title: Different corticostriatal patterns of L-DOPA utilization in patients with untreated schizophrenia and patients treated with classical antipsychotics or clozapine.
abstract: Positron emission tomography (PET) has been shown to be of great importance in elucidating the mechanism of action of antipsychotic drugs. In psychotic patients L-[11C]DOPA PET has been used to demonstrate some differences in dopaminergic activity compared with that in healthy volunteers. Ten healthy volunteers were investigated with PET and L-[11C]DOPA. Ten drug-free patients with psychosis, nine stable schizophrenics treated with clozapine, and nine stable patients treated with classical antipsychotics were also investigated with L-[11C]DOPA. Principal-component analysis was employed for the analysis of L-[11C]DOPA Ki values across a number of corticostriatal brain regions. These data revealed a significant three-component model with clear-cut separation between healthy controls and patients with unmedicated schizophrenia. Stable optimal treatment with either classical neuroleptics or clozapine partially, albeit differentially, reversed the aberrant patterns seen in drug-free schizophrenia. It can thus be concluded that schizophrenia is associated with abnormal patterns of L-[11C]DOPA utilization in corticostriatal systems. Treatment with clozapine or classical neuroleptics induces partial, albeit differential, normalization of the abnormal patterns seen in untreated schizophrenia.
authors.affiliation: Department of Psychiatry, Västerås, Sweden. ola.gefvert@ltvastmanland.se
authors.forename: Ola
authors.initials: O
authors.lastname: Gefvert
authors.forename: Leif H
authors.initials: LH
authors.lastname: Lindström
authors.forename: Nicholas
authors.initials: N
authors.lastname: Waters
authors.forename: Susanna
authors.initials: S
authors.lastname: Waters
authors.forename: Arvid
authors.initials: A
authors.lastname: Carlsson
authors.forename: Joakim
authors.initials: J
authors.lastname: Tedroff
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001921:Brain / Q000000981:diagnostic imaging*; D003024:Clozapine / Q000627:therapeutic use*; D015259:Dopamine Agents / Q000008:administration & dosage*; D006220:Haloperidol / Q000627:therapeutic use; D006801:Humans; D016018:Least-Squares Analysis; D007980:Levodopa / Q000008:administration & dosage*; D025341:Principal Component Analysis; D012559:Schizophrenia / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D014055:Tomography, Emission-Computed
chemical_list: D014150:Antipsychotic Agents; D015259:Dopamine Agents; D007980:Levodopa; D003024:Clozapine; D006220:Haloperidol