Impact of warm mindfulness on emotion regulation: A randomized controlled effectiveness trial.

OBJECTIVE: To determine the effects of mindfulness training for primary care (MTPC), an integrated warm mindfulness training program, on emotion regulation and its relationship with health behavior change. Interventions that improve self-regulation, particularly emotion regulation, are needed for the self-management of comorbid chronic physical and mental illnesses. Mindfulness-based interventions (MBIs) may impact self-regulation and facilitate health behavior change. METHOD: A randomized controlled comparative effectiveness trial was conducted in a population of adult primary care patients to evaluate the impact of MTPC versus a low-dose mindfulness comparator (LDC) on self-reported difficulties in emotion regulation (DERS) total score and other assays of self-regulation at baseline, Weeks 8 and 24. Self-reported action plan initiation was reported between Weeks 8 and 10. Participants had diagnoses of anxiety, depression, or stress-related disorders. MTPC is an 8-week insurance-reimbursable warm MBI designed to cultivate mindfulness and self-compassion and to catalyze chronic illness self-management related health behavior change. RESULTS: Compared to LDC, MTPC participants had statistically significant reductions in DERS total score at 8 weeks (d = -0.59, ß = -12.98, 95% CI [-23.3 to -2.6]; p = .01) and 24 weeks (d = -0.61, ß = -13.35, [-24.3, -2.4]; p = .02). Compared to 38% for LDC, 63% of MTPC participants successfully initiated their action plan within 3 weeks (OR = 2.87, [1.1, 7.9]; p = .04). CONCLUSIONS: This randomized controlled trial demonstrated MTPC enhanced emotion regulation and facilitated initiation of chronic illness self-management and health behavior change among primary care patients with anxiety, depression, and stress-related disorders, replicating previous reports. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Increased insula response to interoceptive attention following mindfulness training is associated with increased body trusting among patients with depression.

Interoceptive dysfunction is often present in anxiety and depression. We investigated the effects of an 8-week intervention, Mindfulness Training for Primary Care (MTPC), on brain mechanisms of interoceptive attention among patients with anxiety and/or depression. We hypothesized that fMRI brain response to interoception in the insula, a region known for interoceptive processing, would increase following the MTPC intervention, and that such increases would be associated with post-intervention changes in self-reported measures of interoceptive awareness. Adults (n = 28) with anxiety and/or depression completed baseline and post-intervention fMRI visits, including a task in which they alternated between focusing on their heartbeat (interoception (INT)) and a control visual attention task (exteroception (EXT)). Following MTPC, we observed increased evoked fMRI response (relative to baseline) in left anterior insula during the INT-EXT task contrast (z > 3.1, p < 0.001 corrected). In patients with moderate-to-severe depression as defined by the Patient Reported Outcomes Measurement Information System (PROMIS), increased post-intervention insula response was associated with increased Body Trusting, a subscale of the Multidimensional Assessment of Interoceptive Awareness (z > 3.1, p = 0.007 corrected). This study demonstrates that patients with mood disorders may respond differentially to mindfulness-based treatment depending on depression severity, and that among those who are more depressed, increased trusting in one's own body sensations and experiencing the body as a safe place to attend to may be necessary components of positive responses to mindfulness-based interventions.

"Today I Can Look in the Mirror and Like Myself": Effects of a Trauma-Informed Mindful Recovery Program on Self-Compassion.

