Stress and Course of Disease in Multiple Sclerosis

Abstract

In this prospective study, 96 healthy controls and 101 multiple sclerosis patients were followed up for as many as 6 years, and self-reported stressful events and health status were assessed. The authors evaluated (a) whether patients reported more stressful life events than healthy controls and (b) the bidirectional relationship between stress and functional deterioration among patients. Healthy controls reported more life events than patients, Odds ratio (OR) = 1.13, p < .0001; and this relationship was attributable to healthy controls' reporting more neutral/positive events than patients. A bidirectional relationship was confirmed between stress and illness: there was an increased risk of disease progression when rate of reported stressful events was higher, OR = 1.13, p < .0003, and an increased risk of reported stressful events when rate of disease progression was higher, OR = 2.13, p < .0001. There were no differences in reported stress by level of baseline disability. The authors concluded that multiple sclerosis patients demonstrate a vicious cycle between stress and disease progression.     

Stressful life events precede exacerbations of multiple sclerosis

OBJECTIVE: We longitudinally monitored life events and health changes in patients with multiple sclerosis (MS) to determine whether stressful events may trigger exacerbation of MS. METHODS: Twenty-three women with MS were followed for 1 year. Each subject completed the Psychiatric Epidemiologic Research Interview on a weekly basis. Further information on potentially stressful events was acquired using the Life Events and Difficulties Schedule. Neurologic symptoms were also monitored on a weekly basis throughout the year. Potential MS exacerbations were confirmed by a neurologist who was blind to the presence and timing of stressors. RESULTS: Eighty-five percent of MS exacerbations were associated with stressful life events in the preceding 6 weeks. Stressful life events occurred an average of 14 days before MS exacerbations, compared with 33 days before a randomly selected control date (p < .0001). Survival analysis confirmed that an increase in frequency of life events was associated with greater likelihood of MS exacerbations (hazard ratio = 13.18, p < .05). CONCLUSIONS: These results are consistent with the hypothesis that stress is a potential trigger of disease activity in patients with relapsing-remitting MS.     

Stressful life events, depression and demoralization as risk factors for acute coronary heart disease

BACKGROUND: While the effect of psychological stress and depression on the course of heart disease is commonly recognized, the relationship between recent life events, major depression, depressive symptomatology and the onset of acute coronary heart disease (CHD) has been less considered. The aim of this study was to investigate the presence of stressful life events, major and minor depression, recurrent depression and demoralization in the year preceding the occurrence of a first acute myocardial infarction (AMI) and/or a first episode of instable angina and to compare stressful life events, also related with mood disorders, in patients and healthy controls. METHODS: 97 consecutive patients with a first episode of CHD (91 with AMI and 6 with instable angina) and 97 healthy subjects matched for sociodemographic variables were included. All patients were interviewed with Paykel's Interview for Recent Life Events, a semistructured interview for determining the psychiatric diagnosis of mood disorders (DSM-IV), a semistructured interview for demoralization (DCPR). Patients were assessed while on remission from the acute phase. The time period considered was the year preceding the first episode of CHD and the year before the interview for controls. RESULTS: Patients with acute CHD reported significantly more life events than control subjects (p < 0.001). All categories of events (except entrance events) were significantly more frequent. 30% of patients were identified as suffering from a major depressive disorder; 9% of patients were suffering from minor depression, 20% from demoralization. Even though there was an overlap between major depression and demoralization (12%), 17% of patients with major depression were not classified as demoralized and 7% of patients with demoralization did not satisfy the criteria for major depression. Independently of mood disorders, patients had a higher (p < 0.001) mean number of life events than controls. With regard to life events, the same significant difference (p < 0.001) compared to controls applied to patients with and without mood disorders. CONCLUSIONS: Our findings emphasize, by means of reliable methodology, the relationship between life events and AMI. These data, together with those regarding traditional cardiac risk factors, may have clinical and prognostic implications to be verified in longitudinal studies.     

