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 actions via α-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.

Genome-wide association analysis of insomnia using data from Partners Biobank

“…Using FUMA (Functional Mapping and Annotation) and MAGMA (Multi-marker Analysis of GenoMic Annotation) pipeline, 8 protein-coding genes were identified in the 10 kb distance window, including LOXL2, ENTPD4, ADAMDEC1, ADAM7, NEFM, EBF2, BNIP3L and ADRA1A. Previous research has linked these genes to sleep related disorders, psychiatric disorders and neurodegenerative disorders (Table 2) [31][32][33][34][35][36][37][38] . 27 other SNPs reached suggestive threshold (5 × 10 −6 ) were also identified ( Table 1).…”

Norepinephrine inhibits the cytotoxicity of NK92‑MI cells via the β2‑adrenoceptor/cAMP/PKA/p‑CREB signaling pathway

“…NK cells are a major source of IFN-γ (25). NE exerts its effects through binding to α-and β-ARs (13). Blockade of NK α-, β1-and β2-ARs could suppress the inhibitory cytotoxicity and expression of perforin, granzyme B and IFN-γ of NK cells by NE.…”

“…NE exerts its effects by binding to α-and β-ARs (13). β2-AR is associated with G proteins via a stimulatory G protein subunit, which positively regulates the adenylate cyclase-cyclic adenosine monophosphate (cAMP) signal transduction pathway and cAMP response element-binding protein (CREB) activation.…”

Synchronization of Fibroblasts Ex Vivo in Psychopharmacology

“…Norepinephrine catabolism occurs by either reuptake via the presynaptic norepinephrine transporter (NET), inactivation through the catabolic enzyme catechol O-methyltransferase (COMT) to normetanephrine (NM), or metabolism by monoamine oxidase (MAO type A and type B) with main brain metabolite 3-methoxy-4-hydroxyphenylglycol [58]. The monoamine hypothesis proposed MAO type A increase as well as serotonin and NE decrease in the brain.…”