The effects of mindfulness-based cognitive therapy on affective memory recall dynamics in depression:A mechanistic model of rumination

Objectives: converging research suggests that mindfulness training exerts its therapeutic effects on depression by reducing rumination. Theoretically, rumination is a multifaceted construct that aggregates multiple neurocognitive aspects of depression, including poor executive control, negative and overgeneral memory bias, and persistence or stickiness of negative mind states. Current measures of rumination, most-often self-reports, do not capture these different aspects of ruminative tendencies, and therefore are limited in providing detailed information about the mechanisms of mindfulness. Methods: we developed new insight into the potential mechanisms of rumination, based on three model-based metrics of free recall dynamics. These three measures reflect the patterns of memory retrieval of valenced information: the probability of first recall (Pstart) which represents initial affective bias, the probability of staying with the same valence category rather than switching, which indicates strength of positive or negative association networks (Pstay), and probability of stopping (Pstop) or ending recall within a given valence, which indicates persistence or stickiness of a mind state. We investigated the effects of Mindfulness-Based Cognitive Therapy (MBCT; N = 29) vs. wait-list control (N = 23) on these recall dynamics in a randomized controlled trial in individuals with recurrent depression. Participants completed a standard laboratory stressor, the Trier Social Stress Test, to induce negative mood and activate ruminative tendencies. Following that, participants completed a free recall task consisting of three word lists. This assessment was conducted both before and after treatment or wait-list. Results: while MBCT participant’s Pstart remained relatively stable, controls showed multiple indications of depression-related deterioration toward more negative and less positive bias. Following the intervention, MBCT participants decreased in their tendency to sustain trains of negative words and increased their tendency to sustain trains of positive words. Conversely, controls showed the opposite tendency: controls stayed in trains of negative words for longer, and stayed in trains of positive words for less time relative to pre-intervention scores. MBCT participants tended to stop recall less often with negative words, which indicates less persistence or stickiness of negatively valenced mental context. Conclusion: MBCT participants showed a decrease in patterns that may perpetuate rumination on all three types of recall dynamics (Pstart, Pstay, and Pstop), compared to controls. MBCT may weaken the strength of self-perpetuating negative associations networks that are responsible for the persistent and “sticky” negative mind states observed in depression, and increase the positive associations that are lacking in depression. This study also offers a novel, objective method of measuring several indices of ruminative tendencies indicative of the underlying mechanisms of rumination

The contributions of focused attention and open monitoring in mindfulness-based cognitive therapy for affective disturbances: A 3-armed randomized dismantling trial

OBJECTIVE: Mindfulness-based cognitive therapy (MBCT) includes a combination of focused attention (FA) and open monitoring (OM) meditation practices. The aim of this study was to assess both short- and long-term between- and within-group differences in affective disturbance among FA, OM and their combination (MBCT) in the context of a randomized controlled trial. METHOD: One hundred and four participants with mild to severe depression and anxiety were randomized into one of three 8-week interventions: MBCT (n = 32), FA (n = 36) and OM (n = 36). Outcome measures included the Inventory of Depressive Symptomatology (IDS), and the Depression Anxiety Stress Scales (DASS). Mixed effects regression models were used to assess differential treatment effects during treatment, post-treatment (8 weeks) and long-term (20 weeks). The Reliable Change Index (RCI) was used to translate statistical findings into clinically meaningful improvements or deteriorations. RESULTS: All treatments demonstrated medium to large improvements (ds = 0.42-1.65) for almost all outcomes. While all treatments were largely comparable in their effects at post-treatment (week 8), the treatments showed meaningful differences in rapidity of response and pattern of deteriorations. FA showed the fastest rate of improvement and the fewest deteriorations on stress, anxiety and depression during treatment, but a loss of treatment-related gains and lasting deteriorations in depression at week 20. OM showed the slowest rate of improvement and lost treatment-related gains for anxiety, resulting in higher anxiety in OM at week 20 than MBCT (d = 0.40) and FA (d = 0.36), though these differences did not reach statistical significance after correcting for multiple comparisons (p\u27s = .06). MBCT and OM showed deteriorations in stress, anxiety and depression at multiple timepoints during treatment, with lasting deteriorations in stress and depression. MBCT showed the most favorable pattern for long-term treatment of depression. CONCLUSIONS: FA, OM and MBCT show different patterns of response for different dimensions of affective disturbance. TRIAL REGISTRATION: This trial is registered at (v NCT01831362); www.clinicaltrials.gov

Development and Validation of the Behavioral Tendencies Questionnaire

At a fundamental level, taxonomy of behavior and behavioral tendencies can be described in terms of approach, avoid, or equivocate (i.e., neither approach nor avoid). While there are numerous theories of personality, temperament, and character, few seem to take advantage of parsimonious taxonomy. The present study sought to implement this taxonomy by creating a questionnaire based on a categorization of behavioral temperaments/tendencies first identified in Buddhist accounts over fifteen hundred years ago. Items were developed using historical and contemporary texts of the behavioral temperaments, described as “Greedy/Faithful”, “Aversive/Discerning”, and “Deluded/Speculative”. To both maintain this categorical typology and benefit from the advantageous properties of forced-choice response format (e.g., reduction of response biases), binary pairwise preferences for items were modeled using Latent Class Analysis (LCA). One sample (n1 = 394) was used to estimate the item parameters, and the second sample (n2 = 504) was used to classify the participants using the established parameters and cross-validate the classification against multiple other measures. The cross-validated measure exhibited good nomothetic span (construct-consistent relationships with related measures) that seemed to corroborate the ideas present in the original Buddhist source documents. The final 13-block questionnaire created from the best performing items (the Behavioral Tendencies Questionnaire or BTQ) is a psychometrically valid questionnaire that is historically consistent, based in behavioral tendencies, and promises practical and clinical utility particularly in settings that teach and study meditation practices such as Mindfulness Based Stress Reduction (MBSR)

