5
IOM Review: Stress, Psychiatric Disorders, and Their Relationship to Physical Signs and Symptoms*

In May 1997, the committee convened a workshop of research and clinical experts in the areas of stress (including military stress), the effects of stress on the endocrine and immune systems, substance abuse, posttraumatic stress disorder (PTSD), depression, and subthreshold depression. Presentations were focused on providing the latest information in these areas that could assist the committee in its review of the adequacy of the Comprehensive Clinical Evaluation Program in diagnosing stress and psychiatric disorders and in determining whether or not effective treatments existed for these conditions.

STRESSORS AND STRESS

As discussed earlier, individuals deployed to the Persian Gulf were exposed to a number of stressors. The term stressors generally refers to the external circumstances that challenge or obstruct an individual. Stress, on the other hand, is the state of arousal resulting from the presence of socioenvironmental demands that tax the ordinary adaptive capacity of the individual. Production of stress is an environment person interaction and is influenced by such characteristics as needs, values, perceived ability to respond, and coping skills.

*  

The material in this section is based, in part, on presentations by Hagop Akiskal, M.D., Carol Aneshensel, Ph.D., Firdaus Dhabhar, Ph.D., MAJ Charles Engel, M.D., David Foy, Ph.D., Walter Ling, M.D., MAJ Michael Roy, M.D., and John D. Wynn, M.D.



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--> 5 IOM Review: Stress, Psychiatric Disorders, and Their Relationship to Physical Signs and Symptoms* In May 1997, the committee convened a workshop of research and clinical experts in the areas of stress (including military stress), the effects of stress on the endocrine and immune systems, substance abuse, posttraumatic stress disorder (PTSD), depression, and subthreshold depression. Presentations were focused on providing the latest information in these areas that could assist the committee in its review of the adequacy of the Comprehensive Clinical Evaluation Program in diagnosing stress and psychiatric disorders and in determining whether or not effective treatments existed for these conditions. STRESSORS AND STRESS As discussed earlier, individuals deployed to the Persian Gulf were exposed to a number of stressors. The term stressors generally refers to the external circumstances that challenge or obstruct an individual. Stress, on the other hand, is the state of arousal resulting from the presence of socioenvironmental demands that tax the ordinary adaptive capacity of the individual. Production of stress is an environment person interaction and is influenced by such characteristics as needs, values, perceived ability to respond, and coping skills. *   The material in this section is based, in part, on presentations by Hagop Akiskal, M.D., Carol Aneshensel, Ph.D., Firdaus Dhabhar, Ph.D., MAJ Charles Engel, M.D., David Foy, Ph.D., Walter Ling, M.D., MAJ Michael Roy, M.D., and John D. Wynn, M.D.

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--> There are two broad types of stressors: (1) eventful changes that have a discrete onset and a discrete cessation and (2) chronic stressors that emerge from ongoing situations until it becomes apparent that there is a problem. Most chronic stressors are related to the ongoing nature of social organization and social roles. Other chronic stressors include daily hassles (e.g., a slowdown on the freeway) and ambient stressors (e.g., deteriorating aspects of a neighborhood). Life event stressors refer to objective changes in life circumstances that are of sufficient magnitude to change a person's usual activities (e.g., acute physical illness). These can be expected to occur throughout the life course, and it is the undesirable events that are stressful for people. Stress proliferation refers to the notion that a particular stressful circumstance is usually not confined in a person's life but tends to spread out and create additional problems in other areas of life (i.e., a primary stressor may produce a secondary stressor). Primary stressors are primary in the sense that they are the root origin of a series of other problematic life circumstances called secondary stressors. These secondary stressors are not necessarily secondary in their potency and refer to the spillover of the primary stressor into other aspects of a person's life (e.g., interference with job, disruption of relationships with family and friends, constriction of social activities). For traumatic events, if secondary adversities or other stressors arise, the effects may be additive, that is, they may proliferate. Once these additional or secondary stressors have been created, they then serve as an independent source of stress. Stress may proliferate for the individual who is the primary target of interest and also for the family and friends of that individual. In general, the duration of an exposure is related to the effects of stress. The more long-term the exposure, the more long-term are the effects. In addition, just because a person is removed from a stressful life circumstance, the effects of having been in that condition or circumstance persist, even though the stressor is absent. The Gulf War had many very stressful experiences, despite the fact that it was a military success. There were many months leading up to the war in which the US troops were uncertain about the strength of Iraqi troops, whether chemical or biological weapons would be used, and whether they would be injured or killed in the engagement. In addition, troops were rapidly and unexpectedly deployed, separated from family and friends, faced with a harsh desert environment and environmental hazards, and exposed to a direct life threat; they also witnessed death and destruction. When individuals deployed to the Gulf returned home, it was assumed that since the war itself was brief and the level of loss of US lives was low, problems associated with the war would be few. The Department of Veterans Affairs did develop a Persian Gulf Registry as a means of addressing questions about

