Neural Mechanisms of Mindfulness-based Cognitive Therapy (MBCT) for Posttraumatic Stress Disorder (PTSD)
Phase: NA
Conditions: Post Traumatic Stress Disorder
Sponsor: Ohio State University

Neural Mechanisms of Mindfulness-based Cognitive Therapy (MBCT) 
for Posttraumatic Stress Disorder (PTSD) 
 
Protocol Number: HUM00153822 
National Clinical Trial Number: <ct.gov> 
Principal Investigator: Anthony King, PhD 
Sponsor: NICCH 
Funded by Grant: #1 R61 AT009867-01 
 
Initial Version: 19 November 2018 
Version Number: 1.3 
<24 January 2020> 
 
 

ii 
 
Amendments 
 
 
 
Date 
Version 
Section(s) 
Changes 
1/24/2020 
1.3 
5.4, 5.6 
A change made to improve feasibility and increase accrual and 
decrease unacceptable wait times for patients enrolled in the 
study.  We have changed recruitment to allow participants who 
consent but are later found to be unable to do fMRI or are missing 
1 PTSD symptom to be allowed to do just the psychotherapy group 
and follow-up assessment.   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

iii 
 
1 
Protocol Summary ................................................................................................................................ 1 
1.1 
Synopsis......................................................................................................................................... 1 
1.2 
CONSORT Schema ......................................................................................................................... 2 
1.3 
Schedule of Activities .................................................................................................................... 3 
2 
Introduction .......................................................................................................................................... 5 
2.1 
Study Rationale ............................................................................................................................. 5 
2.2 
Background ................................................................................................................................... 5 
2.3 
Specific Aims ................................................................................................................................. 8 
2.4 
Risk/Benefit Assessment ............................................................................................................... 9 
3 
Objectives and Endpoints (Go/No-Go Criteria) ................................................................................... 11 
4 
Study Design........................................................................................................................................ 11 
4.1 
Overall Design ............................................................................................................................. 11 
4.2 
Study Description ........................................................................................................................ 11 
4.3 
Randomization ............................................................................................................................ 12 
5 
Study Population ................................................................................................................................. 12 
5.1 
Inclusion Criteria ......................................................................................................................... 13 
5.2 
Exclusion Criteria ......................................................................................................................... 13 
5.3 
Lifestyle Considerations .............................................................................................................. 13 
5.4 
Screen Failures ............................................................................................................................ 13 
5.5 
Lost-to-follow up ......................................................................................................................... 14 
5.6 
Strategies for Recruitment and Retention .................................................................................. 14 
6 
Study Interventions ............................................................................................................................. 15 
6.1 
Justification for Intervention....................................................................................................... 15 
6.2 
Study Intervention: MBCT (Mindfulness-Based Cognitive Treatment) ...................................... 16 
6.3 
Study Intervention: Muscle Relaxation Group (MRG) ................................................................ 17 
6.4 
Measures to Minimize Bias ......................................................................................................... 18 
6.5 
Concomitant Therapy ................................................................................................................. 19 
6.6 
Participant Withdrawal from Intervention and Study ................................................................ 19 
7 
Study Assessments & Procedures ....................................................................................................... 19 
7.1 
Psychiatric Diagnostic Status ...................................................................................................... 19 
7.2 
Quality of Life and Outcome Assessments ................................................................................. 20 
7.3 
Research Procedures .................................................................................................................. 21 
7.4 
Safety Assessments ..................................................................................................................... 22 

iv 
 
7.5 
Adverse Events & Serious Adverse Events .................................................................................. 23 
7.6 
Unanticipated Problems ............................................................................................................. 25 
8 
Statistical Considerations .................................................................................................................... 25 
8.1 
Go/No Go Criteria – Primary mechanistic outcome ................................................................... 25 
8.2 
Secondary Mechanistic Outcome ............................................................................................... 26 
9 
Operational Considerations ................................................................................................................ 26 
9.1 
Informed Consent Process .......................................................................................................... 26 
9.2 
Confidentiality and Privacy ......................................................................................................... 26 
9.3 
Data Handling and Record Keeping ............................................................................................ 27 
9.4 
Data Sharing ................................................................................................................................ 27 
10 
References ...................................................................................................................................... 28 
 
 
 

v 
 
ABBREVIATIONS 
AAQ – Acceptance and Action Questionnaire 
BOLD – blood oxygen level dependent 
BPI – Brief Pain Inventory 
CAPS-5 – Clinician-administered PTSD Scale 
CEN – Central Executive Network 
CEN – central executive network 
CGI – Clinical Global Impressions Scale 
Cx - criteria 
CTQ – Childhood Trauma Questionnaire 
dACC – dorsal anterior cingulate cortex 
DAN – dorsal attention network 
DMN – default mode network 
EQ – Experiences Questionnaire-Decentering Factor 
ERQ – Emotional Regulation Questionnaire  
FEF – frontal eye field 
fMRI – functional magnetic resonance imaging 
GAD – generalized anxiety disorder 
HAM-D – Hamilton Depression Rating Scale 
HIPAA – Health Information Portability and Accountability Act 
ICN – intrinsic connectivity network 
IFG – inferior frontal gyrus 
IRBMED – Institutional Review Board for Michigan Medicine 
LEC – Lifetime Events Checklist 
MBCT – Mindfulness-based Cognitive Treatment 
MBI – Mindfulness-based intervention 
MBSR – Mindfulness-based Stress Reduction 
MDD – Major Depressive Disorder 

vi 
 
MFG – middle frontal gyrus 
MINI – Mini-International Neuropsychiatric Interview 
MMQ-15 – Multifacet Mindfulness Questionnaire 
MRG – Muscle Relaxation Group 
MTG – middle temporal gyrus 
n/a – not applicable 
PCC – posterior cingulate cortex 
PCC-dlPFC – posterior cingulate cortex -corsolateral prefrontal cortex 
PCL-5 – PTSD Checklist 
PHQ-9 – Patient History Questionnaire 
PPC – posterior parietal cortex 
PTSD – Posttraumatic Stress Disorder 
RCT – randomized controlled trial 
rsFC – resting state functional connectivity 
RSQ-RRS – Response Styles Questionnaire, Ruminative Response Subscale  
S – study-paid activity with efforted staff 
sgACC – subgenual anterior cingulate cortex 
sgPFS – subgenual prefontal cortex 
SN – salience network 
SPL – superior parietal lobule 
Sx – symptoms 
VA – Veteran’s Affairs (Ann Arbor Medical Center) 
VAN – ventral attention network 
vmPFC – ventromedial prefrontal cortex 

1 
 
1 PROTOCOL SUMMARY 
1.1 SYNOPSIS 
Title: 
Neural Mechanisms of Mindfulness-based Cognitive Therapy (MBCT) for 
Posttraumatic Stress Disorder (PTSD) 
Study Description: 
A parallel group randomized controlled trial examining the mechanisms 
underlying mindfulness-based cognitive training (MBCT) for posttraumatic 
stress disorder (PTSD) 
Primary Objective 
To show an increase in the resting state functional connectivity between 
the posterior cingulate cortex (PCC) and the dorsolateral prefrontal cortex 
Secondary Objectives 
To show a decrease in the resting state functional connectivity between 
the Insula and the posterior cingulate cortex (PCC) 
Study Population: 
Adult patients with PTSD able to attend therapy sessions in SE Michigan 
Phase: 
n/a 
Description of 
Sites/Facilities Enrolling 
Participants: 
Participants will be enrolled by the University of Michigan; study 
interventions will take place at various locations around campus and the 
greater Ann Arbor and Southeastern Michigan  area; fMRI scans will take 
place at Functional MRI Laboratory on North Campus 
Description of Study 
Intervention: 
Both study interventions (mindfulness-based cognitive training and muscle 
relaxation therapy) involve 8 weeks of group therapy, and include in-
session exercises and daily at-home practice. 
Study Duration: 
20 months 
Participant Duration: 
8 weeks of intervention plus 4 days of assessments; total time enrolled in 
study will depend on accrual and randomization rates 

2 
 
1.2 CONSORT SCHEMA 
 

3 
 
1.3 SCHEDULE OF ACTIVITIES 
 
 
OnCore Segment 
 
Consented/On Study 
On Arm/On Treatment 
Off Study 
 
Study Timeline 
Pre-
study 
Pre-therapy1 
[T1] 
8 sessions of group therapy2 
Post-therapy3 
[T2 and T3] 
 
Notes 
 
Occurs on 2 
different days 
 
Scheduled for consecutive weeks; start date depends on enrollment numbers because 
study is randomizing in groups 
T2 w/MRI scan 
T3 no MRI scan 
Initial Interview 
Pre-screening (for PTSD) 
S 
 
 
 
 
 
 
 
 
 
 
 
 
 
Consent –  
 
Consent 
 
S 
 
 
 
 
 
 
 
 
 
 
 
 
Eligibility Criteria Review 
 
S 
 
 
 
 
 
 
 
 
 
 
 
 
Clinical Assessments –  
MINI 
 
S 
 
 
 
 
 
 
 
 
 
 
S 
 
LEC 
 
S 
 
 
 
 
 
 
 
 
 
 
S 
 
CAPS-5 
 
S 
 
 
 
 
 
 
 
 
 
 
S 
 
HAM-D 
 
S 
 
 
 
 
 
 
 
 
 
 
S 
 
Intervention4 
 
MBCT or MRG 
 
 
 
S 
S 
S 
S 
S 
S 
S 
S 
 
 
 
PHQ (and CSSRS as 
needed)  
 
 
 
S 
S 
S 
S 
S 
S 
S 
S 
 
 
 
PCL-5 
 
 
 
S 
S 
S 
S 
S 
S 
S 
S 
 
 
 
PTCI-9 
 
 
 
S 
S 
S 
S 
S 
S 
S 
S 
 
 
 
SCS 
 
 
 
S 
S 
S 
S 
S 
S 
S 
S 
 
 
 
CGI 
 
 
 
S 
S 
S 
S 
S 
S 
S 
S 
 
 
 
fMRI5 -  
 
fMRI screening 
 
 
S 
 
 
 
 
 
 
 
 
 
 
S 
Pregnancy test (dipstick) 
 
 
S 
 
 
 
 
 
 
 
 
 
 
S 
Resting connectivity 
 
 
S 
 
 
 
 
 
 
 
 
 
 
S 
Self-related processing 
task 
 
 
S 
 
 
 
 
 
 
 
 
 
 
S 
Biomarkers6 
 
Saliva for adrenergic & 
inflammatory function & 
DNA (optional) 
 
S 
 
 
 
 
 
 
 
 
 
 
S 
 
                             
Psychological & QOL 
Self-Report Assessments 
at University of Michigan 
EQ 
 
S 
 
 
 
 
 
 
 
 
 
 
S 
 
AAQ 
 
S 
 
 
 
 
 
 
 
 
 
 
S 
 
MMQ-15 
 
S 
 
 
 
 
 
 
 
 
 
 
S 
 
ERQ 
 
S 
 
 
 
 
 
 
 
 
 
 
S 
 
SCS 
 
S 
 
 
 
 
 
 
 
 
 
 
S 
 
RSQ-RRS 
 
S 
 
 
 
 
 
 
 
 
 
 
S 
 
BPI 
 
S 
 
 
 
 
 
 
 
 
 
 
S 
 
PCL-5 
 
S 
 
 
 
 
 
 
 
 
 
 
S 
 
BDI-II 
 
S 
 
 
 
 
 
 
 
 
 
 
S 
 
PTCI-9 
 
S 
 
 
 
 
 
 
 
 
 
 
S 
 
CTQ 
 
S 
 
 
 
 
 
 
 
 
 
 
 
 

4 
 
1 Baseline testing occurs pre-therapy and will take place over 2 (not necessarily consecutive) days; it is designated as T1 
2 Participants are randomized after completion of all pre-therapy assessments; therapy will not begin until sufficient number of participants are available to randomize as a group.  
3 Post-testing occurs upon completion of therapy sessions and will also take place over 2 (not necessarily) consecutive days; it is designated as T2  
4 The PHQ and CGI will be administered during each therapy session as safety assessments; the CSSRS will only be administered if warranted based on PHQ responses  
5Participants will be scheduled for the fMRI at the North Campus Functional Imaging Laboratory.  
6 Saliva samples will be obtained at the UM fMRI facility and stored for batch analysis.  
7 The timing of randomization relative to T1 assessments will depend on enrollment; participants will be block randomized to one group therapy or another; it’s important to maintain some participant 
homogeneity within the each 8-week therapy group (i.e. combat trauma vs. interpersonal trauma, etc.).  
 

5 
 
2 INTRODUCTION 
2.1 STUDY RATIONALE 
Posttraumatic stress disorder (PTSD) is common, can be chronic and debilitating, and is associated with 
high costs to individuals and society. Existing trauma exposure-based psychotherapies show high 
efficacy, but a recent meta-analysis reported the surprising finding that 30-50% of PTSD patients treated 
do not show clinically meaningful improvement1, suggesting “one size may not fit all” and that 
additional approaches are needed. In recent years, mindfulness-based approaches like Mindfulness-
based Cognitive Therapy (MBCT) have emerged as cost-effective, accessible and effective interventions 
for PTSD2, with recently increasing utilization as population-based interventions for PTSD, warranting 
more research on mechanisms. Accumulating evidence suggests the construct of decentering as a 
primary psychological process involved with MBCT. Decentering, defined as the metacognitive capacity 
to observe thoughts, feelings, memories, and bodily sensations with healthy psychological distance and 
decreased reactivity, is thought to help resolve the automatic negative cognitive-affective responses 
that typify symptoms in depression and PTSD. There is increasing interest to understand neural targets 
and mechanisms underlying MBCT and decentering, and whether these are shared with or distinct from 
targets of other psychotherapy components (and thus potentially complementary). This knowledge will 
allow optimization of effective therapy components.   
There is mounting evidence that dysfunction in large-scale distributed neural connectivity networks may 
underlie psychopathology like PTSD and MDD, and that treatments, including MBCT, target 
strengthening compensatory mechanisms that normalize function of core aberrations within and 
between these networks. Changes in the Default Mode Network (DMN, e.g. ventromedial prefrontal 
cortex [vmPFC], subgenual ACC), the Central Executive Network (CEN, dlPFC, parietal cortex), and the 
Salience Network (SN, e.g. insula, amygdala) may underlie decentering and effects of MBCT. We and 
others report mindfulness-linked increased functional DMN-CEN connectivity2,3,4 (e.g., posterior 
cingulate cortex [PCC] with bilateral dlPFC) that was associated with decreased PTSD symptoms2 and 
decreased plasma inflammatory markers (IL-6)3. Mindfulness may also decrease connectivity between 
SN and DMN (insula-vmPFC), and increase SN-CEN connectivity (insula-dlPFC)5. We need to determine 
whether these effects on DMN, CEN, and SN networks are in fact primary targets of MBCT that can 
mediate mental and physical health-related outcomes. 
2.2 BACKGROUND 
2.2.1 
Clinical Significance 
A considerable proportion of trauma exposed individuals go on to suffer from posttraumatic stress 
disorder (PTSD) or major depression (MDD).  These conditions also show high levels of co-morbidity with 
one another. Trauma-related psychiatric disorders are common and highly debilitating disorders 
associated with immense levels of human suffering and socioeconomic costs7,8. For instance, PTSD has 
lifetime prevalence of ~10% in the general population and higher in subpopulations (e.g. up to 20% in 
combat veterans9-11 and up to 45% in low SES people living in urban areas12. PTSD has high levels of 
disability and family disruption that can last for decades10,11,13-15. Similarly, MDD is very common with a 
lifetime prevalence of ~16%8. Chronic depression is a leading cause of disability, associated with 

6 
 
notoriously high levels of relapse16; and is often associated with trauma; the combination of chronic 
PTSD and chronic depression can be particularly difficult to treat. Although existing trauma-focused 
exposure therapies such as Prolonged Exposure (PE) show high levels of efficacy in randomized 
controlled trials (RCTs)1,17-20, recent meta-analyses1 report 30-50% of patients treated do not show 
clinically meaningful improvement and 62-70% of patients retain their PTSD diagnosis.  Additional 
treatment modalities are needed for both PTSD and MDD, and there is particular interest in 
interventions that may provide orthogonal or complementary effects with existing treatment 
approaches to maximize optimal outcomes.  Recently, mindfulness based cognitive therapy (MBCT), an 
intervention originally designed and evaluated for the prevention of MDD relapse, has emerged as a 
treatment modality with high levels of acceptability in PTSD21-25 that may be useful as an adjunctive 
treatment or alternative for patients who decline first-line treatments. 
2.2.2 
Mindfulness-based Cognitive Therapy (MBCT) 
MBCT is an 8-week group “Mindfulness-based intervention” (MBI) group psychotherapy based on 
Mindfulness-based Stress Reduction (MBSR). MBCT was initially developed for preventing relapse in 
remitted patients with MDD, and a number RCTs and recent meta-analysis suggest high level of efficacy 
for preventing depression relapse16,26,27. MBCT incorporates many elements of MBSR, the prototypic 
“MBI”, including exercises for enhancing sensory, interoceptive, and proprioceptive attention (e.g. raisin 
exercise, bodyscan, and mindful movement), and meta-cognitive awareness / mindfulness of breath and 
experiential engagement and acceptance of sensations, emotional states, and thoughts. MBCT combines 
these with cognitive therapy exercises, including psychoeducation and emotional recognition exercises 
(e.g., pleasant and unpleasant events calendars). It includes both in-session and daily at home practice, 
as well as “mindful inquiry” in each session, inviting patients to discuss their experiences with 
mindfulness exercises and how they find these relevant to mental health and depression, and helping to 
recognize and not get “stuck” in automatic, depressogenic patterns of thought and rumination.   
Findings consistently indicate that MBCT and MBSR are well tolerated and demonstrate efficacy for 
PTSD in studies of both primarily males with combat trauma2,24,25,28-32, and primarily females with adult22 
and childhood23,33 interpersonal violence and sexual abuse.  MBCT / MBSR also shows efficacy for other 
acute psychiatric disorders, as an adjunctive treatment for treatment refractory major depression34-36 
and for generalized anxiety disorder37-39.   
2.2.3 
Role of Alterations in Large-Scale Neural Networks in Trauma-related Psychopathology 
Mounting evidence from basic, translational, and treatment research converges on the view that neural 
underpinnings of psychiatric disorders like PTSD and MDD may be better understood by dysfunctions in 
relationships between large-scale neural networks40-43 rather than micro-circuit “locationist” 
approaches. Resting state functional connectivity (rsFC) analyses find multiple large-scale intrinsic 
connectivity networks (ICNs), distributed brain networks at rest that correspond to task-related 
connectivity patterns44,45. A comprehensive description is not possible here, but the ICNs relevant to the 
nature and treatment of PTSD include the “task-negative” Default Mode Network (DMN), with nodes in 
the posterior cingulate cortex (PCC), ventral medial PFC (vmPFC), and subgenual PFC (sgPFC) associated 
with social cognition, self-referential processing, autobiographical memory, and “mind wandering”, the 
Salience Network (SN), with nodes in insula, dorsal anterior cingulate (dACC) and amygdala, associated 
with detection of salience and threat and integration of interoceptive, autonomic, and emotional 
information. Several conectivity networks have been proposed underlying attention and executive / 

7 
 
cognitive control. The Dorsal Attention Network (DAN), frontal eye field (FEF), superior parietal lobule 
(SPL), is involved in with voluntary deployment of attention and externally-directed cognitions, and the 
Ventral Attention Network (VAN), right inferior frontal gyrus (IFG), middle temporal gyrus (MTG) 
involved reorientation to unexpected events. The Central Executive Network (CEN) or Fronto-Parietal 
Control Network (FPCN), bilateral dlPFC and posterior parietal cortex (PPC), is involved in executive 
functions and “top-down control”. The CEN appears to play a central role in regulating and directing 
distributed systems according to current task goals42, for example, CEN regulates normally anti-
correlated activity in DMN and DAN46, and coordinates with DAN in maintaining voluntary internal trains 
of thought47. The dACC also plays important roles in cognitive conflict and error detection and some 
reports find dACC within cognitive control networks48,49 as well as SN. 
Several research groups, including our own lab, report that individuals with PTSD evidence hyper-
connectivity within SN (e.g. amygdala-insula)50-53, and aberrantly increased DMN-SN (e.g. DMN-
amygdala and insula) cross-network connectivity / desegregation52,54,55. By contrast, individuals with 
PTSD evidence decreased within-network DMN connectivity (PCC-vmPFC and PCC-hippocampus)52,55,56, 
and decreased vmPFC-hippocampus connectivity52,53,57.  We hypothesized increased DMN-SN 
connectivity at rest as potentially underlying PTSD hyperarousal symptoms, associated with intrusive, 
automatic distress reactions to both external cues and internal physiological states. Intriguingly, we have 
also found self-reported rumination correlates with PCC-insula connectivity, and PTSD avoidance 
symptoms negatively correlate with the strength of PCC-dlPFC connectivity. Similar dysfunctional 
vmPFC-insula hyperconnectivity has also been implicated in depression and anxiety58, which is proposed 
to lead to negativity bias and self-referential misinterpretation and amplification of interoceptive 
signals. Abnormalities in ICNs are also seen in MDD.  In contrast to PTSD, hyperactivity in DMN has been 
reported in MDD, and in particular increased connectivity between PCC and subgenual ACC (sgACC)43,59 
which has been though to reflect depressive rumination in the scanner43,59,60. Recent whole-brain 
connectomic studies in rumination induction also find exaggerated DMN sgACC61. MDD is reported to 
show decreased DMN connectivity with dorsal attention network (DAN)62, and decreased connectivity 
between posterior DMN and dorsal CEN, including dlPFC63,64 consistent with the notion of difficulty in 
switching from internalized, self-referential states in which the DMN is dominant, to an “executive 
state” in which the CEN is dominant and attention is directed toward external stimuli43.    
2.2.4 
Changes in Functional Connectivity Networks in Mindfulness Training 
Emerging evidence indicates that psychotherapies such as MBCT and mindfulness practice may exert 
their salutary effects by directly restoring dysfunctional networks, and by engaging compensatory 
effects on networks that modulate the dysfunctional relationships. A handful of studies have examined 
the acute and enduring effects (equivalent to the intensity and duration in MBCT) of mindfulness 
practice (assessed via fMRI) on functional connectivity in a priori nodes within networks. For example, 
Hasenkamp et al. reported four mental states in mindfulness experts during in-scanner mindfulness 
practice associated with differential activations,65 and also with different neural connectivity networks 
at rest66: mind wandering with DMN, awareness of mind wandering with SN, focus on the present 
experience with dlPFC (CEN), and shift of attention back to focus on present experience with dlPFC and 
PPC, suggesting the involvement of executive / control networks in mindfulness practice.  Using a whole-
brain connectomic approach, we also find increased connectivity in DMN-DAN connectivity when people 
with no mindfulness training perform a mindfulness task in the scanner.  Several studies of effects of 
longer-term mindfulness practice, including mindfulness intervention like MBCT, implicate enduring 

