Brain Dopamine Function in Human Obesity

Evidence from neuroimaging studies indicates that aberrant functionality in brain regions that support reward processing and habit formation may be related to an individual's eating behavior and obesity propensity. In particular, our previous research found that increased dopamine D2 receptor binding potential (D2BP) in the dorsal and lateral striatum was positively related to opportunistic eating behaviors, body fat, and body mass index (BMI). However, our findings were contrary to highly-cited previous reports of D2BP correlating with BMI in the opposite direction. The primary aim of this study is to elucidate the reasons for the conflicting results that used somewhat different methodologies. Specifically, our previous study used positron emission tomography (PET) to measure D2BP using the dopamine D2 receptor antagonist radioligand [18F]fallypride following a period of dietary stabilization and 3 hours after a standardized breakfast. Reports finding correlations between D2BP and BMI in the opposite direction have typically investigated subjects with higher BMI using the D2 receptor antagonist radioligand [11C]raclopride. Furthermore, previous studies were typically conducted in the fasted state, but the subjects' prior food intake was not well-controlled. The present study will attempt to resolve the controversy by measuring D2BP using both [18F]fallypride and [11C]raclopride in 39 adults, 13 within each of three BMI strata to represent a large BMI range, under controlled overnight fasting conditions following a period of dietary stabilization. The primary aims are to estimate the mathematical relationship between striatal D2BP and BMI and determine the within-subject correlations of D2BP derived from [18F]fallypride and [11C]raclopride.

• INCLUSION CRITERIA:
• Age 18-45 years, male and female
• Consent to undergoing PET scanning
• Body mass index (BMI) greater than or equal to 18.5 kg/m^2
• Weight stable (less than plus or minus 5% change in the past month)
• Written informed consent
• Estimated intelligence quotient (IQ) greater than or equal to 70, as determined by the National Adult Reading Test (NART) (Scores below 70 are indicative of mental retardation; IQ has been related to alterations in brain structure and function that may confound neuroimaging measures. Failure to meet this eligibility criteria will be documented in the record and communicated to the potential participant as ineligibility based on reading test results )

Exclusion criteria

• Age 46 or greater (Age is a significant confound in the relationship between BMI and dopamine. Dopamine binding has been shown to drastically decrease in the fifth decade of life.
• Body weight > 400 lbs. (weight limit of PET scanner)
• Weigh less than 80% of maximum lifetime weight
• BMI < 18.5 kg/m2
• Past or present history of neurological or psychiatric disease (e.g., depression, anxiety, substance use disorder or psychosis), or eating disorders (e.g., anorexia nervosa, bulimia nervosa, or binge eating disorder) as determined by research team upon review of history/physical, Eating Disorder Examination-Questionnaire and Self-Rated Level 1 Cross-Cutting Symptom Measure.
• Blood pressure >140/90 mm Hg
• Evidence/history of cancer, metabolic disease (e.g. thyroid disease, diabetes) or cardiovascular disease (e.g. coronary artery disease, myocardial infarction, stroke, atherosclerosis), or disease that may influence metabolism
• Current use of prescription medication or other drug that may influence metabolism (diet/weight-loss medication, asthma medication, psychiatric medications such as antidepressants, anti-anxiety medications, and stimulants for attention-deficit/hyperactivity disorder (ADHD), corticosteroids or other medications at the discretion of the PI and/or study team)
• Pregnancy, lactation at any time during study/follow-up period (women only)
• Evidence of vigorous exercising in order to lose weight, change body shape, or to counteract the effects of eating
• Previous bariatric surgery
• Evidence of nicotine dependence as determined by Fagerstrom score greater than or equal to 3 (including chewing or smoking tobacco), any drug use (amphetamines, cocaine, heroin, marijuana), or problematic alcohol use (i.e. diagnosis of alcohol use disorder: meeting greater than or equal to 2 of 11 criteria in past 12 months, ranging from drinking more/longer than intended to experiencing withdrawal symptoms); report of binge drinking: greater than or equal to 5 drinks in 2 hours or greater than or equal 4 drinks in

2 hours for men and women, respectively) over the previous 6 months.

• Volunteers with strict dietary concerns (e.g. kosher diet, milk allergy or lactose intolerance, or food allergies)
• Caffeine consumption > 300 mg/day (roughly greater than or equal to 3 cups coffee or 2-3 energy drinks)
• Having metal implants incompatible with MRI (for example, pacemakers, metallic prostheses such as cochlear implants or heart valves, shrapnel fragments, etc.).
• Having had previous radiation exposure within the last year for either medical or research purposes (e.g. X-rays, PET scans, etc.) that would exceed research limits. Excessive radiation exposure will be determined at the discretion of the PI and/or study team
• Are claustrophobic to a degree that they would feel uncomfortable in the MRI machine.
• Non-English speakers.
• Cannot commit to the schedule of visits to the Clinical Research Center as required by the study timeline