Psychosocial Aspects of Crohn's Disease

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CROHNS DISEASE

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PSYCHOSOCIAL ASPECTS OF CROHN’S DISEASE Yehuda Ringel, MD, and Douglas A. Drossman, MD

Although the understanding of inflammatory bowel disease (IBD) has advanced significantly over the past decade, knowledge of the etiology, natural history, and clinical expression of Crohn‘s disease is still in evolution. Crohn‘s disease varies not only in the extent and severity of intestinal and extraintestinal involvement but also in its clinical presentation. In these circumstances, the management of these patients usually is determined by the presenting type (e.g., inflammatory, fistulizing, or fibrotic), location, activity, and severity of the disease. Several indices have been designed and used to measure the disease activity and severity. These indices usually are based on scoring clinical signs and symptoms (e.g., Crohn‘s Disease Activity Index [CDAI]),Harvey-Bradshaw Index,lo,59 objective endoscopic or laboratory data,lZ1or a combination of physical findings and laboratory data (e.g., Cape Town Index).lZ8 Nevertheless, the activity and severity of the disease usually are insufficient to explain the variability in the clinical presentation of the disease.5oSome physicians care for patients in whom significant discrepancies exist between the “disease” activity and severity, as defined by the disease related factors, and the patients’ symptom experience and behavior (i.e., the ”illness”). For example, with an 8-cm segment of ileitis, one patient may be disabled because of severe symptoms, whereas another may report no complaints and functions normally. Discrepancies between the ”disease” and the ”illness” cannot be

From the Functional Gastrointestinal and Motility Disorders Center, Division of Digestive Diseases and Nutrition, University of North Carolina School of Medicine, Chapel Hill, North Carolina (YR, DAD); and Tel Aviv University, Sackler School of Medicine, Tel Aviv, Israel (YR)

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explained by the biological or morphologic findings; usually they are considered as related to psychosocial factors.43,50 The important influence of psychological and social factors on the clinical expression, response to treatment, and outcome has been shown in various chronic diseases, but studies addressing this issue are limited in IBD. A survey of a random sample of 1000 members of the American Gastroenterological Associati~n~~ showed that physicians believed that psychosocial factors do not contribute to the cause of IBD but that psychosocial factors affect the clinical exacerbation of symptoms. Conversely, more than half of the patients with IBD believe that stress or personality is a major contributor to the development of their disease, and more than 90% think that stress influences their disease a ~ t i v i t y . ~ ~ , ~ ~ Although physicians and patients have considered psychosocial factors as important in the clinical expression of IBD, confusion and controversy still exist as to their precise role, often because opinions are formed from anecdotal observations or from limited scientific data. Also, the general tendency is to view IBD from a purely biomedical perspective and to regard the contributing role of psychosocial factors with speculation or bias. This article reviews the relationship of psychosocial factors with the pathogenesis and clinical expression of Crohn‘s disease. Because much of the literature in this field does not separate between chronic ulcerative colitis and Crohn’s disease, this article relates mainly to Crohn’s disease but, in some parts, to IBD in general. The advances in the scientific understanding of the relationships between the neural, endocrine, and immune systems are reviewed to close the gap between clinical observations and basic investigation. Some of the common psychosocial concomitants and consequences of IBD are discussed. A comprehensive model of illness and disease is suggested, and ways to integrate psychosocial factors and issues in the diagnosis and patient care are presented.

STRESS AND INFLAMMATORY BOWEL DISEASE Human Studies

Social disorganization and major changes in a person’s lifestyle correlate with medical disorders and subsequent illness or injury.13Although several studies link social stress in humans to chronic diseases, only a few have evaluated IBD, and many are anecdotal, retrospective, or uncontrolled studies. Even the few well-designed studies of IBD give mixed results: in a 6-month prospective study, Duffy et a P studied the relationship of monthly major life events with symptoms and disease activity among 124 patients with IBD and found a strong relationship between major life events, particularly health-related events and symptom exacerbation. Also, an association existed for life events that pre-