应激性生活事件对室性心律失常患者血液流变性的影响

目的 :探讨应激性生活事件对室性心律失常患者血液流变性的影响。方法 :采用应激性生活事件量表对 2 0例功能性室性心律失常患者和 2 0例与之在人口统计学方面相匹配的健康人进行了评定并测定血液流变学指标。结果 :病例组高切变率血液粘度 [ηb(H) ]、血浆粘度 ( ηP)、红细胞压积 (HCT)和红细胞聚集性 (AI)与对照组相比差异有非常显著性意义 (P <0 .0 1) ;生活事件紧张总值与上述血液流变学指标呈正性显著相关 (P <0 .0 1)。结论 :应激性生活事件影响血液流变学特性 ,并为应激与室性心律失常关系的研究提供了依据     

甲亢患者病前应激性生活事件研究

目的：探讨甲亢患者病前经历的应激性生活事件的特点及与疾病的联系。方法：采用事件量表（ＬＥＳ）对８２例初发的甲亢患者进行测定,并与正常对照比较。结果：甲亢患者病前经历有影响的负性生活事件频数及总生活事件频数、负性生活紧张值及总生活事件紧张值显著高于对照组（Ｐ〈０．０５）,男性患者正性生活事件紧张值显著高于女性患者。结论：提示患病前经历较多负性生活事件的应激可能与发病有一定联系。     

Macrophage migration inhibitory factor gene: influence on rheumatoid arthritis susceptibility

The macrophage inhibitory factor (MIF) is a cytokine that has been implicated in several inflammatory and autoimmune diseases, including rheumatoid arthritis, systemic lupus, glomerulonephritis, and multiple sclerosis. In rheumatoid arthritis (RA), results ranging from lack of association of MIF polymorphisms with RA, to involvement in either severity or susceptibility to the disease have been reported in the past. We aimed at investigating the role of this gene in RA in the Spanish population. Two well-known MIF promoter polymorphisms were tested in 606 adult RA patients and 886 healthy controls: a single nucleotide polymorphism at -173G/C and a tetranucleotide repeat (CATT)(5-8) located at -794. We found a significant association of the allele -173C with RA (p = 0.01; odds ratio [OR] = 1.31; 95% confidence interval [CI] = 1.06-1.62). The -173C risk allele, previously reported to be transmitted in excess in patients with juvenile idiopathic arthritis, was significantly more frequent in early-onset adult RA patients than in healthy controls (p = 0.003; OR = 1.57; 95% CI = 1.14-2.15), whereas late-onset patients were not significantly different to controls (p = 0.6; OR = 1.09; 95% CI = 0.77-1.55). In conclusion, the -173C allele in the MIF promoter region is associated with increased RA predisposition, mainly in early-onset patients.     

Stress and other psychosocial characteristics of patients with psychogenic nonepileptic seizures

Research on psychogenic nonepileptic seizures (PNES) has focused on childhood abuse, but less is known about other stressors and psychosocial risk factors. The authors compared 25 patients with PNES with 33 control subjects with epilepsy on stressful life events and other risk factors for somatoform disorders. Compared with control subjects, patients with PNES reported significantly more prevalent and stressful negative life events (including adulthood abuse) and more current rumination, stress-related diseases, somatic symptoms, bodily awareness, and marginally more anxiety and depression. However, the relationship of many of these variables to PNES was accounted for by life stress. Groups did not differ on illness worry, alexithymia, or psychotic symptoms. The results suggest that PNES are part of a larger pattern of somatic symptoms responses to a wide range of negative events, including stress in adulthood.     

Stressful life events and changes in substance use among a multiracial/ethnic sample of adolescent boys

This paper presents a comparative analysis of the prevalence of stressful life events and of the relationships between stressful life events and alcohol, illicit drug, and cigarette use among a multi-ethnic community sample (N = 2,446) of early adolescent boys. The data were derived from a longitudinal study of substance use behaviors and their psychosocial correlates among Hispanic, African-American, and White non-Hispanic adolescent boys residing in Dade County, Florida. Similar levels of event exposure were found among the subgroups, with one exception. African Americans were significantly more likely to experience a death-related event in the past year. Stressful life events were not significantly related with substance use among African-American students. Among Hispanics and White non-Hispanics, however, a number of significant positive relationships were found. A number of bidirectional events (i.e., those events that could be either an antecedent to and/or the result of substance use) were significantly related with stressful events, highlighting the importance of longitudinal research in delineating the temporal ordering of events and outcomes. The authors conclude that future stress research with adolescents should pay particular attention to the important moderating influences of culture and ethnicity as well as to the bidirectional nature of life events and substance use.     

