Chikara Ogura

Abnormalities of auditory event-related potentials in schizophrenia prior to treatment.

BACKGROUND P300 amplitude reduction is a consistent finding in schizophrenic patients, but it is unclear if this abnormality predates neuroleptic treatment or is present at onset of illness. METHODS Auditory event-related potentials (ERPs), during a standard oddball paradigm, were recorded from 45 neuroleptic-naive schizophrenics, 56 drug-free, previously treated schizophrenics, and 73 healthy normal controls. Forty-seven of the schizophrenic subjects had their first episode within the past year. RESULTS N200 amplitude did not differ among groups. P300 amplitude was significantly smaller in both neuroleptic-naive and previously treated schizophrenic groups compared to the control groups. There were no significant differences between the two schizophrenic groups in P300 amplitude. N200 and P300 latency were prolonged in previously treated schizophrenics compared to neuroleptic-naive schizophrenics and normal controls. CONCLUSIONS The present study suggests that ERP abnormalities, especially P300 amplitude reduction, are already present prior to the administration of neuroleptic medication in the earliest stage of schizophrenia.

The N400 component of event-related potentials in schizophrenic patients: a preliminary study.

ERPs were recorded during a word recognition task to investigate cognitive dysfunction in schizophrenia. Thirteen medicated schizophrenics and 26 normal controls were tested. In each trial a pair of stimuli, S1 (a word) and S2 (a word or a non-word), were presented. The subjects were required to discriminate between a word and a non-word for S2 (lexical decision task). In a related (R) condition, S2 was the antonym of S1 (e.g., brother-sister); in an unrelated (U) condition, S1 and S2 were semantically unrelated (e.g., brother-drive); in the non-word (N) condition, S2 was a non-word (e.g., brother-grofe). The ERPs for S2 were analyzed, and the contextual effects on the ERPs for S2 observed for both the patients and controls. For both groups, in the U and N conditions S2 elicited a large negative-trending deflection (N370). In contrast, in the R condition it elicited only a small negative-trending notch. There was no difference in the amplitude of N370 between the groups, but its latency was more prolonged or its wave shape more extended for the schizophrenics than for the controls. The N400 amplitude is concluded to remain unchanged in schizophrenics.

N200 component of event-related potentials in depression

Event-related potentials (ERPs) recorded during a two-tone discrimination (oddball) task were examined in 36 drug-free depressed patients and 36 control subjects. At remission, the ERPs of 12 of the depressed patients were reexamined. In the depressed patients, although a group difference was not detected in the peak latency and amplitude of N200 to rare stimuli, the mean amplitude for the N200 latency range in the difference waves was smaller than in the control subjects. Mismatch negativity (N2a), which was elicited by rare stimuli, was reduced in amplitude; but N2b may have been evoked to frequent stimuli more in the patients than in the control subjects. Depressed subjects may have a deviance in the fully automatic cerebral mismatch process that is assumed to be related to mismatch negativity and provoke the controlled mismatch detection process (presumed to be associated with N2b) even to nontarget frequent stimuli. These findings were observed during remission; however, there was a tendency for the N2b amplitude to decrease and recover toward the level of the control subjects.

ERPs in schizophrenic patients during word recognition task and reaction times

Event-related brain potentials (ERPs) were recorded in 28 schizophrenic patients and 26 healthy controls during a word recognition task. In each trial, stimuli consisting of S1 (word) and S2 (word or non-word) were presented. The subjects were required to indicate whether S2 was a word or a non-word by pressing buttons. For both groups, a clear N370 was elicited by S2 which were non-word or semantically unrelated to its S1. The N370 amplitude did not differ between the groups. The schizophrenics responded more slowly than the controls, and the latencies of P200 and N370 were longer for patients than for controls. However, these latencies did not differ between the groups when their reaction times were matched.

N400 abnormalities in unmedicated patients with schizophrenia during a lexical decision task

A lexical decision task was used to investigate semantic processing in schizophrenia. Eighteen unmedicated schizophrenics and 18 gender/age-matched controls were tested. Subjects were visually presented with pairs of words. The target word (S2) was either a non-word, semantically related, or unrelated to preceding word (S1). Subjects decided whether the S2 was a word or non-word. Event related potentials (ERPs) elicited by the S2, including N350, and the late positive component (LPC) were measured. The latency of the N350 was prolonged in schizophrenia. The N400 effect, measured by the mean amplitude (300-500 ms) from difference waves (unrelated word-related word, non-word-related word), was smaller in patients. Peak amplitude of the LPC was reduced and latency of the LPC was delayed in the schizophrenics. Behaviorally, control subjects responded much faster to related words compared to unrelated or non-words, while patients showed little difference in processing speed between word categories. A reduced N400 effect suggested inefficient utilization of the context, while prolonged latency of the ERP components suggested a general delay of semantic information processing in schizophrenia.

