Effectiveness of comprehensive supports for schizophrenic women during pregnancy and puerperium: preliminary study.

The risks of deteriorated psychiatric symptoms/daily life functioning should be warned of in schizophrenic women during pregnancy and puerperium. The purpose of the present paper was to prospectively monitor mental status and functioning of pregnant women with schizophrenia, and investigate the effects of various supports. Subjects were 20 schizophrenic women who visited a clinic providing care and support for pregnant women with psychiatric diseases, consisting of 12 patients with psychotic deterioration (deterioration group) and eight remitted stable patients (stable group). Psychiatric assessments were performed using Positive and Negative Syndrome Scale (PANSS) and Global Assessment of Functioning (GAF) at three time-points: at the first examination, after fixed prescription during pregnancy, and after delivery. The types/doses of drugs and other non-drug-related supports (13 items) were recorded during the study period. Although a higher total PANSS score at the first examination (P = 0.004) and lower GAF scores at the first examination and even after fixed prescription (P = 0.0003) were observed in the deterioration group, those after delivery finally caught up with the levels in the stable group. Doses of antipsychotic drugs were gradually increased in the deterioration group although no significant differences in chlorpromazine equivalent doses were found between the two groups after fixed prescription. There was a positive correlation between the number of non-drug-related supports and amelioration score in PANSS (r(s) = 0.553, P = 0.012). These findings suggest that comprehensive intervention is a requisite in pregnant schizophrenic women, especially with psychotic deterioration, and that non-drug-related supports may also contribute to maintenance of good and stable mental status in these patients.

[Brain volumetric MRI study in healthy elderly persons using statistical parametric mapping].

PURPOSE: To investigate the age-related changes in the brains of healthy elderly subjects, a volumetric MRI was performed using Statistical Parametric Mapping (SPM) and Region of Interest (ROI) methods. We determined the volumes of the whole brain, the gray matter, the prefrontal cortex, the hippocampus and the entorhinal cortex. SUBJECTS AND METHODS: We examined 61 subjects (29 males and 32 females) aged 61 to 91 years (mean +/- SD = 72.4 +/- 7.85) who were residents of Okinawa prefecture, living at home and highly active as demonstrated by sustained participation in senior citizens clubs and/or group activities at senior citizen welfare centers. They had no history of psychiatric disorders, neurological or significant physical illness. They had Mini-Mental State Examination scores of 24 or above (mean +/- SD = 28.3 +/- 1.57), Japanese version of the Geriatric Depression Scale scores of 9 or below, and Tokyo Metropolitan Institute of Gerontology scores of 11 or above. All subjects were dextral. This study received prior approval by the participating medical institution. Informed consent was obtained from the individual subjects. Volumetric MRI was performed using a 1.5 Tesla MRI scanner (Magnetom Vision, Siemens). T1-weighted images were acquired in the coronal plane (perpendicular to anterior commissure-posterior commissure line) using a 3D-FLASH (fast low angle shot) sequence. Imaging parameters were: TR = 35 ms, TE = 5 ms, Flip angle = 45 deg., Field of View = 240 mm, Matrix 256 x 256, Pixel 0.9375 x 0.9375, Slice thickness 1.5 mm, Gapless. MR image data were analyzed by SPM using an imaging analysis software MEDx (Sensor Systems Inc.) running on UNIX workstation (Sun SPARC Solaris 7, Sun Microsystems, Inc.). Volumetry was performed by automatic segmentation technique using SPM for the whole brain and the gray matter, and manual tracing using ROI based quantitative methods for the prefrontal cortex, the hippocampus and the entorhinal cortex. Local volumes were normalized by the intracranial volume and the gray matter volume. Correlation to age was determined by Pearson's correlation coefficient. Volumetric MRI was performed under blinded conditions. RESULTS: Volumetric MRI of normal brain in healthy elderly subjects showed age-related changes. The whole brain (r = -0.568, p < 0.01), the gray matter (r = -0.406, p < 0.01), the prefrontal cortex (r = -0.470, p < 0.01), the hippocampus (r = -0.305, p < 0.05), and the entorhinal cortex (r = -0.455, p < 0.01) volume significantly decreased with age. The age-related hippocampal volume reduction was similar to the gray matter reduction, but the age-related prefrontal cortex and entorhinal cortex volume reductions were greater than the gray matter volume reduction. The prefrontal cortex and the hippocampal volumes differed by sex, being greater in females (p < 0.05). The hippocampal volume was lateralized: right side was greater than the left (p < 0.01). The entorhinal cortex volume was lateralized so that the left side was greater than the right (p < 0.01). CONCLUSION: As a result of volumetric MRI using SPM, age-related changes of normal brain in healthy elderly persons did not always show unified atrophy. The ratio of atrophy was different by a local area. Our findings suggested that the most marked age-related brain volume reductions were seen in the prefrontal cortex and the entorhinal cortex. The age-related hippocampal volume reduction was similar to the gray matter reduction.

