schizophrenia positive symptoms negative symptoms anx/dep aggressive symptoms cognitive symptoms 10-1 Stahl S M, Essential Psychopha (2000)
Schizophrenia positive symptoms negative symptoms anx/dep aggressive symptoms cognitive symptoms 10-1 Stahl S M, Essential Psychopharmacology (2000)
Dec 21, 2015
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schizophrenia
positive symptoms
negative symptoms
anx/dep aggressive symptoms cognitive
symptoms
10-1 Stahl S M, Essential Psychopharmacology (2000)
Positive Symptoms of Schizophrenia
Negative Symptoms of Schizophrenia
10-20 Stahl S M, Essential Psychopharmacology (2000)
100%
50%
0
15 20 40 60
Age in years
Functional Status
hypothalamus
d
c
Nucleus accumbens
Tegmentum
bSubstantia nigra
Basal Ganglia
a
DOPAMINE PATHWAYS
10-7 Stahl S M, Essential Psychopharmacology (2000)
mesolimbic overactivity = positive symptoms of psychosis
10-9 Stahl S M, Essential Psychopharmacology (2000)
Mesolimbic Dopaminergic Hyperactivity in Schizophrenia
Laruelle et al., Ann NY Acad Sci (2003)
Relationship Between Affinity for Dopamine D2 Receptors and Daily Dose for Treating Schizophrenia
primary dopamine deficiency
D2 receptor blockade
secondary dopamine deficiency
mesocortical pathway
increase in negative symptoms
10-11 Stahl S M, Essential Psychopharmacology (2000)
Hypofunction of Mesocortical Dopaminergic Transmission
in Schizophrenia
Laruelle et al., Ann NY Acad Sci (2003)
Dopamine Dyregulation in Schizophrenia
PFC
NAc
VTA
DADA
PFC Glutamatergic transmission
Tonic inhibition of DA in NAc
Tonic excitation of DA in PFC
Mesolimbic systemMesocortical system
Normal Schizophrenia ?
PFC
NAc
VTA
DADA
PFC Glutamatergic lesion
Increases DA in NAc
Decreases DA in PFC
Dysfunctional mesolimbic systemDysfunctional mesocortical system
DA-mediated motivational system functioning normally DA-mediated motivational reward-system deficiency
Courtesy of Alan I. Green, M.D.
Glutamate-Dopamine Interactions in Schizophrenia
Takahata and Moghaddam, J Neurochem (2000)
Kaplan and Hammer, Am Psychiatric Press Inc, 2002
Thesis- Dopamine Dysregulation in Schizophrenia
MechanismMechanism Schizophrenia SxsSchizophrenia Sxs
1. Hypoactivity of PFC1. Hypoactivity of PFC Negative/CognitiveNegative/CognitiveDA Systems DA Systems Sxs Sxs
2. Hyperactivity of NAc 2. Hyperactivity of NAc Positive SxsPositive Sxs DA Systems DA Systems
3. Neuroleptic induced3. Neuroleptic induced Improves Positive Improves Positive
Sxs DA blockade Sxs DA blockade Worsens Negative Worsens Negative SxsSxs
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