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--> possible future effects of air pollutant exposure and other environmental agents, particularly those associated with the oil well fires. However, as time passed, it became apparent that there were concerns about a number of exposure issues. Information on exposures and their health consequences was contradictory and, as such, potentially worsened the already stressful situation by making it ambiguous. Because the perception that one has something wrong with one's body is itself a source of stress, the very vagueness surrounding the information that was forthcoming about agents to which one was exposed and the lack of knowledge of health consequences of such exposures have exacerbated the impact of the stress associated with health complaints. In determining the negative effects created by exposure to stress, it is necessary to look beyond the one primary stressor to the creation of problems in other areas of a person's life and, additionally, in the lives of people with whom he or she is in close association. CONSEQUENCES OF STRESS Research has shown that stressors have been associated with major depression, symptoms of depression and anxiety, alcohol abuse and dependence, and substance abuse and dependence. Many of these conditions are undiagnosed in primary care populations for a number of reasons including the training and experience of the examiner, the time pressure for completing examinations, stigmatization and social attitudes, and the misperception that treatment does not work. Depression The diagnosis of depression in the primary care setting is frequently missed, and when properly diagnosed, depression is often inadequately treated. A 4 year longitudinal study of medical outcomes was begun in the late 1980s and involved more than 20,000 patients in three centers (Boston, Los Angeles, and Chicago) and different financing systems. General medical clinicians saw 364 patients and were aware that the focus of the study was depression. Despite this fact, these primary care physicians missed the diagnosis of depression 50% of the time (Wells and Burnham, 1991). Of the patients found by screening during the primary care visit to have a major ongoing depression, 59% received no medication and were not in psychotherapy. Of those who received medication, 19% received only a minor tranquilizer, and 12% only an antidepressant, and of the ones receiving antidepressants, 39% received homeopathic doses. The underdiagnosis, then, was compounded by undertreatment.

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--> To facilitate the task of diagnosing mental disorders, primary care providers must become familiar with diagnostic categories, historical features, and interview techniques. There are three diagnostic categories of major mental disorders: (1) mood disorders, (2) anxiety disorders, and (3) psychotic disorders. A mood disorder is a diagnosis established on the basis of a recurrent pattern of mood episodes. Mood episodes are a group of signs and symptoms that co-occur for a minimal duration of time. They can be part of a mood disorder, a psychotic disorder, or a general medical disorder. Kinds of mood episodes include major depressive, manic, mixed, and hypomanic. To identify a major depressive episode, one looks for either a persistent depressed mood that occurs every day or most of the day and lasts at least two weeks, or diminished interest or pleasure in all or almost all activities and five of the following: significant weight loss or change in appetite; insomnia or hypersomnia nearly every day; psychomotor retardation or agitation (observable); fatigue or loss of energy; feelings of worthlessness or excessive (or inappropriate) guilt; diminished ability to think, concentrate, or make decisions; recurrent thoughts of death or suicide, or a suicide attempt. A manic episode includes a distinct period of abnormally and persistently elevated, expansive, or irritable mood necessitating hospitalization or lasting at least one week and three or more of the following: inflated self-esteem or grandiosity; decreased need for sleep; greater talkativeness than usual or pressure to keep talking; flight of ideas or racing thoughts; distractibility; or risky measurable activities or endangerment. There are different kinds of mania. The dysphoric or mixed episode is a combination of mania and depression, characterized by marked impairment. The hypomanic episode is not severe enough to show impairment in social or occupational functioning or to necessitate hospitalization, and there are no psychotic features. The language of episodes can be translated into the language of the primary care clinician. An episode is a syndrome (i.e., a collection of signs and symptoms). Syndromes lead to clinical evaluation; to differential diagnosis, and ultimately, to clinical diagnosis, prognosis, and treatment. Disorders are diagnoses. Mood disorders are divided into depressive disorders and bipolar disorders. The depressive disorders include major depression (one or more major depressive episodes), minor depression (sadness and/or anhedonia, at least one more symptom of major depression, and two weeks impairment and/or distress), and dysthymia (2 years or more of a depressed mood for ''more days than not," two or more neurovegetative symptoms, and has never met criteria for major depressive episode). Depression is further divided into melancholic, chronic, and other types. Melancholic depressions often do not respond well to treatment, and result in