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ceded symptom exacerbation by 1 month. When controlling for other sociodemographic and clinical data, antecedent major life events were the factors most explanatory of disease activity (although they accounted for only 7% of the variance of disease activity). Another study evaluated, over a 28-day period, routine daily stressors with bowel symptoms among 10 patients with Crohn's disease.51Using a time-series regression, the investigators found a significant association between acute daily stress and bowel symptoms (e.g., pain, nausea, and diarrhea) even after controlling for major life-event scores. In contrast, North et alg8studied the effects of major life events and mood on bowel symptoms and pain in 32 patients with IBD and found no association between these life events and mood with symptoms 1 or 2 months later but found an association between depression and symptom severity. If stress affects symptom severity or disease activity in patients with IBD, psychotherapeutic intervention may be helpful. A few prospective, controlled studiesg1,lo8 have shown a favorable effect of psychotherapy on certain psychological outcomes (e.g., stress, depression, and anxiety levels) and the course of the disease (e.g., improvement in CDAI and the need for inpatient treatment).91In contrast, a multicenter, randomized, controlled study showed that psychotherapeutic intervention did not have additional benefit over standardized corticosteroid treatment alone.@ The lack of agreement between the studies is not surprising because significant methodologic limitations exist in most 98, 99, log including small sample size, referral bias, retrospective design, lack of control groups, and inappropriate selection of psychological instruments or analysis of data. Also, the complex relationship between psychosocial factors and human illness makes even a well-designed study insufficient or difficult to support a definite conclusion. For example, most studies that concluded a negative relationship between stressors and illness or exacerbation of IBD have not included modulating factors, such as social support and coping style, in the and coping style may have affected clinical outcome.35So, statistically insignificant results may mean only that the study failed to consider all relevant psychosocial measures in the analysis. With this consideration, some conclusions may be drawn: (1)epidemiologic and clinical data have historically indicated an association between various psychosocial stressors and illness exacerbation; (2) data relating life events to IBD exacerbation are inconsistent and conflicting; (3) data linking life events and daily stressors with physiologic effects (e.g., pain and diarrhea) are supported; (4)the major stressors identified in life events research are not unique and include illness or death in the family, divorce or separation, interpersonal conflict, or other major loss; and, (5) the data on effects of psychotherapeutic intervention with the illness or disease activity are insufficient and require additional research with careful design and choice of assessment instruments.

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Animal Studies

The data from animal studies provide linkages between environmental stress and the development of gastrointestinal inflammation and inflammatory disease. Physical restraint, prolonged swimming, premature weaning, and conditioned anxiety all have been shown to produce acute or chronic gut inflammation in several animal models.x,48,115 The cotton-topped tamarin, a New World monkey from Columbia, develops ulcerative colitis and colon cancer only in capti~ity.'~,'~~ Investigators propose that capturing these animals and changing their unique natural social unit, usually at lower temperatures than the jungle habitat, produce sufficient environmental disruption (i.e., social isolation and cold stress) to influence the development of these diseases.36,55, lZ7 No other environmental factors, such as infection, diet, or radiation, have been found to explain why these diseases occur in captivity. Thus, this species may be the closest colitis model to humans that associates disruption of psychosocial and environmental structures with the pathogenesis of the inflammation. SUGGESTIONS FOR PATHOPHYSIOLOGIC MECHANISMS Stress Effects on Gut Function

Psychological and emotional stressors may affect the GI motor, sensory, and secretory function directly or indirectly through the richly innervated nerve plexuses existing between the enteric nervous system, the spinal and autonomic connections, and the CNS (i.e., the "brain-gut 85 Stress effects on intestinal motility have been reported in axis").84* laboratory animals and in humans. Immobilization stress and conditioned fear cause significant changes in intestinal myoelectric activity in laboratory dogs96and rats?" Studies in human subjects using advanced or manometry techniques showed different patterns of intestinal motility (in different segments of the GI tract) in response to physical or psychological stress. Also, psychological stress has been shown to induce more prolonged effect compared with physical stress.3,*02, I3O Psychological factors also have been suggested to be responsible for the reduced pain thresholds in patients with functional GI disorders and to modulate the patients' perception of symptoms and illness behavi0r.3~ Hypothalamic-Pituitary-Adrenal Axis and Neuroendocrinelmmune Regulation

The idea that the nervous system has contributed to the pathogenesis of intestinal inflammation is not new. Several researches in the early 1950s suggested surgical denervation of the inflamed colon as a treat-

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ment option for refractory colitis and Crohn's disease.25,lo9,lZo Today, considerable data show that environmental stress may influence disease susceptibility by the connections between the CNS and humoral and cellular immune or inflammatory pathways. Hypothalamic-Pituitary-Adrenal Axis

