Remote assessment of disease and relapse in major depressive disorder (RADAR-MDD): a multi-centre prospective cohort study protocol.

BACKGROUND: There is a growing body of literature highlighting the role that wearable and mobile remote measurement technology (RMT) can play in measuring symptoms of major depressive disorder (MDD). Outcomes assessment typically relies on self-report, which can be biased by dysfunctional perceptions and current symptom severity. Predictors of depressive relapse include disrupted sleep, reduced sociability, physical activity, changes in mood, prosody and cognitive function, which are all amenable to measurement via RMT. This study aims to: 1) determine the usability, feasibility and acceptability of RMT; 2) improve and refine clinical outcome measurement using RMT to identify current clinical state; 3) determine whether RMT can provide information predictive of depressive relapse and other critical outcomes. METHODS: RADAR-MDD is a multi-site prospective cohort study, aiming to recruit 600 participants with a history of depressive disorder across three sites: London, Amsterdam and Barcelona. Participants will be asked to wear a wrist-worn activity tracker and download several apps onto their smartphones. These apps will be used to either collect data passively from existing smartphone sensors, or to deliver questionnaires, cognitive tasks, and speech assessments. The wearable device, smartphone sensors and questionnaires will collect data for up to 2-years about participants' sleep, physical activity, stress, mood, sociability, speech patterns, and cognitive function. The primary outcome of interest is MDD relapse, defined via the Inventory of Depressive Symptomatology- Self-Report questionnaire (IDS-SR) and the World Health Organisation's self-reported Composite International Diagnostic Interview (CIDI-SF). DISCUSSION: This study aims to provide insight into the early predictors of major depressive relapse, measured unobtrusively via RMT. If found to be acceptable to patients and other key stakeholders and able to provide clinically useful information predictive of future deterioration, RMT has potential to change the way in which depression and other long-term conditions are measured and managed.

Occupational medicine specialist referral triggers: Mixed-methods analysis of teleconsult cases.

Background: Qualitative analyses can yield critical lessons for learning organizations in healthcare. Few studies have applied these techniques in the field of occupational and environmental medicine (OEM). Aims: To describe the characteristics of complex cases referred for OEM subspecialty evaluation and variation by referring provider's training. Methods: Using a mixed methods approach, we conducted a content analysis of clinical cases submitted to a national OEM teleconsult service. Consecutive cases entered between April 2014 and July 2015 were screened, coded and analysed. Results: 108 cases were available for analysis. Local Veterans Health Administration (VHA) non-specialist providers entered a primary medical diagnosis in 96% of cases at the time of intake. OEM speciality physicians coded significant medical conditions based on free text comments. Coder inter-rater reliability was 84%. The most frequent medical diagnosis types associated with tertiary OEM referral by non-specialists were endocrine (19%), cardiovascular (18%) and mental health (16%). Concern for usage of controlled and/or sedating medications was cited in 1% of cases. Compared to referring non-specialists, OEM physicians were more likely to attribute case complexity to musculoskeletal (OR: 2.3, 1.68-3.14) or neurological (OR: 1.69, 1.28-2.24) conditions. Medication usage (OR: 2.2, 1.49-2.26) was more likely to be a source of clinical concern among referring providers. Conclusions: The findings highlight the range of triggers for OEM physician subspecialty referral in clinical practice with employee patients. The results of this study can be used to inform development of provider education, standardized clinical practice pathways, and quality review activities for occupational medicine practitioners.

Predictors of outcome for telephone and face-to-face administered cognitive behavioral therapy for depression.