Life events and prodromal symptoms in bulimia nervosa

BACKGROUND: Little is known about the interaction of life events with prodromal symptoms in bulimia nervosa. METHODS: A semistructured research interview based on Paykel's Interview for Recent Life Events and on the Clinical Interview for Depression for eliciting prodromal symptoms was administered to 30 patients with bulimia nervosa and 30 healthy control subjects matched for sociodemographic variables. RESULTS: Patients reported significantly more stressful life events than controls. Most of the patients reported prodromal symptoms. Anorexia, low self-esteem, depressed mood, anhedonia, generalized anxiety and irritability were the most common prodromal symptoms. CONCLUSIONS: The prodromal phase of bulimia nervosa was found to be characterized by a combination of prodromal symptoms of affective type and stressful life events. Their joint occurrence may increase vulnerability to bulimia nervosa.     

Parenting stress and parental bonding

Attachment experiences are thought to be important because of their implications for later development. The authors' aim with the questionnaire-based study was to investigate the differences between recalled parental bonding regarding 4 types of maternal and paternal bonding with respect to experienced parenting stress caused by child characteristics, parent attributes, and life events under the consideration of the child's gender and age. The authors gathered parental bonding behavior data with the German version of the Parental Bonding Instrument (PBI). The authors assessed parenting stress with their German version of the "Parenting Stress Index (PSI)." They found significant differences among 120 mothers grouped in the 4 maternal and the 4 paternal bonding types regarding parenting stress caused by child, maternal bonding: F(5, 113) = 4.13, p = .002, paternal bonding: F(5, 111) = 8.50, p < or = .0001, and parent characteristics, maternal bonding: F(5, 113) = 3.33, p = .008, paternal bonding: F(5, 111) = 7.80, p < or = .0001. The lowest level of parenting stress was experienced by mothers who themselves recalled the "optimal parental bonding type" with respect to the child and parental domain. The authors did not find any significant differences between the 4 maternal, F(5, 113) = 1.25, p = .29, and the 4 paternal, F(5, 111) = 1.87, p = .106, bonding types with respect to the life stress. According to the authors' findings, the representation of attachment relationships seems to have a special impact on the adult's capacity to cope with challenges and stress, either directly or indirectly as an internal working model of attachment. For the clinical practice, these findings seem to recommend the combination of both the PSI and PBI regarding the diagnostic of stressful mother-child system to plan an optimal intervention program.     

Life events, difficulties and dilemmas in the onset of chronic fatigue syndrome: a case-control study

BACKGROUND: The role of stress in the onset of chronic fatigue syndrome is unclear. Our objectives in this study were first, to determine the relation between the onset of chronic fatigue syndrome and stressful life events and difficulties. Secondly, we examined the role of a particular type of problem, dilemmas, in the onset of chronic fatigue syndrome. METHOD: We used a case-control design with 64 consecutive referrals from an Infectious Diseases/ Liaison Psychiatry Fatigue clinic and 64 age- and sex-matched controls from a general practice population control group in Leeds. We had two main outcome measures; the odds ratios of the risk of developing chronic fatigue syndrome after experiencing a severe life event, severe difficulties or both in the year and 3 months preceding onset; and the proportion of subjects in each group who experienced a dilemma prior to onset. RESULTS: Patients with chronic fatigue syndrome were more likely to experience severe events and difficulties in the 3 months (OR = 9, 95% CI 3.2 to 25.1) and year (OR = 4.3, 95% CI 1.8 to 10.2) prior to onset of their illness than population controls. In the 3 months prior to onset 19 of the 64 patients (30%) experienced a dilemma compared to none of the controls. CONCLUSIONS: Chronic fatigue syndrome is associated with stressful events and difficulties prior to onset. Those events and difficulties characterized as being dilemmas seem to be particularly important.     

No evidence of association of the KLF12 gene with rheumatoid arthritis in Spanish and Dutch cohorts and a meta-analysis of published data

The aim of the present study was to replicate the previously reported association of KLF12 gene polymorphisms with rheumatoid arthritis (RA). Two independent cohorts from Spain (1,360 RA patients and 1,520 controls) and the Netherlands (1,018 RA patients and 1,150 controls) were genotyped for KLF12 rs1887346 and rs9565072 single-nucleotide polymorphisms using a TaqMan 5'-allele discrimination assay. No evidence of association of RA with the minor T allele of rs9565072 (31.82% vs 33.73%; p = 0.14, odds ratios [OR] 0.92 [95% confidence interval (CI) 0.82-1.03]) or the minor A allele of rs1887346 polymorphism (21.60% vs 21.77%; p = 0.88, OR 0.99 [95% CI 0.87-1.13]) was observed in Spanish patients compared with healthy controls. This lack of association was also confirmed in the Dutch cohort: the minor T allele frequency of rs9565072 in Dutch RA patients was 35.34% versus 35.57% in controls; p = 0.87, OR 0.99 (95% CI 0.87-1.12); and the minor A allele frequency of rs1887346 in Dutch RA patients was 27.64% versus 28.17% in controls; p = 0.70, OR 0.97 (95% CI 0.85-1.12). A meta-analysis of published KLF12 gene association with RA revealed a pooled OR of 0.99 (95% CI 0.93-1.04) for rs1887346 and a pooled OR of 0.99 (95% CI 0.95-1.04) for rs9565072. In conclusion, our findings indicate that the KLF12 rs1887346 and rs9565072 polymorphisms do not play a relevant role in RA.     

