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VBR in schizophrenia: Relationship to family history of psychosis and season of birth
81
enlargement. The precise timing of this abnormality in the course of schizophrenic illness and its relationship to neuropsychological dysfunction and premorbid adjustment remains unclear. We have previously shown that VBR could be used to dichotomize a sample of schizophrenics and generate hypotheses regarding premorbid ability and development: ( 1) childhood onset associated with poor premorbid function, low educational achievement, lower IQ, and lower VBR; and (2) later onset with relatively normal childhood function, higher academic achievement and IQ, and increased VBR. To re-examine these questions, we investigated the relationship between VBR, premorbid psychosocial and cognitive ability, and neuropsychological function in another sample of 55 DSM III-R schizophrenic inpatients. Each was rated on BPRS and SANS at baseline and after 4-weeks of antipsychotic treatment. VBR was determined from MRI scans via computerized planimetry. Neuropsychological testing was used to gauge current functioning and to estimate premorbid cognitive ability; the Premorbid Adjustment Scale was used to estimate premorbid psychosocial functioning. Unlike our previous study, VBR was not associated with premorbid cognitive or psychosocial functioning, decline in premorbid ability, or symptom status. Our failure to replicate our own previous findings is another example of the difficulty in obtaining consistently replicable findings in schizophrenia. In part, the discrepant findings may be related to limitations in current methods of image acquisition and analysis. More precise and comprehensive techniques such as shape analysis and image averaging may help to clarify these important issues involved in understanding the development and pathophysiology of schizophrenia.
VBR IN SCHIZOPHRENIA: RELATIONSHIP TO FAMILY HISTORY OF PSYCHOSIS AND SEASON OF BIRTH John R. DeQuardo*, M o n a Goldman, Rajiv Tandon
Schizophrenia Program, University of Michigan, Ann Arbor, MI48109-0116, USA Ventricular enlargement has been consistently demonstrated in schizophrenia using both CT and MRI. Despite this, the structural changes that underlie increased VBR and its relationship to environmental factors (intrauterine viral exposure, obstetric complications) and family history remain poorly defined. Increased VBR has been shown in some studies to correlate with family history of schizophrenia and WinterSpring birth (presumed intrauterine viral exposure). Methodologic issues aside, obtaining a clearer picture of the contribution of environmental and genetic factors to VBR would shed light on the developmental pathophysiology of schizophrenia. To investigate these contributions further, we studied 97 DSM Ill-R, RDC schizophrenia patients admitted to the Schizophrenia Program at the University of Michigan. VBR was determined from head CT scans via computerized planimetry. Family history of psychosis and mood disorder was determined from all available records by a blind rater; any family history of either disorder was coded as positive. Season
of birth was encoded as Winter (Jan.-Mar.), Spring (Apr.~une), Summer (July-Sept.), and Fall (Oct.-Dec.). We found that patients without a family history of psychosis had significantly larger VBR (p<0.02) than patients with such a history; family history of mood disorder was not related to VBR. Season of birth was not predictive of VBR. Family history of psychosis and season of birth were not related to each other. These results are in line with prior work demonstrating an association between increased VBR and sporadic (nonfamilial) schizophrenia, which has been interpreted as indicating an environmental etiology such as intrauterine viral exposure, birth complications, etc. We did not find a relationship between VBR and season of birth, which suggests that in our sample, risk of intrauterine viral exposure and other seasonal environmental factors do not explain the ventricular enlargement in non-familial schizophrenia. The results are consistent with a dichotomization of the etiology of schizophrenia along genetic-sporadic lines. The precise environmental factors and the degree of exposure necessary to produce structural brain changes and the symptoms of schizophrenia require further investigation.
SPATIAL RELATIONSHIPS OF NEUROANATOMIC LANDMARKS SCHIZOPHRENIA
IN
John R. DeQuardo*, Fred L. Bookstein, William D.K. Green, James A. Brunberg, Rajiv Tandon
Schizophrenia Program and Centerfor Human Growth, University of Michigan, Ann Arbor, MI48109-0116, USA The authors sought to investigate the sites and extent of structural neuropathology in schizophrenia demonstrated on mid-sagittal MRI scans utilizing a new technique of morphometric analysis. Utilizing a technique (image averaging and shape analysis) of morphometric analysis that allows the identification of averaged anatomy via joint registration on multiple landmarks simultaneously, MRI scans obtained in the midsagittal plane were analyzed for 14 patients with schizophrenia, with variable levels of chronicity, and compared with 14 neurologic controls. The relation between averaged landmark configuration in the two groups was visualized as a deformation. The data suggest that the neuroanatomic abnormality in schizophrenia is circumscribed (focal), involving primarily the region of the posterior corpus callosum, upper brainstem and superior cerebellum, and secondarily the thickness of the corpus callosum all along its length. There were no large-scale abnormalities noted, although the patients with schizophrenia had significantly smaller brains. The findings are consistent with prior studies suggesting involvement of limbic structures, the corpus callosum, and the cerebellum in the illness. Complementing the "region of interest" method of investigating morphometric abnormalities, this method should contribute to defining the precise location and spatial relationship between relevant structural brain abnormalities in schizophrenia, and will educate future research efforts in the area.
