Anxiety and Reward Interaction and Prediction of Outcomes in Anorexia Nervosa

This study is designed to understand responsiveness to reward in adolescents with restricting-type anorexia nervosa compared with non-clinical controls, and how it is affected by potential-threat perception.

Study Overview

• Status: Completed
• Conditions: Anxiety; Anorexia Nervosa, Restricting Type
• Intervention / Treatment: Other: fMRI

Detailed Description

The objective of this study is to understand the effects of anxiety on reward responsiveness in adolescents with anorexia nervosa (AN), and how this interaction predicts behavioral outcome subsequent to intensive treatment. Investigators plan to test, for the first time, how acute activation of threat related emotional circuitry reciprocally alters reward circuit activity, and to what degree this modulation predicts post treatment relapse. The severity of AN, its resistance to intervention, potential for quick return of illness, risk for long-term chronicity, and premature death, are well appreciated. Various forms of intensive treatment may succeed in at least partial weight restoration, yet early relapse is unusually high. The appearance early in life of prodromal anxiety phenotypes in individuals who subsequently develop AN is well documented and nearly universal. Anxiety proneness in concert with rigid self-discipline may therefore be predisposing substrates for sudden morbid apprehension about weight gain, and may contribute to subsequent behaviors including vigilant scrutiny of body size and shape and inflexible cognitive patterns regarding food and eating. In parallel, persons with restricting-type AN typically exhibit unease and reticence when exposed to novel, high reward environments. Most studies have found low fun-seeking, low novelty seeking, and reduced reward responsiveness in those with AN. In line with these observations, functional magnetic resonance imaging (fMRI) studies demonstrate aberrant reward sensitivity and reward circuit activation. However the interaction of anxiety and reward circuits has never been interrogated. There is substantial evidence of distinct yet overlapping neural systems mediating approach/reward and avoidance/anxiety, which are integrated in balancing and switching between behaviors related to the predominant valence state. Thus investigators posit that high degrees of reactivity of cortico-limbic circuits underlying anxiety may contribute mechanistically and functionally to diminished initial responsiveness to reward stimuli. This may translate clinically to lower motivation to engage in outpatient treatment - in effect, a lower drive to change behaviors and thought patterns necessary for maintaining gains or improving, based on expectancy of benefits of future outcome. The dynamic interaction between reward and anxiety systems in AN, and how dysregulation of connectivity within and between these systems mediates behavioral outcomes, has not previously been tested. Investigators will investigate this interaction using sequential fMRI paradigms and novel integrated functional-by-structural connectivity in individuals who have completed standard treatment on an eating disorder unit. Investigators will then investigate how this neural circuitry may predict degree of relapse during the subsequent 6 months.

• Study Type: Observational
• Enrollment (Actual): 66

Contacts and Locations

• Study Contact: Name: Courtney Sheen, M.A.; Phone Number: 310 206-0468; Email: csheen@mednet.ucla.edu

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • UCLA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 19 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Investigators will enroll 96 participants between the ages of 13 and 19 (48 with anorexia nervosa and 48 non-clinical controls matched by gender.

Description

Inclusion criteria for AN participants:

• Clinical diagnosis of Anorexia Nervosa, Restricting Type within the previous 6 months, (except for the amenorrhea criteria)
• completed treatment in an inpatient, residential, or partial hospitalization program (2-5 times/week) consisting of psychotherapy and dietary monitoring, within the previous 3 weeks
• May be unmedicated, or be taking a serotonin reuptake inhibitor medication at a stable dose for at least 8 weeks at the time of enrollment.

Exclusion criteria for AN participants:

• lifetime Axis I bipolar disorder, lifetime psychotic disorders, lifetime attention deficit hyperactivity disorder, or current post-traumatic stress disorder.
• current substance abuse or dependence, including nicotine
• pathological gambling, as assessed with the South Oaks Gambling Screen
• current neurological disorder
• pregnancy
• current major medical disorders that may affect cerebral metabolism such as diabetes or thyroid disorders
• current risk of suicide with a plan and intent
• a Children's Depression Rating Scale Revised (CDRS-R) score >75 or major depressive disorder with psychotic features
• ferromagnetic metal implantations or devices (electronic implants or devices, infusion pumps, aneurysm clips, metal fragments or foreign bodies, metal prostheses, joints, rods or plates)
• adjusted BMI ≥ 25 (overweight)
• visual acuity worse than 20/35 for each eye as determined by Snellen close vision chart. Acuity may be met with corrective lenses.

Inclusion criteria for controls:

• non-clinical females who score at least 1 standard deviation higher than population norms on the Depression Anxiety Stress Scale (DASS-21)

Exclusion criteria for controls:

• any Axis I disorder
• any psychiatric medication.
• - current substance abuse or dependence, including nicotine
• pathological gambling, as assessed with the South Oaks Gambling Screen
• current neurological disorder
• pregnancy
• current major medical disorders that may affect cerebral metabolism such as diabetes or thyroid disorders
• current risk of suicide with a plan and intent
• a Children's Depression Rating Scale Revised (CDRS-R) score >75 or major depressive disorder with psychotic features
• ferromagnetic metal implantations or devices (electronic implants or devices, infusion pumps, aneurysm clips, metal fragments or foreign bodies, metal prostheses, joints, rods or plates)
• adjusted BMI ≥ 25 (overweight)
• visual acuity worse than 20/35 for each eye as determined by Snellen close vision chart. Acuity may be met with corrective lenses.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Anorexia; fMRI: reward task, anxiety provocation	Other: fMRI; fMRI: reward task, anxiety provocation
Mild anxiety comparison group; fMRI: reward task, anxiety provocation	Other: fMRI; fMRI: reward task, anxiety provocation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood oxygen level dependent (BOLD) percentage signal change as measured by fMRI in anxiety and reward brain regions of interest	Mean BOLD percentage signal change between anxiety and control conditions will be compared across anorexia nervosa and comparison participants during the reward task	within 3 weeks of discharge from an intensive treatment program

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body Mass Index (BMI) in kg/meter squared monthly for 6 months	Trajectory of BMI over 6 months after intensive treatment will be analyzed	6 months
Eating disorder symptoms	Eating Disorder Examination (EDE)	beginning of study and at 6 months

Collaborators and Investigators

• Sponsor: University of California, Los Angeles
• Collaborators: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: Jamie D Feusner, M.D., University of California, Los Angeles

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (Actual): April 30, 2021
• Study Completion (Actual): June 30, 2021

Study Registration Dates

• First Submitted: October 3, 2016
• First Submitted That Met QC Criteria: October 26, 2016
• First Posted (Estimated): October 28, 2016

Study Record Updates

• Last Update Posted (Actual): May 31, 2023
• Last Update Submitted That Met QC Criteria: May 27, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: magnetic resonance imaging; anxiety; recurrence; anorexia nervosa; reward
• Additional Relevant MeSH Terms: Mental Disorders; Signs and Symptoms, Digestive; Feeding and Eating Disorders; Anorexia; Anorexia Nervosa; Anxiety Disorders
• Other Study ID Numbers: 1R01MH105662-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Investigators will share deidentified subject-level data loaded to the new database for the National Institute of Mental Health Research Domain Criteria project (RDoC-db).

The work involves defining data dictionaries for each data structure, cleaning and formatting data, and uploading the data to the appropriate National Institute of Mental Health server. The data so shared will contribute to the building of a large information commons for RDoC that will permit analyses of large data sets that have more power to uncover new relationships among highly multivariate and dimensional data sets.