1. Brookhaven Science Associates U.S. Department of Energy Gene-Jack Wang, M.D. The Addiction-Obesity Connection Brookhaven Science Associates U.S. Department of Energy

3. United States of Obesity Time.com June 7, 2004 Brookhaven Science Associates U.S. Department of Energy

4. Cocaine AlcoholHeroin AbuserControl [ 11 C]raclopride Abuser Control Dopamine D2 images of Drug Addiction CocaineAlcoholHeroin

5. Brookhaven Science Associates U.S. Department of Energy Compulsive overeating shares many of the same characteristics as drug addiction. Obesity Do obese subjects have abnormal levels of D2- receptor? 10 severely obese subjects(BMI: 51±5 kg/m 2 ) 10 age-matched controls (BMI: 25±3 kg/m 2 )

6. Brookhaven Science Associates U.S. Department of Energy Lower dopamine receptors in obese than in control subjects 2 0 ml/gm Control Subjects Obese Subjects [ 11 C]raclopride Wang et al, Lancet 2001 Obese subjects (n = 10) Control subjects (n = 10) BMI Dopamine Receptor Concentration P < 0.002 P < 0.3

7. Brookhaven Science Associates U.S. Department of Energy Food Stimulation

8. Brookhaven Science Associates U.S. Department of Energy Brain Dopamine Response to Food Stimulation (Bmax/Kd) 2.5 3 3 3.5 4 4 Placebo/Neutral MP/Food p < 0.005 1.5 0 0 ml/g Volkow, et al, Synapse 2002 -2 0 0 2 2 4 4 6 6 8 8 10 0 0 5 5 15 20 25 30 Desire for Food % Change Bmax/kd p < 0.01 Neutral Food Brookhaven Science Associates U.S. Department of Energy

9. Cue-induced increases in DA were associated with craving P < 0.002 % Change Bmax/Kd -0.50 0.0 0.50 1.0 1.5 2.0 2.5 -40 -30 -20 -10 0 0 10 20 30 Putamen Change in Craving (Pre - Post) Relationship between Cue-Induced Decreases in [C-11]raclopride Binding and Cocaine Craving Caudate Putamen 2.00 2.50 3.00 3.50 Neutral Cocaine-Cues Bmax/Kd P < 0.05 P < 0.01 Volkow et al, 2006

10. Brookhaven Science Associates U.S. Department of Energy MP 85 0 µmole/100g/min Brain Activation with Methylphenidate Induced Cocaine Craving Placebo Orbitofrontal Activation Volkow et al Am J Psychiatry 1999 -30 -20 -10 0.0 10 20 30 0.02.04.06.08.010 micromol/100g/min (MP - Placebo) Self Report Craving r = 0.79, p < 0.0002 Brookhaven Science Associates U.S. Department of Energy

11. % Changes of feeling of hunger r = 0.84, p = 0.001 85 0 µmole/100g/min Neutral Stimuli Food Stimuli Wang et al, Neuroimage 2004 Orbitofrontal Activation Brain Activation with Food Stimuli Brookhaven Science Associates U.S. Department of Energy

12. Why do some people continue to eat when the stomach is full? 18 FDG-PET (IGS on vs IGS off in obese subjects) Orbitofrontal Cortex (Self-Control) Hippocampus (Memory) Striatum (Motivation) IGS : Implantable gastric stimulator (n=2) 2 3 ONOFF p < 0.04 Wang et al, PNAS USA 2006

13. Brookhaven Science Associates U.S. Department of Energy Decreased brain activation during cognitive inhibition of hunger r = 0.73, p = 0.02 Orbitofrontal cortex Amygdala Hippocampus Cerebellum Cingulate Striatum Food stimulation Cognitive Inhibition

14. Brookhaven Science Associates U.S. Department of Energy New intriguing questions Do obese subjects have the same ability to suppress craving? How about drug addicts? Are there differences between men and women in ability to inhibit hunger? Are the same brain regions involved in cognitive inhibition as involved in gastric stimulation?

15. Brookhaven Science Associates U.S. Department of Energy Thank You! Supported by DOE/OBER Brookhaven Science Associates U.S. Department of Energy