BACKGROUND: Cognitive behavioral therapy (CBT) can be delivered efficaciously through various modalities, including telephone (T-CBT) and face-to-face (FtF-CBT). The purpose of this study was to explore predictors of outcome in T-CBT and FtF-CBT for depression. METHOD: A total of 325 depressed participants were randomized to receive eighteen 45-min sessions of T-CBT or FtF-CBT. Depression severity was measured using the Hamilton Depression Rating Scale (HAMD) and the Patient Health Questionnaire-9 (PHQ-9). Classification and regression tree (CART) analyses were conducted with baseline participant demographics and psychological characteristics predicting depression outcomes, HAMD and PHQ-9, at end of treatment (week 18). RESULTS: The demographic and psychological characteristics accurately identified 85.3% and 85.0% of treatment responders and 85.7% and 85.0% of treatment non-responders on the HAMD and PHQ-9, respectively. The Coping self-efficacy (CSE) scale predicted outcome on both the HAMD and PHQ-9; those with moderate to high CSE were likely to respond with no other variable influencing that prediction. Among those with low CSE, depression severity influenced response. Social support, physical functioning, and employment emerged as predictors only for the HAMD, and sex predicted response on the PHQ-9. Treatment delivery method (i.e. telephone or face-to-face) did not impact the prediction of outcome. CONCLUSIONS: Findings suggest that the predictors of improved depression are similar across treatment modalities. Most importantly, a moderate to high level of CSE significantly increases the chance of responding in both T-CBT and FtF-CBT. Among patients with low CSE, those with lower depressive symptom severity are more likely to do well in treatment.

Do positive or negative stressful events predict the development of new brain lesions in people with multiple sclerosis?

BACKGROUND: Stressful life events have long been suspected to contribute to multiple sclerosis (MS) disease activity. The few studies examining the relationship between stressful events and neuroimaging markers have been small and inconsistent. This study examined whether different types of stressful events and perceived stress could predict the development of brain lesions. METHOD: This was a secondary analysis of 121 patients with MS followed for 48 weeks during a randomized controlled trial comparing stress management therapy for MS (SMT-MS) to a waitlist control (WLC). Patients underwent magnetic resonance imaging (MRI) scans every 8 weeks. Every month, patients completed an interview measure assessing stressful life events and self-report measures of perceived stress, anxiety and depressive symptoms, which were used to predict the presence of gadolinium-enhancing (Gd+) and T2 lesions on MRI scans 29-62 days later. Participants classified stressful events as positive or negative. Negative events were considered 'major' if they involved physical threat or threat to the patient's family structure, and 'moderate' otherwise. RESULTS: Positive stressful events predicted decreased risk for subsequent Gd+ lesions in the control group [odds ratio (OR) 0.53 for each additional positive stressful event, 95% confidence interval (CI) 0.30-0.91] and less risk for new or enlarging T2 lesions regardless of group assignment (OR 0.74, 95% CI 0.55-0.99). Across groups, major negative stressful events predicted Gd+ lesions (OR 1.77, 95% CI 1.18-2.64) and new or enlarging T2 lesions (OR 1.57, 95% CI 1.11-2.23) whereas moderate negative stressful events, perceived stress, anxiety and depressive symptoms did not. CONCLUSIONS: Major negative stressful events predict increased risk for Gd+ and T2 lesions whereas positive stressful events predict decreased risk.

Comparison of psychotherapies for adult depression to pill placebo control groups: a meta-analysis.

BACKGROUND: The effects of antidepressants for treating depressive disorders have been overestimated because of selective publication of positive trials. Reanalyses that include unpublished trials have yielded reduced effect sizes. This in turn has led to claims that antidepressants have clinically insignificant advantages over placebo and that psychotherapy is therefore a better alternative. To test this, we conducted a meta-analysis of studies comparing psychotherapy with pill placebo. METHOD: Ten 10 studies comparing psychotherapies with pill placebo were identified. In total, 1240 patients were included in these studies. For each study, Hedges' g was calculated. Characteristics of the studies were extracted for subgroup and meta-regression analyses. RESULTS: The effect of psychotherapy compared to pill placebo at post-test was g = 0.25 [95% confidence interval (CI) 0.14-0.36, I² = 0%, 95% CI 0-58]. This effect size corresponds to a number needed to treat (NNT) of 7.14 (95% CI 5.00-12.82). The psychotherapy conditions scored 2.66 points lower on the Hamilton Depression Rating Scale (HAMD) than the placebo conditions, and 3.20 points lower on the Beck Depression Inventory (BDI). Some indications for publication bias were found (two missing studies). We found no significant differences between subgroups of the studies and in meta-regression analyses we found no significant association between baseline severity and effect size. CONCLUSIONS: Although there are differences between the role of placebo in psychotherapy and pharmacotherapy research, psychotherapy has an effect size that is comparable to that of antidepressant medications. Whether these effects should be deemed clinically relevant remains open to debate.

