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| Name | Class |
|---|---|
| University of California, Los Angeles | OTHER |
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Anxiety and depression are highly prevalent and disabling conditions that frequently co-occur, and are costly to the individual and society. Despite important advances in our understanding of these disorders, there is a significant unmet need to identify reliable and clinically useful tests that can predict prognosis, inform treatment choice for a given individual, and improve treatment outcomes. The aim of this project is to fill this critical gap by validating a battery of measures including brain imaging, psychophysiology, behavior, and self-report that will reliably assess positive and negative affect, or valence, system functioning in a broad sample of individuals screened for anxiety and depression as part of their routine primary care visits.
Participants presenting to the UCSD and UCLA primary care clinics will be screened as part of their routine visit using the Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder 7 (GAD-7). Participants who call in will be asked to provide verbal informed consent for phone screening and the IRB approved Screening Questionnaire and the Overall Anxiety Severity and Impairment Scale (OASIS) will be administered.
Participants who remain eligible after the phone screening will be asked to return for a Clinical Interview, Behavioral Session, Biomarker blood draw, (and optional genetics), and Neuroimaging Session.
All participants will be contacted approximately 3-months later and invited to complete the same battery of self-report measures completed during the baseline session (described below). The self-report measures will be administered through a secure on-line survey database. This data will allow investigators to (1) confirm that participants continue to meet initial eligibility criteria and are therefore eligible for the full re-test battery and (2) use baseline measures of positive and negative valence domains to predict changes in symptoms and functioning.
A subset of 50 participants (n=25 from each UCSD and UCLA) will be randomly selected to return approximately three months later to complete the same battery of assessments in the Behavioral and Neuroimaging Sessions to establish test-retest reliability of the latent constructs.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Anxiety | elevated anxiety (as indicated by a GAD-7 score of 8 or higher) |
| |
| Depression | elevated anxiety (as indicated by a GAD-7 score of 8 or higher) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| NeuroImaging | Behavioral | standard anatomical and functional imaging |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Relationship of latent constructs of positive and negative valence domains and neural indices of reward sensitivity and fear conditioning in treatment seeking depressed and anxious individuals. | Measure of BOLD % signal difference in brain regions of interest during reward or loss trials for anticipation and outcome phases in a reward paradigm, and conditioning trials in a fear conditioning paradigm. | 4 years |
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Investigators opted to identify individuals with anxiety or depression in a primary care setting, which investigators have used successfully to recruit a significant number of subjects, to maximize generalizability and external validity.
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| Name | Affiliation | Role |
|---|---|---|
| Martin P Paulus, MD | UC San Diego | Principal Investigator |
| Murray B Stein, MD, MPH | UC San Diego | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UCSD Psychiatry Clinical Research | La Jolla | California | 92093-0855 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20595427 | Background | Insel T, Cuthbert B, Garvey M, Heinssen R, Pine DS, Quinn K, Sanislow C, Wang P. Research domain criteria (RDoC): toward a new classification framework for research on mental disorders. Am J Psychiatry. 2010 Jul;167(7):748-51. doi: 10.1176/appi.ajp.2010.09091379. No abstract available. | |
| 12813115 | Background |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Oct 18, 2012 | Oct 9, 2017 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D001008 | Anxiety Disorders |
| D003863 | Depression |
| ID | Term |
|---|---|
| D001523 | Mental Disorders |
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |
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| ID | Term |
|---|---|
| D059906 | Neuroimaging |
| ID | Term |
|---|---|
| D003952 | Diagnostic Imaging |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D003943 | Diagnostic Techniques, Neurological |
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Blood biomarkers: Investigators will assess blood biomarkers including norepinephrine, dopamine, epinephrine, creatinine, soluble cellular adhesion molecules (sICAM, sVCAM), IFN+ (IFN-gamma, IL-6, and TNF-alpha assayed together), and brain-derived neurotrophic factor (BDNF).
Genetics: Furthermore, as noted later in this section of the application, investigators have identified abnormalities in functioning of key structures (e.g., amygdala and insula) within the brain's anxiety circuitry in anxiety-prone subjects and there is evidence that certain genes (e.g., SLC6A4) influence the extent of activation in these regions. The focus of this project is to determine to what extent variation in CRF system genes (i.e., CRF, CRF-R1, CRF-R2, UCN, UCN2, UCN3) is associated with anxiety disorders.
| Psychophysiological |
| Behavioral |
Hear rate, Vagal Tone, Skin Conductance, and Startle Reflex Electromyogram |
|
| Kessler RC, Berglund P, Demler O, Jin R, Koretz D, Merikangas KR, Rush AJ, Walters EE, Wang PS; National Comorbidity Survey Replication. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA. 2003 Jun 18;289(23):3095-105. doi: 10.1001/jama.289.23.3095. |
| 20483968 | Background | Roy-Byrne P, Craske MG, Sullivan G, Rose RD, Edlund MJ, Lang AJ, Bystritsky A, Welch SS, Chavira DA, Golinelli D, Campbell-Sills L, Sherbourne CD, Stein MB. Delivery of evidence-based treatment for multiple anxiety disorders in primary care: a randomized controlled trial. JAMA. 2010 May 19;303(19):1921-8. doi: 10.1001/jama.2010.608. |
| D008919 | Investigative Techniques |