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Most mental disorders first emerge in youth and, in their early stages, surface as subthreshold expressions of symptoms comprising a transdiagnostic phenotype of psychosis, mania, depression, and anxiety. Elevated stress reactivity is one of the most widely studied mechanisms underlying psychotic and affective mental health problems. Thus, targeting stress reactivity in youth is a promising indicated and translational preventive strategy for adverse mental health outcomes that could develop later in life and for improving resilience. Compassion-focused interventions offer a wide range of innovative therapeutic techniques that are particularly amenable to being implemented as ecological momentary interventions (EMIs), a specific type of mobile health intervention, to enable youth to access interventions in a given moment and context in daily life. This approach may bridge the current gap in youth mental health care.
This study aims to investigate the clinical feasibility, candidate underlying mechanisms, and initial signals of the efficacy of a novel, transdiagnostic, hybrid EMI for improving resilience to stress in youth—EMIcompass.
In an exploratory randomized controlled trial, youth aged between 14 and 25 years with current distress, a broad Clinical High At-Risk Mental State, or the first episode of a severe mental disorder will be randomly allocated to the EMIcompass intervention (ie, EMI plus face-to-face training sessions) in addition to treatment as usual or a control condition of treatment as usual only. Primary (stress reactivity) and secondary candidate mechanisms (resilience, interpersonal sensitivity, threat anticipation, negative affective appraisals, and momentary physiological markers of stress reactivity), as well as primary (psychological distress) and secondary outcomes (primary psychiatric symptoms and general psychopathology), will be assessed at baseline, postintervention, and at the 4-week follow-up.
The first enrollment was in August 2019, and as of May 2021, enrollment and randomization was completed (N=92). We expect data collection to be completed by August 2021.
This study is the first to establish feasibility, evidence on underlying mechanisms, and preliminary signals of the efficacy of a compassion-focused EMI in youth. If successful, a confirmatory randomized controlled trial will be warranted. Overall, our approach has the potential to significantly advance preventive interventions in youth mental health provision.
German Clinical Trials Register DRKS00017265; https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00017265
DERR1-10.2196/27462
Youth is a critical life period, and most mental disorders have their onset before the age of 25 years [
Recent rapid advances in digital technologies have led to the development of novel mobile health (mHealth) assessment and intervention techniques, of which ecological momentary assessments (EMAs) [
Underlying transdiagnostic mechanisms may be important intervention targets in youth to prevent transition to and incidence of severe mental disorder. The most widely studied transdiagnostic mechanisms are (1) elevated stress reactivity (ie, more intense emotional reactions to minor stressors in daily life), (2) heightened interpersonal sensitivity, and (3) enhanced threat anticipation. There is evidence that stress reactivity is elevated in individuals with higher familial or psychometric risk, individuals with an ultrahigh risk state for psychosis, first-episode psychosis, severe and enduring psychosis [
Furthermore, our recent EMA findings extended beyond elevated interpersonal and socioenvironmental sensitivity and, consistent with previous research on psychotic, depressive, and anxiety disorders [
Compassion-focused interventions are third-wave cognitive behavioral therapy (CBT) approaches that use a wide range of innovative therapeutic techniques for enhancing emotional resilience by activating emotion regulation systems related to self-compassion, self-acceptance, and positive affect rather than those related to stress, threat, anxiety, and depression [
Against this background, this study will aim to examine the clinical feasibility, underlying mechanisms, and initial signals of efficacy of EMIcompass for improving resilience in an exploratory, randomized controlled trial (RCT) of youth with current psychological distress, a broad CHARMS, or a first episode of severe mental disorder. The EMIcompass intervention will be administered in addition to treatment as usual (TAU) in the experimental condition compared with a control condition of TAU only. Specifically, this study’s aims are as follow:
to establish the clinical feasibility of the trial methodology and deliver the EMIcompass intervention to youth with early mental health problems (based on successful recruitment, assessment of inclusion criteria, randomization, retention in the assessment of outcomes, fidelity of delivering the intervention, compliance with the intervention protocol, satisfaction, and acceptability);
to detect initial signals of the efficacy of the EMIcompass intervention in reducing psychological distress (candidate primary outcome), primary (ie, psychotic, manic, anxiety, or depressive) symptoms, and general psychopathology (candidate secondary outcomes) at postintervention and 4-week follow-up;
to test the effects of the EMIcompass intervention on reducing stress reactivity (primary candidate mechanism), threat anticipation, interpersonal sensitivity, negative affective appraisals, resilience, self-compassion, emotion regulation, and physiological markers of stress reactivity (secondary candidate mechanisms) at postintervention and 4-week follow-up; and
to explore whether the effects of the EMIcompass intervention on psychological distress, primary (ie, psychotic, manic, anxiety, or depressive) symptoms, and general psychopathology are mediated via pathways through stress reactivity, threat anticipation, interpersonal sensitivity, negative affective appraisals, resilience, self-compassion, and emotion regulation.
