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Modifications of auditory ERP and correlations with symptomatology in 50 schizophrenic patients
162S
BIOL. PSYCHIATRY
Schizophrenialantipsychotics
1997;42:15-297S
lients. Moreover It Is possible that autlstlc symptoms are an evidence of severe obstetric complications (0Cs). Methods: The sample included 87 consecutively admitted patients with DSM.III-R chronic schizophrenia. for 65 patients obstetric hlstOlY and for 81 patients age at onset could be obtained. Inclusion criteria were the absence of any focal abnormalities and any diagnosis of organic brain syndrome, substance abuse disorder or mental retardation. The patients were all males, the mean age was 29.9 (SO =7.6) and age at onset was 21.3 (SO =6.7). We used the Scale for the Assessment of Negative Symptoms (SANS) and the Scale for the Assessment of Positive Symptoms (SAPS) to assess current mental state; we selected 8 Items of the SANS (4. 5.6, g, 10, 15, 20 and 23) describing some aspec1 of autistic behaviour. whose sum score was defined as autistic cluster (AlC). In the subjects the severity of OCs was assessed during a semistructured Interview to biological mother by the Midwife Protocol used by Pamas et al. (1982). Brain morphology was evaluated by computerized tomography scan. Results: Autistic cluster did not correlate to neuromorphologlcal mea• sures. There was a significant inverse correlation between AlC and OCs (p .. 0.029) and between AlC and onset (p .. 0.029). Our findings could be viewed as a direct evidenca of a lower environmental influence respec1 to genetic factors on the autistic syndrome in schizophrenia.
163-71 local Chronic MK-801 adminIstration In vivo alters CA 1 circuit Inhibition In vitro H. Grunze 1 , D. RUjescu-Baicu 1 , H.J. MOiler 1 • D. Ralnnie 2, R. Greene 2. 1 Psychiatr. Klinik LMU MOnch6n. Germany, 2 Harvard Moo. SCh.• Boston, USA
Previously we showed that local inbition in the hippocampal CA1 area in rats depends, In part, on NMDA receptor activation. Thus. It can be selectively disrupted by NMDA antagonists, leading to increased network excitability. This mechanism may underlie PCP- psychosis and possibly schizophrenia. as elevated levels of the endogenous partial NMDA antagonist NAAG had been reported in post mortem brains. To simulate this effect of chronic. not acutely toxic NMDA antagonist exposition in rats (age 4Od) we injected 0.02 mglkg KG MK-801 l.p. for 14 days before perfonnlng whole cen patch clamp recordings In vitro from pyramidal cells In the hippocarnpal CAl area (MK-801. n '" 4; saline controls. n '" 3). Nine recordings were obtained In each group. There was no difference of the mean membrane potential. action potential treshold, action potential overshoot. GABA A reversal potential and membrane potential change to local GABA A Injection between groups. However. recurrent Inhibition ellcted by alvear stimulation was significantly reduced In the MK- 801 group (IPSP amplitude -1.6 ± 1.3 mV vs. -3.7 ± 1.2 mV in controls. p < 0.025. Mann-Whitney test). These results are in line with the hypothesis of dysfunctional local inhibition In cortical-limbic areas of schizophrenics due to a partial blockade of Intemeuronal NMDA recep• tors.
163-81 Modifications of auditory ERP and correlations wIth symptomatology In 50 schIzophrenIc patients
Th. Bougerol. A. Benralss, Ch. Lal'llton. D. Bemard. J.C. Scotto. S.H.U dB Psychiatrie. H"Pital Sainte-Marguerife. Maf'S8ille. FI7JfIC{J The aim of the study was to correlate the modifications of auditory ERP to positive and negative symptoms ratings in schizophrenic patients. Method: AuditOlY Event Relaled Potentials were recorded In 50 schizophrenic patients (DSM III-R) and 47 non-psychiatric controls In 3 different experimental settings: standard Auditory Evoked Potentials. pas• sive oddball paradigm and oddball paradigm with an altentional task (silent counting of target stimulus). 3 recording electrodes were used (Fz, Cz, Pz). and the stimuli were tones of 750 Hz (non-target) or 2000 Hz (target). The schizophrenic symptomatology was evaluated with different clinical rating scales: BPRS, SANS. SAPS and PANSS. Results: Schizophrenic patients as a whole were characterized by a re• duced level of cerebral arousal. In atl experimental settings. When classified according to the negatiVe/positive dichotomy, the negative schiZophrenic patients present significant changes In the very earty steps of stimulus anal• ysis and these changes correlate with a depressive dimension of psychotic symptomatology. On the other hand. positive delusional patients are char• acterized by an overarousal state and by more specific modifications of later steps of automatic orientation to the target stimulus. These modifications are not linked to neuroleptic treatments or to the status of care.