Background: Opioid-related deaths continue to rise. Psychological trauma is commonly comorbid with Opioid Use Disorder (OUD). Adverse childhood experiences can disrupt the development of emotion regulation, increasing risk of substance use. Self-compassion may reduce OUD risk and outcomes by facilitating emotion regulation, decreasing the toxicity of shame, and reducing internalized stigma that can hinder recovery. Mindfulness practice enhances self-compassion. Methods: This study is part of a pilot (N = 18) of the Mindful Recovery OUD Care Continuum (M-ROCC) during buprenorphine office-based opioid treatment (OBOT). The present study was conducted to gain a deeper understanding of the intervention's effects on self-compassion development, and to explore differential changes in self-compassion during the intervention among participants with varying intensity of trauma exposure measured by high levels of childhood adversity (defined by 4+ adverse childhood experiences (ACEs) at baseline). We conducted secondary analyses of a subset of qualitative interview data (N = 11 unique participants) collected for the pilot study (weeks 4 and 24, 14 total interviews) to elaborate upon changes in Self-Compassion Scale (SCS-SF) scores. Results: In the primary pilot study, participants' mean SCS-SF scores shifted significantly from baseline to week 24, ß = 0.22, p = 0.028. This change is elaborated upon through interviews. Despite pervasive challenges to becoming more self-compassionate (e.g., trauma histories and substance use), participants reported increased compassionate self-responding and decreased uncompassionate self-responding. Mindfulness training was identified as the primary mechanism underlying the shift. Kindness to self and others and-to a lesser extent an increased sense of common humanity-were also identified as key to overall self-compassion. Compared to those in the lower ACEs group, participants in the higher ACEs group tended to have lower baseline self-compassion scores (d = 1.09, p = 0.055). Conclusion: M-ROCC may increase self-compassion among patients with OUD during OBOT by increasing compassionate, and decreasing uncompassionate, self-responding. Patients with OUD with greater childhood adversity tended to have lower levels of self-compassion, which improved with M-ROCC. Future trials with larger samples are needed to confirm these potential outcomes, mechanisms, and differential impacts between ACEs subgroups.

Mindfulness Training for Primary Care for Portuguese-Speaking Immigrants: A Pilot Study.

Background: Portuguese-speaking immigrants are a growing underserved population in the Unites States who experience high levels of psychological distress and increased vulnerability to mental health disorders such as depression and anxiety. Current evidence shows that mindfulness-based interventions (MBIs) are effective to promote physical and mental health among educated English speakers; nonetheless, the lack of diversity in the mindfulness literature is a considerable limitation. To our knowledge, the feasibility and acceptability of MBIs among Portuguese-speaking immigrants have not yet been investigated. Methods: This single-arm pilot study (N = 30) explored the feasibility, acceptability, and cultural aspects of Mindfulness Training for Primary Care (MTPC)-Portuguese among Portuguese-speaking immigrants in the Boston area. MTPC is an 8-week, primary care-adapted, referral-based, insurance-reimbursable, trauma-informed MBI that is fully integrated into a healthcare system. The study also examined intervention preliminary effectiveness on mental health outcomes (depression and anxiety symptoms) and self-regulation (emotional regulation, mindfulness, self-compassion, interoceptive awareness), and initiation of health behavior was explored. Results: Primary care providers referred 129 patients from 2018 to 2020. Main DSM-5 primary diagnoses were depression (76.3%) and anxiety disorders (6.7%). Participants (N = 30) attended a mean of 6.1 (SD 1.92) sessions and reported a mean of 213.7 (SD = 124.3) min of practice per week. All survey finishers would recommend the program to a friend, found the program helpful, and rated the overall program as "very good" or "excellent," and 93% would participate again, with satisfaction mean scores between 4.6 and 5 (Likert scale 0-5). Participants and group leaders provided feedback to refine MTPC-Portuguese culturally responsiveness regarding materials language, settings, time, food, and community building. Patients exhibited reductions in depression (d = 0.67; p < 0.001) and anxiety (d = 0.48; p = 0.011) symptoms, as well as enhanced emotional regulation (d = 0.45; p = 0.009), and among survey finishers, 50% initiated health behavior change through action plan initiation. Conclusion: This pilot study suggests that MTPC-Portuguese is feasible, acceptable, and culturally appropriate among Portuguese-speaking patients in the Boston area. Furthermore, the intervention might potentially decrease depression and anxiety symptoms, facilitate health behavior change, and improve emotional regulation. MTPC-Portuguese investigation with larger samples in controlled studies is warranted to support its dissemination and implementation in the healthcare system. Clinical Trial Registration: Identifier: NCT04268355.

