Stress & Resilience Study

Goal 1: The investigators will quantify lifetime stress burden and examine mechanisms linking Adverse Childhood Experiences (ACEs) and health. The investigators will quantify the early life and total lifetime stress burden of a representative sample of about 725 adults (aged 18+) across northern and southern California. In addition, the investigators will examine how prior life stress exposure and current stress levels are associated with differences in psychosocial, immune, metabolic, physiologic, and clinical outcomes for all participants at baseline.

Goal 2: The investigators will develop and test a biopsychosocial intervention using existing programs, platforms, resources, and core components from trauma and resilience research that will target five stress-related domains (i.e., cognitive response style, social relationships, eating, sleep, and physical activity) using cognitive restructuring and mindfulness, interpersonal skills training, mindful eating training, sleep training, and behavioral activation/mobility training. The investigators will then assess the efficacy and acceptability of the intervention in about 425 high stress exposure participants from Goal 1. Following their baseline assessment, about 425 participants will be randomly assigned to receive for 12 weeks (a) personalized intervention, (b) environmental education (active control) or (c) nothing (non-active control). The investigators will also assess the efficacy of the personalized intervention by comparing changes in outcomes by condition from baseline (prior to randomization) to immediately after the intervention, and then again after 12 weeks following intervention completion. The interventions will be entirely online/remote.

Aim 1: The investigators will quantify lifetime stress burden and examine mechanisms linking Adverse Childhood Experiences (ACEs) and health. The investigators will quantify the early life and total lifetime stress burden of a representative sample of about 725 adults (aged 18+) across California. In addition, the investigators will examine how prior life stress exposure and current stress levels are associated with differences in psychosocial, immune, metabolic, physiologic, and clinical outcomes for all participants at baseline.

Objective 1.1. Characterize associations between stress levels and psychosocial and clinical functioning by collecting self-report data from participants (see below) and by using any available electronic health records.

Objective 1.2. Examine cross-sectional relations between stress levels and physiological, biological, and behavioral processes using (1) immune and metabolic functioning assessed by non-invasive blood microsampling and the investigators' unique multi-omics approach, and (2) continuously monitored physiologic and behavioral functioning using smartwatches that have the ability to assess a variety of physiologic \& behavioral processes (e.g., cardiac function, sleep, activity levels).

Objective 1.3. Develop a Personal Health Dashboard for processing data with an algorithm that will generate personalized results to inform individualized health risk assessments and provide an opportunity to deliver tailored clinical feedback and biopsychosocial resiliency training by targeting five key stress-related risk factors (see Aim 2).

Aim 2: Reduce ACEs-related health disparities by developing and testing a behavioral intervention for about 425 of the higher stress participants from Aim 1. To reduce negative stress-related effects and bolster resilience, the investigators will examine the acceptability and effectiveness of a 12 week, online, precision behavioral intervention.

Objective 2.1. Develop a behavioral intervention using existing programs, platforms, resources, and core components from trauma and resilience research that will target five stress-related domains (i.e., perceived stress, social relationships, diet, sleep, and physical activity) using cognitive restructuring and mindfulness, interpersonal skills training, personalized diet training, sleep training, and behavioral activation.

Objective 2.2. Assess the efficacy of the above-described intervention in about 425 high stress exposure participants from Goal 1. Following their baseline assessment, participants will be randomly assigned to receive (a) the personalized intervention (about 55 participants per stress-related domain), (b) stress \& health psychoeducation/active control group, or (c) nonactive control group. For participants receiving the intervention, the investigators will identify each person's most dysregulated biobehavioral process using the comprehensive biopsychosocial data obtained from Goal 1, focusing on five major stress-related domains: cognitive response style, social relationships, eating, sleep, and physical activity. The investigators will pilot the use of online coach-assisted personalized interventions to target a dysregulated domain for each participant. The investigators will also assess the efficacy of the intervention by comparing changes in outcomes by condition from baseline (prior to randomization) to immediately after the intervention, and then again several months following intervention completion. The primary outcome of interest will be perceived stress (PSS-10). The secondary outcomes of the RCT include five domain specific surveys: the Five-Factor Mindfulness Scale short form (cognitive response style), Conflict Scale and UCLA Loneliness Scale (social relationship domain), Salzburg Stress Eating Scale (eating domain), Insomnia Severity Index (sleeping domain), and International Physical Activity Questionnaire short form (IPAQ, physical activity domain). Exploratory outcomes include the multiomics measures (including untargeted metabolomics, lipidomics, immune proteins, cytokines and the microbiome), physiological measures from the wearable device (i.e., heart rate variability), and continuous glucose monitoring measures.

Eligibility Criteria:
Inclusion Criteria:

* A participant must meet all of the following criteria to be eligible to participate in this study:

  1. Be able to understand and agree to comply with planned study procedures in English.
  2. Participants must be aged 18 or over.
  3. Participants must reside in the state of California.

Exclusion Criteria:

* A participant who meets any of the following criteria will be excluded from participation in this study:

History of disease(s):

1. Has a positive test result for human immunodeficiency virus (HIV) types 1 or 2 antibodies.
2. Has had a heart attack or stroke within the past year.
3. Has had and/or been treated for any type of cancer in the past two years.

Medication(s):

Participants who check off any of the following medications and/or treatment listed below over the past month will be excluded in the study.

1. Prednisolone (e.g., Omnipred, Pred Mild, Pred Forte, Orapred ODT, Veripred 20, Millipred DP)
2. Prednisone (e.g., Prednisone Intensol, Deltasone, Rayos)
3. Betamethasone (e.g., Celestone Soluspan, Sernivo, Diprolene AF, ReadySharp Betamethasone, Betaloan SUIK, Beta-1)
4. Dexamethasone (e.g., Ozurdex, Maxidex, DexPak 6 Day/10 day/13 Day, LoCort, ZonaCort, ReadySharp dexamethasone, DoubleDex)
5. Hydrocortisone (e.g., Hydrocort, Alphosyl, Aquacort, Cortef, Cortenema, and Solu-Cortef)
6. Methylprednisolone (e.g., Depo-Medrol, Solu-Medrol, Medrol, ReadySharp Methylprednisolone, P-Care D80, and P-Care D40)
7. Deflazacort (e.g., Emflaza)
8. Immunomodulators

   * Cyclosporine (Sandimmune, Neoral, Gengraf, Restasis MultiDose)
   * Tacrolimus (Protopic, Envarsus XR, Astagraf XL, Prograf)
   * Methotrexate (Rheumatrex, Trexall, Otrexup (PF), Xatmep, Rasuvo, Mexate, MTX)
   * Azathioprine (Immuran, Azasan)
   * Mercaptopurine (6-MP, Purinethol, Purixan)
   * Other Immunomodulators not listed above
9. Monoclonal antibody therapy

   * Infliximab (Remicade)
   * Etanercept (Enbrel, Benepali, Erelzi)
   * Adalimumab (Humira)
   * Secukinumab (Cosentyx)
   * Tofacitinib (Xeljanz)
   * Rituximab (Rituxan)
   * Other Monoclonal antibody therapy not listed above
10. Intravenous immunoglobulin treatment (IVIG)