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Neuropsychological
Disease?
Juan J Fumero-Perez MD
Psychiatrist
Juan J. Fumero-Perez, MD
SPEAKER/CONSULTANT FOR:
Merck
Sunovion
MEMBER OF:
SEA VIEW HOSPITAL
San Juan Capestrano Faculty
HealthBookPR
H O N O R A R Y NOT R E C E I V E D
THIS
PRESENTATION
FOR
A simplified version
of homeostatic
regulation of food
intake; focus on
signals from the
digestive system
(ghrelin, CCK, PYY),
adipose tissue
(leptin) and the
pancreas (insulin)
ghrelin signals
hunger (orexigen,
stimulates food
intake), whereas
leptin, insulin,
CCK and PYY
signal satiety
(anorexigen,
inhibit food
intake).
Their targets are
neurons in the
arcuate nucleus,
of which
POMPC/CART
provide an orexic
signal and
AgRP/NPY
NTS, nucleus tractus solitarius
neurons drive the
30
30
BMI = weight (kg)/height (m)2
BMI body mass index
(IMC indice de masse corporelle)
Context
It is necessary to consider:
Obesity research encompasses work of:
Economics
Sociology
Nutrition
Biology
Psychology
Epidemiology
Obesity: Is It A
Neuropsychological Disease?
JuanJFumeroPerezMD
Psychiatrist
Psychosocial Aspects of
Obesity
Obese individuals are subject to
weight-based stigmatization in a
variety of settings,1
Report poorer quality of life
compared with lean individuals.2
1. Obesity 2006;14:18021815.
2. http://www.endotext.com.
Similarities
Similarities among:
Obesity,
Drug addiction
Compulsive behaviors
Suggests that a form of obesity
characterized by compulsive food
consumption should be included as a
mental disorder in DSM-V.1214
1. Am J Psychiatry 2007;164: 708
710.
2. Neuroimage 2008;42:15371543.
3. Nat Neurosci 2005;8:555560.
ADDICTION and
OBESITY
Overlapping Neuronal Circuits
Withdrawal symptoms
Function
Brain region
Motivation
nucleus accumbens
Learning/habits
Amygdala/striatum
Reward value
orbitofrontal cortex
Emotional reactivity
amygdala
Behavioural control
prefrontal cortex
Drugs Activate:
Palatability (&
senses)
Via direct
pharmacologic
effects directly or
indirectly thru
modulation
Involves both
endogenous
Endocannabinoid
Opioid
Via dopamine
increase
Glucose
Insulin concentration
Gaba
Nicotine
Opiate
Cannabinoids
Reward-pleasure
Memory-Learning
Motivation
cognitive control,
in charge of
restraining
cravings
ventral pallidum
Circuits having
interdependent and
overlapping roles in
addiction
26
Trends in Molecular Medicine, Volume 12, Issue 12, December 2006, Pages 559-566
Meja 2008
DADA
DA
Dopamine
DA
DA
DA DA
DA
DA DA
DADA
Reward Circuits
Non Drug Abuser
Brookhaven Science Associates
U.S. Department of Energy
DA
Dopamine
DA
DA
Reward Circuits
Addicted Subject
4.
5
Meth
Alcohol
3.
5
3
2.
5
2
1.
5 1
3. 5
2
0
2
5
3
0
3
5
4
0
4
5
40
45
5
0
2
3
2.8
Bmax/Kd
DAD2ReceptorAvailability
Cocaine
DAD2Receptors
(RatioIndex)
2.6
2.4
2.2
2
1.8
1.6
20
Heroin
control
addicted
25
30
35
50
Dopamine D2 Receptors
[11C]raclopride
2
0
ml/gm
Control Subjects
2.99 (Sd 0.41)
Obese Subjects
2.47 (Sd 0.36)
P < 0.008
p < 0.002
Obese subjects
55
50
Control subjects
BM I
45
BMI
40
35
p = 0.3
30
25
20
1 .8
2 .2 2 .4 2 .6 2 .8 3 3 .2 3 .4 3 .6 3 .8
B m a x Concentration
/K d
Dopamine Receptor
frontal
cortex
nucleus
accumbens
REWARD
& Pleasure
N VP
Ac
c
VTA/SN
% of Basal Release
% of Basal Release
Dopamine
Neurotransmission
1100
1000
900
800
700
600
500
400
300
200
100
0
AMPHETAMINE
1
2
3
4
Time After Amphetamine
5 hr
FOOD
200
150
100
Empty
50 Box Feeding
0
60
120
Time (min)
180
Di Chiara et al.
Hipp
Amyg
MEMORY/
LEARNING
Auditory cue
HerewetestedifconditionedstimuliincreaseDAin
addictedsubjectsanditsrelationshiptodrugcraving
1.5
4
0
3.5
p < 0.11
ml/g
p < 0.02
p < 0.005
MP/Neutral
MP/Food
EXECUTIVE
FUNCTION
PFC
ACG
INHIBITORY OFC
SCC
CONTROL
In addicted subjects or in
obese subjects, are the
changes in DA function
linked with disruption of
frontal activity?
Used multiple tracers to
evaluated in the same
subject DA D2 receptors
and brain glucose
metabolism (marker of
brain function).
MOTIVATION/
DRIVE
D
A
D
D ADA
A D
A
D
A
DA D2 Receptors
DA
signal
Metabolism
Correlations Between
D2 Receptors in Striatum
& Brain Glucose Metabolism
PreF
Mol/100g/min
CG
Striatum
OFC
Cocaine
Abusers
90
umol/100gr/min
OFC
umol/100g/min
OFC
65
60
55
50
45
40
35
30
80
70
60
METH
Abusers
p<
0.005
50
r=0.7,p<0.001 40
DAD2Receptors
(RatioIndex)
70 Cingulate
65
Gyrus
60
55
50
45
40
3.0 3.5 4.0 4.5 5.0
70
Medial
65 Orbitofrontal
60
55
50
45
403.0 3.5 4.0 4.5 5.0
r=0.7,p<0.005
30
2.9 3 3.1 3.2 3.3 3.4 3.5 3.6
DAD2Receptors
(Bmax/kd)
D2R (Bmax/Kd)
85
Neutral
Stimuli
% Metabolic Changes
20
Orbitofrontal
Activation
Food
Stimuli
15
10
5
0
-5
0
mole/100g/min
r = 0.84,
p = 0.001
-10
-10 0 10 20 30 40 50 60 70 80
%Changesoffeelingofhunger
Compared with the non-addicted state, the salience value of a drug (green) and its associated cues (purple) is
enhanced in the addicted state
37
Meja 2007
WhatProvidestheSpecificity?
Drugs
FOOD
Implication
HYP
Glucose
Peptides
Neurohor
mones
Amino
acids
Fatty
acids
Organs
Tissues
Cells
Molecules
work
family
friends
community
nature
food
Sex
sports
music
Dance
Art
drugs
work
work
family
family
friends
friends
community
community
nature
nature
food
food
sex
Sex
tool-making
sports
sports
Music
music
dance
dance
art
crafts
artdrugs
VTA/SN
DOPAMINE
PFC
NAc
Amygdala
Hippocampus
Dorsal Striatum
Motor Complex
drugs
Obesity: Is It A
Neuropsychological
Disease?
Juan J Fumero-Perez MD
Psychiatrist
Gracias Por Su
Atencion.
Juan J Fumero-Perez MD
www.jfbrainwellness.com
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