Mindfulness for Resilience in Early Life
Phase: NA
Conditions: Adolescent With Early Life Stress, Resilience
Sponsor: Laureate Institute for Brain Research, Inc.

 
 
 
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ClinicalTrials.gov Document 
 
Project Title: MindREaL: Mindfulness for Resilience in 
Early Life (MindREaL) 
Identifier: NCT03633903 
Last approved: May 31, 2018 Uploaded: June 30, 2021 
 
 
 
 
Principal Investigator:  
Namik Kirlic PhD, Post-Doctoral Associate, Laureate Institute for Brain Research 
 
Sub-Investigators:  
Martin Paulus, MD, President and Scientific Director, Laureate Institute for Brain Research 
Robin Aupperle, PhD, Principal Investigator, Laureate Institute for Brain Research 
Amanda Morris, PhD  
 
Sponsor: Oklahoma State University and Laureate Institute for Brain Research 
 
 
 
 
 

 
 
 
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ABSTRACT 
Early life stress (ELS) is associated with a number of psychiatric and medical conditions later in life, 
thought to be caused by subsequent disruptions in biological processes involved in regulation of stress 
responses. Given that these alterations have long-lasting effects, there is a great need for effective 
preventative interventions. The long-term goal of this project is to identify early interventions that may 
most powerfully mitigate risk for psychiatric illness among adolescents with exposure to early life stress 
(ELS), with a focus on interventions that can be widely and effectively implemented, have the potential 
for long-lasting benefits, and can effectively engage targeted neurobiological processes and networks. The 
specific aims of the present study are to 1) examine how ELS impacts biological processes associated with 
regulation of stress, and 2) identify how a mindfulness-based intervention (MBI) impacts affective 
symptoms and biological processes dysregulated by ELS. 
The proposed study will utilize a multi-method design to examine the effect of mindfulness on 
biological processes (i.e., stress responses) disrupted by exposure to ELS among adolescents age 13 to 15. 
Adolescents will first complete self-report measures of childhood adverse experiences, trauma, and 
neglect. Forty eligible adolescents will be next randomly assigned to either an eight-session mindfulness-
based stress reduction (MBSR) intervention or treatment as usual (TAU). Pre- and post-intervention 
assessment will include (a) self-report measures of symptoms and emotion regulation, (b) a blood draw 
for assessment of inflammatory markers and gene expression, and (c) a stress task with saliva cortisol 
collected before and after this task. 
 
SPECIFIC AIMS 
The current study will accomplish the following goals.  
Aim 1: Examine how ELS impacts biological processes associated with regulation of stress. 
Hypothesis 1a: ELS severity will relate negatively to cortisol changes with the TSST-C. Hypothesis 1b: ELS 
severity will relate to increased demethylation of the FKBP5 gene and inflammatory markers (IL-6, CRP). 
Aim 2: Identify how MBI impacts affective symptoms and biological processes dysregulated by ELS. 
Hypothesis 2a: MBI adolescents will evidence a clinically significant reduction in internalizing and 
externalizing symptoms, and emotion dysregulation. Hypothesis 2b: MBI adolescents will evidence 
normalization in cortisol reactivity in pre- to post-TSST. Hypothesis 3c: MBI adolescents will evidence a 
normalization in the methylation of the FKBP5 gene and levels of inflammatory markers (IL-6 and CRP). 
 
BACKGROUND AND SIGNIFICANCE 
Early life stress, characterized by childhood sexual abuse, and physical and emotional abuse and 
neglect is the leading preventable risk factor for future adverse physical and mental health outcomes. ELS 
affects more than 700,000 children and adolescents in the United States [1] and is a serious problem in 
Oklahoma, where recent reports suggest that 15,187 of youth (~1.5%) are being abused and neglected [2-
4]. It is estimated that yearly cases of abuse and neglect may impose a cumulative cost to society of $80.3 
billion in direct (e.g., hospitalization, mental health care costs, and child welfare costs) and indirect costs 
(e.g., special education, early intervention, and lost productivity) [4].  
Consequences of ELS exposure are staggering. Several hallmark studies, including the Adverse 
Childhood Experiences (ACE) study, found that adults with >4 ACEs were at a significantly greater risk for 
obesity, cardiovascular, gastrointestinal, and respiratory disease, as well as depression, anxiety, panic, 
suicide attempts, and substance use [5, 6]. Further, ELS is associated with greater severity and 
comorbidity, earlier onset, and poorer response to treatment of psychiatric conditions [6]. 
These negative outcomes are believed to stem from a cascade of ELS-related alterations in biological 
processes responsible for regulation of stress, including epigenetic, HPA axis, brain development, and 
immune system disruptions [7]. Stress activates the HPA axis resulting in the release of cortisol, necessary 
for integration of appropriate responses to stress and the subsequent return to homeostasis via a cortisol-

 
 
 
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based negative feedback loop. The FKBP5 gene regulates glucocorticoid receptor sensitivity and is thus 
crucial in this negative feedback loop. ELS exposure and the excessive cortisol release due to the repeated 
activation of the HPA axis results in the demethylation of the FKBP5 gene, in turn increasing the resistance 
of the glucocorticoid receptors. This, in turn, diminishes the negative feedback loop, and prolongs stress 
hormone activation following a stressor. Overtime, this can lead to dysregulated HPA axis functioning 
(including attenuation of stress responses altogether [8]) and alterations in brain structure and function 
(e.g., hippocampus) and the immune system. ELS is associated with blunted cortisol responses during a 
stress induction task [9, 10], as well as disrupted immune system functioning, characterized by increased 
levels in pro-inflammatory markers [11, 12]. Neuroimaging evidence suggests that ELS alters trajectories 
of brain development in turn impacting network architecture and circuits involved in threat detection, 
emotional regulation, and reward anticipation [13, 14]. For example, a recent study showed aberrant 
amygdala responses to emotional conflict among maltreated youth, and subsequent failure to engage 
pregenual anterior cingulate (ACC)-amygdala inhibitory circuitry during its implicit regulation [7]. 
Together, dysregulation of these systems increases the risk for psychiatric, immune, and metabolic 
disorders [15]  (Figure 1).  
 
