Scientists exposed patients to high heat using an infra-red device or hot yoga and found both modalities to have anti-depressant effects. Heat stress causes the release of beta-endorphins as well as dynorphin, an endogenous opioid. Exercise produces similar results by releasing anti-inflammatory cytokines that may contribute to an anti-depressant outcome. In this clip, Dr. Charles Raison describes how whole-body hyperthermia has the potential for real-world clinical efficacy as a tool in the fight against major depression.
A hormone produced in the brain that blocks the sensation of pain. Beta-endorphin is released in response to a wide range of painful stimuli and stressors, including heat. Beta-endorphin exhibits morphine-like activity, but its effects are up to 33-times more potent than morphine. Both morphine and beta-endorphin act on the μ-opioid receptor.
A broad category of small proteins (~5-20 kDa) that are important in cell signaling. Cytokines are short-lived proteins that are released by cells to regulate the function of other cells. Sources of cytokines include macrophages, B lymphocytes, mast cells, endothelial cells, fibroblasts, and various stromal cells. Types of cytokines include chemokines, interferons, interleukins, lymphokines, and tumor necrosis factor.
A mood disorder characterized by profound sadness, fatigue, altered sleep and appetite, as well as feelings of guilt or low self-worth. Depression is often accompanied by perturbations in metabolic, hormonal, and immune function. A critical element in the pathophysiology of depression is inflammation. As a result, elevated biomarkers of inflammation, including the proinflammatory cytokines interleukin-6 and tumor necrosis factor-alpha, are commonly observed in depressed people. Although selective serotonin reuptake inhibitors and cognitive behavioral therapy typically form the first line of treatment for people who have depression, several non-pharmacological adjunct therapies have demonstrated effectiveness in modulating depressive symptoms, including exercise, dietary modification (especially interventions that capitalize on circadian rhythms), meditation, sauna use, and light therapy, among others.
A potent endogenous opioid peptide. Dynorphin acts on the kappa-opioid receptor and is associated with a transient feeling of dysphoria. It has many different physiological actions, depending upon its site of production, and is involved in addiction, temperature regulation, appetite, circadian rhythm, pain, stress, and depression. Dynorphin may also be involved in the body’s thermoregulatory response to hyperthermia.
The tendency of things to change into their opposites, especially as a supposed governing principle of natural cycles and of psychological development.
Important for the endocrine enhancing properties of exercise. Exerkines are exercise-induced hormonal-like factors which mediate the systemic benefits of exercise through autocrine, paracrine, and/or endocrine properties.
A small organ located within the brain's medial temporal lobe. The hippocampus is associated primarily with memory (in particular, the consolidation of short-term memories to long-term memories), learning, and spatial navigation. Amyloid-beta plaque accumulation, tau tangle formation, and subsequent atrophy in the hippocampus are early indicators of Alzheimer’s disease.
A critical element of the body’s immune response. Inflammation occurs when the body is exposed to harmful stimuli, such as pathogens, damaged cells, or irritants. It is a protective response that involves immune cells, cell-signaling proteins, and pro-inflammatory factors. Acute inflammation occurs after minor injuries or infections and is characterized by local redness, swelling, or fever. Chronic inflammation occurs on the cellular level in response to toxins or other stressors and is often “invisible.” It plays a key role in the development of many chronic diseases, including cancer, cardiovascular disease, and diabetes.
IL-10, also known as human cytokine synthesis inhibitory factor (CSIF), is an anti-inflammatory cytokine with multiple, pleiotropic, effects in immunoregulation and inflammation. It downregulates the expression of Th1 cytokines, MHC class II antigens, and co-stimulatory molecules on macrophages. It also enhances B cell survival, proliferation, and antibody production. A study in mice has shown that IL-10 is also produced by mast cells, counteracting the inflammatory effect that these cells have at the site of an allergic reaction. IL-10 is capable of inhibiting synthesis of pro-inflammatory cytokines such as IFN-γ, IL-2, IL-3, TNFα and GM-CSF made by cells such as macrophages and Th1 T cells.
A proinflammatory cytokine produced by macrophages. IL-1 beta is an important mediator of the body’s inflammatory response. It is involved in a variety of cellular activities, including cell proliferation, differentiation, and apoptosis.
A pro-inflammatory cytokine that plays an important role as a mediator of fever and the acute-phase response. IL-6 is rapidly induced in the context of infection, autoimmunity, or cancer and is produced by almost all stromal and immune cells. Many central homeostatic processes and immunological processes are influenced by IL-6, including the acute-phase response, glucose metabolism, hematopoiesis, regulation of the neuroendocrine system, hyperthermia, fatigue, and loss of appetite. IL-6 also plays a role as an anti-inflammatory cytokine through inhibition of TNF-alpha and IL-1 and activation of IL-1ra and IL-10.
One of four related receptors that bind opioid-like compounds in the brain. Opioid receptors are responsible for mediating the effects of these compounds, which including altering pain, consciousness, motor control, mood, stress, and addiction. Agonism of this receptor produces a transient feeling of dysphoria but also causes an upregulation and sensitization of mu opioid receptors, which interact with beta-endorphin.
Salvinorin A is the main active psychotropic molecule in Salvia divinorum, a Mexican plant which has a long history of use as an entheogen by indigenous Mazatec shamans. Salvinorin A can produce psychoactive experiences in humans with a typical duration of action being several minutes to an hour or so. It is structurally distinct from other naturally occurring hallucinogens, acting on the k-opioid receptor instead of the 5-HT2A (serotonin) receptor.
A proinflammatory cytokine. TNF-alpha is produced by a wide range of cells, including macrophages, lymphocytes, glial cells, and others. TNF-alpha signaling inhibits tumorigenesis, prevents viral replication, and induces fever and apoptosis. Dysregulation of the TNF-alpha signaling pathway has been implicated in a variety of disorders including cancer, autoimmune diseases, Alzheimer’s disease, and depression.
A protein responsible for mediating the effects of agonists such as morphine and beta-endorphin. μ-opioid receptors are involved in the body’s thermoregulatory response to hypothermia.
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