October 2002
Schizophrenia may not be one single disease but rather an array of disorders whose psychiatric and cognitive symptoms vary according to which part of the brain is affected and to what degree. That's the conclusion of a study published in the October issue of Neuropsychology, in which a seven-neuroscientist team linked schizophrenic subtypes with different memory problems and different brain anatomies. The scientists say this is a "first step in our efforts to uncover the specific biological mechanisms of the disorder," which they hope will lead to better diagnosis and treatment of people with schizophrenia. Neuropsychology is published by the American Psychological Association (APA).
Bruce Turetsky, M.D., of the University of Pennsylvania Health System, led the study, which examined 116 patients diagnosed with schizophrenia and 129 normal control participants. The researchers used the California Verbal Learning Test to assess different aspects of learning and memory, including overall recall ability, rate of learning over repeated trials, ability to retain learned material over time, and subsequent item recognition. Using MRI and PET scan images, they also studied the brain anatomy and metabolism of participants.
Analysis of the data revealed three clusters of patients with significantly different profiles of memory and brain measures. This means that there may be several different roads to schizophrenia's profoundly disordered cognition. Turetsky et al. identified the two cognitively impaired subtypes as "cortical" and "subcortical," consistent with the types of dementia observed in Alzheimer's and Huntington's disease, respectively.
The cortical subtype, found in 18 percent of the patients, was the most distinctive. These patients were predominantly male, younger, and with a relatively earlier age of illness onset . Their clinical symptoms were similar to those of the psychiatric diagnostic manual's (DSM-IV) "disorganized schizophrenia" subtype: They had problems maintaining attention, organizing their thoughts, and expressing ideas in a coherent and logical manner. These patients also had structural and functional pathology in their temporal lobes. The temporal lobes were relatively smaller, and metabolic rates were lower in temporal lobe areas linked to language and memory. This indicates that, in this group, focal temporal lobe pathology may underlie the cognitive impairment.
The subcortical subtype, found in 31 percent of the patient sample, showed a different clinical profile, with symptoms suggesting disease in the frontal-striatal region -- an area that can affect both cognition and motor function. Consistent with this, these patients had enlarged ventricles, the fluid-filled central areas of the brain, and scattered reductions in frontal-lobe gray matter. However, unlike patients in the cortical subgroup, they were relatively free of any signs of disease in the temporal lobes.
The other 51 percent of the patient group showed only mild memory impairments. The authors suggest that they might not be a distinct subgroup, but rather a composite mixture of patients who exhibit the same cognitive and neurobiological manifestations as the other two groups, but to a lesser extent.