 
 
Given that these alterations have long-lasting effects, there is a great need for effective interventions. 
Past intervention studies indicate that ELS adolescents and adults with psychiatric illnesses (e.g., 
depression) have significantly poorer relative responses to psycho- and pharmacotherapy [16, 17]. 
However, ELS exposed individuals are underrepresented in intervention studies, and longitudinal 
treatment outcome studies using multiple objective measurements of change, including biomarkers, are 
needed.  
Regulation of stress and emotions are crucial developmental processes often disrupted by ELS 
exposure [18, 19]. Given the increased neural plasticity and ongoing brain development, adolescents 
exposed to ELS may be malleable to long-term normalization in systems subserving stress responses as a 
result of psychological intervention. Previous research has document such changes. For example, rodent 
studies show that optimal maternal rearing results in changes in gene expression in offspring resulting in 
improved stress resilience [20], while neuroimaging studies in adult humans show normalization in activity 
in the prefrontal cortex and limbic regions involved in stress responses following psychological 
intervention [21].  
Mindfulness-based interventions (MBI) promote emotional awareness and regulation by developing 
one’s ability to observe internal experiences and gain control over thoughts, emotions, and behaviors 
[22]. Thus, they are well suited to target biological processes involved in stress regulation. Research in 
both adults and youth shows that MBIs reduce symptoms of depression and anxiety, and improve 
cognitive and relational outcomes [23-26]. Moreover, recent data indicate that mindfulness practice may 
Early Life Stress 
Abuse 
Neglect 
Epigenetics 
DNA  
demethylation 
Immune Function 
Alterations in  
inflammatory  
responses 
HPA activity 
Altered cortisol  
stress response 
Brain development 
Altered brain  
structure  
and function 
Outcomes 
Cardiovascular disease 
Pulmonary disease 
Obesity 
Diabetes 
Chronic pain 
Psychiatric disorders 
Substance use 
Figure 1. A representation of how early life stress impacts mental and physical health by affecting 
relevant biological processes. 

 
 
 
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positively influence processes involved in regulation of stress responses in adults, including gene 
expression (e.g., decreased expression of pro-inflammatory genes) [27], immune and endocrine system 
markers (e.g., reduction in C-reactive proteins and increased cortisol reactivity, respectively) [22, 28], and 
activation in a distributed network of brain regions [29-31]. Scant neuroimaging data suggests that 
mindfulness practice may activate a distributed network of brain regions, including the anterior insula, 
subgenual and rostral ACC, dorsal and ventral PFC [15, 23, 24], and increase amygdala-ventral PFC 
connectivity during emotional tasks. Furthermore, the extent of these neural effects relate to the amount 
of symptom reduction observed[25]. Consequently, it has been proposed that mindfulness exerts its 
observed psychological and behavioral changes by increasing the activity and functional connectivity of 
prefrontal cortical regions involved in top-down regulation, while simultaneously decreasing the activity 
and functional connectivity in neural regions that gate emotional response [11]. Therefore, mindfulness 
represents a potential regulatory intervention that may inhibit or reverse some of the deleterious long-
term effects of ELS exposure.  
In summary, previous research suggests the ELS has long-lasting adverse mental and physical health 
consequences, which likely stem from related disruptions in epigenetic, hormonal, inflammatory, and 
neuronal systems. At this time, it is unclear whether these disruptions can be compensated for or 
altogether reversed with psychological interventions. Given the high prevalence of ELS and difficult 
socioeconomic circumstances in Oklahoma, prevention of ELS adverse outcomes is perhaps one of the 
most important challenges currently facing our community.  
 
CRITERIA FOR SUBJECT SELECTION 
Recruitment 
Adolescents participants will be recruited from the Tulsa metropolitan area through Facebook ads, 
radio ads, and flyers, and contact with local mental health agencies, including Family and Children’s 
Services (FCS) of Tulsa. FCS provides behavioral health care and family services for a range of issues, 
including trauma exposure and neglect. Currently, they serve more than 400 adolescents ages 13 through 
15. Additionally, as part of a consortium, LIBR is currently conducting a large longitudinal study examining 
adolescent brain and development (ABCD; Western IRB: U01DA041089). Recruitment for the current 
study will focus on siblings of the ABCD participants of which more than 100 are estimated to be in the 
13-15 age range. Finally, LIBR is conducting a neuroimaging study of adolescents and their parents (DIBS; 
Oklahoma State University IRB: 2017011). Participants excluded from this study (e.g., due to orthodontic 
braces) may be eligible for the current study. If these participants consent to being contacted by other 
studies conducted at LIBR, they will be recruited. Recruitment materials will be distributed through 
mailings, placement in treatment/research facilities, and contact with treatment providers. Recruitment 
materials are included with this application. 
The racial and ethnic demography in the present study is aimed to match the demographic 
composition of Tulsa, OK based on the U.S. Census Bureau, 2010 Census [32]. The expected racial 
composition is: 69% White and 11% Latino, 10% Black/African-American, 2% Asian, 6% American 
Indian/Alaskan Native, and less than 1% Pacific Islander.  
We will be recruiting up to 80 participants for this study. The advertisement materials will indicate 
that LIBR is conducting a research study designed to better understand how mindfulness training may 
help teens deal with stress and become more resilient. The materials will explain that the mindfulness 
training will consist of 8 biweekly sessions that have been known to help teens manage stress. 
Additionally, recruitment materials will state that a number of participants will be invited to provide 
biological samples (i.e., saliva and blood) to examine their relationship with early positive and negative 
life events and impact of mindfulness on biological responses. We aim to recruit 40 participants with ELS 
for the research study.  
 

 
 
 
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Inclusion Criteria 
- 
Age 13.00 to 15.99 years at time of baseline assessment 
- 
Able to validly and safely complete baseline assessments 
- 
All genders 
- 
All races  
- 
Eligibility as a subject with early life stress will be determined by: 
 
Scoring 4 or greater on Adverse Childhood Experiences (ACE) scale, with at least two 
experiences having occurred prior to age 10. 
 