The relationship between wearable-derived sleep features and relapse in Major Depressive Disorder.

BACKGROUND: Changes in sleep and circadian function are leading candidate markers for the detection of relapse in Major Depressive Disorder (MDD). Consumer-grade wearable devices may enable remote and real-time examination of dynamic changes in sleep. Fitbit data from individuals with recurrent MDD were used to describe the longitudinal effects of sleep duration, quality, and regularity on subsequent depression relapse and severity. METHODS: Data were collected as part of a longitudinal observational mobile Health (mHealth) cohort study in people with recurrent MDD. Participants wore a Fitbit device and completed regular outcome assessments via email for a median follow-up of 541 days. We used multivariable regression models to test the effects of sleep features on depression outcomes. We considered respondents with at least one assessment of relapse (n = 218) or at least one assessment of depression severity (n = 393). RESULTS: Increased intra-individual variability in total sleep time, greater sleep fragmentation, lower sleep efficiency, and more variable sleep midpoints were associated with worse depression outcomes. Adjusted Population Attributable Fractions suggested that an intervention to increase sleep consistency in adults with MDD could reduce the population risk for depression relapse by up to 22 %. LIMITATIONS: Limitations include a potentially underpowered primary outcome due to the smaller number of relapses identified than expected. CONCLUSION: Our study demonstrates a role for consumer-grade activity trackers in estimating relapse risk and depression severity in people with recurrent MDD. Variability in sleep duration and midpoint may be useful targets for stratified interventions.

Implementation and scalability of a digital intervention to reduce depressive symptoms in people with diabetes, hypertension or both in Brazil and Peru: a qualitative study of health system's stakeholders' perspectives.

Two randomized controlled trials (RCTs) in Brazil and Peru demonstrated the effectiveness of CONEMO, a digital intervention supported by trained nurses or nurse assistants (NAs), to reduce depressive symptoms in people with diabetes and/or hypertension. This paper extends the RCTs findings by reflecting on the conditions needed for its wider implementation in routine care services. A qualitative study using semi-structured interviews and content analysis was conducted with nurses/NAs, clinicians, healthcare administrators, and policymakers. Informants reported that CONEMO would be feasible to implement in their health services, but some conditions could be improved before its scale-up: reducing workloads of healthcare workers; raising mental health awareness among clinicians and administrators; being able to inform, deliver and accompany the intervention; assuring appropriate training and supervision of nurses/NAs; and supporting the use of technology in public health services and by patients, especially older ones. We discuss some suggestions on how to overcome these challenges.

Predictors of engagement with remote sensing technologies for symptom measurement in Major Depressive Disorder.

BACKGROUND: Remote sensing for the measurement and management of long-term conditions such as Major Depressive Disorder (MDD) is becoming more prevalent. User-engagement is essential to yield any benefits. We tested three hypotheses examining associations between clinical characteristics, perceptions of remote sensing, and objective user engagement metrics. METHODS: The Remote Assessment of Disease and Relapse - Major Depressive Disorder (RADAR-MDD) study is a multicentre longitudinal observational cohort study in people with recurrent MDD. Participants wore a FitBit and completed app-based assessments every two weeks for a median of 18 months. Multivariable random effects regression models pooling data across timepoints were used to examine associations between variables. RESULTS: A total of 547 participants (87.8% of the total sample) were included in the current analysis. Higher levels of anxiety were associated with lower levels of perceived technology ease of use; increased functional disability was associated with small differences in perceptions of technology usefulness and usability. Participants who reported higher system ease of use, usefulness, and acceptability subsequently completed more app-based questionnaires and tended to wear their FitBit activity tracker for longer. All effect sizes were small and unlikely to be of practical significance. LIMITATIONS: Symptoms of depression, anxiety, functional disability, and perceptions of system usability are measured at the same time. These therefore represent cross-sectional associations rather than predictions of future perceptions. CONCLUSIONS: These findings suggest that perceived usability and actual use of remote measurement technologies in people with MDD are robust across differences in severity of depression, anxiety, and functional impairment.

