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Neuroleptic treatment and MRI brain changes in schizophrenia
P Poster Presentations study investigated those two effects using event-related potentials elicited by congruous sentence compl etions with high expectancy (CH condition). congruous ones with low expectancy (CL condition), incongruous ones (I condition), and digit numbers (N condition). A set of sentences on 4 conditions were presented twice. Healthy subjects were asked to jud ge whether the sentence completion was semantically congruous or not, and to press a left "yes" button or a right "no" button as quickly as possible. N400 effect was more prominent for the I condition than for the CL condition in the 300-600 msec range. The waveforms for the N condition were more positive com pared with the CH condition in the 400- 600 msec range. LPCs were more positive on the seco nd presen tations than on the first presentations for the semantic conditions (CH, CL, and I co ndition). Th ere was a tendency that the durations of N4QO effect were shorte ned on the second presentations, but these differences were not statistically significant.
IP-17-18 \ Effects of Dopamine Related Drugs on
Event-Related Potentials andits Relation to the Lawof Initial Value C. Ogura, N. Nishimura, M. Urasaki, 1. Ota. Department of Psychiatry, University of the Ryukyus , Okinawa, Japan Effects of the dopam ine antagonist sulpiride and agonist bromocriptine on event-related potentials (ERPs) were investigated during an auditory odd ball task in 18 healthy volunteers. Sulpiride (150 or 300 rng) or placebo and bromocriptin e (2.5 mg) or placebo were administered in respective sess ion, according 10 a co mpletely randomized double-blind cross-over design. ERP s were recorded I h after sulpiride medication and 3 h after brom ocriptine medication. Although on the whole sulpiride and bromocriptine had no effect on the amplitudes of ERP components in the subjec ts, both drugs increased the P300 amplitudes in the low P300 amplitude subjects and decreased them in the high P300 amplitude subjects . This tendency for a bidirectional response was also found for the N IOO and N200 amplitudes . It was concluded that the different responses that take place are dependent on the initial values. The results of this study are discussed in relation to the law of initial value (Wilder, 1936).
IP-17-191 Neuroleptic Treatment andMRI Brain Changes in Schizophrenia
M. Jarema , M. Choma . E. Poniatowska, R. Krawczyk. Institute of Psychiatry and Neurology, Warsaw, Poland Clinical response to neuroleptic treatment may depend on various factors. There is the substantial amount of information regarding poorer clinical response to neuroleptic treatment in patients with brain atrophy found in both CT and MR!. We evaluated 40 schizophrenia patients (DSM· IV) treated for 6 weeks with neuroleptics. The presence of cortical atrophy in MRI was evaluated and the width of Sylvian fissures and Evan's index were calcul ated. The 12 relaxation time in dorso-lateral prefrontal cortex was measured. Study revealed cortical atrophy in 16 out of 40 patients (40%). Those patient s showed poorer response to neuroleptic treatment (p 0.057). They also were older, had longer history of schizophrenia and higher num ber of previous hospital admissions. Negative symptoms and affective blunting were significantly more severe in those patients at the end of 6-weeks neuroleptic therapy. Among MRI parameters the TR of grey mailer in right fron tal inferio r gyrus was almost significantly (p 0.07) greater in acute schizophrenia. Patients who improved on perphen azine had higher grey matter TR values in right frontal medial gyrus (p 0.035).