Exclusion Criteria 
- 
No biological parent or legal guardian identified to give permission for minor to participate 
- 
History of neurological disorders including seizure disorder, cerebral palsy, or other conditions 
requiring neurological or medical care, being managed for migraines (e.g., daily prophylactic 
medication, seeing a neurologist for migraines), or a diagnosis of Developmental Delay, including 
severe learning disorder, mental retardation, pervasive developmental disorder, or other 
conditions requiring repeated and persistent specialized education.  
- 
Current psychotic disorder, bipolar disorder, obsessive-compulsive and related disorders, 
substance use disorder, or conduct disorder.  
- 
Current active suicidal ideation. 
- 
Current use of medications with major effects on brain function or blood flow (e.g., antipsychotics, 
mood stabilizers); ADHD medications and SSRIs, that have been stable for at least 6 weeks, are 
not exclusionary since their use is associated with conditions that confer risk for monitored 
disorders that emerge in adolescence, and assessment of these individuals will provide useful data 
to the scientific community. Youth on ADHD medications and SSRIs will not be asked to go off 
their medications.   
- 
Not fluent in English  
- 
Non-correctable vision, hearing or sensorimotor impairments, as protocol elements may not be 
valid. 
- 
Youth planning to move to an area not within reasonable traveling distance of LIBR; knowledge 
at baseline that treatment completion / follow-up will not be possible. 
- 
Youth appears to be high/intoxicated, or withdrawing from the effects of alcohol or drugs at time 
of enrollment.  
- 
Youth / parent who are unable or unwilling to provide biological samples (i.e., blood draws or 
saliva collection). 
- 
Female youth who are pregnant 
- 
Youth who are currently in unsafe environments (e.g., currently living with an abusive parent)  
 
Eligibility will be determined by the PI and trained study staff during screening and baseline 
assessments.  
 
Informed Consent 
Interested youth or parents will call the research site in response to recruitment advertisements or 
the parent will be contacted by study staff using contact information provided by each agency/study. 
Verbal consent and permission will be obtained from a parent/legal guardian initially, and the mindfulness 
training and the research study will be described in more detail. The parent/legal guardian will be 
screened with basic eligibility questions using the Parent Screening Questionnaire. If the family remains 
interested and the youth remains eligible, an in-person assessment session will be scheduled during which 

 
 
 
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documented HIPAA, Parent/Legal Guardian, Permission for Child, Adult (parent, legal guardian, primary 
caregiver) Informed Consent, and Youth Assent forms will be reviewed with the family.  
All participant interactions including consenting will be conducted in private interview/exam rooms 
at the Laureate Institute for Brain Research. These exam rooms are secured from public areas via 
combination locked doors that are only accessible to authorized personnel. Consent and parent 
permission from the enrolled parent will be obtained by members of the research team that have received 
training to obtain consent for this study. Written informed consent will be obtained from each participant 
after they have been provided a full verbal and written explanation of the study purposes, procedures, 
risks, and benefits, and after they have been allowed sufficient opportunity to review this information and 
ask questions concerning any aspect of the study. The researcher will remind the subject that participation 
is strictly voluntary and remind them that they have the right to withdraw at any time without penalty. 
Family members will be allowed to be present and discuss the consenting process with the participant if 
requested.  
During the informed permission and consent process, the parent/legal guardian/primary caregiver 
will be told he/she will not be informed about the child’s substance or medication use and that youth self-
report and lab data are confidential, with the exception of any acute safety issues (e.g., suicidality, medical 
emergency). Recruitment related research procedures present no more than minimal risk of harm to 
subjects and involve no procedures for which written consent is normally required outside of the research 
context. The assent/consent forms include baseline assessments, intervention sessions, and post-
intervention follow up participation; therefore, informed assent/consent will be obtained at study entry. 
However, if the assent/consent forms are amended during the follow up phase of the study, participants 
will be asked to again provide assent/consent/permission. After providing their assent to participate, we 
will ensure youth fully understand the study and the assenting process by administering a Consent Quiz 
consisting of simple questions about the procedures explained in the Youth Assent. 
 
Enrollment 
Eighty adolescents will be enrolled. Randomization will be stratified by ELS exposure, gender, and 
medication use. High-ELS adolescents (n=40) will complete both self-report assessments and biospecimen 
/ behavioral tasks portions at baseline and follow-up visits, while low-ELS adolescents (n=40) will complete 
only self-report assessments at baseline and follow-up visits. Twenty high-ELS and 20 low-ELS adolescents 
will then be randomly assigned to an eight-session mindfulness-based stress reduction (MBSR) 
intervention or treatment as usual (TAU). Adolescents will be informed during the consent that only some 
participants will be asked to complete the more extensive assessments, but they will not be told how that 
determination is made (so as to prevent participants from reporting higher ELS in order to obtain more 
compensation in the study). To remain in the study, participants will be required to complete 6 of 8 
mindfulness sessions.  
 
Participation Compensation 
Adolescent compensation will be as outlined in the table below. Snacks will be provided per request, 
depending on the duration of the study appointment. For subjects who do not complete the baseline or 
follow up visits, they will receive a prorated amount of $10 per hour of participation. Compensation for 
weekly assessments will be made following completion of each assessment. The payment will be given as 
a ClinCard, a reloadable credit card that can be used at stores, online, or for cash at local banks. 
 
 
 
 
 

 
 
 
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Baseline 
Online 
Assessement 1 
Online 
Assessment 2 
Sessions 
1 - 8  
Follow 
up 
Total 
High ELS 
(n=40) 
$90 
$5 
$5 
$40 
$80 
$220 
Low ELS 
(n=40) 
$20 
$5 
$5 
$40 
$20 
$90 
 
 
RESEARCH DESIGN AND METHODS 
Overview  
At the baseline visit, adolescents will complete a number of surveys assessing positive and negative life 
events, childhood trauma history, mental health symptoms, emotion awareness and regulation, 
resiliency, and mindfulness skills. At this time, adolescents will be randomly assigned to either a MBSR 
training group or online assessment only (TAU) group. Particular care will be taken to ensure that 20 
adolescents with ELS are assigned to each group. ELS adolescents in both groups will also complete 
behavioral tasks and provide biospecimens.  
 
MBSR training will commence within two weeks of baseline assessment and consist of 8 sessions over 4 
weeks. Each week, training participants will complete a brief self-report assessment electronically. TAU 
group will complete similar assessments online.  
 