163-91 CAGlCTG repeat expansion detection In familial schIzophrenia F. Thlbaut, C. Laurent, C. Zander. M. Martinez. D. CsmpIon, M. Jay. F. Bonnet·Brilhault, O. Chavand. D. Samolyk, H. Cann, C. Nerl. J. Mallet LGN-eNRS. Paris. FI7JfIC{J. CHS Rouvray, Rouen. FI7JfIC{J. U358. Paris, France. CHS Sf Paul. La Reunion, France The tenn. genetic anticipation. is used to describe the increase In disease severity or the decrease in age of onset in succeeding generations within families. This phenomenon has recently been correlated with expansion of DNA 1rinucleotlde repeat sequences in several neuropsychiatric disorders. In schizophrenia, anticipation has been suggested by several studies. Fur• thermore, several groups have reported the occurrence of expanded CAG 1rinucleotlde repeat sequences In schizophrenia patients. using the repeat expansion detection method (RED). We recently reported data supporting anticipation in 26, two generation family pedigrees from Normandy and the island of Is Reunion, France. The RED method has now been used to analyse genomic DNA for the presence of expanded trtnucleotlde repeat sequences In this sample. The analysis of the data obtained from the schizophrenic families will be presented. No clear evidence of triplet repeal expansion In succeeding generations has been demonstrated so far. Possible eXplana• tions for the clinically observed genetic anticipation in schizophrenia will be discussed.
BIOL. PSYCHIATRY
Schizophrenialantipsychotics
1997;42:15-297S
lients. Moreover It Is possible that autlstlc symptoms are an evidence of severe obstetric complications (0Cs). Methods: The sample included 87 consecutively admitted patients with DSM.III-R chronic schizophrenia. for 65 patients obstetric hlstOlY and for 81 patients age at onset could be obtained. Inclusion criteria were the absence of any focal abnormalities and any diagnosis of organic brain syndrome, substance abuse disorder or mental retardation. The patients were all males, the mean age was 29.9 (SO =7.6) and age at onset was 21.3 (SO =6.7). We used the Scale for the Assessment of Negative Symptoms (SANS) and the Scale for the Assessment of Positive Symptoms (SAPS) to assess current mental state; we selected 8 Items of the SANS (4. 5.6, g, 10, 15, 20 and 23) describing some aspec1 of autistic behaviour. whose sum score was defined as autistic cluster (AlC). In the subjects the severity of OCs was assessed during a semistructured Interview to biological mother by the Midwife Protocol used by Pamas et al. (1982). Brain morphology was evaluated by computerized tomography scan. Results: Autistic cluster did not correlate to neuromorphologlcal mea• sures. There was a significant inverse correlation between AlC and OCs (p .. 0.029) and between AlC and onset (p .. 0.029). Our findings could be viewed as a direct evidenca of a lower environmental influence respec1 to genetic factors on the autistic syndrome in schizophrenia.
