In prehistoric times, the physical changes in response to stress were an essential adaptation for meeting natural threats. Even in the modern world, the stress response can be an asset for raising levels of performance during critical events such as a sports activity, an important meeting, or in situations of actual danger or crisis.

If stress becomes persistent and low-level, however, all parts of the body's stress apparatus (the brain, heart, lungs, vessels, and muscles) become chronically over- or under-activated. This may produce physical or psychologic damage over time. Acute stress can also be harmful in certain situations. Circumstances that are most likely to produce negative physical effects include:

• An accumulation of persistent stressful situations (for example, high-pressured work plus an unhappy relationship).
• Persistent stress following a severe acute response to a traumatic event (such as an automobile accident).
• An inefficient or insufficient relaxation response.
• Acute stress in people with serious illness, such as heart disease.

Psychologic Effects of Stress

Studies suggest that severe stress is associated with the onset of depression or anxiety. In one study, subjects who experienced a stressful situation had nearly six times the risk of developing depression within that month. (In about a third of cases, however, the stress itself was not the cause of the depression. Experts guess that people genetically predisposed to depression also may have a tendency to become involved in high-stress situations.) Certainly, stress diminishes the quality of life by reducing feelings of pleasure and accomplishment, and relationships are often threatened.

Heart Disease

Mental stress is as major a trigger for angina as physical stress. Incidents of acute stress have been associated with a higher risk for serious cardiac events, such as heart rhythm abnormalities and heart attacks, and even death from such events in people with heart disease.

Stress may negatively affect the heart in several ways:

• Sudden stress increases the pumping action and rate of the heart and causes the arteries to constrict, thereby posing a risk for blocking blood flow to the heart.
• Emotional effects of stress alter the heart rhythms and pose a risk for serious arrhythmias in people with existing heart rhythm disturbances.
• Stress causes blood to become stickier (possibly in preparation of potential injury), increasing the likelihood of an artery-clogging blood clot.
• Stress may signal the body to release fat into the bloodstream, raising blood-cholesterol levels, at least temporarily.
• Stress may lead to increased levels of homocystine in the blood, a factor now strongly associated with heart disease.
• In women, chronic stress may reduce oestrogen levels, which are important for cardiac health.
• Stressful events may cause men and women who have relatively low levels of the neurotransmitter serotonin (and therefore a higher risk for depression or anger) to produce more of certain immune system proteins (called cytokines), which in high amounts cause inflammation and damage to cells, including possibly heart cells.
• Stress causes a sudden and temporary increase in blood pressure, although long-term effects are not completely known. In one 20-year study, men who periodically measured highest on the stress scale were twice as likely to have high blood pressure as those with normal stress. The effects of stress on blood pressure in women were less clear. People who regularly experience sudden increases in blood pressure caused by mental stress may, over time, develop injuries in the inner lining of their blood vessels.

More research is needed to confirm the actual harm of stress on the heart. For example, one study of people who work under demanding conditions suggested that heart disease, including high blood pressure, attributed to work stress may simply be due to the way people cope with the stress. People who are trying to deal with stress often resort to unhealthy habits including high-fat and high-salt diets, tobacco use, alcohol abuse, and a sedentary lifestyle. In one study, men were more apt to use alcohol or eat less healthily in response to stress, while women tended to have healthier ways of coping.

Stroke

One survey revealed that men who had a more intense response to stressful situations, such as waiting in line or problems at work, were more likely to have strokes than those who did not report such distress. In some people prolonged or frequent mental stress causes an exaggerated increase in blood pressure. Over time, this effect has been linked to thickening of the carotid arteries, which carry blood to the front half of the brain. Blockage and injury in these arteries are primary causes of stroke.

Susceptibility to Infections

Chronic stress appears to blunt the immune response and increase the risk for infections. (In some studies, stressful events most linked with a higher incidence of infections were interpersonal conflicts, such as those at work or in a marriage.) A number of studies have shown that subjects under chronic stress have low white blood cell counts and are vulnerable to colds. And once any person catches a cold or flu, stress can exacerbate symptoms. Even more serious, some research has found that HIV-infected men with high stress levels progress more rapidly to AIDS when compared to those with lower stress levels. (Support groups can help reduce this stress.)

Cancer

The weight of current evidence does not support to the idea that stress causes cancer. Nevertheless, some animal studies suggest that the negative effects of stress on immune function may contribute to increasing the severity of existing cancers.

Gastrointestinal Problems

General Gastrointestinal Symptoms. Over the long term, prolonged stress can disrupt the digestive system, irritating the large intestine and causing diarrhea, constipation, cramping, and bloating. Excessive production of digestive acids in the stomach may cause a painful burning.

Irritable Bowel Syndrome. Irritable bowel syndrome (or spastic colon) is strongly related to stress. With this condition, the large intestine becomes irritated, and its muscular contractions are spastic rather than smooth and wave like. The abdomen is bloated and the patient experiences cramping along with constipation, diarrhea, or alternating periods of each. Sleep disturbances due to stress can further exacerbate irritable bowel syndrome.