Members 6B and 14 of the TNF receptor superfamily in multiple sclerosis predisposition

TNFRSF6B and TNFRSF14 genes were recently associated with Crohn's disease and rheumatoid arthritis. TNFRSF14 is known as herpes virus entry mediator (HVEM), and herpes viruses have been involved in the aetiology of multiple sclerosis (MS). MS patients present human herpes virus 6 (HHV6) in active plaques and increased antibody responses to HHV6. We aimed to ascertain the role of these genes in MS susceptibility and to investigate the relationship of the gene encoding the widely expressed HVEM receptor with the active replication of HHV6 found in some MS patients. Genotyping of 1370 Spanish MS patients and 1715 ethnically matched controls was performed. HHV6A DNA levels (surrogate of active viral replication) were analysed in serum of MS patients during a 2-year follow-up. Both polymorphisms were associated with MS predisposition, with stronger effect in patients with HHV6 active replication-TNFRSF6B-rs4809330(*)A: P=0.028, OR=1.13; TNFRSF14-rs6684865(*)A: overall P=0.0008, OR=1.2; and HHV6-positive patients vs controls: P=0.017, OR=1.69.     

Life events, difficulties and onset of depressive episodes in later life.

BACKGROUND: The importance of stressful life events and long-term difficulties in the onset of episodes of unipolar depression is well established for young and middle-aged persons, but less so for older people. METHOD: A prospective case-control study was nested in a large community survey of older people. We recruited 83 onset cases during a 2-year period starting 2 1/2 years after the survey, via screening (N = 59) and GP monitoring (N = 24), and 83 controls, a random sample from the same survey population. We assessed depression with the PSE-10 and life stress exposure with the LEDS. RESULTS: Risk of onset was increased 22-fold by severe events and three-fold by ongoing difficulties of at least moderate severity. Severe events accounted for 21% of all episodes but ongoing difficulties for 45%. The association of onset with life stress, often health-related such as death, major disability and hospitalization of subject or someone close, was most pronounced in the cases identified by screening. While a clear risk threshold for events was found between threat 2 and 3 (on a scale of 1-4), the risk associated with difficulties increased more gradually with severity of difficulty. Compared with controls, severe events involved a larger risk for cases without a prior history of depression (OR = 39.48) than for cases with (OR = 8.86). The opposite was found for mild events (OR = 2.94 in recurrent episodes; OR = 1.09 in first episodes). The impact of ongoing difficulties was independent of severity of episode and history of depression. CONCLUSION: Although the nature of life stress in later life, in particular health-related disability and loss of (close) social contacts, is rather different from that in younger persons, it is a potent risk factor for onset of a depressive episode in old age. Severe events show the largest relative risk, but ongoing difficulties account for most episodes. The association of severe events with onset tends to be stronger in first than in recurrent episodes. Mild events can trigger a recurrent episode but not a first one.     

MHC class I chain-related gene A transmembrane polymorphism modulates the extension of ulcerative colitis

Recent evidence from several studies has suggested a genetic predisposition in the pathogenesis of ulcerative colitis (UC), which is especially related with major histocompatibility complex (MHC) genes. The aim of this study was to investigate the possible association of human leukocyte antigen (HLA-B, HLA-DR) and MHC class I chain-related-transmembrane (MICA-TM) polymorphism with the behavior and extension of UC. We selected 121 unrelated patients with UC. These were divided into two groups according to the extension of the disease: 31 patients with distal UC and 90 with wide extension UC; 116 blood donors were also selected as healthy controls, all of whom were typed for HLA-B, HLA-DR, and MICA-TM alleles. HLA-B7 was found to be overrepresented in distal UC patients compared with those with extensive UC (p(c) = 0.007, OR = 5.33) and healthy controls (p(c) = 0.03, OR = 4.09). The MICA-A5.1 allele was also increased in distal UC (p(c) = 0.015, OR = 3.82) when compared with extensive forms. These alleles are in strong linkage disequilibrium in our population. The MICA-A5 allele was significantly increased in extensive forms when compared with healthy controls(p(c) = 0.02, OR = 2.4). According to our results, MICA-A5.1 allele seems to be protective against extensive forms of UC, and MICA-A5 may condition a worse progression of the disease. These results are in agreement with other studies that suggest a similar role of such alleles in other diseases, such as insulin-dependent diabetes mellitus and celiac disease.     

