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.
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.