Effect of cognitive behavioural therapy and yoga for generalised anxiety disorder on sleep quality in a randomised controlled trial: the role of worry, mindfulness, and perceived stress as mediators.

Sleep disturbances are present in ~65% of individuals with generalised anxiety disorder (GAD). Although both Kundalini yoga (KY) and cognitive behavioural therapy (CBT) are effective treatment options for GAD, little is known about how these treatments compare in improving sleep for GAD and what drives these changes. Accordingly, we examined the effects of CBT, KY, and stress education (SEdu; an attention control condition) on subjective sleep quality (as measured by the Pittsburgh Sleep Quality Index [PSQI] and Insomnia Severity Index [ISI]) in a randomised controlled trial of 226 adults with GAD (mean age 33.37 years; 70% female; 79% White). We hypothesised that both CBT and KY would outperform SEdu in improving sleep disturbances. Three potential mediators of sleep improvement (worry, mindfulness, perceived stress) were also examined. In line with hypotheses, PSQI and ISI scores significantly improved from pre- to post-treatment for all three treatment groups (all p < 0.001, all d > 0.97). However, contrary to predictions, sleep changes were not significantly greater for CBT or KY compared to SEdu. In mediation analyses, within-person deviations in worry, mindfulness, and stress each significantly mediated the effect of time on sleep outcomes. Degree of change in sleep attributable to worry (CBT > KY > SEdu) and perceived stress (CBT, KY > SEdu) was moderated by treatment group. Personalised medicine as well as combined treatment approaches should be studied to help reduce sleep difficulties for patients with GAD who do not respond.

Attenuation of Anxiety-Potentiated Startle After Treatment With Escitalopram or Mindfulness Meditation in Anxiety Disorders.

BACKGROUND: Biological markers for anxiety disorders may further understanding of disorder pathophysiology and suggest potential targeted treatments. The fear-potentiated startle (FPS) (a measure of startle to predictable threat) and anxiety-potentiated startle (APS) (startle to unpredictable threat) laboratory paradigm has been used to detect physiological differences in individuals with anxiety disorders compared with nonanxious control individuals, and in pharmacological challenge studies in healthy adults. However, little is known about how startle may change with treatment for anxiety disorders, and no data are available regarding alterations due to mindfulness meditation training. METHODS: Ninety-three individuals with anxiety disorders and 66 healthy individuals completed 2 sessions of the neutral, predictable, and unpredictable threat task, which employs a startle probe and the threat of shock to assess moment-by-moment fear and anxiety. Between the two testing sessions, patients received randomized 8-week treatment with either escitalopram or mindfulness-based stress reduction. RESULTS: APS, but not FPS, was higher in participants with anxiety disorders compared with healthy control individuals at baseline. Further, there was a significantly greater decrease in APS for both treatment groups compared with the control group, with the patient groups showing reductions bringing them into the range of control individuals at the end of the treatment. CONCLUSIONS: Both anxiety treatments (escitalopram and mindfulness-based stress reduction) reduced startle potentiation during unpredictable (APS) but not predictable (FPS) threat. These findings further validate APS as a biological correlate of pathological anxiety and provide physiological evidence for the impact of mindfulness-based stress reduction on anxiety disorders, suggesting that there may be comparable effects of the two treatments on anxiety neurocircuitry.

Comparing Kundalini Yoga, cognitive behavioral therapy, and stress education for generalized anxiety disorder: Anxiety and depression symptom outcomes.

Increasingly, individuals with anxiety disorders are seeking mind-body interventions (e.g., yoga), but their effectiveness is unclear. This report summarizes seven additional, secondary outcomes measuring anxiety and depression symptoms from a study of 226 adults with generalized anxiety disorder who were randomized to 12-week Kundalini Yoga, Cognitive-Behavior Therapy (CBT) or stress education (control). At post-treatment, participants receiving CBT displayed significantly lower symptom severity, compared to those in the control group, on 6 of the 7 measures. Participants who received Yoga (vs. those in the control group) displayed lower symptom severity on 3 of the 7 measures. No significant differences were detected between participants receiving CBT vs those receiving Yoga. At the 6-month follow-up, participants from the CBT continued to display lower symptoms than the control group.

