Transcript stress syl 00 - University of Illinois Archives

PSYCHONEUROIMMUNOLOGY
The concept of a stress response: Physical or psychological stress alters the body's
neuroendocrine systems. Responses are attempts to successfully cope with stress. When
stress is severe or chronic, the altered physiology can cause or exacerbate health
problems.
Holmes life stress scale: statistical association between stress and numerous illnesses.
Negative events are more detrimental than positive ones. [Overhead]
Selye's general adaptation syndrome: Endocrine response to acute and chronic stress.
Stress and disease: immune system cells both synthesize and respond to ACTH and betaendorphins.
Ader: Conditioned immunosuppression in rodents; conditioned immunoactivation.
Pairing exposure to immunoactivators or immunosuppressors with smells.
Chronic stress reduces a variety of immune indices in humans. (Glaser & Kiecolt-Glaser)
Chronic stress decreases resistance to infectious diseases in mice (Ader).
H. Selye: General Adaptation Syndrome:
Stress reaction has 3 stages, Alarm, Resistance and
Exhaustion. Stress disorders represent reaction to chronic
involvement in stage of resistance, "wearing down."
Selye:
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Eustress
(+)
e.g., physical exercise
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Distress
(-)
e.g., environmental pressures
Lazarus emphasized coping vs. vulnerability as a key
dimension as to whether stress resulted in stress disorders.
Stress
v
Neural Activation - Hypothalamus
v
Secretion of Corticotrophin Releasing Factor (CRF)
v
Pituitary Release of Adrenocorticotrophic Hormone
(ACTH)
v
Adrenal Release of Glucocorticoids
v
Metabolic, Immunological, Psychological Responses
STRESS AND DISEASE - Ia
Peptic Ulcers:
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For years there was an established relationship
between peptic ulcers (and other GI irritative diseases) and
psychological stress.
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Marshall and Warren “Unidentified curved bacilli in
the stomach of pts with gastric and peptic ulceration” (Lancet,
1984)
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Very tight causal relation between Helicobacter pylori
and peptic ulcer and other irritative GI diseases.
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Diagnosis of infection (serology, IGG for H.p.; or
endoscopy-biopsy), treat with antibiotics (tetracycline,
metronidazole), is eradicating H. pylori infection in much of
US population
So What Happened to the Relationship to Stress?
STRESS AND DISEASE - Ib
Evidence for a Relationship Between Stress and Ulcers:
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Gastric fluids increase acidity in response to anger, hostility,
resentment, guilt, frustration.
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Stressful situations (surgery, school exams) increase basal gastric
acid secretion.
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Alleviation of stress can reverse peptic ulcer condition.
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Animals exposed to stress develop stomach ulcers.
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Ulcer occurs in the absence of H. pylori infection.
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Most people still have H. pylori infection and do not have ulcers.
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Ulcer patients more likely to exhibit excess stress (Levenstein &
Veylan, J. Clin. Gastroenterol., 1995).
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Psychological stress impedes ulcer healing.
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Other factors also important: sex (choose female), blood type (avoid
O), other genetics, cigarettes, coffee, alcohol consumption patterns,
possibly diet. These are not correlated with presence or degree of H.
pylori infection.
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“Psychosomatic” etiology is preferentially discarded as soon as a
“biological” explanation becomes available.
STRESS AND DISEASE - Ic
Aside from Impaired Treatment of Pts and Widespread
Overprescription of Antibiotics, are there Costs? On the
Horizon:
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Absence of H. pylori infection may be linked to
gastroesophogeal reflux disease (“acid reflux”; Labenz
et al., Gastroenterology, 1997)
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Reflux disease increases risk for gastric adenocarcinoma,
a serious form of malignancy, which has recently also
been linked by co-occurrence to absence of H. pylori
infection.
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H. pylori infection is dropping, especially among SES
levels with good medical care.
•
Stay tuned. And don’t throw out good data just because
something more “biological” comes along. Consider the
whole patient, both in theory and in practice.
STRESS AND DISEASE II
Coronary Artery Disease (Leading US cause of death; 1,250,000 heart attacks/year):
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Type A behavior? (Time urgency, competitive hostility). Controversial,
particularly in details, hostility may be most predictive of CAD.
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Stress can increase serum cholesterol levels.
Sudden Cardiac Death:
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Heart arrhythmias may be associated with chronic stress (animal and human
studies)
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Clear evidence for stress as cause or contributing factor in many human
clinical cases
Hypertension (incidence: 38% of adults); predictor of cardiac and brain disorders:
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Chronic stress leads to hypertension in animal studies
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Human studies suggest greater tendency towards hypertension with stress.
Cancer:
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Rats subjected to stress less likely to reject tumor implants
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Women who respond poorly to stress: cervical cancer incidence higher;
increased incidence of malignacy in breast biopsies
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Depressed mood linked to increased cancer risk
STRESS AND THE IMMUNE SYSTEM
Stress and disease: immune system cells both
synthesize and respond to ACTH and beta-endorphins.
Ader: Conditioned immunosuppression in rodents;
conditioned immunoactivation. Pairing exposure to
immunoactivators or immunosuppressors with smells.
