This is a non-randomized, natural history, non-treatment, longitudinal cohort study.
Participants will be receiving standard of care treatment for depression and other
comorbidities from their treating clinician and will be allowed to continue such
treatments in this study. There are no experimental study procedures, other than methods
used for data capture (questionnaires, blood collection, EEG and MRI). Participants will
be expected to visit study site (s) for repeated collection of data (assessments,
biospecimens, and imaging procedures), up to 4 times a year for 10 years. A reduced
battery of tests is allowable if subject is not able or willing to complete the full
battery after the baseline visit.
2000 research participants will be enrolled and followed over an eight-year period (each
participant will be followed for 10-years) with collection of clinical and depression
measurement assessments, measurement of vital signs, collection of biospecimens for
biochemical and genetic analyses, electroencephalogram (EEG) with behavioral assessments,
and neuroimaging using magnetic resonance imaging (MRI). Skin punch biopsy will be
performed in a sub-set of the research cohort, defined as demonstrating a heritable
phenotype of depression. Stool sample will be performed in a sub-set of the research
cohort, defined as demonstrating a heritable phenotype of depression.
Participants will complete PHQ-9 (Patient Health Questionnaire-9), a brief
self-administered measure of depression severity, and PS (Psychosis Screening)
questionnaire, as part of inclusion and exclusion criteria, respectively. Participants
will then complete all required computer-assisted self-rating and clinician-administered
instruments. The self-rating instruments are expected to take approximately 2.5 hours
using an iPad or laptop computer, and will collect detailed socio-demographic, life
habits, family and medical history, and depression severity and treatment history. After
completing the questionnaires, the research personnel will measure the subject's blood
pressure, height, waist and hip circumference and weight. The subject will then provide
blood, saliva and urine samples (morning blood draw appointments will be offered whenever
participants agree to fast before blood draws but non-fasting blood will also be
collected, when not possible to obtain fasting blood).
For study assessments, specimen collection; and EEG and behavioral phenotyping, Dallas 2K
study participants will require a 6-hour study visit to UT Southwestern. Participants
will be given the option to split their visit into two if that is more convenient, and
visit 2 will be used to perform EEG and behavioral assessments. Participants choosing the
initial visit at an MDN clinician's office will complete screening, assessments and
biospecimen collection at the MDN office but may require a 3-hour visit to UT
Southwestern clinics for EEG and behavioral assessments. The MRI may be performed during
a separate 2-hour visit to UT Southwestern MRI facility.
Schedule of study visits, procedures and duration:
Study A - Assessments and Questionnaires, 3 hours; Study B - EEG and Behavioral
Phenotyping, 3 hours; Study C - Neuroimaging (MRI), 2 hours; Study D - Sub-Study only:
Skin punch biopsy, 30 minutes; Study E - Sub-Study only: Stool Sample, 15 minutes; Study
F - Sub-Study only: mHealth, Continuous monitoring via a wristband (i.e. fitbit) and/or
mhealth application downloaded on a Android operating smartphone.
Studies A and B can be combined into a single 6-hour visit when occurring at UT
Southwestern.
EEG and behavioral phenotyping and Neuroimaging will be performed at 3-month intervals.
For participants in the optional sub-study, skin punch biopsy, Study D will be performed
during any one of the other visits, depending on participants' convenience.
For participants in the optional sub-study stool sample, study E will be performed up to
4 visits per year for 10-years.
For participants in the optional sub-study mhealth study, Study F will be a continuous
monitoring of your physical activity, sleep patterns etc. via a wristband (i.e. Fitbit)
and/or mHealth application downloaded onto an Android operating Smartphone.
In addition, monthly remote assessments are completed between onsite visits starting from
the baseline visit.
Study A will then be repeated at 3-month intervals for up to 4 times a year, during
follow-up study visits.
Phlebotomy Procedures Blood samples will be collected from participants by trained
phlebotomists, who will draw the sample using standard venipuncture procedures, through a
single venipuncture using a small gauge needle. Universal precautions will be observed by
the phlebotomists during all draws. The sample collection tubes, priority and volume
collected are indicated in the protocol. Each tube will be labeled and packaged for
processing and storage.