Moderating effects of coping on the relationship between stress and the development of new brain lesions in multiple sclerosis

OBJECTIVE: Many patients with multiple sclerosis (MS) report that stress can trigger disease exacerbations. Considerable research has supported a relationship between stress and both clinical exacerbation and the development of new brain lesions. However, these relationships are not always consistent either within patients or across patients, suggesting the presence of moderators. This study examined the hypothesis that coping moderates the subsequent relationship between stress and the development of new brain lesions in MS. METHODS: Thirty-six patients (mean age = 44.4; 22 women, 14 men) with relapsing forms of MS were assessed once every 4 weeks for 28-100 weeks. New brain lesions were identified using monthly Gd+ MRI. Stress was measured within 24 hours before MRI using a modified version of the Social Readjustment Rating Scale that assessed Conflict and Disruption in Routine. Coping was measured at baseline using the Coping with Health Injuries and Problems questionnaire, which produces four scales: distraction, instrumental, palliative, and emotional preoccupation. Data were analyzed using mixed effects logistic regression to account for within-subject correlations. Analyses were lagged such that stress assessments predicted new Gd+ MRI brain lesions 8 weeks later. RESULTS: As reported previously, stress was significantly related to the development of new Gd+ brain lesions 8 weeks later (OR = 1.62, p =.009). Greater use of distraction was found to be a significant moderator of the relationship between stress and new Gd+ lesions (OR = 0.69, p =.037) such that greater use of distraction was associated with a decreased relationship between stress and new Gd+ lesions. Increased instrumental coping was marginally associated with a decreased relationship between stress and new Gd+ lesions (OR = 0.77, p =.081), while increased emotional preoccupation was marginally associated with an increased relationship between stress and new Gd+ lesions (OR = 1.46, p =.088). There was no significant moderating effect for palliative coping (p =.27) and no significant main effects for any coping variables and the subsequent development of new Gd+ brain lesions (p values >.21). CONCLUSIONS: These findings provide modest support for the hypothesis that coping can moderate the relationship between stress and the MS disease activity. Several limitations in this study are discussed. While these findings suggest areas of potentially fruitful research, readers are cautioned that these are preliminary results; inferences regarding the clinical importance of these findings are premature.     

Stressful life events promote the manifestation of asthma and atopic diseases

BACKGROUND: Psychosocial stress is known to aggravate asthma. Less is known about the impact of stressful life events on the expression of asthma and atopic disorders. OBJECTIVE: To determine whether the onset of asthma, allergic rhinitis or conjunctivitis, and atopic dermatitis, are associated with stressful life events. METHODS: A postal survey on risk factors for asthma and atopic diseases was carried out among 10 667 Finnish first-year university students aged 18-25 years. Stressful life events, (i) severe disease or death of a family member, and (ii) parental or personal conflicts, were retrospectively recorded during the preceding year, 1-5 years, 6-10 years, and more than 10 years prior to the survey response. In a case-control setting, conditional multiple logistic regression analysis was used to assess the temporal association between major stressful life events occurring during a period either preceding, concomitant or subsequent with subject's diagnoses. RESULTS: Concomitant parental and personal conflicts increased the risk of asthma (OR 1.72, 95% CI 1.10-2.69) when adjusted by parental asthma, education and passive smoking at early age. Concomitant severe disease or death of mother, father or spouse (OR 1.52, 95% CI 1.09-2.16) and precedent parental and personal conflicts (OR 1.75, 95% CI 1.15-2.77) increased the risk of manifestation of allergic rhinoconjunctivitis when adjusted for parental atopic disease, education and passive smoking. Subjects' asthma and atopic dermatitis, but not allergic rhinoconjunctivitis, were related to excess of subsequent stressful life events. CONCLUSION: An association between stressful life events and subjects' asthma, allergic rhinoconjunctivitis and atopic dermatitis is suggested.     

