Changes in Dopamine Levels Before and After Weight Restoration in People With Anorexia Nervosa

Anorexia nervosa (AN) is a disordered eating disease characterized by a persistent pursuit
of thinness, intense fear of weight gain, distorted body image, and obsessive eating habits.
People with AN are at high risk for certain health problems, such as depression,
osteoporosis, substance abuse, and cardiovascular and neurological complications. Current
treatments for AN include different forms of psychotherapy and medications, but the success
of these treatments is highly variable among people with AN. A better pathophysiologic
understanding of AN is needed in order to develop novel therapeutic strategies for
preventing and treating the disorder. Current research is targeting dopamine (DA), a
neurotransmitter that is released in response to pleasurable stimuli, such as food and
drugs. Animal studies have found that chronic food restriction may alter functioning of the
DA system by reducing DA response to food and drug stimuli. A better understanding of the
effects of disordered eating on the DA systems of people with AN may provide insight into
the development of new and improved treatments for people with AN. This study will use
positron emission tomography (PET) imaging to investigate changes in DA systems in people
with AN before and after both weight restoration and administration of methylphenidate, a
psychostimulant medication. The study will also use PET imaging to compare DA systems of
people with AN with DA systems of people who are healthy.

This study will involve both healthy participants and participants with AN. Study
participation for healthy participants will include two PET scans and one magnetic resonance
imaging (MRI) scan, which, if the participants prefer, can all be completed in one study
visit. Study participation for participants with AN will include three PET and two MRI
scans. The first PET and MRI scans will be performed upon entry into the hospital as an
inpatient. The remaining scans will be conducted 2 to 4 weeks after participants have
accomplished weight restoration.

Including preparation, each MRI study will last about 45 minutes and each PET study will
last about 3 hours. For each MRI study, participants will be asked to lie on their backs for
15 minutes in the MRI scanner. For each PET study, participants will first be injected with
a dose of [11C]raclopride, a radioactive drug used in brain imaging, and will then lie on
their backs for 30 minutes in the PET scanner.

One hour before the second PET scan for healthy participants and the third PET scan for
participants with AN, participants will receive an oral dose of methylphenidate. During
these scans, participants will also undergo blood pressure monitoring and an
electrocardiogram (EKG). Once participants no longer feel the effects of the methylphenidate
and their vital signs have returned to normal, they will be discharged from the medical
center and study participation will be complete.

Inclusion Criteria:

Participants with AN:

- Meets DSM-IV criteria for AN or ED-NOS (meets criteria for AN except amenorrhea)

- Sufficiently medically and psychiatrically stable to leave inpatient unit, as
assessed by clinical team

Healthy control participants:

- No current or past psychiatric illness

- Between 80% and 120% of ideal body weight

Exclusion Criteria:

All participants:

- Current use of psychotropic medication such as antipsychotics or antidepressants

- Pregnant or breastfeeding

- History of a substance use disorder

- Significant medical illness

- High blood pressure (resting systolic blood pressure greater than 140 mmHg and
diastolic blood pressure greater than 90 mmHg)

- Current or lifetime history of schizophrenia, bipolar disorder, or other psychotic
disorder as defined by DSM-IV-TR

- Metal implants or paramagnetic objects contained within the body that may interfere
with the MRI scan, as determined in consultation with a neuroradiologist and
according to specified reference book guidelines

- Exposed to radiation in the workplace or has had a nuclear medicine procedure during
the 1 year before study entry

- Previous adverse reaction to psychostimulants