In an exploratory RCT, youth aged 14-25 years will be randomly assigned to the EMIcompass intervention in addition to TAU (experimental condition) or a control condition of TAU only, which will include routine mental health care. Participants will be recruited from mental health services in Mannheim, Germany, and via advertisements on the institute’s webpage, Facebook, and Instagram and via local registries. Candidate mechanisms and outcomes will be assessed before randomization (at
Study flowchart. EMA: ecological momentary assessment, collected eight times per day on 6 consecutive days (including self-reported and activity or electrocardiography sensor); n denotes the total number of participants.
We will recruit and randomize 92 individuals with current psychological distress, CHARMS or a first episode of severe mental disorder based on a modified version of the clinical staging model by Hartmann et al [
The study, titled
Age between 14 and 25 years
Meeting criteria for one of the following stages (based on a modified version of the clinical staging model by Hartmann and colleagues [
High emotional reactivity assessed with a two-item self-report measure (instruction: “Please think of the most unpleasant event in the last week: (1) How sad, disappointed or angry have you been? (2) Have you been sad, disappointed or angry because of your feelings?”) rated on a 7-point Likert scale (ie, a score of ≥3 indicating high reactivity) or by the interviewer-rated Comprehensive Assessment of At-Risk Mental State subscale [
Reduced positive affect (ie, a mean positive affect score below 3.19 for men and 3.05 for women based on normative scores from a representative sample of the German population [
Willingness to participate in the EMIcompass intervention
Ability to provide written informed consent (or consent by parents in the case of minors)
A primary diagnosis of alcohol or substance abuse or dependence, assessed using the Structured Clinical Interview for DSM-5 [
Evidence that symptoms are precipitated by an organic disease
Insufficient command of German so that the intervention cannot be followed, and outcomes cannot be reasonably assessed in German
Diagnosis of a learning disability according to case records
Current suicidal ideation (indicated by a score>4 in the Comprehensive Assessment of At-Risk Mental State [
Inclusion criteria and transdiagnostic sample characteristics based on a modified version of the clinical staging model by Hartmann et al [
Stage and criteria | Measure | ||||
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Psychological distress (K10a score ≥20) but not fulfilling criteria of stage 1b or 2 |
K10 |
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First degree relative with psychosis and SOFASc < 50 in the last 12 months or Or SOFAS 30% below the past level |
Family risk SOFAS |
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Schizotypal personality and SOFAS <50 in the last 12 months or Or SOFAS 30% below the past level |
SCID IId SOFAS |
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Depressed mood or diminished interest or pleasure for at least 1 week as well as two additional criteria of depression: weight loss, sleep disorder, psychomotor disturbances, loss of energy, feelings of worthlessness or guilt, diminished ability to think or concentrate or indecisiveness, suicidality And mood swings for at least 6 months in the lifetime (not symptom-free for a longer period than 2 months consecutively) and at least three symptoms: decreased need for sleep, increased energy, inflated self-esteem or grandiosity, increase in goal-directed activity, restlessness, increased talkativeness, unusual ideas, risky behavior, inappropriate humor (does not have to equal loss of function!) Or first degree relative with bipolar disorder |