Mindfulness-Based Stress Reduction vs Escitalopram for the Treatment of Adults With Anxiety Disorders: A Randomized Clinical Trial.

Importance: Anxiety disorders are common, highly distressing, and impairing conditions. Effective treatments exist, but many patients do not access or respond to them. Mindfulness-based interventions, such as mindfulness-based stress reduction (MBSR) are popular and can decrease anxiety, but it is unknown how they compare to standard first-line treatments. Objective: To determine whether MBSR is noninferior to escitalopram, a commonly used first-line psychopharmacological treatment for anxiety disorders. Design, Setting, and Participants: This randomized clinical trial (Treatments for Anxiety: Meditation and Escitalopram [TAME]) included a noninferiority design with a prespecified noninferiority margin. Patients were recruited between June 2018 and February 2020. The outcome assessments were performed by blinded clinical interviewer at baseline, week 8 end point, and follow-up visits at 12 and 24 weeks. Of 430 individuals assessed for inclusion, 276 adults with a diagnosed anxiety disorder from 3 urban academic medical centers in the US were recruited for the trial, and 208 completed the trial. Interventions: Participants were 1:1 randomized to 8 weeks of the weekly MBSR course or the antidepressant escitalopram, flexibly dosed from 10 to 20 mg. Main Outcomes and Measures: The primary outcome measure was anxiety levels as assessed with the Clinical Global Impression of Severity scale (CGI-S), with a predetermined noninferiority margin of -0.495 points. Results: The primary noninferiority sample consisted of 208 patients (102 in MBSR and 106 in escitalopram), with a mean (SD) age of 33 (13) years; 156 participants (75%) were female; 32 participants (15%) were African American, 41 (20%) were Asian, 18 (9%) were Hispanic/Latino, 122 (59%) were White, and 13 (6%) were of another race or ethnicity (including Native American or Alaska Native, more than one race, or other, consolidated owing to low numbers). Baseline mean (SD) CGI-S score was 4.44 (0.79) for the MBSR group and 4.51 (0.78) for the escitalopram group in the per-protocol sample and 4.49 (0.77) vs 4.54 (0.83), respectively, in the randomized sample. At end point, the mean (SD) CGI-S score was reduced by 1.35 (1.06) for MBSR and 1.43 (1.17) for escitalopram. The difference between groups was -0.07 (0.16; 95% CI, -0.38 to 0.23; P = .65), where the lower bound of the interval fell within the predefined noninferiority margin of -0.495, indicating noninferiority of MBSR compared with escitalopram. Secondary intent-to-treat analyses using imputed data also showed the noninferiority of MBSR compared with escitalopram based on the improvement in CGI-S score. Of patients who started treatment, 10 (8%) dropped out of the escitalopram group and none from the MBSR group due to adverse events. At least 1 study-related adverse event occurred for 110 participants randomized to escitalopram (78.6%) and 21 participants randomized to MBSR (15.4%). Conclusions and Relevance: The results from this randomized clinical trial comparing a standardized evidence-based mindfulness-based intervention with pharmacotherapy for the treatment of anxiety disorders found that MBSR was noninferior to escitalopram. Trial Registration: ClinicalTrials.gov Identifier: NCT03522844.

Targeting Anxiety to Improve Sleep Disturbance: A Randomized Clinical Trial of App-Based Mindfulness Training.

