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The Addiction-Obesity Connection

The Addiction-Obesity Connection. Gene-Jack Wang, M.D. Brookhaven Science Associates U.S. Department of Energy. United States of Obesity. Time .com June 7, 2004. Brookhaven Science Associates U.S. Department of Energy. Dopamine D2 images of Drug Addiction. Alcohol. Heroin. Control.

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The Addiction-Obesity Connection

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

  2. UnitedStates ofObesity Time.com June 7, 2004 Brookhaven Science AssociatesU.S. Department of Energy

  3. Dopamine D2 images of Drug Addiction Alcohol Heroin Control Abuser Control Abuser Control Abuser Cocaine Cocaine Alcohol Heroin [11C]raclopride

  4. Obesity Compulsive overeating shares many of the same characteristics as drug addiction. Do obese subjects have abnormal levels of D2-receptor? 10 severely obese subjects (BMI: 51±5 kg/m2) 10 age-matched controls (BMI: 25±3 kg/m2)

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

  6. Food Stimulation

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

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

  9. Brain Activation with Methylphenidate Induced Cocaine Craving 85 r = 0.79, p < 0.0002 30 20 10 0.0 (MP - Placebo) micromol/100g/min -10 -20 0 -30 0.0 2.0 4.0 6.0 8.0 10 µmole/100g/min Self Report Craving Placebo Orbitofrontal Activation MP Volkow et al Am J Psychiatry 1999 Brookhaven Science AssociatesU.S. Department of Energy

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

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

  12. Decreased brain activation during cognitive inhibition of hunger Food stimulation Orbitofrontal cortex Cognitive Inhibition r = 0.73, p = 0.02 CingulateStriatum AmygdalaHippocampusCerebellum

  13. New intriguing questions • Do obese subjects have the same ability tosuppress 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?

  14. Thank You!Supported by DOE/OBER Brookhaven Science AssociatesU.S. Department of Energy

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