Anxiety and Reward Interaction and Prediction of Outcomes in Anorexia Nervosa
Condition: Anorexia Nervosa, Restricting Type; Anxiety
MeSH terms: Anorexia; Anxiety Disorders; Anorexia Nervosa
Study type: Observational

Summary: 
      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.
    

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.
    

Intervention name(s): fMRI
Intervention type(s): Other
Intervention description(s): fMRI: reward task, anxiety provocation
Observational model: Case-Control
Time perspective: Prospective
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.
      
Keywords: anorexia nervosa; anxiety; reward; recurrence; magnetic resonance imaging