Progression to AIDS: the effects of stress, depressive symptoms, and social support.

OBJECTIVE: We examined the effects of stress, depressive symptoms, and social support on the progression of HIV infection. METHODS: Eighty-two HIV-infected gay men without symptoms or AIDS at baseline were followed up every 6 months for up to 5.5 years. Men were recruited from rural and urban areas in North Carolina as part of the Coping in Health and Illness Project. Disease progression was defined using criteria for AIDS (CD4+ lymphocyte count of <200/microl and/or an AIDS-indicator condition). RESULTS: We used Cox regression models with time-dependent covariates, adjusting for age, education, race, baseline CD4+ count, tobacco use, and number of antiretroviral medications. Faster progression to AIDS was associated with more cumulative stressful life events (p = .002), more cumulative depressive symptoms (p = .008), and less cumulative social support (p = .0002). When all three variables were analyzed together, stress and social support remained significant in the model. At 5.5 years, the probability of getting AIDS was about two to three times as high among those above the median on stress or below the median on social support compared with those below the median on stress or above the median on support, respectively. CONCLUSIONS: These data are among the first to demonstrate that more stress and less social support may accelerate the course of HIV disease progression. Additional study will be necessary to elucidate the mechanisms that underlie these relationships and to determine whether interventions that address stress and social support can alter the course of HIV infection.     

Association of HLA-DR and HLA-DQ genes with susceptibility to pulmonary tuberculosis in Koreans: preliminary evidence of associations with drug resistance, disease severity, and disease recurrence

Only 10% of persons infected with Mycobacterium tuberculosis develop clinical tuberculosis (TB), indicating the existence of host genetic factors regulating disease expression. We investigated the association of human leukocyte antigen (HLA) class II genes with the susceptibility to pulmonary TB in Koreans, with special emphasis on their association with drug resistance, disease severity, and disease recurrence. Human leukocyte antigens (HLA)-DRB1 and -DQB1 gene polymorphisms were analyzed in 160 Korean patients with pulmonary TB and 200 ethnically matched healthy controls. HLA-DRB1*0803 (25.0% vs. 14.5% in controls, OR = 1.97, p = 0.012, corrected p (p(c)) > 0.05) and DQB1*0601 (27.5% vs. 15.5% in controls, OR = 2.07, p = 0.005, p(c) > 0.05) were weakly associated with general susceptibility to TB. DRB1*0803 was significantly associated with drug resistance (30.9% vs. 14.5%, OR = 2.63, p(c) = 0.047) and more advanced lung lesion (29.8% vs. 14.5%, OR = 2.50, p(c) = 0.022). DRB1*0803 showed the strongest association with disease recurrence, especially after curative treatment for the earlier infection (47.4% vs. 14.5%, OR = 5.31, p(c) = 0.00009). DQB1*0601, which is strongly linked to DRB1*0803 in this population showed similar changes in the patients as those of DRB1*0803. It is suggested that DRB1*0803 and DQB1*0601 alleles are associated with disease progression of TB in Koreans, exerting influence on the development of drug resistance, severe disease, and recurrent disease.     

Coping style of individuals with functional dyspepsia

OBJECTIVES: The objectives of the study described here were to 1) examine the coping style of patients with functional dyspepsia (FD) and 2) adopt a new interview questionnaire to examine the extent of discriminativeness in the use of coping strategies across different stressful situations. METHODS: A matched case-control design was adopted to compare differences among a target group of 30 patients with FD, a pain control group of 30 patients with rheumatism, and a control group of 30 healthy persons. A new interview questionnaire, the Coping Flexibility Interview Schedule, was used to assess subjects' experience of stressful life events, use of coping strategies, and perceived severity of major FD symptoms. RESULTS: Subjects with FD perceived their experienced stressors as more uncontrollable and as having a greater impact (p < .05). They also used more direct-action strategies but fewer divert attention, acceptance, social support, and relaxation strategies when handling stressful life events (p < .05). A significant group-by-controllability interaction effect was found (p < .001), indicating that FD subjects tended to use coping strategies nondiscriminatively, whereas both rheumatic and healthy subjects tended to use coping strategies more discriminatively across stressful life events of different extents of controllability. CONCLUSIONS: These results indicate that FD patients are characterized by a nondiscriminative, action-oriented coping style. The implications of this finding for the extant body of research and the advantages of using our interview questionnaire, which has a more flexible format, are discussed.