Schizophrenia and Brain Mapping — New Evidence for a Neurologic Disease
Schizophrenia and Brain Mapping—New Evidence for a Neurologic Disease
abstracts & commentary
Sources: Garey LJ, et al. Reduced dendritic spine density on cerebral cortical pyramidal neurons in schizophrenia. J Neurol Neurosurg Psychiatry 1998;65:446-453; Heckers S, et al. Impaired recruitment of the hippocampus during conscious recollection in schizophrenia. Nature Neurosci 1998; 1(4):318-323; Hirayasu Y, et al. Lower left temporal lobe MRI volumes in patients with first-episode schizophrenia compared with psychotic patients with first-episode affective disorder and normal subjects. Am J Psychiatry 1998;155(10):1384-1391; Csernansky JG, et al. Hippocampal morphometry in schizophrenia by high dimensional brain mapping. Proc Natl Acad Sci USA 1998;95:11406-11411.
Slowly, but unavoidably, it becomes apparent that the devastating, largely predictable symptoms of schizophrenia (SZP) reflect inherent and predictable neurologic abnormalities of brain structure and function. As such, the condition philosophically enters the arena presently occupied by other degenerative neurologic diseases that insidiously attack the post-adolescent brain such as spinocerebellar disorders, Huntington’s, Parkinson’s, and Alzheimer’s diseases. Accordingly, Alert’s neurologic readers may increasingly be recruited to assist in diagnosing and early treatment of patients with SZP.
The identification of SZP and its early symptoms lagged for a considerable time, largely because the neurologic basis of its early behavioral symptoms were not understood by neurologists or psychiatrists. Even more, neither biochemical, behavioral, nor in vivo imaging abnormalities possessed sufficient strength to identify early cases. Even autopsy material was ambiguous in identifying firm anatomic markers. Antipsychotic drugs provided partial improvement, but none had sufficient specificity to restore severe SZP victims to a normal life. Hopefully, however, clinical markers have recently become more dependable and, most importantly, scientific analyses have started to chart the principal cerebral dysfunctions that begin to explain and, hopefully, to clinically diagnose the disease.
During the first years of this Decade of the Brain, several observers have reported the presence of abnormally large ventricles in young persons with SZP. Postmortem analyses confirmed this anatomic clue but could not directly identify cortical neuronal loss. Garey and colleagues, however, speculated that the seeming shrinking of the cerebral cortex might relate to a reduction of neurophil, caused by a sharp reduction of dendritic spines in layer 3 of the cortex. Choosing prefrontal and temporal lobe layers of eight postmortem schizophrenic brains, Garey et al found in autopsied SZP brains dendritic reductions in temporal cortex, controls = 276/mm vs. schizophrenic = 112/mm. Similarly, frontal cortex normal dendrites equalled 299/mm vs. schizophrenics 101; both differences, P = 0.001.
Csernansky and colleagues emphasize that schizophrenics’ defects of memory, attention, abnormal thoughts, and decision making have been suggestively associated with hippocampal dysfunction, but, thus far, little or no firm evidence of anatomic changes in that area have appeared. They used mathematic principles to transform computerized brain templates so as to compare volume and shape qualities on hippocampal structures in 15 matched pairs of schizophrenics and controls. Deformed hippocampal shapes were localized in areas of that structure that project to prefrontal cortex, strengthening the following report.
Hirayasu and colleagues lend strength to the concept that hippocampal and prefrontal cortical brain regions play important roles in schizophrenic behavior. Hirayasu et al compared 1.5 T MRI scans of 17 first appearance SZPs against 16 with affective disorder and 18 age-matched normals. Volumetric calculations revealed significantly smaller gray matter size of the left posterior temporal superior in the gyrus compared to the other 34 persons. Additionally, the left posterior amygdala was also smaller.
commentary
Most intriguing, however, is Heckers and associates’ report of functional brain imaging studies of schizophrenia. Previous studies (see references in their text) have indicated that: 1) poor working memory and intentional behavior associated with hypofunction in dorsolateral prefrontal cortex; 2) absent cognition (apathy/catatonia) relates to abnormalities in prefrontal-thalamic-cerebellar pathways; and 3) auditory hallucinations relate to increased function in medial temporal and limbic structures. Their present studies using functional brain activity (PET) indicate that during memory retrieval efforts, schizophrenics display increased prefrontal activity (the retrieving effort) that fail to stimulate the hippocampus so as to convert the stimulus into expressed memory. Put directly, hippocampal dysfunction impairs episodic memory in schizophrenia. As Fletcher emphasizes in his commentary, past observers lacking current quality instruments and cognitive testing devices have tended to assign the mental-memory dysfunction of schizophrenia as emerging from a hypofunctioning prefrontal lobe. It may not be the ultimate answer, but Heckers et al, Garey et al, Hirayasu et al, and Csernansky et al all emphasize that a functionally-morphologically hippocampus represents an equal, if not even more functionally damaged, structure.
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