Stress Impairs Resistance to Infection in Laboratory
Animals
(Ader)
STRESS AND THE IMMUNE SYSTEM
Evidence that Psychological Stess Affects Human Immune Function
(Kiecolt-Glaser & Glaser, 1987)
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*
*
*
*
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Men whose wives had died of breast cancer had decreased
immune function
Marital disruption is associated with increased morbidity and
mortality
Divorced people more likely to die from pneumonia than married
people
Women who are separated have 30% more appointments for
physical illness
Patients with mental illness have greater numbers of physical
illnesses
Medical students have reduced immune function (Natural Killer
Cell activity) during final exams
STRESS AND PSYCHIATRIC ILLNESS
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Social stressors often associated with depression
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Other medical illnesses increase probability of
psychiatric disorders by about 1/3
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Posttraumatic stress disorder: often see loss of affect,
withdrawal, other signs of depression, some violent
hostile behavior patterns, etc.
*
Up to four-fold increase in incidence of psychiatric
symptoms in people with high stress levels and poor
coping skills vs. people with low stress levels, good
coping skills
STRESS AND THE BRAIN
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Aging memory disorders - non-Alzheimer or other dementias. Associated with hippocampal
neuron loss
Animal model: Chronic stress or glucocorticoid exposure
Stress induces:
– Neuron loss in hippocampus (esp. region CA1) (Sapolsky)
– Adrenalectomy induces hippocampal granule cell loss (Sloviter)
– Individual stress history, indicated by adrenal weight, predicts hippocampal pyramidal
cell loss with aging (Landfield)
Mechanism (?) (Sapolsky)
– Glucocorticoids disrupt hippocampal glucose utilization. This leaves neurons vulnerable
to insults.
– Glucocorticoid administration sensitizes the hippocampus to epilepsy or hypoxia
– Glucose supplements protect the hippocampus
– Likewise, monkeys that died from ulceration had more hippocampal neuron loss than
those that did not.
Early Handling protects against stress-induced neuron loss
BOTTOM LINE: STRESS AFFECTS THE BRAIN, AND THE WRONG KIND OF STRESS
AFFECTS IT NEGATIVELY. THE ANSWERS ARE FAR FROM ALL IN, AND AS A
PHYSICIAN, CONTINUING TO EDUCATE YOURSELF ABOUT THIS WILL BE
IMPORTANT.
NEW TOPIC: PAIN
ACUTE PERIPHERAL PAIN
Epidermal Pain: c-fiber activation by intense physical stimulation
Injurious tissue damage --> bradykinin (peptide), which in turn activates
c-fibers
c-fibers: small, unmyelinated somatosensory fibers that innervate
epidermis, striated muscle, joints, etc.
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most senstive to local anesthetics
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interact with other sensory input to amplify pain sensation
Opiate systems in spinal cord react to diminish this type of pain within a
few minutes.
This system subserves acute pain.
ACUTE PERIPHERAL PAIN
Anti-opiates such as naloxone may increase pain, revealing
effects of the body’s opiate systems.
Placebo (“sugar pill”) administration may sometimes cause
activation of opiate systems if subjects believe the pills are
painkillers. Naloxone-sensitive pain reduction. Psychological
activation of endogenous opiate systems.
However, acute pain can modify central systems on a longer
term basis. It is now commonly recommended that both
peripheral “local” anesthetization and global anesthetic
administration be used in conjunction with pain-inducing
surgical procedures. Repetitious activation of C fibers builds
up the electrical response of neurons to which they project in
the spinal cord. This resembles LTP, a process thought to be
involved in memory.
Shep Siegel Opiate Tolerance stuff here if time allows
CHRONIC PAIN
Chronic Pain: Basis is often much less clear. Incidence: more
than 40% of the population will experience pain at some time in
their lives.
Chronic pain is not merely persistent acute pain. It may occur in
the absence of obvious peripheral or visceral pathology.
All pain has both sensory and affective-evaluative components.
Focusing exclusively on either of these alone is equally
misguided.
With chronic pain there is not a linear relationship between
nociception and pain experience. In chronic pain syndromes,
there are qualitative differences in the affective-evaluative
perception of pain.
Prevalence of chronic pain increases with age
Sources of Chronic Pain
Chronic Benign Pain: Any pain resulting from nonmalignant causes that
is not allieviated by appropriate medical, pharmacotherapy, or surgical
treatment.
Example: Fibromyalgia, widespread aching, local tenderness, absence of
laboratory evidence of inflammation.
American College of Rheumatology defines as involving 3 or more
segments of the body and at least 11 of 18 “tender points.” (e.g.,
trapezius, rib juctions, buttocks, knees)
Steroids and NSAIDS have no more effect than placebo. (Placebos
benefit 50% of patients, at least short-term.) Ketamine (NMDA receptor
antagonist) appears to be effective in 50% of patients.
Some think fibromyalgia is one extreme on a continuum of widespread
chronic pain syndromes. Higher incidence in females.
Opiates remain the most effective medications for managing chronic
pain.
Behavioral Approaches to Chronic Pain Management
It was historically thought that chronic pain patients exaggerated trivial
pain problems--not made of “the right stuff.” This is not therapeutically
helpful.
Chronic pain can have secondary consequences: depressive illness,
marital discord, job problems social withdrawal, sleep disorders.
Biofeedback therapies combine feedback from detectors such as muscle
EMG electrodes with techniques such as muscle relaxation to affect muscle
function.
Biofeedback can be effective for muscle contraction headaches, for
symptoms of chronic stress such as anxiety, and for blood pressure
disorders such as hypertension.
Controlling pain behavior through operant conditioning and other
behavioral approaches has also had success. The approach focuses upon
modifying pain-related behavior separately from the treatment of the pain
itself.
Exercise and conditioning (e.g. stretching) is a very important mitigator of
increased chronic pain with aging. Mild joint and limb pain is very common
in sedentary (inactive) aging people.