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501. White gray matter ratios in the parahippocampal gyrus of paraphrenia
152S
BIOL PSYCHIATRY 2000;47:1S–173S
dol or risperidone versus vehicle-treated rats, with substantially greater volume increases in the haloperidol-treated rats. Following 8 months of drug administration, striatal volume was greater in both haloperidoltreated and risperidone-treated rats, as compared to animals receiving vehicle, although only significantly so in haloperidol-treated animals. This study indicates that chronic neuroleptic treatment produces an adapative responses that leads to substantial and long-lasting alterations in striatal structure. Ongoing studies in our lab include investigation of the cellular and molecular components that may be underlying this hypertrophic response following chronic neuroleptic treatment.
499. GLIAL FIBRILLARY TANGLES IN PATIENTS WITH LATE ONSET SCHIZOPHRENIA M.F. Casanova, J.R. Stevens, R. Brown, C. Royston, C. Bruton
Saturday Abstracts
divided into 3 groups according to age of onset of symptoms: ⬍40, 40 to 60, and over 60 years. Light microscopy revealed that late onset schizophrenic had an abundance of neurofibrillary tangles in the hippocampus. Nineteen out of thirty late onset schizophrenics were classified as Braak stages III and IV. Comparisons between the three diagnoses (normal, paraphrenic, schizophrenic) were made using a mixed-effect analysis of variance to account for repeated measurements made on the individual brains without requiring a balanced design (measurement on both sides for each brain). There were no significant diagnosis (p ⫽ .952), side (p ⫽ .362), or diagnosis*side (p ⫽ .906) effects. The presence of neurofibrillary tangles and lack of pyramidal cell loss suggests that cytoskeletal disruption does not provide a tombstone for cell death. More importantly, neurofibrillary tangles in pyramidal cells of the hippocampus may offer a pathological correlate to symptoms of late onset schizophrenia.
501. WHITE GRAY MATTER RATIOS IN THE PARAHIPPOCAMPAL GYRUS OF PARAPHRENIA
116-A Psychiatry Service, Downtown VAMC, Augusta, GA 30910 Using immunocytochemistry against tau (AT8 clone) this study examined the brains of patients with schizophrenia who died at the Runwell (psychiatric) Hospital for the presence of white matter glial fibrillary tangles. The brains of 62 schizophrenic patients were divided according to age of symptom onset and compared to 20 controls. We also compared brain pathology in cases with onset of illness under age 40 with those whose onset occurred after the age of 40, and those after age 60. Degenerating astrocytes exhibited tau-positive glial tangles primarily surrounding the temporal horn. The periventricular glia cells were identified as subependymal astrocytes. Tau-positive astrocytes were also found in the white matter of the frontal cortex (u fibers), parahippocampal gyrus, basal forebrain and within the gray matter of the tail of the caudate. These glial elements were often associated to a large number of corpora amylacea. The proportion of subjects who were positive for tangles differed significantly among the three groups (p ⫽ .001). Glial tangles were present in 10.0% (2/20) of controls, 37.5% (12/32) of onset ⬍40 years, and 63.3% (19/30) of onset ⬎40. Post-hoc analysis showed that the rates of tangles differed significantly between controls and ⬎40. No other pairwise comparison was significant (controls versus ⬍40; or ⬍40 versus ⬎40). The high prevalence rate of glial fibrillary tangles among late-onset schizophrenic patients helps define a new pathological profile for this neurodegenerative condition.