Losing trust in body sensations: Interoceptive awareness and depression symptom severity among primary care patients.

BACKGROUND: Interoceptive dysfunction is emerging as an important biomarker for mental illnesses, such as depression which is a leading cause of disability and death worldwide. Little empirical research explains the relationship between interoception and depression. METHODS: Using multivariable linear regression models and cross-sectional baseline data from a randomized control trial of primary care patients (N = 281), we analyzed the relationship between depression severity (none/slight, mild, and moderate/severe via the PROMIS depression scale) and the Multidimensional Assessment of Interoceptive Awareness (MAIA) subscales (noticing, not distracting, not worrying, attention regulation, emotional awareness, selfregulation, body listening and trusting). RESULTS: Adjusted results suggest moderate/severe depression was inversely associated with body trusting (p < .001), body listening (p < .01), noticing (p < .01), emotional awareness (p < .01), and self-regulation (p < .05). Mild depression was inversely associated with body trusting (p <.01). After correction for multiple comparisons, the relationship between MAIA body trusting and mild and moderate/severe depression remained significant. LIMITATIONS: Our findings may not be generalizable to other populations or healthcare settings. Additionally, findings cannot be interpreted as causal due to our inability to establish temporality. CONCLUSIONS: Lack of body trust appears important for understanding how individuals with depression interpret or respond to interoceptive stimuli and may represent the leading edge of interoceptive dysregulation seen in depressive disorders. Our findings support a hypothesis about mechanisms of action underlying hypoactivation in depression. Further, these results support clinical identification of subtypes of depression, such as those with high levels of co-occurring anxiety.

Mindfulness and Behavior Change.

Initiating and maintaining behavior change is key to the prevention and treatment of most preventable chronic medical and psychiatric illnesses. The cultivation of mindfulness, involving acceptance and nonjudgment of present-moment experience, often results in transformative health behavior change. Neural systems involved in motivation and learning have an important role to play. A theoretical model of mindfulness that integrates these mechanisms with the cognitive, emotional, and self-related processes commonly described, while applying an integrated model to health behavior change, is needed. This integrative review (1) defines mindfulness and describes the mindfulness-based intervention movement, (2) synthesizes the neuroscience of mindfulness and integrates motivation and learning mechanisms within a mindful self-regulation model for understanding the complex effects of mindfulness on behavior change, and (3) synthesizes current clinical research evaluating the effects of mindfulness-based interventions targeting health behaviors relevant to psychiatric care. The review provides insight into the limitations of current research and proposes potential mechanisms to be tested in future research and targeted in clinical practice to enhance the impact of mindfulness on behavior change.

Insurance-Reimbursable Mindfulness for Safety-Net Primary Care Patients: A Pilot Randomized Controlled Trial.

OBJECTIVES: Mindfulness is effective for reducing anxiety and depression and increasing chronic disease self-management. An accessible, insurance-reimbursable model for implementation in patient-centered medical homes within US healthcare systems has promise for patients with multi-morbid conditions. Clarifying both the dose needed to impact anxiety, depression and self-management, and the design requirements for accessible primary care implementation, is essential. METHODS: We tested feasibility, acceptability, and effectiveness of Mindfulness Training for Primary Care (MTPC), an 8-week, referral-based, insurance-reimbursable mindfulness program integrated within primary care, compared with a Low-Dose Comparator (LDC), consisting of a 60-minute mindfulness introduction plus referral to community and digital resources. Outcome measures were assessed at baseline and 8 weeks. MTPC is trauma-informed, incorporates mindfulness-oriented behavior change skills, and is designed to target anxiety, depression, stress, and chronic illness selfmanagement. Participants schedule a PCP visit to co-create a self-management action plan during week 6. RESULTS: Primary care providers (PCP) referred 344 patients over 14 months. Eighty-one participants with DSM-V anxiety disorders, depressive disorders, trauma- and stress-related disorders participated in this pilot randomized-controlled comparative effectiveness trial [MTPC (n=54); LDC (n=27)]. These data suggest that MTPC was more effective than LDC for reducing anxiety (p=0.01), enhancing mindfulness (p=0.02) and self-compassion (p=0.001), and for catalyzing selfmanagement behavior change through action plan initiation (OR=4.34, p=0.03). CONCLUSIONS: MTPC was successfully integrated into a health system, was billed to insurance, and was acceptable to a diverse primary care population. Replication with a larger study and further accessibility adaptations are needed to confirm and expand these pilot results.

