Description

Introduction

Since the emergence of the COVID-19 pandemic, youth mental health has faced a persistent crisis, further widening the existing gaps (Brown \& Carrington, 2025; Zhang-James, et al 2025). Less than half of youth diagnosed with a psychiatric disorder are estimated to receive treatment (Clinical Update, 2023). The consequences of unmet needs include disruptive behaviors, suicide attempts, challenges with transitioning into adulthood (Heinrich et al., 2023) and risk of chronic illness that are a major cause of morbidity and economic burden and threaten emotional well-being (Schlack, 2021).. Integrative modalities that can be replicated and provided at low cost in group settings are needed with rigorous research to investigate mechanisms of emotional wellbeing for adolescents and young adults, particularly those with psychiatric conditions.

Emotional wellbeing (EWB) is an important public health research priority given its central role in resilience, functioning, and long-term health as well as its association with psychiatric disorders. A multi-dimensional construct, EWB includes emotional valence, reflective features about satisfaction and sense of meaning, and requires multi-faceted innovative techniques to further understanding, particularly among adolescents given that EWB and emotion regulation (ER) are in development. Indeed, ER is a central task of adolescents and young adults and defined "the ability to modify the onset, intensity, duration, and type of emotional response to a situation" and is associated with psychological constructs of emotion reactivity, cognitive appraisal and rumination, as well as physiologic mechanisms of inflammation, stress and HPA axis pathways involved in vasopulmonary constriction.

Adolescents and young adults with psychiatric conditions face multiple challenges to achieving EWB given chronic conditions with high stress and inflammation. Emotion dysregulation is a transdiagnostic construct that is thought to underlie multiple psychiatric disorders and beginning to be understood in terms of physiologic mechanisms such as the links between ED, inflammation, and childhood adversity. It is hypothesized that many adolescents and young adults with psychiatric conditions have high rates of both inflammatory processes and childhood adversity.

While the bulk of evidence for yoga in general and in clinical populations has focused on adults, there is emerging evidence that yoga is feasible, acceptable, and can promote emotional wellbeing for adolescents and young adults. A recent review of yoga practice among youth supports a variety of biological benefits to the sympathetic nervous system, decreased stress, improvements of psychiatric symptoms and improvements to interoceptive awareness, mindfulness, and overall wellbeing, as and outcomes such as improved wellbeing (Kerekes et al., 2026).

Trauma sensitive yoga has been developed for use with populations who may have experienced traumatic events and includes methods to help ensure psychological safety such as for individuals with psychiatric diagnosis and potential trauma histories. Protocols emphasize safe movement, choice, and connection to bodily sensations. Trauma Adapted Yoga is a specific type of trauma sensitive yoga developed by Josefin Wilkstrom and Nora Kerekes for use in psychiatric and medical populations with high prevalence of trauma and nervous system dysregulation. Prior research supports its role in reducing perceived stress, aggression, and self-harm in institutionalized youth. These protocols also emphasize mindfulness, interoception, breathing, and moments of stillness that activate the parasympathetic nervous system, which in essence counters the effects of stress and anxiety on the body.

A previous pilot study by our team demonstrated the feasibility of Trauma Adapted Yoga (TAY) intervention in adolescents participating in psychiatric care on inpatient units. Most adolescents participated in the yoga intervention and found subjective benefit to stress and anxiety (Khoury et al., 2024) as well as demonstrated significant improvement in psychiatric symptoms over the course of their hospitalization (Chung et al., 2026).. Additionally, a preliminary pilot of adolescents in outpatient psychiatric care found improvement in symptoms of stress and anxiety, self-reported resilience and interoceptive awareness as measured by the MAIA-2. Specifically, our pilot data of 10 adolescent participants who completed pre and post assessments demonstrated increased interoceptive awareness, modest resilience gains and symptom reduction across psychiatric symptoms such as PTSD, emotional pain and ADHD. This is consistent with previous research which has implicated interoceptive awareness as one potential mechanism for improvement in PTSD for individuals with trauma (Neukirch et al., 2019)..

Mechanisms of yoga to support wellbeing overall is multifaceted and includes both bottom-up and top-down processes. A model by Gard and colleagues Gard and colleagues (2014) outlines multiple mechanisms by which yoga supports psychological wellbeing. See figure below.

