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
Mar 31, 2015
Brookhaven Science AssociatesU.S. Department of Energy
Gene-Jack Wang, M.D.
The Addiction-Obesity Connection
Brookhaven Science AssociatesU.S. Department of Energy
Brookhaven Science AssociatesU.S. Department of Energy
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are needed to see this picture.
Brookhaven Science AssociatesU.S. Department of Energy
United States of Obesity
Time.com June 7, 2004
Brookhaven Science AssociatesU.S. Department of Energy
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
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)
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
Brookhaven Science AssociatesU.S. Department of Energy
Food Stimulation
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
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
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
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
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
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
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?
Brookhaven Science AssociatesU.S. Department of Energy
Thank You!
Supported by DOE/OBER
Brookhaven Science AssociatesU.S. Department of Energy