Treatment of depression is associated with suppression of nonspecific and antigen-specific T(H)1 responses in multiple sclerosis.

OBJECTIVE: To examine the relationship between depression, treatment of depression, and interferon gamma (IFN-gamma) production by peripheral blood mononuclear cells in patients with comorbid diagnoses of relapsing-remitting multiple sclerosis (MS) and major depressive disorder. DESIGN: A randomized comparative outcome trial of three 16-week treatments for depression. Assessments were conducted at baseline, week 8, and treatment cessation. SETTING: An academic outpatient treatment and clinical research center. PATIENTS: Fourteen patients who met the criteria for relapsing-remitting MS and major depressive disorder. INTERVENTIONS: Individual cognitive behavioral therapy, group psychotherapy, or sertraline therapy. MAIN OUTCOME MEASURES: Depression was assessed using the Beck Depression Inventory. Interferon gamma production by peripheral blood mononuclear cells was measured following stimulation with OKT3 or recombinant human myelin oligodendrocyte glycoprotein (MOG). Variability in immune assays was controlled using 8 nondepressed healthy subjects who were enrolled at times corresponding with the enrollment of MS patients. RESULTS: Results of the Beck Depression Inventory were significantly related to IFN-gamma production stimulated with OKT3 or MOG at baseline (P< or = .03 for all). Level of depression, OKT3-stimulated IFN-gamma production, and MOG-stimulated IFN-gamma production all declined significantly over the 16-week treatment period (P< or = .03 for all). Among controls, there were no significant changes over time in OKT3- or MOG-stimulated IFN-gamma, or in depression (P> or = .25 for all). CONCLUSIONS: These findings suggest that the production of the proinflammatory cytokine IFN-gamma by autoaggressive T cells in relapsing-remitting MS is related to depression and that treatment of depression may decrease IFN-gamma production. Thus, treatment of depression may provide a novel disease-modifying therapeutic strategy as well as a symptomatic treatment for patients with MS.

Treatment of depression improves adherence to interferon beta-1b therapy for multiple sclerosis.

OBJECTIVES: To examine the relationship between patient-reported depression and adherence to therapy with interferon beta-1b (IFN beta-1b) and to test the hypothesis that treatment of depression is associated with improved adherence. DESIGN: Patients with multiple sclerosis were followed up 6 months after initiating therapy with IFN beta-1b. SETTING: A university outpatient multiple sclerosis center, an academic group practice, and a health maintenance organization. PATIENTS: Eighty-five patients with clinically evident multiple sclerosis taking IFN beta-1b. MAIN OUTCOME MEASURE: Follow-up questionnaire. RESULTS: Thirty-five (41%) of the 85 patients reported new or increased depression within 6 months of initiating therapy with IFN beta-1b. Patients experiencing symptoms of depression were more likely to discontinue therapy. Among the patients reporting new or increased depression, 86% who received psychotherapy or antidepressant medication and 38% of the patients who received no therapy for depression continued the IFN beta-1b therapy (P = .003). Although psychotherapy was used as a treatment option more frequently in university and academic group practice-based multiple sclerosis clinics than in the health maintenance organization (P = .02), the treatment adherence patterns were similar across sites. CONCLUSIONS: These findings support previous findings that patients report increased depression after initiating therapy with IFN beta-1b. Although the source of this depression is unclear, these findings suggest that treating patient-reported depression increases adherence to treatment.

Course of depression during the initiation of interferon beta-1a treatment for multiple sclerosis.