A previous pilot study by our team demonstrated the feasibility of Trauma Adapted Yoga (TAY) intervention in adolescents participating in psychiatric care on inpatient units. Most adolescents participated in the yoga intervention and found subjective benefit to stress and anxiety (Khoury et al., 2024) as well as demonstrated significant improvement in psychiatric symptoms over the course of their hospitalization (Chung et al., 2026).. Additionally, a preliminary pilot of adolescents in outpatient psychiatric care found improvement in symptoms of stress and anxiety, self-reported resilience and interoceptive awareness as measured by the MAIA-2. Specifically, our pilot data of 10 adolescent participants who completed pre and post assessments demonstrated increased interoceptive awareness, modest resilience gains and symptom reduction across psychiatric symptoms such as PTSD, emotional pain and ADHD. This is consistent with previous research which has implicated interoceptive awareness as one potential mechanism for improvement in PTSD for individuals with trauma (Neukirch et al., 2019)..

Mechanisms of yoga to support wellbeing overall is multifaceted and includes both bottom-up and top-down processes. A model by Gard and colleagues Gard and colleagues (2014) outlines multiple mechanisms by which yoga supports psychological wellbeing. See figure below.

A previous pilot study by our team demonstrated the feasibility of Trauma Adapted Yoga (TAY) intervention in adolescents participating in psychiatric care on inpatient units. Most adolescents participated in the yoga intervention and found subjective benefit to stress and anxiety (Khoury et al., 2024) as well as demonstrated significant improvement in psychiatric symptoms over the course of their hospitalization (Chung et al., 2026).. Additionally, a preliminary pilot of adolescents in outpatient psychiatric care found improvement in symptoms of stress and anxiety, self-reported resilience and interoceptive awareness as measured by the MAIA-2. Specifically, our pilot data of 10 adolescent participants who completed pre and post assessments demonstrated increased interoceptive awareness, modest resilience gains and symptom reduction across psychiatric symptoms such as PTSD, emotional pain and ADHD. This is consistent with previous research which has implicated interoceptive awareness as one potential mechanism for improvement in PTSD for individuals with trauma (Neukirch et al., 2019)..

Inflammatory pathways and epigenetics.

Yoga has been demonstrated to be acceptable and effective in multiple populations including those with psychiatric conditions and there is growing evidence that yoga can decrease markers of stress and inflammation Estaveo, 2021). A recent systematic review of RCTs involving over 700 adults found that yoga consistently downregulates pro-inflammatory genes- interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and nuclear factor kappa B (NF-kappB) in five studies and upregulated anti-inflammatory and immune regulatory genes-transforming growth factor-beta (TGF-beta), forkhead box P3 (FOXP3), soluble human leukocyte antigen G (sHLA-G) and IL-10- in four studies (Giridharan, 2025). Molecular changes have also been found enhancing expression of genes linked to DNA repair, mitochondrial function, and epigenetic regulation (reduced TNF methylation and increased microRNA-133B) that correlate with clinical benefits such as reduced disease activity in rheumatoid arthritis (RA), improved glycemic control in type 2 diabetes and improved quality of life among breast cancer survivors.

Previous studies suggest that yoga has been proven to be beneficial in regard to enhancing immunity and supporting the management of chronic diseases such as cardiovascular, respiratory, endocrine disorders, obesity, cancer, and metabolic syndrome (Madan et al., 2022). In adults with depression, yoga has been shown to improve depression as well as increase BDNF, a marker of neural plasticity, and reduce serum cortisol (Naveen et al., 2016).. A recent systematic review highlights the evidence that yoga can improve blood pressure, cortisol and cytokine levels including IL-6, TNF-α and IL-1β providing support to the hypothesis that yoga can positively influence the immune response by stress regulation (Estaveo, 2022).. Biomarkers involved in the inflammatory process have been seen to be changed in the short term and longer term, which are promising. Additionally, yoga has been shown to increase salivary IgA in pregnant women after yoga with sustained results that also predicted improved birth outcomes (Chen et al., 2017).

