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Transcript of Brookhaven Science Associates U.S. Department of Energy Gene-Jack Wang, M.D. The Addiction-Obesity...
![Page 1: Brookhaven Science Associates U.S. Department of Energy Gene-Jack Wang, M.D. The Addiction-Obesity Connection Brookhaven Science Associates U.S. Department.](https://reader035.fdocuments.in/reader035/viewer/2022062511/5519b8805503467a578b48bf/html5/thumbnails/1.jpg)
Brookhaven Science AssociatesU.S. Department of Energy
Gene-Jack Wang, M.D.
The Addiction-Obesity Connection
Brookhaven Science AssociatesU.S. Department of Energy
![Page 2: Brookhaven Science Associates U.S. Department of Energy Gene-Jack Wang, M.D. The Addiction-Obesity Connection Brookhaven Science Associates U.S. Department.](https://reader035.fdocuments.in/reader035/viewer/2022062511/5519b8805503467a578b48bf/html5/thumbnails/2.jpg)
Brookhaven Science AssociatesU.S. Department of Energy
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![Page 3: Brookhaven Science Associates U.S. Department of Energy Gene-Jack Wang, M.D. The Addiction-Obesity Connection Brookhaven Science Associates U.S. Department.](https://reader035.fdocuments.in/reader035/viewer/2022062511/5519b8805503467a578b48bf/html5/thumbnails/3.jpg)
Brookhaven Science AssociatesU.S. Department of Energy
United States of Obesity
Time.com June 7, 2004
Brookhaven Science AssociatesU.S. Department of Energy
![Page 4: Brookhaven Science Associates U.S. Department of Energy Gene-Jack Wang, M.D. The Addiction-Obesity Connection Brookhaven Science Associates U.S. Department.](https://reader035.fdocuments.in/reader035/viewer/2022062511/5519b8805503467a578b48bf/html5/thumbnails/4.jpg)
Brookhaven Science AssociatesU.S. Department of Energy
Cocaine Alcohol Heroin
AbuserControl
[11C]raclopride
Abuser AbuserControl Control
Dopamine D2 images of Drug Addiction
Cocaine Alcohol Heroin
![Page 5: Brookhaven Science Associates U.S. Department of Energy Gene-Jack Wang, M.D. The Addiction-Obesity Connection Brookhaven Science Associates U.S. Department.](https://reader035.fdocuments.in/reader035/viewer/2022062511/5519b8805503467a578b48bf/html5/thumbnails/5.jpg)
Brookhaven Science AssociatesU.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/m2)10 age-matched controls (BMI: 25±3 kg/m2)
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Brookhaven Science AssociatesU.S. Department of Energy
Lower dopamine receptors in obese than in control subjects
2
0ml/gm
Control Subjects
Obese Subjects
[11C]raclopride
Wang et al, Lancet 2001
Bmax/Kd
BMIControl subjects
20
25
30
35
40
45
50
55
60
65
1.8 2 2.2 2.4 2.6 2.8 3 3.2 3.4 3.6 3.8
Obese subjects (n = 10)Control subjects (n = 10)
BMI
Dopamine Receptor Concentration
P < 0.002
P < 0.3
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Brookhaven Science AssociatesU.S. Department of Energy
Food Stimulation
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Brookhaven Science AssociatesU.S. Department of Energy
Brain Dopamine Response to Food Stimulation(B
max
/Kd)
(Bm
ax/K
d)
2.52.5
33
3.53.5
44
Placebo/NeutralPlacebo/Neutral MP/FoodMP/Food
p < 0.005p < 0.005
1.51.5
00
ml/gml/g
Volkow, et al, Synapse 2002
-2-2
00
22
44
66
88
1010
00 55 1010 1515 2020 2525 3030D
esire
for F
ood
Des
ire fo
r Foo
d
% Change Bmax/kd% Change Bmax/kd
p < 0.01p < 0.01
NeutralNeutral FoodFood
Brookhaven Science AssociatesU.S. Department of Energy
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Brookhaven Science AssociatesU.S. Department of Energy
Cue-induced increases in DA were associated with craving
P < 0.002
% Change Bmax/Kd% Change Bmax/Kd
-0.50-0.50
0.00.0
0.500.50
1.01.0
1.51.5
2.02.0
2.52.5
-40-40-30-30-20-20-10-1000101020203030
Putamen
Cha
nge
in C
ravi
ngC
hang
e in
Cra
ving
(Pre
- Po
st)
(Pre
- Po
st)
Relationship between Cue-Induced Decreases in [C-11]raclopride Binding and Cocaine Craving
Cau
date
Cau
date
Puta
men
Puta
men
2.002.00
2.502.50
3.003.00
3.503.50
NeutralNeutralCocaine-CuesCocaine-Cues
Bm
ax/K
dB
max
/Kd
P < 0.05P < 0.05
P < 0.01P < 0.01
Volkow et al, 2006
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Brookhaven Science AssociatesU.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
0.0 2.0 4.0 6.0 8.0 10m
icrom
ol/1
00g/
min
(MP
- Pla
cebo
)Self Report Craving
r = 0.79, p < 0.0002
Brookhaven Science AssociatesU.S. Department of Energy
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Brookhaven Science AssociatesU.S. Department of Energy
% Metabolic Changes
-10
-5
0
5
10
15
20
25
-10 0 10 20 30 40 50 60 70 80
% 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 AssociatesU.S. Department of Energy
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Brookhaven Science AssociatesU.S. Department of Energy
Why do some people continue to eat when the stomach is full?18FDG-PET (IGS “on” vs IGS “off” in obese subjects)
Orbitofrontal Cortex(Self-Control)
Hippocampus(Memory)
Striatum(Motivation)
IGS: Implantable gastric stimulator
Emotional eating
3
4
5
6
7
8
9
10
11
12
13
.6 .8 1 1.2 1.4 1.6 1.8 2 2.2 2.4
(n=2)
2
3
ON OFF
p < 0.04
Wang et al, PNAS USA 2006
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Brookhaven Science AssociatesU.S. Department of Energy
Decreased brain activation during cognitive inhibition of hunger
hunger
Absolute metabolic changes
-25
-20
-15
-10
-5
0
5
-8 -7 -6 -5 -4 -3 -2 -1 0
r = 0.73, p = 0.02
Orb
itofr
onta
l cor
tex
AmygdalaHippocampus
Cerebellum
CingulateStriatum
-1
0
1
2
3
4
5
0 10 20 30 40 50
Time (min)
Hunger
Food stimulation
Cognitive Inhibition
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Brookhaven Science AssociatesU.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?
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Brookhaven Science AssociatesU.S. Department of Energy
Thank You!
Supported by DOE/OBER
Brookhaven Science AssociatesU.S. Department of Energy