Immune or inflammatory mediators (i.e., cytokines), such as interleukins, tumor necrosis factor-a, prostaglandin, and platelet-activating factor potently stimulate the hypothalamus to secrete corticotropin-releasing hormone (CRH),llz,113 which, in turn, stimulates the pituitary gland to release adrenocorticotropichormone, which stimulates the adrenal glands to release glucocorticoids. The corticosteroids suppress inflammation and the production of cytokines, thereby completing the negative-feedback circuit. Many chronic conditions are linked to the disruption or dysregulation of this stress-response system.15,112 Neuroendocrine-Immune Pathways

The autonomic nervous system and the CNS have important roles 112 Peripheral in the body's homeostatic stress-adaptation nerves and the autonomic nervous system innervate immune-system and the immune-system cells (e.g., lymphocytes and macrophages) contain receptors for, and respond to, neurotransmitters and ne~ropeptides."~ Various effects of neuropeptides on immune function or regulation have been described, including decreased responsiveness to mitogens and antigens, reduced lymphocyte-mediated cytotoxicity, reduced delayed hypersensitivity, diminished skin-graft rejection and graft-versus-host reactivity, and suppressed antibody response.34,71 Thus, stressors, by their neural and endocrine connections, may influence the immune or inflammatory response in various systems, including the GI system.85,112, 113 Also, the CNS contains neuronal pathways and receptors for cytokines and other substances that are produced by the immunesystem cells, which enables the immune or inflammatory mediators (e.g., cytokines produced in response to gut inflammation) to modulate higher neural functions and behavior.l8f113 Experimental data provide some evidence regarding these mechanisms. Stress-Induced, Centrally Mediated Inflammation

Gue et aP7 showed that stress or administration of intracerebroventricular corticotropin releasing factor (CRF) were associated with increased abdominal contractions in rats on electromyography. Both effects may be blocked by administrating CRF antagonist, suggesting central CRF involvement in stress-induced abdominal contractions in response to rectal distention. Other circumstantial evidence for the role of the hypothalamic-pituitary-adrenal (HPA) axis come from the following ex-

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amples.' The eosinophilia-myalgia syndrome is an inflammatory disease that results from ingestion of impure L-tryptophan and associated with diarrhea and chronic inflammatory (i.e., eosinophilic and mononuclear) mucosal infiltrati~n.~~ Notably, this inflammatory response also is associated with suppression of hypothalamic CRH mRNA expression2' and suppresses CRH release. Thus, the decreased CRH reactivity in this situation is associated with the development of gut immune-mediated inflammation.2Subserosal injection of streptococcal peptidoglycan polysaccharide (PG-APS) in rats morphologically induces enterocolitis similar to human Crohn's disease.lo4Interestingly, the disease develops in Lewis and Sprague-Dawley rats (having genetically deficient HPA-axis reactivity) but not in Fischer or Buffalo rats (having increased HPA-axis reactivity). Similarly, although both strains (i.e., Lewis and Fischer rats) show significant colitis in response to trinitrobenzene, the instillation of superimposed stress was associated with worsening of the colitis only in the Lewis rats. Also, intracerebroventricular administration of CRF resulted in nearly complete healing in the Fischer rats but incomplete healing in the Lewis rats.97 The findings of some other studies still raise some questions regarding the role of centrally mediated mechanisms. Some studies did not find or confirm the relationships between CRH or arginine vasopressin alteration^^^ or HPA-axis dysfunctionlo' and stress reactivation of previously induced trinitrobenzene or dinitrobenzene (DNB) colitis. CRH also was found to be produced peripherally at the site of inflammation, suggesting an autocrine or paracrine Also, the PG-APS-induced colitis in rats is associated with increased tissue interleukin (1L)1 or IL-1 receptor antagonist ratio and increased activation of the Kallikrein-Kinin system,'04 both of which have been associated with the pathogenesis of the disease.s6,Io5 Thus, based on the data, one may conclude that central (i.e., HPA-axis) and peripheral (i.e., immune or inflammatory mucosal) mechanisms have a role in the pathogenesis of the disease.