500. NEUROFIBRILLARY TANGLES AND PYRAMIDAL CELL COUNTS IN PARAPHRENIA M.F. Casanova, D. Buxhoeveden, J.R. Stevens, R. Brown, C. Royston, C. Bruton
M.F. Casanova, E. Lindzen, A. Pathiraja, J.R. Stevens, R. Brown, C. Royston, C. Bruton 116-A Psychiatry Service, Downtown VAMC, Augusta, GA 30910 Previous studies support the idea that temporal lobe pathology may be involved in the pathogenesis of schizophrenia. The initial report of parahippocampal thinning by Bogerts et al. (1985) was soon corroborated by Brown and collaborators (1986). Planimetric analysis of the parahippocampal cortex revealed that the area of maximal gray matter reduction was located at the crest of the gyri as opposed to the walls of the collateral sulcus (Colter et al., 1987). In this study the gray/white matter ratios were obtained for the brains of 62 schizophrenic patients which were divided according to age of symptom onset and compared to 20 controls. Results of ANOVA and t-test comparisons showed that the average gray/white matter ratio in the anterior hippocampus of late onset schizophrenic was significantly larger than schizophrenics (left side p ⫽ 0.05, right side p ⫽ 0.02) and controls (left side p ⫽ 0.03, right side p ⫽ 0.05). The results suggest that late onset schizophrenics have a dysfunction of the larger parahippocampal neurons which alters their projections through the white matter. The importance of this finding is twofold: 1) The white matter abnormality may involve the major afferents to the hippocampal formation by means of the perforant pathway. 2) Contrary to clinical studies, the findings differentiate elderly, schizophrenic patients from those with late-onset schizophrenia. This finding may help justify the distinction between late- and early-life onset of schizophrenia, recently abandoned in DSM III and IV classifications.
502. REDUCED NEUROPIL IN THE AUDITORY CORTEX OF PATIENTS WITH SCHIZOPHRENIA
116-A Psychiatry Service, Downtown VAMC, Augusta, GA 30910 During the last decade many studies have focused on the hippocampus as a probable site of pathology in schizophrenia. This interest has been spurred by both functional and anatomical considerations. The hippocampus plays a pivotal role in processing information and modulating emotional behavior which, if abnormal, could provide a pathological correlate to the schizophreniform syndrome. This study used a computerized image analysis system to count hippocampal pyramidal neurons. The brains of 62 schizophrenic patients were divided according to age of symptom onset and compared to 20 controls. Schizophrenics were
M.F. Casanova, D. Buxhoeveden, A. Switala, E. Roy 116-A Psychiatry Service, Downtown VAMC, Augusta, GA 30910 It has been hypothesized that there is a reduction in the interneuronal space in the prefrontal cortex in Schizophrenia (Selemon et al., 1995). Because the spatial distribution of neurons in the cortex is focused around the minicolumn, we anticipated that the hypothesis of reduced interneu-
BIOL PSYCHIATRY 2000;47:1S–173S
dol or risperidone versus vehicle-treated rats, with substantially greater volume increases in the haloperidol-treated rats. Following 8 months of drug administration, striatal volume was greater in both haloperidoltreated and risperidone-treated rats, as compared to animals receiving vehicle, although only significantly so in haloperidol-treated animals. This study indicates that chronic neuroleptic treatment produces an adapative responses that leads to substantial and long-lasting alterations in striatal structure. Ongoing studies in our lab include investigation of the cellular and molecular components that may be underlying this hypertrophic response following chronic neuroleptic treatment.
499. GLIAL FIBRILLARY TANGLES IN PATIENTS WITH LATE ONSET SCHIZOPHRENIA M.F. Casanova, J.R. Stevens, R. Brown, C. Royston, C. Bruton
Saturday Abstracts
divided into 3 groups according to age of onset of symptoms: ⬍40, 40 to 60, and over 60 years. Light microscopy revealed that late onset schizophrenic had an abundance of neurofibrillary tangles in the hippocampus. Nineteen out of thirty late onset schizophrenics were classified as Braak stages III and IV. Comparisons between the three diagnoses (normal, paraphrenic, schizophrenic) were made using a mixed-effect analysis of variance to account for repeated measurements made on the individual brains without requiring a balanced design (measurement on both sides for each brain). There were no significant diagnosis (p ⫽ .952), side (p ⫽ .362), or diagnosis*side (p ⫽ .906) effects. The presence of neurofibrillary tangles and lack of pyramidal cell loss suggests that cytoskeletal disruption does not provide a tombstone for cell death. More importantly, neurofibrillary tangles in pyramidal cells of the hippocampus may offer a pathological correlate to symptoms of late onset schizophrenia.
