors.affiliation: Medical Affairs - Psychiatry, Lundbeck LLC , Deerfield, IL , USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Eramo
authors.affiliation: Medical Affairs - Psychiatry, Lundbeck LLC , Deerfield, IL , USA.
authors.forename: Keva
authors.initials: K
authors.lastname: Gwin
authors.affiliation: Medical Affairs, Otsuka Pharmaceutical Development and Commercialization, Inc. , Princeton, NJ , USA.
authors.forename: Steve J
authors.initials: SJ
authors.lastname: Offord
authors.affiliation: Medical Affairs, Otsuka Pharmaceutical Development and Commercialization, Inc. , Princeton, NJ , USA.
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Duffy
keywords: antidepressants; antipsychotics; major depressive disorder; norepinephrine; pathophysiology; schizophrenia; valence systems; α-adrenergic receptors