OBJECTIVE: Sleep disturbance is experienced by nearly 20% of Americans and is highly comorbid with anxiety. Sleep disturbances may predict the development of anxiety disorders. Mindfulness training (MT) has shown efficacy for anxiety yet remains limited by in-person-based delivery. Digitally delivered MT may target habitual worry processes, yet its effects on sleep have not been studied. This study tested if app-based MT for anxiety could reduce worry and improve sleep and examined the underlying mechanisms. METHODS: Individuals reporting worry interfering with sleep were randomized to treatment as usual (TAU; n = 40) or TAU + app-based MT (n = 40). Treatment-related changes in worry-related sleep disturbances (WRSDs), worry, nonreactivity, and anxiety were evaluated via self-report questionnaires at 1 and 2 months after treatment initiation. Fitbit devices were used to record total sleep time and estimate sleep efficiency. At 2 months, TAU received access to app-based MT, and both groups were reassessed at 4 months. RESULTS: In a modified intent-to-treat analysis, WRSD scores decreased by 27% in TAU + MT (n = 36) and 6% in TAU (n = 35) at 2 months (median [IQR] change = 11 [4.3] versus 15 [5.0], p = .001). These WRSD reductions were mediated by decreased worry, particularly improved nonreactivity (p values < .001). At 4 months, TAU reported a significant 29% reduction after beginning app-based MT at 2 months and TAU + MT maintained its gains. No significant between-group differences in average estimated total sleep time or sleep efficiency were found after 2 months of using the app. CONCLUSIONS: Few mindfulness-related apps have been evaluated for clinical efficacy and/or mechanism. Results from this study demonstrate a mechanistic link between MT and increased emotional nonreactivity, decreased worry, and reduction in reported sleep disturbances, suggesting that app-based MT may be a viable option to help individuals who report that worry interferes with their sleep.Trial Registration: ClinicalTrials.gov identifier: NCT03684057.

Clinical Efficacy and Psychological Mechanisms of an App-Based Digital Therapeutic for Generalized Anxiety Disorder: Randomized Controlled Trial.

BACKGROUND: Current treatments for generalized anxiety disorder (GAD) often yield suboptimal outcomes, partly because of insufficient targeting of underlying psychological mechanisms (eg, avoidance reinforcement learning). Mindfulness training (MT) has shown efficacy for anxiety; yet, widespread adoption has been limited, partly because of the difficulty in scaling in-person-based delivery. Digital therapeutics are emerging as potentially viable treatments; however, very few have been empirically validated. OBJECTIVE: The aim of this study is to test the efficacy and mechanism of an app-delivered MT that was designed to target a potential mechanism of anxiety (reinforcement learning), based on which previous studies have shown concern regarding feedback and the perpetuation of anxiety through negative reinforcement. METHODS: Individuals with GAD were recruited using social media advertisements and randomized during an in-person visit to receive treatment as usual (n=33) or treatment as usual+app-delivered MT (Unwinding Anxiety; n=32). The latter was composed of 30 modules to be completed over a 2-month period. Associated changes in outcomes were assessed using self-report questionnaires 1 and 2 months after treatment initiation. RESULTS: We randomized 65 participants in this study, and a modified intent-to-treat approach was used for analysis. The median number of modules completed by the MT group was 25.5 (IQR 17) out of 30; 46% (13/28) of the participants completed the program. In addition, the MT group demonstrated a significant reduction in anxiety (GAD-7) compared with the control group at 2 months (67% vs 14%; median change in GAD-7: -8.5 [IQR 6.5] vs -1.0 [IQR 5.0]; P<.001; 95% CI 6-10). Increases in mindfulness at 1 month (nonreactivity subscale) mediated decreases in worry at 2 months (Penn State Worry Questionnaire; P=.02) and decreases in worry at 1 month mediated reductions in anxiety at 2 months (P=.03). CONCLUSIONS: To our knowledge, this is the first report on the efficacy and mechanism of an app-delivered MT for GAD. These findings demonstrate the clinical efficacy of MT as a digital therapeutic for individuals with anxiety (number needed to treat=1.6). These results also link recent advances in our mechanistic understanding of anxiety with treatment development, showing that app-delivered MT targets key reinforcement learning pathways, resulting in tangible, clinically meaningful reductions in worry and anxiety. Evidence-based, mechanistically targeted digital therapeutics have the potential to improve health at a population level at a low cost. TRIAL REGISTRATION: ClinicalTrials.gov NCT03683472; https://clinicaltrials.gov/ct2/show/NCT03683472.

Mind-Body Interventions for Anxiety Disorders: A Review of the Evidence Base for Mental Health Practitioners.

