Real-Time Mobile Cognitive Behavioral Intervention for Serious Mental Illness
Phase: NA
Conditions: Schizophrenia, Bipolar Disorder
Sponsor: University of California, San Diego

 
 
DEPARTMENT OF PSYCHIATRY 
VOICE: 858-822-4251 
9500 GILMAN DRIVE, MC 0603V 
FAX: 858-534-5475 
LA JOLLA, CA 92093-0603 
 
May 17, 2019 
 
Re: Cover Letter for Clinical Trials.gov NCT 02035202 (Depp) 
 
 
This Cover Letter accompanies Study Protocol for this trial NCT012035202 which completed. 
Sincerely, 
 
 
Colin A Depp, Ph.D. 
 
Director, Education and Training Division, Clinical and Translational Research Institute (CTRI) 
Associate Professor 
Department of Psychiatry 
UCSD School of Medicine 
La Jolla, CA 92093-0603 
Email: cdepp@ucsd.edu 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page | 2 

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STUDY PROTOCOL 
1. 
PROJECT TITLE 
A Clinical Trial of Mobile Telephone based Assessment and Intervention for Persons with Bipolar 
Disorder or Schizophrenia 
2. 
PRINCIPAL INVESTIGATOR 
PI: Colin A Depp, Ph.D., Associate Professor, Department of Psychiatry 
3. 
FACILITIES 
UCSD Medical center; UCSD La Jolla campus 
4. 
ESTIMATED DURATION OF THE STUDY 
5 Years 
5. 
LAY LANGUAGE SUMMARY OR SYNOPSIS (no more than one paragraph) 
The purpose of this study is to evaluate the effectiveness of a mobile real-time cognitive behavioral 
intervention for serious mental illness (SMI) and to identify the facilitators, barriers, and costs of 
implementation. We would like to determine whether the addition of a mobile phone monitoring 
software program to a brief behavioral intervention for bipolar disorder or schizophrenia improves 
symptoms arising from the disorders. In this study we will be assessing the feasibility, acceptability 
and short term effect of the mobile phone enhanced intervention for bipolar disorder and 
schizophrenia. In addition, we will gather data from self-report measures and neuroscience-based 
tests from participants to inform future efforts in designing interventions aimed at diminishing risk of 
suicide in this population. 
6. 
SPECIFIC AIMS 
The goal of the study is to evaluate the effectiveness of a mobile real-time cognitive behavioral 
intervention for serious mental illness (SMI) and to identify the facilitators, barriers, and costs of 
implementation. 
Our intervention called CBT2go builds on our extensive preliminary work using mobile devices, 
integrating ecological momentary assessment (EMA) with CBT content in BD and SZ. EMA is an 
ambulatory data collection technique1-3 that allows the in vivo assessment of moods, symptoms, 
medication adherence, social interactions and other daily activities. CBT2go delivers personalized 
thought challenging and behavioral coping interventions based on EMA’s real-time reports. CBT2go 
is a 12-week intervention that involves a single in-person session followed by personalized yet 
automated responding on a mobile device, targeting affective and psychotic symptoms, medication 
adherence, socialization, and relapse prevention. 
We are proposing a 6-month randomized controlled trial, with 255 participants recruited from the San 
Diego County public mental health system who have no current access to CBT. Participants will be 
stratified by diagnosis (BD or SZ), and will be randomized to receive CBT2go, EMA only, or Standard 
Care. This design will evaluate the added benefit of CBT components over EMA only (device contact, 
medication reminders, symptom monitoring), as well as the benefits of these components relative to 
Standard Care. Individuals will be assessed at baseline, mid-point (6 weeks), post-treatment (12 
weeks) and 3-month follow up (24 weeks). Our primary and secondary outcomes will be measured 
with lab-based clinical ratings as well as EMA-based outcomes. We will also identify moderators 
(diagnostic group, cognitive ability) and mechanisms of change with respect to the elements of CBT 

4 
 
theory (changes in insight and dysfunctional attitudes). To inform pathways to implementation, we will 
evaluate the costs, barriers and facilitators to adopting CBT2go, with innovative methods from our 
implementation research. In addition, we would like to perform multiple blood draws on a subset of 
BD participants to determine whether variability in inflammatory markers, mood and cognitive 
performance predicts future suicide ideation in this population. 
Aim 1 (Effectiveness): To determine the impact of CBT2go on primary and secondary outcomes. 
Hypotheses 1 (Primary Outcome): Compared to EMA and Standard Care, the CBT2go 
intervention will be associated with greater improvement in global psychopathology (as measured by 
BPRS Total Score). 
Hypotheses 2 (Secondary Outcomes): Compared to EMA and Standard Care, the CBT2go 
intervention will be associated with greater improvement in EMA and standard lab-based measures 
of medication adherence, social functioning, and hospitalization and emergency service utilization. 
Aim 2 (Moderators and Mediators): To determine the impact of moderators and mechanisms on 
outcomes. 
Hypothesis 3 (Cognitive Impairment and Diagnosis): Neurocognitive ability will account for 
more variation in device compliance and treatment response than diagnostic group. 
Hypothesis 4 (Awareness and Attitudes): Improvement in illness awareness and reduction 
in dysfunctional beliefs will mediate incremental benefit of CBT2go over comparison conditions. 
Exploratory Aim 3: Explore a predictive model for suicidal ideation in bipolar disorder that includes 
direct and indirect effects of cognitive performance, inflammatory cytokine levels, and trajectories of 
negative affect. 
Supplement Aim 1: To evaluate the association between baseline trait and dynamic impulsivity/social 
threat with lifetime suicide risk and intensity of and intra-individual variability in suicidal ideation 
Hypothesis 1: Impaired performance on impulsivity and social threat measures will be associated with higher 
lifetime rates of suicide attempts, and more severe and more variable suicidal ideation over 24 weeks 
Exploratory: We will examine these effects by diagnostic group and treatment group assignment 
Supplement Aim 2: Test the accuracy of prediction models with intensive longitudinal data in the two- 
week window of time before increases in suicidal ideation 
Hypothesis 2: Accuracy of our prediction method will be greater than AUC=0.85 in predicting increases and 
will be greater than that associated with baseline suicide risk 
7. 
BACKGROUND AND SIGNIFICANCE 
Schizophrenia (SZ) and bipolar disorder (BD) are among the top ten causes of disability in the United 
States4, produce approximate excess mortality of 20 years per person5,6, and together cost over 100 
billion dollars per year7,8. Meta-analyses of cognitive behavioral therapy (CBT)9-12 for BD and SZ 
indicate clinically significant improvements in symptoms and reductions in disability. Nevertheless, at 
present, less than 5% of patients with SMI receive any evidence-based psychotherapies including 
CBT13. Policy changes may continue to shrink access (e.g., California’s Medicaid stopped 
reimbursing for most psychological services in 2009). Implementation of CBT for SMI faces major 
barriers including the small geographically restricted pool of trained providers and its resource 
intensity (e.g., 20 in-person contacts). Our preliminary studies indicate mobile technology can deliver 