IP-17-20 I Discrimination among Schizophrenic, Depressive and Normal Control Groups Using NeurophysiologIcal Tests
S. Takahashi I , E. Tanabe 1, M.L. Xia 1, T. Sakai I, M. Matsuura 1, T. Koj ima I , E. Matsushima 2, S. Obayashi 2. I Department of Neuropsychiatry, Nihon Unive rsity School of Medicine, Tokyo, Japan; 2 Department of Neuropsy chiatry, Faculty ofMedicine, Tokyo Medical and Dental University, Tokyo, Japan Exploratory eye movement (EEM ), P300, and reaction time (RT) performances were recoded in 36 schizophrenics (mean age, 26.8 years; 23
181 males, 13 females; disorganized type 8. paranoid type 18, residual type 4, undifferentiated type 6), 15 depressives (mean age. 30.6 years; 12 males, 3 females; bipolar disorder 4, major depression 9, dysthymia 2) and 36 normal controls (mean age, 26.6; 18 males, 18 females) . We measured 10 parameters: 4 from the EEM test; I) number of eye fixations (N), 3) total eye scanning length (TESL), 4) cog nitive search score (CSS) and 5) responsive search score (RSS): 2 from P300 test; 1) latency (LAT ) and 2) amplitude (AMP): and 4 from RT test; I) simple reaction time (SRT). set index (51). reaction time crossove r pattern value (RTX value) and coefficient of variation (CV). Co ncerning the comparison of values of all parameters among three groups, our results almost were consistent with the results of previous study. The stepwise regress ion analysis selected 4 parameters; RSS. SRT, CSS and P300_LAT as the best subset of predictor variables between schizophrenic and non-schizophrenic (depressives and normal controls) groups. Additionally, we found that the RSS was the most important of 4 parameters for predicting. Furthermore. the discriminant analysis test on 4 of the parameters; RSS. SRT. CSS and P30(LLAT yielded a sensitivity of 94.4% and a specificity of 92.2%.
IP-17-21 I Synaptic Loss in the Thalamus of Schizophrenics K. Blennow, N. Bogdanovic, P. Davidsson, R. Ekman. C.G. Gottfries, B. Grenfeldt, 1. Karlsson. University of Goteborg, Institute ofClinical Neu roscience, Dept of Psychiatry and Neurochemis try, Motndal, Sweden To assess loss of synapses in the thalamus of schizophrenic brains, the vesicle-specific protein rab3a was quantified. The sample included 19 brains of schizophrenic patients and 39 age-matched co ntrol subjects. Rab3a was significantly lower in the left thalamus in the schizophrenic group (0.45 ± 0.19; p < 0.000 1) than in the control group ( 1.00 ± 0.18). In the right thalamus. a significant reduction of rab3a was also found in the schizophrenic group (0.82 ± 0.13; p < 0.0005) co mpared with the control group (1.0 ± 0.22). Within the schizophrenic group, a sign ificant correlation was found between duration of disease and rab3a levels in the thalamus (Spearman' s r = -0.55; P < 0.05), while the correl ation in the right thalamus only bordered on significance (r = - 0.07). A marked reduction of rab3a immunoreactivity was also found in the left thalamus and frontal cortex in one case of schizophrenia. Thes e findings suggest that schizophrenia may be a degenerative brain disorder, which is in agreement with the evidence for thalamic degeneration that has been found with magnetic resonance image averaging [I]. [I] Andreasen, NC, et al, Science 266 ( 1994) 294.
I P-17-221
Loss of Cerebral Asymmetry in Familial Schizophrenia - A Volumetric StUdy Using Unbiased Stereology
T. Sharma , S.w. L. Lewis, 1. Sigmundsson, E. Lancaster. P. Barta, G. Pearlson, H. Gurling, R.M.M. Murray. Department of Psychological Medicine, Institute of Psychiatry, London, U.K. The goal of the study was to determine whether familial schizophrenic patients differed from healthy subjects in regional cerebral asym metries. Regional VOlumes correspo nding to prefrontal, premotor, sensorimotor, occipitoparietal, and temporal lobes in each hemis phere were measured on contiguous 1.5 mm 3D magnetic resonance images in 28 patients, 55 relatives and 39 controls using a new software capable of unbiased volume estimation. This study revealed a significant abnorm ality of cerebral hem ispheric volume asymmetries in patients with schizophrenia. The healthy comparison subjects showed a systematic pattern of asymrnetries, with prefrontal, premotor and temporal regions larger on the right and sensory motor and occi pito-parietal regions larger on the left In contrast. the patients did not show this pattern; they had low absolute asymmetry of all regions and reversed asymmetry of the occipito-parietal and prefrontal regions. The loss of asym metry was present in both dextra l and non-dextral schizophrenic subject s. In addition, transm itting parents (presumed obligate carriers), who are themselves unaffected showed the same reversal as the schizophrenic family members. The absence of normal asymmetry in familial schizophrenia and the unaffected parents suggests a neurodevelopmental abnormality in the illness that could be genetic in origin.
