Negative Valence Brain Targets and Predictors of Anxiety and Depression Treatment

Sponsor

University of Illinois at Chicago (Other)

Overall Status

Completed

CT.gov ID

NCT01903447

Collaborator

National Institutes of Health (NIH) (NIH), National Institute of Mental Health (NIMH) (NIH)

271

Enrollment

Location

Arms

50.3

Actual Duration (Months)

5.4

Patients Per Site Per Month

Study Details

Study Description

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

Study Design

Study Type:

Interventional

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 :

Dec 13, 2013

Actual Primary Completion Date :

Feb 21, 2018

Actual Study Completion Date :

Feb 21, 2018

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Brain NVS Construct Measure (Composite) [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)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

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