Schizophrenia is a disorder heterogeneous with respect to cognitive dysfunctions. This heterogeneity is presumed to reflect heterogeneity in brain pathophysiology, although this has not been experimentally verified. The primary goal of this project is to use functional and structural MRI to confirm hypothesized differences in brain dysfunction between two groups of schizophrenic patients that in preliminary studies differed markedly in cognitive dysfunction. Three independent pilot studies demonstrated and confirmed the existence of the subgroups. One group has large deficits in auditory verbal working memory but normal performance on more difficult tasks of auditory nonverbal working memory. The other group has marked deficits on both the verbal and nonverbal tests as well as on simple perceptual tasks. Each subgroup represents about 20 percent of patients with schizophrenia. The second goal of this project is to characterize further the cognitive differences between the groups using a broad ranging neurocognitive test battery. 150 patients and 50 controls will participate in this study of cognition. Patients will be selected for functional and structural MR who on the basis of cognitive test performance meet criteria for one or the other of the two subgroups identified in the preliminary studies (n=25 in each). Groups of controls matched to each patient group in gender, age and parental education (n=25 in each) will also participate in MRI. Functional studies will use verbal and nonverbal auditory working memory activation tasks to specifically target the brain systems that underlie the cognitive dysfunctions in the two groups. Structural MRI will focus on the frontal and temporal lobes, both of which have been reported to be smaller in volume in patients with schizophrenia and both of which are part of the brain systems of working memory. If hypothesized differences between the two groups of patients in brain and cognitive dysfunction are confirmed, it will support the value of cognitive measures in subtyping and help characterize two pathophysiologically distinct subgroups. Identification of such subgroups is essential for future studies of etiology and treatment.
| Colibazzi, Tiziano; Wexler, Bruce E; Bansal, Ravi et al. (2013) Anatomical abnormalities in gray and white matter of the cortical surface in persons with schizophrenia. PLoS One 8:e55783 |
| Wexler, Bruce E; Zhu, Hongtu; Bell, Morris D et al. (2009) Neuropsychological near normality and brain structure abnormality in schizophrenia. Am J Psychiatry 166:189-95 |