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--> decreasing activity and marked sleep disturbances with a worse prognosis. The chronic type of depression lasts at least 2 years in a row without any remission of more than 2 months, and later intervention results in slower recovery. This is not dysthmia. Misdiagnosis is often to due to the fact that there is an overlap in the signs and symptoms of depression with many medical conditions. A common error begins with the idea, "Well wouldn't you be depressed if you were so sick?" In addition, the clinical presentation of depression includes confusing or ambiguous (nonmood) complaints such as pervasive boredom, decreased energy, insomnia, and fatigue. Another presentation is irritability. Patients may say they feel sad all the time-or depressed, hopeless, pessimistic, or blue. There are some patients who seek care because they have vague or nonspecific physical complaints such as fatigue, loss of energy, sleep difficulties, or unexplained somatic symptoms. A number of instruments can be used to screen for depression. These include the Beck Depression Inventory, the Zung Self-rating Depression Scale (SDS), the Center for Epidemiological Studies-Depression Scale (CES-D), and the Inventory to Diagnose Depression (IDD). When in doubt about a diagnosis of any mental disorder, a physician should schedule early follow-up to confirm or deny the diagnosis and to let the patient know that the physician is concerned. It has been shown that as many as 15% of patients with inadequately treated depression kill themselves. In diagnosing depression in primary care, it is important to screen populations at elevated risk, to increase the clinical sensitivity of primary care providers, to ensure that there is adequate time to perform the evaluation, to remove barriers to specialty care, to encourage multidisciplinary management, to assess comorbidity, and to overcome stereotypes. Posttraumatic Stress Disorder Posttraumatic stress disorder (PTSD) appeared as an official diagnosis in the American Psychiatric Association's 1980 publication of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III). PTSD was recognized as a new disorder, linked to external stressors that are overwhelming and extreme. PTSD has been found to be frequent in veterans of military combat and represents an important concern in providing care to the veteran population. In the National Vietnam Veterans Readjustment Study, investigators found that an estimated 15.2% of all male Vietnam War theater veterans (about 479,000 American men) met the criteria for current PTSD at the time the data were compiled (Rundell and Ursano, 1996). A study by Southwick et al. (1995) found that in a 2-year follow-up to a study of Persian Gulf veterans conducted 6 months after the war's end, "although symptoms were relatively mild, there was

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--> an overall increase in PTSD symptoms at 2 years, and not before." They go on to suggest that it may take time for the consequences of traumatic exposure to become apparent. The required features of PTSD are a traumatic event that precipitates symptoms of a crisis reaction in the individual (i.e., the individual was overwhelmed physiologically and showed signs of extreme horror, helplessness, or grief, in the case of a tragic loss). This is frequently referred to as Criterion A. Other required features are that the trauma be reexperienced in dreams or thoughts or that it be reenacted, that there be a numbing of responsiveness, and that at least two of the following symptoms occur: hyperalertness (exaggerated startle response), sleep disturbance, guilt, trouble concentrating, avoidance of activities prompting recall of the original event, and worsening of symptoms by exposure to events resembling the original event (Helzer et al., 1987). For providers not experienced in the diagnosis of PTSD, the most common error is to make the assumption that the only requirement for satisfying Criterion A is to determine whether the individual personally experienced a traumatic event (e.g., served in a hostile fire zone). However, the provider must go beyond this to elicit the individual's response to the trauma (i.e., the extent to which he or she experienced reactions such as intense fear, helplessness, and horror). Although direct exposure is probably the most potent, observational experiences (e.g., observing horrific things happening to others) cannot be disregarded as traumatic events. Vicarious exposure, especially in the case of close social distance to the victim, is also capable of producing PTSD symptoms. It has been well documented from both clinical and epidemiological data that combat-related PTSD is frequently associated with other psychiatric morbidity, and it has been suggested that alcohol and substance use have a role in precipitating anxiety and mood-related symptoms (Mellman et al., 1992). In addition, individuals with PTSD are at risk for developing secondary affective, alcohol and substance abuse, as well as panic and phobic disorders. Treatment of these comorbid conditions is essential to the management of PTSD (Marmar et al., 1993). According to Marmar et al., the severity and course of PTSD are influenced by the interaction of the traumatic stress exposure with a background of individual psychological and biological vulnerability. Substance Abuse Substance abuse problems are fairly prevalent in primary care. About 20% to 30% of patients who visit primary care physicians do so for problems that relate in some way to substance abuse or misuse. Substance abuse results from addiction, which is a disease process characterized by the compulsive use of a