Following mindfulness training sessions, a follow-up visit will be scheduled during which baseline 
procedures will be repeated. Adolescents and parents may be contacted via text message to remind them 
of upcoming sessions as well as reminders to complete online portions of questionnaires.  
 
Self-Report Assessments 
Parent characteristics will be assessed, including age, educational attainment, race and ethnicity, and 
marital status. Current family income will be obtained, as well as sources of subsidized income such as 
WIC, food stamps, AFDC (TANF), Social Security, or Disability. Child age, gender, race and ethnicity will be 
assessed. 
History of ELS will be assessed using the ACE Study Questionnaire [33]. This measure assesses which 
assesses instances (answered yes or no) of physical abuse, sexual abuse, emotional abuse, neglect, and 
household dysfunction before the age 18. Household dysfunction consists of living with a substance 
abuser or a parent with mental illness, witnessing domestic violence, having parents divorced or 
separated, or having a family member go to prison. 
Protective and Compensatory Experiences (PACEs) assess ten experiences children need to prevent 
adverse childhood experience and promote resilience, including stable caregiving, stable home and school 
environments, positive adult and peer relationships, and involvement in extracurricular activities.  
The Life Chart (LC) is a structured interview that is used to obtain life history related to significant 
negative or positive events and the associated mood ratings in a person’s life.  
Traumatization history, including its severity, will be assessed with the Childhood Trauma 
Questionnaire (CTQ; [34]). The CTQ consists of 28 items, comprising five subscales: (1) Physical abuse, 
(2) Sexual abuse, (3) Emotional abuse, (4) Physical neglect, and (5) Emotional neglect.   
Adolescents’ depressive symptoms will be assessed with the 13-item Short Mood and Feelings 
Questionnaire – Child Version (SMFQ-C; [35]). A range of other internalizing and externalizing symptoms 
will be assessed with the widely-used Youth Self Report (YSR) scales [36].  
Adolescents will also complete the Sadness and Anger Management Scales (SAMS; [37]) to assess 
emotion regulation. Behavioral responses for each emotion are rated for dysregulated expression (e.g., “I 

 
 
 
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cry and carry on when I’m sad”), and coping (e.g., “I try to calmly deal with what is making me feel mad”). 
Difficulties in Emotion Regulation Scale (DERS), a comprehensive measure of emotion regulation and 
dysregulation, will assess the following domains: a) awareness and understanding of emotions, b) 
acceptance of emotion, c) the ability to engage in goal-directed behavior / refrain from impulsive 
behavior, and d) access to effective emotion regulation strategies [38].  
Mindful Attention Awareness Scale – Adolescent (MAAS-A; [39]) is a self-report measure that assesses 
mindfulness in adolescents across 14 items, such as “It seems I am ‘running on automatic’ without much 
awareness of what I’m doing.” This is the adapted version of the adult measure, which has been found to 
be sensitive to change in mindfulness as a result of MBSR training. 
Connor-Davidson Resilience Scale (CD-RISC 10; [40]) is a brief measure that assesses stress coping 
abilities. This measure was found to have adequate reliability and validity. However, subsequent factor 
analyses demonstrated that a briefer version of the measures, utilizing just 10 items was sufficient to obtain 
the same information as that obtained from the full scale.  
Adolescent Alcohol and Drug Involvement Scale (AADIS; [41]) will assess adolescent history of drug use 
for a range of alcohol and non-prescription drugs.  
Suicide Behavior Questionnaire – Revised (SBQ-R; [42]) has four items that assess for previous suicidal 
ideation and attempts, frequency of suicidal ideation, threat of a suicide attempt, and likelihood of suicidal 
behavior in the future. This questionnaire had been used and validated with adolescent and college samples. 
A cutoff score of 7 has been suggested as associated with risk for suicidal behavior and further follow-up. In 
order to take a more conservative approach, we will follow-up with any student scoring >7 total score, or >2 
on question #4 (indicating they are unlikely to very likely to commit suicide someday). The timeline for the 
questions will be revised to specify the time duration since their last survey (rather than “in the past year”) – 
for example, “since your last survey 3 months ago”. Those who score greater than these specified cutoffs will 
be contacted by the PI or other clinically-trained staff to further assess for suicidal ideation, plan, and intent 
using the Columbia-Suicide Severity Rating Scale. 
Columbia-Suicide Severity Rating Scale (CSSR; [43]) supports suicide risk assessment through a series of 
simple, plain-language questions that anyone can ask. The answers help users identify whether someone is 
at risk for suicide, assess the severity and immediacy of that risk, and gauge the level of support that the 
person needs. In cases of a positive screen for suicidal ideation (see above description of the SBQ-R), the full 
CSSR Interview (last month only) will be completed by the PI or other clinically-trained staff to further assess 
suicidal ideation, plan, and intent. 
Adolescents will report on unsupportive parenting using the punitive parenting/harsh discipline scale 
of the Alabama Parenting Questionnaire (APQ; [44]), which includes questions assessing corporal 
punishment and hostility. 
 
Behavioral Tasks 
ELS participants will complete a standardized task that induces stress reactions, as well as an 
emotional conflict task, at baseline and follow-up time points.  
Trier Social Stress Test for Children (TSST-C; [45]) is the adapted version of the TSST for the use in 
children and adolescents aged 7-16 years of age. Participants will be instructed that this task consists of 
two portions, a public speaking and mental arithmetic components. The speaking task begins with the 
adolescent given the stem of a story, and he or she will be asked to complete the story in an interesting 
and exciting way. Additionally, the adolescent will be told that the story ending should be better than that 
provided by other participants. The participant will have a 5-minute preparation period and then must 
complete the story over the course of 5 minutes. If the adolescent finishes the story in less than 5 min, 
they will be asked to continue, and this request is delivered in a friendly, supportive manner. Following 
the story component, the adolescent will complete a serial subtraction task, with encouragement to 
complete it as quickly and as accurately as possible. Salivary cortisol will be collected before and 10-20 

 
 
 
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minutes after the task. TSST-C will be delivered by two research assistants on the study. 
During the Emotion Conflict Task (ECT; [46]) participants will view images of happy or fearful facial 
expression, overlaid with the words “FEAR” or “HAPPY”. Participants will be instructed to identify the 
underlying facial emotional expression (fearful or happy) while ignoring an overlying emotion word 
(‘FEAR’ or ‘HAPPY’). Trials will vary such that emotional distracter words either match (‘congruent’ (C)) or 
conflict (‘incongruent’ (I)) with the underlying facial expression. The task will be adapted for children by 
utilizing an established set of child emotion-face stimuli of varied ethnicities, ages 10–17 years [47].  
During the Learning and Decision-making Task, participants will make trial-by-trial predictions about 
task outcomes, following which the actual outcome is shown. Participants make choices based on 
accumulated knowledge after each new trial. The task will examine learning and decision-making 
processes in a controlled environment.  
Presentation of behavioral tasks will be counterbalanced across participants.  
 
