Role of Opioidergic System in Regulating Depression Pathophysiology

2020 ◽  
Vol 26 (41) ◽  
pp. 5317-5334
Author(s):  
George Anderson ◽  
Michael Maes

Background: There is a clear clinical need for a better understanding of the biological underpinnings of major depressive disorder (MDD), allowing for the development of a treatment that is targeted to pathophysiology. Recent data indicate a role for the endogenous opioidergic system in MDD. This article reviews the roles and physiological interactions of the endogenous opioidergic system in the pathophysiology and heterogeneity of MDD. Methods: Articles on the pathophysiology of MDD, as well as on the endogenous opioidergic system and mitochondrial function, form the basis of this review article. Results: The endogenous opioidergic system is intimately linked to wider MDD pathophysiology, including alterations in the gut microbiome, gut permeability, circadian rhythm, amygdala-prefrontal cortex interactions, and mitochondrial function. A decrease in the μ-/κ-opioid receptor ratio is an important mediator of the changes in mood in MDD, with effects not only on neurons, but also on glia and immune cells. Conclusion: The endogenous opioidergic system is intimately interwoven with MDD pathophysiology and provides a relevant target for novel treatment development, as well as providing a focus for the integration of wider MDD pathophysiology.

2019 ◽  
Vol 254 ◽  
pp. 139-140
Author(s):  
B. Christopher Frueh ◽  
Summer G. Danner ◽  
Alok Madan ◽  
Benjamin Weinstein ◽  
Elizabeth Newlin ◽  
...  

1961 ◽  
Vol 1 (3) ◽  
pp. 89-98
Author(s):  
Karol J. Krotki

Discussions about the role of small enterprise in economic development tend to remain inconclusive partly because of the difficulty of assessing the relative importance of economic and non-economic objectives and partly because of the dearth of factual information on which to base an economic calculus. It is probably true, moreover, that, because of a lack of general agreement as to the economic case for or against small enterprise, non-economic considerations, including some merely romantic attitudes toward smallness and bigness, tend to exert an undue influence on public policies. There may, of course, be no clear-cut economic case. And noneconomic considerations should and will inevitably weigh significantly in policy decisions. If, however, some of the economic questions could be settled by more and better knowledge, these decisions could more accurately reflect the opportunity costs of pursuing non-economic objectives.


Author(s):  
Md. Junaid ◽  
Yeasmin Akter ◽  
Syeda Samira Afrose ◽  
Mousumi Tania ◽  
Md. Asaduzzaman Khan

Background: AKT/PKB is an important enzyme with numerous biological functions, and its overexpression is related to the carcinogenesis. AKT stimulates different signaling pathways that are downstream of activated tyrosine kinases and phosphatidylinositol 3-kinase, hence functions as an important target for anti-cancer drugs. Objective: In this review article, we have interpreted the role of AKT signaling pathways in cancer and natural inhibitory effect of Thymoquinone (TQ) in AKT and its possible mechanism. Method: We have collected the updated information and data on AKT, their role in cancer and inhibitory effect of TQ in AKT signaling pathway from google scholar, PubMed, Web of Science, Elsevier, Scopus and many more. Results: There are many drugs already developed, which can target AKT, but very few among them have passed clinical trials. TQ is a natural compound, mainly found in black cumin, which has been found to have potential anti-cancer activities. TQ targets numerous signaling pathways, including AKT, in different cancers. In fact, many studies revealed that AKT is one of the major targets of TQ. The preclinical success of TQ suggests its clinical studies on cancer. Conclusion: This review article summarizes the role of AKT in carcinogenesis, its potent inhibitors in clinical trials, and how TQ acts as an inhibitor of AKT and TQ’s future as a cancer therapeutic drug.


Author(s):  
Priya Vishal Naik ◽  
Prachi Datta Dalvi U.

The WHO theme for the year 2017 is Depression. Depression (major depressive disorder) is a common and serious medical illness that negatively affects how a person feels, thinks and behaves. Psychotherapy if incorporated along with medications can be of substantial help in depression. It is also called ‘talking therapy’ and is based on personal interaction with the patient. Patients suffering from this disorder do not easily accept it and hence do not feel the need to seek medical intervention or counselling. In this process the symptoms might get aggravated and suicidal tendency (which is the worst effect of this disease) may develop. So it is extremely essential for the patient, family and society to accept, talk, discuss and seek treatment for this disease. This ‘talking therapy’ is of utmost importance in today’s life where concept of privacy is taking its toll. This therapy is mentioned in Ayurveda as Aashwasan Chikitsa. Aashwasan Chikitsa consists of good, pleasing and benevolent thoughts, spiritual ideas, positive attitude, ethics and communication with near ones. So in the treatment of psychological disorders, along with medications counselling therapy plays a very important role. Finally counselling can act as a part of preventive, curative therapy and also aids to avoid recurrence in the patients of depression.


Author(s):  
Divya Kajaria

Role of cholesterol in the pathogenesis of diabetes is the emergent are of research with full of potential; it not only open a vast area of therapeutic interventions but also can change the prevailing treatment modality. Ayurveda, the Indian system of medicine materialize the concept of lipocenteric approach for the management of diabetes even thousands of years back. According to Ayurveda, the natural properties of lipid are deranged that causes diabetes. It may prove beneficial to quest the search of herbal remedies that can harmonize the lipid balance and uproot the pathogenesis. In the presenting review article, role of cholesterol in the pathogenesis of diabetes is discussed along with detailed description of Ayurvedic concepts regarding pathogenesis and a brief description of herbal management.


2021 ◽  
Vol 22 (11) ◽  
pp. 5495
Author(s):  
Felipe Borges Almeida ◽  
Graziano Pinna ◽  
Helena Maria Tannhauser Barros

Under stressful conditions, the hypothalamic-pituitary-adrenal (HPA) axis acts to promote transitory physiological adaptations that are often resolved after the stressful stimulus is no longer present. In addition to corticosteroids (e.g., cortisol), the neurosteroid allopregnanolone (3α,5α-tetrahydroprogesterone, 3α-hydroxy-5α-pregnan-20-one) participates in negative feedback mechanisms that restore homeostasis. Chronic, repeated exposure to stress impairs the responsivity of the HPA axis and dampens allopregnanolone levels, participating in the etiopathology of psychiatric disorders, such as major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). MDD and PTSD patients present abnormalities in the HPA axis regulation, such as altered cortisol levels or failure to suppress cortisol release in the dexamethasone suppression test. Herein, we review the neurophysiological role of allopregnanolone both as a potent and positive GABAergic neuromodulator but also in its capacity of inhibiting the HPA axis. The allopregnanolone function in the mechanisms that recapitulate stress-induced pathophysiology, including MDD and PTSD, and its potential as both a treatment target and as a biomarker for these disorders is discussed.


2020 ◽  
Author(s):  
Samuel David Clark

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.


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