Stress-Induced, Immune-Mediated Inflammation Collins et all9 and Qiu et allo1showed that restraint stress may rekindle an inflammatory response in Wistar-Kyoto and Sprague-Dawley rats that recovered from experimental trinitrobenzene sulfonic acidinduced colitis. The investigators showed an increase tissue inflammatory response by both, increased myeloperoxidase activity,19 and evidence of morphologic (i.e., macroscopic and microscopic) colitis.lO' By using this model, the same group of investigators showed that stressinduced reactive inflammation did not occur in athymic mice, mice with severe combined immunodeficiency, or in CD,+-depleted Balblc knockout mice, but they were able to induce stress-reactive inflammation with the transfer of CD,+-enriched cells from mice with acute colitis to mice with severe combined immunodeficiency. These results provide objective evidence of the causal effect of stress on the exacerbation of

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intestinal inflammation and a preliminary suggestion for the mechanism of this effect by showing that stress-induced reactive inflammation is immune-mediated and requires CD,' lymphocytes. Stress-Induced Increase in Gut Mucosal Permeability

Some studies have shown that, *in Wistar-Kyoto rats, when physically restrained, intestinal mucin is decreased and intestinal mucosal permeability is increased,lol,lo6 which is consistent with the theory that defects in the mucosal barrier function are an important component of disease pathogenesis.80Disruption of the mucosal barrier allows antigens to cross the intestinal mucosa and activate the inflammatory response. Reciprocal Effects of Gut Inflammation on CNS and Illness Behavior

The gut mucosal cells can express cytokine genes and synthesize and release cytokines. Studies have shown that inflammation may increase the expression of mRNA and the production of several inflammatory cytokines (e.g., IL-la, IL-lb, IL-6, and tumor necrosis factor-a).20,70 Thus, the intestinal mucosal cells actively participate in the inflammatory response by elaborating proinflammatory cytokines. Also, the inflammatory process may cause structural and functional abnormalities in the enteric nervous system. Interestingly, these changes are not restricted to the inflamed site but may involve nerves and bowel segments that are remote from the inflammation site.9,53, 63 These sustained or prolonged structural and functional alterations in the gut neuromuscular pathways may provide a possible mechanism for the association of IBD and inflammatory bowel syndrome (IBS). Also, the inflammatory process in the gut, through the effect of inflammatory cytokines, also may affect the autonomic nervous system9and CNS function,18,113 thus providing a possible explanation or mechanism for the altered or illness behavior. The evidence for the reciprocal affect of gut inflammation on behavior are limited. Some studies suggest that peripherally activated inflammatory cytokines mediate the significant reduction in food intake and the exaggerated postprandial satiety in hapten-induced colitis and systemic inflammation.87,88, 113, 124

PSYCHOSOCIAL CONCOMITANTS ANDCONSEQUENCESOF INFLAMMATORY BOWEL DISEASE

In addition to the influencing role of psychosocial factors on the pathogenesis or exacerbation of Crohn's disease, once the disease devel-

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ops, psychosocial concomitants must be understood and considered to understand the clinical expression of the illness and to provide proper care. As with any chronic and painful illness, Crohn’s disease may have emotional and psychological consequences. The spectrum of the psychological disorders that may be associated with Crohn‘s disease is beyond the scope of this article. The data regarding these disorders in Crohn‘s disease are limited and may be found e l ~ e w h e r eTherefore, .~~ this section will focus on a broader view of the psychosocial effects of Crohn’s disease and some modulators that may affect them. Psychological Impact of the Disease Psychological Diagnosis and Mood States Transient psychological distress or mood states, such as depression or anxiety, are common in patients with Crohn‘s disease and relate to living with the disease. Also, some drugs used in treating IBD patients, such as corticosteroids or narcotics, may exacerbate depression. These psychological states may lower pain thresholds, amplify illness behavior, increase healthcare and diminish the response to treatment.66 When other psychiatric diagnoses occur, they also need to be recognized and treated. The most common psychiatric diagnosis in patients with Crohn‘s disease is major depressive disorder,’jObut other psychiatric disorders, such as anxiety disorder and somatization (i.e., somatoform), also may occur as in other chronic medical illnesses.34 Numerous studies have shown a frequency of concurrent psychiatric morbidity in patients with Crohn’s disease that is higher than in healthy controls, patients with ulcerative colitis, and patients with other chronic medical illnesses.4,60, 73, 116 The prevalence is as high as 35% for current and 65% for lifetime psychiatric disorders,lZ2but because psychiatric disorders may influence the severity of the disease, healthcare seeking, and physician visits,’j6the high rates probably reflect the selection of patients with more severe psychological distress, who exhibit greater healthcare use and more of whom are in tertiary care.38The greater degree of psychological disturbance in Crohn‘s disease than ulcerative colitis or controls relates to the greater severity of disease.38,39, 89, lzz For example, in a United States random study of persons belonging to the Crohn‘s and Colitis Foundation of patients with Crohn’s disease had greater psychological dysfunction and psychological distress than did patients with ulcerative colitis, but, controlling for disease severity, these differences were not statistically signifi~ant.~~ Also, comparisons between IBD members with active (CDAI, > 182) and inactive disease confirmed that all psychosocial measures were significantly higher in patients with more active disease.38 Personality Disturbance Researchers have tried to understand some diseases as linked to specific personality features (so-called specificityhypothesis),’ unconscious