Physiological Monitoring 
 
Adolescents will be fitted with an Equivital Life Monitoring Sensory system (an ambulatory, multi-
sensor, continuous monitoring vest for collecting, analyzing, and reporting health data.) The Equivital 
System is able to collect reliable objective physiologic data through various sensors, which measure 
electrical activity of the myocardium via a 3-lead EKG, and activity/posture via a two-axis accelerometer.  
The sensor array of the Equivital System is embedded in a strap worn across the chest, made of washable 
material that fits snugly and can be worn comfortably for extended periods by individuals of varying height 
and weight.   
 
Biospecimens 
Saliva and blood samples will be collected at LIBR and transported for processing and storage to the 
Biomarker Core at the OU-Tulsa Integrative Immunology Center. Saliva will be collected using passive 
drool SalivaBio collection tubes (Salimetrics) and then centrifuged, aliquoted and stored at 80oC. Blood 
will be collected using standard CPT (for PBMC isolation) and serum vacutainer tubes. A total of about 
200 mL (less than 14 tablespoons) of blood will be drawn during the entire study by a trained 
phlebotomist. PBMCs will be aliquoted and stored in liquid nitrogen and serum will be aliquoted and 
stored at 80oC. Biomarker assays will be performed at the CIRCA Biomarker Core. Cortisol concentrations 
in saliva samples will be determined using Salimetrics High Sensitivity Salivary Cortisol EIA kits. IL-6 and 
CRP levels in the serum samples will be assayed using MesoScale Discovery V-PLEX assay kits. RNA will be 
isolated from PBMCs and a cDNA bank will be created. Gene expression analyses by qPCR for a project 
specific gene and one control gene for each subject at baseline and follow up will be done.  
 
TREATMENT  
Mindfulness-based Stress Reduction for teens (MBSR-T; [48, 49]) is an adapted version of adult MBSR. 
It consists of 8 weekly 1.5 hour sessions. Sessions are focused around three core elements: (1) intention 
(direction of effort toward mindfulness practice), (2) attention (experiencing what is taking place in the 
moment rather than categorizing or ruminating upon events based on memory), and (3) attitude 
(nonjudgmental or open experience of even difficult cognitive, emotional, or somatic experiences). 
Adolescents will receive a workbook to reinforce instruction, and a CD with sitting and body scan 
mediations for at-home practice (consisting of 20-35 minutes daily). TAU will consist of any treatments or 
activities in which the enrolled participant is engaged, including psychotherapy, pharmacotherapy, or 
other services provided through various agencies. TAU participants not connected with services will be 
given appropriate referrals. MBSR-T participants will not be asked to discontinue any other intervention 
for the duration of the study.  
MBSR-A will be delivered by the PI (Namik Kirlic, PhD; a clinical psychologist expected to be fully 

 
 
 
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licensed in the state of Oklahoma by the start of the study) and a clinical psychologist in training (a 
practicum student in the University of Tulsa clinical psychology doctoral program), supervised by a 
licensed clinical psychologist (Dr. Robin Aupperle, project mentor). Dr. Kirlic will receive training in MBSR-
T delivery via the online training conducted by the MBSR-T creator, Gina Biegel, LMFT  
(https://www.stressedteens.com). Clinical psychologists in training will be provided training and 
supervision in the treatment protocols from Dr. Kirlic. A treatment manual will be developed for the 
purposes of training and adherence.  
Measures will be taken to promote treatment fidelity, according to previous recommendations [50]. 
Each session will be recorded and up to 20% sessions will be randomly selected for fidelity ratings by 
research staff and expert consultants. Skill acquisition and fidelity will be assessed using CBT competencies 
developed for the Improving Access to Psychological Therapies (IAPT) Program [51]. Subject compliance 
will be assessed using (1) session attendance, (2) Homework Rating Scale to assess between-session 
compliance and (3) Working Alliance Inventory for Children and Adolescents (WAI-CA) therapist and client 
versions, to assess subject compliance and therapist behavior intra-session [52]. SMFQ-C will be 
completed weekly to assess symptom severity.  
 
GENDER/MINORITY/PEDIATRIC INCLUSION FOR RESEARCH 
The study will include 80 adolescents ages 13, 14, and 15. This is justified by the focus of the study on 
the biological processes associated with ELS exposure in adolescents and their changes as a result of 
treatment, and will allow for meaningful analyses. The selection of this age range ensures that the 
adolescents have entered into puberty, thus eliminating potential confounds of pubertal development on 
the data. Women and minorities will be included in the study without prejudice according to their 
representation in the study population. Subjects will be recruited from the greater Metro Tulsa area and 
should thus share the racial and ethnic composition of this area. All efforts will be made to ensure that 
our subject population closely resembles the gender, ethnic, and racial composition of the greater Tulsa 
area. 
 
PARTICIPANT RISKS AND PLANS TO MINIMIZE RISKS 
Risks associated with coercion 
Risk: Undue pressure on youth to provide informed assent 
Risk minimization: Youth assent will be obtained separately and independently from parental 
consent, and as both are required for the youth to participate, the risk of coercion because of the 
youths' minor status is limited. 
 
