Kappa Opioid Receptors in the Pathology and Treatment of Major Depressive Disorder

2021 ◽  
Author(s):  
Caroline A. Browne ◽  
Hildegard Wulf ◽  
Irwin Lucki
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Opioid Receptors ◽  
Kappa Opioid Receptors ◽  
Kappa Opioid ◽  
Major Depressive

scholarly journals The Role of Dynorphin and the Kappa Opioid Receptor in Schizophrenia and Major Depressive Disorder: A Translational Approach

2020 ◽  
Author(s):  
Samuel David Clark
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Healthy Volunteers ◽  
Opioid Receptor ◽  
Clinical Data ◽  
Potential Role ◽  
Kappa Opioid Receptor ◽  
Kappa Opioid ◽  
Major Depressive

AbstractThe kappa opioid receptor (KOR) and its endogenous ligands dynorphins (DYN) have been implicated in the development or symptomatology of a variety of neuropsychiatric disorders. This review covers a brief history of the development of KOR agonists and antagonists, their effects in healthy volunteers, and the potential role of DYN/KOR dysfunction in schizophrenia and major depressive disorder from a translational perspective. The potential role of DYN/KOR dysfunction in schizophrenia is based on several lines of evidence. Selective KOR agonists induce affective states in healthy volunteers with similarities to the symptoms of schizophrenia. Studies have shown increased DYN in patients with schizophrenia, although the data have been mixed. Finally, meta-analytic data have shown that opioid antagonists are associated with reductions in the symptoms of schizophrenia. The potential role of DYN/KOR dysfunction in major depressive disorder is also based on a combination of preclinical and clinical data. Selective KOR agonists have shown pro-depressive effects in human volunteers, while selective KOR antagonists have shown robust efficacy in several preclinical models of antidepressant activity. Small studies have shown that nonselective KOR antagonists may have efficacy in treatment-resistant depression. Additionally, recent clinical data have shown that the KOR may be an effective target for treating anhedonia, a finding relevant to both schizophrenia and depression. Finally, recommendations are provided for translating preclinical models for schizophrenia and major depressive disorder into the clinic.

scholarly journals Data-driven analysis of kappa opioid receptor binding in major depressive disorder measured by positron emission tomography

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kelly Smart ◽  
Ashley Yttredahl ◽  
Maria A. Oquendo ◽  
J. John Mann ◽  
Ansel T. Hillmer ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Rating Scale ◽  
Kappa Opioid Receptor ◽  
Anterior Cingulate ◽  
Emission Tomography ◽  
Kappa Opioid ◽  
Major Depressive ◽  
Positron Emission

AbstractPreclinical studies have implicated kappa opioid receptors (KORs) in stress responses and depression-related behaviors, but evidence from human studies is limited. Here we present results of a secondary analysis of data acquired using positron emission tomography (PET) with the KOR radiotracer [11C]GR103545 in 10 unmedicated, currently depressed individuals with major depressive disorder (MDD; 32.6 ± 6.5 years, 5 women) and 13 healthy volunteers (34.8 ± 10 years, 6 women). Independent component analysis was performed to identify spatial patterns of coherent variance in KOR binding (tracer volume of distribution, VT) across all subjects. Expression of each component was compared between groups and relationships to symptoms were explored using the 17-item Hamilton Depression Rating Scale (HDRS). Three components of variation in KOR availability across ROIs were identified, spatially characterized by [11C]GR103545 VT in (1) bilateral frontal lobe; (2) occipital and parietal cortices, right hippocampus, and putamen; and (3) right anterior cingulate, right superior frontal gyrus and insula, coupled to negative loading in left middle cingulate. In MDD patients, component 3 was negatively associated with symptom severity on the HDRS (r = −0.85, p = 0.0021). There were no group-wise differences in expression of any component between patients and controls. These preliminary findings suggest that KOR signaling in cortical regions relevant to depression, particularly right anterior cingulate, could reflect MDD pathophysiology.

scholarly journals Major Depressive Disorder and Kappa Opioid Receptor

2016 ◽  
Vol 3 (2) ◽  
Author(s):  
Li Wei ◽  
◽  
Sun Huijiao ◽  
Chen Hao ◽  
Yang Xicheng ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Opioid Receptor ◽  
Kappa Opioid Receptor ◽  
Kappa Opioid ◽  
Major Depressive

scholarly journals Pharmacotherapy of Major Depressive Disorder: Focus on Desvenlafaxine Succinate

2010 ◽  
Vol 2 ◽  
pp. CMT.S74
Author(s):  
Antolin C. Trinidad ◽  
Benjamin Bregman
Keyword(s):  
Major Depressive Disorder ◽  
Drug Interaction ◽  
Depressive Disorder ◽  
Opioid Receptors ◽  
Lower Risk ◽  
Parent Compound ◽  
The Other ◽  
Major Depressive ◽  
Muscarinic Cholinergic ◽  
Future Utility

The newest antidepressant, desvenlafaxine (DVS) was approved by the FDA in early 2008 and since then, has been available in the market for general use. DVS is dual acting, a serotonin-norepinepherine reuptake inhibitor (SNRI). Like its parent compound, venlafaxine (VEN), DVS inhibits the neuronal re-uptake of both serotonin and norepinepherine while having minimal affinity for muscarinic cholinergic, H1-histaminergic, alpha1-adrenergic and opioid receptors. DVS is moderately effective for MDD at doses ranging from 100–400 milligrams per day. Its possible advantage is its lower risk of drug-drug interaction. There is no extant evidence that it is especially effective over and above the other existing antidepressants. Its niche will be defined by time but one speculation, given preliminary but un-replicated proof of its efficacy in vasomotor instability in peri-menopause, is that it may have a future utility for depressed women entering menopause.

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