Correlation between P50 suppression and psychometric schizotypy among non-clinical Japanese subjects.

The link between P50 suppression and psychometric schizotypy was previously reported in non-clinical English-speaking subjects; however, whether a similar relationship exists within a different ethnic sample is unknown. Furthermore, whether such a relationship can also be accounted for by such basic personality characteristics as extraversion or neuroticism has not yet been reported. In the present study, we investigated the correlations of P50 suppression with psychometric schizotypy, and with extraversion or neuroticism among non-clinical Japanese. Subjects were 34 healthy volunteers. The auditory P50 potential was obtained using a paired stimulus paradigm. Psychometric schizotypy was assessed using schizotypal personality questionnaire (SPQ). Extraversion and neuroticism were assessed using Maudsley personality inventory (MPI). P50 suppression correlated not only with total SPQ score, but also with extraversion and with neuroticism. However, the partial correlation analysis revealed a significant partial correlation of P50 suppression with SPQ when controlled for extraversion or neuroticism, and a non-significant partial correlation of P50 suppression with extraversion or neuroticism when controlled for SPQ. When subjects were divided into two subgroups according to the mean SPQ score, the degree of P50 suppression was lower in the high than in the low SPQ scorers. Our results indicate that P50 suppression is one of the neurobiological substrates underlying psychometric schizotypy, and that this relationship cannot be accounted for by measures of extraversion or neuroticism.

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.

The N200 abnormalities of auditory event-related potentials in patients with panic disorder.

Cognitive impairment in patients with panic disorder (PD) has been studied using event-related potentials (ERPs). However, previous studies obtained ERP data only at a few scalp sites, and seldom investigated N200 measurements from the difference waveforms. In the present study, auditory ERPs were recorded at 16 scalp sites during an active discrimination task of oddball paradigm. Fourteen PD patients (8 with agoraphobia; 6 without agoraphobia) were compared with 14 sex- and age-matched control subjects. For the nontarget waveforms, P2 amplitude was reduced in PD patients. For the target waveforms, a topographical difference between female PD patients and female controls was found for N200 amplitude, which attenuated in female PD patients over the parietal area. Two subcomponents of N200, N2a and N2b, were measured from the difference waveforms. A significant group difference was found for N2b amplitude, which reduced in PD patients compared with unaffected control subjects. It is suggested that N2b reduction reflects an abnormally controlled processing of stimulus information in PD.

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.

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.

Psychophysiological index during auditory selective attention correlates with visual continuous performance test sensitivity in normal adults.

The continuous performance test (CPT) provides a reliable index of cognitive function, but it is still unclear what aspects of processing this test measures. This study aimed to investigate the contribution of different aspects of cognitive function to the performance on degraded stimulus CPT (DSCPT), which requires a higher level of mental effort than the conventional CPT. Event-related potential (ERP) components, MMN, N2b, and early and late Nds were measured at 16 electrode sites in 19 right-handed normal volunteers using an auditory selective attention task. The association between CPT sensitivity ratings (sensitivity A') and amplitudes of each component was examined for each electrode site. The CPT sensitivity A' showed a significant positive correlation with the N2b amplitude in the fronto-central and temporal regions, predominantly in the right hemisphere and specifically to the right ear of stimulation. This finding suggests that the controlled deviance detection process was related to DSCPT performance.

The effects of benzodiazepines on event-related potential indices of automatic and controlled processing in schizophrenia: a preliminary report.

The effects of benzodiazepines on cognitive function in schizophrenic patients were investigated using event-related potential (ERP) measurement during an auditory selective attention task. In this study, the authors compared the mismatch negativity (MMN) and N2b components between two subgroups of schizophrenic patients: one is comprised of patients who received no benzodiazepines (NT group, n = 7) and the other is comprised of those administered benzodiazepines in the daytime (T group, n = 7). There were no significant differences in MMN and N2b amplitudes between the two subgroups, whereas the N2b latency was significantly prolonged in the T group relative to the NT group. This suggested that benzodiazepines induce delayed stimulus classification processing in schizophrenic patients.