8 
 
changes in increased connectivity between DMN and CEN (dlPFC).  The PI, King, et al., recently reported 
that a 16-week group intervention with mindfulness training (based on MBCT) in PTSD patients led to 
increased DMN-CEN connectivity (i.e. PCC seed connectivity with bilateral dlPFC)2. Furthermore, the 
PCC-dlPFC connectivity was associated with decreases in PTSD avoidance and hyperarousal symptoms. 
Consistent with our findings, Brewer et al. found highly similar PCC-DLPFC and PCC-dACC connectivity 
increases in long-term meditators4, and Creswell et al. found highly similar PCC-dlPFC increases 
following a 3-day intensive mindfulness training3 that correlated with decreased plasma IL-6 3 months 
later. They also found increased resting connectivity between the dlPFC seed (CEN) and both DAN 
(superior parietal lobule, supplementary eye field, MFG) and VAN (right IFG, MTG) regions, suggesting 
mindfulness training leads to greater coordination / integration between CEN, DAN, and VAN, and that 
increased executive / attentional capacity may lead to greater capacity for salutary emotional 
regulation. Accumulating evidence indicates that MBCT / mindfulness training may decrease 
connectivity between DMN and SN. While interoception and both acute mindfulness65 and MBSR5 all 
lead to increased activity in insula (SN), Farb et al. report MBSR and mindfulness training also lead to 
decreased coupling between DMN and SN (i.e. vmPFC-insula)5, and suggested this “uncoupling” of 
vmPFC and insula leads to less automatic negative appraisals and cognitions. Further consistent with 
this, Creswell et al. report that a brief intensive mindfulness training led to decreased amygdala-sgACC 
connectivity67, providing further evidence that MBCT might decrease SN-DMN connectivity as well as 
increase DMN-CEN connectivity. 
2.2.5 
Mindfulness, Decentering, Metacognitive Awareness, and Related Psychological Processes 
Potentially Mediating Effects of MBCT 
Beyond the considerable clinical efficacy indicating that MBCT reduces depression symptoms, 
mindfulness interventions also appear to act upon theoretically predicted psychological processes, 
including decreased rumination, worry, and emotional reactivity, and increases in various self-report 
measures mindfulness, meta-awareness and decentering, and self-compassion (for meta-
analyses/reviews16,68-70 that may mediate the therapeutic effects of MBCT.  Low levels of decentering are 
associated with anxiety and depression symptoms and psychosocial disability71,72.  There is accumulating 
evidence that changes in these psychological processes (e.g., mindfulness, decentering / meta-
awareness, negative reactivity, and rumination and worry (reviewed70,73) statistically mediate the clinical 
efficacy of MBCT / MBSR.  Two recent studies report decentering statistically mediates therapeutic 
effects of MBSR on anxiety74 and mediates effects of mindfulness on depression by complementary 
mediation and indirect-only mediation75; thus suggesting decentering as a psychological process 
mediating therapeutic effects of MBCT. Decentering can be defined as a metacognitive capacity of 
individuals to observe mental phenomena as they arise in the mind (e.g., thoughts, feelings, memories, 
etc.) as transient psychological events rather than necessarily as “facts”   i.e. inherent aspects of the self 
or accurate representations of reality72,76,77. Thus decentering allows for appropriate psychological 
distancing and disengagement from, and decreased “over-personalization” of negative internal 
experiences, and thus is expected to result in decreased negative reactivity to thoughts76. 
2.3 SPECIFIC AIMS 
We will use 3T fMRI paradigms: resting state functional connectivity (rsFC), psycho-physiological 
interaction (PPI), and powerful whole-brain connectomics methods (e.g. joint independent components 

9 
 
analysis, ICA) to identify effects of MBCT on connectivity during rest and self-related tasks compared to 
MRG: 
• 
To evaluate rsFC using seed-based (PCC, vmPFC, insula, dlPFC) and whole-brain connectomics 
analyses in MBCT vs. MRG.  We hypothesize that MBCT will increase DMN-CEN (PCC-dlPFC) 
connectivity.   
• 
To evaluate self-related processing using self-relatedness vs. momentary experience task5, using 
PPI and whole brain connectomics.  We hypothesize that MBCT will decrease DMN-SN (vmPFC-
insula) connectivity. 
2.4 RISK/BENEFIT ASSESSMENT 
2.4.1 
Known Potential Risks 
Psychotherapy groups and Psychological assessment. It is possible that any psychotherapy or 
psychological assessment may increase distressing thoughts and nightmares about an individual’s past 
trauma. Likewise, participants might feel uncomfortable disclosing distressing thoughts in front of others 
during therapy.  Safeguards are in place to protect against this risk – participants will have weekly 
contact with therapists, and will also complete brief symptom self-report measures as part of each 
session.  The therapist will review these forms each session for risk factors and clinical worsening.  If 
deemed at acute risk the therapist will schedule an individual meeting for further assessment.  All 
assessments and therapy sessions are conducted in private rooms (i.e. with a door that closes, used by 
one person or group at a time). 
Magnetic Resonance Imaging. Risks from the functional MRI scanner include minor risk of discomfort 
because of the prolonged supine position; and some individuals might feel anxious from being confined 
in the scanner.  Other possible but extremely unlikely adverse effects include:  
• 
Injury due to the main magnetic field attracting ferromagnetic/metallic objects whether inside 
the body or external to the scanner  
• 
Temporary hearing loss due to loud noises associated with fMRI scanning 
• 
Potential of exacerbated symptoms of PTSD when going into the fMRI 
• 
Peripheral nerve stimulation (PNS) from the fast imaging sequences used in this study; this is 
described as light touching sensation on the skin surface and may cause mild discomfort, but is 
not harmful to the participant.  The scanner is operated within FDA guidelines so the potential 
for inducing PNS is very low. 
• 
Burns caused by wearing transdermal medication patches (because of the aluminized backing) 
during an MRI scan 
• 
Incidental clinical findings of brain abnormalities (e.g. tumor) previously unknown to the 
participant 
To reduce any potential risks, we will:  
• 
Screen anyone allowed in the room for metallic objects prior to entering the scan room to 
minimize the risk of the main magnetic field attracting ferromagnetic/metallic objects towards 
the magnet.  
• 
Screen for transdermal medication patches.  

10 
 
• 
Require participants to wear foam earplugs or other hearing protection, as is routine for clinical 
patients, to prevent risk of hearing damage due to the inherently loud noise of MR scanning.  
• 
Use custom pads and pillows to make participants as comfortable as possible. 
• 
Tell participants that they can talk with the operator or researcher through an intercom at all 
times, and that they can able to trigger an audible alarm for immediate attention or to get out 
of the MRI machine. 
• 
Notify the participant if an abnormality is detected on an MRI image.  While the research team is 
not formally trained to diagnose brain abnormalities from MRI images, they can help advise 
participants on appropriate follow-up actions. 
Video & Audio recording.  All therapy sessions will be recorded.  While the recording equipment will be 
trained on the therapist, it is likely that participants’ voices will be audible.  This means there is a chance 
that someone could be identified by their voice alone.  Recordings are considered part of the research 
record and will be afforded the same level confidentiality.  The recordings are not transcribed, but 
rather reviewed for therapist compliance with the intervention.  The video files will be stored on 
Michigan Medicine servers and will be available only to authorized study staff (via access restrictions 
and password protections).     
Genomic analysis.  There are no physical risks associated with the collection of saliva for the genomic 
analysis portion of the study. .  There is a risk are associated with a potential confidentiality breach (very 
rare) whether by accident or because the researchers publish information about the groups to which a 
particular subject might belong (e.g. sex and gender, age, racial and ethnic groups).  Preserving data 
integrity and the separation of identifying factors from genetic data will be accomplished by: 
• 
Labeling each sample with a unique code rather than personal information 
• 
Use password protections and access restrictions to authorized users only 
• 
Only share information with authorized users for approved purposes 
Additionally, the participant and their data are protected by the Federal genetic non-discrimination law 
(GINA) and an NIH-issued Certificate of Confidentiality.   
Privacy and Confidentiality.  There is a risks to a participant’s privacy associated with any research study 
or clinical interaction with the health system.  The nature of group therapy involves sharing personal 
thoughts in the presence of others.  The treating therapists will instruct group members to respect the 
privacy of their fellow participants.  All participant interactions with the study team member (e.g. phone 
screenings, study visits, therapy sessions) will be conducted in private space.  The information collected 
for this study will stored in a HIPAA-compliant database housed on Michigan Medicine servers; access 
will be restricted based on study role and job responsibilities.  Hard copies of case report forms, 
informed consent documents, etc. will be stored in a double locked environment. 
2.4.2 
Known Potential Benefits 
Participants will be informed that while it is possible that some participants may derive benefit from the 
study interventions (“mindfulness training” or muscle relaxation) or participation in the study alone, the 
primary purpose of the study is to improve our scientific understanding of mindfulness training and 
PTSD which could benefit others with PTSD. Participants may experience satisfaction of knowing that 
they have contributed to science. 

11 
 
2.4.3 
Assessment of Potential Risk & Benefits 
This research will generate new knowledge about brain activity associated with effective treatments for 
PTSD.  The improved understanding of such neural mechanisms is expected to direct development of 
targeted PTSD treatments, ultimately improving social functioning and quality of life of people with 
PTSD.  The risks are comparable to those ordinarily encountered during routine mental health and 
medical examination, and the knowledge to be gained weighs favorably against these risks. 
3 OBJECTIVES AND ENDPOINTS (GO/NO-GO CRITERIA) 
Primary Objective 
Endpoint/Outcome 
Timeframe 
Change in resting state 
functional connectivity between 
the PCC and dlPFC by the MBCT 
group compared to the MRG 
Statistically significant increase 
in PCC-dlPFC functional 
connectivity (effect size d>0.60) 
Post-treatment (after 8-weeks 
of therapy) 
Secondary Objective 
Endpoint/Outcome 
Timeframe 
Change in resting state 
functional connectivity between 
Insula and PCC by the MBCT 
group compared to the MRG 
Statistically significant decrease 
in Insula-PCC functional 
connectivity 
Post-treatment (after 8-weeks 
of therapy) 
4 STUDY DESIGN 
4.1 OVERALL DESIGN 
Study Design 
• 
Mechanistic study 
• 
Parallel groups randomized controlled trial 
Study Arms 
• 
Experimental Group: Mindfulness-based Cognitive Therapy  
• 
Control Group: Muscle Relaxation 
4.2 STUDY DESCRIPTION 
This study is a randomized controlled trial evaluating underlying mechanisms of two different non-
pharmacological therapies for PTSD.  Our hypothesis, based upon our work2 and that of others3-6 is that 
alterations in default mode network (DMN), salience network (SN), and the central executive network 
(CEN) are central mechanisms underlying therapeutic effects of MBCT. We propose that MBCT leads to 
(i) increased DMN-CEN connectivity and (ii) decreased DMN-SN connectivity related to decentering and 
metacognitive emotional regulation. Our rationale is (i) increased DMN-CEN connectivity is linked to 
increased meta-cognitive attentional capacity, (ii) decreased DMN-SN connectivity is related to 

12 
 
increased ability to dispersonalize aversive cues and interoceptive signals and decreased negative 
reactivity to these signals. 
Potential participants will complete a pre-screening interview with a research assistant for signs and 
symptoms of PTSD prior to enrollment in the study.  Individuals passing this eligibility review will be 
scheduled for an in-person baseline evaluation (T1, pre-therapy) at our research lab.  At this evaluation, 
individuals will complete the informed consent process and undergo a clinical intake assessment for 
PTSD and other eligibility criteria.  If eligible and consented, participants will complete the remaining 
self-reported psychological and QOL assessments,  undergo saliva collection for biomarkers and/or DNA, 
and an fMRI.  The fMRI is typically scheduled for a subsequent day at the North Campus Functional MRI 
Laboratory (http://fmri.research.umich.edu/). 
Participants will be randomized to a study arm with the goal running 8-12 treatment groups (MBCT or 
MRG) over the study period.  Treatment groups will consist of a minimum of 4 people, preferably 
comprised of 5-8 individuals.  After 8 consecutive weeks of treatment (at T2, post-therapy), participants 
will repeat the clinical and outcome assessments, including the fMRI. 
Post-therapy assessments will mirror the pre-therapy assessments.  Like at baseline, participants will 
complete the clinical and self-reported assessments on one day and the fMRI on a subsequent day.   
4.3 RANDOMIZATION 
This study will use block randomization to assign people to a study arm.  The study statistician is 
responsible for performing the randomization procedure and will be the sole holder of the key until the 
blind is broken.  Randomization will occur once a sufficient number of participants have enrolled to 
ensure desired group size including withdrawals. 
5 STUDY POPULATION 
The population under study includes male and female adults (aged 18-72 years) with PTSD who are 
willing to travel to study locations (e.g. Rachel Upjohn Building, North Campus fMRI lab, etc.) for 
multiple outcome assessments and treatment sessions.  At the request of the sponsor we are excluding 
certain sub-types of PTSD based on the potential for different underlying neural mechanisms.  Other 
than that, the eligibility criteria were minimalized to enhance generalizability.   
The study sample will represent persons with PTSD living in the Ann Arbor/South East Michigan area.  
The incidence of PTSD is approximately twice as high in women as in men, and thus we do not anticipate 
difficulty in recruiting sufficient numbers of women. Based upon demographics of our geographic 
region, we expect our sample will be approximately 11% African America, 8% Asian American, 1% Native 
American, and 80% European American, and approximately 8% Hispanic ethnicity.  An upper age limit 
will be set at age 60 because there is evidence that neurocircuitry of a range of cognitive processes is 
significantly influenced by the aging process. To ensure subject safety and data validity, individuals will 
be excluded from neuroimaging if they present contraindications for MRI and valid data, such as 
presence of metal implants or foreign metallic objects, claustrophobia, inability to tolerate the scanning 
procedures (e.g., lie still on back for 60 minutes), neurological disorders, and medical conditions (e.g., 
uncontrolled diabetes, stroke, seizures, etc.). 

13 
 
5.1 INCLUSION CRITERIA 
• 
Aged 18-72 years 
• 
Meets current DSM-5 criteria for PTSD (with or without MDD); type of trauma can include 
interpersonal violence, combat, and sexual assault, etc.  
5.2 EXCLUSION CRITERIA 
• 
Dissociative PTSD 
• 
Delayed-onset PTSD 
• 
MRI contraindications (e.g. metal in body, inability to be in the scanner – claustrophobia, severe 
back pain, etc.) 
• 
Serious medical or neurologic conditions (e.g. stroke, seizures) 
• 
Suicide risk 
• 
Psychosis 
• 
Life history of schizophrenia 
• 
Life history of bipolar disorder 
• 
Current substance dependence 
• 
Other factors that preclude safe and meaningful participation in the study, at discretion of the PI 
and study team 
5.3 LIFESTYLE CONSIDERATIONS 
Individuals with a history of drug or alcohol dependence (highly prevalent in PTSD) or pre-existing 
current treatment with psychotropic medications will not be excluded; however, patients taking these 
medications must have clearance from psychiatrist.  
5.4 SCREEN FAILURES 
Participants will be considered screen failures if, post-consent, they are deemed ineligible at the initial 
intake visit or fMRI scan: 
• 
Intake assessment reveals an excluded PTSD sub-type 
• 
Intake assessment reveals a contraindicated psychiatric diagnosis 
• 
Unable to participate in the initial fMRI either because of contraindications or inability to lie still 
in the scanner or complete the tasks 
• 
Otherwise does not fulfill eligibility criteria 
Participants who are found to be screen-failures post-consent will not be enrolled in the clinical trial.  
However, to improve recruitment and retention of enrolled participants, consented participants who 
screen-fail due to (a) inability do fMRI scan or (b) who are missing a single PTSD symptom may be 
allowed to participate in the group psychotherapy and assessment part of the study (whichever their 
cohort is cluster randomized to, MBCT or MRG). (See section 5.6.1 below). 

14 
 
5.5 LOST-TO-FOLLOW UP 
Participants who are lost-to-follow up are those were participating in the study (i.e. enrolled) and are no 
longer participating in study activities and who do not respond to repeated attempts to contact.  In our 
previous studies, the rates of lost-to-follow up were lower than our non-completion/withdrawal rate as 
most treatment non-completers were responsive to study team contact and willing to return for 
outcome assessments. 
See Subject Accrual & Recruitment Plan 
5.6 STRATEGIES FOR RECRUITMENT AND RETENTION 
See Study Accrual & Retention Plan 
Patient participants will be recruited from the Ann Arbor/SE Michigan community, which includes three 
major universities (University of Michigan, Eastern Michigan University, and Wayne State University), 
and two large VA Hospitals (VA Ann Arbor and VA Detroit).  Our extended research group, under the 
leadership of the Israel Liberzon, MD, who is an Attending Psychiatrist of the VA Mental Health Service, 
has successfully recruited at least several hundred PTSD patients for a number of fMRI and PET 
neuroimaging and treatment studies over the past 10 years.  In the past 5 years, the PI, Dr. King and 
colleagues have recruited over 200 persons with PTSD from the community.  
The recruitment process consists of several stages for providing information to the potential participant 
allowing time for the individual to consider involvement.  The initial contact is a telephone pre-screening 
interview during which the study coordinator will administer a brief PTSD screener, share details and 
parameters of the study, and provide an opportunity for questions.  For those are pass the initial 
screening and express interest in the study, a baseline study visit will be scheduled.  The individual will 
meet with study staff where at which time they will again listen to an explanation of the study, have 
time to read the consent document and ask questions.  During this discussion, the staff member will 
inquire about the ability of the patient to understand the nature of a research protocol.  Signed consent 
may be provided at this time, or at a subsequent interview if the potential participant would like more 
time to consider their options. It will be made very clear that the research study offers two 8-week 
interventions that are experimental manipulations but are not considered a mental health treatment for 
PTSD.  We will request permission to discuss with the participant’s PCP and mental health provider(s).  
We will ask the participant if they would like referral to mental health treatment for PTSD, and if they 
do, will provide several referrals to local licensed mental health professionals. When the patient signs 
the consent, the complete assessment process will begin. 
Participants who consent to the study but are found to be screen-failures post-consent because they 
cannot do fMRI scan or are missing a single PTSD symptom will not be formally enrolled in the clinical 
trial.  However, they will be allowed to participate in the group psychotherapy (whichever their cohort is 
cluster randomized to, MBCT or MRG) and follow-up assessments only. They will sign a separate consent 
indicating they do not meet the inclusion criteria for the clinical trial / full study, but will be offered the 
treatment-and-assessment-only parts of the study.  The purpose for including screen-fails in the 
psychotherapy groups is to improve feasibility – i.e. to increase study flow and to avoid unacceptable 

15 
 
wait times for enrolled participants (i.e. who have full PTSD and who have done fMRI). However, to 
measure and control for group characteristics in multi-level modeling, we will also collect weekly self-
report and follow-up assessment on the “treatment-only non-fMRI” participants.   
5.6.1 
Participant Incentives 
Participants will be paid up to $320.00 for completing the study.  The payment includes incentive for 
participation in study procedures and a small travel allowance.  Participants will be paid only for the 
parts of the study completed. Participants who screen-fail fMRI but are allowed to do the treatment will 
not be paid for the fMRI part of the study. 
• 
$25 per clinical assessment (up to $50) 
• 
$75 per fMRI (up to $150) 
• 
$10 per visit (study assessments and treatment sessions) as travel stipend (up to $120) 
6 STUDY INTERVENTIONS 
6.1 JUSTIFICATION FOR INTERVENTION 
6.1.1 
Study of MBCT targets and mechanisms in acute psychiatric disorder (PTSD) 
While originally designed as a treatment for depression relapse prevention in remitted patients, there is 
a growing appreciation that MBCT and related forms of attention training may be a useful approach as 
an adjunctive treatment or treatment component for acute psychiatric disorders, including hard-to-treat 
disorders like treatment resistant depression, GAD, anxious depression (chronic comorbid MDD-
GAD)78,79. Several studies now suggest that mindfulness-based interventions like MBCT are well 
tolerated and demonstrate efficacy for PTSD in studies of both primarily males with combat 
trauma2,24,25,28-32 and primarily females with interpersonal violence and sexual abuse23,33. Over the past 
decade, mindfulness-based approaches have become more common in PTSD treatment; indeed one 
recent report found that 77% of Department of Veterans Affairs (VA) PTSD specialty programs offered 
some type of mindfulness training80. However, there has been less mechanistic study of effects of MBCT 
on acute psychiatric disorders. Initial work showing mindfulness may lead to alteration in large scale 
connectivity networks in PTSD patients2 (and highly stressed persons3,81) is exciting because it suggests 
the possibility MBCT / other forms of mindfulness training may engage novel treatment targets / novel 
mechanisms that might combined with other forms of psychotherapy interventions (e.g. exposure, 
cognitive restructuring, etc.) for persons with acute psychiatric disorders to maximize effects.      
6.1.2 
Large-scale connectivity networks as targets of MBCT treatment effects 
Important findings from translational neuroimaging studies of psychotherapy interventions have 
identified the importance of alterations in amygdala, insula, and sgACC for example, in treatment of 
PTSD, MDD, and anxiety disorders (for review82) but only recently has research been focused on the 
effects of psychotherapies or other treatments on the strength of functional connectivities within and 
between large scale brain networks (reviewed83,84). This has mainly focused on seed-based analyses in 
subcortical regions and role of DMN in depression. Interestingly, in studies of antidepressant 
medication, while findings of altered connectivity between prefrontal and limbic areas have been 
reported, most studies have not found strong changes in DMN that correlated with symptom change, 