5 
 
low intensity personalized cognitive behavioral intervention that is feasible, acceptable, and effective 
in BD and SZ14,15. If mobile interventions can produce the same effects as in-person CBT, more 
people with SMI could gain access and benefit at 15-20% of the cost. 
Individuals with BD and SZ are also at a greater risk for suicidal behavior16 and often display altered 
levels of inflammatory cytokines17 and deficits in cognitive processing18-20. Several studies have 
linked inflammation to suicidal behavior21-23 and cognitive decline24-26. Further, altered cognitive 
processing has also been demonstrated in suicidal individuals18-20. However, less is known about 
relationship between cytokine levels, cognitive performance, and suicidal ideation in BD. The 
potential mediating role of fluctuations in mood state (as measured by the EMA technology), 
inflammatory status and cognition will also be addressed in order to understand neurobiological 
aspects of suicidality in BD and develop sensitive, but straightforward, markers of suicide risk. 
Relatedly, emerging theories of near-term suicide risk posit that aberrant decision making in the 
realm of risk taking may be associated with elevated likelihood of suicidal ideation and behavior. 
People with BD and SZ are at risk for impulsive decision making, which may be a trait like aspect of 
these illnesses as well a state-like variable that fluctuates along with psychiatric symptoms. 
Moreover, dysfunctional social beliefs, such as the overperception of threat in other people, may also 
contribute to social isolation and risk of suicidal thoughts. Thus, dysfunctional social beliefs and 
impulsivity may help explain the elevated risk of suicidal thinking in bipolar disorder and 
schizophrenia, and can be assessed with objective laboratory based tests performed via computer as 
well as by self report. No studies to our knowledge have linked these two constructs to suicidal 
thoughts in serious mental illnesses and our clinical trial provides a unique opportunity to gather data 
on these constructs in the context of the other data gathered already.  The National Institute of 
Mental Health and the National Strategy for Suicide Prevention detail a high priority in leveraging 
ongoing data resources to aid in understanding near term suicide risk in populations with high base 
rates of suicide (such as people with serious mental illnesses). 
8. 
PROGRESS REPORT 
We are in Year 3 of the 4 year NIMH Award and have recruited and randomized 143 people out of the 
targeted 255 participants. We have submitted all required data to our sponsor, the NIMH, and have 
met or exceeded all recruitment targets to date. There are approximately 112 more people to 
randomize. We have had excellent retention in the trial (96%) and we have had no complaints from 
participants. We have not reported any data from this trial as the randomization is not locked. The study 
is listed on Clinical Trials.gov and its actively recruiting. 
There have been no Adverse Events in our research study. We have participated in two annual DSMB 
meetings, the most recent of which was in January 2015. The board voted to approve the study and 
raised no concerns that required changing any of the protocols, commending the study on its success 
in recruiting and retention of participants. 
9. 
RESEARCH DESIGN AND METHODS 
Participants: The subject population in this study will be a total of 255 men and women, with DSM- 
IV TR diagnoses of bipolar disorder I (BD), schizophrenia (SZ), or schizoaffective disorder, who 
reside in San Diego. Our inclusion and exclusion criteria were selected in order to increase the 
generalizability of our sample and broad reach of the mobile intervention. Participants will be of either 
gender and any race/ethnicity, with an age range of 18-65 years 

6 
 
We may enroll participants who are currently participating in other studies, where the PI of this study 
(Colin Depp, Ph.D.) is a co-investigator. Specifically, some of our participants maybe concurrently 
enrolled in “Psychosis and Aging” (HRPP# 101631, P.I. Jeste) or “Dynamic Inflammatory and Mood 
Predictors of Cognitive Aging in Bipolar Disorder” (HRPP #141474, P.I. Eyler). There is overlap 
between the assessments of those studies and this protocol. Thus, in order to reduce participant 
burden, we will use existing data from those studies instead of asking participants to repeat a 
recently completed assessment battery. Participants will be informed of this as part of the informed 
consent process. 
Participant Inclusion/Exclusion Criteria: Participants will be required to have a minimum 
level of impairment on at least one of the target outcomes, defined as a score of ≥ 3 (moderate) on 
the BPRS depression, mania, hallucinatory behavior, or sociality items. Prior to study entry, 
participants will be on stable medications, defined as the same regimen for at least 60 days and a 
constant therapeutic dose for at least 30 days. Patients enrolled in any current psychotherapy or with 
prior exposure to CBT within the past 5 years will be excluded. All participants must be willing to sign 
a release of information form in order for study staff to be able to inform treating clinicians of 
symptom exacerbations/suicidality. We will exclude participants who are not English-speaking, and in 
the future we will program CBT2go in other languages (e.g., Spanish). Participants must also be able 
to read and manipulate the touch screen device, assessed via direct observation and Snelling eye 
chart performance. Participants with a diagnosis of dementia or head trauma with loss of 
consciousness for greater than 30 minutes will be excluded. The study population is at risk for 
diminished capacity to consent to research, so participants will be assessed for capacity to consent 
for this study with the UBACC test27, developed at UCSD. 
Randomization: Participants will be randomized to CBT2go, EMA-only or Standard Care, 
stratified by diagnosis (BD v. SZ). 
Participants will receive $70 dollars at each assessment (weeks 0, 6, 12, & 24) and a bonus $50 if they 
complete at least 3 assessments for a total of $330 if all assessments are completed. 
Measures Overview: We have selected measures based on 4 criteria: 1) importance for testing our 
conceptual model, 2) psychometric properties, 3) brevity, and 4) demonstrated validity in BD and SZ 
studies. Participants will be assessed at Baseline, 6 weeks, 12 weeks and 24 weeks. 
We propose to add several measures to the protocol as detailed below. 
Summary of Measures (Total estimated time= 4 hours baseline; 2.5 hours follow up): 
Table 1. Summary of Measures in Original and Supplement 
Measure 
Specific Aim 
Construct Assessed 
Time (Min.) 
PARENT STUDY 
MINI 
Inc/Aim 
3 
(Moderator) 
Diagnosis 
25 
Demographics, Meds 
Descriptive 
Sample Characterization 
15 
BPRS 
Aim 1 (Primary) 
Global Psychopathology 
15 
EMA Outcomes 
Aim 2 (Secondary) Mood/psychotic symptom severity, 
medication adherence, 
socialization 
Various 

7 
 
Tablet Routine Quest. 
Aim 2 (Secondary) Self-reported medication 
adherence 
2 
Pharm. Record 
Aim 2 (Secondary) Objective medication adherence 
-- 
Adherence 
Social Functioning Scale 
Aim 2 (Secondary) Social functioning 
30 
PSR Toolkit 
Aim 2 (Secondary) Objective real-world function 
-- 
MCCB (Baseline Only) 
Aim 3 (Moderator) Cognitive Impairment 
60 
Beck Cog. Insight Scale 
Aim 3 (Mediator) 
Self-reflectiveness and evaluation 
10 
Aim 3 (Mediator) 
Maladaptive attitudes 
10 
Dysfunc. Attitudes Scale 
Safety 
Suicidal ideation and behavior 
10 
Columbia Suic. Severity 
NEW MEASURES FROM 
SUPPLEMENT 
10 
Scale for Suicidal 
Supplement 
Aim Suicidal ideation 
(B,6,12,24) 
Ideation 
1,2 
Exploratory 
Deterrents to Suicide 
10 (B, 12) 
Reasons for Living 
Inventory 
Iowa Gambling Task 
Supplement Aim 1 Impulsive decision making 
15 (B) 
UPPS Impulsivity Scale 
Supplement Aim 1 Impulsive traits 
15 (B) 
ER40 
Supplement Aim 1 Social emotion recognition 
5 (B,12) 
Interpersonal Needs 
Supplement Aim 1 Social beliefs related to suicide risk 5 (B,12) 
  Ques. 
Diagnosis and Background Characteristics: Diagnosis will be obtained by administering 
the Mini-International Neuropsychiatric Inventory (MINI)28, rather than the more lengthy SCID. 
Global Psychopathology (Primary Outcome): The primary outcome will be the Brief 
Psychiatric Rating Scale – 24 item expanded version 4.0 (BPRS-24)29. The BPRS-24 is a clinician 
rated measure that includes 24 items that cover depression, anxiety, mania, suicidality, 
delusions/hallucinations, and unusual behavior. 
EMA Measures of Symptoms, Medication Adherence, and Socialization (Secondary 
Outcome): EMA ratings are single-item, thrice daily 1-7 scales (1 “not at all” to 7 “extremely”) for 
severity of depression, voices, and mania, along with medication adherence (binary yes or no 
response) and socialization (number of social interactions). 
Beck Anxiety Inventory (Secondary Outcome): The BAI is a 21-item self-report inventory 
rated on a scale from 0 to 3. This will allow us to determine how the subject has been feeling in the 
last month in terms of severity of anxiety. Each item is related to subjective, somatic, or panic-related 
symptoms of anxiety and the responses range from “not at all” to “severely”30 
Medication Adherence (Secondary Outcome): Self-report: The Medication Adherence 
Rating Scale31 will be used, which asks about the willingness and ability to take your medications 
every day. It has been used to measure medication adherence in psychosis32,33 
Social Functioning Scale (Secondary Outcome): We will assess social function with the 
Birchwood Social Functioning Scale (SFS)34, a 79-item self-report of social functioning across 7 
domains: 1) social engagement, 2) interpersonal behavior, 3) prosocial activities, 4) recreation, 5) 
independence/competence, 6) independence/performance, and 7) employment. The SFS is 
 

