Reward Systems and Food Avoidance in Eating Disorders

Anorexia nervosa (AN), a characteristically relentless pursuit of thinness with an intense fear of weight gain despite significantly low body weight, is a serious psychiatric disorder with high rates of morbidity and mortality. Low weight eating disorders (LW-ED), the broader category of eating pathology that includes AN and similar variants, are characterized by a chronic course, poor response to treatment, and food avoidance. Emerging neuroimaging evidence suggests that deficits in insula-amygdala-ventral striatum (IAVS) neurocircuitry contribute to individual variability in aversive and reward learning, and that these brain regions demonstrate abnormal responses to food/eating stimuli. The researchers' pilot data suggest that patients with LW-ED experience difficulty extinguishing food-cue associations in a reversal learning paradigm compared to healthy controls, a difficulty that is related to psychophysiological measures of aversive disgust (not fear). The researchers have also successfully piloted an interoceptive exposure intervention for this population that targets visceral sensitivity and seeks to increase 'top-down' regulation of the IAVS neurocircuit. The proposed project will (a) use novel fMRI-EMG to test the relationship between effective connectivity within amygdala-insula-ventral striatum network and its relationship to psychophysiological and behavioral measures of acute threat and reward learning in 60 adolescents with LWEDs and 30 healthy controls, (b) test the sensitivity of this network to an experimental interoceptive exposure paradigm relative to patients receiving family based therapy for weight restoration using dynamic causal modeling of fMRI-EMG data pre-post experimental conditions, (c) validate this model against objective measures of laboratory and real world eating behavior. The results of this study will help better understand the core neurocircuitry that underlies both threat processing and reward/aversive learning and how this circuit relates to objective behavior. Further, the researchers will determine the modifiability of this neurocircuitry via two distinct behavioral interventions chosen to target different aspects of affective processing and reward learning. These data will be used to inform future clinical interventions targeting aversive/reward learning within this population and dysregulation in insula-amygdala-ventral striatum subcircuits.

Low Weight ED Patients

Inclusion criteria

• Females,
• Adolescents ages 12-18,
• Speak English,
• Seeking treatment
• Refusal to maintain greater than minimally low body weight based on BMI for age percentiles and growth trajectories,
• Clinically significant restriction of food intake on the dietary restraint subscale of the EDE or evidence of persistent food avoidance as reported by patient or guardians.
• Given medical clearance from pediatrician or equivalent.

Exclusion criteria

• Current psychotropic medication that would have an effect on performance on behavioral tasks (i.e., anti-anxiety medication),
• Comorbid psychotic or bipolar disorder,
• Active suicidal ideation,
• Major medical illness known to influence eating or weight,
• Current substance dependence,
• Previous exposure therapy for LW-ED.
• Physical limitation that would prevent participation (e.g., allergic to chocolate),
• For patients with current or a history of sexual or physical abuse by parents, siblings, or guardians, perpetrators of the abuse will be excluded from treatment; if physical or sexual abuse by a family member occurs during the course of treatment, perpetrators will be excluded from ongoing treatment

Healthy Comparison Adolescents

Inclusion criteria

• Females,
• Adolescents ages 12-18,
• Speak English.

Exclusion criteria

• Current psychotropic medication that would have an effect on performance on behavioral tasks (i.e., stimulant medication),
• Current or lifetime history of any psychiatric disorder, including eating disorders by K-SADS,
• Current or lifetime history of learning disorder or developmental disability
• Active suicidal ideation,
• Major medical illness,
• Other physical limitation that would prevent participation (e.g., allergic to chocolate).