16 
 
and have not found changes in CEN83,84.  In contrast, studies of ECT and studies of transcranial 
stimulation have found increased connectivity in dlPFC83; thus findings that MBCT increases PCC-dlPFC 
connectivity are of considerable interest.  Furthermore, unlike most previous studies, we are proposing 
here to use whole-brain connectomics to test changes in distributed networks. Our co-investigator Dr. 
Sripada is a leader in development and use of such powerful connectomics methods in studies of 
psychiatric disorders and now treatment, and our Neuroimaging Methods Core has functional 
processing streams for the joint ICA connectomics approaches we are proposing here. We are also 
currently actively developing and testing additional connectomic methods for dynamic connectomics 
and other applications adding to innovative abilities to interrogate large scale networks in both resting 
and task-based paradigms. 
Based upon previous work by our group and others reviewed above, we propose a mechanistic model in 
which the syndrome of PTSD is driven in part by hyperconnectivity within the SN (in particular, 
amygdale-insula), and dysregulated / exaggerated between SN and DMN that is associated with 
intrusive, automatic distress reactions to both external cues and internal physiological states. Similar 
dysfunctional vmPFC-insula hyperconnectivity has also been implicated in depression and anxiety58. 
Neuroimaging evidence suggests aberrant functional connectivity in large-scale networks may underlie 
negativity bias, over-identification and misinterpretation of interoceptive cues, and negative rumination 
in anxiety, depression, and PTSD.   
We propose that MBCT / mindfulness training leads to enhanced connectivity between DMN-CEN and 
normalized connectivity in DMN-SN that underlie the psychological mechanisms leading to therapeutic 
change. Several studies find mindfulness training leads to increased connectivity between DMN and CEN 
/ cognitive control networks (e.g. increased PCC-dlPFC, and vmPFC-dlPFC), and decreased DMN-SN 
connectivity (sgACC-amygdala), both in healthy people and in people with and acute psychiatric disorder 
(PTSD). These MBCT effects on network connectivity are expressed psychologically as increased 
decentering (and related psychological constructs of metacognitive awareness, mindfulness, distancing, 
defusion, etc.), the psychological processes mediating positive mental health outcomes of MBCT.  
Recent theoretical and empirical work by Fresco et al.76,85 has further elaborated the construct of 
decentering into three components: the attentional practice of meta-awareness enables the capacity for 
dis-identification from internal experience, and reduced reactivity to thought content.  
6.2 STUDY INTERVENTION: MBCT (MINDFULNESS-BASED COGNITIVE TREATMENT)  
MBCT is a well-documented intervention initially designed for prevention of depression relapse, which 
has since been successfully adapted to a number of disorders, including depression, GAD, and PTSD. We 
will use our previously published adaption for PTSD24. MBCT includes a number of mindfulness exercises 
and group discussion; exercises include a) mindful eating (the 'raisin exercise'), b) the 'body-scan' 
exercise, c) mindful stretching, d) sitting mindfulness of breath exercise and e) the “3-Minute Breathing 
Space” (a brief mindfulness of breath exercise).  
• 
Group therapy 
• 
8-weeks 
• 
2 hours/session 
• 
MBCT exercises at home for ~20-30 minutes on 5 or more days/week 
o Assisted by audio recordings 

17 
 
• 
Co-led by two trained therapists 
6.2.1 
MBCT Fidelity 
Our consultant Mark Lau, PhD, R. Psych. is an expert trainer in Mindfulness-based Cognitive Therapy 
(MBCT), certified by the Canadian Association of Cognitive and Behavioural Therapies and the Academy 
of Cognitive Therapy (ACT).  
• 
To insure adherence and fidelity to the MBCT model, Dr. Lau will consult with therapists via 
videoconferencing on clinical delivery before and during each MBCT group, including review of 
session content, and will review video recording of therapists delivering each treatment 
component. 
• 
MBCT therapists in the study will be licensed mental health professionals with training in PTSD 
psychotherapy with MBCT Teacher Qualification from UCSD (or equivalent). 
• 
Therapists will have a checklist and materials for each session, and each session will be video 
recorded. A trained MS-level student will review each session to record that each treatment 
component was delivered (and start-stop time of each component), and note any divergence 
from protocol.  Relevant portions of videos will be reviewed by therapists before each 
videoconference with Dr. Lau and will be discussed in consultation.  
• 
Treatment fidelity of therapists will be assessed by delivery of treatment components and 
therapist competencies, using Mindfulness-Based Interventions-Teaching Assessment Criteria 
(MBI-TAC) 
• 
Participants will complete treatment logs which will be reviewed at each session  
6.3 STUDY INTERVENTION: MUSCLE RELAXATION GROUP (MRG) 
The control intervention was developed by study consultant, Dr. David Fresco, for use in medical 
patients with PTSD-material.  It is well-balanced with MBCT in terms of time, number of sessions, 
therapist contact, group support and home practice.  The primary difference between MRG and MBCT is 
the lack of mindfulness instruction and practice in decentering.  It is a common active comparator in 
studies of PTSD, and is a plausible intervention with demonstrated tolerability and efficacy. 
Participants will learn progressive muscle relaxation techniques that involve alternately tensing and 
relaxing various muscle groups to achieve a state of global body relaxation.   
• 
Group sessions 
• 
8-weeks 
• 
2 hours/session 
• 
Home exercises comparable duration to MBCT 
o Includes audio recordings to facilitate compliance 
6.3.1 
MRG Fidelity 
• 
To insure adherence and fidelity to the MRG manual, Dr. Fresco will consult with therapists via 
videoconferencing on clinical delivery before and during each MRG group. 
• 
MRB therapists in the study will be therapists trained to instruct and guide participants in 
muscle relaxation exercises. 

18 
 
• 
Therapists will have a checklist and materials for each session, and each session will be video 
recorded. A trained MS-level student will review each session to record that treatment content 
was delivered, and note any divergence from protocol, relevant portions of videos will be 
reviewed by therapists before each videoconference with Dr. Fresco and will be discussed in 
consultation.  
• 
Approximately 20% of video recordings will be reviewed by Dr. Fresco or his designee for 
compliance the intervention and delivery techniques.   
• 
Participants will complete treatment logs that will be reviewed each session. 
6.4 MEASURES TO MINIMIZE BIAS 
The majority of the study team will be blinded until the data are fully collected and the database locked.  
The table below offers a description of the various study personnel and their blinding status.  A NO 
indicates that a particular stakeholder will not be blinded and a YES indicates that they will be blinded. 
Stake holder 
Intervention group 
assignment 
Primary 
Mechanistic 
Outcome Measure 
Clinical/ Functional 
Outcome Measure 
Study Participants 
No. Participants 
cannot be blinded to 
the type of therapy 
they receive; 
however, both 
therapies will be 
presented as 
plausible 
treatments, and 
cross contamination 
will be minimized 
Yes.  The 
mechanistic 
outcome is a brain 
connectivity 
measure; patients 
will not be 
appraised of brain 
scan outcome data. 
Yes.  While PTSD 
symptoms and pain 
will be obvious to 
patients, 
decentering and 
physiological 
measures will not. 
Instructors/Practitioners 
No.  The instructors 
will know which 
therapy they are 
delivering 
Yes.  Practitioners 
will not have access 
/ not be appraised 
of brain scan data 
Yes.  Practitioners 
will not have access 
/ not be appraised 
of outcome data 
Outcome Assessors 
Yes. Assessors will 
be blinded to group 
assignment 
Yes.  Assessors will 
not have access / 
not be appraised of 
brain scan data 
Yes. Assessors will 
be blinded to group 
assignment 
Data 
Analysts/Statistician 
Yes. Analysts will not 
know group 
assignment until 
blind is broken 
Yes. Analysts will 
not know group 
until blind is broken 
Yes. Analysts will 
not know group 
until blind is broken 
Principal Investigators 
Yes. PIs will not 
know group 
Yes. PIs will not 
know group 
Yes. PIs will not 
know group 

19 
 
assignment until 
blind is broken 
assignment until 
blind is broken 
assignment until 
blind is broken 
 
6.5 CONCOMITANT THERAPY 
Participants will be allowed to continue with their usual and customary PTSD treatments including 
psychotropic medications under the direction of their psychiatrist.  It is expected that these treatments 
are to remain stable for the duration of an individual’s participation.   
6.6 PARTICIPANT WITHDRAWAL FROM INTERVENTION AND STUDY 
Participants may be withdrawn from the treatment or study for a number of different reasons: 
• 
It is not in the best interest of the participant to continue (e.g. worsening of symptoms 
incompatible with continuing with the treatment or study) 
• 
An individual becomes ineligible (classified as withdrawn if occurs after the initial study visit) 
• 
A change in condition that requires treatment that is not permitted under the protocol 
• 
PI and/or study team can withdraw a participant for not following study instructions or other 
reasons related to data integrity and safety 
• 
A participant can change their mind about participation 
When possible, we will perform study assessments as feasible (i.e. collect self-report measures, but not 
fMRI), and information related to reason for withdrawal.  All data and saliva collected up the point of 
withdrawal will be retained in the study database to minimize data loss and preserve data integrity. 
7 STUDY ASSESSMENTS & PROCEDURES 
7.1 PSYCHIATRIC DIAGNOSTIC STATUS 
7.1.1 
Mini-International Neuropsychiatric Interview (MINI 7.0.2) 
The MINI is a brief structured diagnostic interview instrument to assess for major psychiatric disorders 
that can be administered in ~15 minutes.   
7.1.2 
Clinician-administered PTSD Scale (CAPS-5) 
The CAPS-5 is a 30-item clinician-administered PTSD assessment.  It is used to make both current and 
lifetime diagnoses of PTSD as well assess recent symptoms.  The full interview takes ~45-60 minutes to 
complete. 
7.1.3 
PTSD Checklist (PCL-5) 
The PCL-5 is a 20-item self-report instrument that assesses DSM-5 PTSD symptoms.  It is used to 
monitoring symptom change and as a screening tool.   

20 
 
7.1.4 
Hamilton Depression Scale (HAM-D) 
The HAM-D is a 21-item clinician-administered instrument for determining depression severity before, 
during and after treatment.  It takes approximately 15-20 minutes to administer and score (only the first 
17 items are used to calculate the score) 
7.1.5.     Matrix reasoning 
This is a sub-scale of the Wechsler Adult Intelligence Scale-IV (WAIS-IV). This is an untimed, nonverbal 
reasoning task in which individuals are asked to identify patterns in designs. It usually takes between 8-
15 min to complete. This subtest measures: non-verbal reasoning skills, broad visual intelligence, and 
perceptual organization skills related to fluid intelligence (gF).  This measure will be used as a cross-
validation for the fMRI connectivity analyses.    
7.2 QUALITY OF LIFE AND OUTCOME ASSESSMENTS 
7.2.1 
Beck Depression Inventory (BDI-II) 
The BDI-II is a 21-item self-report measure of depressive symptoms.  Scores range from 0-63 with higher 
numbers suggesting more severe depression. 
7.2.2 
Experiences Questionnaire – Decentering Factor (EQ) 
The EQ is an 11-item self-report measure that captures both decentering and rumination.  Scores range 
from 11-55 with higher values suggesting greater decentering.  
7.2.3 
Acceptance and Action Questionnaire (AAQ) 
The AAQ is a 9-item self-report measure of experiential avoidance and psychological inflexibility.  Higher 
scores suggest greater avoidance and immobility while lower scores reflect greater acceptance and 
action. 
7.2.4 
Multifacet Mindfulness Questionnaire (MMQ-15) 
The MMQ-15 is a 15-item self-report measure of trait-like tendencies to mindful in everyday life.  It 
includes the facets of describing, acting with awareness, nonjudging, and nonreactivity.  Scores for each 
facet range from 3-15. 
7.2.5 
Emotional Regulation Questionnaire (ERQ) 
The ERQ is a 10-item self-report measure of the tendency to regulate emotions in two different ways: 
cognitive reappraisal and expressive suppression.  Each facet is scored separately. 
7.2.6 
Response Styles Questionnaire, Ruminative Response Subscale (RSQ-RRS) 
The RSQ-RRS is an 11-item self-report measure of ruminative tendencies in response to negative 
emotion.  Higher scores suggestion greater rumination. 
7.2.7 
Brief Pain Inventory (BPI) 
The BPI is a self-report measure of pain intensity (3 items) and pain interference (9 items) with everyday 
activities.  Higher scores reflect greater intensity and more interference. 

21 
 
7.2.8 
Life Events Checklist (LEC) 
The LEC is a self-report measure designed to screen for potentially traumatic events in an individual’s 
lifetime.  It includes 16 events known to potentially contribute to the development of PTSD or ongoing 
distress, and includes an additional item for “other” events no otherwise captured by the list. 
7.2.9 
Childhood Trauma Questionnaire (CTQ) 
The CTQ is a self-report measured designed to capture potentially traumatic experiences that occurred 
in childhood and in the teenage years. 
7.2.10 Self-Compassion Scale 
Short form (12-item) self-report measure of self-compassion.  It includes 4 items for self-kindnes vs self-
criticism, 4 items for mindfulness, 4 items for recognizing common humanity aspects of one’s actions. 
7.2.11 Posttraumatic Cognitions Inventory (PTCI-9) 
The PTCI-9 is a brief form  9-item self-report instrument that assesses cognitions associated with PTSD 
risk, including 3 items each related to negative self views, dangerous world, and self-blame. 
7.3 RESEARCH PROCEDURES 
7.3.1 
Functional Magnetic Resonance Imaging (fMRI) 
Neural mechanisms (BOLD – blood oxygen-level-dependent imaging – activity) will be assessed using 
two paradigms that will be counter-balanced to control for order effects: 
Resting Connectivity – Participants are asked to “remain still, keep your eyes open and on the fixation 
mark, let your mind wander freely and do not fall asleep.”  This scan lasts approximately 10 minutes. 
Resting Connectivity – Participants are asked to “remain still, keep your eyes open and on the fixation 
mark, and do not fall asleep. Please bring your attention to the sounds in the scanner and the feelings 
and sensations in your body.  When you notice your mind wandering, please bring your attention back 
to the sensations in your body”.  This scan lasts approximately 10 minutes. 
Context Separation and Completion Task: To assess pattern separation and pattern completion abilities 
specific to complex contextual scenes, participants will view two target images of rooms with different 
configurations of furniture (“room A” and “room B”), and then shown a series of images of rooms with 
various configurations of furniture and asked to choose whether it is most similar to “room A” or “room 
B”.  These mages will have items replaced or moved to create varying degrees of similarity to the 
original scenes A or B. This will allow us to determine each subject’s threshold for pattern completion 
(categorizing the previously viewed image correctly), pattern separation (categorizing the new image as 
never seen before) and overgeneralization (incorrect categorization). This task will take approx. 15 mins 
to complete.  MRI will be used to examine hippocampal and PFC activation related to context 
discrimination abilities.  
Self-related Processing Task5 – This task consists of viewing eight sets of words, each containing six 
personality-trait adjectives (e.g. lively, productive, indecisive, clumsy).  Participants will view the sets of 
words.  Each word in the set will be displayed for 4 seconds each (with a 2 second delay between 
words), for a total of 36 seconds per set.  Before the display of each word “set” there will be an 
instructions displayed, saying to perform either the “Narrative” or “Experiential” task.  The participant 

22 
 
will be asked to perform one of these two ‘tasks’ while viewing the words.  “Narrative” consists of 
viewing each word and thinking about what the trait word means to the participant, whether it 
describes the participant, and allowing oneself to become “caught up in a given train of thought”.  
“Experiential Focus” will involve engaging present-centered self-reference, sensing what is occurring in 
one’s thoughts, feelings and body state, without purpose or goal, other than noticing how things are 
from one moment to the next.  Each participant will complete 2 runs in the scanner (each run will be 
two repetitions of each condition, so the total task will consist of a total of 8 lists, or ~8 min in length.  
Participants will be trained in how to engage in these different forms of self-focus before the scan (~10 
min), and after the scan will be asked to recall which words they remember. 
7.3.2 
Pregnancy test 
Each female participant of child-bearing age will take a urine (dipstick) pregnancy before each scan.  
Individuals testing positive not go through the scan.   
7.3.3 
Saliva specimen collection for adrenergic and inflammatory biomarkers 
Participants will provide saliva samples by passive drool (spitting into plastic tubes) at 4 points during 
the MRI scan – upon arrival, immediately before entering and after exiting the scanner, and before 
departing the MRI facility. 
7.3.4     Measures of emotional engagement. In the assessment session before the CAPS interview, 
patients be administered the “standardized trauma interview”118 (STI, a very common interview that is in 
first session of PE) and will be video-recorded and heart rate responses (ECG) and skin conductance 
(SCR) measures taken using a mobile (tablet controlled) psychophysiology system as previous 
described119. The videos will be stored and later scored at VA Ann Arbor using the Levels of Engagement 
Scale (LES) by raters on three dimensions of a) willingness, b) psychological contact with trauma 
memories, and c) emotional responsiveness. Heart rate responses (HRR) and skin conductance 
responses (SCR) to the trauma memory will be calculated as previously reported119.   
 
7.4 SAFETY ASSESSMENTS 
See Data & Safety Monitoring Plan 
7.4.1 
MRI screening 
Individuals are pre-screened by the study team for MRI contraindications, and then the technicians 
screen prior to each scan 
7.4.2 
PHQ-9 
The PHQ-9 is a brief self-report assessment that measures depression symptoms and suicidal ideation.  
It will be scored in real-time so that any indication of suicide risk can be addressed immediately. 
7.4.3 
Columbia Suicide Severity Ratings Scale (C-SSRS) 
The C-SSRS is 6-item assessment tool that evaluates suicidal ideation and behavior.  It will only be 
administered if indicated by participants’ responses on the PHQ-9.  

23 
 
7.4.4 
Clinical Global Impressions Scale (CGI) 
The CGI has two components – severity (“Considering your total clinical experience with this particular 
population, how mentally ill is the patient at this time?” scored on a 7-point scale ranging from normal 
to among the most extremely ill patients) and Improvement (“Compared to the patient's condition at 
admission to the project, this patient's condition is…” scored on a 7-point scale ranging from very much 
improved to very much worse. 
7.4.5 
PCL-5 
The PCL-5 is a 20-item self-report instrument that assesses DSM-5 PTSD symptoms.  It is used to 
monitoring symptom change and as a screening tool (see Section 6.7.3).   
7.5 ADVERSE EVENTS & SERIOUS ADVERSE EVENTS 
See Data & Safety Monitoring Plan 
7.5.1 
Suicidal Ideation 
Study participants are people with current PTSD with or without co-morbid with major depression. 
Clinical epidemiology estimates the annual incidence of suicidal ideation in the US general population to 
be ~5% with higher rates observed in both PTSD and depressed patients.  At baseline and throughout 
the study (assessments, scans, and therapy sessions), participants will complete a number of survey 
measures to assess clinical status and potential suicidal ideation.  
• 
The PHQ-9 will be scored in real-time so that any indication of suicide risk can be dealt with 
immediately.   
• 
If suicidal ideation or behavior is indicated at any time in conjunction with the study, UM study 
personnel will immediately take measures to assess the severity of the risk, and apply safety 
measures as appropriate and clinically indicated.   
• 
Suicide risk severity will be assessed using the Columbia Suicide Severity Rating Scale, 
considered a “gold standard” for suicide risk assessment.  
If suicide risk is assessed to be moderate or high with potential for imminent danger, the study 
therapists / other study team will work with the participant to ensure clinically appropriate care, 
including contact with and possible transportation by ambulance to University of Michigan (UM) 
Psychiatric Emergency Services (PES).   
• 
The PI and the UM medical monitor (respectively) will be notified immediately and will be 
available to assist with assessment and coordination of safety measures and clinical care. 
• 
The PI and all participating University of Michigan study personnel carry pagers and can be 
reached at any time through PES, which is open 24 hours a day, 365 days per year. Our project 
team is comprised of four Board Certified Psychiatrists and two Licensed Psychologists, all of 
whom will be available to study psychotherapists (who are also licensed mental health 
providers) and other study staff (e.g. study coordinator, independent assessors) should concerns 
arise to determine the need for a higher level of care and support the study staff and study 
psychotherapists in making make appropriate recommendations and referrals. 

24 
 
• 
This will also be reported to IRB as an AE or a SAE, depending upon how the situation is 
resolved. 
7.5.2 
Clinical Worsening 
While the majority of PTSD patients show improvement and decrease in symptoms in response to MBCT 
and MRT, some patients do not improve, and a small proportion experience clinical worsening and 
increased psychiatric symptoms during treatment. Clinical worsening could occur due to treatment-
specific factors as well as factors not related to the treatments per se (e.g. experience of stressful life 
events during the study).   
Clinical worsening will be defined as clinically significant increase in psychiatric symptoms (based on 
current accepted professional standards) assessed from self-report measures used in the study (PCL-5 or 
PHQ-9) or worsening on clinician-rated Clinical Global Clinical Impression (CGI, e.g. rating of 6-much 
worse or 5-very much worse) that occurs over two consecutive weeks.  Intermittent worsening of 
symptoms, as well as worsening that is below current accepted professional thresholds of “clinically 
significant” will also be reported to the PI and Co-Is at weekly Team Meeting, and on case-by-case basis, 
could also trigger report to medical monitor and clinical review to determine whether alternate or 
higher-level psychiatric care is necessary. 
• 
Psychiatric symptoms will be monitored weekly by study therapists  
• 
Clinically significant worsening of symptoms whether or not they are deemed related to the 
study treatments will be reported to both PI and medical monitor within 24 hours, and will 
trigger a clinical review to determine whether an alternate or higher level of psychiatric care is 
necessary for the patient.  
o This may include further psychiatric evaluation of the participant by the PI and/or study 
medical monitor 
o Such occurrences will be reported to IRB as AE or ORIO, and the participant may be 
required to exit the study if alternative care is found to be necessary.  Referrals for 
alternate psychiatric care will be made by the medical monitor or their designee 
7.5.3 
Assessment and management of participants with PTSD who have panic symptoms or an 
exacerbation of PTSD symptoms when they are undergoing an MRI scan or are in the MRI center.  
 