Mindfulness Training Enhances Self-Regulation and Facilitates Health Behavior Change for Primary Care Patients: a Randomized Controlled Trial.

BACKGROUND: Self-management of health is important for improving health outcomes among primary care patients with chronic disease. Anxiety and depressive disorders are common and interfere with self-regulation, which is required for disease self-management. An insurance-reimbursable mindfulness intervention integrated within primary care may be effective for enhancing chronic disease self-management behaviors among primary care patients with anxiety, depression, trauma, and stress-related and adjustment disorders compared with the increasingly standard practice of referring patients to outside mindfulness resources. OBJECTIVE: Mindfulness Training for Primary Care (MTPC) is an 8-week, referral-based, insurance-reimbursable program integrated into safety-net health system patient-centered medical homes. We hypothesized that MTPC would be more effective for catalyzing chronic disease self-management action plan initiation within 2 weeks, versus a low-dose comparator (LDC) consisting of a 60-min mindfulness introduction, referral to community and digital resources, and addition to a 6-month waitlist for MTPC. PARTICIPANTS: Primary care providers (PCPs) and mental health clinicians referred 465 patients over 12 months. All participants had a DSM-V diagnosis. DESIGN AND INTERVENTIONS: Participants (N = 136) were randomized in a 2:1 allocation to MTPC (n = 92) or LDC (n = 44) in a randomized controlled comparative effectiveness trial. MTPC incorporates mindfulness, self-compassion, and mindfulness-oriented behavior change skills and is delivered as insurance-reimbursable visits within primary care. Participants took part in a chronic disease self-management action planning protocol at week 7. MAIN MEASURES: Level of self-reported action plan initiation on the action plan initiation survey by week 9. KEY RESULTS: Participants randomized to MTPC, relative to LDC, had significantly higher adjusted odds of self-management action plan initiation in an intention-to-treat analysis (OR = 2.28; 95% CI = 1.02 to 5.06, p = 0.025). CONCLUSIONS: An 8-week dose of mindfulness training is more effective than a low-dose mindfulness comparator in facilitating chronic disease self-management behavior change among primary care patients.

Leaderless Transcripts and Small Proteins Are Common Features of the Mycobacterial Translational Landscape.

RNA-seq technologies have provided significant insight into the transcription networks of mycobacteria. However, such studies provide no definitive information on the translational landscape. Here, we use a combination of high-throughput transcriptome and proteome-profiling approaches to more rigorously understand protein expression in two mycobacterial species. RNA-seq and ribosome profiling in Mycobacterium smegmatis, and transcription start site (TSS) mapping and N-terminal peptide mass spectrometry in Mycobacterium tuberculosis, provide complementary, empirical datasets to examine the congruence of transcription and translation in the Mycobacterium genus. We find that nearly one-quarter of mycobacterial transcripts are leaderless, lacking a 5' untranslated region (UTR) and Shine-Dalgarno ribosome-binding site. Our data indicate that leaderless translation is a major feature of mycobacterial genomes and is comparably robust to leadered initiation. Using translational reporters to systematically probe the cis-sequence requirements of leaderless translation initiation in mycobacteria, we find that an ATG or GTG at the mRNA 5' end is both necessary and sufficient. This criterion, together with our ribosome occupancy data, suggests that mycobacteria encode hundreds of small, unannotated proteins at the 5' ends of transcripts. The conservation of small proteins in both mycobacterial species tested suggests that some play important roles in mycobacterial physiology. Our translational-reporter system further indicates that mycobacterial leadered translation initiation requires a Shine Dalgarno site in the 5' UTR and that ATG, GTG, TTG, and ATT codons can robustly initiate translation. Our combined approaches provide the first comprehensive view of mycobacterial gene structures and their non-canonical mechanisms of protein expression.

