title: Dopamine synthesis capacity in patients with treatment-resistant schizophrenia.
abstract: OBJECTIVE
  Elevated presynaptic striatal dopaminergic function is a robust feature of schizophrenia. However, the relationship between this dopamine abnormality and the response to dopamine-blocking antipsychotic treatments is unclear. The authors tested the hypothesis that in patients with schizophrenia the response to antipsychotic treatment would be related to the severity of presynaptic dopamine dysfunction, as indexed using [(18)F]-DOPA uptake positron emission tomography (PET).
  
  
  METHODS
  Twelve patients with treatment-resistant schizophrenia, twelve patients with schizophrenia who had responded to antipsychotics, and twelve healthy volunteers matched for gender, age, ethnicity, weight, and cigarette smoking underwent [(18)F]-DOPA PET scanning. [(18)F]-DOPA influx rate constants (K(i)(cer) values) were measured in the striatum and its functional subdivisions.
  
  
  RESULTS
  Patients who had responded to antipsychotic treatment showed significantly higher K(i)(cer) striatal values than did patients with treatment-resistant illness (effect size=1.11) and healthy volunteers (effect size=1.12). The elevated [(18)F]-DOPA uptake was most marked in the associative (effect size=1.31) and the limbic (effect size=1.04) striatal subdivisions. There were no significant differences between patients with treatment-resistant illness and healthy volunteers in the whole striatum or any of its subdivisions.
  
  
  CONCLUSIONS
  In some patients with schizophrenia, antipsychotic treatment may be ineffective because they do not exhibit the elevation in dopamine synthesis capacity that is classically associated with the disorder; this may reflect a different underlying pathophysiology or a differential effect of antipsychotic treatment.
authors.affiliation: Department of Psychosis Studies, Biomedical Research Centre, Institute of Psychiatry, King's College, London, UK. arsime.demjaha@kcl.ac.uk
authors.forename: Arsime
authors.initials: A
authors.lastname: Demjaha
authors.forename: Robin M
authors.initials: RM
authors.lastname: Murray
authors.forename: Philip K
authors.initials: PK
authors.lastname: McGuire
authors.forename: Shitij
authors.initials: S
authors.lastname: Kapur
authors.forename: Oliver D
authors.initials: OD
authors.lastname: Howes
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003342:Corpus Striatum / Q000187:drug effects / Q000503:physiopathology; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives*; D004298:Dopamine / Q000378:metabolism*; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008032:Limbic System / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D011569:Psychiatric Status Rating Scales; D017661:Receptors, Presynaptic / Q000187:drug effects* / Q000502:physiology*; D012016:Reference Values; D012559:Schizophrenia / Q000188:drug therapy* / Q000503:physiopathology*; D012565:Schizophrenic Psychology
chemical_list: D014150:Antipsychotic Agents; D017661:Receptors, Presynaptic; C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine; D004298:Dopamine