Indeed, yoga practice has been shown to promote hormone regulation, autonomic nervous system regulation, physical health, as well as metabolism, circulation, oxidative stress, and inflammation (McCall, 2013). Less is known about these mechanisms in adolescents and young adults. Childhood inflammation has nevertheless been shown to be a risk factor in the development of mental and cardiometabolic disorders in early adulthood (Palmer, 2024). Elevated levels of inflammatory markers were consistently associated with an increased risk of suicidal behavior across diverse populations, and preliminary evidence suggests anti-inflammatory interventions may reduce suicidality (Baldini, 2025). Further, a meta-analysis of 22 studies (n=20,791) found a positive association between depression and concurrent and future inflammation for children and adolescents (Colasanto, 2020).. In addition, sex-based differences found in inflammatory-related pathways involved in the production of cytokines and in interferon and complement signaling as associations found for only adolescent females with depression Zonca, 2024).

In terms of measurement, previous studies have demonstrated that salivary enzymes can decrease immediately after or within 30-60 minutes after a yoga session (Ali \&Neter, 2022) . Patients with high inflammation at baseline may benefit more from this type of intervention and certain patients with psychiatric illness are found to have markers of high inflammatory states, such as patients with mood disorders, anxiety and PTSD as well as sleep disorders, which are highly associated with psychiatric disorders and functional impairment.

An emerging and innovative area in yoga research involves epigenetics and gene expression modification (Giridharan, 2023).. An RCT with psychologically stressed women demonstrated reduced DNA methylation in the genes associated with IL-6, TNF in the yoga group (Harkess 2016. Studies with adult veterans with PTSD have demonstrated that DNA methylation and markers of epigenetics can change post mindfulness or yoga interventions (Bishop, 2018).. Additionally, decreases in DNA methylation of TNF region found in women participating in a bi-weekly yoga intervention for 8 weeks (Harkess et al., 2016).. Bishop and colleagues demonstrated that FKBP5 methylation may be modified by non-pharmacological interventions and that regulatory regions thought to represent relatively stable methylated regions are in fact malleable through therapies that may help patients regulate stress feedback32. Current evidence supports the potential impact of mindfulness-related interventions such as yoga on the regulation of FKBP5 to feedback on glucocorticoid hyperactivity to reduce stress. Other implicated epigenetic markers include CRH and NR3C1 methylation levels, as this has been investigated as potential biomarkers for determining the success of psychological therapies, for example, in adults with severe PTSD (Lewis et al., 2023; Wilker et al., 2023).. The potential to change epigenetics through alternations in DNA sequencing is promising in its ability to modify disease onset and progression for vulnerable populations, as well as to improve wellbeing for subsequent generations.

Interoception

Interoception has been implicated in a variety of psychiatric disorders with interoceptive dysregulation being associated with depressive disorders, anxiety disorders, substances, and eating disorders (Khoury et al., 2019).. Interoception and inflammation may be associated in that chronic inflammation may distort internal body-state representation that interferes with interoceptive regulation and activates immune pathways (Zheng et al, 2021).. Nord \& Garfinkel support the notion that interoceptive circuits may offer new targets for mind-body interventions by bridging peripheral inflammation and psychiatric symptoms37. Nevertheless, Eggart and colleagues investigated the association between self-report interoceptive awareness and CRP in individuals with Major Depressive Disorder and did not find correlation (Eggart and colleagues). But depressed patients with raised CRP have demonstrated functional connectivity impairment in ventral striatum and medial prefrontal reward and motivation processing areas. Mixed results thus far warrant further exploration.

It may be that yoga acts on interoception and inflammation through different physiologic pathways given some studies showing independence (Eggart et al., 2023; Feldman eta l., 2023). Both improved interoceptive awareness and decreased inflammation can improve whole body health. This study utilizes an adapted yoga intervention to examine changes in inflammatory pathways and epigenetics that have been implicated in trauma (primary outcome), as well as psychiatric symptoms, interoceptive awareness, resilience and whole-body health (secondary outcome) in vulnerable populations, adolescents and young adults with psychiatric conditions.

Despite the widespread interest in yoga among adolescents and young adults and the research demonstrating improved wellbeing for healthy youth, there is a dearth of research studying the mechanisms of yoga for adolescents and young adults with psychiatric conditions. Additionally, systematic exploration of mechanisms of inflammation and epigenetics in rigorous controlled trials is lacking. This is important to understand mechanisms to support emotional wellbeing for this at-risk population whose psychiatric conditions put them at greater risk for negative outcomes, including chronic illness. Larger sample-sized randomized controlled trials with longer term follow up are needed to identify optimal treatment regimens with more representative and appropriately powered samples (Estaveo, 2022).. In addition, a yoga protocol that has been utilized in research studies previously and can be replicated and taught to clinical providers is critical to advance understanding of what kind of yoga may be useful for which populations.

