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Negative Valence Brain Targets and Predictors of Anxiety and Depression Treatment

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01903447
Recruitment Status : Completed
First Posted : July 19, 2013
Last Update Posted : October 11, 2018
National Institutes of Health (NIH)
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
K. Luan Phan, MD, University of Illinois at Chicago

Brief Summary:

Internalizing psychopathologies (IPs) involving depression and anxiety are among the most prevalent, costly and disabling illnesses. Treatments for IPs are available but the extent to which individual patients respond is quite heterogeneous. Little information exists, particularly in the biological domain, which helps to explain individual differences in treatment response. IPs share similar patterns of dysfunction within the Fronto-Limbic Affect Regulation and Emotional Salience (FLARES) brain circuit, and two commonly used, 'gold standard' treatments - selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioral therapies (CBTs) - are equally effective for both anxiety and depressive disorders, and appear to change brain activity in the same areas within the FLARES circuit. The overarching goal of the project is delineate what are common versus specific FLARE brain targets for SSRI and CBT and identify specific aspects of FLARE dysfunction that might better predict response to both and to a specific modality of treatment. This experiment integrates emotion and its interaction with cognition across several stages of emotional experience, encompassing studies that probe sensitivity to acute and potential threat and automatic and volitional forms of affect regulation in relation to the FLARES brain network.

We will enroll 200 patients presenting to our Mood and Anxiety Disorders Program seeking treatment for disabling 'anxiety, worry, depressed mood' (IPs, including those characterized as Not Otherwise Specified) and randomize them to a 12-week course of SSRI or CBT. Dimensional, transdiagnostic negative valence systems (NVS) constructs, including FLARES function, will be measured before and after each treatment. Specifically, the project will examine 2 Specific Aims: 1) Where and how do SSRI and CBT treatments exert their effects on NVS constructs?; and 2) Which NVS construct can predict the likelihood of success from SSRI and CBT treatment? Such findings can be used to guide the right patients to the right treatments with the highest likelihood of success. They also elucidate a pathophysiologically-driven mechanistic model of where and how treatments work in the brain and thus hasten the development of new treatments that target the underlying pathophysiology across internalizing conditions.

Condition or disease Intervention/treatment Phase
Internalizing Psychopathologies (IPs) Depression and Anxiety Drug: SSRI Behavioral: CBT Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 271 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Negative Valence Brain Targets and Predictors of Anxiety and Depression Treatment
Actual Study Start Date : December 13, 2013
Actual Primary Completion Date : February 21, 2018
Actual Study Completion Date : February 21, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anxiety

Arm Intervention/treatment
Active Comparator: SSRI
sertraline: 100-200mg, citalopram 20-40mg, escitalopram 10-20mg, paroxetine 20-60mg; fluoxetine 20-80mg
Drug: SSRI
Active Comparator: CBT
12 weeks of individual cognitive behavioral therapy
Behavioral: CBT

Primary Outcome Measures :
  1. Brain NVS Construct Measure (Composite) [ Time Frame: Change from Week 0 to Week 12 ]
    Brain: functional magnetic resonance imaging (fMRI) BOLD percent signal change [PSC] within region of interests [ROIs: amygdala, bed nucleus of stria terminalis, striatum, hippocampus, anterior cingulate cortex (including dorsal, rostral, & subgenual subdivisions), anterior insula, ventro/dorso-medial prefrontal cortex, orbitofrontal cortex, ventro/dorso-lateral prefrontal cortex for Emotional Face Assessment Task (EFAT), Emotional Face Interference Task (EFIT), Contextual Threat Task (CTT), Emotion Regulation Task (ERT)

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • Generally medically and neurologically healthy
  • Chief complaint(s) of "anxiety, worry, and/or depressed mood

Exclusion Criteria:

  • Current or past manic/hypomanic episode or psychotic symptoms
  • Suicidal ideation
  • Presence of contraindications (e.g., history of SSRI adverse events) or prior history of SSRI resistance (no response to > 2 SSRI trials with adequate duration and dose)
  • Obsessive compulsive disorder (OCD)
  • Current cognitive dysfunction (traumatic brain injury, mental retardation, dementia)
  • Current alcohol and substance dependence
  • Ongoing therapy/medication treatment of any kind outside of this study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01903447

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United States, Illinois
University of Illinois at Chicago
Chicago, Illinois, United States, 60608
Sponsors and Collaborators
University of Illinois at Chicago
National Institutes of Health (NIH)
National Institute of Mental Health (NIMH)
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Principal Investigator: K. Luan Phan, MD University of Illinois at Chicago
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: K. Luan Phan, MD, Professor of Psychiatry, Director, University of Illinois at Chicago Identifier: NCT01903447    
Other Study ID Numbers: 2013-0325
R01MH101497 ( U.S. NIH Grant/Contract )
First Posted: July 19, 2013    Key Record Dates
Last Update Posted: October 11, 2018
Last Verified: January 2018
Keywords provided by K. Luan Phan, MD, University of Illinois at Chicago:
Internalizing psychopathologies
medication treatment
brain function
Additional relevant MeSH terms:
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Depressive Disorder
Anxiety Disorders
Behavioral Symptoms
Mood Disorders
Mental Disorders