Behavior, Biology and Well-Being Study

Not Applicable

Completed

Conditions: Depression
Psychological Distress

Registration Number: NCT06213701

Lead Sponsor: University of Wisconsin, Madison

Brief Summary: The central aim of this pilot study is to compare markers of inflammation and gut microbial diversity with users of the Healthy Minds Program (HMP) app, an intervention designed to promote well-being. The investigators plan to conduct a randomized controlled trial (RCT) involving 300 participants comparing 4-weeks of the HMP app with an active control (Psychoeducation \[HMP without meditation practice\]), and a waitlist control in a sample of United States adults with elevated depression symptoms.

Detailed Description: Depression is highly prevalent and associated with extreme personal and societal costs. Meditation training reduces depression symptoms and psychological distress, but access to in-person programs is limited due to associated cost and lack of available services. Research on neurocognitive and biological mechanisms of mediation training in alleviating depression is at a preliminary stage, and an obstacle limiting research progress is over-reliance on retrospective self-report measures, which are vulnerable to a host of biases. This project will use gold-standard behavioral measures and explore novel measures of relevant neurocognitive and behavioral processes, namely pattern separation, self-referential thought, and video-based assessment of emotional well-being. Furthermore, the project will investigate effects on the gut microbiome (with fecal samples) and inflammation (with dried blood spots), which reflect biological systems hypothesized to be mechanistically related to benefits of meditation and well-being training.

Specific Aims:

* Aim 1. Determine the feasibility and acceptability of assessing inflammatory activity and gut microbiome within the context of a fully remote randomized controlled trial (RCT). Participants with elevated depression symptoms from an RCT (n = 1,100; registered to NCT05183867) comparing the Healthy Minds Program (HMP) app with an active control (HMP with didactic content only) and wait-list will be invited to provide dried blood spots (DBS) for inflammatory protein analysis and fecal samples for gut microbial analysis at baseline and 3-month follow-up. Hypotheses: It will be feasible to recruit 300 participants to provide DBS and fecal samples and 80% will provide samples at both time points (completer n = 240) with no differences in completion rates between non-Hispanic White and racial/ethnic minority participants.

* Aim 2. Characterize the association between self-reports of well-being, inflammatory activity at baseline, and microbiota diversity at baseline. Hypotheses: Well-being will correlate inversely with both protein biomarkers of inflammation (CRP, IL-6) and mRNA-derived indicators of pro-inflammatory transcriptional activity. Well-being will correlate positively with alpha diversity of the gut microbiome. These associations will not be moderated by participant race/ethnicity.

* Aim 3. Evaluate intervention effects on inflammatory activity and microbiota diversity. Hypotheses: Participants randomized to HMP or the active control will show larger reductions in inflammation vs. wait-list at 3-month follow-up and larger increases in alpha diversity of the gut microbiome vs. wait-list at 3-month follow-up. HMP will show larger reductions in inflammation vs. active control at 3-month follow-up and larger increases in alpha diversity vs. active control at 3-month follow-up.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 300

Inclusion Criteria

Elevated PHQ-8 or PHQ-9 ≥ 5 at screening and pre-baseline interview
Proficient in English
Able to provide informed consent
Have access to a smartphone that can download apps from Google Play or the Apple App Store
For payment purposes, must be a US citizen or a permanent US resident

Exclusion Criteria

Regular daily meditation practice for past 6 months or regular weekly meditation practice for past 12 months
Attended a meditation retreat or a yoga/body practice retreat with a significant meditation component
- Previous use of Healthy Minds Program app
Current suicidal intent and/or high self-injury risk (determined from the interview)
Self-reported history of psychosis
Self-reported history of mania
Current psychopathology that interferes with study participation as assessed by interview
Living or traveling outside the US during the whole study participation period (trips outside US after the interview phase is not an exclusion)
Alcohol Use Disorders Identification Test (AUDIT) score ≥ 13 for women and AUDIT score ≥ 15 for men
Drug Use Disorders Identification Test (DUDIT) score ≥ 8 for women and men

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Feasibility of DBS Collection as Measured by Number of Participants Who Provide DBS	Baseline and 3 month follow-up	Feasibility is defined as 80% of participants providing samples at both time points (completer n = 240) with no differences in completion rates between non-Hispanic White and racial/ethnic minority participants.
Feasibility of Fecal Sample Collection as Measured by Number of Participants Who Provide Fecal Samples	Baseline and 3 month follow-up	Feasibility is defined as 80% of participants providing samples at both time points (completer n = 240) with no differences in completion rates between non-Hispanic White and racial/ethnic minority participants.

