Overgeneralization of Conditioned Fear as a Pathogenic Marker of Anorexia Nervosa

Anorexia nervosa is a chronic mental health condition characterized by maladaptive food consumption (i.e., hypophagia) and distorted body image. There is substantial evidence of a phenotypic overlap between anorexia nervosa and anxiety disorders, as well as data suggesting the two share a common genetic pathway. Despite these findings, little research has examined fear conditioning among individuals with anorexia nervosa, and no research has examined whether individuals with anorexia nervosa have a propensity to overgeneralize conditioned fear stimuli, one of the more robust fear-conditioning markers of anxiety disorders. The current study assesses generalization of conditioned fear with fear-potentiated startle: the cross-species enhancement of the startle reflex when an organism is in a state of fear. Animal data, as well as an emerging literature in humans, tightly links fear-potentiated startle to the amygdala-based fear circuit. Thus, evidence of overgeneralized fear-potentiated startle in anorexia nervosa would link this eating disorder to hypersensitivity of the fear circuit and could inform the development of novel pharmacologic and psychological treatments for anorexia nervosa based on treatment models used in the anxiety disorders literature.

Study Overview

• Status: Completed
• Conditions: Anorexia; Generalized Anxiety

Detailed Description

The overarching objective of the current proposal is to examine the feasibility of applying a generalization of conditioned fear-potentiated startle paradigm, which has been used successfully to measure the sensitivity of fear networks in anxiety disorders, to adults with anorexia nervosa. The specific aim will be to examine whether conditioned-fear generalization gradients in anorexia nervosa participants differ from those in healthy controls. It is hypothesized that anorexia nervosa participants will display stronger generalization as indicated by less quadratic generalization gradients (i.e., a more gradual decline in conditioned fear as the generalization stimuli deviate from the conditioned fearful stimuli), which is indicative of a heightened sensitivity, or lower thresholds of activation, in the fear circuit (i.e., less danger information necessary to trigger the fear).

• Study Type: Observational
• Enrollment (Actual): 26

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Fifteen adults with anorexia nervosa and 15 healthy, age- and sex- matched control participants will be recruited.

Description

Inclusion Criteria:

• Adults (age≥18)

  a. Anorexics

• Meet criteria for Diagnostic and Statistical Manual (DSM-5) anorexia nervosa

  b. Controls

• age matched
• sex-matched

Exclusion Criteria:

• Criteria are met for a current or past Axis I disorder.
• Inability to read English
• Pregnancy/lactation
• Acute suicidality
• Medical instability as determined by a medical history visit and serum electrolyte testing,
• Medical conditions that may place the participant at risk (e.g., cardiovascular condition)
• Current use of medication that alter central nervous system function

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Controls
Anorexics

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary outcome variable is startle response (eye blink).	Within 2 weeks

Collaborators and Investigators

• Sponsor: University of Minnesota
• Investigators: Principal Investigator: Kelly C. Berg, PhD, University of Minnesota

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): July 1, 2016

Study Registration Dates

• First Submitted: May 20, 2014
• First Submitted That Met QC Criteria: May 22, 2014
• First Posted (Estimate): May 28, 2014

Study Record Updates

• Last Update Posted (Actual): July 12, 2019
• Last Update Submitted That Met QC Criteria: July 10, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Fear; Anorexia; Generalized anxiety
• Additional Relevant MeSH Terms: Mental Disorders; Signs and Symptoms, Digestive; Feeding and Eating Disorders; Anorexia; Anorexia Nervosa
• Other Study ID Numbers: 1312M46141