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10/21/2008
1
The Silent Conspirator:The Effects of Stressin Medical Illness
Teresa Gevedon, MD
Associate Professor
UK Department of Psychiatry
Objectives
• Discuss the nature of the stress response
• Describe the physiological effects of stress based on current research
• Recognize the role of stress in illness
• Identify risk factors and design interventions for patient stress reduction
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Introduction
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Distress may be apparent, but impact on disease
may be covertmay be covert.
Stress?
“Stressed out?”
What are we talking about?
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Stress Response
i d b i d h / h ll• Triggered by perceived threat/challenge
• Includes physiological, emotional and behavioral changes
• Goal is to maintain integrity/safety
• Protective
• Adaptive
Stress Response (cont’d)
This complex dance of events is directed pon the stage of the brain involving the
• Pre‐frontal cortex*
• Hippocampus*• Hippocampus*
• Amygdala*
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Stress Response (cont’d)
...and extends through the HPA axis.
Neuroendocrine Response (Non‐Linear)
Release of
• Catecholamines
• Cortisol
• Pro‐ and anti‐inflammatory cytokinesPro and anti inflammatory cytokines
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Neuroendocrine Response (Non‐Linear) (cont’d)
Involvement of
• Sympathetic nervous system
• Parasympathetic nervous system
Neuroendocrine Response (Non‐Linear) (cont’d)
Result: All systems on ALERT!!Result: All systems on ALERT!!
• Increased heart rate: Decreased digestion
• Increased blood pressure: Decreased immune functionimmune function
• Increased BS: Increased anxiety
• Shunting of blood: Etc.
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Acute Stress Response
• Immediate, intense
• “Fight or Flight”
• Or “Excite?”
• Generally beneficial adaptive• Generally beneficial, adaptive
• Resolves to baseline
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Chronic Stress
• Ongoing stressors
• Not “turning off the response” when not needed
• Results in “wear and tear” on system
Allostasis:(Sterling & Eyer, 1988)
• Active process by which the body responds to daily events and maintains homeostasis
• Achieving stability through change
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Allostasis:(Sterling & Eyer, 1988) (cont’d)
Dysregulation of allostasis, chronic stress, can result in pathology via these same systems which become inefficient.
Allostatic Overload:(McEwen, 1993)
“Wear and tear” due to chronic stressWear and tear due to chronic stress. Includes changes in behavior (poor sleep, increased eating and drinking, smoking, decreased exercise)
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Effects on the Brain: (McEwen, 1998, 1007, 2008)
“Hyperactivity of stress responses results in changes over time in the circuitry of the brain.”
Effects on the Brain: (McEwen, 1998, 1007, 2008) (cont’d)
Adrenal steroids interact with neurochemicals (serotonin, GABA, excitatory amino acids like glutamate). Dendrites are then reorganized and h t dshortened.
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Structural Plasticity
Hippocampus
• Numerous cortisol receptors
• One of the most malleable areas
• And important to cognitive functionAnd important to cognitive function
Structural Plasticity (cont’d)
Chronic stress is associated with
• Decreased grey matter
• Decreased hippocampal volume
• Decreased memory and focus
• Increased fear and aggression (“stressed out”)
• ? BDNF (research unclear)
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Effects on CVD, Stroke
• Increased blood pressure
• Increased heart rate
• Constriction of coronary arteries
• Deposition of fat around the abdomenDeposition of fat around the abdomen (“apple”)
h d
Effects on CVD, Stroke (cont’d)
When stressed
Increased appetite for “comfort foods”
Increased tendency to smoke
Decreased exerciseec eased e e c se
(Increased “allostatic load”)
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S i d d di h (T k b )
Effects on CVD, Stroke (cont’d)
Stress‐induced cardiomyopathy (Takotsubo) –
“Broken Heart Syndrome”
Effects on angina, MI –Effects on angina, MI
Whitehall StudyINTERHEART Study
Effects on Depression/Anxiety
• Long accepted that stress hormones/Long accepted that stress hormones/ cortisol involved (remember DST?)
• Decreased volume of hippocampus (depression, PTSD)
Suggests HPA dysfunction–Suggests HPA dysfunction
• Serotonin, NE, decreased dopamine levels
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Effects on Diabetes
• Stress Increased blood gl cose• Stress – Increased blood glucose
• Insulin resistance
• Increased appetite, weight gain
• Poor glucose control associated with decreased hippocampal volume
Effects on GI System
• IBS• IBS
–Most common, most influenced by stress
• Stress – Decreased small bowel activity increased large bowelactivity, increased large bowel activity
•With IBS – Decreased synchronicity; one/other overreacts
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Effects on GI System (cont’d)
• Ulcer (JAMA 1999)• Ulcer (JAMA, 1999)
–Stress – Increased stomach acid, decreased production of mucus lining
I d l bilit t–Increased vulnerability to H. pylori
Effects on Immunity
• Stress leads to decreased immune function which leads to increased vulnerability towhich leads to increased vulnerability to infection.