8 
 
administered in interview (versus self-report) and best estimate ratings are based on observations 
Specific Levels of Functioning Scale (Secondary Outcome): The SLOF is a 
multidimensional behavioral survey administered to the caseworker or caregiver of a patient with 
schizophrenia35. The scale assesses the patient’s current functioning and behavior across six 
different domains. We will be looking at only 4 of them: Interpersonal Relationships, Social 
Acceptability, Activities of Community Living, and Work Skills. Each of these questions is rated on a 
5-point Likert scale. The lower the total score means the better overall functioning of the patient. 
PSR Toolkit (Secondary Outcome): The PSR Toolkit36 is used to collect objective 
information on employment, residential situation, and hospitalizations/ER visits. The measure 
requires no subject testing burden, because research staff complete the PSR Toolkit (with participant 
release of information) by obtaining medical records, employment status records, visiting residential 
settings to determine level of services (With release of information for each of these obtained). 
Columbia-Suicide Severity Rating Scale (Secondary Outcome): The C-SSRS is a semi- 
structured interview used to measure both behavior and ideation of suicidality37. It is evidence-based, 
and well-supported. 
Cognitive ability (Moderator, Baseline only): Cognitive ability will be measured with the 
MATRICS Consensus Cognitive Battery (MCCB) developed through systematic selection and 
psychometric evaluation of the tests involved38. 
5 Choice-Continuous Performance Task (5C-CPT): The 5C-CPT is a computer task of 
sustained attention and response inhibition that was developed based on a rodent paradigm. 
Suicide Related Phenotypes: As noted above, we already administer the Columbia Suicide Severity Rating 
Scale (CSSRS) Lifetime (baseline) and Interval assessments (follow-ups). The CSSRS is part of the PhenX 
Suicide Specialty Collection. The CSSRS provides indices related to active ideation and behavior, but we lack 
more subtle measures of ideation or protective factors. The SSI will be the primary dependent variable for 
Supplement Aims 1 and 2. 
 
Scale for Suicidal Ideation16 (Baseline, 6, 12, 24): The Scale for Suicide Ideation (SSI) is a 21-item, 
interviewer-administered scale assessing intensity attitudes, behaviors, and plans to commit suicide on 
the day of the interview. This scale will provide additional continuous information about the intensity of 
current ideation beyond that already collected in the CSSRS. We will omit the final 2 questions that 
concern historical attempts, because that information is already gathered by the CSSRS. The SSI is a 
recommended measure from the Suicide Specialty Collection of the PhenX toolkit. 
 
Deterrents to Suicide (Baseline and 12 weeks): The Reasons for Living (RFL)17 inventory is a 48 
item self-report measure of potential reasons for living versus attempting or committing suicide. 
Subscales include coping, family and children, fear of suicide, social disapproval and moral objection. 
The scale is also included in the PhenX toolkit. The total score will be used for analyses and 
exploratory analyses will examine subscales (particularly beliefs about social disapproval or the 
absence thereof) 
Impulsivity Related Phenotypes: We will include, for Aim 1, both behavioral and additional self-report 
measures for impulsivity. These are: 
 
Iowa Gambling Task (Baseline Only): The Iowa Gambling Task18,19 is the most commonly 
administered behavioral task of impulsive decision making and is part of the PhenX Toolkit. It is a 
computer-administered task involving strategy in decision making yielding indices that represent 
advantageous and disadvantageous decisions in a simulated gambling paradigm. The total score is the 
difference between the number of advantageous and disadvantageous choices. A number of studies 
have linked aberrant performance to suicide-related phenotypes20, as well as impairment in 
performance compared to normal controls in SMI21. Due to practice effects, the IGT will only be 
administered at baseline. 
 
UPPS (Baseline only): The UPPS Impulsive Behavior Scale22 contains 59 self-administered 
questions that are scored as five subscales (urgency, premeditation, perseverance, sensation seeking, 
and positive urgency). The UPPS is widely used in the study of adult psychopathology and has been 
 

9 
 
previously associated with increased risk of suicidal behavior, in particular lack of premeditation and 
positive urgency in the presence of negative affect23. The choice of the UPPS over other measures of 
impulsivity (Barratt impulsivity scale) reflected our desire to measure multiple sub-constructs of 
impulsivity in relationship to suicide risk, given prior work identifying differentiation among constructs in 
sucidality. We will use the total score as the primary predictor. As the UPPS reflects trait-like aspects 
of impulsivity, it will only be administered at baseline. 
Social Threat Related Phenotypes: We will include, for Aim 1, both behavioral and additional self-report 
measures for social threat. These are: 
 
ER40 The Penn Emotion Recognition Task (Baseline, 12 weeks). The ER4024 is a measure of 
emotion recognition. It is comprised of 40 photographs of actors expressing one of four basic emotions 
(happiness, sadness, anger, fear) or a neutral expression. Photos are presented in a random order, 
and participants are asked to identify the emotion expressed by each face, and both the response and 
response time are recorded. The primary outcome is the number of correct responses. The ER40 was 
selected as a high performing measure with strong reliability, tolerability and concurrent validity with 
functional outcome in a recent psychometric study of social cognition in schizophrenia (SCOPES 
study)25. We will examine the tendency to over attribute anger to neutral faces as in previous studies26.
 
