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.
The existence of categorically different subtypes may help to explain some of the inconsistencies in findings from prior studies of patients with schizophrenia. "One of the reasons we haven't been successful in identifying 'the cause' of schizophrenia," says lead researcher Bruce Turetsky, M.D., "may be because we are studying mixed groups of individuals who don't really have the same thing wrong with them. I suspect that studying such heterogeneous samples has been a very large barrier to progress."
"There is no laboratory test or X-ray that can tell you if a person has schizophrenia," he continues. "Because it's so variable, clinical subtypes, such as paranoid, catatonic, etc., have always been included as part of the DSM diagnosis. What has never been clear is whether these clinical subtypes represent different physiological problems or causes."
"Our results," Turetsky concludes, "indicate that there are different neurobiological profiles associated with different presentations of schizophrenia. We may be dealing with more than one disease." Researchers hope next to study whether these subtypes are stable over the course of schizophrenic illness. If they are, he adds, "then knowledge of these subtypes would facilitate both diagnosis and neurobiological research. Ultimately, this may allow us to target specific treatments to different groups of patients."
Medication can now fairly effectively quell hallucinations and delusions. A new understanding of schizophrenia's cognitive impairments and underlying brain abnormalities may help reduce the remaining problems -- the long-term social and occupational disabilities that can so profoundly disrupt the lives of people with schizophrenia.
Article: "Memory-Delineated Subtypes of Schizophrenia: Relationship to Clinical, Neuroanatomical, and Neurophysiological Measures," Bruce I. Turetsky, M.D.; Paul J. Moberg, Ph.D.; Lyn Harper Mozley, Ph.D.; Stephen T. Moelter, Ph.D.; Rachel N. Agrin, B.A.; Ruben C. Gur, Ph.D.; and Raquel E. Gur, M.D.; University of Pennsylvania; Neuropsychology, Vol. 16, No. 4.
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Reporters: Bruce Turetsky's email is firstname.lastname@example.org. He can also be reached by phone at 215-662-2826.
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