Risks associated with Screening and Evaluation 
Risk: Some of the questions in the interviews may be distressing or uncomfortable to answer due to their 
personal or emotionally relevant nature.  
Risk minimization: The researchers are trained to frequently inquire the subjects about their 
willingness and ability to continue with testing.  If the participants express concerns about continuing 
with testing, the research assistants will stop testing, offer a break, or, in case the subject is not 
willing to continue, terminate the testing session. If subjects report psychological distress, suicidal 
ideation, or intent to harm self or others, Dr. Kirlic or Dr. Aupperle, will be contacted immediately to 
ensure appropriate care and compliance with mandated reporting to authorities. Subjects may be 
referred for professional intervention, as deemed appropriate, including calling emergency 
personnel (911) if needed. A current list of local mental health treatment programs will be provided 
to all subjects at screening. Information reported will be kept in confidence with the exception that 
disclosure of suicidality, homicidality, or child or elder abuse warrant reporting to appropriate 
authorities. 

 
 
 
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Risks associated with blood draw and saliva collection 
Risk: Blood draws may be associated with mild pain, bruising, and infection at the puncture site as well as 
possible risk of fainting or dizziness. 
Risk minimization: Adolescents will be told about the potential discomforts associated with blood 
draws and saliva collection. Samples will be taken by a trained phlebotomist and the subject will be 
informed that the blood draw may be associated with mild pain, bruising and infection at the 
puncture site, as well as a possible risk of fainting or dizziness.   
Adolescents and parents/guardians will be informed that this research study will not include 
diagnostic testing of genetic information to confirm any findings that may result from self-report 
findings. Any incidental findings of clinical significance will be shared with the parent/guardian to 
follow up with a physician. There is a minimal risk of undue stress or concern if the finding is 
determined to be benign or not clinically significant. Furthermore, data from this study, including 
genomic information likely to be generated in future analyses, will be available in controlled-access 
data repositories for broad sharing. While these repositories will not contain personally identifying 
information, it is possible that the participants’ genetic or medical information in these databases 
could be linked to them. For example, someone could compare information in the databases with 
information from relatives residing in another database and be able to identify the participants. 
Some genetic variations can help predict future health problems or can be used by law enforcement 
agencies to identify a person or his/her blood relatives. Therefore, participants’ genetic information 
potentially could be used in ways that could cause him/her or the family distress, such as by 
revealing that a child (or a blood relative) carries a genetic disease. There also may be other privacy 
risks that we have not foreseen. A Federal law, called the Genetic Information Nondiscrimination 
Act (GINA), generally makes it illegal for health insurance companies, group health plans, and most 
employers to discriminate against individuals based on their genetic information.  This law generally 
will protect the participants in the following ways: 
- 
Health insurance companies and group health plans may not request genetic information 
obtained in this research.   
- 
Health insurance companies and group health plans may not use genetic information when 
making decisions regarding eligibility or premiums.   
- 
This new Federal law does not protect against genetic discrimination by companies that sell life 
insurance, disability insurance, or long-term care insurance. 
 
Risks associated with behavioral testing 
Risk: The subjects may experience feelings of discomfort and fatigue due to mild to moderate demands 
on the attention and cognition, as wells as feeling uncomfortable or anxious due to the stressful and 
emotional nature of the stimuli used during the tasks, including the social stress task. 
Risk minimization: The researchers are trained to frequently inquire with the participants about their 
willingness and ability to continue with testing. If the participants express concerns about continuing 
with testing, the research assistants will stop testing, offer a break, or, in case the participant is not 
willing to continue, terminate the testing session. If participants report psychological distress, 
suicidal ideation, or intent to harm self or others, Dr. Kirlic or Dr. Aupperle will be contacted 
immediately to ensure appropriate care and compliance with mandated reporting to authorities. 
Participants may be referred for professional intervention, as deemed appropriate, including calling 
emergency personnel (911) if needed. A current list of local mental health treatment programs will 
be provided to all subjects at screening.  Information reported will be kept in confidence with the 
exception that disclosure of suicidality, homicidality, or child or elder abuse warrant reporting to 
appropriate authorities. 

 
 
 
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Risks associated with treatment  
Risk: it is not expected to occur, but participants may experience adverse effects to treatment in the form 
of worsening symptoms. 
Risk minimization: First, adolescents will be informed that there are no known risks associated 
with participating in mindfulness-based psychological interventions. We will share with them that 
these interventions have been shown to have a positive impact on psychological well-being, 
including a reduction of psychological symptoms and emotional reactivity, and improved emotion 
regulation. Symptoms will be monitored weekly, and in case of worsening, we will follow the 
contingency plan as outlined below. 
For adolescents who wish to or are in need of treatment for psychological symptoms, trauma, or 
life stress, an alternative to participation in this study would be to participate in a different type 
of treatment available through the community. Mindfulness interventions have been shown to 
reduce symptoms of psychopathology in a range of samples, and therefore many of the 
adolescents are expected to benefit from it. TAU condition is necessary to delineate the effect of 
mindfulness intervention on biological processes related to ELS. In both conditions, adolescents 
will not be asked to stop any intervention that they are currently undergoing to participate in this 
study. An alternative to participation for healthy controls would be to not participate; however, 
they will also be provided with mental health and substance abuse resources in the community. 
Finally, all adolescents will be provided with referral information.  
 
If an adolescent should become uncomfortable during any procedures, he/she can stop the procedures 
or withdraw from the study at any time. If any medical problem arises, 911 will be contacted immediately. 
If psychological distress, suicidal ideation, or another problem should occur, the designated licensed 
professional (MD or Ph.D.-level clinical psychiatrist/psychologist) will be contacted immediately. 
Adolescents with significant substance use or psychopathology (i.e., psychosis, bipolar disorder) are 
excluded at baseline; however, substance use and psychopathology may emerge during the course of the 
study. In such a case, we will follow the contingency plan as outlined below. 
 