Mind-body interventions have gained increasing popularity for use with anxiety symptoms; however, it is unclear what role they play in the treatment of anxiety disorders, such as generalized anxiety disorder, panic disorder, and social anxiety disorder. Although psychopharmacology and psychotherapy treatment interventions are available, mind-body interventions may be low-stigma options that can serve as effective alternatives. The goal of this review is to provide clinicians with an overview of high-quality studies for the most well researched mind-body interventions. This review involved a search of the primary literature, including meta-analyses, systematic reviews, and randomized controlled trials (RCTs), that evaluated mind-body interventions for the treatment of anxiety disorders. When published evidence was limited, lower-quality studies were reviewed. Overall, data were limited on the efficacy of most mind-body modalities for anxiety disorders. The highest-quality data existed for yoga, mindfulness-based interventions, and applied relaxation for anxiety disorders. However, findings were sometimes inconsistent across studies, and some studies were limited by small sample sizes, poorly defined randomization and blinding procedures, and inadequate control groups. Although not enough data exist to recommend mind-body interventions as primary treatment options, they may be considered as part of a larger treatment plan given their relatively low levels of risk. Future steps for researchers include conducting additional RCTs with adequate control groups, comparing mind-body treatments with existing treatments, and examining long-term effects of mind-body interventions.

Emotion-related constructs engaged by mindfulness-based interventions: A systematic review and meta-analysis.

OBJECTIVES: Mindfulness-based interventions (MBIs) have been widely implemented to improve self-regulation behaviors, often by targeting emotion-related constructs to facilitate change. Yet the degree to which MBIs engage specific measures of emotion-related constructs has not been systematically examined. METHODS: Using advanced meta-analytic techniques, this review examines construct and measurement engagement in trials of adults that used standardized applications of the two most established MBIs: Mindfulness-Based Stress Reduction (MBSR) and Mindfulness-Based Cognitive Therapy (MBCT), or modified variations of these interventions that met defined criteria. RESULTS: Seventy-two studies (N=7,378) were included (MBSR k=47, MBCT k = 21, Modified k=4). MBIs led to significant improvement in emotion-related processing overall, compared to inactive controls (d=0.58; k =36), and in all constructs assessed: depression (d=0.66; k=26), anxiety (d =0.63; k=19), combined mental health (d =0.75; k=7 ) and stress (d =0.44; k=11). Reactions to pain, mood states, emotion regulation, and biological measures lacked sufficient data for analysis. MBIs did not outperform active controls in any analyses. Measurement tool and population-type did not moderate results, but MBI-type did, in that MBCT showed stronger effects than MBSR, although these effects were driven by a small number of studies. CONCLUSIONS: This review is the first to examine the full scope of emotion-related measures relevant to self-regulation, to determine which measures are most influenced by MBCT/MBSR. Compared to extant reviews, which typically focused on MBI outcomes, this work examined mechanistic processes based on measurement domains and tools. While effect sizes were similar among measurement tools, this review also includes a descriptive evaluation of measures and points of caution, providing guidance to MBI researchers and clinicians for selection of emotion-related measurement tools.

Efficacy of Yoga vs Cognitive Behavioral Therapy vs Stress Education for the Treatment of Generalized Anxiety Disorder: A Randomized Clinical Trial.

