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Clozapine in treatment-resistant schizophrenic patients: Clinical, neuropsychological and neuroanatomical correlates of outcome
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P Poster Presentations Conclusions: Depression and negative symptoms appear to be different dimensions of psychopathology that can be differentiated using appropriate scales. Using depression as an exclusion criterion for the deficit syndrome changes levels of depression but not levels of negative symptoms between deficit and non-deficit patients. These findings do not support the exclusion of depression as a necessary criterion for the deficit syndrome.
IP-7-21 I Negative Symptoms and Neuropsychologic Dysfunction are Independent Features of SChizophrenia 1. Maltez, M. Guerreiro, F. Cavaglia, A. Matos-Pires, M. Botelho. Dept. ofPsychiatry and Neuropsychology, Hospital Santa Maria, Lisbon, Portugal The presence of deficit symptoms in schizophrenia is an old and widely accepted recognition. Whether it reflects a psychopathologic "negative syndrome", a set of cognitive abnormalities or, at least in some extent, the secondary effects of neuroleptics is a matter of debate. In order to address these issues we conducted a study in drug free paranoid schizophrenic out-patients presenting mainly negative symptomatology. The objective was to correlate the psychopathologic profile with cognitive performance. Our hypothesis was that cognitive deficit and negative symptoms are independent features of the disease. We present the preliminary results of a sample of 10 chronic schizophrenic patients. The mean age was 29.3 (5.3 SD) with a mean illness evolution of 5.3 years (2.6 SD). The wash-out period from medication was 2 months for "depot" and 2 weeks for oral ones. Diagnosis was established using DSM III-R criteria. Patients with other axis I diagnosis were excluded as well as those with duration of illness longer than 10 years. The PANSS scale was used to quantification of symptoms (mean values were - total: 84.7,24.5 SD; negative subscale: 28.6, 8.5 SD; positive: 15.1, 7.6 SD). Neuropsychologic evaluation was performed blindly by one of us. Results were compared with a portuguese population matched for age, sex and education. A 2SD from this control sample were considered abnormal. A brain CT scan was done on the same week of evaluation. One way ANOVA was performed to compare the psychopathologic and overall clinical characteristics of deteriorated from cognitive preserved patients. Seven patients presented global neuropsychologic dysfunction. The more significant differences were obtained in overall frontal function (p = 0.01), visual memory (p = 0.035) and verbal abstraction (p = 0.048). We found no significant differences between the two groups regarding age, age of illness onset, years of evolution, total PANSS or either positive or negative subscales scores. Only three patients presented signs of cortical atrophy in brain CT scans. No significant association was found between this finding and the other variables under study. We did confirm the usual and frequent frontal and temporal function abnormalities described in schizophrenia. Our initial hypothesis regarding the independence of negative and more specific cognitive symptoms seems to receive some support from these preliminary results.
IP-?-221
PanicAttacks in Chronic Schizophrenia a Complication of Long-Term Antipsychotic Medication
H. Higuchi, M. Kamata, M. Yoshimoto, K. Yoshida, Y. Hishikawa. Department ofNeuropsychiatry, Akita University School of Medicine, Akita, Japan It has been reported that panic attacks are found in seven out of 20 patients with chronic schizophrenia, and that the symptom has been improved by reduction of doses or discontinuation of antipsychotics in two of the patients [I). We studied the frequency of panic attacks, clinical features of psychotic symptoms, varieties of antipsychotic drugs and their amount used in patients with chronic shizophrenia (DSM-IIIR). Panic attacks meeting the diagnostic criteria for panic disorder (DSM-IIIR) were found in nine (20%) of the 45 patients. The scores of the Hamilton Depression Rating Scale and the Simpson Angus Scale were significantly higher in the group of patients with panic attacks than in the rest of the patients. The patients with panic attacks tended to be taking larger doses of antipsychotics than the rest of the patients. This result suggests that a
long-term antipsychotic medication is closely related to the occurrence of panic attacks in chronic schizophrenia. (I] Argyle N. Br J Psychiat. 157(1990) 430-433.
I P-?-231
Clozapine in Treatment-Resistant Schizophrenic Patients: Clinical, Neuropsychological and Neuroanatomical Correlates of Outcome
C.L. Shrigui I , L. Annable 2, G. Bouchard I , P. Grondin J , M. Dufour I . I Department of Psychiatry and Radiology, Laval University, Quebec, Canada; 2 McGill University, Montreal, Quebec, Canada Cognitive functions, psychopathology, and extrapyramidal symptoms were assessed in 13 treatment-resistant schizophrenic patients before treatment wit clozapine, and at 6 month intervals thereafter for up to two years. Cognitive performance was assessed using the Wisconsin Card Song Test, Random Number Generation Test, and Stroop Color-Word Test. Subjects also underwent and MRI brain scan. Patients were classified as treatment responders or non-responders on the basis of a rating of much improved on the COl, and a reduction of at least 25% in the baseline total score of the Positive and Negative Symptom Scale at 6 months and every 6 months thereafter, Three of the 13 patients met the criteria for treatment response (however, one of these three patients subsequently developed leucopenia and clozapine was discontinued), 7 were classified as non-responders , and 3 were withdrawn from clozapine because of a refusal of blood monitoring (n = 2) or side effects (n = l). Treatment responders showed a non-significant (p > 0.05) trend for greater improvement than non-responders on the neuropsychological tests, and there was some evidence of significant correlation between improvement in psychopathology and cognitive function. These results are consistent with previous report of improvement in psychiatric symptoms and cognitive functions in treatment-refractory patients receiving clozapine [I). [1] Hagger C. Buckley P. Kenny IT, Friedman L, Ubogy D, Meltzer HY, BioI. Psychiat, 34 (1993) 704-712.
