Psychological Stress and the Mind-Body C

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Information about Psychological Stress and the Mind-Body C
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Published on December 16, 2008

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Psychological Stress and Cytokines:Where Mind and Body Meet : Psychological Stress and Cytokines:Where Mind and Body Meet Barry Thompson, MD Seattle University October, 2007 This Talk Will Cover : This Talk Will Cover I. Basic definitions II. How the body responds to stress III. What pro-inflammatory cytokines are IV. How they act V. Their contribution to physical and psychological disorders within the “mind-body” dynamic Stress Defined : Stress Defined The state which results from some physical or psychological threat to one’s homeostasis that in turn activates certain systems within the body, resulting in physiological change and a response to the threat. Medical Definitions : Medical Definitions Autonomic nervous system (sympathetic and parasympathetic divisions): blood pressure, heart rate, sweating, digestion, pupil size, etc. Endothelial cells: line blood vessels Atherosclerosis: narrowing of blood vessels by “plaques” in blood-vessel lining (“hardening of the arteries”) Glial cells (mainly astrocytes): cells that “support” neurons in the brain Medical Definitions : Medical Definitions Blood-brain barrier: specialized barrier between bloodstream and the brain Peripheral nerves: nerves to parts of the body, extending outward from the brain and spinal cord Paraganglia: local groupings of nerve cells outside of the CNS HPA axis: regulates stress response Hypothalamic-Pituitary-Adrenal Axis (HPA-Axis) : Hypothalamic-Pituitary-Adrenal Axis (HPA-Axis) Mechanism by which the body responds to a stressful stimulus (such as “fight-or-flight”) Hypothalamus stimulates pituitary to stimulate the adrenal glands Adrenal glands release adrenaline, cortisol (“stress hormone”) Results in increased blood pressure, heart rate, alertness, readiness to respond to threat Also results in proinflammatory cytokine elevation HPA Axis : HPA Axis Maier, Watkins (1998) What Are Cytokines? : What Are Cytokines? A diverse group of medium-sized proteins Act in very small concentrations (ppm, ppb) Regulate the activities of a wide variety of cells and tissues Are active in both normal and pathological conditions Cytokines : Cytokines Generally act over short distances and time spans Made widely in the body-brain, liver, immune system, fat cells, endothelial cells (cells that line blood vessels) Are able to cross the blood-brain barrier Slide 10: What Do They Do? Cell differentiation (how specialized cells develop) Regulate cell growth and repair Crucial role in inflammation Act as messengers between the brain and immune system Different cells may respond differently to the same cytokine Act by binding to specific membrane receptors Pro-Inflammatory Cytokine Images: : Pro-Inflammatory Cytokine Images: Interleukin Family Tumor Necrosis Factor (TNF) Source: http://www.copewithcytokines.de/ Specific Pro-inflammatory Cytokines : Specific Pro-inflammatory Cytokines Interleukin-1 Interleukin-2 Interleukin-6 Tumor necrosis factor alpha Interferon gamma IL-6, TNF-alpha increase with normal aging (higher levels in men) Cytokines Are Part of the Neuro-Immune System : Cytokines Are Part of the Neuro-Immune System An interdependent network involving communication between the nervous system, immune system, and endocrine system (specialized glands that secrete hormones) Forms the basis of what has come to be known as the “mind-body connection” The Neuro-Immune System : The Neuro-Immune System A highly complex sensory organ Senses changes in environment, and responds HPA axis, cytokines able to powerfully influence bodily systems Directly links the CNS and the rest of the body The Neuro-Immune System : The Neuro-Immune System Information exchanged back and forth between immune system and brain Communication via cytokines as well as by direct cell contact Emotional factors play a crucial role in cytokine release Via cytokines, emotions can have major impact upon long-term health Therefore, the nervous system is no longer considered to act in an isolated manner; via cytokines, the brain is able to directly influence both inflammation and cell regulation in a wide variety of processes. : Therefore, the nervous system is no longer considered to act in an isolated manner; via cytokines, the brain is able to directly influence both inflammation and cell regulation in a wide variety of processes. Cytokine Effects : Cytokine Effects Outside the brain: Atherosclerosis-increases risk of heart attack, high blood pressure Thrombosis (clotting within blood vessels) Increased risk of diabetes Lead to development of certain cancers (leukemia, Non-Hodgkin’s Lymphoma, Multiple Myeloma) Implicated in auto-immune diseases (arthritis, lupus) Osteoporosis Slide 18: Inside the brain: Released