enlargement. The precise timing of this abnormality in the course of schizophrenic illness and its relationship to neuropsychological dysfunction and premorbid adjustment remains unclear. We have previously shown that VBR could be used to dichotomize a sample of schizophrenics and generate hypotheses regarding premorbid ability and development: ( 1) childhood onset associated with poor premorbid function, low educational achievement, lower IQ, and lower VBR; and (2) later onset with relatively normal childhood function, higher academic achievement and IQ, and increased VBR. To re-examine these questions, we investigated the relationship between VBR, premorbid psychosocial and cognitive ability, and neuropsychological function in another sample of 55 DSM III-R schizophrenic inpatients. Each was rated on BPRS and SANS at baseline and after 4-weeks of antipsychotic treatment. VBR was determined from MRI scans via computerized planimetry. Neuropsychological testing was used to gauge current functioning and to estimate premorbid cognitive ability; the Premorbid Adjustment Scale was used to estimate premorbid psychosocial functioning. Unlike our previous study, VBR was not associated with premorbid cognitive or psychosocial functioning, decline in premorbid ability, or symptom status. Our failure to replicate our own previous findings is another example of the difficulty in obtaining consistently replicable findings in schizophrenia. In part, the discrepant findings may be related to limitations in current methods of image acquisition and analysis. More precise and comprehensive techniques such as shape analysis and image averaging may help to clarify these important issues involved in understanding the development and pathophysiology of schizophrenia.
VBR IN SCHIZOPHRENIA: RELATIONSHIP TO FAMILY HISTORY OF PSYCHOSIS AND SEASON OF BIRTH John R. DeQuardo*, M o n a Goldman, Rajiv Tandon
Schizophrenia Program, University of Michigan, Ann Arbor, MI48109-0116, USA Ventricular enlargement has been consistently demonstrated in schizophrenia using both CT and MRI. Despite this, the structural changes that underlie increased VBR and its relationship to environmental factors (intrauterine viral exposure, obstetric complications) and family history remain poorly defined. Increased VBR has been shown in some studies to correlate with family history of schizophrenia and WinterSpring birth (presumed intrauterine viral exposure). Methodologic issues aside, obtaining a clearer picture of the contribution of environmental and genetic factors to VBR would shed light on the developmental pathophysiology of schizophrenia. To investigate these contributions further, we studied 97 DSM Ill-R, RDC schizophrenia patients admitted to the Schizophrenia Program at the University of Michigan. VBR was determined from head CT scans via computerized planimetry. Family history of psychosis and mood disorder was determined from all available records by a blind rater; any family history of either disorder was coded as positive. Season
of birth was encoded as Winter (Jan.-Mar.), Spring (Apr.~une), Summer (July-Sept.), and Fall (Oct.-Dec.). We found that patients without a family history of psychosis had significantly larger VBR (p<0.02) than patients with such a history; family history of mood disorder was not related to VBR. Season of birth was not predictive of VBR. Family history of psychosis and season of birth were not related to each other. These results are in line with prior work demonstrating an association between increased VBR and sporadic (nonfamilial) schizophrenia, which has been interpreted as indicating an environmental etiology such as intrauterine viral exposure, birth complications, etc. We did not find a relationship between VBR and season of birth, which suggests that in our sample, risk of intrauterine viral exposure and other seasonal environmental factors do not explain the ventricular enlargement in non-familial schizophrenia. The results are consistent with a dichotomization of the etiology of schizophrenia along genetic-sporadic lines. The precise environmental factors and the degree of exposure necessary to produce structural brain changes and the symptoms of schizophrenia require further investigation.
SPATIAL RELATIONSHIPS OF NEUROANATOMIC LANDMARKS SCHIZOPHRENIA
IN
John R. DeQuardo*, Fred L. Bookstein, William D.K. Green, James A. Brunberg, Rajiv Tandon
Schizophrenia Program and Centerfor Human Growth, University of Michigan, Ann Arbor, MI48109-0116, USA The authors sought to investigate the sites and extent of structural neuropathology in schizophrenia demonstrated on mid-sagittal MRI scans utilizing a new technique of morphometric analysis. Utilizing a technique (image averaging and shape analysis) of morphometric analysis that allows the identification of averaged anatomy via joint registration on multiple landmarks simultaneously, MRI scans obtained in the midsagittal plane were analyzed for 14 patients with schizophrenia, with variable levels of chronicity, and compared with 14 neurologic controls. The relation between averaged landmark configuration in the two groups was visualized as a deformation. The data suggest that the neuroanatomic abnormality in schizophrenia is circumscribed (focal), involving primarily the region of the posterior corpus callosum, upper brainstem and superior cerebellum, and secondarily the thickness of the corpus callosum all along its length. There were no large-scale abnormalities noted, although the patients with schizophrenia had significantly smaller brains. The findings are consistent with prior studies suggesting involvement of limbic structures, the corpus callosum, and the cerebellum in the illness. Complementing the "region of interest" method of investigating morphometric abnormalities, this method should contribute to defining the precise location and spatial relationship between relevant structural brain abnormalities in schizophrenia, and will educate future research efforts in the area.