Importance: Generalized anxiety disorder (GAD) is common, impairing, and undertreated. Although many patients with GAD seek complementary and alternative interventions, including yoga, data supporting yoga's efficacy or how it compares to first-line treatments are lacking. Objectives: To assess whether yoga (Kundalini yoga) and cognitive behavioral therapy (CBT) for GAD are each more effective than a control condition (stress education) and whether yoga is noninferior to CBT for the treatment of GAD. Design, Setting, and Participants: For this randomized, 3-arm, controlled, single-blind (masked independent raters) clinical trial, participants were recruited from 2 specialty academic centers starting December 1, 2013, with assessment ending October 25, 2019. Primary analyses, completed by February 12, 2020, included superiority testing of Kundalini yoga and CBT vs stress education and noninferiority testing of Kundalini yoga vs CBT. Interventions: Participants were randomized to Kundalini yoga (n = 93), CBT for GAD (n = 90), or stress education (n = 43), which were each delivered to groups of 4 to 6 participants by 2 instructors during twelve 120-minute sessions with 20 minutes of daily homework. Main Outcomes and Measures: The primary intention-to-treat outcome was acute GAD response (Clinical Global Impression-Improvement Scale score of much or very much improved) after 12 weeks as assessed by trained independent raters. Results: Of 538 participants who provided consent and were evaluated, 226 (mean [SD] age, 33.4 [13.5] years; 158 [69.9%] female) with a primary diagnosis of GAD were included in the trial. A total of 155 participants (68.6%) completed the posttreatment assessment. Completion rates did not differ (Kundalini yoga, 60 [64.5%]; CBT, 67 [74.4%]; and stress education, 28 [65.1%]: χ2 = 2.39, df = 2, P = .30). Response rates were higher in the Kundalini yoga group (54.2%) than in the stress education group (33.%) (odds ratio [OR], 2.46 [95% CI, 1.12-5.42]; P = .03; number needed to treat, 4.59 [95% CI, 2.52-46.19]) and in the CBT group (70.8%) compared with the stress education group (33.0%) (OR, 5.00 [95% CI, 2.12-11.82]; P < .001; number needed to treat, 2.62 [95% CI, 1.91-5.68]). However, the noninferiority test did not find Kundalini yoga to be as effective as CBT (difference, 16.6%; P = .42 for noninferiority). Conclusions and Relevance: In this trial, Kundalini yoga was efficacious for GAD, but the results support CBT remaining first-line treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT01912287.

Can mindfulness mechanistically target worry to improve sleep disturbances? Theory and study protocol for app-based anxiety program.

OBJECTIVE: Anxiety is associated with sleep disturbance and insomnia. Mindfulness-based interventions, such as mindfulness-based stress reduction, have shown consistent anxiety reduction. Mindfulness training has been theorized to affect reinforcement learning, affecting habitual behaviors such as smoking and overeating, but a direct mechanistic link between the use of mindfulness training for anxiety reduction and improvement in sleep has not been studied. Moreover, the mechanisms by which mindfulness might affect worry and subsequent sleep disturbances have not been elucidated. This study protocol evaluates the impact an app-based mindfulness training program for anxiety might have on decreasing worry and improvement in sleep. METHOD: A randomized controlled study will be conducted in approximately 80 adults with worry that interferes with their sleep. Participants will be randomly allocated (1:1) to two groups: treatment-as-usual (TAU) or TAU + App-Based Mindfulness Training (Unwinding Anxiety app). The primary outcomes will be the non-reactivity subscale of the Five Facet Mindfulness Questionnaire and Patient-Reported Outcomes Measurement Information System sleep quality measures (Baer et al., 2008; Yu et al., 2011). Secondary outcomes will include the Penn State Worry Questionnaire, Generalized Anxiety Disorder-7, and Multidimensional Assessment of Interoceptive Awareness Scale (Mehling et al., 2012; Meyer, Miller, Metzger, & Borkovec, 1990; Spitzer, Kroenke, Williams, & Löwe, 2006). DISCUSSION: This study will be the first to test the mechanism of app-based mindfulness training on worry and sleep disturbance. Testing the mechanistic effects of mindfulness training using the science of behavior change framework will help move the field forward both in further elucidation of potential mechanisms of mindfulness (e.g., targeting reinforcement learning) and determining whether such a platform might be a viable method for delivering high-fidelity treatment at scale and for a low cost. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Physician Anxiety and Burnout: Symptom Correlates and a Prospective Pilot Study of App-Delivered Mindfulness Training.