Interpersonal Needs Questionnaire27 (Baseline, 12 weeks): The INQ measures key constructs in 
the Interpersonal Psychological Theory of Suicide. There are two subcales, Thwarted Belongingness 
and Feeling of Burdensomeness. Of particular import to the proposed study, Thwarted Belongingness 
represents the tendency to feel alienated from others and society. Based on our preliminary data, our 
hypothesis is that social alienation is associated with suicidal ideation in psychopathology associated 
with schizophrenia. Based on prior work comparing versions of the INQ, we opted to use the 15-item 
version of the INQ based on the strengths of its psychometric properties28. The total score on the 
Thwarted Belongingness subscale will be used.
Mediators: Our two mediators, cognitive insight and negative performance beliefs, will be 
measured with the Beck Cognitive Insight Scale (BCIS) and Dysfunctional Attitudes Scale (DAS, 
Form A, both self-report scales. 
Satisfaction Questionnaire (12 week only): Participants in the CBT2go and EMA-only 
conditions will complete seven 5-point Likert-type and 4 open-ended questions (modified from Kimhy 
and colleagues39 and used in our prior research40) about experiences with the device and 
suggestions for future usability. 
Quality Assurance: The PI will train and supervise raters by reviewing videotapes of 
interviews. Consistency between raters will be established prior to data collection using gold standard 
videos, with a standard inter-rater agreement of 0.80. Checks of inter-rater reliability will be 
conducted semi-annually thereafter. To preserve the blinding of the study and minimize rater bias, 
raters will not be involved in the treatment. Participants will also be instructed not to disclose their 
treatment assignment during assessments. If such disclosure is made, the rater will stop the 
assessment and another rater will continue the assessment. 
Intervention Procedures (CBT2go, EMA-Only, and Standard Care Conditions): 
Device: As in previous trials, we will use the touch-screen Samsung Fascinate, a 4G Android 
OS smartphone. These devices will have a data plan (and can receive incoming calls). We will 
provide this device to participants.  Participants will be informed that if they lose or damage the 
device they will not be held responsible. 
Device Training: Device training covers how to operate the device, the meaning of all 
questions and response choices, and procedures for carrying the device and responding to alarms. 
Participants will also be trained in how to access and use crisis lines. This session will be individually- 
tailored to the learning needs of each participant, until participants can complete a trial run and feels 

10 
 
comfortable with the device. The Project Therapist or PI will be available to answer questions every 
day. 
EMA Protocol: Interactions are triggered by a text message sent via an SMS gateway (with 
a “shortcode” referenced to our study), which automatically opens the browser wrapper that displays 
questions and alerts participants with vibration or ringtone. The timing can be adjusted to 
accommodate each participant’s preferences (e.g., sleep and wake schedules) and alarms can be 
silenced for 30-minute intervals (e.g., during driving). All data entries will be time stamped and 
responses recorded in real time. Data are accessible at all times only to study staff on a password 
protected server. If participants stop responding before the end of the questions, the data are still 
recorded; participants cannot “backfill” surveys as they expire in 15 minutes of the terminal alarm. 
Labeled on the back of the device is the investigator contact information and crisis line information. 
Participants will be instructed to answer the surveys and then return with the device at Week 12. 
EMA Questions: Participants will respond to surveys three times per day for 12 weeks. The 
frequency (3 times per day, morning, mid-day, evening) and timing (random initiation at 
approximately 2 hour intervals) of EMA surveys are based on preliminary data described above. In 
each of morning, mid-day, and evening surveys, participants will be prompted to answer multiple- 
choice questions (i.e., they do NOT type in answers) asking: What are you doing? (e.g., working, 
non-physical leisure), Who are you with? (e.g., alone, with family), Where are you? (e.g., at home, at 
work), and 7-point Likert scales are used to rate mood and symptoms (e.g., Are you sad? “Not at all” 
to “Extremely” or Have you been bothered by voices? “No voices” to “Extremely”). They also report 
whether or not they have taken prescribed medications and the number of social interactions since 
the last signal. The format of these questions is identical between EMA-only and CBT2go. 
GPS Data: In addition to sending surveys, the device will be collecting data on the location of the 
participant via GPS. Our purpose in collecting this data is to provide a proxy measure of physical 
activity which we hypothesize will be correlated with self-reported mood and activity ratings. If our 
results are consistent with this hypothesis, there is considerable potential benefit to future mobile 
health care programs in reducing participant burden of manually providing self-report data, if 
unobtrusively gathered data on location can serve as a suitable proxy. The data, which are 
geographic coordinates, are encrypted (base 64 encryption) so that the potential for breach of 
confidentiality is minimized. The data are de-identified and not stored on the local device and so 
therefore cannot be accessed should the device be lost or misplaced. This de-identified data and 
kept in a file separate from other self-reported data in a locked location in a password-protected 
computer. Once we calculate the distance between coordinates obtained, we will erase the data on 
the specific coordinates prior to merging these data with other self-reported data. This process 
mitigates any possibility that individuals could be identified through specific coordinates in case the 
unlikely event that there is a breach of confidentiality of stored data. Participants have the option to 
refuse this action during the consent process and at any time thereafter if they elect to stop this form 
of data collection by notifying the investigator or research staff. 
EMA-only Single In-Person Session: To match the EMA-only and CBT2go conditions for 
therapist contact, after device training at baseline, participants in the EMA-only condition will receive 
standard psychoeducation about their mental illness (reviewing NIMH patient educational material) 
and instructions in accessing community crisis lines and related resources in a single individual in- 
person meeting for one hour and will receive telephone contact every two weeks to troubleshoot 
device operation. 

11 
 
A subset of 30 Bipolar participants in the EMA-only condition who indicate interest on their consent 
form (see below) will be approached about obtaining a total of 3 blood draws and cognitive 
assessments over the first two weeks of the study by participating in two additional encounters. 
During their in-person session, these participants will undergo the consenting process for these 
additional procedures, and if they agree to participate, they will immediately be administered the 5 
Choice Continuous Performance test of attention and have 5 ml of blood drawn by a trained 
phlebotomist on staff. Blood pressure will also be measured. This will add one hour to the in-person 
session for eligible and willing participants. On day 7 (plus or minus 2 days if necessary for 
scheduling) Home Visit 1 will occur in the participant’s home. A phlebotomist will draw a blood 
sample of 5 ml, obtain a blood pressure measurement, and administer the 5 choice continuous 
performance task and digit symbol coding subtest from the MCCB battery. To assess for suicidal 
ideation, participants will be asked to complete the Columbia Suicide Severity Rating scale. Home 
Visit 1 is estimated to last 1 hour. On day 14 (plus or minus 2 days if necessary for scheduling) 
Home Visit 2 will occur with the same assessments as Home Visit 1. Home Visit 2 is estimated to 
last 1 hour. 
CBT2go Condition, Single In-Person Session: After device training, participants in the 
CBT2go condition will participate in a single individual in-person meeting for one hour of contact. 
These sessions will be conducted individually by a Master’s level clinician trained and supervised as 
detailed in below. In this session, education about the generic cognitive model (i.e., that thoughts, 
feelings and behaviors are related) is provided, thoughts and feelings are identified and labeled, and 
patients complete exercises demonstrating how dysfunctional beliefs can impact feelings and 
behavior (e.g., that “Nobody would want to talk to me” leads to sadness and isolation). The notion 
that correcting mistakes in thinking can change undesirable feelings and behaviors to more adaptive 
outcomes is introduced. This session includes a structured interview that elicits unhelpful and helpful 
beliefs associated with mood and psychotic symptoms, medication adherence, and social activities. 
Evidence used to challenge unhelpful beliefs is garnered (“You said depression always goes away 
eventually”), as well as a behavioral experiments that can be employed (“Try ignoring the voices and 
keep track of how you feel”). Participants provide at least three benefits of taking medications and 
socializing, and at least three coping strategies for depression, manic symptoms, or voices (if 
present). This information is used to create personalized thought-challenging messages (“But you 
said taking medications helps you to [personalized benefit]”). For Relapse Prevention, participants 
identify at least 3 illness triggers or early warning signs of illness exacerbations and form 
implementation intention statements around these – these are simple “if-then” statements that specify 
a thought or action that can be taken and the benefit of doing so (“If my mother starts to stress me, 
then I will take a walk outside so I can avoid an argument”). These statements are programmed to 
the device from a secure website and used in the automated CBT2go interventions. 
CBT2go Condition, Automated Interventions: In CBT2go, responses to surveys branch to 
intervention content with a focus on challenging dysfunctional beliefs. For instance, if a patient 
reports that s/he missed a medication dose because “medication is not helpful”, a personalized 
message is presented that challenges accuracy of this belief and the consistency of the non- 
adherence behavior with previously established values (“You said taking your medication has helped 
improve your sleep before and that you valued getting a good night’s rest”). Similarly, if a patient 
reports that auditory hallucinations cannot be controlled, personalized contradictory evidence to 
challenge the belief is presented (“But talking with your mother has quieted your voices in the past.”). 
Moreover, for illness triggers that have been identified, “if-then” statements provide strategies that 
were successful in the past (“when you’ve felt lonely, it helped to take the dog for a walk”). Patients 
are also reinforced by the mobile device for endorsing freedom from symptoms for when describing 