SCID-5e Family risk |
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CAARMSf global rating score of 3-6 and frequency of 3-6 on the subscales: unusual thought content, nonbizarre ideas, perceptual abnormalities, disorganized speech Or global rating score of 6 and frequency of 3 on the subscales: unusual thought content, nonbizarre ideas, perceptual abnormalities, disorganized speech |
CAARMS |
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Elevated, expansive or unusually irritable mood on at least 2 consecutive days And 2 (or in case of only irritable mood 3) additional criteria: inflated self-esteem or grandiosity, decreased need for sleep, increased talkativeness, flight of ideas or subjective experience that thoughts are racing, distractibility, increase in goal-directed activity or psychomotor agitation, unusual ideas, increased involvement in activities that are pleasurable in short time but have a high potential for long-term damage For a duration of 3 days maximum if 3 or more (or in case of only irritable mood 4 or more) additional criteria are met and there are functional disturbances or others notice the mood or functional disturbances For a duration of 6 days maximum if 3 or more (or in case of only irritable mood 4 or more) additional criteria are met or there are functional disturbances or others notice the mood or functional disturbances Exclusion: hospitalization, severe impairment in social or professional functioning, no psychotic elements |
CAARMS |
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Mild or moderate depression (current or lifetime), that is, at least 1 cardinal symptom, 5 additional symptoms And HAM-Dg>17 (cutoff) |
SCID-5 HAM-D |
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Global rating of 6 on the subscales: unusual thought content or nonbizarre ideas Or global rating of 5 or 6 on the subscale perceptual abnormalities And/or global rating of 6 on the subscale disorganized speech present for less than a week And frequency of 4-6 on all above mentioned scales |
CAARMS |
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Mild or moderate panic disorder /agoraphobia (current or lifetime) Or not fully meeting criteria for GADi, that is, symptoms for less than 6 months or less than four symptoms met Or mild or moderate social phobia (current or lifetime) And HAM-Aj>9 (cutoff) |
SCID-5 HAM-A |
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Psychosis | CAARMS | |||
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Severe major depression (current or lifetime) | SCID-5 | |||
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Mania or hypomania | SCID-5 | |||
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Severe anxiety disorder (current or lifetime); eg, agoraphobia, GAD | SCID-5 |
aK10: Kessler Distress Scale [
bCHARMS: Clinical High At-Risk Mental State.
cSOFAS: Social and Occupational Functioning Assessment Scale [
dSCID II: Structured Clinical Interview for DSM-IV Axis II Personality Disorders,
eSCID-5: Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) [
fCAARMS: Comprehensive Assessment of At-Risk Mental State [
gHAM-D: Hamilton Depression Rating Scale [
hBLIPS: brief limited intermittent psychotic symptoms.
iGAD: Generalized Anxiety Disorder.