While the vast majority of PTSD patients we have scanned over the past 12 years have not had panic 
reactions or exacerbation of PTSD symptoms in the MRI scanner or center, such situations have 
occurred and is a possible occurrence.  In order to minimize the risk of an anxiety reaction/panic attacks 
induced by confinement in the scanner, the subjects are allowed to communicate with the machine 
operator via an intercom and may trigger an audible alarm at any time.  Before the subject is placed in 
the magnet, he or she is reminded that they are free to stop the study at any time if they become 
uncomfortable.  In the event of an adverse event due to anxiety reaction/panic attacks leading to 
participant triggering the alarm in the MRI, or communicating that they wish to stop, or if the study 
research personnel determines that a participant is having an anxiety reaction or panic attack at any 
time in the MRI facility, the experiment would be immediately terminated and the participant would be 
immediately removed from the scanner.  Research personnel will be trained to monitor for this and 
notify the PI immediately, and will take appropriate acute counseling measures. The PI Dr King is a 
licensed psychologist at Michigan Medicine Outpatient Psychiatry Anxiety Disorders Clinic specializing in 

25 
 
PTSD and anxiety, co-Is Dr Favorite and Dr Fresco are licensed psychologists specializing in PTSD and 
anxiety, co-Is Dr Abelson, Dr Muzik, and Dr Sripada are all board-certified psychiatrists at Michigan 
Medicine specializing in Anxiety and/or PTSD.  The PI and/or clinical co-Is will be notified immediately by 
pager or cellphone contact, and will provide immediate onsite counseling and referral to an appropriate 
psychological or psychiatric facility (e.g. Michigan Medicine Psychiatry or Psychological Clinic) in case of 
crisis or need for debriefing that day, or if they want referral after the scan. In addition, even if the 
participant does not receive a referral for mental health treatment, follow-up telephone calls would be 
made within 1-3 days of an episode to confirm the transient nature of their reaction. 
• 
Psychiatric symptoms will be monitored at the MRI by study team  
• 
Clinically significant anxiety reaction, panic attack, or exacerbation of PTSD symptoms at the 
MRI center, whether or not they are deemed related to the study treatments, will be reported 
to both PI and medical monitor within 24 hours, and will trigger a clinical review to determine 
whether an alternate or higher level of psychiatric care is necessary for the patient.  
o This may include further psychiatric evaluation of the participant by the PI and/or study 
medical monitor 
o Such occurrences will be reported to IRB as AE or ORIO, and the participant may be 
required to exit the study if alternative care is found to be necessary.  Referrals for 
alternate psychiatric care will be made by the medical monitor or their designee 
7.6 UNANTICIPATED PROBLEMS 
See Data & Safety Monitoring Plan 
8 STATISTICAL CONSIDERATIONS 
8.1 GO/NO GO CRITERIA – PRIMARY MECHANISTIC OUTCOME 
Our primary hypothesis that dictates GO to R33 is that MBCT will lead to specific changes in specific 
circuits within DMN and CEN.  Specifically, our R61 Go/No-Go criteria is increased functional 
connectivity between dlPFC and PCC in the MBCT condition compared to the MRG active control 
reflected in a clear effect size (d>0.60).  This will be tested in analyses of resting state functional 
connectivity (using a PCC-seed) using group contrast and repeated measures ANOVA (RM-ANOVA) 
approach in spm: specifically testing for between-group difference in PCC-dlPFC rsFC post-intervention, 
and/or a Group x Time spreading interaction between treatment group (MBCT vs MRG) and Time (pre vs 
post treatment) 
To test PCC-dlPFC rsFC, we will use a search region ROI mask using the Wake Forest University PickAtlas 
Automatic Anatomical Labeling atlas consisting of the left and right middle frontal cortex (based upon 
findings of Brewer et al., 2011, Creswell, et al., 2016; King et al., 2016). We must find a cluster of rsFC in 
dlPFC region defined above that is statistically significant in a pre-post between-group comparison 
(MBCT > MRG). 

26 
 
8.2 SECONDARY MECHANISTIC OUTCOME 
We hypothesize we will also see change in our secondary brain mechanism (decreased Insula-PCC rsFC) 
that is related to decrease in PTSD symptoms following both interventions.  We hypothesize that this is a 
treatment target common to MBCT and other approaches, whereas increased PCC-dlPFC is specific to 
MBCT.  We further hypothesize that increased PCC-dlPFC rsFC from MBCT will drive increased 
engagement in naturalistic vivo exposures and thereby decrease PTSD symptoms and thereby Ins-PCC 
rsFC. 
9 OPERATIONAL CONSIDERATIONS 
9.1 INFORMED CONSENT PROCESS 
The recruitment through enrollment process consists of several stages for providing information to the 
potential participant.  At the initial study visit the study staff will meet with individuals to explain the 
study again and to review the consent document.  The proceeding discussion will focus on the voluntary 
nature of the research study, that it is distinct from clinical care or therapy for PTSD, a review of study 
procedures and participant responsibilities, and risks-benefits of participation.  The study staff will 
inquire about the ability of the potential participation to understand the nature of the protocol.  
Documented informed consent may occur at this time, or at a subsequent time if the potential 
participant would like more time to consider their decision.   
The consent process will take place in private space.   
9.2 CONFIDENTIALITY AND PRIVACY 
All encounters with potential and enrolled participants will take place in private space (e.g. exam room, 
research room, office, etc.).  Study staff will be trained in Michigan Medicine privacy practices and 
dealing with confidential or sensitive information.  Therapy sessions will be closed, and participants 
instructed to respect one another’s privacy. 
Data elements and saliva samples will be coded with identifiers stored in a password-protected HIPAA-
compliant database.  All research data and samples will be under the purview of the PI and access will 
be restricted based on job role. 
9.2.1 
Source Document and Data Management 
See Data & Safety Monitoring Plan 
9.2.2 
Data Retention for Study Record Keeping 
All study identifiable data and information from this study will be retained for the duration of this study 
and at least through the accrual period of the subsequent R33 portion of the funding mechanism.  Study 
records will be coded, and the link to identifiers stored in the HIPAA-compliant study database.  Access 
will be under the purview of the PI and restricted to authorized study staff.  We are retaining these data 
to prevent co-enrollment in both the R61 and R33 and preserve data integrity. 

27 
 
• 
Pre-screening information will not be retained for those individuals deemed ineligible or 
otherwise unsuitable for the study.  The records will be destroyed after the interview. 
The de-identified study database will be archived and stored on Michigan Medicine servers.  Hard copies 
of identifiable study records (e.g. consent document) will be retained for at least 3 years beyond 
submission of the final progress report or publication of the primary manuscript, whichever is later.  
Health-related data will be retained for at least 7 years beyond submission of the final progress report. 
• 
Recordings will be stored in the study database and be used for ongoing therapist training. 
9.2.3 
Future Use of Specimens and Data 
Identified data will be retained for possible future research use for a minimum of 2 years beyond the 
completion of the current study to allow for potential long-term follow-up assessments.  We will not 
undertake these assessments, or other future unspecified research without additional IRBMED-
approval.   
• 
Identified data will be stored in a HIPAA-compliant database on Michigan Medicine servers 
• 
Access to the database will be under the PI’s purview and access-restricted 
• 
Datasets shared with collaborators will stripped of identifiers and date-shifted 
9.3 DATA HANDLING AND RECORD KEEPING 
See Data & Safety Monitoring Plan 
9.4 DATA SHARING 
Data and materials generated under this project will be administered in accordance with NIH Sharing 
policies, including NIH Policy on Dissemination of NIH-Funded Clinical Trial Information (8/2016), and the 
NIH Grants Policy Statement (Availability of Research Results) (11/2015) - Section of the NIH Grants 
Policy Statement which discusses the availability of research results developed with NIH funding, 
including publications, data, unique research resources, and intellectual property (inventions and 
patents. 
Depending on such NIH policies, data and materials generated by this project may be transferred to 
others under the terms of a data or material transfer agreement. Access to databases generated by the 
project will be available for educational, research and non-profit purposes.   
9.4.1 
Publication of Results 
Publication of data will occur during or shortly after the completion of the project, consistent with 
normal scientific practices.   
 
9.4.2 
fMRI Data 
We plan to make available data from fMRI scans from human subjects initially to collaborators for 
independent replication / data pooling.  We also plan to make the de-identified brain scans available to 
the broad scientific community in public databases once the main findings from the finalized research 

28 
 
dataset have been accepted for publication. However, additional redaction steps may need to be made 
to brain scans to ensure subject confidentiality / inability to identify individuals from brain scans.  
9.4.3 
De-identified Research Data 
Completely de-identified research data (redacted according to NIH practice to prevent disclosure of 
personal identifiers) which documents the research findings will be made available after the main 
findings from the finalized research dataset have been accepted for publication.   
9.4.4 
Genome Wide Association Studies 
Not applicable 
10 REFERENCES 
1. Steenkamp MM, Litz BT, Hoge CW, Marmar CR. Psychotherapy for Military-Related PTSD: A Review 
of Randomized Clinical Trials. Jama. 2015;314(5):489-500. 
2. King AP, Block SR, Sripada R, et al. Altered Default Mode Network (DMN) Resting State Functional 
Connectivity Following a Mindfulness-based Exposure Therapy for Posttraumatic Stress Disorder 
(PTSD) in Combat Veterans of Afghanistan and Iraq. Depression and Anxiety. 2016;in press. 
3. Creswell JD, Taren AA, Lindsay EK, et al. Alterations in Resting-State Functional Connectivity Link 
Mindfulness Meditation With Reduced Interleukin-6: A Randomized Controlled Trial. Biol Psychiatry. 
2016;80(1):53-61. 
4. Brewer JA, Worhunsky PD, Gray JR, Tang YY, Weber J, Kober H. Meditation experience is associated 
with differences in default mode network activity and connectivity. Proceedings of the National 
Academy of Sciences of the United States of America. 2011;108(50):20254-20259. 
5. Farb NA, Segal ZV, Mayberg H, et al. Attending to the present: mindfulness meditation reveals 
distinct neural modes of self-reference. Social cognitive and affective neuroscience. 2007;2(4):313-
322. 
6. Creswell JD TA, Lindsay EK, Greco CM, Gianaros PJ, Fairgrieve A, Marsland AL, Brown KW, Way, BM, 
Rosen RK, Ferris JL. Alterations in Resting State Functional Connectivity link Mindfulness Meditation 
with Reduced Interleukin-6. Biological Psychiatry. 2016 (in press). 
7. Kessler RC. Posttraumatic stress disorder: the burden to the individual and to society. The Journal of 
clinical psychiatry. 2000;61 Suppl 5:4-12; discussion 13-14. 
8. Kessler RC, Berglund P, Demler O, et al. The epidemiology of major depressive disorder: results from 
the National Comorbidity Survey Replication (NCS-R). Jama. 2003;289(23):3095-3105. 
9. Fulton JJ, Calhoun PS, Wagner HR, et al. The prevalence of posttraumatic stress disorder in 
Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) Veterans: a meta-analysis. Journal 
of anxiety disorders. 2015;31:98-107. 
10. Hoge CW, Castro CA, Messer SC, McGurk D, Cotting DI, Koffman RL. Combat duty in Iraq and 
Afghanistan, mental health problems, and barriers to care. N Engl J Med. 2004;351(1):13-22. 

29 
 
11. Kang HK, Natelson BH, Mahan CM, Lee KY, Murphy FM. Post-traumatic stress disorder and chronic 
fatigue syndrome-like illness among Gulf War veterans: a population-based survey of 30,000 
veterans. Am J Epidemiol. 2003;157(2):141-148. 
12. Gillespie CF, Bradley B, Mercer K, et al. Trauma exposure and stress-related disorders in inner city 
primary care patients. Gen Hosp Psychiatry. 2009;31(6):505-514. 
13. Kulka RA, Schlenger, W. E., Fairbanks, J. A., Hough, R. L., Jordan, B. K., Marmar, C. R., Weiss, D. S. 
Trauma and the Vietnam War generation : report of findings from the National Vietnam veterans 
readjustment study. 1990. 
14. Kang HK, Mahan CM, Lee KY, et al. Evidence for a deployment-related Gulf War syndrome by factor 
analysis. Arch Environ Health. 2002;57(1):61-68. 
15. Kessler RC, Sonnega A, Bromet E, Hughes M, Nelson CB. Posttraumatic stress disorder in the 
National Comorbidity Survey. Arch Gen Psychiatry. 1995;52(12):1048-1060. 
16. Kuyken W, Warren FC, Taylor RS, et al. Efficacy of Mindfulness-Based Cognitive Therapy in 
Prevention of Depressive Relapse: An Individual Patient Data Meta-analysis From Randomized Trials. 
JAMA psychiatry. 2016. 
17. Bradley R, Greene J, Russ E, Dutra L, Westen D. A multidimensional meta-analysis of psychotherapy 
for PTSD. Am J Psychiatry. 2005;162(2):214-227. 
18. Forbes D, Lloyd D, Nixon RD, et al. A multisite randomized controlled effectiveness trial of cognitive 
processing therapy for military-related posttraumatic stress disorder. Journal of anxiety disorders. 
2012;26(3):442-452. 
19. Schnurr PP, Friedman MJ, Engel CC, et al. Cognitive behavioral therapy for posttraumatic stress 
disorder in women: a randomized controlled trial. Jama. 2007;297(8):820-830. 
20. Rothbaum BO, Astin MC, Marsteller F. Prolonged Exposure Versus Eye Movement Desensitization 
and Reprocessing (EMDR) for PTSD Rape Victims. Journal of Traumatic Stress. 2005;18(6):607-616. 
21. Kearney DJ, McDermott K, Malte C, Martinez M, Simpson TL. Effects of participation in a 
mindfulness program for veterans with posttraumatic stress disorder: a randomized controlled pilot 
study. Journal of clinical psychology. 2013;69(1):14-27. 
22. Kelly A, Garland EL. Trauma-Informed Mindfulness-Based Stress Reduction for Female Survivors of 
Interpersonal Violence: Results From a Stage I RCT. Journal of clinical psychology. 2016;72(4):311- 
328. 
  
23. Kimbrough E, Magyari T, Langenberg P, Chesney M, Berman B. Mindfulness intervention for child 
abuse survivors. Journal of clinical psychology. 2010;66(1):17-33. 
24. King AP, Erickson TM, Giardino ND, et al. A pilot study of group mindfulness-based cognitive therapy 
(MBCT) for combat veterans with posttraumatic stress disorder (PTSD). Depress Anxiety. 
2013;30(7):638-645. 

30 
 
25. Polusny MA, Erbes CR, Thuras P, et al. Mindfulness-Based Stress Reduction for Posttraumatic Stress 
Disorder Among Veterans: A Randomized Clinical Trial. Jama. 2015;314(5):456-465. 
26. Segal ZV, Bieling P, Young T, et al. Antidepressant monotherapy vs sequential pharmacotherapy and 
mindfulness-based cognitive therapy, or placebo, for relapse prophylaxis in recurrent depression. 
Arch Gen Psychiatry. 2010;67(12):1256-1264. 
27. Segal ZV, Walsh KM. Mindfulness-based cognitive therapy for residual depressive symptoms and 
relapse prophylaxis. Curr Opin Psychiatry. 2016;29(1):7-12. 
28. Goulao B, MacLennan GS. Mindfulness-Based Stress Reduction for Veterans With PTSD. Jama. 
2016;315(1):87-88. 
29. Kahn JR, Collinge W, Soltysik R. Post-9/11 Veterans and Their Partners Improve Mental Health 
Outcomes with a Self-directed Mobile and Web-based Wellness Training Program: A Randomized 
Controlled Trial. J Med Internet Res. 2016;18(9):e255. 
30. Kearney DJ, McDermott K, Malte C, Martinez M, Simpson TL. Association of participation in a 
mindfulness program with measures of PTSD, depression and quality of life in a veteran sample. 
Journal of clinical psychology. 2012;68(1):101-116. 
31. Khusid MA, Vythilingam M. The Emerging Role of Mindfulness Meditation as Effective Self- 
Management Strategy, Part 1: Clinical Implications for Depression, Post-Traumatic Stress Disorder, 
and Anxiety. Mil Med. 2016;181(9):961-968. 
32. King AP, Block SR, Sripada RK, et al. A Pilot Study of Mindfulness-Based Exposure Therapy in OEF/OIF 
Combat Veterans with PTSD: Altered Medial Frontal Cortex and Amygdala Responses in Social-
Emotional Processing. Frontiers in psychiatry. 2016;7:154. 
33. Earley MD, Chesney MA, Frye J, Greene PA, Berman B, Kimbrough E. Mindfulness intervention for 
child abuse survivors: a 2.5-year follow-up. Journal of clinical psychology. 2014;70(10):933-941. 
34. Eisendrath SJ, Gillung E, Delucchi K, et al. A Preliminary Study: Efficacy of Mindfulness-Based 
Cognitive Therapy versus Sertraline as First-line Treatments for Major Depressive Disorder. 
Mindfulness. 2015;6(3):475-482. 
35. Eisendrath SJ, Gillung EP, Delucchi KL, et al. Mindfulness-based cognitive therapy (MBCT) versus the 
health-enhancement program (HEP) for adults with treatment-resistant depression: a randomized 
control trial study protocol. BMC complementary and alternative medicine. 2014;14:95. 
36. de Jong M, Peeters F, Gard T, et al. A Randomized Controlled Pilot Study on Mindfulness-Based 
Cognitive Therapy for Unipolar Depression in Patients With Chronic Pain. The Journal of clinical 
psychiatry. 2017. 
37. Hoge EA, Bui E, Marques L, et al. Randomized controlled trial of mindfulness meditation for 
generalized anxiety disorder: effects on anxiety and stress reactivity. The Journal of clinical 
psychiatry. 2013;74(8):786-792. 
38. Hoge EA, Bui E, Palitz SA, et al. The effect of mindfulness meditation training on biological acute 
stress responses in generalized anxiety disorder. Psychiatry research. 2017. 

31 
 
39. Hoge EA, Holzel BK, Marques L, et al. Mindfulness and self-compassion in generalized anxiety 
disorder: examining predictors of disability. Evidence-based complementary and alternative 
medicine : eCAM. 2013;2013:576258. 
40. Alexopoulos GS, Hoptman MJ, Kanellopoulos D, Murphy CF, Lim KO, Gunning FM. Functional 
connectivity in the cognitive control network and the default mode network in late-life depression. J 
Affect Disord. 2012;139(1):56-65. 
41. Anticevic A, Cole MW, Murray JD, Corlett PR, Wang XJ, Krystal JH. The role of default network 
deactivation in cognition and disease. Trends Cogn Sci. 2012;16(12):584-592. 
42. Cole MW, Repovs G, Anticevic A. The frontoparietal control system: a central role in mental health. 
Neuroscientist. 2014;20(6):652-664. 
43. Hamilton JP, Chen MC, Gotlib IH. Neural systems approaches to understanding major depressive 
disorder: an intrinsic functional organization perspective. Neurobiology of disease. 2013;52:4-11. 
  
44. Fox MD, Snyder AZ, Vincent JL, Corbetta M, Van Essen DC, Raichle ME. The human brain is 
intrinsically organized into dynamic, anticorrelated functional networks. Proceedings of the National 
Academy of Sciences of the United States of America. 2005;102(27):9673-9678. 
45. Yeo BT, Krienen FM, Sepulcre J, et al. The organization of the human cerebral cortex estimated by 
intrinsic functional connectivity. J Neurophysiol. 2011;106(3):1125-1165. 
46. Gao W, Lin W. Frontal parietal control network regulates the anti-correlated default and dorsal 
attention networks. Hum Brain Mapp. 2012;33(1):192-202. 
47. Smallwood J, Brown K, Baird B, Schooler JW. Cooperation between the default mode network and 
the frontal-parietal network in the production of an internal train of thought. Brain Res. 
2012;1428:60-70. 
48. Breukelaar IA, Antees C, Grieve SM, et al. Cognitive control network anatomy correlates with 
neurocognitive behavior: A longitudinal study. Human Brain Mapping. 2017;38(2):631-643. 
49. Cole MW, Schneider W. The cognitive control network: Integrated cortical regions with dissociable 
functions. NeuroImage. 2007;37(1):343-360. 
50. Sripada RK, King AP, Garfinkel SN, et al. Altered resting-state amygdala functional connectivity in 
men with posttraumatic stress disorder. Journal of psychiatry & neuroscience : JPN. 2012;37(4):241-
249. 
51. Rabinak CA, Angstadt M, Welsh RC, et al. Altered amygdala resting-state functional connectivity in 
post-traumatic stress disorder. Frontiers in psychiatry. 2011;2:62. 
52. Sripada RK, King AP, Welsh RC, et al. Neural dysregulation in posttraumatic stress disorder: evidence 
for disrupted equilibrium between salience and default mode brain networks. Psychosomatic 
medicine. 2012;74(9):904-911. 