163-71 local Chronic MK-801 adminIstration In vivo alters CA 1 circuit Inhibition In vitro H. Grunze 1 , D. RUjescu-Baicu 1 , H.J. MOiler 1 • D. Ralnnie 2, R. Greene 2. 1 Psychiatr. Klinik LMU MOnch6n. Germany, 2 Harvard Moo. SCh.• Boston, USA
Previously we showed that local inbition in the hippocampal CA1 area in rats depends, In part, on NMDA receptor activation. Thus. It can be selectively disrupted by NMDA antagonists, leading to increased network excitability. This mechanism may underlie PCP- psychosis and possibly schizophrenia. as elevated levels of the endogenous partial NMDA antagonist NAAG had been reported in post mortem brains. To simulate this effect of chronic. not acutely toxic NMDA antagonist exposition in rats (age 4Od) we injected 0.02 mglkg KG MK-801 l.p. for 14 days before perfonnlng whole cen patch clamp recordings In vitro from pyramidal cells In the hippocarnpal CAl area (MK-801. n '" 4; saline controls. n '" 3). Nine recordings were obtained In each group. There was no difference of the mean membrane potential. action potential treshold, action potential overshoot. GABA A reversal potential and membrane potential change to local GABA A Injection between groups. However. recurrent Inhibition ellcted by alvear stimulation was significantly reduced In the MK- 801 group (IPSP amplitude -1.6 ± 1.3 mV vs. -3.7 ± 1.2 mV in controls. p < 0.025. Mann-Whitney test). These results are in line with the hypothesis of dysfunctional local inhibition In cortical-limbic areas of schizophrenics due to a partial blockade of Intemeuronal NMDA recep• tors.
163-81 Modifications of auditory ERP and correlations wIth symptomatology In 50 schIzophrenIc patients
Th. Bougerol. A. Benralss, Ch. Lal'llton. D. Bemard. J.C. Scotto. S.H.U dB Psychiatrie. H"Pital Sainte-Marguerife. Maf'S8ille. FI7JfIC{J The aim of the study was to correlate the modifications of auditory ERP to positive and negative symptoms ratings in schizophrenic patients. Method: AuditOlY Event Relaled Potentials were recorded In 50 schizophrenic patients (DSM III-R) and 47 non-psychiatric controls In 3 different experimental settings: standard Auditory Evoked Potentials. pas• sive oddball paradigm and oddball paradigm with an altentional task (silent counting of target stimulus). 3 recording electrodes were used (Fz, Cz, Pz). and the stimuli were tones of 750 Hz (non-target) or 2000 Hz (target). The schizophrenic symptomatology was evaluated with different clinical rating scales: BPRS, SANS. SAPS and PANSS. Results: Schizophrenic patients as a whole were characterized by a re• duced level of cerebral arousal. In atl experimental settings. When classified according to the negatiVe/positive dichotomy, the negative schiZophrenic patients present significant changes In the very earty steps of stimulus anal• ysis and these changes correlate with a depressive dimension of psychotic symptomatology. On the other hand. positive delusional patients are char• acterized by an overarousal state and by more specific modifications of later steps of automatic orientation to the target stimulus. These modifications are not linked to neuroleptic treatments or to the status of care.
163-91 CAGlCTG repeat expansion detection In familial schIzophrenia F. Thlbaut, C. Laurent, C. Zander. M. Martinez. D. CsmpIon, M. Jay. F. Bonnet·Brilhault, O. Chavand. D. Samolyk, H. Cann, C. Nerl. J. Mallet LGN-eNRS. Paris. FI7JfIC{J. CHS Rouvray, Rouen. FI7JfIC{J. U358. Paris, France. CHS Sf Paul. La Reunion, France The tenn. genetic anticipation. is used to describe the increase In disease severity or the decrease in age of onset in succeeding generations within families. This phenomenon has recently been correlated with expansion of DNA 1rinucleotlde repeat sequences in several neuropsychiatric disorders. In schizophrenia, anticipation has been suggested by several studies. Fur• thermore, several groups have reported the occurrence of expanded CAG 1rinucleotlde repeat sequences In schizophrenia patients. using the repeat expansion detection method (RED). We recently reported data supporting anticipation in 26, two generation family pedigrees from Normandy and the island of Is Reunion, France. The RED method has now been used to analyse genomic DNA for the presence of expanded trtnucleotlde repeat sequences In this sample. The analysis of the data obtained from the schizophrenic families will be presented. No clear evidence of triplet repeal expansion In succeeding generations has been demonstrated so far. Possible eXplana• tions for the clinically observed genetic anticipation in schizophrenia will be discussed.