Peptic Ulcers. It is now well established that most peptic ulcers are either caused by the H. pylori bacteria or by the use of nonsteroidal anti-inflammatory (NSAID) medications (such as aspirin and ibuprofen). Nevertheless, studies still suggest that stress may predispose someone to ulcers or sustain existing ulcers. Some experts, in fact, estimate that social and psychologic factors play some contributing role in 30% to 60% of peptic ulcer cases, whether they are caused by H. pylori or NSAIDs. In any case, some experts believe that the anecdotal relationship between stress and ulcers is so strong that attention to psychological factors is still warranted.

Inflammatory Bowel Disease. Although stress is not a cause of inflammatory bowel disease (Crohn's disease or ulcerative colitis), there are reports of an association between stress and symptom flare-ups. One study, for example, found that while short term (past month) stress did not significantly exacerbate ulcerative colitis symptoms, long term perceived stress tripled the rate of flare-ups compared to patients who did not report feelings of stress.

Weight Problems.

Stress can have varying effects on weight.

Weight Loss. Some people suffer a loss of appetite and lose weight. In rare cases, stress may trigger hyperactivity of the thyroid gland, stimulating appetite but causing the body to burn up calories at a faster than normal rate.

Weight Gain. Others, however, develop cravings for salt, fat, and sugar to counteract tension and, thus, may gain weight. And the weight gained from such stress-related eating is often abdominal fat, a predictor of diabetes and heart problems. Even with a healthy diet, stress appears to be associated with abnormal obesity.

Diabetes

Chronic stress has been associated with the development of insulin-resistance, a condition in which the body is unable to use insulin effectively to regulate glucose (blood sugar). Insulin-resistance is a primary factor in diabetes. Stress can also exacerbate existing diabetes by impairing the patient's ability to manage the disease effectively.

Pain

Muscular and Joint Pain. Chronic pain caused by arthritis and other conditions may be intensified by stress. Back pain is also a common complaint. Some studies have clearly associated job dissatisfaction and depression to back problems, although it is still unclear if stress is a direct cause of the back pain.

Headaches. Tension-type headache episodes are highly associated with stress and stressful events. (Sometimes the headache doesn't even start until long after a stressful event is over.) Some research suggests that tension-type headache victims may actually have some biological predisposition for translating stress into muscle contraction. Among the wide range of possible migraine triggers is emotional stress (although the headaches often erupt after the stress has eased). One study suggested that women with migraines tend to have personalities that over-respond to stressful situations.

Sleep Disturbances

The tensions of unresolved stress frequently cause insomnia, generally keeping the stressed person awake or causing awakening in the middle of the night or early morning.

Sexual and Reproductive Dysfunction

Sexual Function. Stress can lead to diminished sexual desire and an inability to achieve orgasm in women. Stress response can also cause temporary impotence in men. Part of the stress response involves the release of brain chemicals that constrict the smooth muscles of the penis and its arteries. This constriction reduces the blood flow into and increases the blood flow out of the penis, which can prevent erection.

Premenstrual Syndrome. Some studies indicate that the stress response in women with premenstrual syndrome may be more intense than in those without the syndrome.

Fertility. Stress may even affect fertility. Stress hormones have an impact on the hypothalamus gland, which produces reproductive hormones. Severely elevated cortisol levels can even shut down menstruation. One interesting small study reported a significantly higher incidence of pregnancy loss in women who experienced both high stress and prolonged menstrual cycles. Another reported that women with stressful jobs had shorter periods than women with low-stress jobs.

Effects on Pregnancy. Old wives' tales about a pregnant woman's emotions affecting her baby may have some credence. Maternal stress during pregnancy has been linked to a 50% higher risk for miscarriage. It is also associated with lower birth weights and increased incidence of premature births, both of which are risk factors for infant mortality. One study suggested that stress experienced by expectant mothers can even influence the way in which the baby's brain and nervous system will react to stressful events. Stress may cause physiologic alterations, such as increased adrenal hormone levels or resistance in the arteries, that may interfere with normal blood flow to the placenta.

Memory, Concentration, and Learning

Stress has significant effects on the brain, particularly on memory. The typical victim of severe stress suffers loss of concentration at work and at home and may become inefficient and accident-prone. Severe stress may even break down the blood-brain barrier, a physiological mechanism that helps protect the brain from toxins, bacteria, and other potentially harmful substances that may be carried in blood.

Effect of Acute Stress on Memory. Studies indicate that the immediate effect of acute stress is to impair short-term memory, particularly verbal memory. In one interesting 2000 study, subjects took pills containing either cortisone, a stress hormone, or a placebo (a dummy pill). Those taking the cortisone performed significantly worse on memorization tests than those taking the placebo pill did. In an earlier study, when individuals were subjected to four days of stress, verbal memory was also impaired. Fortunately, in such cases, memory is restored after a period of relaxation.