jHAM-A: Hamilton Anxiety Rating Scale [
Participants allocated to the TAU control condition will continue to receive all the treatment they received before the start of the study. This will include good standard care delivered according to local and national service guidelines and protocols by their general practitioner, psychiatrist, and other providers of (mental) health care. Service contacts will be assessed for the duration of the trial using the Client Service Receipt Inventory [
The EMIcompass intervention will be delivered by trained psychologists within a 6-week period in addition to TAU to individuals allocated to the experimental condition. TAU consists of all the treatment individuals received before inclusion in the study, including their general practitioner, psychiatrist, and clinical psychologist, except for treatment using elements of third-wave CBT. The manualized EMIcompass intervention consists of four biweekly sessions (three training sessions and one review session) with a duration of 45-60 minutes administered face-to-face or using a certified and encrypted video conferencing system and a 6-week compassion-focused EMI. An optional on-demand session will be offered if participants are unable to complete tasks between sessions or report acute psychological distress so that a scheduled session cannot be followed as per the manual. The EMI, which translates the training from the intervention sessions into individuals’ daily lives, will be administered through a smartphone-based app (movisensXS, movisens GmbH) running on dedicated study smartphones. The first three sessions are based on elements of compassion-focused therapy [
The app will offer EMI tasks according to three types of delivery schemes: (1) enhancing, (2) consolidating, and (3) interactive EMI tasks that aim for ecological translation of therapeutic principles and techniques to daily life. Participants will be asked to complete one
Participants will be instructed in detail in the semantic meaning of the 7-point Likert and bipolar scales and encouraged to carefully observe moment-to-moment variation in, and make use of the full range when rating, these scales on EMA items that have been previously used and validated to measure moment-to-moment variation in stress or negative affect. Given that a crucial element of compassion-focused therapy is for individuals to use compassionate imagery in moments of high stress or negative affect, these interactive tasks reflect an important component of the EMIcompass intervention. Participants can decline the EMI tasks in each delivery scheme. After completing the intervention period, participants will return the study devices and will no longer have access to the app.
Momentary stress was operationalized as unpleasant events, activities, and social situations in daily life. In line with previous research, we distinguished three different types of stress, that is, event-related stress, activity-related stress, and social stress [
Six items will be used to assess negative affect (anxiousness, loneliness, insecurity, anger, annoyance, and feeling down), using 7-point Likert scales ranging from “not at all” (rating of 1) to “very much” (rating of 7)
In case participants report negative affect (ratings >3), two items on how they cope with their negative affect will be displayed: “I want to change my negative feelings” and “I would like to get rid of my negative feelings” using two 7-point Likert scales
Positive affect will be assessed by four items (cheerfulness, satisfaction, enthusiasm, and feeling relaxed) using 7-point Likert scales ranging from “not at all” (rating of 1) to “very much” (rating of 7)
The ecological momentary assessment measure comprises three items in line with [
Three items will be rated on a 7-point Likert scale ranging from “not at all” (rating of 1) to “very much” (rating of 7): “I feel guilty,” “I doubt myself,” “I feel disappointed about myself”
Three items will be rated on a 7-point Likert scale ranging from “not at all” (rating of 1) to “very much” (rating of 7): “I like myself,” “I feel safe,” “I feel benevolent”
Psychotic experiences will be assessed using eight items on thought problems and hallucinations (“I see things that aren’t really there,” “I hear things that aren’t really there,” “I feel suspicious,” “It's hard to express my thoughts in words,” “I feel unreal,” “My thoughts are influenced by others,” “I can’t get these thoughts out of my head,” “I feel like I am losing control”) that will be rated on 7-point Likert scales ranging from “not at all” (rating of 1) to “very much” (rating of 7)
If participants indicate that there was a negative event (valence −3 or −2), then the item “I had difficulties to recover” will be rated on a 7-point Likert scale
In line with previous research, we will ask participants to rate the likelihood of negative events happening to them in the future [
“This prompt disturbed me” will be rated at the end of each assessment on a 7-point Likert scale from “not at all” (rating of 1) to “very much” (rating of 7)
