Mitochondria: A Connecting Link in the Major Depressive Disorder Jigsaw

Background: Depression is a widespread phenomenon with varying degrees of pathology in different patients. Various hypotheses have been proposed for the cause and continuance of depression. Some of these include, but not limited to, the monoamine hypothesis, the neuroendocrine hypothesis, and the more recent epigenetic and inflammatory hypotheses. Objective: In this article, we review all the above hypotheses with a focus on the role of mitochondria as the connecting link. Oxidative stress, respiratory activity, mitochondrial dynamics and metabolism are some of the mitochondria-dependent factors which are affected during depression. We also propose exogenous ATP as a contributing factor to depression. Result: Literature review shows that pro-inflammatory markers are elevated in depressive individuals. The cause for elevated levels of cytokines in depression is not completely understood. We propose exogenous ATP activates purinergic receptors which in turn increase the levels of various proinflammatory factors in the pathophysiology of depression. Conclusion: Mitochondria are integral to the function of neurons and undergo dysfunction in major depressive disorder patients. This dysfunction is reflected in all the various hypotheses that have been proposed for depression. Among the newer targets identified, which also involve mitochondria, includes the role of exogenous ATP. The diversity of purinergic receptors, and their differential expression among various individuals in the population, due to genetic and environmental (prenatal) influences, may influence the susceptibility and severity of depression. Identifying specific receptors involved and using patient-specific purinergic receptor antagonist may be an appropriate therapeutic course in the future.

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Depression – Let’s Talk - Role of Aashwasan Chikitsa

Journal of Ayurveda and Integrated Medical Sciences (JAIMS) ◽

10.21760/jaims.v2i3.8234 ◽

2017 ◽

Vol 2 (3) ◽

Author(s):

Priya Vishal Naik ◽

Prachi Datta Dalvi U.

Keyword(s):

Major Depressive Disorder ◽

Depressive Disorder ◽

Positive Attitude ◽

Medical Intervention ◽

Medical Illness ◽

Suicidal Tendency ◽

Major Depressive ◽

Curative Therapy ◽

Personal Interaction

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.

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

10.1007/164_2020_396 ◽

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.

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