I P-?-241 Correlations Between Neurophysiological Abnormalities and Brain Morphological Changes in Schizophrenia E. Tanabe I, S. Takahashi I, M.L. Xia I, T. Sakai I, M. Matsuura I, T. Kojima 1, E. Matsushima 2, S. Obayashi 2. I Department of Neuropsychiatry, Nihon University School ofMedicine, Tokyo, Japan; 2 Department ofNeuropsychiatry, Faculty ofMedicine, Tokyo Medical and Dental University, Tokyo, Japan It is said that schizophrenic patients have various neurophysiological abnormalities and brain morphological abnormalities. This study was designed to investigate (I) differences between schizophrenia and normal control in the three types of neurophysiological tests and (2) correlations between neurophysiological parameters and brain morphological changes in schizophrenia. (I) Thirty-nine patients (mean age, 27.4 years; 23 men, 16 women) diagnosed as schizophrenia according to DSM-III-R criteria were included in the subject. Thirty-one normal controls were matched to the patient sample for age and gender (mean age, 26.9 years; IS men. 16 women). All the subjects were informed and consented to the examinators. Exploratory eye movement (EEM), auditory P300 and reaction time (RT) were examined on all patients and normal controls. Between the two groups, significant differences were found in responsive search score, cognitive search score, number of eye fixation, total eye scanning length (EEM test), P300 amplitude and latency, simple reaction time and their coefficient of variation (RT test). (2) MRI scans were performed on twenty schizophrenic patients and the correlations between above neurophysiological parameters and brain morphological variables were investigated. Responsive search score in EEM test was correlated negatively with the size of the third ventricle. The P300 latency and coefficient of variation in RT test were correlated positively with ventricular brain ratio. These results suggest an underlying dysfunction in the information-processing system in schizophrenics, and minimal brain morphological changes at the circumference of the ventricles is implicated in the information-processing dysfunction.
P Poster Presentations Conclusions: Depression and negative symptoms appear to be different dimensions of psychopathology that can be differentiated using appropriate scales. Using depression as an exclusion criterion for the deficit syndrome changes levels of depression but not levels of negative symptoms between deficit and non-deficit patients. These findings do not support the exclusion of depression as a necessary criterion for the deficit syndrome.
IP-7-21 I Negative Symptoms and Neuropsychologic Dysfunction are Independent Features of SChizophrenia 1. Maltez, M. Guerreiro, F. Cavaglia, A. Matos-Pires, M. Botelho. Dept. ofPsychiatry and Neuropsychology, Hospital Santa Maria, Lisbon, Portugal The presence of deficit symptoms in schizophrenia is an old and widely accepted recognition. Whether it reflects a psychopathologic "negative syndrome", a set of cognitive abnormalities or, at least in some extent, the secondary effects of neuroleptics is a matter of debate. In order to address these issues we conducted a study in drug free paranoid schizophrenic out-patients presenting mainly negative symptomatology. The objective was to correlate the psychopathologic profile with cognitive performance. Our hypothesis was that cognitive deficit and negative symptoms are independent features of the disease. We present the preliminary results of a sample of 10 chronic schizophrenic patients. The mean age was 29.3 (5.3 SD) with a mean illness evolution of 5.3 years (2.6 SD). The wash-out period from medication was 2 months for "depot" and 2 weeks for oral ones. Diagnosis was established using DSM III-R criteria. Patients with other axis I diagnosis were excluded as well as those with duration of illness longer than 10 years. The PANSS scale was used to quantification of symptoms (mean values were - total: 84.7,24.5 SD; negative subscale: 28.6, 8.5 SD; positive: 15.1, 7.6 SD). Neuropsychologic evaluation was performed blindly by one of us. Results were compared with a portuguese population matched for age, sex and education. A 2SD from this control sample were considered abnormal. A brain CT scan was done on the same week of evaluation. One way ANOVA was performed to compare the psychopathologic and overall clinical characteristics of deteriorated from cognitive preserved patients. Seven patients presented global neuropsychologic dysfunction. The more significant differences were obtained in overall frontal function (p = 0.01), visual memory (p = 0.035) and verbal abstraction (p = 0.048). We found no significant differences between the two groups regarding age, age of illness onset, years of evolution, total PANSS or either positive or negative subscales scores. Only three patients presented signs of cortical atrophy in brain CT scans. No significant association was found between this finding and the other variables under study. We did confirm the usual and frequent frontal and temporal function abnormalities described in schizophrenia. Our initial hypothesis regarding the independence of negative and more specific cognitive symptoms seems to receive some support from these preliminary results.