IP-17-18 \ Effects of Dopamine Related Drugs on
Event-Related Potentials andits Relation to the Lawof Initial Value C. Ogura, N. Nishimura, M. Urasaki, 1. Ota. Department of Psychiatry, University of the Ryukyus , Okinawa, Japan Effects of the dopam ine antagonist sulpiride and agonist bromocriptine on event-related potentials (ERPs) were investigated during an auditory odd ball task in 18 healthy volunteers. Sulpiride (150 or 300 rng) or placebo and bromocriptin e (2.5 mg) or placebo were administered in respective sess ion, according 10 a co mpletely randomized double-blind cross-over design. ERP s were recorded I h after sulpiride medication and 3 h after brom ocriptine medication. Although on the whole sulpiride and bromocriptine had no effect on the amplitudes of ERP components in the subjec ts, both drugs increased the P300 amplitudes in the low P300 amplitude subjects and decreased them in the high P300 amplitude subjects . This tendency for a bidirectional response was also found for the N IOO and N200 amplitudes . It was concluded that the different responses that take place are dependent on the initial values. The results of this study are discussed in relation to the law of initial value (Wilder, 1936).
IP-17-191 Neuroleptic Treatment andMRI Brain Changes in Schizophrenia
M. Jarema , M. Choma . E. Poniatowska, R. Krawczyk. Institute of Psychiatry and Neurology, Warsaw, Poland Clinical response to neuroleptic treatment may depend on various factors. There is the substantial amount of information regarding poorer clinical response to neuroleptic treatment in patients with brain atrophy found in both CT and MR!. We evaluated 40 schizophrenia patients (DSM· IV) treated for 6 weeks with neuroleptics. The presence of cortical atrophy in MRI was evaluated and the width of Sylvian fissures and Evan's index were calcul ated. The 12 relaxation time in dorso-lateral prefrontal cortex was measured. Study revealed cortical atrophy in 16 out of 40 patients (40%). Those patient s showed poorer response to neuroleptic treatment (p 0.057). They also were older, had longer history of schizophrenia and higher num ber of previous hospital admissions. Negative symptoms and affective blunting were significantly more severe in those patients at the end of 6-weeks neuroleptic therapy. Among MRI parameters the TR of grey mailer in right fron tal inferio r gyrus was almost significantly (p 0.07) greater in acute schizophrenia. Patients who improved on perphen azine had higher grey matter TR values in right frontal medial gyrus (p 0.035).
IP-17-20 I Discrimination among Schizophrenic, Depressive and Normal Control Groups Using NeurophysiologIcal Tests
S. Takahashi I , E. Tanabe 1, M.L. Xia 1, T. Sakai I, M. Matsuura 1, T. Koj ima I , E. Matsushima 2, S. Obayashi 2. I Department of Neuropsychiatry, Nihon Unive rsity School of Medicine, Tokyo, Japan; 2 Department of Neuropsy chiatry, Faculty ofMedicine, Tokyo Medical and Dental University, Tokyo, Japan Exploratory eye movement (EEM ), P300, and reaction time (RT) performances were recoded in 36 schizophrenics (mean age, 26.8 years; 23
181 males, 13 females; disorganized type 8. paranoid type 18, residual type 4, undifferentiated type 6), 15 depressives (mean age. 30.6 years; 12 males, 3 females; bipolar disorder 4, major depression 9, dysthymia 2) and 36 normal controls (mean age, 26.6; 18 males, 18 females) . We measured 10 parameters: 4 from the EEM test; I) number of eye fixations (N), 3) total eye scanning length (TESL), 4) cog nitive search score (CSS) and 5) responsive search score (RSS): 2 from P300 test; 1) latency (LAT ) and 2) amplitude (AMP): and 4 from RT test; I) simple reaction time (SRT). set index (51). reaction time crossove r pattern value (RTX value) and coefficient of variation (CV). Co ncerning the comparison of values of all parameters among three groups, our results almost were consistent with the results of previous study. The stepwise regress ion analysis selected 4 parameters; RSS. SRT, CSS and P300_LAT as the best subset of predictor variables between schizophrenic and non-schizophrenic (depressives and normal controls) groups. Additionally, we found that the RSS was the most important of 4 parameters for predicting. Furthermore. the discriminant analysis test on 4 of the parameters; RSS. SRT. CSS and P30(LLAT yielded a sensitivity of 94.4% and a specificity of 92.2%.