The effect of 6-mercaptopurine on natural killer-cell activities in Crohn's disease

Crohn's disease patients on long-term 6-mercaptopurine therapy (more than 4 months) were evaluated for activity of peripheral blood natural killer cells. Natural killer-cell cytolytic activity against K-562 tumor-cell targets was examined, as was natural killer-cell suppression of lymphoblastoid B-cell antibody production. In addition, these patients were studied for their ability to generate antitetanus-specific IgG antibody-producing lymphoblastoid B cells following in vivo booster immunization. Crohn's disease patients on 6-mercaptopurine therapy had significant reductions in peripheral blood natural killer-cell activity against K-562 targets compared to normals, disease controls, and Crohn's disease patients not on 6-mercaptopurine. Natural killer-cell suppression of lymphoblastoid B-cell antibody production was like-wise decreased in 6-mercaptopurine-treated patients compared to normal controls. In contrast, the in vivo generated lymphoblastoid B-cell antibody responses of Crohn's disease patients on 6-mercaptopurine therapy were not decreased compared to normal, while Crohn's disease patients not on 6-mercaptopurine therapy had significantly impaired IgG antitetanus antibody responses. These findings suggest that 6-mercaptopurine therapy in Crohn's disease affects several lymphoid subpopulations, resulting in a decreased natural killer-cell cytotoxic activity against K-562 target cells and a decreased natural killer-cell ability to suppress lymphoblastoid B-cell antibody production, as well as an improved humoral immune response following tetanus toxoid booster immunization.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44846/1/10875_2004_Article_BF00915512.pd

The Effect of Mindfulness-based Programs on Cognitive Function in Adults: A Systematic Review and Meta-analysis.

peer reviewedMindfulness-based programs (MBPs) are increasingly utilized to improve mental health. Interest in the putative effects of MBPs on cognitive function is also growing. This is the first meta-analysis of objective cognitive outcomes across multiple domains from randomized MBP studies of adults. Seven databases were systematically searched to January 2020. Fifty-six unique studies (n = 2,931) were included, of which 45 (n = 2,238) were synthesized using robust variance estimation meta-analysis. Meta-regression and subgroup analyses evaluated moderators. Pooling data across cognitive domains, the summary effect size for all studies favored MBPs over comparators and was small in magnitude (g = 0.15; [0.05, 0.24]). Across subgroup analyses of individual cognitive domains/subdomains, MBPs outperformed comparators for executive function (g = 0.15; [0.02, 0.27]) and working memory outcomes (g = 0.23; [0.11, 0.36]) only. Subgroup analyses identified significant effects for studies of non-clinical samples, as well as for adults aged over 60. Across all studies, MBPs outperformed inactive, but not active comparators. Limitations include the primarily unclear within-study risk of bias (only a minority of studies were considered low risk), and that statistical constraints rendered some p-values unreliable. Together, results partially corroborate the hypothesized link between mindfulness practices and cognitive performance. This review was registered with PROSPERO [CRD42018100904]

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

Meditation and Depression

Although meditation-based interventions have been associated with improvement in depressive symptoms and prevention of relapse, the physiological mechanisms of meditation's therapeutic effects are unknown. At the same time, a growing body of literature has shown that meditation has profound effects on numerous physiological systems that are involved in the pathophysiology of depression. The first paper reviews many of the physiological abnormalities found in depression and the reversal or normalization of these same systems by meditation. The paper includes 1) a review of the physiological concomitants of depression, 2) a description of mindfulness meditation and its effects on mood disturbance, 3) the physiological effects of mindfulness and other related forms of meditation, and 4) suggestions for future research.The second paper summarizes the results of a randomized controlled trial of mindfulness meditation training on one of the previously identified candidate systems: sleep, as measured by overnight polysomnographic sleep studies as well as subjective reports (sleep diaries). The results indicate that mindfulness has an arousing effect on objectively measured sleep that corresponds with subjectively reported improvements in mood and sleep. This pattern is similar to the one observed in responders to antidepressant medications

Women Benefit More Than Men in Response to College-based Meditation Training

Objectives: While recent literature has shown that mindfulness training has positive effects on treating anxiety and depression, there has been virtually no research investigating whether effects differ across genders—despite the fact that men and women differ in clinically significant ways. The current study investigated whether college-based meditation training had different effects on negative affect for men and women.Methods: Seventy-seven university students (36 women, age = 20.7 ± 3.0 years) participated in 12-week courses with meditation training components. They completed self-report questionnaires of affect, mindfulness, and self-compassion before and after the course.Results: Compared to men, women showed greater decreases in negative affect and greater increases on scales measuring mindfulness and self-compassion. Women’s improvements in negative affect were correlated to improvements in measures of both mindfulness skills and self-compassion. In contrast, men showed non-significant increases in negative affect, and changes in affect were only correlated with ability to describe emotions, not any measures of experiential or self-acceptance.Conclusion: These findings suggest that women may have more favorable responses than men to school-based mindfulness training, and that the effectiveness of mindfulness-based interventions may be maximized by gender-specific modifications