Dopaminergic, Functional, Structural, and Cognitive Disturbances in First-episode Schizophrenia
Condition: Schizophrenia
MeSH terms: Schizophrenia
Study type: Interventional

Summary: 
      We wanted to compare dopamine D2 receptor activity, brain structure, brain function, sensory
      gating and cognition in neuroleptic-naive schizophrenic patients and matched healthy
      controls. Additionally, we wanted to examine the effects of 3 months of treatment with either
      low doses of a typical or an atypical antipsychotic compound on the same functions. The
      hypotheses were that schizophrenic patients suffered from disturbances in brain function and
      structure, information processing, and extrastriatal D2 receptor activity, and that these
      disturbances would be related to each other and to psychopathology. Additionally, we expected
      the atypical compound to have an effect on some of the disturbances in information
      processing, and that the atypical compound - in contrast to the typical drug - would show
      extrastriatal over striatal selectivity.
    

Detailed description: 
      31 neuroleptic-naive schizophrenic patients and 25 matched controls were recruited from the
      greater Copenhagen area. The patients were randomized to treatment with either low doses of
      the typical antipsychotic compound, zuclopenthixol, or the atypical drug, risperidone.
      Patients and controls were examined at base-line and patients were re-examined after 3 months
      of treatment.The study has resulted in two finish Ph.D. theses (Torben Mackeprang and
      Birgitte Fagerlund).

      The data has in part been published in:

      Mackeprang T, Tjelle Kristiansen K, Glenthoj B. Prepulse inhibition of the startle response
      in drug-naïve, first-episode schizophrenic patients before and after 3 months of treatment
      with a typical or an atypical antipsychotic drug. Biological Psychiatry 2002; 52(9): 863-873.

      and

      Fagerlund B, Mackeprang T, Gade A, Hemmingsen R, Glenthoj BY. Effects of Low-Dose Risperidone
      and Low-Dose Zuclopenthixol on Cognitive Functions in First-Episode Drug-Naïve Schizophrenic
      Patients. CNS Spectr. 2004; 9: 364-74.

      and

      Glenthoj BY, Mackeprang T, Svarer C, Rasmussen H, Pinborg L, Friberg L, Baaré W, Hemmingsen
      R, Videbæk C. Frontal dopamine D2/3 receptor binding in drug-naïve first-episode
      schizophrenic patients correlates with positive psychotic symptoms and gender. Biological
      Psychiatry 2006; in press. Mar 30; [Epub ahead of print]. PMID: 16784819 [PubMed - as
      supplied by publisher].

      We are at present conducting a five-year follow-up study of the same cohort of patients and
      controls and plan a ten-year follow-up as well. The follow-up studies focus on brain
      structure (MRI), brain function, information processing, and psychopathology. We will
      correlate changes in structure and function to treatment, but no interventions
      (pharmacological or otherwise) are planned.
    

Intervention name(s): zuclopenthixol; risperidone
Intervention type(s): Drug; Drug
Intervention description(s): Patients will be administered zuclopenthixol orally in doses between 4 -24 mg/day, depending on an effective reduction of symptoms; Patients will be administered risperidone orally in doses between 1-6 mg/day, depending on an effective reduction of symptoms
Other intervention name(s): Cisordinol; Risperdal
Intervention MeSH terms: Risperidone; Clopenthixol
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: drug-naive; epidepride; single tomography; D2 receptor; information processing; PPI; antipsychotic treatment; MRI; fMRI; cognitive disturbances