Shigeru Nohara

Regional changes in brain gray and white matter in patients with schizophrenia demonstrated with voxel-based analysis of MRI

This study examined regional structural changes in the whole brain in 45 medicated patients with schizophrenia (23 males and 22 females), comparing with 42 age- and sex-matched healthy volunteers (22 males and 20 females). Automated voxel-based analysis on three-dimensional magnetic resonance imaging (MRI) was conducted using statistical parametric mapping (SPM). Compared with the controls, relative gray matter in the patients was significantly reduced in the left superior temporal, left middle and inferior frontal, right inferior frontal, and bilateral anterior cingulate and medial temporal areas. Gray matter reductions in the left superior temporal and prefrontal areas were found predominantly in the male patients, while the anterior cingulate gray mater reduction was more striking in the female patients. On the contrary, significant gray matter increases in the patients were found in the parietal areas and the cerebellum. In the white matter, significant reduction was found in the bilateral anterior limbs of the internal capsule and the superior occipitofrontal fasciculus, whereas the bilateral parietal white matter showed significant increases. These results suggest that a pathological process in schizophrenia predominantly affects the fronto-temporolimbic-paralimbic regions. Reduced white matter in the connecting bundles, which was first found in this study, may imply morphological substrates for abnormalities in the fronto-thalamic and fronto-temporolimbic connectivity in schizophrenia.

The effect of tandospirone, a serotonin1A agonist, on memory function in schizophrenia

BACKGROUND The purpose of this study was to test the hypothesis that the addition of tandospirone, a 5-HT(1A) partial agonist, to ongoing treatment with typical antipsychotic drugs, would improve memory function in patients with schizophrenia. METHODS Eleven outpatients (male/female = 7/4) with schizophrenia who had been on stable doses of haloperidol and biperiden were given tandospirone, 30 mg/day, for 4 weeks. The Wechsler Memory Scale-Revised (WMS-R) was administered at baseline and 4 weeks after the addition of tandospirone. The Brief Psychiatric Rating Scale (BPRS; Total, Positive, and Negative subscale scores) and the Simpson-Angus Scale for Extrapyramidal Symptoms (SAS) were also completed on the two occasions. To exclude the possibility of a practice effect on the WMS-R test, 11 age-matched patients with schizophrenia (M/F = 7/4) were tested at baseline and after a 4-week interval. RESULTS Repeated measures analysis of variance revealed a significant time by group (patients with or without tandospirone) effect for the Verbal-, but not the Visual Memory composite scores of the WMS-R test; no significant change was observed in patients without tandospirone, whereas improvement in the Verbal Memory score was noted in patients receiving tandospirone. Moreover, there was improvement in the Inclusion score, an index of memory organization as measured by the Logical Memory subtest of WMS-R, only in patients with tandospirone. Scores on the BPRS and SAS were improved during treatment with tandospirone, but the effects did not reach statistical significance. CONCLUSIONS The results suggest that adjunctive treatment with 5-HT(1A) agonists may improve some types of memory function in schizophrenia.

Structural brain differences in patients with schizophrenia and schizotypal disorder demonstrated by voxel–based morphometry

AbstractBrain abnormalities of schizophrenia probably consist of deviation related to the vulnerability and pathological changes in association with overt psychosis. We conducted a cross–sectional comparison in brain morphology between patients with overt schizophrenia and schizotypal disorder, a schizophrenia–spectrum disorder without florid psychotic episode. Voxelbased morphometry was applied to assess gray matter volume in 25 patients with schizophrenia, 25 patients with schizotypal disorder, and 50 healthy control subjects. In comparison with controls, schizophrenia patients showed gray matter reductions in the bilateral medial frontal, inferior frontal, medial temporal, and septal regions, and the left middle frontal, orbitofrontal, insula, and superior temporal regions, and an increased gray matter in the left basal ganglia. Schizotypal disorder patients showed reductions in the left inferior frontal, insula, superior temporal, and medial temporal regions. There was a significant reduction in the left orbitofrontal region of schizophrenia compared with schizotypal disorder. Gray matter reductions that are common to both patient groups such as those in the left medial temporal and inferior frontal regions may represent vulnerability to schizophrenia, and additional involvement of several frontal regions may be crucial to florid psychosis.

Decreased volume and increased asymmetry of the anterior limb of the internal capsule in patients with schizophrenia

BACKGROUND The anterior limb of the internal capsule (ALIC) contains the anterior thalamic peduncle connecting the medial and anterior thalamic nuclei with the prefrontal cortex and the cingulate gyrus. The purpose of this study was to detect the volumetric changes in the ALIC in view of the putative abnormal frontothalamic connectivity in schizophrenia. METHODS High-resolution, three-dimensional magnetic resonance imaging was acquired from 53 schizophrenia patients and 48 age- and gender-matched control subjects. Volumetric analysis was performed using consecutive 1-mm-thick coronal slices rostral to the anterior commissure, on the ALIC, caudate nucleus, and lentiform nucleus. White matter concentration over the whole brain was compared using the voxel-based morphometry (VBM) with Statistical Parametric Mapping 99. RESULTS The patients had significantly decreased volumes in the bilateral ALIC and showed significantly increased right-greater-than-left asymmetry of the ALIC; VBM revealed a reduction in white matter concentration of the bilateral internal capsule in patients. No volumetric difference was found in the rostral part of the caudate and lentiform nucleus between groups. CONCLUSIONS Decreased volume found in the ALIC supports the hypothesis of abnormal frontothalamic connectivity in schizophrenia. Increased asymmetry of the internal capsule seems consistent with the notion of predominantly left-side pathology of schizophrenia.