501. WHITE GRAY MATTER RATIOS IN THE PARAHIPPOCAMPAL GYRUS OF PARAPHRENIA
116-A Psychiatry Service, Downtown VAMC, Augusta, GA 30910 Using immunocytochemistry against tau (AT8 clone) this study examined the brains of patients with schizophrenia who died at the Runwell (psychiatric) Hospital for the presence of white matter glial fibrillary tangles. The brains of 62 schizophrenic patients were divided according to age of symptom onset and compared to 20 controls. We also compared brain pathology in cases with onset of illness under age 40 with those whose onset occurred after the age of 40, and those after age 60. Degenerating astrocytes exhibited tau-positive glial tangles primarily surrounding the temporal horn. The periventricular glia cells were identified as subependymal astrocytes. Tau-positive astrocytes were also found in the white matter of the frontal cortex (u fibers), parahippocampal gyrus, basal forebrain and within the gray matter of the tail of the caudate. These glial elements were often associated to a large number of corpora amylacea. The proportion of subjects who were positive for tangles differed significantly among the three groups (p ⫽ .001). Glial tangles were present in 10.0% (2/20) of controls, 37.5% (12/32) of onset ⬍40 years, and 63.3% (19/30) of onset ⬎40. Post-hoc analysis showed that the rates of tangles differed significantly between controls and ⬎40. No other pairwise comparison was significant (controls versus ⬍40; or ⬍40 versus ⬎40). The high prevalence rate of glial fibrillary tangles among late-onset schizophrenic patients helps define a new pathological profile for this neurodegenerative condition.
500. NEUROFIBRILLARY TANGLES AND PYRAMIDAL CELL COUNTS IN PARAPHRENIA M.F. Casanova, D. Buxhoeveden, J.R. Stevens, R. Brown, C. Royston, C. Bruton
M.F. Casanova, E. Lindzen, A. Pathiraja, J.R. Stevens, R. Brown, C. Royston, C. Bruton 116-A Psychiatry Service, Downtown VAMC, Augusta, GA 30910 Previous studies support the idea that temporal lobe pathology may be involved in the pathogenesis of schizophrenia. The initial report of parahippocampal thinning by Bogerts et al. (1985) was soon corroborated by Brown and collaborators (1986). Planimetric analysis of the parahippocampal cortex revealed that the area of maximal gray matter reduction was located at the crest of the gyri as opposed to the walls of the collateral sulcus (Colter et al., 1987). In this study the gray/white matter ratios were obtained for the brains of 62 schizophrenic patients which were divided according to age of symptom onset and compared to 20 controls. Results of ANOVA and t-test comparisons showed that the average gray/white matter ratio in the anterior hippocampus of late onset schizophrenic was significantly larger than schizophrenics (left side p ⫽ 0.05, right side p ⫽ 0.02) and controls (left side p ⫽ 0.03, right side p ⫽ 0.05). The results suggest that late onset schizophrenics have a dysfunction of the larger parahippocampal neurons which alters their projections through the white matter. The importance of this finding is twofold: 1) The white matter abnormality may involve the major afferents to the hippocampal formation by means of the perforant pathway. 2) Contrary to clinical studies, the findings differentiate elderly, schizophrenic patients from those with late-onset schizophrenia. This finding may help justify the distinction between late- and early-life onset of schizophrenia, recently abandoned in DSM III and IV classifications.
502. REDUCED NEUROPIL IN THE AUDITORY CORTEX OF PATIENTS WITH SCHIZOPHRENIA
116-A Psychiatry Service, Downtown VAMC, Augusta, GA 30910 During the last decade many studies have focused on the hippocampus as a probable site of pathology in schizophrenia. This interest has been spurred by both functional and anatomical considerations. The hippocampus plays a pivotal role in processing information and modulating emotional behavior which, if abnormal, could provide a pathological correlate to the schizophreniform syndrome. This study used a computerized image analysis system to count hippocampal pyramidal neurons. The brains of 62 schizophrenic patients were divided according to age of symptom onset and compared to 20 controls. Schizophrenics were
M.F. Casanova, D. Buxhoeveden, A. Switala, E. Roy 116-A Psychiatry Service, Downtown VAMC, Augusta, GA 30910 It has been hypothesized that there is a reduction in the interneuronal space in the prefrontal cortex in Schizophrenia (Selemon et al., 1995). Because the spatial distribution of neurons in the cortex is focused around the minicolumn, we anticipated that the hypothesis of reduced interneu-