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conflicts,l or disturbed interpersonal re1ation~hips.l~~ Although attempts to validate the specificity of these personality factors for medical diseases have been made? ll1 the methodology and results were not convincing.5, 33, 43 More researchers have reported a higher prevalence of neuroticism and introversion in patients with Crohn's disease than in patients with ulcerative colitis or other medical disorders? 52, 60, lo3but the importance of these findings is unclear. A different personality construct of alexithymia is of possible clinical relevance. Alexithymia (from the Greek, absence of words for emotions) has been described in the past 25 years in various medical conditions, 117 Patients with alexiincluding ulcerative colitis and Crohn's disea~e.4~~ thymia have chronic difficulties recognizing and verbalizing emotions. Investigators believe that alexithymia develops in response to early traumatic experiences, such as abuse, severe childhood illness, or depravation. Patients with alexithymia may express strong emotions, such as anger or sadness, in relation to their illness, but they know little about the psychological basis for these feelings and cannot link them with past experience or current illness.l18This limits their ability to regulate emotions, use coping strategies effectively, and adjust to their chronic condition. Their tendency to communicate emotional distress through somatic symptoms and illness behavior rather than verbally may be associated with more frequent physician visits and a poorer prognosis.82 Finally, some investigator^^^, 122 suggest that patients with refractory Crohn's disease should undergo psychiatric evaluation for "psychogenicity." This approach is not widely accepted, but the authors believe that, in some cases in which the illness presentation is greater than evident from disease activity, a significant psychological or emotional diagnosis may coexist with the disease. In this case, identifying and addressing these factors may help to improve responsiveness to treatment, outcome, and well-being. Modulators of Psychological Disturbances and Stressors

The effect of Crohn's disease and the effects of concomitants psychological distresses on patients may be modulated by environmental, behavioral, and social factors. Early Experience and Life Events

Early life experience, such as living with a family member who suffers from GI symptoms or familial dysfunction (e.g., conflicts or divorce) and recent major or stressful life events (e.g., the breakup of a close relationship or loss of a loved one) may cause additional psychological and emotional stress that may magnify the illness and lead to adverse health outcomes. Special attention or consideration should be given to a history of physical or sexual abuse. Abuse history is common

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among patients with chronic medical and gastrointestinal illnesses.4o,41,74 It is associated with functional disability and increased psychological distress, abdominal and extra-abdominal pain, healthcare seeking, physician visits, and surgery.4o,41 Disease-Related Concerns

Having IBD requires working through the personal meaning of the illness and its possible consequences, including fears about pain or incontinence; impaired physical or social functioning; financial hardship; adjusting to perineal disease or an ostomy; or, the prospect of future surgery, cancer, or death. Patients’ concerns regarding their illness and disease affect their health status, adjustment to the illness, and treatment plan. To obtain and quantify IBD-specific worriers and concerns, the authors developed the Rating Form of IBD Concerns (RFIPC), which includes the 25 most common concerns of patients with IBD.4zIn a study of randomly selected patients belonging to the Crohn’s and Colitis Foundation of America, the authors found that the unclear nature of the disease, medication side effects, energy level, surgery (and having an ostomy bag), being a burden to others, loss of bowel control, and the possible development of cancer are the most important concerns in these patients. Differences in concerns between patients with Crohn‘s disease and patients with ulcerative colitis are also noted. Other studies using the RFIPC instrument showed a higher rate of IBD-related concerns in blacks than in whites (E. C. De Rooy et al, unpublished observations, 1996), different concerns-severity scores vary across countries, with some country-related differences on individual items.77Also, IBD-related concerns correlate negatively with the patients’ knowledge about the disease42,95 (i.e., lower information level is associated with higher level of concerns). Because patients’ ability to adjust to their disease is higher when they are informed about the nature and effects of their illness (G. Moser and D. A. Drossman, unpublished observations, 1999), one may speculate that adequate information through counseling and education may reduce patients’ concerns, increase their adjustment to the illness, and improve their health status and outcome. RFIPC correlates with patient self-perceptions of well-being, and other quality-of-life measuresz7,42 and was found to be responsive to surgical t~eatment,2~? lz9 but RFIPC does not necessarily correlate with physical symptoms, which suggests that IBD-related concerns are a separate domain of health status of these patients. Therefore, it may be used as a disease-specific instrument for the evaluation of these patients’ health status and outcomes. Coping and Social Support

