CClinicalTrials.gg
Active, not recruitingNCT05531604ACANUpdated Mar 27, 2026

Appetitive Conditioning in Anorexia Nervosa

An observational study in Anorexia Nervosa, sponsored by Centre for Addiction and Mental Health. Active, not recruiting at 1 site in Canada. Open to female participants aged 12 Years to 22 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-03-27.

Sponsored by Centre for Addiction and Mental Health · Observational

Study type
Observational
Model
Case-control
Time perspective
Prospective
Enrollment
90
Ages
12 Years to 22 Years
Sex
Female
01

Study 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.

Read the detailed description

Individuals with anorexia nervosa (AN) suffer from anxiety, reduced pleasure from normally rewarding situations (anhedonia), and disturbed body image. However, restriction of calories from their morbid fear of weight gain, resulting in starvation, typically brings them to attention and has been the primary focus of most treatments and many research studies. Yet, treatments have largely been inadequate, with remission rates less than 25%. Anhedonia and disturbances in reward may be important targets of new treatment approaches. Those with AN report little pleasure in food consumption, social domains, and pursuit of novelty and fun. Neuroimaging studies demonstrate disturbances in reward circuits in response to food- and body-related stimuli and monetary rewards, but results are inconsistent. This may be due to confounding effects of anxiety triggered by symptom-related stimuli. Further, a fundamental process of the overall reward response that has not been studied in AN is reward learning - how one's brain learns to associate stimuli with the experience of reward ("appetitive Pavlovian conditioning"). To investigate this, the investigators will enroll 30 underweight individuals with AN, 30 with weight-restored AN, and 30 healthy controls ages 12-22 to perform a reward conditioning paradigm. The investigators will use infant laughter, a social reward with robust effects that is unlikely to be confounded by other co-occurring symptoms. To understand associated neural activity and physiological responses, the investigators will perform conditioning and examine reinstatement 24-hours later, while obtaining functional magnetic resonance imaging, heart rate deceleration, and pupil dilation data, in addition to subjective degrees of positive experience. Data from underweight and weight-restored AN will further allow us to probe starvation state-related effects. Results will advance our understanding of how reward stimuli are learned and the associated aberrant neural or physiological markers. This will yield a comprehensive mechanistic understanding of hedonic functioning in AN to rationally inform future novel treatment development.

02

Conditions studied

  • Anorexia Nervosa

Browse trials for

Keywords

  • appetitive conditioning
  • pavlovian conditioning
  • reward learning
  • reinforcement learning
  • associative learning
  • extinction
03

In context

Anorexia Nervosa

455 studies on the registry are indexed under Anorexia Nervosa; 126 are open to participants now.

This study's planned enrollment of 90 is above the median of 72 across 135 observational studies indexed under Anorexia Nervosa.

Browse Anorexia Nervosa studies →

Lead sponsor

Centre for Addiction and Mental Health is the lead sponsor of 328 studies on the registry; 51 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
12 Years to 22 Years
Sexes eligible
Female
Accepts healthy volunteers
Yes
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).

Eligibility criteria

Inclusion Criteria:

  1. AN-Restricting (AN-R) Group

    Inclusion criteria:

    1. Females from any racial or ethnic background
    2. Ages between 12 and 22 years
    3. Meet DSM-5 criteria for AN - restricting subtype
    4. 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 ):
    5. 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
    6. Not taking psychiatric medications or taking serotonin-reuptake inhibitor or serotonin-norepinephrine reuptake inhibitor medications at stable doses
  2. History of AN-Restricting Group:

    Inclusion criteria:

    1. Females from any racial or ethnic background
    2. Ages between 12 and 22 years
    3. 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)
    4. History of AN - meeting full criteria, diagnosed by a licensed clinician
    5. Not taking psychiatric medications or taking serotonin-reuptake inhibitor or serotonin-norepinephrine reuptake inhibitor medications at stable doses
  3. Healthy controls:

Inclusion criteria:

  1. Healthy females from any racial or ethnic background
  2. Ages 12-22 years

Exclusion Criteria:

  • AN-R and History of AN-R groups:

    1. Antipsychotic medications
    2. Change in dose of psychotropic medication over the previous 4 weeks
    3. Current psychotic disorder

Healthy controls:

  1. Any current Axis I disorder
  2. Eating Disorder Examination Questionnaire score greater than established community norms (>2)
  3. Met criteria for AN (in the past or present)

All:

  1. Neurological disorder
  2. Infants or children of their own
  3. Pregnancy
  4. Current risk of suicide with a plan and intent
  5. Ferromagnetic metal implantations or devices (electronic implants or devices, infusion pumps, aneurysm clips, metal fragments or foreign bodies, metal prostheses, joints, rods or plates)
05

Study design

Observational model
Case-control
Time perspective
Prospective
Enrollment
90 participants (estimated)
Patient registry
No

Groups and cohorts

  • 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

  • Behavioralappetitive conditioning

    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.

06

What researchers measure

Primary outcomes

  1. Positive valence

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

    Time frame: Day 1

  2. Positive valence

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

    Time frame: Day 2

  3. Pupillary dilation

    Measured with an eye-tracking camera

    Time frame: Day 1

  4. Pupillary dilation

    Measured with an eye-tracking camera

    Time frame: Day 2

  5. Heart rate deceleration

    Measured with an electrocardiogram

    Time frame: Day 1

  6. Heart rate deceleration

    Measured with an electrocardiogram

    Time frame: Day 2

  7. Brain activation

    Neural activation in reward circuits measured with functional magnetic resonance imaging

    Time frame: Day 1

  8. Brain activation

    Neural activation in reward circuits measured with functional magnetic resonance imaging

    Time frame: Day 2

07

Study locations

1 site
  • Centre for Addiction and Mental Health
    Toronto, Ontario M6J 1H3, Canada
08

References and documents

Publications

  • 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. PubMed 35538507 ↗

Individual participant data

Plan to share: No

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 27, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT05531604
Lead sponsor
Centre for Addiction and Mental Health
Collaborators
University of Southern California, University of Toronto, California Institute of Technology, Klarman Family Foundation
Responsible party
Sponsor
First posted
Sep 8, 2022
Start date
Sep 30, 2022
Primary completion
Dec 25, 2025
Completion
Jun 30, 2026 (estimated)
Last update
Mar 27, 2026

Study contacts

Jamie D Feusner, M.D.
principal investigator · Centre for Addiction and Mental Health
Stuart Murray, Ph.D.
principal investigator · University of Southern California

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is active, not recruiting, as verified in Nov 2025. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Start the discussion