BACKGROUND: Physician burnout is on the rise, yet little is known about its relationship to anxiety. Mindfulness-based stress reduction has demonstrated decreases in anxiety, yet physicians have reported reluctance to engage in it due to significant time commitments. OBJECTIVE: The aims of this study are to assess whether app-based mindfulness training can reduce anxiety in physicians and to explore if anxiety and burnout are correlated, thus leading to a reduction in both anxiety and burnout. METHODS: This was a nonrandomized pilot study comprised of 34 physicians who worked in a large US health care network and reported having anxiety. The intervention was an app-based mindfulness program. The main outcome measure was anxiety, measured by the Generalized Anxiety Disorder-7 (GAD-7). The secondary outcome measures assessed burnout: cynicism and emotional exhaustion items from the Maslach Burnout Inventory. RESULTS: GAD-7 scores decreased significantly at posttreatment (1 month after treatment initiation, 48% reduction, P<.001) and at the 3-month follow-up (57% reduction, P<.001). There was a significant correlation between anxiety and burnout (cynicism: r=.43; P=.01; emotional exhaustion: r=.71; P<.001). There was also a significant decrease in cynicism (50% reduction, P=.003 at posttreatment; 50% reduction, P=.009 at follow-up) and emotional exhaustion at both time points (20% reduction, P<.001 at posttreatment; 20% reduction, P=.003 at follow-up). CONCLUSIONS: This pilot study is the first to test an app-based mindfulness training program targeted at reducing anxiety with physicians and to demonstrate that in physicians, anxiety is correlated with burnout. These findings suggest that this may be an effective tool to reduce anxiety and burnout in physicians. TRIAL REGISTRATION: ClinicalTrials.gov NCT04137081; https://www.clinicaltrials.gov/ct2/show/NCT04137081.

Investigating the Role of Interpretation Bias in Mindfulness-Based Treatment of Adults With Generalized Anxiety Disorder.

Although mindfulness-based interventions (MBIs) have garnered empirical support for a wide range of psychological conditions, the psychological processes that mediate the relationship between MBIs and subsequent symptomatic improvement are less well-understood. In the present study we sought to examine, for the first time, the relationship between mindfulness, negative interpretation bias as measured by the homophone task, and anxiety among adults with Generalized Anxiety Disorder (GAD). Forty-two individuals with GAD completed measures of mindfulness, interpretation bias, and anxiety before and after treatment with Mindfulness-based Stress Reduction (MBSR). Contrary to prior research, we did not find evidence of an indirect relationship between baseline levels of mindfulness and anxiety via negative interpretation bias. MBSR did result in significant reductions in negative interpretation bias from baseline to post-treatment; however, we did not find evidence of an indirect relationship between changes in mindfulness and changes in anxiety via changes in interpretation bias. Taken together, these results provide minimal support for the hypothesized relationship between mindfulness, negative interpretation bias, and anxiety among adults with GAD. Limitations and specific suggestions for further inquiry are discussed.

Treatment for anxiety: Mindfulness meditation versus escitalopram (TAME): Design of a randomized, controlled non-inferiority trial.

Anxiety disorders (generalized anxiety disorder, social anxiety disorder, panic disorder, and agoraphobia) are common, distressing, and impairing. While pharmacotherapy and psychotherapy are first-line treatment strategies for anxiety disorders, many patients are reluctant to take psychiatric medication, and many prefer to avoid any kind of mental health treatment due to stigma or distrust of traditional medical care. We present the trial protocol for the first study comparing first-line medication treatment with Mindfulness-Based Stress Reduction (MBSR), a popular mindfulness meditation training program, for the treatment of anxiety disorders. We will use a non-inferiority, comparative effectiveness trial design, in which individuals with diagnosed anxiety disorders will be randomized to either pharmacotherapy with escitalopram or MBSR for 8 weeks of treatment. Treatment outcome will be based on gold standard symptom severity measures assessed by trained independent evaluators blind to treatment allocation. Secondary outcomes will include key symptom and function measures, as well as tolerability and satisfaction with treatment. Findings will provide crucial information to inform decision making about the relative benefits of MBSR versus a first line medication for anxiety disorders by patients, medical care providers, healthcare insurers and other stakeholders.

Considerations for mood and emotion measures in mindfulness-based intervention research.