Coping involves the efforts to appraise or manage the illness.” Effective coping strategies may mitigate some of the major domains of

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the illness, such as depression, anxiety, and somatic symptoms.” A maladaptive coping strategy occurs when patients view their health state with pessimism (e.g., “It’s never going to be better.”) and with little perceived control (e.g., ”catastrophizing” and “perceived controllability”).68Studies that have looked at coping patterns in patients with IBD35,72 have shown that these patients are more likely to use problemfocused, relative to emotion-focused, strategies. Different coping styles may have adaptive or maladaptive effects on a patient’s health status and outcome. Effective or adaptive coping strategies may help to reduce psychological distress and improve health status and daily n,76 In contrast, maladaptive ”catastrophizing” style and low perceived controllability correlate strongly with depression, have negative effects on health status,54,68, 69 and predict poor health outcome among patients with GI symptoms.22Behavioral treatment methods may improve coping style in patients with IBD.lo7 The availability of social-support networks may buffer the adverse effects of these stresses on one’s health status. The effects of socialsupport networks have not been studied in patients with IBD, but investigators report that patients with strong social support networks have a greater sense of control over illness and have lower stress levels than patients who do Conversely, people with poor social-support networks are at greater risk for mortality.8 Impact on Outcome Health-Related Quality of Life

The inability of objective markers of disease activity or severity (e.g., CDAI) to measure the effects of important environmental and psychosocial variables on a patient’s health status or well-being sets the need for the development of a more sensitive clinical assessment instrument. The integrated effects of physiologic state, psychological state, physical function, and social interactions on an individual’s overall general sense of personal well-being is encompassed in the term quality of life (QOL).lloHealth-related QOL (HRQOL), also called health status, is a global measure that incorporates the patient’s perceptions, attributions, and daily level of function in response to an It incorporates the contributions of the biological nature of the disease and the psychological, social, and cultural factors. HRQOL has become an important patient-oriented clinical-outcome measure for many chronic diseases, in45* 119 cluding chronic GI diseases.28* Several instruments have been developed to measure HRQOL, including generic measures (e.g., Sickness Impact Profile7 and Medical Outcome Study SF-36123)and disease (condition)-specificmeasures. Several disease-specific QOL instruments have been developed for IBD. A commonly used instrument is the Inflammatory Bowel Disease Ques-

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tionnaire, which was shown to be reliable, valid, and responsive to changes relating to medical treatment.62More information about the Inflammatory Bowel Disease Questionnaire and other disease-specific QOL instruments for IBD may be found elsewhere.28Also, the RFIPC represents an independent domain on health status and also can be used as a disease-specific QOL measure.42 Results from clinical studies of HRQOL in IBD or Crohn’s disease show that, despite the potential adverse consequences of having IBD, most patients maintain good physical and social functioning,38,39, 46, 62, 81 at least comparable to other ambulatory patients with other diseases. Assessing patients’ health status by using HRQOL has further emphasized the major or significant impact of psychosocial factors on the patients’ well-being. The impairment in HRQOL was found to be greater in the psychological and social dimension than in the physical dimenhealthcare utilization and scores of well-being correlate ~ i o n 39, . ~95~Also, , better with the daily functional status related to IBD than with the physician’s rating of the disease activity.39 Illness Behavior The patient’s behavior in the face of chronic illness (e.g., Crohn’s disease) is not determined only by the disease type, severity, or activity. Psychological factors, psychosocial modifiers (e.g., coping, social support, and previous experiences), and the person’s social (i.e., family and society) and cultural environments also influence when and how the disease is experienced and the individual’s attitudes and behaviors relating to it.90 NEED FOR AN INTEGRATED MODEL OF ILLNESS AND DISEASE