by glial support cells (mainly astrocytes) in response to psychological stress Initiate inflammatory response Help regulate HPA-axis May worsen certain auto-immune brain disorders, such as multiple sclerosis High concentrations of IL-2 receptors in hippocampus (important in memory) Act on multiple neurotransmitter systems (dopamine, serotonin, acetylcholine, noradrenaline) that affect mood and cognition Promote neuronal degeneration and death Cytokines and Physical Stress : Cytokines and Physical Stress Immune system ? brain pathway (direct): cytokines released by WBC’s in response to infection, injury cytokines can enter the brain by crossing the blood-brain barrier Maier, Watkins (1998) Cytokines and Physical Stress : Cytokines and Physical Stress Immune system ? brain pathway (indirect): communicate with the brain by way of the peripheral nerves Maier, Watkins (1998) Either directly or indirectly, once the cytokine “message” gets to the brain: : Bind to other support cells (astrocytes) + neurons Support cells then make their own cytokines Result ? typical “sick” feeling and behavior: ? appetite confused thinking ? anxiety sleep disturbances ? pleasure (anhedonia) HPA axis ? more cytokines released outside brain Either directly or indirectly, once the cytokine “message” gets to the brain: Cytokines and Psychological Stress : Cytokines have been shown to rise inside and outside the brain in relation to psychological stress such as: performance of a stressful task exposure to a psychological stressor Cytokines and Psychological Stress Cytokines and Psychological Stress : Cytokines and Psychological Stress Involves the sympathetic nervous system: Cytokine levels in rats rise even when adrenals have been removed Cytokines and Psychological Stress : Cytokines and Psychological Stress Steptoe et al (2001): incongruous color naming mirror tracing with high expectations Cytokines measured at 45 minutes & 2 hours: blood levels of IL-6 ? 56% Cytokines and Chronic Psychological Stress : Cytokines and Chronic Psychological Stress Robles et al (2005): Adults caring for spouse with Alzheimer’s showed 4x annual increase in IL-6 production This did not change even several years after caregiving ceased (followed for 6 years) Chronic stress can result in long-term increases in pro-inflammatory cytokines, above and beyond normal aging, even after stressor removed Cytokines and the Brain in Chronic Stress : Cytokines and the Brain in Chronic Stress ? Neuron formation ? Neuron loss, including hippocampus (memory) Regular exercise may mitigate effects of chronic stress by way of ? brain cytokines Implicated in Alzheimer’s Disease, Parkinson’s Disease, pseudo-dementia, depression Cytokines and Depression : Cytokines and Depression Depression is common in many medical conditions; implies more than just primary psychological cause Major depression common in interferon therapy in cancer and hepatitis C (36%) Antidepressant drugs possess some anti-inflammatory properties–may partly account for their effects (by blocking cytokine-induced inflammation) Cytokines released during a viral illness may cause relapse Cytokines and Depression : Cytokines and Depression Initially increase serotonin activity Simultaneously inhibit serotonin synthesis Net effect: ?? serotonin Also acts on serotonin receptors to ? activity Therefore, chronic stress reduces serotonin and contributes to depression Brain Serotonin Pathways : Brain Serotonin Pathways Widely distributed throughout the brain Particularly numerous in cortex, limbic system (emotions and memory), basal ganglia, and hypothalamus May explain why depression affects not only mood, but sleep, libido, appetite, memory Cytokines and Schizophrenia : Cytokines and Schizophrenia IL-2 can cause schizophrenia-like symptoms (directly proportional to dose) Up to 65% of patients receiving high-dose IL-2 developed delusions and severe cognitive impairment ? IL-6 levels in blood of people with schizophrenia Neuroleptics inhibit production and/or release of cytokines Cytokines and Aging : Cytokines and Aging Serum IL-6 and TNF-alpha increase with normal aging (higher levels in men) Higher levels correlate with impaired cognitive ability and may predict future cognitive decline Increased risk of vascular dementia ? IL-6 levels associated with higher morbidity/mortality even after controlling for demographic factors and health behaviors Summary: Risks : Summary: Risks Atherosclerosis, diabetes High blood pressure, stroke, heart attack Certain cancers Vascular dementia, AD, PD Depression Premature aging, general physical decline Arthritis, osteoporosis What Can Be Done? : What Can Be Done? Mitigate stress level (relaxation exercises, meditate, alter lifestyle, or anything else that reduces personal stress) Regular exercise (lowers cytokine levels) Diet: higher omega-3/omega-6 PUFA levels reduce pro-inflammatory cytokine response to stress Think Happy Thoughts!

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