Evaluating a Novel Method of Generalizing Emotion Regulation

Difficulties regulating emotional arousal in a skillful manner are common across many
psychiatric disorders and may be central to some of the most severe and difficult-to-treat
populations (e.g., borderline personality disorder). To immediately decrease negative
affect, individuals who have difficulties regulating negative emotions often rely on
maladaptive behaviors that are significant public health problems, including substance use,
suicidal behavior, binging/purging, and other negatively reinforced behavior. Conventional
approaches to generalization of emotion regulation skills outside the clinic (e.g.,
assigning therapy homework) are insufficient. New interventions are needed that directly and
immediately reduce acute negative emotions and do not rely on patient compliance with
homework assignments or other top-down approaches. Accordingly, the primary aim of this
project is to evaluate whether novel habituation reminders (HRs) introduced following
personally-relevant emotional stressors reduce acute negative emotions and psychological
distress outside of an original learning context. Using a team of basic and applied
scientists, over 4 years investigators will recruit 420 adult outpatients to enroll 250
participants who have extreme difficulties with emotion regulation to participate in 3
experiments.

Before being recruited into the study, potential participants will complete a phone screen—a
pre-experiment screening questionnaire or an online questionnaire to assess certain
exclusion and inclusion criteria. Eligible participants will be invited to the study office
to provide written informed consent and receive a clinical assessment, during which full
inclusion and exclusion criteria will be assessed.

Using the method developed by Pitman and colleagues and used in studies of adults with PTSD,
BPD, and other diagnoses, investigators will create four negative emotional arousal scripts
that will be used in a random order during Exp. 1. In brief, the Clinical Assessor will ask
the participant to describe five of the most recent (i.e., past two weeks) moderate
stressors in their lives. Participants will write a description of each event, and the
clinical assessor will work with the participant to establish a clear story for each event
that can be recited in approximately 30 seconds. The assessor will then review the script,
ask for any clarification, and then ask the participant to rank them from most to least
stressful. Following the assessment, the clinical assessor or same sex experimenter will
digitally record these scripts into .mp3 files, which will be used in random order as the
emotional stressors in Exp. 1.

Experiment 1

-Design-In Exp. 1, the investigators will use a 2 (Learning Phase: HR v. No HR) X 2 (Testing
Phase: Context same v. different) X 2 (Testing Phase: HR v. No HR) between-subjects
factorial design.

Randomization-All participants will be randomized to condition, with oversampling for HR
groups, by using an urn randomization procedure by the off-site study statistician. Urn
randomization will be conducted using age and gender as matching variables.

Learning Phase (Day 1)Baseline-First, baseline subjective units of general psychological
distress (SUDS; visual analogue scale from 0-100) and emotional arousal will be assessed
using self-reported and psychophysiological (galvanic skin response) measures. The Study
Coordinator will affix electrodes using standard procedures, and will use Biopac MP150
hardware and AcKnowledge software for data acquisition. The galvanic skin response device is
not being tested for safety or efficacy in this study, and is not being used as a diagnostic
device. Participants will complete a five-minute baseline, sitting in a comfortable chair
quietly without sleeping in a temperature controlled, sound attenuated room. SUDS and
self-reported baseline emotion (SAM) will be obtained at the end of baseline.

Next, the emotional stressor task will be administered to all participants by playing a
stressful script which was created during the clinical assessment. Prior to hearing the
script, participants will be instructed to listen carefully and to attempt to imagine the
event as vividly as possible. The task proceeds as follows: (1) the stressor will be heard
via headphones (30s), (2) participants are instructed via standardized instructions to
imagine as vividly as possible the stressful experience (30s), (3) silence (30s), (3)
self-report of emotional arousal and valence (SAM; 30s) will be obtained via a computer.
This sequence will repeat a minimum of two and a maximum of four times, until habituation
has occurred (return to mean baseline arousal). Habituation will be continuously monitored
using a real-time monitoring program currently being used in the lab that samples arousal
(GSR) every 500ms relative to the average baseline arousal. This method allows idiographic
analyses of habituation to the stressor, and ensures that the HR is administered during
habituation. Individuals who continue to have high levels of emotional arousal after
completing the emotional stressor task will be asked to sit in silence for 10 more minutes
(receiving the SAM every 120 seconds), and if habituation has yet to occur, they will be
prompted to focus on their breath to help with relaxation for the next 10 minutes. Based on
findings using this emotional stressor task suggesting that habituation occurs within 3
minutes for veterans with PTSD, the investigators are confident that the approach will
result in habituation. Once habituation occurs, the HR will be heard via headphones 3 times
(for a total of 6s) by participants randomized to hear the HR, whereas the No-HR
participants will hear nothing.

