Similarity Of Obesity And Addiction Viewed In The Light Of

Brain Imaging

Gene-Jack Wang, MD, Sr. Clinician, Laboratory of

Neuroimaging, National Institute of Alcohol Abuse and

Alcoholism

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Hypothalamus

Ventral tegmental area(Reward)

Emotional Factors

(Stress)

Intrinsic factorsLeptin, Insulin, Ghrelin, PYY

Extrinsic factorsfood-related cue

& availability

(Nutritional need)

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VTA/SNnucleus accumbens

frontalcortex

0

50

100

150

200

0 60 120 180Time (min)

% o

f B

asal R

ele

ase

Empty

Box Feeding

Di Chiara et al.

FOOD

0100200300400500600700800900

10001100

0 1 2 3 4 5 hr

Time After Amphetamine

% o

f B

asa

l R

ele

ase

AMPHETAMINE

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PET Scanner PET Image

U

C

L

A

Ovarian Cancer

lung metastases

18FDG

511 kev + - 511 kev

180o

DA Transporters

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DA

DA

DA

DA DADA

DA

signal

DA Receptors

Metabolism

Dopamine Cell

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Cocaine

Alcohol

DA

DA

DA

DA DADA

DA

Reward Circuits

DADA DA

DA

DA

Reward Circuits

DA

DA

DA

DA DA

DA

Drug Abuser

Non-Drug Abuser

Heroin

Meth

Volkow et al., 2002.

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10 Control Subjects(BMI: 25±3 kg/m2)

10 Obese Subjects(BMI: 51±5 kg/m2)

[11C]raclopride

Wang GJ et al, Lancet 2001

Obese subjects (n = 10)

Control subjects (n = 10)

BMI

Dopamine Receptor Concentration

P < 0.002

P < 0.3

Dopamine modulates motivation and

reward circuits and hence dopamine

deficiency in obese subjects may

perpetuate pathologic eating as a

means to compensate for the

decrease activation of reward circuits.

2

0

ml/gm

2/5/2015 RiverMend Health, LLC 8Volkow ND, Wang GJ,

et al, Obesity 2008

Orbitofrontal cortexAnt.

Cingulate

• 21 healthy subjects (BMI 19 to 37) studied during baseline condition.

• Negative correlation between BMI and metabolic activity in prefrontal regions.

• Metabolism in these prefrontal regions was positively associated with performance in tests of memory (California verbal learning tests) and executive function (Stoop interference and Symbol digit modality tests).

• Deleterious effects of excessive weight on cognitive function in healthy individuals may be mediated in part via its association with decreased activity of prefrontal regions.

p < 0.005

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p < 0.005

3.0 3.5 4.0 4.5 5.0

40

45

50

55

60

65

70

D2R (Bmax/Kd)

Medial Orbitofrontal

3.0 3.5 4.0 4.5 5.0

40

45

50

55

60

65

70Cingulate Gyrus

Mo

l/100

g/m

in

Control Subjects Obese Subjects

2

0

ml/gm

The association between DA D2 receptors and metabolism in orbitofrontal cortices and cingulate gyrus suggests that D2 receptor-mediated dysregulation of regions implicated in inhibitory control may underlie the inability to control their food intake despite their conscious attempts to do so.

Volkow ND, Wang GJ, et al,

NeuroImage 2008

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Striatum

CG

PreF

OFC

30

35

40

45

50

55

60

65

1.8 2 2.2 2.4 2.6 2.8 3 3.2 3.4DA D2 Receptors (Ratio Index)

OF

Cum

ol/1

00g/

min

r = 0.7, p < 0.001

30

40

50

60

70

80

90

2.9 3 3.1 3.2 3.3 3.4 3.5 3.6

OF

Cum

ol/1

00gr

/min

DA D2 Receptors (Bmax/kd)

Cocaine Abusers

r = 0.7, p < 0.005

METH Abusers

control Volkow et al., AJP 2001.

Cocaine abuser

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Drive

OFCSaliency

NAc

Memory

Amygdala

Control

CG

Non-Addicted Brain

STOP

GODrive

Memory

Saliency

Control

Drive

Memory

Saliency

Adapted from: Volkow et al.,

J Clin Invest 2003.