Clinical feasibility will be assessed in relation to the trial methodology and the delivery of the EMIcompass intervention to youth with early mental health problems. The feasibility of the trial methodology will be assessed based on the following criteria: (1) successful recruitment of at least 96 participants during the study period; (2) assessment of inclusion criteria in 95% of potential participants after obtaining written consent; (3) successful randomization of at least 92 participants after completion of eligibility and baseline assessment; and (4) a retention rate of at least 85% for assessment of outcomes at least at one of the two time points at postintervention and 4-week follow-up. In addition, the following criteria will be used for establishing the feasibility of delivering the EMIcompass intervention, including its acceptability, intervention adherence, and intervention fidelity: (1) satisfaction with the EMIcompass intervention in general, ease of use, accessibility and comprehensiveness of various components of the intervention in a debriefing questionnaire [
After obtaining written informed consent, all eligible participants will be assessed on candidate mechanisms and outcomes before randomization (
The primary candidate mechanism is a reduction in stress reactivity acquired by EMA from baseline to postintervention for the experimental condition compared with the control condition. EMA will include eight assessments per day, scheduled at random within set blocks of time, for 6 consecutive days at baseline, postintervention, and follow-up [
Secondary candidate mechanisms (
The candidate primary outcome of this exploratory RCT is psychological distress measured using the well-validated Kessler Psychological Distress Scale [
Secondary outcomes include primary (ie, psychotic, manic, anxiety, or depressive) symptoms and general psychopathology. These will be assessed using the following observer-rated measures: the Brief Psychiatric Rating Scale [
Other study parameters will include basic sociodemographic characteristics, familial risk factors for psychopathology, and other parameters (including age, sex, alcohol or substance use, and childhood trauma [
A formal sample size calculation is not essential for this exploratory trial, which primarily seeks to establish feasibility, effects on candidate mechanisms, and initial signals of efficacy. In planning, we aimed to determine the sample size in such a way as to establish the feasibility of the methodology for conducting an RCT and delivering the EMIcompass intervention to youth with early mental health problems and initial signals of the efficacy of EMIcompass in reducing psychological distress as a candidate primary outcome (see Statistical Analysis Plan [
Participants will be randomized at a 50:50 ratio to the experimental or control condition at the level of the individual participant after completion of the baseline assessment. Block randomization in blocks of four will be performed by an independent research assistant through a computer-generated sequence, with stratification for the three stages (ie, stages 1a, 1b, and 2). The assessors will be blind to the allocation of participants when assessing outcomes at postintervention and follow-up. Any data specific to the intervention group (eg, clinical feasibility) will be stored in a separate database. Breaks in masking will be documented, and another (blinded) researcher will repeat the assessment to maintain masking.
Serious adverse events (SAEs) will be monitored throughout the entire study period and reported to the accredited Medical Ethics Review Committee, the Data Monitoring and Ethics Committee (DMEC), and, where required, the Trial Steering Committee (TSC). SAEs are any serious incidents that result in death, persistent or significant disability or incapacity that require hospitalization, or life-threatening situations. SAEs are not expected to occur as a result of the intervention. If there are doubts about safety or ethical concerns, the TSC will terminate the trial. The DMEC will advise on safety and ethical concerns, monitor evidence for harm by the intervention (eg, SAEs) in the experimental condition, and review whether these events are in line with expectations. If deemed necessary, the DMEC can recommend to the principal investigator (PI) and TSC for interim analyses to be conducted and the trial to be terminated prematurely.
The primary objective of this exploratory RCT is to establish the feasibility of the trial methodology and intervention delivery and initial signals of efficacy on the candidate primary outcome (ie, psychological distress) as a basis for a future definitive trial. In addition, this trial seeks to obtain parameter estimates (95% CI) for the effects on primary and secondary candidate mechanisms and candidate secondary outcomes. A detailed Statistical Analysis Plan [
The trial is ongoing. It started recruitment on July 15, 2019, and the first enrollment was conducted in August 2019. We are currently working with trial protocol version 5 (June 24, 2020). The last changes to the protocol were related to adaptations because of the COVID-19 pandemic, such as introducing the option of using video conferencing systems. As of May 2021, enrollment and randomization were completed (n=92 participants). Assessment of outcomes at postintervention and follow-up is still ongoing, with the last assessment for the last participant being scheduled for August 2021. Data will then be entered, checked, and the database locked (by September 2021). We expect results to be published in 2022.
