Positive Symptoms of Schizophrenia Negative Symptoms of - - PDF document

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Positive Symptoms of Schizophrenia Negative Symptoms of - - PDF document

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schizophrenia negative positive symptoms symptoms aggressive anx/dep cognitive symptoms symptoms Stahl S M, Essential 10-1 Psychopharmacology (2000) Positive Symptoms of Schizophrenia Negative Symptoms of Schizophrenia 1 Functional

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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

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10-20 Stahl S M, Essential Psychopharmacology (2000)

100% 50% 15 20 40 60 Age in years

Functional Status hypothalamus

d

c

Nucleus accumbens Tegmentum

b

Substantia 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)

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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)

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Hypofunction of Mesocortical Dopaminergic Transmission in Schizophrenia

Laruelle et al., Ann NY Acad Sci (2003)

Dopamine Dyregulation in Schizophrenia

PFC NAc VTA

DA DA PFC Glutamatergic transmission Tonic inhibition of DA in NAc Tonic excitation of DA in PFC Mesolimbic system Mesocortical system

Normal Schizophrenia ?

PFC NAc VTA

DA DA PFC Glutamatergic lesion Increases DA in NAc Decreases DA in PFC Dysfunctional mesolimbic system Dysfunctional 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)

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Kaplan and Hammer, Am Psychiatric Press Inc, 2002

Thesis- Dopamine Dysregulation in Schizophrenia

Mechanism Mechanism Schizophrenia Schizophrenia Sxs Sxs 1.

  • 1. Hypoactivity

Hypoactivity of PFC

  • f PFC

Negative/Cognitive Negative/Cognitive DA Systems DA Systems Sxs Sxs

  • 2. Hyperactivity of
  • 2. Hyperactivity of NAc

NAc Positive Positive Sxs Sxs DA Systems DA Systems 3.

  • 3. Neuroleptic

Neuroleptic induced induced Improves Positive Improves Positive Sxs Sxs DA blockade DA blockade Worsens Negative Worsens Negative Sxs Sxs