32 
 
53. Herringa RJ, Birn RM, Ruttle PL, et al. Childhood maltreatment is associated with altered fear 
circuitry and increased internalizing symptoms by late adolescence. Proceedings of the National 
Academy of Sciences of the United States of America. 2013;110(47):19119-19124. 
54. Rabellino D, Tursich M, Frewen PA, et al. Intrinsic Connectivity Networks in post-traumatic stress 
disorder during sub- and supraliminal processing of threat-related stimuli. Acta psychiatrica 
Scandinavica. 2015;132(5):365-378. 
55. Lanius RA, Bluhm RL, Coupland NJ, et al. Default mode network connectivity as a predictor of post- 
traumatic stress disorder symptom severity in acutely traumatized subjects. Acta psychiatrica 
Scandinavica. 2010;121(1):33-40. 
56. Bluhm R, Williamson P, Lanius R, et al. Resting state default-mode network connectivity in early 
depression using a seed region-of-interest analysis: decreased connectivity with caudate nucleus. 
Psychiatry and clinical neurosciences. 2009;63(6):754-761. 
57. Birn RM, Patriat R, Phillips ML, Germain A, Herringa RJ. Childhood maltreatment and combat 
posttraumatic stress differentially predict fear-related fronto-subcortical connectivity. Depress 
Anxiety. 2014;31(10):880-892. 
58. Paulus MP, Stein MB. Interoception in anxiety and depression. Brain Struct Funct. 2010;214(5-
6):451- 463. 
59. Berman MG, Peltier S, Nee DE, Kross E, Deldin PJ, Jonides J. Depression, rumination and the default 
network. Social cognitive and affective neuroscience. 2011;6(5):548-555. 
60. Greicius MD, Flores BH, Menon V, et al. Resting-state functional connectivity in major depression: 
abnormally increased contributions from subgenual cingulate cortex and thalamus. Biol Psychiatry. 
2007;62(5):429-437. 
61. Berman MG, Misic B, Buschkuehl M, et al. Does resting-state connectivity reflect depressive 
rumination? A tale of two analyses. NeuroImage. 2014;103:267-279. 
62. Lois G, Wessa M. Differential association of default mode network connectivity and rumination in 
healthy individuals and remitted MDD patients. Social cognitive and affective neuroscience. 2016. 
63. Abbott CC, Lemke NT, Gopal S, et al. Electroconvulsive therapy response in major depressive 
disorder: a pilot functional network connectivity resting state FMRI investigation. Frontiers in 
psychiatry. 2013;4:10. 
64. Manoliu A, Meng C, Brandl F, et al. Insular dysfunction within the salience network is associated 
with severity of symptoms and aberrant inter-network connectivity in major depressive disorder. 
Front Hum Neurosci. 2013;7:930. 
65. Hasenkamp W, Wilson-Mendenhall CD, Duncan E, Barsalou LW. Mind wandering and attention 
during focused meditation: a fine-grained temporal analysis of fluctuating cognitive states. 
NeuroImage. 2012;59(1):750-760. 
  

33 
 
66. Hasenkamp W, Barsalou LW. Effects of meditation experience on functional connectivity of 
distributed brain networks. Front Hum Neurosci. 2012;6:38. 
67. Taren AA, Gianaros PJ, Greco CM, et al. Mindfulness meditation training alters stress-related 
amygdala resting state functional connectivity: a randomized controlled trial. Social cognitive and 
affective neuroscience. 2015;10(12):1758-1768. 
68. Alsubaie M, Abbott R, Dunn B, et al. Mechanisms of action in mindfulness-based cognitive therapy 
(MBCT) and mindfulness-based stress reduction (MBSR) in people with physical and/or psychological 
conditions: A systematic review. Clinical psychology review. 2017;55:74-91. 
69. Newby JM, McKinnon A, Kuyken W, Gilbody S, Dalgleish T. Systematic review and meta-analysis of 
transdiagnostic psychological treatments for anxiety and depressive disorders in adulthood. Clinical 
psychology review. 2015;40:91-110. 
70. van der Velden AM, Kuyken W, Wattar U, et al. A systematic review of mechanisms of change in 
mindfulness-based cognitive therapy in the treatment of recurrent major depressive disorder. 
Clinical psychology review. 2015;37:26-39. 
71. McCracken LM, Gutierrez-Martinez O, Smyth C. "Decentering" reflects psychological flexibility in 
people with chronic pain and correlates with their quality of functioning. Health Psychol. 
2013;32(7):820-823. 
72. Teasdale JD, Moore RG, Hayhurst H, Pope M, Williams S, Segal ZV. Metacognitive awareness and 
prevention of relapse in depression: empirical evidence. Journal of consulting and clinical 
psychology. 2002;70(2):275-287. 
73. Gu J, Strauss C, Bond R, Cavanagh K. How do mindfulness-based cognitive therapy and mindfulness- 
based stress reduction improve mental health and wellbeing? A systematic review and meta-
analysis of mediation studies. Clinical psychology review. 2015;37:1-12. 
74. Hoge EA, Bui E, Goetter E, et al. Change in Decentering Mediates Improvement in Anxiety in 
Mindfulness-Based Stress Reduction for Generalized Anxiety Disorder. Cognitive therapy and 
research. 2015;39(2):228-235. 
75. Gecht J, Kessel R, Forkmann T, et al. A mediation model of mindfulness and decentering: sequential 
psychological constructs or one and the same? BMC Psychol. 2014;2(1):18. 
76. Bernstein A, Hadash Y, Lichtash Y, Tanay G, Shepherd K, Fresco DM. Decentering and Related 
Constructs: A Critical Review and Metacognitive Processes Model. Perspectives on psychological 
science : a journal of the Association for Psychological Science. 2015;10(5):599-617. 
77. Fresco DM, Moore MT, van Dulmen MH, et al. Initial psychometric properties of the experiences 
questionnaire: validation of a self-report measure of decentering. Behav Ther. 2007;38(3):234-246. 
78. Mennin DS, Fresco DM, Ritter M, Heimberg RG. An Open Trial of Emotion Regulation Therapy for 
Generalized Anxiety Disorder and Cooccurring Depression. Depress Anxiety. 2015;32(8):614-623. 
79. Renna ME, Quintero JM, Fresco DM, Mennin DS. Emotion Regulation Therapy: A Mechanism- 
Targeted Treatment for Disorders of Distress. Front Psychol. 2017;8:98. 

34 
 
80. Libby DJ, Pilver CE, Desai R. Complementary and alternative medicine in VA specialized PTSD 
treatment programs. Psychiatr Serv. 2012;63(11):1134-1136. 
81. Taren AA, Gianaros PJ, Greco CM, et al. Mindfulness Meditation Training and Executive Control 
Network Resting State Functional Connectivity: A Randomized Controlled Trial. Psychosomatic 
medicine. 2017. 
82. Weingarten CP, Strauman TJ. Neuroimaging for psychotherapy research: current trends. Psychother 
Res. 2015;25(2):185-213. 
83. Brakowski J, Spinelli S, Dorig N, et al. Resting state brain network function in major depression - 
Depression symptomatology, antidepressant treatment effects, future research. J Psychiatr Res. 
2017;92:147-159. 
84. Gudayol-Ferre E, Pero-Cebollero M, Gonzalez-Garrido AA, Guardia-Olmos J. Changes in brain 
connectivity related to the treatment of depression measured through fMRI: a systematic review. 
Front Hum Neurosci. 2015;9:582. 
85. Shepherd KA, Coifman KG, Matt LM, Fresco DM. Development of a self-distancing task and initial 
validation of responses. Psychol Assess. 2016;28(7):841-855. 
86. Liston C, Chen AC, Zebley BD, et al. Default mode network mechanisms of transcranial magnetic 
stimulation in depression. Biol Psychiatry. 2014;76(7):517-526. 
87. Wei X, Shen H, Ren J, et al. Altered resting-state connectivity in college students with nonclinical 
depressive symptoms. PloS one. 2014;9(12):e114603. 
  
88. Wu J, Dong D, Jackson T, Wang Y, Huang J, Chen H. The Neural Correlates of Optimistic and 
Depressive Tendencies of Self-Evaluations and Resting-State Default Mode Network. Front Hum 
Neurosci. 2015;9:618. 
89. Sheehan DV, Lecrubier, Y., Sheehan, K.H., Amorim, P., Janvas, J., et al. . The Mini-international 
neuropsychiatric interview (MINI): The development and validation of a structured diagnostic 
psychiatric interview for DSM-IV and ICD-10. . Journal of Clinical Psychiatry 1998;59((Supp20)):22-
33. 
90. Foa EB, Tolin DF. Comparison of the PTSD Symptom Scale-Interview Version and the Clinician- 
Administered PTSD scale. J Trauma Stress. 2000;13(2):181-191. 
91. Fresco DM, Roy AK, Adelsberg S, et al. Distinct Functional Connectivities Predict Clinical Response 
with Emotion Regulation Therapy. Front Hum Neurosci. 2017;11:86. 
92. Bieling PJ, Hawley LL, Bloch RT, et al. Treatment-specific changes in decentering following 
mindfulness-based cognitive therapy versus antidepressant medication or placebo for prevention of 
depressive relapse. Journal of consulting and clinical psychology. 2012;80(3):365-372. 
93. Gross JJ, John, O.P.Gross, J.J., Richards, J.M., John, O.P., . Individual differences in two emotion 
regulation processes: implications for affect, relationships, and well-being.  Journal of 
EmotionPersonality and Social Psychology 2003;85:348-362. 

35 
 
94. Nolen-Hoeksema S, Morrow, J., & Fredrickson, B. L. Response styles and the duration of episodes of 
depressed mood. . Journal of Abnormal Psychology. 1993;102:20-28. 
95. Crane RS, Kuyken W, Williams JM, Hastings RP, Cooper L, Fennell MJ. Competence in Teaching 
Mindfulness-Based Courses: Concepts, Development and Assessment. Mindfulness. 2012;3(1):76-
84. 
96. Segal ZV, Teasdale JD, Williams JM, Gemar MC. The mindfulness-based cognitive therapy adherence 
scale: Inter-rater reliability, adherence to protocol and treatment distinctiveness. Clin Psychol 
Psychot. 2002;9(2):131-138. 
97. Birn RM, Molloy EK, Patriat R, et al. The effect of scan length on the reliability of resting-state fMRI 
connectivity estimates. NeuroImage. 2013;83:550-558. 
98. Murphy K, Birn RM, Bandettini PA. Resting-state fMRI confounds and cleanup. NeuroImage. 
2013;80:349-359. 
99. Patriat R, Molloy EK, Meier TB, et al. The effect of resting condition on resting-state fMRI reliability 
and consistency: a comparison between resting with eyes open, closed, and fixated. NeuroImage. 
2013;78:463-473. 
100. Kessler D, Angstadt M, Sripada C. Growth Charting of Brain Connectivity Networks and the 
Identification of Attention Impairment in Youth. JAMA psychiatry. 2016;73(5):481-489. 
101. Kessler D, Angstadt M, Welsh RC, Sripada C. Modality-spanning deficits in attention- 
deficit/hyperactivity disorder in functional networks, gray matter, and white matter. J Neurosci. 
2014;34(50):16555-16566. 
102. Sripada C, Kessler D, Fang Y, Welsh RC, Prem Kumar K, Angstadt M. Disrupted network 
architecture of the resting brain in attention-deficit/hyperactivity disorder. Hum Brain Mapp. 
2014;35(9):4693-4705. 
103. Skevington SM, Lotfy M, O'Connell KA, Group W. The World Health Organization's WHOQOL-BREF 
quality of life assessment: psychometric properties and results of the international field trial. A 
report from the WHOQOL group. Qual Life Res. 2004;13(2):299-310. 
104. DV. S. The Anxiety Disease. . Charles Scribners Sons: New York, NY, USA; 1983. 
105. Fishbain DA, Pulikal A, Lewis JE, Gao J. Chronic Pain Types Differ in Their Reported Prevalence of 
Post -Traumatic Stress Disorder (PTSD) and There Is Consistent Evidence That Chronic Pain Is 
Associated with PTSD: An Evidence-Based Structured Systematic Review. Pain Med. 2016. 
106. Lang KP, Veazey-Morris K, Andrasik F. Exploring the role of insomnia in the relation between PTSD 
and pain in veterans with polytrauma injuries. J Head Trauma Rehabil. 2014;29(1):44-53. 
107. Anheyer D, Haller H, Barth J, Lauche R, Dobos G, Cramer H. Mindfulness-Based Stress Reduction 
for Treating Low Back Pain: A Systematic Review and Meta-analysis. Ann Intern Med. 2017:1-9. 
108. Cherkin DC, Sherman KJ, Balderson BH, et al. Effect of Mindfulness-Based Stress Reduction vs 
Cognitive Behavioral Therapy or Usual Care on Back Pain and Functional Limitations in Adults With 
Chronic Low Back Pain: A Randomized Clinical Trial. Jama. 2016;315(12):1240-1249. 

36 
 
109. Lauche R, Cramer H, Dobos G, Langhorst J, Schmidt S. A systematic review and meta-analysis of 
mindfulness-based stress reduction for the fibromyalgia syndrome. J Psychosom Res. 
2013;75(6):500- 510. 
110. Sullivan MJL, Bishop SR, Pivik J. The Pain Catastrophizing Scale: Development and validation. 
Psychol Assessment. 1995;7(4):524-532. 
111. Baker DG, Nievergelt CM, O'Connor DT. Biomarkers of PTSD: neuropeptides and immune signaling. 
Neuropharmacology. 2012;62(2):663-673. 
112. Wang Z, Young MR. PTSD, a Disorder with an Immunological Component. Front Immunol. 
2016;7:219. 
113. Hendrickson RC, Raskind MA. Noradrenergic dysregulation in the pathophysiology of PTSD. Exp 
Neurol. 2016;284(Pt B):181-195. 
114. Foa EB. Prolonged exposure therapy: past, present, and future. Depress Anxiety. 
2011;28(12):1043- 1047. 
115. Smith ER, Porter KE, Messina MG, et al. Prolonged Exposure for PTSD in a Veteran group: a pilot 
effectiveness study. Journal of anxiety disorders. 2015;30:23-27. 
116. Muthén LKaM, B.O. (1998-2017). . Mplus User’s Guide. Eighth Edition. Los Angeles, CA: Muthén & 
Muthén; 2017. 
117. Preacher KJ, Zyphur MJ, Zhang Z. A general multilevel SEM framework for assessing multilevel 
mediation. Psychol Methods. 2010;15(3):209-233. 
118.   Foa, E., Hembree, E.A., & Rothbaum, B.O. (2007). Prolonged exposure therapy for PTSD: Emotional 
process of traumatic experiences: Therapist Guide. New York, NY: Oxford University Press 
119.   Hinrichs R, Michopoulos V, Winters S, Rothbaum AO, Rothbaum BO, Ressler KJ, Jovanovic T. 
Mobile assessment of heightened skin conductance in posttraumatic stress disorder.Depress 
Anxiety. 2017 Jun;34(6):502-507. doi: 10.1002/da.22610. 
 
 

 
Tool Revision History: 
Version 
 
Number 
Date 
Summary of Revisions Made: 
1.0 
07Sept2018 
First approved version 
 
 
 

NCCIH DSMP  
Version Date: 9/15/2018 
2 
 
 
 
 
Data and Safety Monitoring Plan (DSMP) 
Independent Monitoring Committee 
Protocol for Neural Mechanisms of Mindfulness-based Cognitive Therapy 
(MBCT) for Posttraumatic Stress Disorder (PTSD) 
 
 
Name of Sponsor: National Center for Complementary and 
Integrative Health 
Grant Number: 1 R61 AT009867-01 
Version Date: 15 September 2018 
Version Number: 1.0 
 

NCCIH DSMP  
Version Date: 9/15/2018 
3 
DATA SAFETY MONITORING PLAN (DSMP) 
 
1. STUDY OVERVIEW 
 
1.1 
Purpose of Study 
 
The purpose of the proposed research is to generate new knowledge about changes in 
brain activity and connectivity associated with mindfulness-based Cognitive Therapy 
(MBCT) for posttraumatic stress disorder (PTSD), and how these are related to the 
therapeutic mechanism of action of MBCT.  Understanding the mechanisms of action of 
MBCT, and whether they are different from other forms of therapy, such as exposure, 
will be crucial for designing more efficient and effective PTSD interventions.   
 
The R61 phase is designed to identify specific MBCT-linked changes in brain 
connectivity.  We hypothesize increased connectivity between the dorsolateral 
prefrontal cortex (dlPFC), involved in attentional control, and the posterior cingulate 
cortex (PCC), involved in mind-wandering and self-referential processing, as a 
putative treatment target.  We will compare the effects of MBCT to a well-matched 
control intervention, group muscular relaxation therapy (MRG). 
 
The R33 phase is designed to optimize effects of MBCT and this dlPFC-PCC target 
by combining MBCT with another non-trauma-focused group intervention, In vivo 
Exposure.  We will compare MBCT+In vivo Exposure vs MRG+In vivo Exposure and 
perform formal testing of mediation by targets of improvements in psychological 
health, PTSD symptoms, and additional functional outcomes. We will test for 
treatment group differences in network target engagement and its mediation of 
changes in decentering, PTSD symptoms, acceptance, stress reactivity, functionality, 
and quality of life.  The improved understanding of such neural mechanisms and their 
relationships to psychological and physiological functioning is expected to direct 
development of targeted PTSD treatments, with the promise to ultimately improve 
social functioning and quality of life of people afflicted by PTSD.  
 
1.2 
Adherence Statement 
The Data Safety Monitoring Plan (DSMP) outlined below will adhere to the protocol 
approved by the University of Michigan and VA Ann Arbor IRBs. 

NCCIH DSMP  
Version Date: 9/15/2018 
4 
2 PROTOCOL AMENDMENTS 
All protocol amendments, other than minor administrative changes as defined by the 
NCCIH Guidance on Changes in Clinical Studies in Active Awards will be submitted in a 
prospective manner to NCCIH except when necessary to protect the safety, rights, or 
welfare of subjects. Prior to submission to NCCIH the proposed changes will be 
reviewed and approved by the Independent Monitor(s).  IRB-approval will not be sought 
until after NCCIH approval of the protocol amendment has been obtained. 
3 MULTI-SITE STUDIES 
Not applicable, though we will recruit throughout the Ann Arbor / Detroit area, this will be 
a single “site” and institution (University of Michigan), with a single study coordination 
and data management team.  

NCCIH DSMP  
Version Date: 9/15/2018 
5 
4  CONFIDENTIALITY 
4.1 
Protection of Subject Privacy 
Subject confidentiality is strictly held in trust by the investigators, study staff, and the 
sponsor(s) and their agents.  This confidentiality is extended to cover testing of 
biological samples in addition to any study information relating to subjects. 
The study protocol, documentation, data, and all other information generated will be 
held in strict confidence.  No information concerning the study or the data will be 
released to any unauthorized third party without prior written approval of the sponsor. 
The study monitor or other authorized representatives of the sponsor may inspect all 
study documents and records required to be maintained by the investigator, including 
but not limited to, medical records (office, clinic, or hospital) for the study subjects.  The 
clinical study site will permit access to such records. 
4.2 
Confidentiality During Adverse Event (AE) Reporting  
 
AE reports and annual summaries will not include subject or group-identifiable material. 
Each report will only include the identification code. 

NCCIH DSMP  
Version Date: 9/15/2018 
6 
5 EXPECTED RISKS  
Expected risks to the subject are as follows: 
 
• Clinical assessment. There is a risk of loss of confidentiality and/or feeling 
uncomfortable about sensitive information such as psychiatric history. Such 
information could be inadvertently and inappropriately shared with third parties. 
We will take extensive steps to safeguard confidentiality, and thus this risk is 
considered to be unexpected and extremely infrequent. 
• Magnetic resonance imaging. The presence of metal implants or foreign metallic 
objects could cause serious injury. However, our scanning facility take measures 
to reduce risk including redundant safety monitoring and this expected risk is 
highly infrequent.  The noise of the scanner may be harmful to hearing. Subjects 
may experience discomfort due to lying still during the 75-minute scan, or 
experience an anxiety reaction due to confinement in the scanner. They may 
experience peripheral nerve stimulation (described as a light touching sensation 
on the skin surface) which may be uncomfortable but is not harmful. Imaging may 
reveal an abnormality that is already in the brain, such as a cyst of tumor. Many 
such incidental findings are not clinically significant, but the subject may want to 
investigate them further. Given the precautions described below (Protection 
Against Risk), we believe that the frequency and thus likelihood of harm from 
these potential risks is very low. The local IRB has determined studies we have 
conducted that are similar to the present study as presenting “no more than 
minimal risk,” meaning that the risks are comparable to those ordinarily 
encountered in daily life or during routine physical or psychological examinations.  
 
• Inserting a needle for blood sampling and placing a venous catheter for injection 
or infusion can be associated with some discomfort and bruising, and very rarely 
with inflammation and infection of the arm veins. 
 
These risks are considered to be minimal and are addressed in the protocol and 
consent form. 
 
• Psychiatric disorders like PTSD and their treatment are associated with risk, 
including distress and suicidal ideation and behavior.  Therefore all study 
participants will be monitored at frequent intervals (weekly) during this part of the 
study and followed for a sufficient period of time (1 month) after the procedure to 
ensure stabilization.   
 
Participants who meet criteria for psychiatric disorders at the conclusion of the 
study but are not in current treatment will be offered referral to appropriate 
treatment in the community.   

