Yasuhiro Kawasaki

We measured duration mismatch negativity (dMMN), P3a, and reorienting negativity (RON) in subjects with at-risk mental state (ARMS), patients with first-episode or chronic schizophrenia, and healthy volunteers. The main interest was to determine if these event-related potentials provide a biomarker associated with progression to overt schizophrenia in ARMS subjects. Nineteen ARMS subjects meeting the criteria of the Comprehensive Assessment of ARMS, 38 patients with schizophrenia (19 first-episode and 19 chronic), and 19 healthy controls participated in the study. dMMN, P3a, and RON were measured with an auditory odd-ball paradigm at baseline. During the follow-up period (2.2 years), 4 out of the 19 ARMS subjects transitioned to schizophrenia (Converters) while 15 did not (non-Converters). dMMN amplitudes of Converters were significantly smaller than those of non-Converters at frontal and central electrodes before onset of illness. dMMN amplitudes of non-Converters did not differ fr...

Although clinical and neuropsychological findings have implicated functional deficits of the orbitofrontal cortex (OFC) in schizophrenia, structural magnetic resonance imaging (MRI) studies of this region have yielded inconsistent findings. In addition, it remains elusive whether the OFC morphology in first-episode patients is related to their clinical features. MR images were acquired from 42 (24 males, 18 females) first-episode schizophrenia patients and 35 (20 males, 15 females) age-, gender-, and parental socio-economic status (SES)-matched healthy subjects. The OFC sub-regions (orbital gyrus and straight gyrus) were measured on contiguous 1-mm-thick coronal slices. The OFC sulco-gyral pattern was also evaluated for each subject. Furthermore, the relationships between OFC morphology and clinical measures were examined. The volumes of the bilateral orbital gyri were significantly reduced in schizophrenia patients compared with healthy subjects, whereas the volumes of the straight gyri did not show differences between the groups. Among the schizophrenia patients, the volume of the left orbital gyrus was inversely correlated with their SES and illness duration. The OFC sulco-gyral patterns were significantly different between the patients and controls in the right hemisphere. This study demonstrated morphologic abnormalities of the OFC in first-episode schizophrenia patients, which may have reflected neurodevelopmental aberrations and neurodegenerative changes during the first episode of the illness. Our findings also suggest that such brain structural changes are related to the social dysfunction observed in schizophrenia.

The purpose of this study was to determine if perospirone, a second generation antipsychotic drug and partial agonist at serotonin-5-HT(1A) receptors, enhances electrophysiological activity, such as event-related potentials (ERPs), in frontal brain regions, as well as cognitive function in subjects with schizophrenia. P300 current source images were obtained by means of standardized low resolution brain electromagnetic tomography (sLORETA) before and after treatment with perospirone for 6 months. Perospirone significantly increased P300 current source density in the left superior frontal gyrus, and improved positive symptoms and performance on the script tasks, a measure of verbal social cognition, while verbal learning memory tended to be improved. There was a significant correlation between the changes in P300 amplitude on the left frontal lead and those in social cognition. These results suggest the changes in three-dimensional distribution of cortical activity, as demonstrated by sLORETA, may mediate some of the actions of antipsychotic drugs. The distinct cognition-enhancing profile of perospirone in patients with schizophrenia may be related to its actions on 5-HT(1A) receptors.

This longitudinal MRI study investigated the pituitary volume in 17 patients with chronic schizophrenia and 17 matched controls. In contrast to previous findings of pituitary expansion during the first episode of schizophrenia, the chronic patients showed non-significant mild pituitary atrophy, suggesting that the pituitary volume changes differently at different illness stages.

Seventy Japanese DSM-III-R schizophrenic patients were assessed for 30 clinical symptoms using the Positive and Negative Syndrome Scale (PANSS) of Kay et al. Principal component analysis was applied to the full item set of this scale and disclosed 5 orthogonal independent symptom groups: negative, hostile/excited, thought-disordered, delusional/hallucinatory and depressive components. Our results provided further support of the contention that more than 2 (i.e., positive and negative) dimensions are required to account for structures of the schizophrenic symptoms.