Disease activity and severity are insufficient to explain the variability in the patient’s symptoms or behavior (i.e., the illness).50Other domains of the patient’s health, such as psychological factors and environmental modulators, have to be included and considered to allow for a more comprehensive assessment of the patient’s health status (or illness). The biopsychosocial modelz9,30, 47 permits a broader and more practical framework to deal with the complexity of the patient’s illness. It presumes that physiologic, psychological, behavioral, and environmental factors interact simultaneously at multiple levels to define the illness. Also, the illness may reciprocate and affect its determinants, leading to varying effects on the individual. Consistent with the biopsychosocial model (Fig. l),genetic and environmental factors early in life determine the susceptibility to IBD. Then, psychosocial factors and modifiers interacting with the physiologic or pathologic state influence when and how the disease is experienced symptomatically; the individual’s illness

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Emotions

Psychosoeial Factors (Psychiatricdiag., Personality, Coping Culture, Social support etc.)

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I

Psychosocial Status

Early life Genetic

_ _ _ _ ~

Envimnnenr

Behavior Neuroendocrindimmune

I Outcome Dailyfuncrion Health care use Work absenteeism

Intestinal Functiou/Disease (secretory, motor,sensory,

PhysiologicaVPathologicalStatus Figure 1. Biopsychosocial understanding of inflammatoty bowel disease (IBD). Early in life, genetic and environmental factors determine the susceptibility to IBD. Later, psychosocial factors and modifiers interacting with the physiologic/pathologicstates will influence when and how the disease is experienced symptomatically, the individual’s illness behavior, and the clinical outcome.

behavior; and, ultimately, the clinical outcome. Negative factors, such as life stress or concurrent psychiatric diagnosis, lead to more severe illness or, potentially, disease activation. Conversely, health-promoting factors, such as strong social-support networks or effective coping style, ameliorate the effects of disease and improve outcome (i.e., symptoms, wellbeing, daily function, utilization of healthcare, and the patient’s HRQOL). For example, one stressor, such as a death or other traumatic experience, could affect the patient’s psychological state, physiologic state (e.g., the inflammatory process), the severity of symptoms, and the patient’s behavior. Also, the patient’s physiologic status (as determined by the type, activity and severity of the ”disease”) may affect not only the patient’s symptoms and behavior but also (in a reciprocal manner) the patient’s psychological state. The later effects depend also on preexisting psychiatric status, social-support networks, or coping style. Thus, by integrating the disease with the other domains of illness, the biopsychosocial model enables a more comprehensive assessment and understanding not only of the ”disease” but also its perception, experience, expression, and their effects in an individual patient. This may explain the variation in the illness condition and clinical outcome. Some patients may have poor health status with little evidence for active disease,

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whereas other patients with severe disease function well because of little psychological morbidity, good social support, and effective coping methods.

INTEGRATING PSYCHOSOCIAL FACTORS IN DIAGNOSIS AND TREATMENT Assessment and Evaluation of Psychosocial Factors

The assessment of a patient’s psychosocial well-being is an essential part of diagnosis and patient care. The data collection requires the willingness to address the biologic and psychosocial aspects of the illness.31Physicians should create a trusting clinical environment so that the patients will feel comfortable disclosing their thoughts and feelings. Nevertheless, some patients (e.g., patients with alexithymia) have difficulty in expressing their feelings or relating them to their illness. These patients should be encouraged to tell the story in their own way, so that the events contributing to the illness unfold naturally.79,93 The traditional medical and social histories should be elicited together so that the symptoms are understood in the context of the psychosocial events surrounding the illness. This is important in cases in which the patient’s symptoms are not fully explained by the disease or do not respond to anti-inflammatory therapy. Some of the important variables to be inquired and assessed in history taking include: Perceived (subjective) severity of the illness Current life stress (e.g., job demands, health care expenses, and insurance coverage) Psychiatric comorbidity Personality characteristics Disease-related worries and concerns Patient’s adaptation to the illness and coping Quality of social support Quality of life Patient’s treatment expectations The patient’s report must be appraised together with the results of objective studies, and physicians should determine the relative contribution of the medical and psychosocial dimensions to the patient’s illness. This process is helpful to establish priorities for further evaluation or treatment and to avoid unnecessary studies, treatments, or even surgical intervention.26Also, physicians should corroborate patients’ reports with those of their families. Some patients may hold back disclosing the degree of functional impairment (i.e., ”to be strong”), whereas others, at risk of losing family attention, work relief, or compensation, may subconsciously amplify the degree of disability, at least at first.