NCCIH DSMP  
Version Date: 9/15/2018 
7 
6 ADVERSE EVENT/ UNANTICIPATED PROBLEMS 
6.1 
Definitions  
6.1.1 
Adverse Event (AE) 
An adverse event (AE) is any untoward medical occurrence in a subject during 
participation in the clinical study or with use of the experimental agent being studied. An 
adverse finding can include a sign, symptom, abnormal assessment, or any 
combination of these regardless of relationship to participation in the study. 
6.1.2 
Unanticipated Problems (UP) 
The Office for Human Research Protections (OHRP) considers unanticipated problems 
involving risks to subjects or others to include, in general, any incident, experience, or 
outcome that meets all of the following criteria: 
• Unexpected in terms of nature, severity, or frequency given (a) the research 
procedures that are described in the protocol-related documents, such as the 
IRB-approved research protocol and informed consent document; and (b) the 
characteristics of the subject population being studied; 
• Related or possibly related to participation in the research (“possibly related” 
means there is a reasonable possibility that the incident, experience, or outcome 
may have been caused by the procedures involved in the research); and 
• Suggests that the research places subjects or others at a greater risk of harm 
(including physical, psychological, economic, or social harm) than was previously 
known or recognized. 
6.1.3 
Serious Adverse Event (SAE) 
A serious adverse event (SAE) is one that meets one or more of the following criteria: 
• Results in death 
• Is life-threatening (places the subject at immediate risk of death from the event 
as it occurred) 
• Results in inpatient hospitalization or prolongation of existing hospitalization 
• Results in a persistent or significant disability or incapacity 
• Results in a congenital anomaly or birth defect   
An important medical event that may not result in death, be life threatening, or require 
hospitalization may be considered an SAE when, based upon appropriate medical 

NCCIH DSMP  
Version Date: 9/15/2018 
8 
judgment, the event may jeopardize the subject and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition. 
6.2 
Time Period and Frequency for Event Assessment and Follow-Up 
Unanticipated problems will be recorded in the data collection system throughout the 
study. The PI will record all reportable events with start dates occurring any time after 
informed consent is obtained until 7 (for non-serious AEs) or 30 days (for SAEs) after the 
last day of study participation.  At each study visit, the investigator will inquire about the 
occurrence of AE/SAEs since the last visit.  Events will be followed for outcome 
information until resolution or stabilization. 
6.2.1 Procedures for participants who report suicidal ideation or experience clinical 
worsening during study participation 
Psychiatric risk including suicide risk will be assessed at each meeting of study staff 
with participants (recruitment / consent, assessments, fMRI scans, and therapy groups), 
and measures to protect participants will be in place throughout the study.  Participants 
will have contact with psychotherapists (who are licensed mental health providers) on a 
weekly basis while they are engaged in the therapy groups, and will also complete brief 
symptom self-report measures including assessment of suicidal ideation as part of 
weekly therapy.  The therapists and assessors will assess acute risk factors and current 
psychiatric state and progress for each participant each week, based upon self-report 
measures as well as clinical observation. 
6.2.2.  Suicidal Ideation:  
Study participants are people with current PTSD, which is often co-morbid with major 
depression. Clinical epidemiology estimates the annual incidence of suicidal ideation in 
the US general population to be ~5%, and both PTSD and depression are associated 
with considerably higher rates of suicidal ideation. Since suicidal ideation is associated 
with increased risk for suicidal behaviors, we will take appropriate safety measures to 
insure safety in study participants who are assessed to have suicidal ideation. At 
baseline and throughout the study (assessments, scans, and therapy sessions), 
participants will complete a number of survey measures. Measures that provide 
indication of risk for suicide (PHQ-9) will be collected and scored immediately after 
participants complete them so that any indication of risk for suicide can be responded to 
immediately.  If suicidal ideation or behavior is indicated at any time in conjunction with 
the study, UM study personnel will immediately take measures to assess the severity of 
the risk, and apply safety measures as appropriate and clinically indicated.  Suicide risk 
severity will be assessed using the Columbia Suicide Severity Rating Scale, considered 
a “gold standard” for suicide risk assessment. If suicide risk is assessed to be moderate 
or high with potential for imminent danger, the study therapists / other study team will 
work with the participant to ensure clinically appropriate care, including contact with and 
possible transportation by ambulance to University of Michigan (UM) Psychiatric 
Emergency Services (PES), for participants recruited from the community and engaging 
in treatment through the study at UM. For participants recruited from the VA Ann Arbor 

NCCIH DSMP  
Version Date: 9/15/2018 
9 
and engaging in treatment through the study at VA Ann Arbor, clinically appropriate care 
will include contact with and personal escort to the VA Ann Arbor Emergency Service, 
located onsite at the VA Ann Arbor Medical Center.  The PI and the UM or VA medical 
monitor (respectively) will be notified immediately and will be available to assist with 
assessment and coordination of safety measures and clinical care. This will also be 
reported to IRB as an Adverse Event or a Serious Adverse Event, depending upon how 
the situation is resolved. The PI and all participating University of Michigan study 
personnel carry pagers and can be reached at any time through Psychiatric Emergency 
Services, which is open 24 hours a day, 365 days per year. Our project team is 
comprised of four Board Certified Psychiatrists and two Licensed Psychologists, all of 
whom will be available to study psychotherapists (who are also licensed mental health 
providers) and other study staff (e.g. study coordinator, independent assessors) should 
concerns arise to determine the need for a higher level of care and support the study 
staff and study psychotherapists in making make appropriate recommendations and 
referrals. 
6.2.3.  Participants who experience clinical worsening during study participation  
While the majority of PTSD patients show improvement and decrease in symptoms in 
response to both trauma-focused and non-trauma-focused psychotherapy (such as 
being used in this study), some patients do not improve, and a small proportion 
experience clinical worsening and increased psychiatric symptoms during treatment. 
Clinical worsening could occur due to treatment-specific factors as well as factors not 
related to the treatments per se (e.g. experience of stressful life events during the 
study).  Psychiatric symptoms will be monitored by study therapists weekly by clinical 
observation of patients, and by symptom self-report measures.  Clinically significant 
worsening of symptoms assessed during the study treatments, whether or not they are 
deemed to be related to the study treatments, will be reported to both PI and medical 
monitor within 24 hours and will trigger a clinical review to determine whether an 
alternate or higher level of psychiatric care is necessary for the patient. This may 
include further psychiatric evaluation of the participant by the medical monitor or a 
clinician delegated by the medical monitor who wil report back to the medical monitor. 
Such occurences will also be reported to IRB as an Adverse Event (AE) or Other 
Reportable Information or Occurrence (ORIO), and the participant may be required to 
exit the study if alternative care is found to be necessary by the medical monitor. If 
necessary, referrals for alternate psychiatric care will be made by medical monitor or 
their designate. “Clinical worsening” will be defined as clinically significant increase in 
psychiatric symptoms (based on current accepted professional standards) assessed 
from self-report measures used in the study (PCL-5 or PHQ-9) or worsening on 
clinician-rated Clinical Global Clinical Impression (CGI, e.g. rating of 6-much worse or 5-
very much worse) that occurs over two consecutive weeks.  Intermittent worsening of 
symptoms, as well as worsening that is below current accepted  professional thresholds 
of “clinically significant” will also be reported to the PI and Co-Is at weekly Team 
Meeting, and on case-by-case basis, could also trigger report to medical monitor and 
clinical review to determine whether alternate or higher-level psychiatric care is 
necessary.  

NCCIH DSMP  
Version Date: 9/15/2018 
10
 
6.3 
Characteristics of an Adverse Event 
6.3.1 
Relationship to Study Intervention 
To assess relationship of an event to study intervention, the following guidelines are 
used: 
1. Related (Possible, Probable, Definite) 
a. The event is known to occur with the study intervention. 
b. There is a temporal relationship between the intervention and event onset. 
c. The event abates when the intervention is discontinued. 
d. The event reappears upon a re-challenge with the intervention. 
2. Not Related (Unlikely, Not Related) 
a. There is no temporal relationship between the intervention and event 
onset. 
b. An alternate etiology has been established. 
6.3.2 
Expectedness of SAEs 
The Study PI and Independent Monitoring Committee will be responsible for 
determining whether an SAE is expected or unexpected.  An adverse event will be 
considered unexpected if the nature, severity, or frequency of the event is not consistent 
with the risk information previously described for the intervention.   
6.3.3 
Severity of Event 
The following scale will be used to grade adverse events: 
1. Mild: no intervention required; no impact on activities of daily living (ADL) 
2. Moderate: minimal, local, or non-invasive intervention indicated; moderate impact 
on ADL 
3. Severe: significant symptoms requiring invasive intervention; subject seeks 
medical attention, needs major assistance with ADL 

NCCIH DSMP  
Version Date: 9/15/2018 
11
6.4 
Reporting Procedures 
6.4.1 
Unanticipated Problem Reporting  
Incidents or events that meet the OHRP criteria for unanticipated problems require the 
creation and completion of an unanticipated problem report form.  OHRP recommends 
that investigators include the following information when reporting an adverse event, or 
any other incident, experience, or outcome as an unanticipated problem to the IRB: 
• Appropriate identifying information for the research protocol, such as the title, 
investigator’s name, and the IRB project number; 
• A detailed description of the adverse event, incident, experience, or outcome;  
• An explanation of the basis for determining that the adverse event, incident, 
experience, or outcome represents an unanticipated problem;  
• A description of any changes to the protocol or other corrective actions that have 
been taken or are proposed in response to the unanticipated problem. 
To satisfy the requirement for prompt reporting, unanticipated problems will be reported 
using the following timeline:   
• Unanticipated problems that are serious adverse events will be reported to the 
IRB, Independent Safety Monitor(s), and NCCIH within 7 days of the investigator 
becoming aware of the event.  
• Any other unanticipated problem will be reported to the IRB, Independent Safety 
Monitor(s), and NCCIH within 14 days of the investigator becoming aware of the 
problem.  
All unanticipated problems should be reported to appropriate institutional officials (as 
required by an institution’s written reporting procedures), the supporting agency head 
(or designee), and OHRP within one month of the IRB’s receipt of the report of the 
problem from the investigator. 
 
 
 
6.4.2 
Adverse Event Reporting of Non-IND Studies 
This psychotherapy study does not include any medications or INDs.  SAEs that are 
unanticipated, serious, and possibly related to the study intervention will be reported to 
the Independent Safety Monitor(s), IRB, and NCCIH in accordance with requirements.   

NCCIH DSMP  
Version Date: 9/15/2018 
12
• Unexpected fatal or life-threatening AEs related to the intervention will be 
reported to the NCCIH Program Officer, and Independent Safety Monitor(s) 
within 3 days of the investigator becoming aware of the event.  Other serious and 
unexpected AEs related to the intervention will be reported within 7 days. 
• Anticipated or unrelated SAEs will be handled in a less urgent manner but will be 
reported to the Independent Safety Monitor(s), IRB, and other oversight 
organizations in accordance with their requirements. and will be reported to 
NCCIH on an annual basis.    
• All other AEs documented during the course of the trial will be reported to NCCIH 
on an annual basis by way of inclusion in the annual report and in the annual AE 
summary which will be provided to NCCIH and to the Independent Monitors.  The 
Independent Safety Monitor(s) Report will state that all AEs have been reviewed. 
6.4.3 
Reporting of Pregnancy 
Because this study involves fMRI brain scanning, pregnant women will be excluded.  
Pregnancy tests will be completed at time of recruitment and before scans.  Currently 
very similar interventions (Mindful Yoga for High Risk Pregnant Women) is being offered 
by our collaborator Dr Maria Muzik, and is found to be well tolerated and lead to 
improvements in psychiatric symptoms.  Women who are pregnant will be referred to 
similar treatment options if interested. 
6.5 
Halting Rules 
Serious, unexpected, and related AEs would prompt temporary suspension of 
enrollment and/or study interventions until a complete safety review is convened (either 
routine or ad hoc). The objective of the safety review is to determine whether the study 
(or intervention for an individual or study cohort) should continue per protocol, proceed 
with enhanced monitoring, be further investigated, be discontinued, or be modified and 
then proceed.  Suspension of enrollment (for a particular group, a particular study site or 
for the entire study) is a potential outcome of a safety review. 
Subsequent review of serious, unexpected, and related AEs by the Medical Monitor, 
DSMB/ Independent Safety Monitor(s), IRB, or relevant local regulatory authorities may 
also result in suspension of further study interventions/administration of study product at 
a site. The FDA and study sponsor(s) retain the authority to suspend additional 
enrollment and study interventions/administration of study product for the entire study, 
as applicable.  Findings that might trigger a safety review are the number of overall 
SAEs (e.g. increases in suicidal ideation or behaviors), the number of occurrences of a 
particular type of SAE, severe AEs, or increased frequency of events. 

NCCIH DSMP  
Version Date: 9/15/2018 
13
7 QUALITY CONTROL AND QUALITY ASSURANCE 
Quality Management activities by the study team will include establishing and ensuring 
the quality of processes, data, and documentation associated with clinical research 
activities.  This psychotherapy study will have standard operating procedures (SOPs) 
that are briefly described here:   
• Staff training methods - all study staff will be trained annually good clinical 
practice, research ethics, data security, etc using the computerized CITI training 
system and The University of Michigan human subjects training system. Training 
will be tracked for all study staff by training certificates which will be in the study 
regulatory binder. 
• Data will be evaluated for compliance with the protocol and for accuracy in 
relation to source documents by the study coordinator and data manager, 
deviations will be reported to study PI on weekly basis. Data documents to be 
reviewed include data sheets, questionnaires, and specimen tracking logs. 
• In addition, we will conduct quality / fidelity assurance for our Mindfulness-based 
Cognitive Therapy (MBCT) intervention as well as fidelity measurement of 
therapist competencies. Our consultant Mark Lau, PhD, R. Psych. is an expert 
trainer in MBCT, certified by the Canadian Association of Cognitive and 
Behavioural Therapies and the Academy of Cognitive Therapy (ACT). To insure 
adherence and fidelity to the MBCT model, Dr Lau will consult with therapists via 
videoconferencing on clinical delivery before and during each MBCT group, 
including review of session content, and will review video recording of therapists 
delivering each treatment component. Therapists will have a checklist and 
materials for each session, and each session will be videorecorded. A trained 
MS-level student will review each session to record that each treatment 
component was delivered (and start-stop time of each component) and note any 
divergence from protocol, relevant portions of videos will be reviewed by 
therapists before each videoconference with Dr Lau and will be discussed in 
consultation. Treatment fidelity of therapists will be assessed by delivery of 
treatment components and therapist competencies, using Mindfulness-Based 
Interventions-Teaching Assessment Criteria (MBI-TAC) and Mindfulness-based 
Cognitive Therapy Adherence Scale (MBCT-AS)..  
• The PI will be responsible for addressing quality assurance issues (correcting 
procedures that are not in compliance with protocol) and quality control issues 
(correcting errors in data entry). A statement reflecting the results of the ongoing 
data review will be incorporated into the Annual Report for the Independent 
Safety Monitor(s). 
• Frequency of QA/QC checks is shown in Table A below. 
 

NCCIH DSMP  
Version Date: 9/15/2018 
14
7.1 
Subject Accrual and Compliance 
7.1.1 
Measurement and Reporting of Subject Accrual 
 Review of the rate of subject accrual and compliance with inclusion/exclusion criteria 
will occur monthly during the recruitment phase to ensure that a sufficient number of 
participants are being enrolled, in keeping with proposed recruitment projections, and 
that they meet eligibility criteria and fulfill the targeted ethnic diversity goals outlined in 
the grant proposal (Targeted/Planned Enrollment Table).The study site will submit 
accrual reports to NCCIH at least every 4 months.   
7.1.2 
Measurement and Reporting of Participant Adherence to Treatment 
Protocol  
Data on adherence to the treatment protocol will be collected weekly by research staff 
and reviewed monthly by the PI/Internal QA Reviewer.  Adherence of participants will be 
evaluated by attendance of at least 5 of 8 group sessions, and turning in “homework” 
practice logs indicating engaging in mindfulness or in vivo exposure at least once a 
week.  Available data on the use of MBCT in PTSD suggests an overall compliance rate 
of ~80% completion rate.  If adherence falls below the suggested rate, which might 
inhibit the ability of the study to test its primary hypotheses, the Internal QA Reviewer 
will suggest a conference call for study investigators to discuss methods for improving 
adherence. 
7.2 
Justification of Sample Size  
 
R61 Phase - sample size justification and power analyses: we are proposing to study a 
total of N=60 participants with PTSD in a two-group, longitudinal “pre-post” design, 
based upon our preliminary data and feasibility within the mechanism. We will compare 
MBCT (N=30, N~22 completers) with Muscular Relaxation Group (MRG, N=30, N~22 
completers). Our pilot data using seed-based DMN rsFC pre-post MBCT compared 
BOLD activity of the two groups at the post-treatment time-point extracted from a dlPFC 
ROI centered on the group x time interaction (a conservative comparison), and found 
difference statistic of (t=3.29, p<.005), from which we estimate a small N-adjusted effect 
size (Hedge’s g) of 1.44.  In our revised design, we will randomize N=30 to MBCT and 
N=30 to PE-in vivo to obtain N~22 completers in each group (assuming 25% drop rate), 
Based upon pilot effect size, power estimates (using G*Power) find sufficient power to 
detect effect sizes to d=0.6 difference in PCC-dlPFC with beta >80% in between-group 
two-sample t-tests at the post-treatment time-point.   
 
 
 

NCCIH DSMP  
Version Date: 9/15/2018 
15
 
R33 Phase - sample size justification and power analyses: The R33 has 3 scans: (1) at 
intake (2) after MBCT or MRG, and (3) after PE In vivo.  We hypothesize MBCT will 
show greater increase in dlPFC-PCC connectivity than MRG (between-groups 
comparison of scan 2).  We are proposing increased dlPFC-PCC as our primary 
mechanism unique to MBCT, that will not be induced by Relaxation (as recently also 
reported by Creswell et al., 2016).  We also hypothesize that MBCT+PE will show 
greater increase in dlPFC-PCC, greater decrease in Insula-PCC connectivity at Scan 3, 
and greater improvement in PTSD and functional outcomes than MRG-PE. As stated 
above, we hypothesize that MBCT will lead to greater capacity for successful 
engagement in subsequent in vivo exposure, and thus will lead to additive effects with in 
vivo exposure, as two therapeutic mechanisms will be engaged (increased dlPFC-PCC 
from MBCT, and decreased Anterior Insula-PCC from in vivo exposure).   
 
Our Power Analysis (GPower 3.1) to test increased dlPFC-PCC in the MBCT group at 
time 2 and time 3 will be based on our pilot data (as in R61 phase) of Hedge’s g = 1.44. 
With our proposed sample size in the optimization study (randomize N=54 in each 
group to conservatively obtain at least N=41 at time 2 and at least N=30 “completers” at 
time 3) we are sufficiently powered to detect increased dlPFC-PCC at time 2 and at time 
3 (beta > 0.95).  We do not yet have pilot data for an effect of previous MBCT to lead to 
greater decrease in Anterior Insula-PCC connectivity, but our design with N=30 per 
group at time 3 will be powered to detect an effect size of increased Anterior Insula-
PCC connectivity in MBCT+PE vs MRG+PE effect size d=0.65 at 0.80 power (critical 
t=1.67), and d=0.85 with 0.95 power.   
7.3 
Stopping Rules  
 
This study will be stopped prior to its completion if: (1) the intervention is associated 
with adverse effects that call into question the safety of the intervention; (2) difficulty in 
study recruitment or retention will significantly impact the ability to evaluate the study 
endpoints; (3) any new information becomes available during the trial that necessitates 
stopping the trial; or (4) other situations occur that might warrant stopping the trial.”  
7.4 
Designation of a Monitoring Committee   
 
The Independent Safety Monitoring Committee for this study will comprised of two 
expert clinicians with longstanding expertise in PTSD and anxiety disorders (Professor 
Tracy Simpson, PhD of University of Washington and Professor Elizabeth Hoge, MD of 
Georgetown University) both with extensive experience in clinical trials for mindfulness-
based interventions, an expert in PTSD psychophysiology and neurobiology (Professor 
Tanja Jovanovic, PhD of Emory University), and an experienced and qualified 
statistician (Shokoufeh Khalatbari, MS, Statistician Staff Manager, Biostatistics Program 

NCCIH DSMP  
Version Date: 9/15/2018 
16
Michigan Institute for Clinical & Health Research, The University of Michigan) who has 
extensive experience in managing clinical trials.  These expert Independent Study 
Monitors are not associated with this research project and all work independently of the 
PI, Dr. Anthony King. They are not part of the key personnel involved in this grant, and 
will not have co-published with the PI within the past three years. They are qualified to 
review the patient safety data generated by this study because of their unique expertise. 
The CVs of all members of the IMC will be supplied to NCCIH for approval.  
7.5 
Safety Review Plan  
 
Study progress and safety will be reviewed monthly (and more frequently if needed).  
Progress reports, including patient recruitment, retention/attrition, and AEs will be 
provided to the Independent Monitor semi-annually.  An Annual Report will be compiled 
and will include a list and summary of AEs.  In addition, the Annual Report will address 
(1) whether AE rates are consistent with pre-study assumptions; (2) reason for dropouts 
from the study; (3) whether all participants met entry criteria; (4) whether continuation of 
the study is justified on the basis that additional data are needed to accomplish the 
stated aims of the study; and (5) conditions whereby the study might be terminated 
prematurely.  The Annual Report will be sent to the Independent Monitor(s) and will be 
forwarded to the IRB and NCCIH.  The IRB and other applicable recipients will review 
progress of this study on an annual basis 
7.6 
Study Report Outline for the Independent Monitors(s) (Interim or Annual 
Reports)  
 
The study team will generate Study Reports for the Independent Monitor and will 
provide information on the recruitment / consent to the study, performing the intake 
assessment, performing the fMRI scan and associated activities, attending MBCT (or 
comparison therapy) sessions, turning in homework sheets, and adherence to 
treatment. The Study Report tables will be generated only from aggregate (not by group 
assignment) baseline and aggregate safety data for the study population. 
 
7.7 
Submission of On-Site Monitoring/Audit and Inspection Reports 
 
The IRB, IMC, and NCCIH Program Officials will receive copies of all study 
monitoring/audit or inspection reports within 14 day of PI receipt.   
 