A large and growing body of work has examined the effects of Mindfulness-Based Interventions (MBI's), such as Mindfulness-Based Stress Reduction and Mindfulness-Based Cognitive Therapy, on emotion-related outcomes, both in mental health settings and general populations. These studies vary widely in the approach to measurement of emotion-related measurements after MBI's. A systematic review of randomized clinical trials of MBIs was conducted with a focus on identifying what emotion-related assays were able to detect changes with MBI's, including scales and instruments (both self-report and clinician-rated) on constructs such as depression, anxiety, emotion regulation, and other mood states. In this paper, we reflect on these findings and discuss considerations of outcome measures in MBI research. There are previously established practices for clinical trials research on emotion-related outcomes which may provide some useful methodological standards and study design options for use by the MBI research field.

Prospective association between major depressive disorder and leukocyte telomere length over two years.

BACKGROUND: Reduced leukocyte telomere length (LTL) has been found to be associated with multiple common age-related diseases, including heart disease, diabetes, and cancer. A link has also been suggested between shortened LTL and major depressive disorder (MDD), suggesting that MDD may be a disease of accelerated aging. This prospective, longitudinal study examined the association between depression diagnosis at baseline and change in LTL over two years in a well-characterized sample of N = 117 adults with or without MDD at baseline, using rigorous entry criteria. METHODS: Participants aged 18-70 were assessed with validated instruments by trained, doctoral-level clinician raters at baseline and at two-year follow-up, and blood samples were obtained at both visits. LTL was assayed under identical methods using quantitative polymerase chain reaction (qPCR). The effect of an MDD diagnosis at baseline on change in LTL over two years was examined via hierarchical mixed models, which included potential confounders. RESULTS: Individuals with MDD at baseline had greater LTL shortening over two years than individuals without MDD (p = 0.03), even after controlling for differences in age, sex, and body mass index (BMI). In the sub-sample of individuals with MDD diagnoses at baseline, no significant associations between LTL change and symptom severity or duration were found. CONCLUSION: A baseline diagnosis of MDD prospectively predicted LTL shortening over two years. Our results provide further support for MDD as a disease associated with accelerated aging in a well-characterized sample using validated, clinician-rated measures.

The effect of mindfulness meditation training on biological acute stress responses in generalized anxiety disorder.

Mindfulness-Based interventions have increased in popularity in psychiatry, but the impact of these treatments on disorder-relevant biomarkers would greatly enhance efficacy and mechanistic evidence. If Generalized Anxiety Disorder (GAD) is successfully treated, relevant biomarkers should change, supporting the impact of treatment and suggesting improved resilience to stress. Seventy adults with GAD were randomized to receive either Mindfulness-Based Stress Reduction (MBSR) or an attention control class; before and after, they underwent the Trier Social Stress Test (TSST). Area-Under-the-Curve (AUC) concentrations were calculated for adrenocorticotropic hormone (ACTH) and pro-inflammatory cytokines. MBSR participants had a significantly greater reduction in ACTH AUC compared to control participants. Similarly, the MBSR group had a greater reduction in inflammatory cytokines' AUC concentrations. We found larger reductions in stress markers for patients with GAD in the MBSR class compared to control; this provides the first combined hormonal and immunological evidence that MBSR may enhance resilience to stress.

A Randomized Controlled Pilot Study on Mindfulness-Based Cognitive Therapy for Unipolar Depression in Patients With Chronic Pain.