OBJECTIVE: To examine the hypothesis that increases in depression after initiation of treatment with interferon beta-1a for multiple sclerosis can be explained as representing a return to pretreatment levels of depression. DESIGN: Level of depression in patients with multiple sclerosis was assessed at 3 time points: 2 weeks before initiation of interferon beta-la treatment, at initiation of treatment, and at 2-month follow-up. SETTING: A health maintenance organization. PATIENTS: Fifty-six patients with confirmed relapsing forms of multiple sclerosis. MAIN OUTCOME MEASURE: The depression-dejection scale of the Profile of Mood States. RESULTS: Patients who scored high on the depression measure 2 weeks before the initiation of interferon beta-1a treatment showed significant reduction in depression at the initiation of treatment. However, depression returned nearly to initial levels within 2 months. CONCLUSIONS: These findings suggest that increases in depression after initiation of interferon beta-1a treatment are related to level of depression 2 weeks before initiation of treatment. Physicians should assess history of depression for all patients in whom interferon beta-1a treatment is initiated. Patients with a recent history of depression are at risk for increased depression within 2 months after starting interferon beta-1a treatment, even though they may not be depressed at the time of treatment initiation.

Psychological stress and the subsequent appearance of new brain MRI lesions in MS.

OBJECTIVE: To examine the relationship between stressful life events and psychological distress, and the subsequent development of gadolinium-enhancing (Gd+) brain lesions. BACKGROUND: It has long been speculated that stressful life events and psychological distress are associated with disease exacerbation in MS. This is the first prospective longitudinal study of the relationship between stressful life events, psychological distress, and disease activity as measured by Gd+ brain MRI. METHODS: Thirty-six patients (mean age, 44.4 years; 22 women, 14 men) with relapsing forms of MS were assessed once every 4 weeks for 28 to 100 weeks. Assessments included Gd+ MRI, the Social Readjustment Rating Scale (SRRS), the Hassles Scale, and the Profile of Mood States. The SRRS was altered in the following manner: 1) three items that confounded with MS were eliminated, 2) endorsed items were rated for intensity, and 3) the scale was divided into three subscales: major negative events, conflict and disruption in routine, and positive life events. Data were analyzed using mixed-effects logistic regression to account for intrasubject correlations. Stress and distress measures were used to predict concurrent and future MRI activity. RESULTS: For the total sample of patients, increased conflict and disruption in routine was followed by increased odds of developing new Gd+ brain lesions 8 weeks later (odds ratio, 1.64; p = 0.00083). There was no strong evidence of a relationship between psychological stress or distress and clinical exacerbation. CONCLUSIONS: These data provide support for the notion that conflict and disruption in routine are related to subsequent disease activity in MS. However, this relationship is not sufficiently robust to predict clinical exacerbations reliably in individual patients.

The psychosocial impact of multiple sclerosis: exploring the patient's perspective.

This study examined subjective patient experiences of the psychosocial consequences of multiple sclerosis (MS). Fifty patients were interviewed regarding the effects MS had on their lives and interpersonal relationships. These statements were collated and administered with a 5-point Likert scale to 94 MS patients. The responses were subjected to factor analysis. Three areas of subjective patient experience of the psychosocial consequences of MS emerged: demoralization, benefit-finding, and deteriorated relationships. Of particular interest was benefit-finding, which included a deepening of relationships, enhanced appreciation of life, and an increase in spiritual interests. Although benefit-finding was related to adaptive coping strategies such as positive reappraisal and seeking social support, it was unrelated to depression and was related to higher levels of anxiety and anger. These findings indicate that benefit-finding is a substantial and poorly understood part of the illness experience for MS patients.

Comparative outcomes for individual cognitive-behavior therapy, supportive-expressive group psychotherapy, and sertraline for the treatment of depression in multiple sclerosis.