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--> specific psychoactive substance. An individual engages in a set of behaviors regarding the substance that can lead to a dependence disorder or an abuse disorder. In terms of substance abuse, the role of the primary care physician is twofold. First, the primary care physician must assess and treat the medical problems related to substance abuse. There are, for example, a number of medical diseases related to parenteral drug use such as endocarditis, acute hepatitis, cirrhosis, bleeding ulcers, pancreatitis, stroke, seizures, amnesia, dementia, and certain cardiovascular and pulmonary diseases, as well as overdose, trauma, and hormonal abnormalities. Medical problems that result from alcohol abuse include neurological problems, liver disease, pancreatic disease, and hematologic diseases. There is also a great deal of comorbidity between substance abuse and psychiatric disorders such as schizophrenia, affective disorders, anxiety disorders, and antisocial personality disorders. The second major responsibility of the primary care physician is to conduct substance abuse screening. If a patient presents with a medical problem related to substance abuse, the primary care physician should screen for abuse as a cause of the problem. A very important component of this screening is to determine the severity of the problem and the risk of complications. To conduct effective screening, the physician must interview the patient concerning his or her general health habits, diet and exercise, use of prescriptions, use of over the counter and home remedies, smoking, drinking, and use of marijuana and other drugs. In addition, the primary care physician should use one of the substance abuse screening instruments (e.g., CAGE, MAST/DAST, AUDIT, HSS, and the T-ACE/TWEAK; see Appendix I for copies of the instruments). Other Consequences Stress has also been associated with various physical health problems, particularly immune system functioning. A study by Cohen et al. (1991) showed that for individuals inoculated with a cold virus (rhinovirus type 2, 9, or 14, respiratory syncytial viruses, or coronavirus type 229E), there was an increased infection rate in those who reported a high level of recent stress. According to work conducted recently at Rockefeller University, it appears that moderate stress (i.e., stress that is circumscribed both in its physical duration and its perception), maintained in a healthy individual, seems to enhance cell-mediated immunity. There is also evidence that it might enhance humoral or antibody-dependent immunity. However, chronic stress disrupts equilibrium and decreases cell-mediated immunity (Dhabhar presentation, 1997). There are other potential consequences of stress for health outcomes, for example, the effects of stress on health behavior. Some behaviors may produce positive effects (e.g., running as a coping mechanism), whereas many are

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--> unhealthy (e.g., smoking, drinking, overeating). Stress exerts an indirect effect on health via these kinds of behaviors. There are also stress effects on illness behavior, that is, what a person does who perceives him or herself as having some sort of sickness. It has been accepted for many years that persons who engage in certain types of stressful behavior are at higher risk of developing coronary heart disease (Williams, 1995). Less well known is the fact that those who suffer from clinical depression experience a 5-fold higher mortality following myocardial infarction than nondepressed patients. According to Chrousos and Gold (1992), a stress system within the body produces pathophysiologic states that can make a person vulnerable to a range of disorders, including endocrine, inflammatory, and psychiatric disorders. It has also been shown that jobs that place high demands on a worker while allowing little latitude in deciding how the demands are met create high job strain. Employment in high-strain jobs has been associated with increased ambulatory blood pressure levels (Schnall et al., 1992). Friedman and Schnurr (1995) conducted a review of the literature on physical health outcomes associated with traumatic events including exposure to a war zone, sexual or other criminal victimization, natural or human-made disasters, and serious accidents. They concluded that "the trauma and health literature is impressive for the consistency of results showing that exposure to catastrophic stress is associated with adverse health reports, medical utilization, morbidity, and mortality among survivors." Although there is some concern that this literature includes work with methodological flaws, Friedman and Schnurr (1995) emphasized that there was "general consistency of findings across diverse trauma populations and outcomes . . .," including morbidity and mortality data that supported self-report and utilization data.