12 
 
positive states (e.g., “What is helping?”). 
Technical and Follow-Up Support (EMA-only and CBT2go): Participants will be contacted 
by phone in the first week after receiving the device and thereafter every two weeks to briefly check 
in (target 10 minutes) about their experience with the device. Although this contact is minimal, 
substantial research suggests human oversight of technology-based interventions is associated with 
greater adherence and efficacy41-43. In case of crises (see Human Subjects for safety precautions) or 
difficulties with the device, participants can notify Project Manager or PI through the device, and a log 
will be kept of all ad-hoc contacts. Participants can obtain a new device at no cost in case of 
malfunction or loss. 
Standard Care Condition: Participants will not be provided with a device or receive any study 
interventions, but will receive all study assessments and continue to participate in all ongoing 
treatments in the community. As seen Human Subjects, participants in crisis will be evaluated and 
referred to services. 
Intervention Fidelity: We will address the relevant components of Treatment Integrity: 
Competence, Therapist and Participant Adherence, and Treatment Differentiation43. Competence will 
be addressed by requiring the Project Therapist to have at least a Master’s level of training, previous 
clinical experience with SMI, and attend a full day training on the intervention by Drs Depp, 
Perivoliotis, and Granholm. Therapist Adherence to the manualized protocol will be assessed via 
audiotapes, supervision, and submitted checklists measuring conformance to session content. 
Therapist adherence will be monitored by Dr. Perivoliotis via audiotape for 25% of randomly-selected 
participants on an ongoing basis. Participant adherence is assessed objectively via device obtained 
data. Treatment Differentiation is assessed by blinded random selection of 25% of audiotapes 2/year 
and ratings by Dr. Depp the conformance of sessions to condition assigned. Any observed carry- 
over effects result in ad-hoc retraining in the elements of each of the active conditions. Participants 
will be asked to sign a separate consent to have these contacts audiotaped. Participants can still 
participate in the study if they elect not to be audiotaped. 
Intervention Fidelity: We will address the relevant components of Treatment Integrity: 
Competence, Therapist and Participant Adherence, and Treatment Differentiation43. Competence will 
be addressed 
10. 
HUMAN SUBJECTS 
We will recruit 255 participants in the according to the table below, with Year 5 for completing 
interventions, follow-up assessments, and the implementation component of the project. 
Complete Inclusion/Exclusion Criteria are as follows: 
Participants in this study will be included if: male or female, any race/ethnicity and age 18-65; have a 
DSM-IV-TR diagnosis of BD, SZ, or schizoaffective disorder based on the MINI; minimum level of 
impairment on at least one of the target outcomes, defined as a score of ≥ 3 on the BPRS 
depression, mania, hallucinatory behavior, or asociality items; current outpatient participation in 
 
Recruitment Goals and Number of Contacts (i.e., Intervention and Assessments) 
Year 1 
Year 2 
Year 3 
Year 4 
Year 5 
CBT2go Intervention Condition 
15 
23 
24 
23 
0 
EMA-Only Condition 
15 
23 
24 
23 
0 
Standard Care Condition 
15 
23 
24 
23 
0 
Total In-Person Contacts/year 
180 
276 
288 
276 
138 

13 
 
routine psychiatric care and on stable medications, defined as the same regimen for at least 60 days 
and a constant therapeutic dose for at least 30 days; willing to sign a release of information form in 
order for study staff to be able to inform treating clinicians of symptom exacerbations/suicidality; able 
to speak and read English ; and capable of and willing to provide signed informed consent and pass 
the UBACC test for decisional capacity for research (see below). 
Participants will be excluded if: diagnosis of dementia or past head trauma with loss of 
consciousness for > than 30 minutes; cannot complete the assessment battery; visual acuity 
(assessed with Snellen chart) and manual dexterity sufficient to navigate a touch screen device. 
INCLUSION OF WOMEN AND MINORITIES 
According to the 2010 US Census, for adults in San Diego County, 47% were male and 71% were 
Caucasian. We will strive to achieve a similar sample composition, so that the data will generalize to 
the larger population. In our preliminary studies, the proportion of patients who identified as 
Caucasian was 72% and the proportion of men was 52%. Notably, our sample ascertainment for the 
proposed study will be more likely to include members of ethnic minorities, as we will be recruiting 
directly and exclusively from the San Diego County Mental Health System. As described in a recent 
Annual Report of San Diego County Mental Health (viewable at 
http://www.sdcounty.ca.gov/hhsa/programs/bhs/documents/AMHS_0809.pdf), a total of 48% of 
system users were members of ethnic minority groups (Hispanic/Latino, 19%; African-American, 
12%). The gender distribution of San Diego County Mental Health users was evenly divided among 
men and women. Therefore, we anticipate being able to recruit an ethnically diverse sample with 
equal proportions of men and women. Neither gender nor ethnicity will be a criterion for inclusion or 
exclusion of subjects. We will continuously monitor the gender distribution for this study, as well as 
the ethnicity characteristics of the sample as it accrues. We will keep all research assistants and 
referral sources informed regarding our progress and our current priorities for recruitment of women 
and minorities. Thus, we plan to have an ongoing process through which we ensure that women and 
minorities are included and appropriately represented. 
INCLUSION OF CHILDREN 
We will include children between the ages of 18 and 21. Patients younger than 18 will not be 
included, since the use of such subjects would require modification of the neuropsychological battery, 
psychiatric interview and functional assessments, thereby substantially changing the research 
design. Further, the functional abilities of individuals under the age of 18 tend to be different than 
those of adults and expectations regarding the type and nature of social interactions, independent 
living, and financial self-support are notably different under the age of 18. 
11. 
RECRUITMENT 
Recruitment of participants and informed consent procedures will follow established methods in 
previous ACISIR studies. The referral sources for this study will be the clinics and other outpatient 
service sites of the San Diego County Adult and Older Adult Mental Health System (AOAMHS), 
which serves over 43,000 persons per year (see Resources). Our recruitment efforts will include 
community clinics with mental health clinics throughout the San Diego County AOAMHS that serve 
primarily Hispanic and African American populations. Participants will be recruited by a variety of 
methods, including direct referrals from providers, posted flyers and informative brochures, staff in- 
services and community outreach meetings. These recruitment methods have been honed in our 
long-standing academic-community partnership with the San Diego County Mental Health System as 
described in our previous publications44-46 