Contingency plans for monitoring suicidality, worsening clinical symptoms, or other mental health 
emergencies  
All participants who are deemed a serious suicide risk will be excluded from the study. In the 
evaluation of suicidal risk, we will exclude from participation any adolescent who endorses having 
developed a plan or intent to attempt suicide, or has made a serious suicide attempt within the preceding 
six months. Any volunteer who is excluded from participation for these reasons will be referred for 
emergency care according to written LIBR policies for managing potentially suicidal patients, as described 
below. 
While the participants are in this study they will be monitored for the development of suicide risk or 
for worsening in their clinical illness by a clinician. This will be conducted using the weekly self-report 
assessments and clinical observation, as described above. If concerns arise when the participant is 
physically present at the Laureate Institute for Brain Research, psychologists Namik Kirlic, PhD and Robin 
Aupperle, PhD are available on site to address any concerns that arise. If Dr. Kirlic or Dr. Aupperle are 
unavailable or further evaluation is deemed necessary, psychiatrists Drs. Martin Paulus, and Sahib Khalsa 
will be available.  
For participants who are at the LIBR facility and are deemed to constitute a serious risk for suicide, 
the LIBR policy requires that they be escorted by two clinicians to the onsite, 24-hour emergency facility 
at Laureate Psychiatric Clinic and Hospital (which is located about 100 yards from the LIBR facility). If 
participants refuse to be escorted to this facility and leave the LIBR premises, the study clinician will 

 
 
 
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contact the Community Outreach Psychiatric Emergency Services (COPES – 918 744 4800), which is 
available 24 hours per day to send a mobile unit to the person’s home. 
For participants who develop serious suicidal ideation while not on the LIBR premises, these 
participants will be instructed to call 911 or to go to the nearest emergency room if they feel they are a 
threat to themselves or others. They will also be given the contact details of the Tulsa Community 
Outreach Psychiatric Emergency Services (COPES – 918 744 4800). 
If adolescent presents intoxicated during either the research or treatment component of the study, 
he or she will not participate in that visit. The parent will not be informed of the positive results, unless 
the intoxication is life-threatening. To ensure the youth’s safety, he/she will be asked to remain on the 
premises until his/her breathalyzer reading is 0.00/ saliva re-test is negative. If a safe drive with their 
parent/legal guardian is not available, transportation (i.e., taxi service) will be arranged from the research 
site back to the youth’s address. If results are not those anticipated by the adolescent (i.e., causing 
distress), PI will discuss the test results with the participant with the objective of reducing their concerns.  
For participants who have clinical issues that do not reflect a psychiatric emergency, they will be given 
a telephone number where they can reach a LIBR clinician during those hours when LIBR is officially staffed 
by clinicians (weekdays between 0800 and 1700). For weekends and off-hours (evenings and nights) they 
are provided a second telephone number where they can reach the 24-hour per day on call service for 
LIBR, which is provided through the Call Center of Laureate Psychiatric Clinic and Hospital. 
Upon study completion, participants who are currently under treatment by an external provider will 
be referred to their own clinician. Participants who are dropped from study participation, or participants 
who complete the study and are not under the care of a clinician, will be provided a referral to a 
psychiatrist or other mental health professional at one of the following clinics (regardless of the reported 
level of post-treatment symptoms): 
 
Outpatient (insured) 
Laureate Psychiatric Clinic and Hospital 
6655 South Yale Ave 
Tulsa OK, 74136 
(918) 481-4000 
 
Department of Psychiatry (sliding scale) 
University of Oklahoma College of Medicine 
Tulsa OK, 74136 
(918) 619 4400  
 
Outpatient (uninsured) 
Tulsa Center for Behavioral Health (sliding scale) 
2323 South Harvard Ave 
Tulsa, OK, 74114 
(918) 239 2100 
 
Associated Centers for Therapy (sliding scale) 
7010 South Yale Ave, Suite 215 
Tulsa OK, 74136 
(918) 492 2554 
 
Inpatient 
Laureate Psychiatric Clinic and Hospital 

 
 
 
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6655 South Yale Ave 
Tulsa OK, 74136 
 
(918) 481 4000 
 
Shadow Mountain Behavioral Health System  
6262 South Sheridan Road 
Tulsa OK, 74133 
 
Individually tailored referrals will be made for participants who reside outside of the Tulsa region, so 
that they will be referred to psychiatric services that are located near their home or workplace.  
 
Potential Benefits  
Participation in this study involves minimal risk for adolescents, yet has the potential for providing 
substantial long-term benefits to them, as well as toward understanding the extent to which symptoms, 
emotion regulation, epigenetic factors, and functioning of the HPA axis associated with ELS are mitigated 
by mindfulness-based intervention.  
 
Risk/Benefit Ratio 
Given the minimal risk to adolescents involved, the prevalence of ELS exposure and its substantial 
short- and long-term adverse psychological and health outcomes, positive psychological impact of 
mindfulness intervention, and the information gained from this study on how a range of psychological 
and biological processes dysregulated by ELS may change as a result of intervention, we believe that the 
risk/benefit ratio is acceptable. 
 
Expense to Participants 
The only anticipated expense to adolescents and their families is the amount of time spent in research 
/ intervention.  
 
DATA AND SAFETY MONITORING PLAN 
Data safety and monitoring will be carried out to ensure and maintain the scientific integrity of this 
project and to protect the safety of adolescents. Data and Safety Monitoring Board will consist of the PI, 
primary (Dr. Robin Aupperle) and co-mentors (Dr. Martin Paulus and Dr. Amanda Morris), and research 
assistant. Review of accumulated outcome data for groups of adolescents will be carried out to determine 
if any of the procedures practiced should be altered or stopped. Study will be stopped in case of a a 
significant adverse event or majority of participant showing a worserning of symptoms. Continuous, close 
monitoring of participant safety will prompt reporting of safety data (i.e., adverse/serious adverse events) 
to the local IRB. Serious adverse events will be reported to the IRB within 48 hours of the time project 
staff become aware of the incident. The PIs will provide a summary of the safety conduct of the study to 
CIRCA as part of the progress report, which will parallel the written report required by the IRB as part of 
the annual IRB renewal. The review of data and procedures may result in early termination of the study, 
amendment to the protocol, or changes to the data collection plan. Should the protocol or data collection 
plans be amended as a result of data review, the relevant IRBs will be notified and the amendment 
approved prior to study amendment implementation. In addition, the participants will be notified of any 
significant new findings that develop during the course of research (e.g., other potential risks) that may 
affect their wish to continue participation in the study.  
Each subject will be given a unique identifier with a code. Information for each participant is entered 
into the Laureate Institute for Brain Research subject database and they are automatically given a LIBR ID 
e.g. AA001. The code key that links the unique identifier to the subjects’ names is kept in a separate file. 

