Anxiety and Reward Interaction and Prediction of Outcomes in Anorexia Nervosa

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.

Inclusion criteria for AN participants:

- Clinical diagnosis of Anorexia Nervosa, Restricting Type within the previous 6 months,
(except for the amenorrhea criteria)

- completed treatment in an inpatient, residential, or partial hospitalization program
(2-5 times/week) consisting of psychotherapy and dietary monitoring, within the
previous 3 weeks

- May be unmedicated, or be taking a serotonin reuptake inhibitor medication at a stable
dose for at least 8 weeks at the time of enrollment.

Exclusion criteria for AN participants:

- lifetime Axis I bipolar disorder, lifetime psychotic disorders, lifetime attention
deficit hyperactivity disorder, or current post-traumatic stress disorder.

- current substance abuse or dependence, including nicotine

- pathological gambling, as assessed with the South Oaks Gambling Screen

- current neurological disorder

- pregnancy

- current major medical disorders that may affect cerebral metabolism such as diabetes
or thyroid disorders

- current risk of suicide with a plan and intent

- a Children's Depression Rating Scale Revised (CDRS-R) score >75 or major depressive
disorder with psychotic features

- ferromagnetic metal implantations or devices (electronic implants or devices, infusion
pumps, aneurysm clips, metal fragments or foreign bodies, metal prostheses, joints,
rods or plates)

- adjusted BMI ≥ 25 (overweight)

- visual acuity worse than 20/35 for each eye as determined by Snellen close vision
chart. Acuity may be met with corrective lenses.

Inclusion criteria for controls:

- non-clinical females who score at least 1 standard deviation higher than population
norms on the Depression Anxiety Stress Scale (DASS-21)

Exclusion criteria for controls:

- any Axis I disorder

- any psychiatric medication.

- - current substance abuse or dependence, including nicotine

- pathological gambling, as assessed with the South Oaks Gambling Screen

- current neurological disorder

- pregnancy

- current major medical disorders that may affect cerebral metabolism such as diabetes
or thyroid disorders

- current risk of suicide with a plan and intent

- a Children's Depression Rating Scale Revised (CDRS-R) score >75 or major depressive
disorder with psychotic features

- ferromagnetic metal implantations or devices (electronic implants or devices, infusion
pumps, aneurysm clips, metal fragments or foreign bodies, metal prostheses, joints,
rods or plates)

- adjusted BMI ≥ 25 (overweight)

- visual acuity worse than 20/35 for each eye as determined by Snellen close vision
chart. Acuity may be met with corrective lenses.