The HR will be a series of neutral novel sounds lasting 6s, and will be the same series of
sounds being used in current lab ongoing studies testing extinction reminders. After the HR
is played, the Study Coordinator will use standardized instructions to tell participants to
remember this sound as a reminder of calming down. Lastly, SUDS and self-reported emotional
arousal measure will be assessed (SAM). Physiological data will be continuously measured
throughout this period. Although it is not expected to occur frequently, data from
participants who do not habituate will not be used in analyses, and additional participants
run. After completing the stressor task, there will be a 15 minute break, followed by a
second and third administration of the stressor task using the procedures outlined above,
but with a different personalized stressor recording each time. Investigators will randomize
the order of the recordings that the participants described during the clinical assessment.
At the end of the third emotional stressor task, participants will be scheduled for their
Testing Phase one week later.

Testing Phase (Day 2)-One week after the Learning Phase, participants will complete the
Testing Phase for Exp. 1. Upon arrival, half of the participants will be randomly assigned
to be tested in the original laboratory room from the Learning Phase (same room as Day 1)
and the other half to a new room. In line with the investigators' previous learning studies
using context manipulations, the new room in the Testing Phase will represent a very
different context compared to the room from the Learning Phase. The novel testing room will
have different size, lighting, and furniture. Using a scent machine, the novel room will
have the smell of mint released during testing. In addition, to ensure that the experimenter
does not function as a reminder of habituation from the Learning Phase, testing in the novel
room will be done by a different experimenter than in the original Learning Phase. In both
the original and novel testing rooms, the Testing Phase will begin with a baseline (same
procedures as above). Next, a new recording of a personally relevant stressor will be played
(same procedures as in Learning Phase). Participants in both rooms will be randomly assigned
to hear the HR or hear nothing (No HR). The HR will be presented through headphones every 10
seconds after the onset of the stressor task. Measures of psychological distress and
emotional arousal will be obtained (same procedures as in the Learning Phase). As in the
Learning Phase, after 10 minutes or when habituation occurs as operationalized above, the
stressor will end and self-reported psychological distress and emotional arousal will be
assessed.

Experiment 2

-In both the original and novel testing rooms, the Testing Phase will begin with a baseline
(same procedures as above). Next, a new recording of a personally relevant stressor will be
played (same procedures as in Learning Phase). Participants in both rooms will be randomly
assigned to hear the HR or hear nothing (No HR). The HR will be presented through headphones
every 10 seconds after the onset of the stressor task. Measures of psychological distress
and emotional arousal will be obtained (same procedures as in the Learning Phase). As in the
Learning Phase, after 10 minutes or when habituation occurs as operationalized above, the
stressor will end and self-reported psychological distress and emotional arousal will be
assessed. Because groups 5 and 7 from Exp. 1 will have only heard the HR during the Testing
Phase, and it may therefore be associated with the emotional stressor but not habituation,
these participants will not be randomized into Exp. 2. The participants in Exp. 2 will be
randomized to either hear the HR or a sham sound delivered via the automated server and
cellular phone platform when negative emotions are endorsed. The result is a 2 (Day 1 HR v.
No HR) X 2 (Phone HR v. sham sound) Latin square experimental design.

Procedure. At the conclusion of Exp. 1, the Clinical Assessor will orient participants to
Exp. 2. Over the next week, participants receive eight calls each day (approximately one
call every two waking hours), with each call lasting 1-2 minutes. For both experimental
conditions (HR v. Sham), calls on the first day will be used to establish baseline levels of
psychological distress (SUDS; 0-9), emotional valence (positive vs. negative; 1-9 scale;
endpoints from the SAM used) and strength of emotional arousal (1-9; SAM), while no HRs will
be delivered. On all other days, when participants report high emotional arousal (i.e., >4)
and low valence (i.e., negative affect; <5), they will automatically hear the HR or sham
sound based on randomization to Exp. 2 condition. The sham sound will be a series of neutral
percussive sounds unrelated to the HR in form but equivalent on other relevant parameters
(e.g., amplitude, length). After the HR or sham sound, all participants will provide
self-reported psychological distress (SUDS) and emotional valence/arousal, in order to
evaluate differential changes due to the HR or sham sound. After one week, participants will
return to the laboratory to return the phone, receive compensation, and be debriefed. To
further evaluate clinically meaningful changes due to the HR, the experimenter will collect
pre-, and post-Exp. 2 assessments of symptoms of clinical outcome measures (e.g., symptoms
of anxiety and depression When beginning Exp. 2, information will be given on how to use the
phone (with hands-free headset), keep its battery charged, and how to call study staff.
Phones will be restricted to study-related access and emergency numbers only. All calls will
be conducted using a dedicated server and existing software in the lab. The software uses
automated dialing and recorded prompts that ask participants to provide ratings on the phone
keypad.

