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Grey and white matter changes in the aesop first-onset psychosis study: A voxel-based analysis of brain structure
192 structural and functional abnormalities of the thalamus in subjects with schizophrenia using a variety of methods including histopathology, structural neuroimaging via MR1 and functional tools such as PET and fMRI. Although several reports have documented the effects of neuroleptics on the morphology of subcortical structures such as the candate and putamen, no studies to date have evaluated the effect of nemoleptics on the morphology of the thalamus in a prospective design. The current study evaluated 2l subjects with schizophrenia who were neuroleptic naive at the time of MRI scanning. These subjects were followed as a part of our prospective longitudinal study and had repeat MRI scans two years after intake. Volume of the whole thalamus was obtained using an automated neural net method. These measures were compared at time one and follow-up to a group of 11 healthy controls who also had scans obtained two years apart. Interim neuroleptic exposure for the patient group was calculated using a dose-year formula, which accounts for both dose and duration of exposure. At intake, the volume of the thalamus was nonsignificantly larger in patients compared to controls (mean adjusted volume for patients = 14.4 cc and for controls = 13.7 cc). At follow-up, the volumes for both groups were almost identical (14.7 cc for patients and 14.5 cc for controls). A difference score was computed by subtracting time 2 volume from time 1 volume. There was no significant difference between the two groups in terms of change in thalamic volume. However, there were robust relationships within the patient group between neuroleptic exposure and change in volume over time. As a group, this correlation was r = -.56, p = 0.01. This robust inverse relationship (the greater the drug exposure, the decrease in volume over time) was present for both those subjects exposed to atypical neuroleptics (n=13) as well as to those who had been treated with typical neuroleptics (n:8). These findings suggest that change in thalamic morphology over time may be related to neuroleptic exposure.
CLINICAL AND PSYCHOPHYSIOLOGY CORRELATES OF A LARGE CAVUM SEPTUM PELLUCIDUM IN SCHIZOPHRENIA J. A. Crippa,* A. W. Zuardi, G. E Busatto, J. E. Hallak, R. E Sanches, A. C. Santos, E S. G u i m a r a e s , D. Araujo, R R Allen, R K. M c G u i r e
Psychological Medicine, Institute of Psychiatry, London, United Kingdom Patients with schizophrenia appear to have an increased incidence of both an enlarged large cavum septum pellucidum (CSP) and electrodermal (EDA) hyporesponsivity. While each of these findings is relatively well established, the relationship between them is unknown. An enlarged CSP in schizophrenia could reflect dysgenesis of either the hippocampus or corpus callosum, and abnormalities in both these structures have been associated with electrodermal hyporesponsivity. The present study was designed to evaluate the relationship between abnormal CSP and EDA in schizophrenia. Three groups were studied: patients with schizophrenia and an enlarged CSP (n=8), patients without an enlarged CSP (n=16), and healthy volunteers (n=16). The groups were matched according to sex, age, years of education, parental and personal socioeconomic status and handedness. In addition, the doses of anti-psychotic medication (in chlorpromazine equivalents) and anticholinergic medication did not differ significantly between the two patient groups. Psychopathology was assessed using the PANSS. All subjects had previously been examined using a 1.5T magnetic resonance imaging
13. Neuroimaging, Structural (MRI) scanner. The length of the CSP was measured by counting the number of consecutive l m m coronal slices in which it appeared. A CSP > 6mm long was rated as large. Subjects with other brain abnormalities were excluded. In the control group and in the schizophrenia group without an enlarged CSP, only subjects with a CSP < 3mm were included. Skin conductance was assessed using computerized physiological recording system. The number of skin conductance responses (SCR) elicited by neutral tones stimuli was recorded, as well as the skin conductance level (SCL) between adjacent stimuli and the number of spontaneous fluctuations (SF) of skin conductance. The number of SCRs and the number of SF did not differ significantly between groups. The SCL was significantly lower in the two patient groups relative to the healthy controls, which may reflect an effect of anticholinergics. There were no differences in SCL, number of SF, number of SCORs and PANSS scores between the two schizophrenic groups. Overall, these findings indicate that patients with schizophrenia and an enlarged CSP did not differ in their pattern of autonomic system activity from patients without this abnormality, or from controls. The neural mechanisms that underlie electrodermal hyporesponsivity in schizophrenia remain unclear.
GREY AND WHITE MATTER CHANGES IN THE AESOP FIRST-ONSET PSYCHOSIS STUDY: A VOXEL-BASED ANALYSIS OF BRAIN STRUCTURE R D a z z a n , * K. D. M o r g a n , J. Suckling, X. Chitnis, R. Mallett, J. Left, R. M. M u r r a y
Division of Psychological Medicine, Institute of Psychiatry, Denmark Hill, London, United Kingdom Structural neuroimaging studies have established that there are brain structural abnormalities in schizophrenia, but it is not known whether these are relatively fixed, or change over the course of the disorder. Investigating patients at the first episode of the illness can clarify whether these brain abnormalities are part of an underlying neurodysfunction rather than the consequence of degenerative processes or psychopharmacological treatment. This study investigated the brain structure of an epidemiologically-based sample of 74 patients at the first episode of a schizophrenic or affective psychosis, and compared this with 89 healthy community controls. Dual echo MRI data were acquired at 1.5T on 74 patients (n=43 female; mean age 27, SD8 years; n=29 DSM IV Affective Psychosis, n=45 DSM IV Schizophrenia/Schizophreniform) and 89 controls (n=53 female; mean age 30, SD9 years). Differences in grey and white matter between patients and controls were estimated at each intracerebral voxel after registration of images in standard space. In comparison to controls, patients showed (p<0.02): 1) Grey matter: Smaller total grey matter volume; regional grey matter excesses of basal ganglia and bilateral lingual gyms. Patients with affective psychosis also showed deficits of bilateral anterior cingulate and right insula. 2) White matter: Smaller total white matter volume. There were no regional differences. Regional differences remained significant when we controlled (ANCOVA) for diagnosis, sex, age, years of education, ethnicity, IQ, and total tissue volume. A number of brain structural abnormalities are already present at the onset of psychosis. Furthermore, patients with affective psychoses show distinctive brain deficits in regions that have previously been associated with affective disorders. The study is funded by the UK Medical Research Council. We would also like to thank the Stanley Medical Research Institute for their support.