–JAMA, 1998 – If stress, particularly financial concerns, lasts longer than one month, there is a greater susceptibility to , g p ycolds
–Decreased rate of wound healing–Increased autoimmune/allergy symptoms
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Effects on Obesity
• Increased “comfort foods” Increased comfort foods (? Increase ghrelin)
• Increased fatigue, decreased exercise interest
Abd i l f t d it• Abdominal fat deposits
Effects on Sex
• Female – Irregular cycles ovulationFemale Irregular cycles, ovulation, infertility
• Male – Erectile dysfunction
• Both – Impaired desire
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Effects on Sleep
• Decreased sleep quality leads toDecreased sleep quality leads to decreased ability to make good decisions
• Increased fatigue and irritability
• Disrupted circadian rhythm
l bl– Increased cortisol, blood pressure
–Study of night shift workers revealed increased obesity, DM and CAD
Effects on Aging
• Cells bombarded by stress signalsCells bombarded by stress signals
• Little recovery time
• Decreased telomeres
• Increased cell “shrinkage”/death
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But we don’t all cope with stress the same way . . .
Risk Factors
• EnvironmentEnvironment
• Genetics
• Early experiences/temperament
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Environment
• Sense of control importantSense of control important
• Whitehall studies indicate increased heart disease with low job control
• Social support system
Genetics
• ? Role of serotonin transporter gene? Role of serotonin transporter gene
• ? BDNF gene
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Early Experiences/Temperament
• TraumaTrauma
• Abuse/neglect
• Deprivation
• Low self‐esteem
Stress Reduction Interventions
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Exercise
d• Increased BDNF, neurogenesis in hippocampus
• New guidelines (HHS, / ) h / k10/08) – 2.5 hrs/wk
• Out in nature is best
Sleep
• 6‐8 hrs/night6 8 hrs/night
• Very important!
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Diet
• Regular balanced mealsRegular balanced meals
• Avoid/limit alcohol, nicotine
• ? Multivitamin
• Breathing exercises
Relaxation/Meditation
Breathing exercises
–Slowly inhale through nose to count of four
–Slowly exhale through mouth to count fof seven
• Tai chi, yoga
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Music
• Type not importantType not important
• Simple rhythm, slower tempo, pauses
–Decreased heart rate and respiratory rate
–Decreased stress hormones, increased immune activity
Socialization
• Social network – friends family churchSocial network friends, family, church
• Community service
• Avoid isolation
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Positive Outlook
• Decreased cortisol production and CRPDecreased cortisol production and CRP
• Humor! Laughter!
• Communicate
• Positive reinforcement
• Realistic expectations
Positive Outlook (cont’d)
• CounselingCounseling
• Brief use of symptomatic meds
–Beware of dependence, side effects
• ? Use of Omega‐3s
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To Suggest
1 Why Zebras Don’t Get Ulcers by1. Why Zebras Don t Get Ulcers, by Robert Sapolsky, PhD
2. “Stress: Portrait of a Killer,” National Geographic/KET
3 N i h lth ih J 2007 i3. Newsinhealth.nih.gov – Jan 2007 issue on stress
References
1. Bosma H, Marmot MG, Hemingway H, Nicholson AG, Brunner E, Stansfeld A. “Low Job Control and Risk of Coronary Heart Disease in Whitehall II (Prospective Cohort) Study. BMJ, 1997; Volume 314:558‐65.
2. Marmot MG, Smith GD, Stansfield S, Patel C, North F, Head J, White I, Brunner E, Feeney A. “Health Inequalities among British Civil Servants: TheInequalities among British Civil Servants: The Whitehall II Study.” The Lancet, 1991; 337:1397‐93.
3. McEwen BS. “Protective and Damaging Effects of Stress Mediators.” N. Engl. J. Med., 1998; 338:171‐79.
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References (cont’d)
4. McEwen BS. “The Physiology and Neurobiology y gy gyof Stress and Adaptation, Central Role of the Brain.” Physiol. Rev., 2007; 87:873‐904.
5. Sapolsky RM. “The Influence of Social Hierarchy on Primate Health.” Science, 2005; 308, 5722:648‐52.
6 Hairston IS Little MT Scanlon MD Barakat MT6. Hairston IS, Little MT, Scanlon MD, Barakat MT, Palmer TD, Sapolsky RM, Heller HC. “Sleep Restriction Suppresses Neurogenesis Induced by Hippocampus‐Dependent Learning.” J Neurophysiol, 2005.
References (cont’d)
7. Sapolsky RM, Romero LM, Munck AU. “How Do Glucocorticoids Influence Stress Responses? Integrating Permissive, Suppressive, Stimulatory, and Preparative Actions.” Endocr. Rev., 2000; 21:55‐89.
8. Seeman TE, Singer BH, Ryff CD, Dienberg G, Levy‐Storms L. “Social Relationships, Gender and Allostatic Load across Two Age Cohorts.” Psychosom. Med., 2002; 64:395‐406.
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References (cont’d)
9. McEwen BS. “Central Effects of Stress Hormones in Health and Disease: Understanding the Protective and Damaging Effects of Stress and Stress Mediators.” European Journal of Pharmacology, 2008; 583:174‐185.
10.Up‐to‐date website.