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Integrating Psychosocial Aspects into Patient Care

Consistent with the biopsychosocial model, physicians should achieve control of the inflammatory process (i.e., the disease) as part of a more comprehensive management plan. By addressing the psychosocial factors that also contribute to the illness, a more patient-focused model of care is established that addresses not only the disease but also the disease modifiers and psychological consequences (i.e., the illness). Following are some general recommendations for establishing a more comprehensive therapeutic approach. Detailed guidelines are described elsewhere.31.32.43 Establish an effective physician-patient relationship by actively listening to patients’ thoughts and concerns, empathetically and nonjudgmentally responding to them, and providing information consistent with patients’ interests and needs. Help patients learn and accept the disease by providing education and reas~urance.~~ Help patients appraise and adapt to stressors. Knowing and recognizing the association between bowel symptoms and psychosocial stress may help patients to modify all factors affecting the illness condition. Help patients take responsibility for the healthcare. Patients should be apprised of the risks and benefits of treatment alternatives and actively participate in healthcare decisions. This process helps patient to achieve a greater sense of control over the illness, which ultimately improves health outcome. Involve the family. The support and encouragement provided by the patients’ families is an important asset with any care plan. Sometimes family members may feel helpless, guilty, or angry, but expressing such feelings may be unacceptable. Physicians may help to ameliorate these feelings by acknowledging them, enlisting family participation in the treatment, and recommending family counseling when necessary. Reinforce health-promoting behaviors by encouraging patients to take responsibility, to learn to cope with a chronic illness (rather than to expect cure), and limit discussion of symptoms to no more than is needed to satisfy medical concerns. Specific Therapeutic Issues

Medications with central or psychotropic effects (e.g., antidepressants) may be used to treat comorbid affective or psychiatric disorders (e.g., depression or anxiety). Treating depressive disorders is the same as treating patients without Crohn’s disease, and usually it involves antidepressant medication or psychotherapy. Some specific issues should be considered when choosing antidepressant therapy for patients with

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Crohn’s disease, including side effects (e.g., constipation with tricyclic antidepressants) and pharmacologic properties (e.g., poor oral absorption). Independent of their effects on mood, antidepressants also act as “central analgesics” to raise perception threshold and may therefore be considered when pain associated with disability is a common feature.16,32 Low doses of tricyclic antidepressants, such as desipramine or amitriptyline have been best studied and seem to be effective. Low-dose serotonin reuptake inhibitors may be preferred in patients with constipation because of their low or absent anticholinergic effects. Treatment should be maintained for 6 to 12 months before tapering. Patients should be informed that as much as several weeks may be required for these medications to work; they are not addictive; and side effects, if they occur, ameliorate over 1 or 2 weeks. Some new medications directed to reduce gut sensitivity (i.e., 5-HT3 antagonists) have been approved for treating patients with IBS,‘* but no data are available regarding their use in patients with Crohn’s disease or ulcerative colitis. Other drugs are currently undergoing clinical trials, including 5-HT3= and 5-HT4 antagonists and K-opioid antagonists.= Psychiatric consultation should be considered when (1) a patient has a psychiatric illness, major life stress, loss, or abuse requiring treatment; (2) a patient’s daily functioning (e.g., ability to work) or family relationships are severely impaired; and (3) diagnostic and therapeutic strategies are being considered based on patient complaints without supportive medical data.

SUMMARY

Patients and clinicians have always recognized the importance of psychosocial factors as consequences of IBD and as predeterminants for symptom exacerbati~n.~~ Over the past decade, improvements in psychosocial assessment and clinical research design methodology, coupled with new data in brain-gut physiology and psychoneuroimmunology, have led investigators and clinicians to accept a broader approach to illness and disease (i.e., the biopsychosocial model). Based on this understanding and the evidence presented in this article, several conclusions can be made: 1. The pathophysiology of IBD is best understood in terms of dysregulation of homeostatic systems (i.e., neural, endocrine, immune, and inflammatory) in a biologically predisposed host rather than as conditions caused by specific etiologic factor(s). 2. Psychosocial factors contribute to the onset, severity, clinical expression, and outcome of IBD. Determination of the precise role for these factors requires further study.

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3. Identifiable psychosocial factors (e.g., psychiatric diagnosis, personality, life stress, coping, and social support) correlate with the overall severity of the condition; they are not specific for IBD. 4. Physicians must identify psychosocial factors unique to each individual that contribute to the clinical expression of the disorder. 5. Optimal care requires the establishment of a comprehensive, effective therapeutic approach.

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