OBJECTIVE: Chronic pain is a disabling illness, often comorbid with depression. We performed a randomized controlled pilot study on mindfulness-based cognitive therapy (MBCT) targeting depression in a chronic pain population. METHOD: Participants with chronic pain lasting ≥ 3 months; DSM-IV major depressive disorder (MDD), dysthymic disorder, or depressive disorder not otherwise specified; and a 16-item Quick Inventory of Depressive Symptomatology-Clinician Rated (QIDS-C16) score ≥ 6 were randomly assigned to MBCT (n = 26) or waitlist (n = 14). We adapted the original MBCT intervention for depression relapse prevention by modifying the psychoeducation and cognitive-behavioral therapy elements to an actively depressed chronic pain population. We analyzed an intent-to-treat (ITT) and a per-protocol sample; the per-protocol sample included participants in the MBCT group who completed at least 4 of 8 sessions. Changes in scores on the QIDS-C16 and 17-item Hamilton Depression Rating Sale (HDRS17) were the primary outcome measures. Pain, quality of life, and anxiety were secondary outcome measures. Data collection took place between January 2012 and July 2013. RESULTS: Nineteen participants (73%) completed the MBCT program. No significant adverse events were reported in either treatment group. ITT analysis (n = 40) revealed no significant differences. Repeated-measures analyses of variance for the per-protocol sample (n = 33) revealed a significant treatment × time interaction (F1,31 = 4.67, P = .039, η²p = 0.13) for QIDS-C16 score, driven by a significant decrease in the MBCT group (t18 = 5.15, P < .001, d = >1.6), but not in the control group (t13 = 2.01, P = .066). The HDRS17 scores did not differ significantly between groups. The study ended before the projected sample size was obtained, which might have prevented effect detection in some outcome measures. CONCLUSIONS: MBCT shows potential as a treatment for depression in individuals with chronic pain, but larger controlled trials are needed. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01473615.

Effects of mindfulness meditation on occupational functioning and health care utilization in individuals with anxiety.

OBJECTIVES: To examine the effect of mindfulness meditation on occupational functioning in individuals with Generalized anxiety disorder (GAD). METHODS: Fifty-seven individuals with GAD (mean (SD) age=39 (13); 56% women) participated in an 8-week clinical trial in which they were randomized to mindfulness-based stress reduction (MBSR) or an attention control class. In this secondary analysis, absenteeism, entire workdays missed, partial workdays missed, and healthcare utilization patterns were assessed before and after treatment. RESULTS: Compared to the attention control class, participation in MBSR was associated with a significantly greater decrease in partial work days missed for adults with GAD (t=2.734, df=51, p=0.009). Interestingly, a dose effect was observed during the 24-week post-treatment follow-up period: among MBSR participants, greater home mindfulness meditation practice was associated with less work loss and with fewer mental health professional visits. CONCLUSION: Mindfulness meditation training may improve occupational functioning and decrease healthcare utilization in adults with GAD.

Inflammatory cytokines in major depressive disorder: A case-control study.

INTRODUCTION: There is mixed evidence in the literature on the role of inflammation in major depressive disorder. Contradictory findings are attributed to lack of rigorous characterization of study subjects, to the presence of concomitant medical illnesses, to the small sample sizes, and to the limited number of cytokines tested. METHODS: Subjects aged 18-70 years, diagnosed with major depressive disorder and presenting with chronic course of illness, as well as matched controls ( n = 236), were evaluated by trained raters and provided blood for cytokine measurements. Cytokine levels in EDTA plasma were measured with the MILLIPLEX Multi-Analyte Profiling Human Cytokine/Chemokine Assay employing Luminex technology. The Wilcoxon rank-sum test was used to compare cytokine levels between major depressive disorder subjects and healthy volunteers, before (interleukin [IL]-1ß, IL-6, and tumor necrosis factor-α) and after Bonferroni correction for multiple comparisons (IL-1α, IL-2, IL-3, IL-4, IL-5, IL-7, IL-8, IL-10, IL-12(p40), IL-12(p70), IL-13, IL-15, IFN-γ-inducible protein 10, Eotaxin, interferon-γ, monotype chemoattractant protein-1, macrophage inflammatory protein-1α, granulocyte-macrophage colony-stimulating factor and vascular endothelial growth factor). RESULTS: There were no significant differences in cytokine levels between major depressive disorder subjects and controls, both prior to and after correction for multiple analyses (significance set at p ⩽ 0.05 and p ⩽ 0.002, respectively). CONCLUSION: Our well-characterized examination of cytokine plasma levels did not support the association of major depressive disorder with systemic inflammation. The heterogeneity of major depressive disorder, as well as a potential sampling bias selecting for non-inflammatory depression, might have determined our findings discordant with the literature.