14 
 
Upon contact with staff, potential participants will undergo a brief telephone screening interview (or 
in-person in rare cases), during which the Project Manager will introduce the study and review the 
inclusion/exclusion criteria and study procedures. If the participant is appropriate for inclusion into the 
study and interested in participation, a staff member will describe the requirements of the study, 
including questionnaires, assessments, and randomization to interventions. In all cases, fully 
informed consent will be obtained and Dr. Depp and other co-investigators will be directly available to 
answer questions, should any be raised by the participant. 
BD participants who have been randomized to the EMA-only condition who have indicated on their 
consent that they are willing to learn about participating in additional procedures (blood draws and 
home visits for the first 2 weeks) will be approached at their single in-person session to undergo the 
consent process for these assessments. 
12. 
INFORMED CONSENT 
Individuals are provided with a copy of the consent document and a copy of the Experimental 
Subject’s Bill of Rights. Potential participants are encouraged to ask questions throughout this 
process. Those who are eligible are fully informed and consented for the full study and provided with 
a copy of that consent documentation. All research subjects are informed regarding applicable 
HIPAA protections and sign a separate HIPAA document. To enhance comprehension, the informed 
consent documents are written at the 8th grade level of language. All participants will informed of the 
possibility of additional compensated procedures for an eligible subset of participants, and will be 
asked to indicate their interest in learning about these home visits and blood draws (described 
above).Informed consent will be documented with the IRB-approved written consent form that each 
participant will sign prior to participation. Signed and witnessed consent forms will be kept on file in a 
specially secured cabinet. 
Our screening protocol contains a direct assessment of decisional capacity, in light of the elevated 
base rate of cognitive impairment among participants with bipolar disorder or schizophrenia that can 
lead to diminished capacity to understand, appreciate, and apply sound reasoning in the decision to 
participate in research. In order to ensure that all participants have adequate decisional capacity to 
participate in this research study, we will administer the University of California San Diego Brief 
Assessment of Capacity to Consent (UBACC)29, which is a 10-item questionnaire that is tailored to 
the specific procedures of the study. This measure queries participants about the basic procedures, 
risks, benefits, and purpose of the study, along with participant rights. 
If a potential participant is unable to achieve a perfect score on the first or second administration of 
the quiz or if there is any other reason to suspect that the individual may lack the capacity to give 
informed consent because of decisional impairment, that individual is assessed by a study clinician. 
The final determination regarding decision-making capacity is made by the clinician and documented 
in the research record. If an individual is unable to demonstrate the capacity to consent as detailed 
above, the individual will be excluded from the present study. 
13. 
ALTERNATIVES TO STUDY PARTICIPATION 
Participating in the study will not alter participant’s care. For participants who are interested we will 
provide referrals to them for community mental health providers and the free depression bipolar 
support group held weekly at the VA Hospital. Alternative to study participation is to not participate in 
this study. 
14. 
POTENTIAL RISKS 
 

15 
 
Assessment: The interviews, questionnaires, computer-based assessments, and 
neuropsychological tests are non-invasive clinical assessments associated with minimal risk. All 
measures are physically non-invasive, have been used in prior studies with seriously mentally ill 
participants, and have been found to elicit minimal distress and discomfort. Nevertheless, 
participation in the psychosocial evaluation and responding to questions on the mobile device will 
require time and attention. Some participants may become bored or fatigued completing the 
evaluation. Some participants may also become distressed during the psychiatric evaluation, which 
requires them to discuss their current symptoms, as well as the history of their symptoms. 
Intervention: Risks involved in participating in this intervention are minimal. During the Baseline 
assessment and follow-up assessments, participants may experience feelings of anxiety or 
discomfort while talking about themselves and/or symptoms. Participants may also become fatigued 
by filling out questionnaires or answering questions in person, or, if they are randomized to the 
experimental conditions that involve mobile devices, on the device. 
Confidentiality: As with any intervention study, a risk of disclosure of personal material exists. 
Blood Draw: A subset of interested subjects in the EMA-only condition will be asked to give 3 blood 
samples over the course of their participation. For most individuals, needle punctures for blood draws 
do not cause any serious problems. However, there is a small risk of bleeding, bruising, discomfort, 
infections and/or pain at the needle site or dizziness. 
15. RISK MANAGEMENT PROCEDURES AND ADEQUACY OF RESOURCES 
Assessment: During in-person interviews, trained raters will closely monitor for signs of stress, 
fatigue, and distress. Rest breaks will be provided as needed during all assessments to reduce 
fatigue and boredom. Also, subjects may refuse to answer any specific questions or to complete any 
given tests. We provide snacks, water and recommend breaks to participants if they report feeling 
fatigue. We also provide participants the option of splitting the assessments, particularly the baseline 
assessment which is longer than the other assessments, on different days. They will also be advised 
that they can withdraw from the study at any point and can still receive the compensation. If a 
participant discloses that he or she is experiencing suicidal ideation during diagnostic interviewing or 
on standard clinical measures, the rater will immediately contact the PI to ensure that steps are taken 
to ensure the participant’s safety. The two measures that directly elicit information about current 
suicidal thoughts are the Columbia Suicide Severity Rating Scale and the Scale for Suicide Ideation. 
Any report of ideation on these instruments that exceeds “none” will result in an immediate contact to 
the PI to ensure participant safety.  These steps will include a formal risk assessment and may lead 
to contacting the participant’s providers (with signed consent to do so) and arranging emergency care 
for the participant. Our research center has a Clinical Response Team (of which the PI is the 
Associate Director) that will provide additional back-up; this team includes board-certified 
psychiatrists and psychologists who will are available and on site at all times. 
In-Person Session (CBT2go): The Project Therapist will receive intensive training from supervising 
psychologists and will be provided supervision on a weekly basis by Dr. Perivoliotis. Participants will 
be closely monitored and additional (in session) assistance will be provided to those participants 
experiencing frustration or distress. Should a participant be observed to be exhibiting an acute 
symptom exacerbation and/or suicidal or homicidal ideation, the Project Therapist member will notify 
Drs. Perivoliotis or Depp immediately and they will conduct a formal evaluation of the participant with 

16 
 
additional back-up from the Clinical Response Team. Given that all participants must be currently 
participating in stable outpatient care, the need for immediate emergency services will be unlikely. 
Nevertheless, based on our experience conducting clinical research in serious mental illness, we 
have developed the above plan to intervene appropriately should such a need arise. 
Experimental Conditions (Week 1 through Week 12): Participants in the CBT2go and EMA-only 
conditions will be provided a smart-phone device with which to answer questions about their mood, 
activities and contexts. After baseline interview (and in-person session if in the CBT2go condition), 
participants will be asked to respond to questionnaires on the device until Week 12. Participants in 
the Standard Care condition will not be provided a device. We have taken several steps to ensure 
participant safety during the periods of no in-person contact. All participants will be provided with staff 
contact information and emergency resources in a printed manual, and they will be instructed that 
they may call the PI or project manager at any time in case of questions or emergencies. Participants 
must provide release of information for our staff to contact treating psychiatrists or other appropriate 
healthcare provider, so any emergent crises will be relayed to that participant’s provider. In the 
CBT2go and EMA-only condition, responses at the severe spectrum of the mood or voices scales are 
accompanied with a screen that instructs participants to contact both emergency services (911 can 
be directly accessed via the device) AND project staff, if in crisis. We will monitor these protocols 
during the course of the study and will make adjustments to inclusion/exclusion criteria in case of 
adverse events. 
Data and Safety Monitoring Board: The study will be reviewed annually through the UCSD DSMB. 
The board consists of non-UCSD faculty in psychiatry, community members, and bioethicists. 
Blood Draw: Blood samples will be drawn only by research staff trained and certified in phlebotomy. 
Staff will take care to assure the participant is comfortable and participants will be provided with the 
necessary medical equipment (e.g. band-aids) to care for any irritation at the site of the blood draw. 
16. PRIVACY AND CONFIDENTIALITY CONSIDERATIONS INCLUDING DATA ACCESS AND MANAGEMENT 
Confidentiality: In order to protect confidentiality, all participant data will be de-identified by 
assigning each participant a unique ID in computer files, and all physical files from the study will be 
kept in a locked cabinet in our offices at the Stein Clinical Research Building at UCSD. All electronic 
data and files will be stored on a secure server. Only study investigators and personnel will have 
access to these data. All documentation will identify participants only by their Unique ID number and 
not other personally identifying information. 
On the device, participant data is not stored locally and cannot be accessed by anyone if the device 
is lost or stolen. Data are encrypted upon transfer to our server and linked by unique ID that is de- 
identified. Since we will be providing the devices to participants, there is no risk of loss of 
confidentiality associated with access to personal telephone numbers. Should the participants lose 
the device, we have taken the additional step of incorporating the Auto wipe application on all study 
deices which enables remote factory reset of the device, erasing all data. If participants lose or 
damage the device, they will not be held responsible for the cost of the device or any other costs. 
Data and Safety Monitoring Plan 
Data safety will be of utmost importance in this project. Data will be coded by subject number only 
and will be filed in locked file cabinets in locked staff offices. In addition, signed consent forms will be 
filed in a separate location from the raw data. A codebook linking subject identifying information with 