First, to mitigate the possibility that the phone will be stolen, sold, or not used, the
Study Coordinator and participants will create a plan to use the phone. Second, self-report
scales will be the same as those from Exp. 1. Third, calls will be during times that the
patient will normally be awake. No participant identifying information will be accessible in
the cell phone. All data from the phone are stored in real-time in a password-protected
computer in the lab.

Experiment 3

-The primary aim of Exp. 3 is to evaluate the feasibility, acceptability, and preliminary
effect size estimates of a self-initiated HR (n = 50. on psychological distress and acute
negative emotions by hearing the HRs over two weeks. Investigators will examine: (1)
frequency of calls in to hear the HR within and across participants at times in their daily
life when they are having acute negative emotions, and (2) how laboratory HR training
affects psychological distress and emotional arousal/valence in naturalistic settings over
time.

Procedures. At the conclusion of Exp. 1, the Clinical Assessor will orient participants to
Exp. 3. Participants will be asked to call the automated server during the next two weeks
when they are feeling acute negative emotions. To facilitate use of the HR, the assessor
will discuss expected upcoming stressful events, in particular those that occur daily or
frequently, and explain how the phone can be used to cope with these stressful or
emotionally arousing situations. Participants will also be told that they will receive three
automated calls a day, beginning the next day. During the 2 week period, participants
calling in to the lab will hear a brief greeting and an assessment of present SUDS,
emotional arousal and valence. If the participant indicates emotional arousal >4 and valence
< 5, the automated system will ask if they would like to hear the HR. If the participant
does not meet these requirements or indicates that they do not want to hear the HR, they
will instead hear a brief message thanking them for calling in. After the HR or thank you
message, all participants will then be again asked to report SUDS, emotional arousal and
valence, after which the call will end. The procedure for calls out will be identical to
Exp. 2, except that all participants will receive 3 calls a day, have access to the HRs, and
be able to choose whether to hear the HR. After two weeks, participants will return to the
lab, give back the cell phone, complete an exit interview, and receive compensation.

Exp. 3 compliance enhancement strategies are the same as in Exp. 2, except for the incentive
structure.

Interviews-Diagnostic exclusions and current/past prevalence of Axis I and II diagnoses will
be determined by the Structured Clinical Interview for Mental Disorders-I and II.
Intelligence Quotient (IQ) will be assessed with the Peabody Picture Vocabulary Test—Third
Edition (PPVT-III). The Treatment History Interview (THI)will be used to assess previous and
ongoing psychiatric services received. The THI will be administered at pre- and
post-experiment time points. All interviews will be videotaped, and investigators will
determine the reliability of every tenth interview. Exit interviews will be conducted at the
end of Exp. 3 to assess participants' acceptability of the HR.

Physiological Measurement-Skin conductance will be measured using Ag-AgCl electrodes on the
middle phalanx of the middle and ring fingers of the participant's non-dominant hand. The
electrodes will be connected to a Biopac MP150 device in an adjacent room. Amplified signals
of analog data are converted to digital form and filtered using Biopac's AcKnowledge
Software, and are stored in a database on the computer.

Biochemical measures-Urinalyses (UA's) are conducted at diagnostic intake to rule out
participants currently taking illicit or prescription substances known to affect
psychophysiological arousal. The specimens will be screened on-site using the Biosite Triage
Meter Plus.. Urine will be tested for cocaine, marijuana, opiates, methadone, amphetamines,
barbiturates, and benzodiazepines. Results will be available within 30 minutes.

Inclusion Criteria:

- Age 18-55

- Currently receiving outpatient psychiatric treatment

- Elevated overall score on Difficulties with Emotion Regulation Scale (Mean DERS total
score >= 90)

- Urine test negative for presence of substances (illicit substances; e.g., cocaine,
opioids, methamphetamine, PCP, THC, Methadone). If urine test is positive for
amphetamine, barbiturates and benzodiazepines and subjects take them as prescribed,
these subjects are allowed.

Exclusion Criteria:

- Current mania

- Meets full criteria for any current psychotic disorder

- Currently/chronically homeless

- Current suicidal ideation with intent

- Psychiatric hospitalization within past 6 months

- Substance use disorder within past 6 months

- Unable to read, blind, or deaf

- PPVT < 70

- Suicide Attempt within past 6 months

- Not currently in outpatient psychiatric treatment (i.e. psychotherapy, medication
management, etc)