IP-?-221
PanicAttacks in Chronic Schizophrenia a Complication of Long-Term Antipsychotic Medication
H. Higuchi, M. Kamata, M. Yoshimoto, K. Yoshida, Y. Hishikawa. Department ofNeuropsychiatry, Akita University School of Medicine, Akita, Japan It has been reported that panic attacks are found in seven out of 20 patients with chronic schizophrenia, and that the symptom has been improved by reduction of doses or discontinuation of antipsychotics in two of the patients [I). We studied the frequency of panic attacks, clinical features of psychotic symptoms, varieties of antipsychotic drugs and their amount used in patients with chronic shizophrenia (DSM-IIIR). Panic attacks meeting the diagnostic criteria for panic disorder (DSM-IIIR) were found in nine (20%) of the 45 patients. The scores of the Hamilton Depression Rating Scale and the Simpson Angus Scale were significantly higher in the group of patients with panic attacks than in the rest of the patients. The patients with panic attacks tended to be taking larger doses of antipsychotics than the rest of the patients. This result suggests that a
long-term antipsychotic medication is closely related to the occurrence of panic attacks in chronic schizophrenia. (I] Argyle N. Br J Psychiat. 157(1990) 430-433.
I P-?-231
Clozapine in Treatment-Resistant Schizophrenic Patients: Clinical, Neuropsychological and Neuroanatomical Correlates of Outcome
C.L. Shrigui I , L. Annable 2, G. Bouchard I , P. Grondin J , M. Dufour I . I Department of Psychiatry and Radiology, Laval University, Quebec, Canada; 2 McGill University, Montreal, Quebec, Canada Cognitive functions, psychopathology, and extrapyramidal symptoms were assessed in 13 treatment-resistant schizophrenic patients before treatment wit clozapine, and at 6 month intervals thereafter for up to two years. Cognitive performance was assessed using the Wisconsin Card Song Test, Random Number Generation Test, and Stroop Color-Word Test. Subjects also underwent and MRI brain scan. Patients were classified as treatment responders or non-responders on the basis of a rating of much improved on the COl, and a reduction of at least 25% in the baseline total score of the Positive and Negative Symptom Scale at 6 months and every 6 months thereafter, Three of the 13 patients met the criteria for treatment response (however, one of these three patients subsequently developed leucopenia and clozapine was discontinued), 7 were classified as non-responders , and 3 were withdrawn from clozapine because of a refusal of blood monitoring (n = 2) or side effects (n = l). Treatment responders showed a non-significant (p > 0.05) trend for greater improvement than non-responders on the neuropsychological tests, and there was some evidence of significant correlation between improvement in psychopathology and cognitive function. These results are consistent with previous report of improvement in psychiatric symptoms and cognitive functions in treatment-refractory patients receiving clozapine [I). [1] Hagger C. Buckley P. Kenny IT, Friedman L, Ubogy D, Meltzer HY, BioI. Psychiat, 34 (1993) 704-712.
I P-?-241 Correlations Between Neurophysiological Abnormalities and Brain Morphological Changes in Schizophrenia E. Tanabe I, S. Takahashi I, M.L. Xia I, T. Sakai I, M. Matsuura I, T. Kojima 1, E. Matsushima 2, S. Obayashi 2. I Department of Neuropsychiatry, Nihon University School ofMedicine, Tokyo, Japan; 2 Department ofNeuropsychiatry, Faculty ofMedicine, Tokyo Medical and Dental University, Tokyo, Japan It is said that schizophrenic patients have various neurophysiological abnormalities and brain morphological abnormalities. This study was designed to investigate (I) differences between schizophrenia and normal control in the three types of neurophysiological tests and (2) correlations between neurophysiological parameters and brain morphological changes in schizophrenia. (I) Thirty-nine patients (mean age, 27.4 years; 23 men, 16 women) diagnosed as schizophrenia according to DSM-III-R criteria were included in the subject. Thirty-one normal controls were matched to the patient sample for age and gender (mean age, 26.9 years; IS men. 16 women). All the subjects were informed and consented to the examinators. Exploratory eye movement (EEM), auditory P300 and reaction time (RT) were examined on all patients and normal controls. Between the two groups, significant differences were found in responsive search score, cognitive search score, number of eye fixation, total eye scanning length (EEM test), P300 amplitude and latency, simple reaction time and their coefficient of variation (RT test). (2) MRI scans were performed on twenty schizophrenic patients and the correlations between above neurophysiological parameters and brain morphological variables were investigated. Responsive search score in EEM test was correlated negatively with the size of the third ventricle. The P300 latency and coefficient of variation in RT test were correlated positively with ventricular brain ratio. These results suggest an underlying dysfunction in the information-processing system in schizophrenics, and minimal brain morphological changes at the circumference of the ventricles is implicated in the information-processing dysfunction.