Atypical Antipsychotic Treatment Effect On Brain Function In Schizophrenia Measured By FMRI
Condition: Schizophrenia
MeSH terms: Schizophrenia
Study type: Interventional

Summary: 
      The general aim is to compare the effects of typical and atypical antipsychotic medication on
      brain structure and function. A parallel group treatment trial will be utilized to compare
      the effects of the typical antipsychotic thiothixene versus the atypical antipsychotics
      risperidone (RIS) and olanzapine (OLZ) on brain structure and function in schizophrenia in an
      effort to determine the neuroanatomic basis for cognitive pathology in schizophrenia and its
      amelioration by atypical antipsychotic drugs.
    

Detailed description: 
      The general aim of this study was to determine the neuroanatomic basis for cognitive
      pathology in schizophrenia, as well as the effects of treatment with typical and atypical
      antipsychotics on clinical symptoms, neurocognition and brain function, as measured with
      function magnetic resonance imaging. Subjects underwent a randomized parallel group treatment
      trial that consisted of: a four-week Thiothixene treatment period, followed by randomization,
      two-weeks cross titration, and six-weeks of double blind treatment with Risperidone (RIS) or
      Olanzapine (OLZ). Twenty-three patients with schizophrenia or schizoaffective disorder and
      fifteen healthy control subjects were initially enrolled. Diagnosis was established with the
      SCID. Subjects were assessed at two time points, at baseline after four weeks of Thiothixene
      treatment and at follow up, after eight weeks of double-blind atypical antipsychotic
      treatment. Controls were assessed once. Symptom severity was assessed using the PANSS.
      Cognitive functions associated with frontal and temporal cortical regions were probed with a
      neurocognitive testing battery using standardized attention, executive function and working
      memory tasks. Frontal and temporal cortical function was assessed with fMRI during the
      performance of visual and auditory oddball tasks. The visual task oddball task consisted of
      identifying an infrequent square presented within a series of frequent squares. The auditory
      oddball task consisted of identifying an infrequent pitch-deviant target tone embedded within
      a series of frequent standard tones. Thirteen patients and eleven controls completed fMRI at
      baseline and follow-up.

      The results indicated that patients treated with the typical neuroleptic Thiothixene showed
      significantly smaller extents of activations in superior temporal, anterior cingulate and
      thalamic regions as compared to control subjects during the auditory oddball task. Although
      treatment with atypical neuroleptics considerably reduced group differences in cortical
      activation between controls and patients, the current sample size proved to be insufficient
      to yield statistically significant group by time interactions. The percent signal change data
      was in the same direction, but proved to be less sensitive to group differences than the
      extent of activation. The group differences were not pronounced during the visual oddball
      task, but were in the same direction.
    

Intervention name(s): Risperidone; Olanzapine
Intervention type(s): Drug; Drug
Intervention description(s): 6mg/day or highest dose tolerated for 8 weeks, following 4 weeks baseline treatment of Thiothixene; 20mg/day for 8 weeks, following 4 weeks of baseline Thiothixene.
Other intervention name(s): risperidol, risperidal; Zydis, Zyprexa
Intervention MeSH terms: Olanzapine; Risperidone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science