 
 
 
 
 
 

NCCIH DSMP  
Version Date: 9/15/2018 
17
7.8 
Table A – Reporting Schedules  
Data type 
Frequency of review 
Reviewer 
Subject accrual (including 
compliance with protocol 
enrollment criteria) 
Monthly 
PI, Internal QA Reviewer 
Semi-annually 
Independent Monitor(s) 
Status of all enrolled subjects, as 
of date of reporting  
Monthly 
PI, Internal QA Reviewer 
Semi-annually 
Independent Monitors 
Data entry quality control checks 
on chart review 
Weekly 
QA Reviewer 
Adherence data regarding study 
visits and intervention 
Monthly 
PI, Internal QA Reviewer 
Semi-annually 
Independent Monitors 
AEs and rates (including out-of-
range lab values) 
Monthly 
PI, Internal QA Reviewer 
Semi-annually 
 
Independent Monitors 
Annually 
NCCIH 
SAEs (unexpected and related) 
Per occurrence 
PI, Independent  Monitor 
NIH / NCCIH 
SAEs (expected or unrelated) 
Per Occurrence 
PI, Internal QA Reviewer 
Annually 
Independent Monitor, 
NIH/NCCIH 
Unanticipated Problems 
Monthly 
PI, Internal QA Reviewer 
Per Policy 
IRB 

NCCIH DSMP  
Version Date: 9/15/2018 
18
8 DATA HANDLING AND RECORD KEEPING 
The PI is responsible for ensuring the accuracy, completeness, legibility, and timeliness 
of the data collected by the team and reported, and he will be assisted by the study 
coordinator under his delegation.  All source documents will be completed in a neat, 
legible manner to ensure accurate interpretation of data.  The investigators will maintain 
adequate case histories of study subjects, including accurate case report forms (CRFs), 
and source documentation. 
8.1 
Data Management Responsibilities 
Data collection and accurate documentation are the responsibility of the study staff 
under the supervision of the PI and the Clinical Trials Support Unit (CTSU) at The 
University of Michigan.  All source documents and laboratory reports must be reviewed 
by the study team and data entry staff, who will ensure that they are accurate and 
complete.  Unanticipated problems and adverse events must be reviewed by the 
investigator or designee.   
8.2 
Database Protection  
 
This study will use OnCore database, an enterprise Clinical Trials Management System 
(CTMS) that is administered by the Michigan Clinical Trials Support Unit.  OnCore is a 
comprehensive CTMS recently implemented at the University of Michigan Medical 
School and Michigan CTSU. Our study-specific database will be set up with support of 
CTSU and maintained by the study coordinator and data manager in coordination and 
oversight of CTSU administration, with electronic audit trail capability with person and 
date-stamp, and with oversight by CTSU and study statistician.  The database will be 
secured with password protection.  The database will not contain personally identifying 
information (PII), participant contact information (for study and treatment follow-up, 
payment, etc.) will be stored in a separate database, with a single copy of a key in a 
password-protected file accessible only to study coordinator and PI.  The statistician 
and data manager will receive only coded information that is entered into the database 
under those identification numbers, managed by CTSU.  Electronic communication with 
outside collaborators will involve only unidentifiable information. The database 
incorporates an electronic audit trail to show change(s) to data after original entry 
including the date/time and user making the change. 
8.3 
Source Document Protection 
All paper and electronic source document records for all enrolled subjects, i.e., case 
report forms, laboratory reports, subject study binders, etc.) will be coded only by 
participant ID code, and will be kept in separate locked cabinets at the University of 
Michigan and the VA Ann Arbor   

NCCIH DSMP  
Version Date: 9/15/2018 
19
8.4 
Schedule and Content of Reports 
Weekly reports will be made to PI and monthly to internal QA regarding monitoring of 
study enrollment, study conduct, and reports for interim data analysis and study 
progress.   
The R61 Phase is a two-group single-blinded fMRI neuroimaging study comparing  
MBCT intervention to a well-matched active control intervention, Muscular Relaxation 
Group therapy of PTSD.  Interim analyses will not be performed on outcome data. The 
primary outcomes will be engagement of the neural target (i.e. fMRI between-groups t-
test at post and group x time interaction in RM-ANOVA).  Additional functional outcomes 
will be collected at multiple time points, including PTSD and depression diagnosis and 
symptom severity, and self-report measures of decentering, PTSD, rumination, and 
other measures.  These secondary measures are exploratory but will not be included in 
the R61 Go/No-Go Criteria. 
The R33 phase will be a single-blinded RCT comparing MBCT vs a Relaxation group 
therapy control, each followed by PE in vivo group.  The data from the independent 
assessor (blinded to therapy condition) will be entered into the database; the blind on 
subject assignment will not be broken until the completion of recruitment and study-
related activities, at which point the database will also be locked for analyses. 
Interim analyses will not be performed on outcome data. 
When blind is broken, we will conduct Group x Time fMRI analyses, as well as formal 
mediation analyses (in SEM) utilizing all unblended, locked data.  

NCCIH DSMP  
Version Date: 9/15/2018 
20
9 INFORMED CONSENT 
Informed consent is a process that is initiated prior to the individual agreeing to 
participate in the study and continues throughout study participation.  Extensive 
discussion of risks and possible benefits of study participation will be provided to 
subjects and their families, if applicable.  A consent form describing in detail the study 
procedures and risks will be given to the subject.  Consent forms will be IRB-approved, 
and the subject is required to read and review the document or have the document read 
to him or her.  The investigator or designee will explain the research study to the subject 
and answer any questions that may arise.  The subject will sign the informed consent 
document prior to any study-related assessments or procedures.  Subjects will be given 
the opportunity to discuss the study with their surrogates or think about it prior to 
agreeing to participate.  They may withdraw consent at any time throughout the course 
of the study.  A copy of the signed informed consent document will be given to subjects 
for their records.  The rights and welfare of the subjects will be protected by 
emphasizing to them that the quality of their clinical care will not be adversely affected if 
they decline to participate in this study. 
The consent process will be documented in the clinical or research record. 
To complete the informed consent process at the end of study participation, study staff 
will inform the subject when his/her participation has come to an end and will document 
the discussion in the study record. 
 
9   REPORTING CHANGES IN STUDY STATUS 
During the funding of this study, any action by an IRB, the Independent Monitoring 
Committee, Clinical Trials Support Unit, or one of the study investigators that results 
in a temporary or permanent suspension of the study will be reported to the NCCIH 
Program Official within 3 business days of notification.  
 
 

Study ID: HUM00152509   IRB: IRBMED   Date Approved: 8/12/2020   Expiration Date: 8/11/2021
Page 1 of 17
Consent Subtitle: ________________________
Consent Version: ________________________
UNIVERSITY OF MICHIGAN
CONSENT TO BE PART OF A RESEARCH STUDY
1.  KEY INFORMATION ABOUT THE RESEARCHERS AND THIS STUDY  
Study title: 
Neural Mechanisms of Mindfulness-based Cognitive Therapy (MBCT) for Posttraumatic Stress Disorder 
(PTSD)
Company or agency sponsoring the study: 
NIH - National Center for Complementary and Integrative Health
Names, degrees, and affiliations of the principal investigator and study coordinator (if applicable):
Principal Investigator: Anthony King, PhD, Department of Psychiatry, Michigan Medicine 
Study Coordinator: Elizabeth Hinckley, BA, Department of Psychiatry, Michigan Medicine 
1.1 Key Study Information
You may be eligible to take part in a research study.  This form contains important information that will 
help you decide whether to join the study.  Take the time to carefully review this information.  You 
should talk to the researchers about the study and ask them any questions you have.  You may also wish 
to talk to others such as your family, friends, or other doctors about joining this study.  If you decide to 
join the study, you will be asked to sign this form before you can start study-related activities.  Before 
you do, be sure you understand what the research study is about.
A research study is different from the regular medical care you receive from your doctor.  Research 
studies hope to make discoveries and learn new information about diseases and how to treat them.  You 
should consider the reasons why you might want to join a research study or why it is not the best 
decision for you at this time.  
Research studies do not always offer the possibility of treating your disease or condition.  Research 
studies also have different kinds of risks and risk levels, depending on the type of the study.  You may 
also need to think about other requirements for being in the study.  For example, some studies require 
you to travel to scheduled visits at the study site in Ann Arbor or elsewhere. This may require you to 
arrange travel, change work schedules, find child care, or make other plans.  In your decision to 
participate in this study, consider all of these matters carefully.  
This research is studying the effects of different kinds of group therapy as a treatment for PTSD, and as a 
stress-management intervention for people with trauma history living in areas heavily impacted by the 
COVID-pandemic, and with elevated stress related to the COVID, and/or distress or worry (who don’t 
necessarily have to meet current full criteria for PTSD)  This research will also see how brain activity in 
people with PTSD is affected by the two differentMind-Body group therapies. We want to learn more 
about how these treatments work so we can put together better treatments for people with PTSD and 
for people with trauma history impacted by COVID and elevated stress and/or worry .  We will provide 
participants with either one or the other kind of therapy (50/50 chance, like a coin toss). We will collect 

Study ID: HUM00152509   IRB: IRBMED   Date Approved: 8/12/2020   Expiration Date: 8/11/2021
Page 2 of 17
Consent Subtitle: ________________________
Consent Version: ________________________
information (data) about levels of PTSD symptoms using questionnaires before and after the treatment. 
We will also collect data about brain activity using MRI scans before and after treatment.    
There can be risks associated with joining any research study.  The type of risk may impact whether you 
decide to join the study.  For this study, some of these risks may include increase in distressing thoughts; 
it is possible that any psychotherapy or psychological assessment may increase distressing thoughts and 
dreams about your past trauma. Safeguards are in place to protect against this risk – you will have 
weekly contact with therapists, and will also complete brief symptom self-report measures as part of 
each session. For participants who do the fMRI brain scans, risks from the functional MRI scanner 
include minor risk of discomfort because you’re lying still for more than an hour.  Some people may feel 
more anxious from being confined in the scanner. Because we are recording the therapy sessions and 
your voice can be heard there is a chance that someone might be able to identify you. Being in any study 
or interacting with a medical system involves the possibility that someone sees your information who is 
not supposed to. More detailed information will be provided later in this document.
This study may not offer any benefit to you now, but then again it is possible that you might feel like 
your PTSD symptoms are better. Your contribution to this study may help others with PTSD in the future 
by increasing our understanding of how the brain and body respond to different therapies.  There might 
be other ways to treat your PTSD including many different kinds of non-drug therapies as well as some 
medicines that can help with anxiety and depression symptoms.  There might even be other 
experimental treatments. More information will be provided later in this document.
 
We expect the total amount of time you will participate in the study over the 10-12 weeks of the study 
will be 8 hrs on study-related assessment and data collection and 16 hrs of therapy.  Each assessment 
will take about 1.5-2 hours. Additionally, you attend 8 weekly therapy sessions which are about 2 hrs 
each. For participnats who do the brain scans, each fMRI will take about 2 hours.  You will do each of 
these before you start therapy and again after you finish.  
You can decide not to be in this study.  Alternatives to joining this study to treat your PTSD include many 
different kinds of non-drug therapies as well as some medicines that can help with anxiety and 
depression symptoms.  There might even be other experimental treatments.  Ask your doctor about 
these other options, ideally before you decide to be in this study.
Even if you decide to join the study now, you are free to leave at any time if you change your mind.
More information about this study continues in Section 2 of this document.

Study ID: HUM00152509   IRB: IRBMED   Date Approved: 8/12/2020   Expiration Date: 8/11/2021
Page 3 of 17
Consent Subtitle: ________________________
Consent Version: ________________________
2. PURPOSE OF THIS STUDY
2.1 Study purpose: 
The purpose of this study is to see how two different kinds of Mind-body group therapies– Mindfulness-
based Cognitive Therapy (MBCT) and Muscle Relaxation Therapy are helpful for people with PTSD, and 
for helping with stress and worry in people living in areas heavily impacted by the COVID pandemic.   We 
are also interested in how brain activity in PTSD patients might be differently affected by these therapies 
(both of these therapies can help people manage stress and are helpful for people with PTSD).  We want 
to learn more about how these treatments work so we can put together better treatments for people 
with PTSD.
3. WHO MAY PARTICIPATE IN THE STUDY
Taking part in this study is completely voluntary.  You do not have to participate if you don't want to.  
You may also leave the study at any time.  If you leave the study before it is finished, there will be no 
penalty to you, and you will not lose any benefits to which you are otherwise entitled. 
3.1 Who can take part in this study?
This study is open to people ages 18-72 who either have (a) certain types of PTSD, including those with 
interpersonal violence, sexual assault, and combat traumas, or (b) who reside in an area that is heavily 
impacted by the COVID pandemic, who have trauma history, and who have elevated levels of COVID-
related stress and/or worry. 
Because part of the study involves getting into an MRI machine you will not be able to be in that part of 
the study if you are claustrophobic or are very uncomfortable lying in tight enclosed spaces, or if you 
have metal anywhere in your body (e.g. implanted stimulators, pacemakers, embedded metal in your 
skin, etc.).  Having metallic braces on your teeth and fillings are OK.
3.2 How many people are expected to take part in this study?
120 people
4.  INFORMATION ABOUT STUDY PARTICIPATION
4.1 What will happen to me in this study?  
If you agree to be in this study you will attend 8 weekly group therapy sessions of either Mindfulness-
based Cognitive Therapy (MBCT) or Muscle Relaxation Therapy (MRT).  You will not get to choose which 
therapy you receive.  Instead you will be randomly assigned to one or the other using a computerized 
coin flip.  You have a 50-50 chance of being assigned to each group.  Before you begin a therapy group 
you will undergo an assessment related to your trauma history and symptoms of depression, worry, and 
PTSD (over a web-based online “Zoom” interview session), and fill out surveys on a secure web portal.  , 
If you participate in the brain scan part of the study, you will come in person to UM to have an fMRI 
brain scan performed and provide a saliva sample.  You will repeat this series of tests after you finish the 
8 weeks of therapy.
As a participant in this study you have certain responsibilities.  These are to protect you and to make 
sure the information we collect from you can be included in the study.  We ask that you answer 
questions honestly, attend all of your scheduled appointments, and report any new or changing 
symptoms you might experience during the study.

Study ID: HUM00152509   IRB: IRBMED   Date Approved: 8/12/2020   Expiration Date: 8/11/2021
Page 4 of 17
Consent Subtitle: ________________________
Consent Version: ________________________
Assessment Interview and Surveys
You will be asked to “meet” with a mental health provider on a remote, web-based online “Zoom” 
videovisit.  This will be a secure and encrypted channel.  We will ask you to answer a number of 
questions about your trauma experiences and depression and PTSD symptoms. You will also fill out 
surveys on a secure “web portal” asking you about your symptoms and the different ways you think 
about and experience things.  You will do these things both before you start therapy and again after you 
finish therapy.  This part of the study will about 1.5 - 2 hours to finish each time.
fMRI (functional magnetic resonance imaging)
If you take part in the fMRI brain scanning part of the study, you will have an MRI of your head before 
and after therapy to so we can look at patterns of brain activity while you look at different words.  This 
will be on a different day from your clinical interview.  Before the scan begins, you will get instructions 
on any study tasks. At four times (on arrive, before scan, after scan, on departure times during the 
session, we will collect about a teaspoon of saliva to measure your bodies level of adrenalin system 
function. While you are in the MRI machine you will have to lie as still as possible while your body is 
placed in a long, narrow tube which is the MRI camera.  Just your head and upper body are in the 
scanner.  Pictures of your brain are taken by means of magnetic pulses.  You will hear loud mechanical 
sounds that may be unpleasant, but do not cause any sensation or discomfort.  Before beginning the 
scan, small patches will be strapped to your fingers to measure heart rate and skin resistance.  A video 
monitor will be placed about 15 inches in front of your eyes.  You will be shown positive and negative 
words (like “cheerful” and “unhappy”) on the screen, and asked to think about how these words may or 
may not describe you.  In another part, you will be asked to just rest, and in another to rest and pay 
attention to your breath and body sensations.  After the scan, you will be shown some words, and asked 
if you remember seeing them before. This portion of the study will take about 2 hours in total.  
Therapies used in the Study
You will be assigned to either the MBCT or MRT therapy.  Both will be delivered via a remote, web-based 
online “Zoom” videovisit.  This will be a secure and encrypted channel.  Both treatments involve 8 weeks 
of group therapy including learning mind-body skills, and both do not include talking about your 
traumatic experiences in the group.  Sessions are led by mental health therapists, and will meet at the 
University of Michigan or VA Ann Arbor.  All therapy sessions will be videotaped to help us make sure 
that the therapist follows the therapy plan and doesn’t forget anything. You will not be seen on the 
video, but your voice may be heard.
Mindfulness-based Cognitive Therapy (MBCT)
Each session is approximately 2 hours long.  Over the 8-week Zoom group,  you will learn several 
mindfulness meditation techniques.  You will practice paying attention to your bodily 
sensations, thoughts, and emotions.  Each session will also involve group discussion and 
feedback.  You will be asked to practice these techniques at home, and keep a log of your mood, 
and stress ratings. You will receive audio files with exercises so you can practice at home 
between sessions.  
Muscle Relaxation Therapy (MR)

Study ID: HUM00152509   IRB: IRBMED   Date Approved: 8/12/2020   Expiration Date: 8/11/2021
Page 5 of 17
Consent Subtitle: ________________________
Consent Version: ________________________
Each MR session is approximately 2 hours.  Over the 8-week Zoom group,  you will learn how to 
relax your body using a step-by-step process in which you alternate between squeezing and 
relaxing your muscles.  You will learn about your body’s natural response to stress and how to 
use muscle relaxation during your everyday life.  Each session will also involve group discussion 
and feedback.  You will be asked to practice these techniques at home, and keep a log of your 
mood, and stress ratings. You will receive audio files with exercises so you can practice at home 
between sessions.  
Photography or video/audio.
We will video-record part of our interview (about 20 min) during the PTSD assessmentThese recordings 
will be rated by trained raters for emotional responses, and then destroyed.  We will also video-record 
the therapy sessions (with the camera on the therapists) to be able to make sure the therapists are 
delivering the therapy correctly.  The recordings will be rated by trained study team members and then 
destroyed
Genetic Material Data Collection
This part of the study is optional, and only for the people who do the fMRI brain scanning part of the 
study. We would like your permission to collect and analyze your saliva for information about your 
genes (DNA and RNA).  We will look for changes in the expression (turning on and turning off) of certain 
genes like those in the immune system that might be related to PTSD and how it responds to treatment.  
This information will add what we know about PTSD, and help us design better treatments.  To do this, 
we will combine the information about your DNA with the other information we collect about you for 
the main study (for example, MRI results, to see how different DNA profiles might be linked to different 
brain responses,, etc.)
This procedure requires 1 extra tube of saliva (~1 teaspoons worth) that will be collected at the same 
time as the saliva sample for the main study.  You can be in the main study (looking at MBCT and MRT) 
without consenting to this additional tube of saliva and test.  If you say yes today, but then change your 
mind later, we will do our best to destroy your sample.  However, it’s important to know that once your 
saliva sample is analyzed it might not be possible to remove the test results from our research.  If your 
results were part of a larger set of results that we shared with collaborators, we might not be able to get 
it back.
Because your genetic information is unique to you, there is always a chance that someone could trace it 
back to you.  Your saliva sample and results will not have your name on them.  Instead, they will be 
labeled with a code that only a few people will have access to (just like in the main study).  There are 
federal laws that protect your genetic information.  GINA – or the Genetic Information Non-
discrimination Act – generally makes it illegal for groups like health insurance companies and plans, and 
most employers, to discriminate against you based on your genes. GINA does not protect you against 
discrimination from life insurance companies, disability insurance, and long-term care insurance.  
Specifically, under this law:

Health insurance companies and group health plans may not request your genetic information 
that we obtain from this research

Study ID: HUM00152509   IRB: IRBMED   Date Approved: 8/12/2020   Expiration Date: 8/11/2021
Page 6 of 17
Consent Subtitle: ________________________
Consent Version: ________________________

Health insurance companies and group health plans may not use your genetic information when 
making decisions regarding your eligibility or premiums

Employers with 15 or more employees may not use your genetic information that we obtain 
from this research when making a decision to hire, promote, or fire you or when setting the 
terms of your employment
GINA does not apply to the following groups; however, these groups have policies in place that offer 
similar protections against discrimination:

Members of the US Military receiving care through Tricare

Veterans receiving care through the Veteran’s Administration (VA)

The Indian Health Service

Federal employees receiving care through the Federal Employees Health Benefits Plans
Finally, because this research is paid for by the NIH we might share your genetic information in a public 
repository for other researchers to use.  We will label your genomic information with a code, instead of 
your name or other information that people could use to directly identify you. Even so, there is a chance 
that when your genomic information is combined with other information available to researchers they 
might be able to identify a group you belong to (like an ethnic group or a disease population).  It is far 
less likely that these other researchers could identify you personally. NIH prohibits people from trying 
to identify individuals whose genomic information is in an NIH-designated repository. 
Researchers will have controlled access to your specific genomic information. Controlled access means 
that researchers will need approval from NIH in order to obtain genomic information from the 
repository.  If you allow us to put your genomic information in the repository, you can change your mind 
later and ask us to remove it. Keep in mind, however, that we cannot take back information that other 
researchers have already obtained from the repository. The genomic summary results from this study 
will only be made available through controlled access. 
4.2 How much of my time will be needed to take part in this study? 
Each of the two assessments (Zoom interview and self-report questionnaires on the web portal) will 
take about 1.5-2 hours, and for people who do the fMRI scans, each of the two fMRI will take about 2 
hours.  You will do each of these before you start therapy and again after you finish.  Additionally, you 
will spend 8 weeks attending 2 hr therapy sessions and practicing at home.
4.3 When will my participation in the study be over? 
Your time in the study will be over after you complete the second follow-up assessment, which will be 
two months (8 weeks) after the completion of the 8 week (two month) therapy group) so the time in the 
study altogether is generally about 16-18 weeks (about four and a half months) total study time.
4.4 What will happen with my information and/or biospecimens used in this study?
Your biospecimens and collected information may be shared with our sponsor, the National Center for 
Complimentary and Integrative Health (part of the National Institutes of Health or NIH).  
With appropriate permissions, your biospecimens and collected information may also be shared with 
other researchers, here, around the world, and with companies.