IP-17-21 I Synaptic Loss in the Thalamus of Schizophrenics K. Blennow, N. Bogdanovic, P. Davidsson, R. Ekman. C.G. Gottfries, B. Grenfeldt, 1. Karlsson. University of Goteborg, Institute ofClinical Neu roscience, Dept of Psychiatry and Neurochemis try, Motndal, Sweden To assess loss of synapses in the thalamus of schizophrenic brains, the vesicle-specific protein rab3a was quantified. The sample included 19 brains of schizophrenic patients and 39 age-matched co ntrol subjects. Rab3a was significantly lower in the left thalamus in the schizophrenic group (0.45 ± 0.19; p < 0.000 1) than in the control group ( 1.00 ± 0.18). In the right thalamus. a significant reduction of rab3a was also found in the schizophrenic group (0.82 ± 0.13; p < 0.0005) co mpared with the control group (1.0 ± 0.22). Within the schizophrenic group, a sign ificant correlation was found between duration of disease and rab3a levels in the thalamus (Spearman' s r = -0.55; P < 0.05), while the correl ation in the right thalamus only bordered on significance (r = - 0.07). A marked reduction of rab3a immunoreactivity was also found in the left thalamus and frontal cortex in one case of schizophrenia. Thes e findings suggest that schizophrenia may be a degenerative brain disorder, which is in agreement with the evidence for thalamic degeneration that has been found with magnetic resonance image averaging [I]. [I] Andreasen, NC, et al, Science 266 ( 1994) 294.
I P-17-221
Loss of Cerebral Asymmetry in Familial Schizophrenia - A Volumetric StUdy Using Unbiased Stereology
T. Sharma , S.w. L. Lewis, 1. Sigmundsson, E. Lancaster. P. Barta, G. Pearlson, H. Gurling, R.M.M. Murray. Department of Psychological Medicine, Institute of Psychiatry, London, U.K. The goal of the study was to determine whether familial schizophrenic patients differed from healthy subjects in regional cerebral asym metries. Regional VOlumes correspo nding to prefrontal, premotor, sensorimotor, occipitoparietal, and temporal lobes in each hemis phere were measured on contiguous 1.5 mm 3D magnetic resonance images in 28 patients, 55 relatives and 39 controls using a new software capable of unbiased volume estimation. This study revealed a significant abnorm ality of cerebral hem ispheric volume asymmetries in patients with schizophrenia. The healthy comparison subjects showed a systematic pattern of asymrnetries, with prefrontal, premotor and temporal regions larger on the right and sensory motor and occi pito-parietal regions larger on the left In contrast. the patients did not show this pattern; they had low absolute asymmetry of all regions and reversed asymmetry of the occipito-parietal and prefrontal regions. The loss of asym metry was present in both dextra l and non-dextral schizophrenic subject s. In addition, transm itting parents (presumed obligate carriers), who are themselves unaffected showed the same reversal as the schizophrenic family members. The absence of normal asymmetry in familial schizophrenia and the unaffected parents suggests a neurodevelopmental abnormality in the illness that could be genetic in origin.