DNA replication fidelity in Mycobacterium tuberculosis is mediated by an ancestral prokaryotic proofreader.

The DNA replication machinery is an important target for antibiotic development in increasingly drug-resistant bacteria, including Mycobacterium tuberculosis. Although blocking DNA replication leads to cell death, disrupting the processes used to ensure replication fidelity can accelerate mutation and the evolution of drug resistance. In Escherichia coli, the proofreading subunit of the replisome, the ɛ exonuclease, is essential for high-fidelity DNA replication; however, we find that the corresponding subunit is completely dispensable in M. tuberculosis. Rather, the mycobacterial replicative polymerase DnaE1 itself encodes an editing function that proofreads DNA replication, mediated by an intrinsic 3'-5' exonuclease activity within its PHP domain. Inactivation of the DnaE1 PHP domain increases the mutation rate by more than 3,000-fold. Moreover, phylogenetic analysis of DNA replication proofreading in the bacterial kingdom suggests that E. coli is a phylogenetic outlier and that PHP domain-mediated proofreading is widely conserved and indeed may be the ancestral prokaryotic proofreader.

Sterilization of granulomas is common in active and latent tuberculosis despite within-host variability in bacterial killing.

Over 30% of the world's population is infected with Mycobacterium tuberculosis (Mtb), yet only ∼5-10% will develop clinical disease. Despite considerable effort, researchers understand little about what distinguishes individuals whose infection progresses to active tuberculosis (TB) from those whose infection remains latent for decades. The variable course of disease is recapitulated in cynomolgus macaques infected with Mtb. Active disease occurs in ∼45% of infected macaques and is defined by clinical, microbiologic and immunologic signs, whereas the remaining infected animals are clinically asymptomatic. Here, we use individually marked Mtb isolates and quantitative measures of culturable and cumulative bacterial burden to show that most lung lesions are probably founded by a single bacterium and reach similar maximum burdens. Despite this observation, the fate of individual lesions varies substantially within the same host. Notably, in active disease, the host sterilizes some lesions even while others progress. Our data suggest that lesional heterogeneity arises, in part, through differential killing of bacteria after the onset of adaptive immunity. Thus, individual lesions follow diverse and overlapping trajectories, suggesting that critical responses occur at a lesional level to ultimately determine the clinical outcome of infection. Defining the local factors that dictate outcome will be useful in developing effective interventions to prevent active TB.

A new system for comparative functional genomics of Saccharomyces yeasts.

Whole-genome sequencing, particularly in fungi, has progressed at a tremendous rate. More difficult, however, is experimental testing of the inferences about gene function that can be drawn from comparative sequence analysis alone. We present a genome-wide functional characterization of a sequenced but experimentally understudied budding yeast, Saccharomyces bayanus var. uvarum (henceforth referred to as S. bayanus), allowing us to map changes over the 20 million years that separate this organism from S. cerevisiae. We first created a suite of genetic tools to facilitate work in S. bayanus. Next, we measured the gene-expression response of S. bayanus to a diverse set of perturbations optimized using a computational approach to cover a diverse array of functionally relevant biological responses. The resulting data set reveals that gene-expression patterns are largely conserved, but significant changes may exist in regulatory networks such as carbohydrate utilization and meiosis. In addition to regulatory changes, our approach identified gene functions that have diverged. The functions of genes in core pathways are highly conserved, but we observed many changes in which genes are involved in osmotic stress, peroxisome biogenesis, and autophagy. A surprising number of genes specific to S. bayanus respond to oxidative stress, suggesting the organism may have evolved under different selection pressures than S. cerevisiae. This work expands the scope of genome-scale evolutionary studies from sequence-based analysis to rapid experimental characterization and could be adopted for functional mapping in any lineage of interest. Furthermore, our detailed characterization of S. bayanus provides a valuable resource for comparative functional genomics studies in yeast.