Study Goals and Objectives

Based on the existing evidence, we hypothesize that TAY will improve emotional wellbeing for adolescents and young adults primarily through emotion and stress regulation, although the pathways may involve more top-down processing for young adults and bottom-up processing for adolescents as EWB evolves in development. Main pathways examined in this RCT include psychologic and physiologic mechanisms of stress and emotion regulation.

We hypothesize that TAY intervention will be feasible and accepted intervention given its flexibility and adaptability to unique needs of young adults with psychiatric illness. We believe the saliva swab noninvasive technique will be acceptable and feasible for young adults. We expect to see trends of improved resilience and emotional regulation and hypothesize that these mechanisms can improve psychiatric symptoms for those in intervention arm more than those in the control arm. Further, we hypothesize that 6-week twice weekly TAY will have benefits in psychiatric symptoms through improving emotion regulation and interoceptive awareness. Additionally, we hypothesize that epigenetic changes in HPA-axis and emotion response regulation may be appreciable post intervention.

Interventional Methods

Following consent and completion of the pre-intervention assessment, participants will be randomized using a computerized program to either TAY or a physical-activity control condition. TAY will be provided as a complementary intervention alongside usual outpatient or intensive outpatient care. Participants will attend closed-group, 60-minute sessions twice weekly for 6 weeks. Facilitators will be trained in human-subjects research and trauma-adapted yoga. Participants will be offered choices during the sessions and may decline any activity that causes discomfort.

Control participants will be asked to engage in physical activity of their choice twice weekly during the times scheduled for the yoga sessions, with Fitbit reminders. Weekly telephone calls will be used in both groups to support retention and provide reminders.

Assessments will be completed within 2 weeks before and after the intervention. Post-intervention procedures will include repeat questionnaires, saliva collection, chart-based measures, and a qualitative interview about the participant's experience. Participants on the control arm may elect to switch groups and complete an additional 6-week yoga period. Their pre- and post-intervention assessment will be collected for the cross-over TAY group, as permitted by the approved protocol. Any crossover, intervention changes, or deviations from the assigned condition will be documented and incorporated into the analysis. For the main study, the crossover policy should be finalized before registration and statistical analysis.

Data Management

Each participant will receive a unique study identification code. Identifying information and consent documents will be stored separately from research data in locked, access-restricted locations. The linkage file connecting participant names with study codes will be maintained separately and will be accessible only to the principal investigator and authorized study personnel.

Questionnaire, interview, chart-review, Fitbit, and saliva data will be coded with the study identification number. Paper records will be stored in locked research files, and electronic data will be maintained on password-protected institutional computers, secure institutional servers, Redcap, or approved Upstate OneDrive locations. Research staff with required human-subjects training will have access only to the de-identified data necessary for their responsibilities.

Fitbit data will be retrieved through the authorized Google Health API connection using encrypted HTTPS and OAuth 2.0 procedures. Saliva specimens will be labeled only with study codes and shipped to TruDiagnostics for DNA-methylation analysis. Raw and processed methylation files will be stored on password-protected, encrypted institutional systems.

The principal investigator will oversee data transmission. Any shared data will be de-identified, encrypted, and limited to authorized collaborators identified in the consent materials. Individual saliva or incidental genetic results will not be returned to participants, family members, or treating clinicians. Study data will be retained for at least 10 years.

Data Analysis

Demographic and clinical characteristics will be summarized using descriptive statistics, including means, medians or modes, ranges, and frequencies, as appropriate. Feasibility outcomes will include eligibility and enrollment, retention, completion of assessments, intervention participation, and completion of saliva and Fitbit procedures.

Continuous psychological, physical-health, HRV, and biological measures will be summarized at baseline and post-intervention. Pre-to-post changes within each group and exploratory differences between groups will be examined using t-tests or nonparametric alternatives when distributional assumptions are not met. Results will emphasize estimated changes, effect sizes, confidence intervals, and descriptive feasibility findings rather than definitive claims of effectiveness.

Qualitative interviews will be reviewed using thematic analysis to identify participants' and staff members' experiences of the yoga intervention, barriers to participation, perceived benefits, and recommendations for future implementation. Missing assessments, withdrawals, intervention switching, and protocol deviations will be reported by group. No imputation will be performed unless specified in a subsequently approved analysis plan.