The CIMH is the trial sponsor. The study has received ethical approval by the local ethics committee (EC) of the Medical Faculty Mannheim, Heidelberg University (2017-602N-MA). Amendments to the study protocol will be submitted to the EC and sent to the DMEC, TSC, and study sponsor. The trial is registered at the clinical trial register, and changes to the protocol will be updated. Deviations from the protocol will be documented in the study folder using a breach report form and will be reported to the TSC. The trial does not involve the collection or storage of biological samples. All data will be handled confidentially and will be coded using a number according to the order of study entry. Data will be securely stored in line with the European General Data Protection Regulation. Personal data will be kept separately from pseudonymized data. The PI has overall responsibility for the trial. The trial research team will meet regularly and will be chaired by the PI. It will manage the day-to-day running of the study, monitor the progress of the trial (ie, recruitment and assessment), and oversee the preparation of presentations and reports to EC, TSC, and DMEC. The TSC will meet biannually and provide independent overall supervision, monitor the progress of the trial (eg, recruitment, data completion rates, and adherence to the protocol), and approve the protocol and any amendments. The DMEC will meet at least once per year, advise on ethical or safety concerns, monitor SAEs and other evidence of intervention harm and whether this is in line with expectations. If deemed necessary, the DMEC can recommend that the PI and TSC are granted access to all trial data, to perform interim analyses and to terminate the trial prematurely.
Transdiagnostic mechanisms implicated in the development of severe mental disorders are important targets for prevention and early intervention. Ecological translation of compassion-focused intervention components to individuals’ daily lives through an EMI offers new avenues for tangible prevention strategies delivering real-world and real-time interventions that are easily accessible by youth [
The present exploratory RCT is the first to establish feasibility, evidence on underlying mechanisms, and preliminary signals of efficacy of a compassion-focused, hybrid EMI for reducing stress reactivity (EMIcompass) in youth at different clinical stages. Preliminary evidence from a pilot study of the EMIcompass intervention in help-seeking youth showed reductions in clinical symptoms and stress reactivity [
Standard Protocol Items: Recommendations for International Trials (SPIRIT) figure.
cognitive behavioral therapy
Clinical High At-Risk Mental State
Central Institute of Mental Health
Diagnostic and Statistical Manual of Mental Disorders
Data Monitoring and Ethics Committee
ethics committee
electrocardiography
ecological momentary assessment
ecological momentary intervention
mobile health
principal investigator
randomized controlled trial
Research Electronic Data Capture
serious adverse event
treatment as usual
Trial Steering Committee
This work is funded by a German Research Foundation project grant (#389626655) and German Research Foundation Heisenberg professorship (#389624707) to UR. The sponsor and funding agency do not have any role in the trial design, data collection, statistical analysis, interpretation of data, writing of the manuscript, or the decision to submit reports for publication. AML is supported by German Federal Ministry of Education and Research (BMBF, grant 01EF1803A) Ministry of Science, Research and the Arts of the State of Baden-Wuerttemberg, Germany (MWK, grant 42-5400/136/1); Ministry of Science, Research and the Arts of the State of Baden-Wuerttemberg, Germany (MWK, grant 42-04HV.MED(16)/16/1); and Ministry of Science, Research and the Arts of the State of Baden-Wuerttemberg, Germany (MWK, grant 42-04HV.MED(16)/27/1). The authors are indebted to all individuals who participated, past and present, in the EMIcompass study and are essential for its successful completion. The authors are grateful to Professor Stefan Priebe, Professor Stefan Wellek, Dr Jan R Böhnke, Professor Nicolas Rüsch, Dr Thomas Vaessen, Professor Maria Blettner, Professor Sebastian von Peter, and Professor Georg Schomerus for their membership in the TSC and DMEC, respectively. The authors also thank all trained psychologists (Isabell Paetzold, Dr. Sebastian Butz, and Leonie Schültke) and research assistants.
UR designed the study, is the PI, and has managerial responsibility for the successful completion of the study. JB is the trial statistician. BB provides supervision for the trained psychologists who deliver the intervention. AS, UR, CR, and IP drafted the manuscript. All authors were involved in writing, reading, and approving the final manuscript.
None declared.