International Congress on Schizophrenia Research 2003
CLINICAL AND PSYCHOPHYSIOLOGY CORRELATES OF A LARGE CAVUM SEPTUM PELLUCIDUM IN SCHIZOPHRENIA J. A. Crippa,* A. W. Zuardi, G. E Busatto, J. E. Hallak, R. E Sanches, A. C. Santos, E S. G u i m a r a e s , D. Araujo, R R Allen, R K. M c G u i r e
Psychological Medicine, Institute of Psychiatry, London, United Kingdom Patients with schizophrenia appear to have an increased incidence of both an enlarged large cavum septum pellucidum (CSP) and electrodermal (EDA) hyporesponsivity. While each of these findings is relatively well established, the relationship between them is unknown. An enlarged CSP in schizophrenia could reflect dysgenesis of either the hippocampus or corpus callosum, and abnormalities in both these structures have been associated with electrodermal hyporesponsivity. The present study was designed to evaluate the relationship between abnormal CSP and EDA in schizophrenia. Three groups were studied: patients with schizophrenia and an enlarged CSP (n=8), patients without an enlarged CSP (n=16), and healthy volunteers (n=16). The groups were matched according to sex, age, years of education, parental and personal socioeconomic status and handedness. In addition, the doses of anti-psychotic medication (in chlorpromazine equivalents) and anticholinergic medication did not differ significantly between the two patient groups. Psychopathology was assessed using the PANSS. All subjects had previously been examined using a 1.5T magnetic resonance imaging
13. Neuroimaging, Structural (MRI) scanner. The length of the CSP was measured by counting the number of consecutive l m m coronal slices in which it appeared. A CSP > 6mm long was rated as large. Subjects with other brain abnormalities were excluded. In the control group and in the schizophrenia group without an enlarged CSP, only subjects with a CSP < 3mm were included. Skin conductance was assessed using computerized physiological recording system. The number of skin conductance responses (SCR) elicited by neutral tones stimuli was recorded, as well as the skin conductance level (SCL) between adjacent stimuli and the number of spontaneous fluctuations (SF) of skin conductance. The number of SCRs and the number of SF did not differ significantly between groups. The SCL was significantly lower in the two patient groups relative to the healthy controls, which may reflect an effect of anticholinergics. There were no differences in SCL, number of SF, number of SCORs and PANSS scores between the two schizophrenic groups. Overall, these findings indicate that patients with schizophrenia and an enlarged CSP did not differ in their pattern of autonomic system activity from patients without this abnormality, or from controls. The neural mechanisms that underlie electrodermal hyporesponsivity in schizophrenia remain unclear.
GREY AND WHITE MATTER CHANGES IN THE AESOP FIRST-ONSET PSYCHOSIS STUDY: A VOXEL-BASED ANALYSIS OF BRAIN STRUCTURE R D a z z a n , * K. D. M o r g a n , J. Suckling, X. Chitnis, R. Mallett, J. Left, R. M. M u r r a y
Division of Psychological Medicine, Institute of Psychiatry, Denmark Hill, London, United Kingdom Structural neuroimaging studies have established that there are brain structural abnormalities in schizophrenia, but it is not known whether these are relatively fixed, or change over the course of the disorder. Investigating patients at the first episode of the illness can clarify whether these brain abnormalities are part of an underlying neurodysfunction rather than the consequence of degenerative processes or psychopharmacological treatment. This study investigated the brain structure of an epidemiologically-based sample of 74 patients at the first episode of a schizophrenic or affective psychosis, and compared this with 89 healthy community controls. Dual echo MRI data were acquired at 1.5T on 74 patients (n=43 female; mean age 27, SD8 years; n=29 DSM IV Affective Psychosis, n=45 DSM IV Schizophrenia/Schizophreniform) and 89 controls (n=53 female; mean age 30, SD9 years). Differences in grey and white matter between patients and controls were estimated at each intracerebral voxel after registration of images in standard space. In comparison to controls, patients showed (p<0.02): 1) Grey matter: Smaller total grey matter volume; regional grey matter excesses of basal ganglia and bilateral lingual gyms. Patients with affective psychosis also showed deficits of bilateral anterior cingulate and right insula. 2) White matter: Smaller total white matter volume. There were no regional differences. Regional differences remained significant when we controlled (ANCOVA) for diagnosis, sex, age, years of education, ethnicity, IQ, and total tissue volume. A number of brain structural abnormalities are already present at the onset of psychosis. Furthermore, patients with affective psychoses show distinctive brain deficits in regions that have previously been associated with affective disorders. The study is funded by the UK Medical Research Council. We would also like to thank the Stanley Medical Research Institute for their support.
International Congress on Schizophrenia Research 2003