Effects of the dopamine-related drug bromocriptine on event-related potentials and its relation to the law of initial value

Abstract Effects of the dopamine‐related drug bromocriptine (BCT) on event‐related potentials (ERP) were investigated in 18 healthy volunteers. Bromocriptine 2.5 mg or an inactive placebo was administered according to a completely randomized double‐blind, cross‐over design. The ERP were recorded 3 h after medication was given. Although BCT prolonged the P300 latency, it had no effect on the amplitudes of the ERP components as a whole. Bromocriptine increased the latencies of N100, P200 and P300 in the respective short‐latency subject group, and decreased the latency of N200 in the long‐latency subject group. It increased the amplitude of N200 in the low‐amplitude subject group. It was concluded that the prolongation of P300 latency as a whole and the different responses that take place are dependent on the initial values and were recognized in the effect of a single administration of BCT 2.5 mg. The results of this study are discussed in relation to the law of initial value.

N2 and P3b components of the event-related potential in students at risk for psychosis

The N2 and P3b components of event-related potentials (ERPs) were studied in students who were identified as being at high risk for psychosis on the basis of their scores on the Chapman Psychosis Proneness Scales (PPS). The Magical Ideation subscale (MIS), the Perceptual Aberration subscale (PABS), and the Social Anhedonia subscale (SAS) were administered to 2,022 undergraduate university students. To determine if there were any relationships between these psychometric instruments and electrophysiological measures, 40 high-risk students were compared with 40 age- and gender-matched control students using auditory ERPs obtained from three midline electrodes (Fz, Cz, Pz) in a standard oddball paradigm. N2 (rare stimuli) and N2b latencies were significantly longer in the high-risk than in the control subjects, and the high-risk group also evidenced significantly smaller amplitude of the P3b component. No significant correlations between scores on the PPS or its three subscales and the amplitudes or latencies of the P3b or N200 component were found. These findings suggest that the N2 and P3b ERP components might serve as trait markers for psychosis and that individuals psychometrically identified as being at high risk for psychosis have deficits in the maintenance of attention and in decision-making.

Increased rate of P300 latency prolongation with age in drug-naive and first episode schizophrenia

OBJECTIVE Previous studies have found an increased rate of P300 latency prolongation with age in medicated chronic patients with schizophrenia, suggesting a pathological neurodegenerative process. In this study, we investigated whether this abnormality was identified in drug-naive and first episode patients with schizophrenia. METHODS P300 from auditory stimuli was recorded from 20 drug naive and first episode male patients with schizophrenia and compared with 23 age and handedness matched healthy male controls. The relationship of P300 latency and P300 amplitude to age in each group was evaluated using polynomial regression analyses. RESULTS Reduction of P300 amplitude was significant in drug-naive and first episode schizophrenia patients. P300 amplitude negatively correlated with age in schizophrenia patients but not in controls. Although the prolongation of P300 latency with age was observed in both groups, the regression slope for P300 latency with age was significantly steeper in patients with schizophrenia than in normal controls. Significant overall curvilinear correlations with age were also found for P300 latency and amplitude in patients with schizophrenia, and for P300 latency in normal controls. CONCLUSIONS The greater increase in P300 latency and reduction in P300 amplitude with age may be a primary neuropathological effect of schizophrenia. SIGNIFICANCE This study suggests that neurodegenerative processes are involved in the etiology of schizophrenia.

Abnormalities of auditory P300 cortical current density in patients with schizophrenia using high density recording.

While P300 current density analysis has been performed in schizophrenic patients, the event-related potential data have never been obtained using a high density recording, nor have their cortical images been well demonstrated. In this study, the auditory P300 elicited by an oddball paradigm was recorded using a high density recording system of 128 channels. Thirteen male patients who met DSM-IV criteria for schizophrenia were compared with 20 healthy male controls. The cortical current density analysis of low resolution electromagnetic tomography (LORETA) was applied to the P300 component, and this resulted in the values of 6222 current density points over the surface of a cortex model. The inter-group difference of P300 current density was assessed using a point-by-point comparison by t-test. While the normal controls demonstrated the cortical activation of bilateral frontal, temporal and parietal cortex during the oddball paradigm, visual inspection suggested that in the schizophrenic patients these areas were less activated. The inter-group significance of P300 current density was dominant over the left hemisphere, and particularly over the left prefrontal area. It is concluded that the LORETA current density analysis localizes the neural activity from the cortical fronto-temporo-parietal network as the neural substrates of the scalp recorded P300. The dysfunction of such a network, especially over the left hemisphere, possibly subserves the scalp recorded P300 abnormality in schizophrenia.

Comparative Study of the Effects of 9 Antidepressants on Several Physiological Parameters in Healthy Volunteers

Effects on physiological parameters were compared among 9 antidepressants (amitriptyline 50 mg, imipramine 50 mg, nortriptyline 50 mg, amoxapine 50 mg, maprotiline 50 mg, mianserin 20 mg, zimelidine 100 mg, nomifensine 50 mg, and Y-8894 50 mg) after a single oral administration in healthy volunteers. Critical fusion frequency of flicker, body sway distance, salivary flow rate, near blurred point, and pulse rate were employed as parameters. The degree of the drug effects on the physiological parameters could be roughly classified into two to four groups according to maximum percent deviation of each parameter.