 
 
 
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All data analysis is performed on de-identified data. Other than the PI, there is no need for personally 
identifying information to be known to other investigators.    
All research documents containing Personally Identifiable Information (PII) and collected research 
data will be stored electronically on the LIBR Network and/or REDCap. Access to the LIBR Network and to 
REDCap is granted only to authorized personnel. The LIBR Network is protected by the Palo Alto PA-5250 
Layer 7 firewall with licenses for Wildfire, AV, Threat Prevention, and URL filtering. All LIBR Network data 
is stored on site. REDCap is a secure web application for building and managing online surveys and 
databases. While REDCap can be used to collect virtually any type of data (including 21 CFR Part 11, FISMA, 
and HIPAA-compliant environments), it is specifically geared to support online or offline data capture for 
research studies and operations. The REDCap Consortium, a vast support network of collaborators, is 
composed of thousands of active institutional partners in over one hundred countries who utilize and 
support REDCap in various ways. 
Study information will be made available to the subjects when there has been sufficient data analysis 
to make reasonable aggregate conclusions. We can share general study characteristics (how many people 
were recruited, age, primary disorder etc.) early in the process, but will not share study results with 
subjects until the quality of the data is close to publication level.   
If the PI leaves LIBR, and agreement will be made between LIBR and the PI new institution to transfer 
the data so that the study can continue.   
 
CONFIDENTIALITY 
Confidentiality risks are important are to consider in this study. This study collects a variety of sensitive 
data, in particular with respect to the risk of disclosure of childhood abuse and neglect, illicit substance 
use, and genetic, mental health, and physical health information. Since personal information is gathered, 
there exists risk of possible invasion of privacy. Procedures described below minimize the possible breach 
of confidentiality and invasion of privacy. 
Participants will be assured that records and samples will be kept confidential in research files located 
in a locked office and/or entered into a password-protected computer located behind a secure and 
maintained firewall. All forms of data described above will be recorded on computerized or paper and 
pencil data forms that do not contain identifying information. All biological samples (including saliva for 
genetic and hormone analysis) will be de-identified, and those collected for future analysis will be securely 
stored on site in locked cabinet and/or freezer, or shipped to the designated lab. Breach of confidentiality 
is highly unlikely as all personally identifying information will be kept separate from other data collected, 
and will be linked only by a master subject identification list which is maintained by the project 
coordinator and PI. Confidentiality may be broken in case when disclosure is required by the law, including 
disclosure of suicidality, homicidality, or child or elder abuse which warrant reporting to appropriate 
authorities.  
All participants will be informed about the limits of confidentiality, including that the information 
provided for this research study will not be shared a) between youth and parent (legal guardian, caregiver) 
with the exception of situations concerning safety (e.g., suicidal during a study session) or b) with the 
youth’s school. No personally identifying information will be coded on the questionnaires, interviews, 
biological samples, brain imaging data, or scoring sheets. Subject identification numbers are assigned to 
each participant. Only the PI and limited research staff have access to the file that links subject name with 
subject number. All data are stored in locked file cabinets in locked offices or password-protected 
computers located behind secure and maintained firewalls. 
Breach of confidentiality is highly unlikely because all personally identifying information will be kept 
separate from data collected, and will be linked only by a master subject identification list maintained by 
the lead research associate and the PI. We will inform both youth and parents from the start of the 
participation and at each follow-up that we will not inform the parents of what the youth informs us 

 
 
 
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concerning substance use. We will provide all participants and parents with information about substance 
abuse and mental health services in their area, including free and youth specific services. Parents do have 
the right to request copies of some types of protected health information. However, as suggested in the 
NIAAA Alcohol Screening and Brief Intervention for Youth: A Practitioner’s Guide, we will make it clear, 
prior to any such information release, that reading this information may compromise our ability to work 
with the youth and make it more difficult to elicit honest and accurate information. We will inform 
parents, and other authorities as required by the situation, if we learn that a minor is a danger to self or 
others.  
All research staff will complete on-line training in human subject research, HIPAA, FERPA, and clinical 
practices, training in respective labs on research data management and confidentiality, and training to 
criterion on project protocol. As an additional protection to participants, we will seek a a certificate of 
confidentiality from the NIH for this study.  
 
ANALYSES AND POWER.  
Statistical analysis will be carried out using R statistical package. Robust methods, non-parametric 
tests, or data transformations will be used to address any issues of non-normality. With N=20 per group 
and 20% attrition, we will have 80% power to detect medium size effects (f=.25) between groups from 
baseline to follow up (Aim 2), and pre- to post-TSST cortisol differences (Aim 2). We are 80% powered to 
detect large effect sizes (r=.5) for regression analyses (Aims 1 & 2). While potentially under-powered for 
regression and more complex analyses involving additional covariates, results will be crucial for estimating 
effect sizes for future study design and grant applications.  
Aim 1: Examine how ELS impacts biological processes associated with regulation of stress.  
Hypothesis 1a: ELS severity will relate negatively to cortisol changes with the TSST. Hypothesis 1b: ELS 
severity will relate to increased demethylation of the FKBP5 gene and inflammatory markers (IL-6, CRP). 
Paired-samples t-tests will evaluate the differences in levels of saliva cortisol pre- to post-TSST (cortisol 
reactivity). Huber robust regression analyses will examine the relationship between intensity of ELS 
exposure and cortisol reactivity and inflammatory markers.  
Aim 2: Identify how MBI impacts affective symptoms and biological processes dysregulated by 
ELS. Hypothesis 2a: MBI adolescents will evidence a clinically significant reduction in internalizing and 
externalizing symptoms, and emotion dysregulation. Hypothesis 2b: MBI adolescents will evidence 
normalization in cortisol reactivity in pre- to post-TSST. Hypothesis 3c: MBI adolescents will evidence a 
normalization in the methylation of the FKBP5 gene and levels of inflammatory markers (IL-6 and CRP). 
We will use linear mixed effect (LME) analyses (with subject and time entered as random effects) to 
examine changes from baseline to follow-up time points between the MBSR and TAU groups.  
 
 
 

 
 
 
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