17 
 
subject number will be kept on a computer that is password protected and, within that, a file that is 
password protected. 
Adverse events in this research project are expected to be extremely rare. However, we have 
established plans for resolving any adverse event should one occur. First, during screening for the 
project, trained research personnel will assess (using standardized screening tools) for any serious 
medical or psychological conditions that may require immediate medical attention or psychiatric 
treatment. The rationale for this is because the presence of serious medical or psychiatric conditions 
would make these individuals inappropriate for the proposed research study. Should attention be 
required, staff will provide these individuals with information about suitable referrals, including local 
hospitals, clinics, and/or relevant health-care and mental health professionals, and they will strongly 
encourage the individuals to follow up with these referrals. 
Second, UCSD’s IRB requires regular updates on the status of research projects, including the 
number of participants enrolled, adverse events or unanticipated problems, number of withdrawals 
from the project, complaints about the research, and any protocol changes. The IRB also monitors 
the consent forms and ensures that appropriate HIPAA information is included. 
Third, the Data and Safety Monitoring Board of the Research Center will review the project yearly. 
Taken together, use of these methods should allow for adequate evaluation of, and response to, both 
potential enrollees and actual participants. 
17. POTENTIAL BENEFITS 
As these are experimental interventions, there may be no direct benefit to participants. However, 
benefits to the individual participants may include decreased emotional distress and improved 
functioning from cognitive and behavioral changes facilitated by the interventions. Participants may 
gain an increased understanding of the role thoughts and behaviors play in the symptoms of 
schizophrenia or bipolar disorder and may learn to reduce their symptoms by changing these 
thoughts and behaviors. 
18. RISK/BENEFIT RATIO 
The risks of this proposal are minimal. Protection of subject confidentiality and privacy are rigorously 
guarded by the assignment of coded numbers to each subject's data. Keys to these codes are stored 
in a locked file cabinet in the Stein Clinical Research Building. The dangers of adverse effects 
associated with this intervention are minimal. The benefits to the individual participants may be 
minimal, but may include decreased emotional distress from behavioral changes that they achieve. 
We judge the importance of knowledge resulting from this study and the potential for maximizing 
independence among psychiatrically stable individuals with bipolar disorder or schizophrenia to be 
quite significant; therefore, the risk to benefit ratio is low. 
19. EXPENSE TO PARTICIPANT 
There are no expenses to the participants. Participants will not be asked to pay for the device if it is 
lost or broken. 
20. COMPENSATION FOR PARTICIPATION 
Patients will be assessed (4-hour battery) at baseline, and a 2.5 hour testing battery at mid-point (6 
weeks), post-treatment (12 weeks) and 3-month follow up (24 weeks) and paid $70 for each 
assessment (there is no payment for treatment participation). 
Participants will be provided a total of $330 for completing all assessments – the compensation 

18 
 
structure is graded such that a $50 bonus is provided for returning the device or attending all of the 
assessments. If the participant elects to drop out of the study, s/he will be offered the opportunity to 
return the equipment and complete assessment for $50 compensation and will be notified that the 
mobile device will be deactivated remotely. 
The SLOF questionnaire has three versions which are completed by the interviewer, the participant, 
and an informant of the participant. We will be providing informants with a small gift for completing 
the SLOF at each visit (baseline, 6 week, 12 week, and 24 week follow up). The gift will most likely 
be a small box of chocolates or some sort of snack valued less than 5 dollars 
Those BD participants in EMA-only group who agree to participate in additional cognitive testing and 
blood draws over a 2 week period will be compensated an additional $150.00. They will receive 
$40.00 at the baseline visit, $40.00 at home visit 1 and the remaining $70.00 at home visit 2. 
21. PRIVILEGES/CERTIFICATIONS/LICENSES AND RESEARCH TEAM RESPONSIBILITIES 
Colin A. Depp, Ph.D.: UCSD Dept. of Psychiatry. Dr. Depp is a researcher in the department of 
psychiatry and is a licensed clinical psychologist with clinical privileges at UCSD Medical Center and 
the San Diego VA. 
Eric Granholm, Ph. D., UCSD Dept. of Psychiatry. Dr. Granholm is a researcher in the department of 
psychiatry and is a licensed clinical psychologist. 
Dimitri Perivoliotis, Ph.D. UCSD Dept. of Psychiatry. Dr. Perivoliotis is a researcher in the 
department of psychiatry and is a licensed clinical psychologist. 
Wes Thompson, Ph.D. UCSD Dept. of Psychiatry. Dr Thompson is an assistant professor in the 
department of psychiatry and a statistician. 
Lisa T. Eyler, Ph.D. UCSD Dept. of Psychiatry. Dr. Eyler is a researcher in the department of psychiatry 
and is a licensed clinical psychologist. 
Cris Achim, Ph.D., UCSD Dept. of Psychiatry. Dr. Achim is a researcher in the department of psychiatry 
and will oversee the processing of collected blood samples. 
Benchawanna Soontornniyomkij, Ph.D., UCSD Dept. of Psychiatry. Dr. Soontornniyomkij is a 
researcher in the department of psychiatry and will be conducting the blood assays. 
Dilip V. Jeste, M.D. UCSD Dept. of Psychiatry. Dr. Jeste is a researcher in the department of 
psychiatry, as well as California licensed and board certified geriatric psychiatrist. 
Jason Holden, Ph.D.: Project Coordinator 
Rosa Gutierrez, B.A.: Psychometrist 
Mary Linges: Psychometrist 
Jennifer Villa, Student Assistant, will be providing general lab assistance. She will also be trained in 
administering assessments and help staff with contacting participants. 