This study compared the efficacy of 3 16-week treatments for depression in 63 patients with multiple sclerosis (MS) and major depressive disorder (MDD): individual cognitive-behavioral therapy (CBT), supportive-expressive group therapy (SEG). and the antidepressant sertraline. Significant reductions were seen from pre- to posttreatment in all measures of depression. Intent-to-treat and completers analyses using the Beck Depression Inventory (BDI; A. T. Beck, C. H. Ward. M. Medelson. J. Mock, & J. Erbaugh, 1961) and MDD diagnosis found that CBT and sertraline were more effective than SEG at reducing depression. These results were largely supported by the BDI-18, which eliminates BDI items confounded with MS. However, the Hamilton Rating Scale for Depression (M. Hamilton, 1960) did not show consistent differences between treatments. Reasons for this inconsistency are discussed. These findings suggest that CBT or sertraline is more likely to be effective in treating MDD in MS compared with supportive group treatments.

Identification of patients at risk for nonresponse and negative outcome in psychotherapy.

This study evaluated the use of pretherapy patient variables as correlates of 3 categorical types of outcome: negative response (negative change of more than 1 normative SEest on depression measure); nonresponse (change within +/- 1 SEest on depression measure); and positive response (positive change of more than 1 SEest on depression measure) to psychotherapy among 62 patients with major depressive disorder. By using 4 scales from the Brief Symptom Inventory, the Inventory of Interpersonal Problems, age, and sex, 75.8% of the Ss were correctly classified into the 3 groups. Negative responders were characterized by high levels of interpersonal difficulty and low levels of subjective distress. Nonresponders displayed moderate levels of both interpersonal difficulties and subjective distress. Positive responders displayed high levels of both interpersonal difficulties and subjective distress.

Telephone-administered cognitive-behavioral therapy for the treatment of depressive symptoms in multiple sclerosis.

This study examined the efficacy of an 8-week telephone-administered cognitive-behavioral therapy (CBT) for the treatment of depressive symptomatology in multiple sclerosis (MS) patients. The treatment, Coping with MS (CMS), included a patient workbook designed to structure the treatment, provide visual aids, and help with homework assignments. Thirty-two patients with MS, who scored at least 15 on the Profile of Mood States Depression-Dejection scale, were randomly assigned to either the telephone CMS or to a usual-care control (UCC) condition. Depressive symptomatology decreased significantly in the CMS condition compared with the UCC condition. Furthermore, adherence to interferon beta-1a, a disease-modifying medication for the treatment of MS, was significantly better at the 4-month follow-up among patients who received CMS as compared with those in the UCC condition.

Blood transcriptomic biomarkers in adult primary care patients with major depressive disorder undergoing cognitive behavioral therapy.

An objective, laboratory-based diagnostic tool could increase the diagnostic accuracy of major depressive disorders (MDDs), identify factors that characterize patients and promote individualized therapy. The goal of this study was to assess a blood-based biomarker panel, which showed promise in adolescents with MDD, in adult primary care patients with MDD and age-, gender- and race-matched nondepressed (ND) controls. Patients with MDD received cognitive behavioral therapy (CBT) and clinical assessment using self-reported depression with the Patient Health Questionnaire-9 (PHQ-9). The measures, including blood RNA collection, were obtained before and after 18 weeks of CBT. Blood transcript levels of nine markers of ADCY3, DGKA, FAM46A, IGSF4A/CADM1, KIAA1539, MARCKS, PSME1, RAPH1 and TLR7, differed significantly between participants with MDD (N=32) and ND controls (N=32) at baseline (q< 0.05). Abundance of the DGKA, KIAA1539 and RAPH1 transcripts remained significantly different between subjects with MDD and ND controls even after post-CBT remission (defined as PHQ-9 <5). The ROC area under the curve for these transcripts demonstrated high discriminative ability between MDD and ND participants, regardless of their current clinical status. Before CBT, significant co-expression network of specific transcripts existed in MDD subjects who subsequently remitted in response to CBT, but not in those who remained depressed. Thus, blood levels of different transcript panels may identify the depressed from the nondepressed among primary care patients, during a depressive episode or in remission, or follow and predict response to CBT in depressed individuals.

Behavioral interventions in multiple sclerosis: a biopsychosocial perspective.

