Medical Symptoms without Identified Pathology: Relationship to Psychiatric Disorders, Childhood and Adult Trauma, and Personality Traits

In the past two decades, carefully designed studies examining the biopsychosocial causes of common physical symptoms have shown that most health care visits are made because of common symptoms for which no identified pathology is found (1). In this paper, we summarize the relationship between common medical symptoms without identified pathology and a range of psychosocial variables, such as stressful life events, psychological distress, psychiatric disorders, and predisposing emotional vulnerabilities. We also review the association between psychiatric illness and specific clusters of physical symptoms (such as the chronic fatigue syndrome) that are considered syndromes with ill-defined pathologic mechanisms. Medical symptoms without identified pathology are defined as physical symptoms appearing in patients who do not have proportional tissue abnormalities. In most studies reviewed here, a symptom was considered to have no identified pathology when a patient visited a medical physician and was told that 1) no structural changes could be found to explain the symptom or 2) the symptom was secondary to stress or psychiatric illness. Our medical language to describe these symptoms is imperfect; advances in research suggest that many medical symptoms without identified pathology may actually be caused by problems in psychophysiologic or brainbody pathways, such as abnormalities in smooth-muscle tone in the gastrointestinal tract during stress in patients with the irritable bowel syndrome (2). Recent research also suggests that links between perturbations in brain physiology and physical symptoms are bidirectional. Changes in brain physiology secondary to stressful life events cause functional abnormalities in the body (such as abnormalities in smooth-muscle tone in the gut), and these functional abnormalities in the body are also associated with changes in brain physiology (3). The identification of medical symptoms and syndromes without identified pathology may be broken down into a four-part process (4, 5). First, a person has a symptom (presumably, a neurophysiologic event brings it to awareness). Second, the person uses his or her knowledge, experience, and beliefs about the symptom and its cause to assign the symptom a level of medical importance. Most symptoms do not lead to medical visits because patients assign them a relatively low level of medical importance. Third, the person with the symptom seeks care. Whether a person will seek care can be predicted by that person's beliefs about the symptom's significance and by his or her attitude toward the medical system. The fourth and final step is the interaction of the patient's beliefs and expectations with those of the physician. This step may be associated with decreased worry about the symptom's medical implications when the patientphysician interaction goes well, or it may lead to frustration and doctor-shopping when the interaction is problematic. The litigious nature of western society may also lead the physician to order tests because of anxiety about missing a medical problem. This may inadvertently reinforce the patient's worry over having a medical illness. Spectrum of Severity The fourth edition of Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) has developed dichotomous classifications of patients with unexplained symptoms, such as somatization disorder, conversion disorder, hypochondriasis, and pain disorder. In general, these dichotomous diagnoses apply to only a small percentage of primary care patients and do not point to specific treatment regimens. Most primary care patients who have medical symptoms without identifiable pathology have associated stressful life events or anxiety and depressive diagnoses (or both) and do not have the severity or the chronicity needed to qualify for diagnosis with the somatoform disorders mentioned above (6-8). Several research groups have shown that there is not a sharp dichotomy between patients with multiple somatic symptoms (such as those with the somatization disorder) and patients with medical symptoms without identified pathology but actually a spectrum of severity of somatization (9). As the number of medical symptoms without identified pathology increases, the number of psychological distress symptoms, the number of anxiety and depressive diagnoses, and the degree of functional impairment increase linearly (9-13). Thus, increasing numbers of medically unexplained symptoms have been found to be proxy measures of the degree of psychological distress and functional impairment (9-11). Longitudinal studies that have examined predictors of chronicity in patients who have medical symptoms without identified pathology have found the baseline number of physical symptoms to be the best predictor of persistent impairment (14). Epidemiology Physical symptoms are common among community respondents and are responsible for approximately 50% of all physician visits (1). Epidemiologic surveys of community respondents have found high rates of such symptoms as headache (15), fatigue (16), and abdominal pain (17). One health care diary study (18) reported that participants had a new physical symptom every 5 to 7 days, and more than 90% of these symptoms were not brought to a physician's attention. Another study found that 85% to 95% of community respondents had at least one symptom every 2 to 4 days (19). People in the United States have been found to restrict activities because of symptoms an average of 9.7 days per year and to visit physicians an average of 2.7 times per year (20). Researchers have sought to understand factors predicting medical visits for common physical symptoms, such as headache or fatigue. Studies of community participants with migraine headaches (15), fatigue (16), and common gastrointestinal symptoms (17) have shown that compared with persons who do not seek health care, persons who do seek health care have significantly more stressful life events (21, 22), have psychological distress, and are significantly more likely to meet the criteria for a DSM-IV anxiety or depressive disorder. Epidemiologic studies have found that 25% to 35% of primary care patients meet the criteria for a DSM psychiatric disorder, most often an anxiety or depressive disorder (8, 23). Researchers have shown that approximately half of patients with a DSM anxiety or depressive disorder do not receive an accurate diagnosis by primary care physicians (7, 8, 23). This may be because 50% to 80% of patients with a DSM anxiety or depressive disorder initially present with physical symptoms (7, 8). Compared with patients with psychiatric illness who present with psychological symptoms, significantly more patients with psychiatric illness who present with physical symptoms do not receive an accurate diagnosis by a primary care physician (7, 8). Patients with common anxiety and depressive disorders have significantly more medical symptoms without identified pathology than do patients without psychiatric illness (24, 25). In the Epidemiologic Catchment Area study (25), 50% of community respondents with five or more medically unexplained symptoms over a 6-month period met the criteria for a DSM-III psychiatric disorder; only 5% of respondents without these symptoms met the criteria. Spitzer and colleagues, in the Primary Care Evaluation of Mental Disorders (PRIME-MD) 1000 study (26), showed that as the number of medical symptoms increased, so did the percentage of patients who met the criteria for a DSM-III-R anxiety or depressive disorder (10). This was true both for symptoms that the primary care physician rated as not explained by medical pathology and for symptoms that the physician labeled as probably due to a medical illness. Two other large primary care studies (9, 11) also found a relationship between more medical symptoms without identified pathology and a higher likelihood of a DSM-IV anxiety or depressive disorder. This relationship between the number of medical symptoms and psychiatric disorders holds true for patients with subsyndromal psychiatric disorders. Mental health researchers (27, 28) have shown that as the number of self-rated psychological symptoms increases, so does the number of self-rated physical symptoms, with a correlation of about 0.5 between psychological scales of distress and self-rated physical symptom checklists. Health Care Utilization Patients with depressive and anxiety disorders are often high utilizers of medical services, perhaps because they have an increased number of physical symptoms. In the Epidemiologic Catchment Area Study of five United States cities (29), community respondents with one or more with psychiatric disorders were significantly more likely than respondents without psychiatric disorders to be high utilizers of medical services. A study in a large health maintenance organization (HMO) (30) found that patients with depression who were treated with antidepressants incurred about twice the health care costs of age- and sex-matched patients without depression, even after adjustment for comorbid chronic medical illness. These differences in medical costs were found in every component measured, including primary care, medical specialty, and mental health visits; in-patient medical days; laboratory costs; emergency department costs; and radiography (30). Elderly patients in an HMO who had positive results on screening tests for depression were found to incur 30% to 50% more overall costs than did nondepressed elderly persons after adjustment for comorbidity (31). A retrospective casecontrol study (32) showed that patients with a specific type of anxietypanic disorderhad increased medical costs in every year over a 10-year period compared with age- and sex-matched controls. This association between psychiatric disorders and health care utilization is also evident if patients are identified by utilization patterns. High utilizers of medical services have been shown to h