Positive Symptoms of Schizophrenia Negative Symptoms of - PDF document

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 Status 100% 50% 0 15 20 40 60 Age in years Stahl S M, Essential 10-20 Psychopharmacology (2000) DOPAMINE PATHWAYS Basal Ganglia Nucleus accumbens a Substantia c b nigra hypothalamus d Tegmentum Stahl S M, Essential 10-7 Psychopharmacology (2000) mesolimbic overactivity = positive symptoms of psychosis Stahl S M, Essential 10-9 Psychopharmacology (2000) 2

Mesolimbic Dopaminergic Hyperactivity in Schizophrenia Laruelle et al., Ann NY Acad Sci (2003) Relationship Between Affinity for Dopamine D 2 Receptors and Daily Dose for Treating Schizophrenia primary dopamine deficiency D2 receptor blockade increase in negative secondary symptoms dopamine deficiency mesocortical pathway Stahl S M, Essential 10-11 Psychopharmacology (2000) 3

Hypofunction of Mesocortical Dopaminergic Transmission in Schizophrenia Laruelle et al., Ann NY Acad Sci (2003) Dopamine Dyregulation in Schizophrenia Normal Schizophrenia ? PFC PFC NAc NAc DA DA DA DA VTA VTA PFC Glutamatergic PFC Glutamatergic transmission lesion Tonic inhibition of DA in NAc Increases DA in NAc Decreases DA in PFC Tonic excitation of DA in PFC Mesocortical system Mesolimbic system Dysfunctional mesocortical system Dysfunctional mesolimbic 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) 4

Kaplan and Hammer, Am Psychiatric Press Inc, 2002 Thesis- Dopamine Dysregulation in Schizophrenia Mechanism Mechanism Schizophrenia Sxs Schizophrenia Sxs 1. Hypoactivity 1. Hypoactivity of PFC of PFC Negative/Cognitive Negative/Cognitive DA Systems DA Systems Sxs Sxs 2. Hyperactivity of NAc NAc Positive Sxs Sxs 2. Hyperactivity of Positive DA Systems DA Systems 3. Neuroleptic 3. Neuroleptic induced induced Improves Positive Sxs Improves Positive Sxs DA blockade DA blockade Worsens Negative Sxs Worsens Negative Sxs 5