Secondary Outcome Measures

Name	Time	Method
Change in Microbiome Alpha Diversity: Species Richness	Baseline and 3 month follow-up	Genetic analyses of the microbiome of the fecal sample (microorganism DNA, not that of the person) will be performed. Reported here are the observed (total number of distinct taxa) and calculated (Chao1 = N + S2 / (2 D), where N is the number of observed OTUs (Operational Taxonomic Units), S is the number of singleton OTUs, and D is the number of doublet OTUs) number of species represented in the sample. Chao1 is a species richness calculator that accounts for rare species.
Change in Microbiome Alpha Diversity: Shannon Diversity Index (H')	Baseline and 3 month follow-up	Genetic analyses of the microbiome of the fecal sample (microorganism DNA, not that of the person) will be performed. Shannon Diversity Index quantifies both the richness and the evenness of a community. It takes into account the number of taxa (richness) and their relative abundances (evenness). A higher Shannon index value indicates greater diversity, with both a high number of taxa and more even distribution of abundances among them. It is often used to assess the balance between species in a community. Typically ranges from 0-5 with higher numbers indicating increasing species diversity.
Change in Microbiome Alpha Diversity: Inverse Simpson (1/D)	Baseline and 3 month follow-up	Genetic analyses of the microbiome of the fecal sample (microorganism DNA, not that of the person) will be performed. Simpson is the probability that any two microbes are the same species, ranging from 0-1. Inverse Simpson (1 / Simpson) considers both richness and evenness. It places greater weight on the more abundant taxa. A higher inverse Simpson index suggests a more even distribution of taxa, with fewer dominant species. The inverse Simpson index is sensitive to the presence of dominant species and may emphasize diversity loss when one or a few species dominate the community.
Change in Microbiome Alpha Diversity: Pielou Evenness Index (J)	Baseline and 3 month follow-up	Genetic analyses of the microbiome of the fecal sample (microorganism DNA, not that of the person) will be performed. Pielou Evenness Index measures how evenly the individuals are distributed across the taxa in a sample. It is calculated by dividing the Shannon diversity index by the maximum possible value of the Shannon index (which occurs when all taxa are equally abundant). The Pielou index ranges from 0 (no evenness, where one species dominates) to 1 (perfect evenness, where all species are equally abundant).
Change in Microbiome Alpha Diversity: Simpson's Dominance Index (D)	Baseline and 3 month follow-up	Genetic analyses of the microbiome of the fecal sample (microorganism DNA, not that of the person) will be performed. Simpson's Dominance Index measures the probability that two randomly selected individuals from a community belong to the same species (or taxon). It ranges from 0 to 1, where 0 indicates perfect diversity (no dominance of a single species) and values closer to 1 indicate that one or a few species dominate the community. A lower Simpson's dominance score suggests a more diverse community, while a higher score indicates a community dominated by a few taxa.
Change in Inflammatory Biomarkers: C-reactive Protein	Baseline and 3 month follow-up	Dried blood spot samples will be used to measure inflammatory cytokines (C-reactive protein (CRP) and interleukin-6 (IL-6)). Additionally mRNA assays will be used to detect and quantify inflammatory gene expression detect and monitor cellular immune responses. Analyses will focus on transcripts from \~200 genes known to be involved in the regulation of inflammation, and will consider key transcripts (e.g., IL-1beta, TNF-alpha) as well as summary measures reflecting the activity of transcriptional networks that coordinate inflammation (NF-kB, AP-1).
Change in Inflammatory Biomarkers: TNF-Alpha, IL-6, IL-10	Baseline and 3 month follow-up	Dried blood spot samples will be used to measure inflammatory cytokines (C-reactive protein (CRP) and interleukin-6 (IL-6)). Additionally mRNA assays will be used to detect and quantify inflammatory gene expression detect and monitor cellular immune responses. Analyses will focus on transcripts from \~200 genes known to be involved in the regulation of inflammation, and will consider key transcripts (e.g., IL-1beta, TNF-alpha) as well as summary measures reflecting the activity of transcriptional networks that coordinate inflammation (NF-kB, AP-1).
Change in Depression Symptoms Measured by Patient Health Questionnaire - 8 (PHQ-8) Score	Baseline, week 1, week 2, week 3, week 4 (of intervention period), and 3 month follow-up	The PHQ-8 is an 8-item questionnaire where participants report how often in the past 2 weeks they were bothered by specific problems. It is scored on a 4-point Likert scale where 0 = not at all to 3 = nearly every day. The total possible range of scores is 0-24 where higher scores indicate more depressive symptoms.
Change in Flourishing Measured by the Flourishing Index Score	Baseline, week 1, week 2, week 3, week 4 (of intervention period), and 3 month follow-up	The Flourishing Index is a 10-item questionnaire where participants report their general level of flourishing (e.g., well-being, health, etc.). It is scored on a 0 to 10-point scale, with anchors varying across items. The total score ranges from 0 to 100 with higher scores indicating higher flourishing.