Managing uncertainty is a major challenge associated with the diagnosis of multiple sclerosis (MS). In addition to physical symptoms, neuropsychiatric symptoms are highly prevalent in this disease. Depression in particular is more common in MS than in other chronic diseases. While substantial achievements have been made in the therapy of MS and an increasing number of immunomodulatory treatments are now available, the long-term benefits of these are still a matter of debate. Importantly, while the approved therapies show good efficacy on inflammatory lesions and relapse rate, and may slow certain aspects of disease progression, improvements in function have rarely been reported. On the other hand, behavioral interventions have recently been shown to significantly improve fatigue and depression as well as motor function. In addition, recent evidence suggests that group education or face-to-face behavioral interventions may decrease inflammatory disease activity (such as relapse rate or lesion formation measured by MRI). Therefore, behavioral interventions not only ameliorate symptoms but may have the potential to modify the disease process itself.

Stress and the risk of multiple sclerosis.

OBJECTIVE: Several studies have shown that stressful life events are associated with a subsequent significant increase in risk of multiple sclerosis (MS) exacerbations. We wanted to study prospectively whether stress can increase the risk of developing the disease itself. METHODS: We studied 2 cohorts of female nurses: the Nurses' Health Study (NHS) (n = 121,700) followed from 1976 and the Nurses' Health Study II (NHS II) (n = 116,671) followed from 1989. The risk of MS after self-report on general stress at home and at work in the NHS in 1982 was studied prospectively using Cox regression. Logistic regression was used to retrospectively estimate the effects of physical and sexual abuse in childhood and adolescence collected in the NHS II 2001. We identified 77 cases of MS in the NHS by 2005 and 292 in the NHS II by 2004. All analyses were adjusted for age, ethnicity, latitude of birth, body mass index at age 18, and smoking. RESULTS: We found no increased risk of MS associated with severe stress at home in the NHS (hazard ratio 0.85 [95% confidence interval (CI)] 0.32-2.26). No significantly increased risk of MS was found among those who reported severe physical abuse during childhood (odds ratio [OR] 0.68, 95% CI 0.41-1.14) or adolescence (OR 0.77, 95% CI 0.46-1.28) or those having been repeatedly forced into sexual activity in childhood (OR 1.47, 95% CI 0.87-2.48) or adolescence (OR 1.21, 95% CI 0.68-2.17). CONCLUSIONS: These results do not support a major role of stress in the development of the disease, but repeated and more focused measures of stress are needed to firmly exclude stress as a potential risk factor for MS.

MS quality of life, depression, and fatigue improve after mindfulness training: a randomized trial.

OBJECTIVE: Health-related quality of life (HRQOL) is often much reduced among individuals with multiple sclerosis (MS), and incidences of depression, fatigue, and anxiety are high. We examined effects of a mindfulness-based intervention (MBI) compared to usual care (UC) upon HRQOL, depression, and fatigue among adults with relapsing-remitting or secondary progressive MS. METHODS: A total of 150 patients were randomly assigned to the intervention (n = 76) or to UC (n = 74). MBI consisted of a structured 8-week program of mindfulness training. Assessments were made at baseline, postintervention, and 6 months follow-up. Primary outcomes included disease-specific and disease-aspecific HRQOL, depression, and fatigue. Anxiety, personal goal attainment, and adherence to homework were secondary outcomes. RESULTS: Attrition was low in the intervention group (5%) and attendance rate high (92%). Employing intention-to-treat analysis, MBI, compared with UC, improved nonphysical dimensions of primary outcomes at postintervention and follow-up (p < 0.002); effect sizes, 0.4-0.9 posttreatment and 0.3-0.5 at follow-up. When analyses were repeated among subgroups with clinically relevant levels of preintervention depression, fatigue, or anxiety, postintervention and follow-up effects remained significant and effect sizes were larger than for the total sample. CONCLUSIONS: In addition to evidence of improved HRQOL and well-being, these findings demonstrate broad feasibility and acceptance of, as well as satisfaction and adherence with, a program of mindfulness training for patients with MS. The results may also have treatment implications for other chronic disorders that diminish HRQOL. CLASSIFICATION OF EVIDENCE: This trial provides Class III evidence that MBI compared with UC improved HRQOL, fatigue, and depression up to 6 months postintervention.