Study ID: HUM00152509   IRB: IRBMED   Date Approved: 8/12/2020   Expiration Date: 8/11/2021
Page 7 of 17
Consent Subtitle: ________________________
Consent Version: ________________________
Your identifiable private information or identifiable biospecimens may be stripped of identifiers and 
used for future research studies or distributed to another researcher for future research studies without 
additional informed consent. 
We also want to keep your information linked to your identity because we might want to answer 
different research questions later.  One thing we might want to look at is long-term effects of MBCT and 
MRT.  So we are asking your permission to keep your information for at least 2 years after this study 
ends.  We are also asking permission to possibly contact you again at some point in the future, to see 
how you’re doing.  
You can say no to us keeping your information after the study is over and to being re-contacted.  Doing 
so will not change your ability to be in this study or your relationship with the study team.
5.  INFORMATION ABOUT STUDY RISKS AND BENEFITS
5.1 What risks will I face by taking part in the study?  What will the researchers do to protect me 
against these risks?
There are some risks associated with being in any research study.  We have described the ones we know 
about below, and included an explanation of how we will reduce your chance of experiencing them.  
There might also be risks that we don’t know about or don’t expect.  If we learn about any new risks, we 
will share them with you.
Remote (online “Zoom”) therapy groups and remote online psychological assessment interviews: It is 
possible that any psychotherapy or psychological assessment may increase distressing thoughts and 
dreams about your past trauma. You may feel uncomfortable disclosing your distressing thoughts to 
other group participants.  Safeguards are in place to protect against this risk – You will have weekly 
contact with therapists, and will also complete brief symptom self-report measures as part of each 
session.  The therapist will review these forms each session and set up an individual meeting with you if 
it looks like things are getting too distressing in that moment.
Magnetic Resonance Imaging: For those people who do the fMRI brain scans, risks from the functional 
MRI scanner include minor risk of discomfort because you’re lying still for more than an hour.  Some 
people may feel more anxious from being confined in the scanner.  Other possible but extremely 
unlikely adverse effects include: 

Injury due to the main magnetic field attracting ferromagnetic/metallic objects towards you. 

Temporary hearing loss due to loud noises associated with fMRI scanning.  

Potential of exacerbated psychiatric symptoms (such as increased anxiety, panic, or PTSD 
symptoms) when going into the fMRI scanner

Fast imaging sequences, such as those employed in this study, have the potential to induce 
peripheral nerve stimulation (PNS). PNS can be described as light touching sensation on the skin 
surface and may cause mild discomfort, but is not harmful to the subject.  The MRI machine is 
operated within FDA guidelines so the potential for inducing PNS is very low.

Transdermal medication patches that are placed on the skin to deliver a time release dose of 
medication through the skin and into the bloodstream, like nicotine patches like those that 

Study ID: HUM00152509   IRB: IRBMED   Date Approved: 8/12/2020   Expiration Date: 8/11/2021
Page 8 of 17
Consent Subtitle: ________________________
Consent Version: ________________________
deliver nicotine, testosterone and nitroglycerin, can cause burns if worn during an MRI 
procedure. That's because some transdermal patches have an aluminized backing.
To reduce any potential risks, the following will be done: Anyone allowed in the room will be screened 
for metallic objects prior to entering the scan room to minimize the risk of the main magnetic field 
attracting ferromagnetic/metallic objects towards the magnet. We will also screen for transdermal 
medication patches. You will be required to wear foam earplugs or other hearing protection, as is 
routine for clinical patients, to prevent risk of hearing damage due to the inherently loud noise of MR 
scanning. The risk of discomfort will be minimized by custom pads and pillows to make you as 
comfortable as possible. 
You will be able to talk with the operator or researcher through an intercom at all times during the scan 
and will also be able to trigger an audible alarm (using a squeeze ball held in left hand) at any time if you 
are feeling uncomfortable or experiencing feelings of anxiety or panic for immediate attention or to get 
out of the MRI machine. If, at any point during your time at the MRI facility you experience discomfort, 
you should inform the investigator and the study can be stopped at any point.  If you experience anxiety, 
panic, or worsening of PTSD symptoms you will be provided counseling by the PI or other study team 
members who are licensed psychologists or psychiatrists at the MRI facility or another place later that 
day.  If necessary we will refer you for additional care that day or options for additional or alternate 
care, and we will follow up with you over the next few days to see how you are doing and if you need 
further assistance or referral. 
There is also a chance that the MRI will reveal abnormalities in the brain, e. g. a tumor, previously 
unknown to you.  While the research team is not formally trained to diagnose brain abnormalities from 
MRI images, if an abnormality is detected on an MRI image, we will notify you and help advise you about 
what to do next.
Video & Audio recording: Audio-video recordings of the interview and therapy sessions will stored on a 
secure, encrypted, HIPPA-compliant UM computer server and/or on a hard drive kept in a locked 
cabinet in UM research office space. The recordings will be reviewed and rated by trained study team 
staff, and they will be permanently destroyed after they are rated. 
Privacy and Confidentiality:  Being in any study or interacting with a medical system involves the 
possibility that someone sees your information who is not supposed to.  We talk about these kinds of 
risks in Section 9 of this form.
5.2 What happens if I get hurt, become sick, or have other problems as a result of this research?
The researchers have taken steps to minimize the risks of this study.  Even so, you may still have 
problems or side effects, even when the researchers are careful to avoid them. Please tell the 
researchers listed in Section 10 about any injuries, side effects, or other problems that you have during 
this study.  You should also tell your regular doctors.
5.3 If I take part in this study, can I also participate in other studies?

Study ID: HUM00152509   IRB: IRBMED   Date Approved: 8/12/2020   Expiration Date: 8/11/2021
Page 9 of 17
Consent Subtitle: ________________________
Consent Version: ________________________
Being in more than one research study at the same time, or even at different times, may increase the 
risks to you.  It may also affect the results of the studies.  You should not take part in more than one 
study without approval from the researchers involved in each study.  
5.4 How could I benefit if I take part in this study?  How could others benefit?  
You may not receive any personal benefits from being in this study, but then again it is possible that you 
might feel like your PTSD symptoms are better.  Your contribution to this study will help future PTSD 
patients by increasing our understanding of how the brain and body respond to different therapies.  
5.5 Will the researchers tell me if they learn of new information that could change my willingness to 
stay in this study?
Yes, the researchers will tell you if they learn of important new information that may change your 
willingness to stay in this study. If new information is provided to you after you have joined the study, it 
is possible that you may be asked to sign a new consent form that includes the new information.
6.  ALTERNATIVES TO PARTICIPATING IN THE STUDY
6.1 If I decide not to take part in this study, what other options do I have?
There can be other ways to treat your PTSD and/or stress and worry including many different kinds of 
non-drug therapies as well as some medicines that can help with anxiety and depression symptoms.  
There might even be other experimental treatments.  Ask your doctor about these other options, ideally 
before you decide to be in this study.
7.  ENDING THE STUDY
7.1 If I want to stop participating in the study, what should I do?
You are free to leave the study at any time.  If you leave the study before it is finished, there will be no 
penalty to you. You will not lose any benefits to which you may otherwise be entitled.  If you choose to 
tell the researchers why you are leaving the study, your reasons for leaving may be kept as part of the 
study record. If you decide to leave the study before it is finished, please tell one of the persons listed in 
Section 10 “Contact Information”.
7.2 Could there be any harm to me if I decide to leave the study before it is finished? 
No
7.3 Could the researchers take me out of the study even if I want to continue to participate?
Yes. There are many reasons why the researchers may need to end your participation in the study.  
Some examples are:

The researcher believes that it is not in your best interest to stay in the study.

You become ineligible to participate.

Your condition changes and you need treatment that is not allowed while you are taking part in 
the study.

You do not follow instructions from the researchers.

The study is suspended or canceled.
8.  FINANCIAL INFORMATION

Study ID: HUM00152509   IRB: IRBMED   Date Approved: 8/12/2020   Expiration Date: 8/11/2021
Page 10 of 17
Consent Subtitle: ________________________
Consent Version: ________________________
8.1 Who will pay for the costs of the study?  Will I or my health plan be billed for any costs of the 
study?  
There are no costs or billing for this study. By signing this form, you do not give up your right to seek 
payment if you are harmed as a result of being in this study.
8.2 Will I be paid or given anything for taking part in this study?
You will be paid (in the form of a gift card given to you in person or a check mailed to your house) for 
finishing each segment of the study up to a total of $345:

$25 for each clinical assessment (Zoom interviews & surveys)

$120 reimbursement for use of two months personal internet / data services for Zoom, or if I do 
not have current secure internet and Zoom capable device, I will be provided a Zoom-capable 
smart phone and sufficient months of unlimited data plan to complete the study    
Participants who do the brain scan part of the study will be paid $75 for each fMRI scan
8.3 Who could profit or financially benefit from the study results?
No one associated with this study will profit or benefit financially from the study results.
Research can lead to new discoveries, such as new tests, drugs, or devices. Researchers, 
their organizations, and other entities, including companies, may potentially benefit from 
the use of the data or discoveries. You will not have rights to these discoveries or any 
proceeds from them.
9. CONFIDENTIALITY OF SUBJECT RECORDS AND AUTHORIZATION TO RELEASE YOUR PROTECTED 
HEALTH INFORMATION
The information below describes how the confidentiality of your research records will be protected in 
this study, and any sub-studies described in this document.  
9.1 How will the researchers protect my information? 

Only authorized people can access your information and saliva sample.

We keep your information, including things that identify you like your name or phone number, 
password-protected and restricted-access databases that are protected by Michigan Medicine 
computer systems.

Paper records that have your name on them, like this document, are kept separate from your 
other research records.  We keep these records in locked cabinets in locked offices.

Recordings of therapy sessions are stored in password-protected restricted-access database.

Your saliva samples are not labled with your name.  Instead we use a study code on these things 
so that it’s harder for someone to know that it’s yours.

The link between your name and the study code is kept confidential and only available to 
authorized study team members.  Your name or other things that identify you will not be 
included in any reports or publications. 
Certificate of Confidentiality

Study ID: HUM00152509   IRB: IRBMED   Date Approved: 8/12/2020   Expiration Date: 8/11/2021
Page 11 of 17
Consent Subtitle: ________________________
Consent Version: ________________________
This research is covered by a Certificate of Confidentiality from the National Institutes of Health. The 
researchers with this Certificate may not disclose or use information, documents, or biospecimens that 
may identify you in any federal, state, or local civil, criminal, administrative, legislative, or other action, 
suit, or proceeding, or be used as evidence, for example, if there is a court subpoena, unless you have 
consented for this use. Information, documents, or biospecimens protected by this Certificate cannot be 
disclosed to anyone else who is not connected with the research except, if there is a federal, state, or 
local law that requires disclosure (such as to report child abuse or communicable diseases but not for 
federal, state, or local civil, criminal, administrative, legislative, or other proceedings, see below); if you 
have consented to the disclosure, including for your medical treatment; or if it is used for other scientific 
research, as allowed by federal regulations protecting research subjects. 
The Certificate cannot be used to refuse a request for information from personnel of the United States 
federal or state government agency sponsoring the project that is needed for auditing or program 
evaluation by the SPONSOR which is funding this project or for information that must be disclosed in 
order to meet the requirements of the federal Food and Drug Administration (FDA).  You should 
understand that a Certificate of Confidentiality does not prevent you from voluntarily releasing 
information about yourself or your involvement in this research. If you want your research information 
released to an insurer, medical care provider, or any other person not connected with the research, you 
must provide consent to allow the researchers to release it.
The Certificate of Confidentiality will not be used to prevent disclosure as required by federal, state, or 
local law of child abuse and neglect, or harm to self or others.
The Certificate of Confidentiality will not be used to prevent disclosure for any purpose you have 
consented to in this informed consent document.
Because this study is sponsored by the NIH your information and saliva samples are also protected by a 
Certificate of Confidentiality.  This means that we cannot be forced to disclose or use any of your private 
identifiable information (e.g. documents, saliva sample, other study information) that might identify you 
in any federal, state, or local civil, criminal, administrative, legislative, other or proceeding (e.g. court 
subpoena) unless you give us permission. 
Information, documents, or saliva samples protected by this Certificate cannot be disclosed to anyone 
else who is not connected with the research except when:

There is a federal, state, or local law that requires us to, like in cases of child abuse or 
communicable diseases 

You have consented to the disclosure, including for your medical treatment
It is used for other scientific research as allowed by federal regulations protecting research subjects
Clinicaltrials.gov
A description of this clinical trial will be available on http://www.clinicaltrials.gov/, as required by U.S. 
Law. This Web site will not include information that can identify you. At most, the Web site will include a 
summary of the results. You can search this Web site at any time.

Study ID: HUM00152509   IRB: IRBMED   Date Approved: 8/12/2020   Expiration Date: 8/11/2021
Page 12 of 17
Consent Subtitle: ________________________
Consent Version: ________________________
9.2 What protected health information (PHI) about me could be seen by the researchers or by other 
people?  Why?  Who might see it?
Signing this form gives the researchers your permission to obtain, use, and share information about you 
for this study, and is required in order for you to take part in the study.  
Medical information and billing records are protected by the privacy regulations of the federal Health 
Insurance Portability and Accountability Act of 1996 (HIPAA).  This type of information is called 
protected health information (PHI).  PHI about you may be obtained from any hospital, doctor, and 
other health care provider involved in your care, including:

Hospital/doctor's office records, including test results (X-rays, blood tests, urine tests, etc.)

Mental health care records (except psychotherapy notes not kept with your medical records)

Alcohol/substance abuse treatment records

HIV/AIDS status

Sexually transmitted disease and/or other communicable disease status

Genetic counseling/genetic testing records

Health plan/health insurance records

All records relating to your condition, the treatment you have received, and your response to 
the treatment

Billing information

Demographic information

Personal identifiers

Other information
There are many reasons why information about you may be used or seen by the researchers or others 
during or after this study.  Examples include:

The researchers may need the information to make sure you can take part in the study.  

The researchers may need the information to check your test results or look for side effects.  

University, Food and Drug Administration (FDA) and/or other government officials, auditors, 
and/or the IRB may need the information to make sure that the study is done in a safe and 
proper manner.   

Study sponsors or funders, or safety monitors or committees, may need the information to: 
o
Make sure the study is done safely and properly
o
Learn more about side effects 
o
Analyze the results of the study 

Insurance companies or other organizations may need the information in order to pay your 
medical bills or other costs of your participation in the study.

The researchers may need to use the information to create a databank of information about 
your condition or its treatment.

Information about your study participation may be included in your regular UMHS medical 
record.

If you receive any payments for taking part in this study, the University of Michigan accounting 
department may need your name, address, Social Security number, payment amount, and 
related information for tax reporting purposes.

Study ID: HUM00152509   IRB: IRBMED   Date Approved: 8/12/2020   Expiration Date: 8/11/2021
Page 13 of 17
Consent Subtitle: ________________________
Consent Version: ________________________

Federal or State law may require the study team to give information to government agencies. 
For example, to prevent harm to you or others, or for public health reasons. 
The results of this study could be published in an article, but would not include any information that 
would let others know who you are. 
9.3 What happens to information about me after the study is over or if I cancel my permission to use 
my PHI?
As a rule, the researchers will not continue to use or disclose information about you, but will keep it 
secure until it is destroyed.  Sometimes, it may be necessary for information about you to continue to be 
used or disclosed, even after you have canceled your permission or the study is over.  
Examples of reasons for this include:

To avoid losing study results that have already included your information 

To provide limited information for research, education, or other activities. (This information 
would not include your name, social security number, or anything else that could let others 
know who you are.) 

To help University and government officials make sure that the study was conducted properly
As long as your information is kept within the University of Michigan Health System, it is protected by 
the Health System’s privacy policies.  For more information about these policies, ask for a copy of the 
University of Michigan “Notice of Privacy Practices”.  This information is also available on the web at 
http://www.uofmhealth.org/patient+and+visitor+guide/hipaa.  Note that once your information has 
been shared with others as described under Question 9.2, it may no longer be protected by the privacy 
regulations of the federal Health Insurance Portability and Accountability Act of 1996 (HIPAA).  
9.4 When does my permission to use my PHI expire?  
Your permission expires at the end of the study, unless you cancel it sooner. You may cancel your 
permission at any time by writing to the researchers listed in Section 10 "Contact Information" (below).  
If you withdraw your permission, you may no longer be eligible to participate in this study.
10. CONTACT INFORMATION
10.1 Who can I contact about this study?
Please contact the researchers listed below to:

Obtain more information about the study

Ask a question about the study procedures or treatments

Talk about study-related costs to you or your health plan 

Report an illness, injury, or other problem (you may also need to tell your regular doctors)

Leave the study before it is finished

Express a concern about the study

Study ID: HUM00152509   IRB: IRBMED   Date Approved: 8/12/2020   Expiration Date: 8/11/2021
Page 14 of 17
Consent Subtitle: ________________________
Consent Version: ________________________
Principal Investigator:  Anthony King, PhD
Mailing Address: 2747 Rachel Upjohn Building / 4250 Plymouth Road, Ann Arbor, MI 48109
Telephone: 734-936-4955
Study Coordinator: Elizabeth Hinckley, BA
Mailing Address:  Rachel Upjohn Building / 4250 Plymouth Road, Ann Arbor, MI 48109
Telephone: 734-764-9527
You may also express a question or concern about a study by contacting the Institutional Review 
Board listed below:
University of Michigan Medical School Institutional Review Board (IRBMED)
2800 Plymouth Road
Building 520, Room 3214
Ann Arbor, MI 48109-2800
Telephone: 734-763-4768  (For International Studies, include the appropriate calling codes.)
Fax: 734-763-1234
e-mail: irbmed@umich.edu 
If you are concerned about a possible violation of your privacy or concerned about a study you may 
contact the University of Michigan Health System Compliance Help Line at 1-866-990-0111.
When you call or write about a concern, please provide as much information as possible, including the 
name of the researcher, the IRBMED number (at the top of this form), and details about the problem.  
This will help University officials to look into your concern.  When reporting a concern, you do not have to 
give your name unless you want to.
11.  RECORD OF INFORMATION PROVIDED
11.1 What documents will be given to me?
Your signature in the next section means that you have received copies of all of the following 
documents:

This "Consent to be Part of a Research Study" document.  (Note: In addition to the copy you 
receive, copies of this document will be stored in a separate confidential research file and may be 
entered into your regular University of Michigan medical record.)
12.  SIGNATURES

Study ID: HUM00152509   IRB: IRBMED   Date Approved: 8/12/2020   Expiration Date: 8/11/2021
Page 15 of 17
Consent Subtitle: ________________________
Consent Version: ________________________
Sig-A
Consent to Participate in the Research Study
I understand the information printed on this form.  I have discussed this study, its risks and potential benefits, 
and my other choices with [NAME OF STUDY TEAM MEMBER OBTAINING CONSENT] ______________________.  
My questions so far have been answered.  I understand that if I have more questions or concerns about the 
study or my participation as a research subject, I may contact one of the people listed in Section 10 (above).  I 
understand that I will receive a copy of this form at the time I sign it and later upon request.  I understand that if 
my ability to consent or assent for myself changes, either I or my legal representative may be asked to re-
consent prior to my continued participation in this study.
Print Legal Name: ___________________________________________________________________
Signature: _________________________________________________________________________
Date of Signature (mm/dd/yy): ________________________
Sig-B
Consent to video & audio recording for purposes of this research
This study involves video and/or audio recording and/or photography. If you do not agree to be recorded, you 
cannot take part in the study.
_____ Yes, I agree to be video/audio recorded/photographed.
_____ No, I do not agree to be video/audio recorded/photographed.
Print Legal Name: _________________________________________________________________
Signature: _______________________________________________________________________
Date of Signature (mm/dd/yy): ____________________________

Study ID: HUM00152509   IRB: IRBMED   Date Approved: 8/12/2020   Expiration Date: 8/11/2021
Page 16 of 17
Consent Subtitle: ________________________
Consent Version: ________________________
Sig-D
Consent to Collect for Unspecified Future Research
This project involves the option to allow the study team to keep your identifiable saliva for use in future 
research.  I understand that it is my choice whether or not to allow future use of my specimens.  I understand 
that if my ability to consent or assent for myself changes, either I or my legal representative may be asked to re-
consent prior to my continued participation in this study.
_____ Yes, I agree to let the study team keep my saliva for future research.
_____ No, I do not agree to let the study team keep my saliva for future research.
Print Legal Name: ___________________________________________________________________
Signature: _________________________________________________________________________
Date of Signature (mm/dd/yy): ______________________________
Sig-x
Consent to be contacted again for later research
We might want to contact you in the future.  You can say “yes, re-contact me” today, and change your mind 
later.  If you change your mind, please call us so we can take you off the re-contact list.  
There are different reasons why we might want to contact you again.  For example, we might want to see if there 
are any long-term effects of MBCT or MRT.   Saying no does not impact your eligibility for this study.
_____ Yes, I agree to being re-contacted.
_____ No, I do not agree to being re-contacted.
Print Legal Name: ___________________________________________________________________
Signature: _________________________________________________________________________
Date of Signature (mm/dd/yy): ______________________________

Study ID: HUM00152509   IRB: IRBMED   Date Approved: 8/12/2020   Expiration Date: 8/11/2021
Page 17 of 17
Consent Subtitle: ________________________
Consent Version: ________________________
Sig-C
Consent to Participating in an Optional Procedure – Genetic Material Data Collection
This project involves an optional saliva test for genetic analysis.  I understand that it is my choice whether or 
not to take part in this extra test.  I understand that if my ability to consent or assent for myself changes, either 
I or my legal representative may be asked to re-consent prior to my continued participation in this study.
_____ Yes, I agree to take part in the optional sub-study.
_____ No, I do not agree to take part in the optional sub-study.
Print Legal Name: ___________________________________________________________________
Signature: _________________________________________________________________________
Sig-G
Principal Investigator or Designee
I have provided this participant and/or his/her legally authorized representative(s) with information about this 
study that I believe to be accurate and complete.  The participant and/or his/her legally authorized 
representative(s) indicated that he or she understands the nature of the study, including risks and benefits of 
participating.
Printed Legal Name: __________________________________________________________________
Title: ______________________________________________________________________________
Signature: _________________________________________________________________________
Date of Signature (mm/dd/yy): ________________________