Effect of Chronic Stress on Memory in Adults. Although some memory loss occurs with age, stress may play an even more important role than simple aging in this process. In one study older people with low stress hormone levels tested as well as younger people in cognitive tests: those with higher stress levels tested between 20% and 50% lower. Prolonged exposure to cortisol (the major stress hormone) is now believed to actually damage brain cells in the hippocampus. Two studies reported that groups who suffered from post-traumatic stress disorder (Vietnam veterans and women who suffered from sexual abuse) displayed up to 8% shrinkage in the hippocampus. It is not yet known if this shrinkage is reversible.

Effect of Chronic Stress on Learning in Children. In children, the physiologic responses to stress can clearly inhibit learning. A 1999 study of middle school children found that training in stress and anger management led to significant improvements in the children's emotional balance, focus, and relationships.

Allergy-Like Reactions

Research suggests that stress, not indoor pollutants, may actually be a cause of the so-called sick-building syndrome, which produces allergy-like symptoms, such as eczema, headaches, asthma, and sinus problems, in office workers. Stress plays a role in exacerbating a number of skin conditions, including hives, psoriasis, acne, rosacea, and eczema. Unexplained itching may also be caused by stress.

Self-Medication with Unhealthy Lifestyles

People under chronic stress frequently seek relief through drug or alcohol abuse, tobacco use, abnormal eating patterns, or passive activities, such as watching television. The damage these self-destructive habits cause under ordinary circumstances is compounded by the physiologic effects of stress itself. And the cycle is self-perpetuating; a sedentary routine, an unhealthy diet, alcohol abuse, and smoking promote heart disease, interfere with sleep patterns, and lead to increased rather than reduced tension levels. Drinking four or five cups of coffee, for example, can cause changes in blood pressure and stress hormone levels similar to those produced by chronic stress. Animal fats, simple sugars, and salt are known contributors to health problems.

RECENT LITERATURE

Causal relationship between stressful life events and the onset of major depression. Am J Psychiatry. 1999 Jun;156(6):837-41.

Destabilizing effects of mental stress on ventricular arrhythmias in patients with implantable cardioverter-defibrillators. Circulation. 2000 Jan 18;101(2):158-64.

Evidence that stress and surgical interventions promote tumor development by suppressing natural killer cell activity. Int J Cancer. 1999 Mar 15;80(6):880-8.

Sleep disturbance influences gastrointestinal symptoms in women with irritable bowel syndrome. Dig Dis Sci. 2000 May;45(5):952-9.

Anxiety and helplessness in the face of stress predisposes, precipitates, and sustains gastric ulceration. Behav Brain Res. 2000 Jun 1;110(1-2):161-74. Review.

The very model of a modern etiology: a biopsychosocial view of peptic ulcer. Psychosom Med. 2000 Mar-Apr;62(2):176-85. Review.

Stress and exacerbation in ulcerative colitis: a prospective study of patients enrolled in remission. Am J Gastroenterol. 2000 May;95(5):1213-20.

Anger, hostility, and visceral adipose tissue in healthy postmenopausal women. Metabolism. 1999 Sep;48(9):1146-51.

Headache in children in Dutch general practice. Cephalalgia. 1999 Apr;19(3):147-50.

Symptoms of stress and depression as correlates of sleep in primary insomnia. Psychosom Med. 2000 Mar-Apr;62(2):227-30.

Stress and pregnancy among African-American women. Paediatr Perinat Epidemiol. 2000 Apr;14(2):127-35.

Acute cortisone administration impairs retrieval of long-term declarative memory in humans. Nat Neurosci. 2000 Apr;3(4):313-4. No abstract available.

The impact of an emotional self-management skills course on psychosocial functioning and autonomic recovery to stress in middle school children. Integr Physiol Behav Sci. 1999 Oct-Dec;34(4):246-68.

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Well-Connected reports are written and updated by experienced medical writers and reviewed and edited by the in-house editors and a board of physicians, including faculty at Harvard Medical School and Massachusetts General Hospital. The reports are distinguished from other information sources available to patients and health care consumers by their quality, detail of information, and currency. These reports are not intended as a substitute for medical professional help or advice but are to be used only as an aid in understanding current medical knowledge. A physician should always be consulted for any health problem or medical condition.

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Board of Editors

Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital

Stephen A. Cannistra, MD, Oncology, Associate Professor of Medicine, Harvard Medical School; Director, Gynecologic Medical Oncology, Beth Israel Deaconess Medical Center

Masha J. Etkin, MD, PhD, Gynecology, Harvard Medical School; Physician, Massachusetts General Hospital

John E. Godine, MD, PhD, Metabolism, Harvard Medical School; Associate Physician, Massachusetts General Hospital

Daniel Heller, MD, Pediatrics, Harvard Medical School; Associate Pediatrician, Massachusetts General Hospital; Active Staff, Children's Hospital

Paul C. Shellito, MD, Surgery, Harvard Medical School; Associate Visiting Surgeon, Massachusetts General Hospital

Theodore A. Stern, MD, Psychiatry, Harvard Medical School; Psychiatrist and Chief, Psychiatric Consultation Service, Massachusetts General Hospital

Carol Peckham, Editorial Director

Cynthia Chevins, Publisher