Electrophysiology (EEG) Procedures: Participants will undergo electrophysiology measures
at baseline and at 3-month intervals. Procedures for each of these measures are outlined
below. Detailed EEG procedures will be described in the EEG and Behavioral Tasks
Procedures Manual, respectively. The EEG markers in this study can be divided into three
groups. Participants will first undergo resting EEG. Resting EEG is measured during four,
2 minute periods, half the time with the participants' eyes open, and the other half with
the participants' eyes closed. The second EEG measure will specifically localize theta
activity using a technique called Low Resolution Electromagnetic Tomography (LORETA).
Finally, participants will have head-phones placed, and will be presented with 1000 Hz
tones at 5 different intensity levels. The loudness dependency of auditory evoked
potential (LDAEP) will be measured during this time. The total time estimate for
completion of the EEG collection at each visit is approximately 2 hours. The EEG
workgroup will ensure that adequate training, standardization of measures, and validation
of equipment is maintained for data consistencies and quality control purposes.
Behavioral Phenotyping: The investigators will administer five distinct tasks to
participants, to assess four domains: 1) psychomotor slowing, 2) cognitive control, 3)
working memory, and 4) reward responsiveness. To assess these domains, the investigators
plan to administer the following tasks: psychomotor slowing, Choice RT task (5 min) and
word fluency task (5 min); cognitive control, the Flanker task (10 min); working
memory, the A not B task (10 min); and reward responsiveness, the Probabilistic Reward
task (~10 min). This task measures the subject's ability to modify behavior in response
to rewards. On each trial, the subject sees a cartoon face with a short or long mouth.
The task is to indicate whether a short or long mouth was presented by pressing one of
two buttons. Critically, the size difference between the short and long mouths is very
small, and correct responses of one type (e.g., short mouth) are followed by monetary
rewards three times more frequently than correct responses of the other type (e.g., long
mouth). The primary dependent measure is response bias: the degree to which the subject
preferentially chooses the response that is more frequently rewarded (in this example,
short mouth vs. long mouth). Other dependent measures include RT and a measure of the
subject's ability to discriminate between the mouth sizes (28). All tasks will be
presented using Eprime software, under standardized procedures across sites. The
Behavioral Phenotyping workgroup will ensure that quality control is maintained and that
adequate training and standardization of measures is obtained prior to study related
activities commencing. The total time the investigators estimate for completion of
behavioral tasks at each study visit is about 1 hour.
Neuroimaging: Eligible participants will undergo neuroimaging at baseline and at 3-month
intervals. Neuroimaging includes both functional MRI and structural acquisitions. A brief
description of procedures for each of these is outlined below; detailed descriptions will
be in the Neuroimaging Procedures Manual. In total, the investigators estimate that
approximately 90 minutes will be spent in the scanner per visit. In addition, research
personnel will spend about 30 minutes preparing participants. Neuroimaging will be
performed at baseline (study entry) and at 3-month intervals, for a total of 10 total
neuroimaging sessions for the study duration.
The collection of socio-demographics, lifestyle, clinical and other health-related
information obtained through self-report questionnaires and clinician interviews will
complement the physical, biological, neuroimaging (including EEG) measurements collected
at study visits. The information obtained will form a database that allows a wide range
of research questions, both anticipated and unforeseen, to be addressed in the future.
Some questionnaires will be given to participant parents as required for minors.
Additional assessments completed with minors will be done with study staff to assist with
any questions or difficulty with the assessments.
Note: The schedule of assessments to be completed will vary from time to time within this
longitudinal study to help balance the data between age, gender and diagnosis breakdown
of our enrolled participants for data analyses. The schedule of assessments will NOT
exceed the following:
Monthly Surveys: 12 times a year
MRI: 4 times a year
EEG: 4 times a year
Biospecimen collection: 4 times a year
Cognitive Behavioral Tasks (e.g. NIH Toolbox / Cogstate / Emoticom)
Extensive Self-report and Clinician rated assessments: 4 times a year
Optional Stool Sample collection: 4 times a year
Optional Dermal Biopsy: 1 time only
Optional M-health: Duration of the study (starting from Baseline)