Lower striatal dopamine transporter binding in neuroleptic-naive schizophrenic patients is not related to antipsychotic treatment but it suggests an illness trait

Psychopharmacology (Berl). 2007 Apr;191(3):805-11. doi: 10.1007/s00213-006-0570-5. Epub 2006 Sep 22.

Abstract

Introduction: Drug induced parkinsonism (DIP) is directly related to dopamine D2 receptor blockade. However, there are many references describing parkinsonian signs (PS) in naive-patients. In our previous study, we observed lower DAT binding in a group of first-episode schizophrenic patients after short-term treatment with risperidone, compared with age-matched healthy controls.

Aim: To clarify if DAT decrease could be an illness trait, excluding the effect of antipsychotics on DAT availability, and to determine whether DAT availability before treatment with antipsychotics may predict subsequent development of PS.

Materials and methods: A new series of 20 neuroleptic-naive schizophrenic patients and 15 healthy subjects was recruited. SPECT with [(123)I] FP-CIT (DaTSCAN(R)) was performed before starting antipsychotics and after 4 weeks of treatment. PS and psychopathological status were assessed by the Simpson-Angus (SAS), CGI and PANSS scales. Quantitative analyses of SPECTs were performed using ROIs placed in the caudate, putamen and occipital cortex.

Results: Schizophrenic patients showed lower DAT binding compared with the healthy subjects at baseline (p<0.001) and after a 4-week-treatment period (p=0.001). Six out of eight schizophrenic patients of the DIP group were symptomatic for PS at baseline, in comparison to two out of 12 in the NoDIP group. Nonetheless, no differences were observed on DAT between DIP and NoDIP, neither at baseline (p=0.360) nor at endpoint (p=0.984). Finally, no differences between baseline-endpoint DAT binding were observed, neither in the DIP group (p=0.767) nor in the NoDIP group (p=0.093).

Conclusion: Our new series of first-episode naive-schizophrenic patients (1) points out DAT dysfunction as an illness trait due to the significantly lower DAT binding in schizophrenic patients in comparison to healthy subjects; (2) supports the results of other authors who describe PS in never-treated patients; (3) confirms that [(123)I] FP-CIT does not allow us to predict which patients will develop parkinsonism due to the lack of differences between DIP and NoDIP patients; and (4) confirms a null effect of antipsychotics on DAT due to the lack of differences in [(123)I] FP-CIT before and after a 4-week-treatment period.

Publication types

  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / therapeutic use*
  • Caudate Nucleus / metabolism
  • Dopamine Plasma Membrane Transport Proteins / drug effects
  • Dopamine Plasma Membrane Transport Proteins / metabolism*
  • Down-Regulation
  • Female
  • Humans
  • Male
  • Neostriatum / diagnostic imaging
  • Neostriatum / drug effects
  • Neostriatum / metabolism*
  • Parkinson Disease, Secondary / etiology*
  • Parkinson Disease, Secondary / metabolism
  • Psychiatric Status Rating Scales
  • Putamen / metabolism
  • Risperidone / adverse effects
  • Risperidone / therapeutic use*
  • Schizophrenia / complications
  • Schizophrenia / diagnostic imaging
  • Schizophrenia / drug therapy*
  • Schizophrenia / metabolism
  • Schizophrenic Psychology*
  • Severity of Illness Index
  • Tomography, Emission-Computed, Single-Photon / methods
  • Tropanes / metabolism

Substances

  • Antipsychotic Agents
  • Dopamine Plasma Membrane Transport Proteins
  • Tropanes
  • 2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane
  • Risperidone