19 
 
Shirleen Cheng, trained and licensed phlebotomist, will administer informed consent, administer 
clinical and cognitive assessments, and perform blood draws to a subset of BD participants. 
Sheena Dev, B.S., and Ashley N. Sutherland, M.A., will be involved in consenting and administering 
clinical and cognitive assessments to the subset of 30 BD subjects who elect to participate in the 
blood draws. 
Savannah Raye, Student Assistant, will be providing general lab assistance, such as data entry and 
other office duties. 
Yang Jiao, Student Assistant, will be providing general lab assistance, such as data entry and other 
office duties. 
22. BIBLIOGRAPHY 
LITERATURE CITED 
1. 
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2009;43(11):987-996. 
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Shiffman S. Ecological Momentary Assessment. Annu Rev Clin Psychol. Mar 6 2006. 
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Granholm E, Loh C, Swendsen J. Feasibility and validity of computerized ecological momentary assessment in schizophrenia. 
Schizophrenia Bulletin. May 2008;34(3):507-514. 
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Murray CJ, Lopez AD. Global mortality, disability, and the contribution of risk factors: Global Burden of Disease Study. 
Lancet. May 17 1997;349(9063):1436-1442. 
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Miller B, Paschall CB, Svendsen D. Mortality and medical comorbidity among patients with serious mental illness. Psychiatric 
Services. 2006;57(10):1482-1487. 
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Colton CW, Manderscheid RW. Congruencies in increased mortality rates, years of potential life lost, and causes of death 
among public mental health clients in eight states. Preventing chronic disease. Apr 2006;3(2):A42. 
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Wu EQ, Birnbaum HG, Shi L, et al. The economic burden of schizophrenia in the United States in 2002. The Journal of clinical 
psychiatry. Sep 2005;66(9):1122-1129. 
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Dilsaver SC. An estimate of the minimum economic burden of bipolar I and II disorders in the United States: 2009. Journal of 
Affective Disorders. Mar 2011;129(1-3):79-83. 
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Pfammatter M, Junghan UM, Brenner HD. Efficacy of psychological therapy in schizophrenia: conclusions from meta- 
analyses. Schizophrenia Bulletin. Oct 2006;32 Suppl 1:S64-80. 
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Gregory VL, Jr. Cognitive-behavioral therapy for depression in bipolar disorder: a meta-analysis. Journal of evidence-based 
social work. Jul 2010;7(4):269-279. 
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Szentagotai A, David D. The efficacy of cognitive-behavioral therapy in bipolar disorder: a quantitative meta-analysis. The 
Journal of clinical psychiatry. Jan 2010;71(1):66-72. 
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Wykes T, Steel C, Everitt B, Tarrier N. Cognitive behavior therapy for schizophrenia: effect sizes, clinical models, and 
methodological rigor. Schizophrenia Bulletin. May 2008;34(3):523-537. 

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13. 
Drake RE, Bond GR, Essock SM. Implementing evidence-based practices for people with schizophrenia. Schizophrenia 
Bulletin. Jul 2009;35(4):704-713. 
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Depp C, Mausbach B, Granholm E, et al. Mobile Interventions for Severe Mental Illnesses: Preliminary Data from Three 
Approaches. Journal of Nervous and Mental Disease. 2010;198(10):715-721 
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Granholm E, Ben-Zeev D, Link PC, Bradshaw KR, Holden JL. Mobile Assessment and Treatment for Schizophrenia (MATS): 
A Pilot Trial of An Interactive Text-Messaging Intervention for Medication Adherence, Socialization, and Auditory 
Hallucinations. Schizophrenia Bulletin. May 2012;38(3):414-425. 
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Miller IW, Norman WH, Bishop SB, Dow MG. The Modified Scale for Suicidal Ideation: reliability and validity. Journal of 
Consulting and Clinical Psychology. 1986;54(5):724. 
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Linehan MM, Goodstein JL, Nielsen SL, Chiles JA. Reasons for staying alive when you are thinking of killing yourself: the 
reasons for living inventory. Journal of consulting and clinical psychology. 1983;51(2):276. 
18. 
Bechara A. Iowa gambling task professional manual. Psychological Assessment Resources, Inc. 2007. 
19. 
Toplak ME, Sorge GB, Benoit A, West RF, Stanovich KE. Decision-making and cognitive abilities: A review of associations 
between Iowa Gambling Task performance, executive functions, and intelligence. Clinical psychology review. 2010;30(5):562- 
581. 
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Jollant F, Bellivier F, Leboyer M, et al. Impaired decision making in suicide attempters. 2014. 
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Malloy-Diniz LF, Neves FS, Abrantes SSC, Fuentes D, Corrêa H. Suicide behavior and neuropsychological assessment of 
type I bipolar patients. Journal of Affective Disorders. 2009;112(1):231-236. 
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Whiteside SP, Lynam DR, Miller JD, Reynolds SK. Validation of the UPPS impulsive behaviour scale: a four-factor model of 
impulsivity. European Journal of Personality. 2005;19(7):559-574. 
23. 
Klonsky ED, May A. Rethinking impulsivity in suicide. Suicide and Life-Threatening Behavior. 2010;40(6):612-619. 
24. 
Kohler CG, Turner TH, Bilker WB, et al. Facial emotion recognition in schizophrenia: intensity effects and error pattern. 
American Journal of Psychiatry. 2003;160(10):1768-1774. 
25. 
Pinkham AE, Penn DL, Green MF, Harvey PD. Social Cognition Psychometric Evaluation: Results of the Initial Psychometric 
Study. Schizophrenia bulletin. 2015:sbv056. 
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Pinkham AE, Brensinger C, Kohler C, Gur RE, Gur RC. Actively paranoid patients with schizophrenia over attribute anger to 
neutral faces. Schizophrenia research. 2011;125(2):174-178. 
27. 
Van Orden KA, Cukrowicz KC, Witte TK, Joiner Jr TE. Thwarted belongingness and perceived burdensomeness: Construct 
validity and psychometric properties of the Interpersonal Needs Questionnaire. Psychological Assessment. 2012;24(1):197. 
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Hill RM, Rey Y, Marin CE, Sharp C, Green KL, Pettit JW. Evaluating the Interpersonal Needs Questionnaire: comparison of 
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Arch Gen Psychiatry. Aug 2007;64(8):966-974. 

21 
 
23. FUNDING SUPPORT FOR THIS STUDY 
NIMH Grant MHR01 100417; NIMH Grant Supplement MH 100417 
24. BIOLOGICAL MATERIALS TRANSFER AGREEMENT 
As described above, we will obtain three 5 ml blood samples from a subset of willing BD participants. 
Blood will be drawn into a blood collection tube and placed in a biohazard container for 
transportation. The staff phlebotomist will transport the specimen directly to Dr. Cris Achim’s 
laboratory at UCSD immediately after visit completion and the blood samples will be stored at room 
temperature until assay. 
25. INVESTIGATIONAL DRUG FACT SHEET AND IND/IDE HOLDER 
Not applicable 
26. IMPACT ON STAFF 
There is no anticipated impact on staff at UCSD 
27. CONFLICT OF INTEREST 
None 
28. SUPPLEMENTAL INSTRUCTIONS FOR CANCER-RELATED STUDIES 
None 
29. OTHER APPROVALS/REGULATED MATERIALS 
Not applicable 
30. PROCEDURES FOR SURROGATE CONSENT AND/OR DECISIONAL CAPACITY ASSESSMENT 
There will be no surrogate consent obtained in this study. 
Our screening protocol contains a direct assessment of decisional capacity, in light of the elevated 
base rate of cognitive impairment among participants with bipolar disorder or schizophrenia that can 
lead to diminished capacity to understand, appreciate, and apply sound reasoning in the decision to 
participate in research. In order to ensure that all participants have adequate decisional capacity to 
participate in this research study, we will administer the University of California San Diego Brief 
Assessment of Capacity to Consent (UBACC)29, which is a 10-item questionnaire that is tailored to 
the specific procedures of the study. This measure queries participants about the basic procedures, 
risks, benefits, and purpose of the study, along with participant rights. 
If a potential participant is unable to achieve a perfect score on the first or second administration of 
the quiz or if there is any other reason to suspect that the individual may lack the capacity to give 
informed consent because of decisional impairment, that individual is assessed by a study clinician. 
The final determination regarding decision-making capacity is made by the clinician and documented 

22 
 
in the research record. If an individual is unable to demonstrate the capacity to consent as detailed 
above, the individual will be excluded from the present study.