Appetitive Conditioning in Anorexia Nervosa

NCT05531604 | Active Not Recruiting

• 1 other identifier: 20202201
• Study Type: observational
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

Anorexia nervosa (AN) is characterized by a reduced drive to pursue rewarding experiences and stimuli. Food consumption - which is almost universally experienced as pleasurable - is not described as rewarding by those with AN. This is thought to be underpinned by abnormalities around reward learning. However, the most fundamental question relating to reward in AN - whether those with AN may learn positive associations - remains unaddressed. In this study, the investigators will identify the patterns of how those with AN acquire positive associations, how they diminish, and their relationships to physiology (heart rate and pupil responses) and brain activation. In assessing the robustness of this learning, the investigators will investigate the extent to which this association is reactivated after 24 hours, and the extent to which a memory prompt will help reinstate this previously learned positive association. This project will allow for important advances in our understanding of the neurobiology of AN. The investigators will first identify if, and how, those with AN come to learn positive associations to cues, and secondly, the extent to which learned positive associations remain over time. Moreover, the investigators will use machine learning to ascertain whether reward learning can be predicted by physiological and neural biomarkers.

Conditions

Anorexia Nervosa

Keywords

appetitive conditioning; pavlovian conditioning; reward learning; reinforcement learning; associative learning; extinction

Outcome Measures

Primary Outcomes (8)

• Positive valence

  A 10-point Likert scale will assess self-reported pleasantness and arousal for each conditioned stimulus, and unconditioned stimulus expectancy

  Day 1

• Positive valence

  A 10-point Likert scale will assess self-reported pleasantness and arousal for each conditioned stimulus, and unconditioned stimulus expectancy

  Day 2

• Pupillary dilation

  Measured with an eye-tracking camera

  Day 1

• Pupillary dilation

  Measured with an eye-tracking camera

  Day 2

• Heart rate deceleration

  Measured with an electrocardiogram

  Day 1

• Heart rate deceleration

  Measured with an electrocardiogram

  Day 2

• Brain activation

  Neural activation in reward circuits measured with functional magnetic resonance imaging

  Day 1

• Brain activation

  Neural activation in reward circuits measured with functional magnetic resonance imaging

  Day 2

Study Arms (3)

AN-Restricting (AN-R)

Meet Diagnostic and Statistical Manual (DSM-5) criteria for anorexia nervosa, restricting subtype

Behavioral: appetitive conditioning

Weight Restored AN-Restricting (WRAN-R)

* History of anorexia nervosa, restricting type - previously meeting full DSM-5 criteria. * Eating Disorder Examination Questionnaire (EDE-Q) ≤ 2 (within 1 standard deviation \[SD\] of community norms and lower than 1 standard deviation from clinical norms for female anorexia nervosa, restricting type populations)

Behavioral: appetitive conditioning

Healthy controls

Healthy females from any racial or ethnic background, not meeting DSM-5 criteria for any psychiatric disorder.

Behavioral: appetitive conditioning

Interventions

appetitive conditioning BEHAVIORAL

The investigators will examine acquisition and extinction of learned associations to positively-valenced, socially rewarding yet symptom-neutral infant laughter sounds in an appetitive conditioning paradigm. The investigators will also examine spontaneous recovery of this association 24 hours later when re-presented with these cues, and the reinstatement of this association when re-exposed to infant laughter.

AN-Restricting (AN-R); Healthy controls; Weight Restored AN-Restricting (WRAN-R)

Eligibility Criteria

• Age: 12 Years - 22 Years
• Gender Eligibility Details: We will ask participants to report their identified gender.
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Investigators will enroll 90 female participants between the ages of 12 and 22 (30 with current anorexia nervosa - restricting type, 30 with a history of anorexia nervosa - restricting type, and 30 non-clinical healthy controls).

You may qualify if:

• AN-Restricting (AN-R) Group
• Females from any racial or ethnic background
• Ages between 12 and 22 years
• Meet DSM-5 criteria for AN - restricting subtype
• Medically stable designated by their physician in the past month (having any of the following measurements taken by a physician or nurse within the past month preceding the telephone screen: (i) orthostasis: drop in systolic blood pressure \> 20 mm Hg or diastolic blood pressure \> 10 mm Hg, or an increase in heart rate (HR) \> 20 bpm upon standing for 3 minutes after lying down; (ii) resting HR \<45; or (iii) resting blood pressure of \<80 mm Hg systolic or \<50 mm Hg diastolic 99. Prospective participants who do not meet the medical instability criteria and otherwise pass the telephone screen, will be invited to proceed to the consent process. If they have not had these measurements done in the month prior, we will encourage them to visit their doctor or nurse to have these done and then to recontact us with the results ):
• BP and pulse measured at the day of the scan by the investigators
• Heart rate ≥ 45 at rest
• Resting blood pressure of ≥80 mm Hg systolic and ≥50 mm Hg diastolic
• Lying and standing (after 3 min.) BP drop of ≤20 systolic and ≤10 diastolic and increase in HR ≤20 bpm
• Not taking psychiatric medications or taking serotonin-reuptake inhibitor or serotonin-norepinephrine reuptake inhibitor medications at stable doses
• History of AN-Restricting Group:
• Females from any racial or ethnic background
• Ages between 12 and 22 years
• EDE-Q ≤ 2 (puts them within 1 standard deviation \[SD\] of community norms and lower than 1 SD from clinical norms for female AN-R)
• History of AN - meeting full criteria, diagnosed by a licensed clinician

You may not qualify if:

• AN-R and History of AN-R groups:
• Antipsychotic medications
• Change in dose of psychotropic medication over the previous 4 weeks
• Current psychotic disorder
• Healthy controls:
• Any current Axis I disorder
• Eating Disorder Examination Questionnaire score greater than established community norms (\>2)
• Met criteria for AN (in the past or present)
• All:
• Neurological disorder
• Infants or children of their own
• Pregnancy
• Current risk of suicide with a plan and intent
• Ferromagnetic metal implantations or devices (electronic implants or devices, infusion pumps, aneurysm clips, metal fragments or foreign bodies, metal prostheses, joints, rods or plates)

Sponsors & Collaborators

• University of Southern California: collaborator
• University of Toronto: collaborator
• California Institute of Technology: collaborator
• Klarman Family Foundation: collaborator
• Centre for Addiction and Mental Health: lead

Study Sites (1)

Centre for Addiction and Mental Health

Toronto, Ontario, M6J 1H3, Canada

Location

Related Publications (1)

• Murray SB, Zbozinek TD, Craske M, Tadayonnejad R, Strober M, Bari AA, O'Doherty JP, Feusner JD. Neural, physiological, and psychological markers of appetitive conditioning in anorexia nervosa: a study protocol. J Eat Disord. 2022 May 10;10(1):68. doi: 10.1186/s40337-022-00546-5.

  PMID: 35538507 BACKGROUND

Related Links

• Published manuscript of the study protocol

MeSH Terms

Conditions

Anorexia Nervosa

Condition Hierarchy (Ancestors)

Feeding and Eating Disorders; Mental Disorders

Study Officials

• Jamie D Feusner, M.D.

  Centre for Addiction and Mental Health

  PRINCIPAL INVESTIGATOR

• Stuart Murray, Ph.D.

  University of Southern California

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2022
• First Posted: September 8, 2022
• Study Start: September 30, 2022
• Primary Completion: December 25, 2025
• Study Completion (Estimated): June 30, 2026
• Last Updated: March 27, 2026

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)