Lack of normal structural asymmetry of the anterior cingulate gyrus in female patients with schizophrenia: a volumetric magnetic resonance imaging study

We investigated anterior cingulate gyrus (ACG) volume in 40 patients with schizophrenia (20 males, 20 females) and 40 age-and sex-matched normal controls using three-dimensional magnetic resonance imaging (MRI). Volumes of the whole brain and both the gray and white matter of the ACG were measured on consecutive coronal 1-mm slices. There was no significant difference between the patients with schizophrenia and the normal controls in the whole brain volume. Right ACG gray matter volume was significantly reduced in the female patients with schizophrenia as compared with the female controls. Furthermore.in the female controls, ACG gray matter volume was significantly larger on the right than on the left, while this asymmetry was not significant in the female patients. ACG white matter findings were similar to those of the ACG gray matter in that the volume was significantly larger on the right in the female controls, and this normal structural asymmetry was reduced in the female patients. These results suggest that gender may play an important role in the structural asymmetry anomalies in schizophrenia.

Neural correlates of memory organization deficits in schizophrenia A single photon emission computed tomography study with 99mTc-ethyl-cysteinate dimer during a verbal learning task

Abstract Regional cerebral blood flow (rCBF) during a verbal learning task was measured using 99m Tc-ethyl-cysteinate dimer and single photon emission computed tomography in 10 patients with schizophrenia and nine normal controls. Verbal repetition was used as a control task. The schizophrenic patients showed failure to spontaneously utilize implicit category information to learn the word lists. In the normal controls, rCBF in the left inferior frontal and left anterior cingulate regions was significantly increased during the verbal learning task, compared with the verbal repetition task. In contrast, there was no significant frontal lobe activation by the verbal learning in the schizophrenic patients. The patients had lower rCBF during the verbal learning task than the controls in the bilateral inferior frontal, left anterior cingulate, right superior frontal, and bilateral middle frontal regions. Activation in the left inferior frontal region was significantly positively correlated with categorical clustering in the task in the controls, but no such correlation was found in the patients. These results indicate that memory organization deficits in schizophrenia may be related to dysfunction in the prefrontal areas, especially in the left inferior frontal region.

Anomalous Cerebral Asymmetry in Patients with Schizophrenia Demonstrated by Voxel-Based Morphometry

BACKGROUND Evaluating cerebral asymmetry in schizophrenia patients potentially leads to understanding the extent to which the disorder involves a neurodevelopmental failure. We sought to clarify in which brain regions of the patient the normal cerebral asymmetry is disrupted and the extent of disruption. METHODS Voxel-based morphometry to evaluate gray matter asymmetry was carried out with magnetic resonance images from a total of 120 right-handed subjects. They comprised four groups of 30 subjects (i.e., male schizophrenia, female schizophrenia, male control, and female control). To examine gray matter asymmetry we generated images of the lateralization index. RESULTS The analysis within each of four groups revealed a consistent pattern of gray matter asymmetry over all groups. However group comparison between all patients and all healthy subjects showed significant difference in the cerebral lateralization in the pars triangularis and planum temporale. Frequency distributions of the lateralization index showed a skew toward rightward asymmetry in the pars trianglaris and a reduction in leftward asymmetry in the planum temporale in patients relative to control subjects. CONCLUSIONS A disturbance of cerebral asymmetry in schizophrenia was suggested to be present in language-related regions, which might reflect a perturbation in the lateralization process underlying left cerebral dominance for language.

Disorganization of semantic memory underlies alogia in schizophrenia: an analysis of verbal fluency performance in Japanese subjects.

Patients with schizophrenia exhibit impaired semantic memory as well as deficits in a wide range of language-related functions, such as verbal fluency, comprehension and production of complex sentences. Since language and memory disturbances may underlie some of the psychotic symptoms of schizophrenia, the present study investigated the specific association between alogia (i.e. poverty of speech, poverty of content of speech, blocking, and increased latency of response) and semantic memory organization using the category fluency task (CFT) as a measure of verbal fluency. Thirty-eight patients with schizophrenia and an equal number of normal controls entered the study. Semantic structure was derived from multidimensional scaling analysis using sequential word outputs from the CFT. Patients with schizophrenia revealed disorganized semantic structure (e.g. irregular association of category members) compared with controls, consistent with previous reports. The patients were then divided into two groups, i.e. alogia- and non-alogia subjects, based on the Alogia scores from the Scale for the Assessment of Negative Symptoms (SANS). The symptom-based analysis showed that the semantic structure for the alogia group (Alogia score < or =2) was more disorganized than that for the non-alogia group (Alogia score <1) although the number of words produced did not differ between the two groups. The results of cluster analysis revealed the presence of bizarre coherence specifically in the alogia group. These results indicate that semantic memory disorganization may contribute to the symptom of alogia in schizophrenia. In addition, this is one of the few studies that examined verbal fluency in Japanese patients with schizophrenia and suggest that the language abnormalities in schizophrenia are universal.

Volumetric magnetic resonance imaging study of the anterior cingulate gyrus in schizotypal disorder

Abstract. Lack of normal structural asymmetry of the anterior cingulate gyrus (ACG) in patients with schizophrenia has been reported in our previous study. However, to our knowledge, no morphological studies of the brain have examined changes in ACG volume in patients with schizotypal features. We investigated the volume of the gray matter and the white matter of the ACG by three-dimensional magnetic resonance imaging (MRI) in 24 patients who met the ICD-10 criteria for schizotypal disorder (12 males, 12 females) in comparison with 48 age- and gender-matched healthy control subjects (24 males, 24 females) and 40 patients with schizophrenia (20 males, 20 females). As we reported previously, right ACG gray matter volume was significantly reduced in the female patients with schizophrenia compared with the female controls. On the other hand, the gray and white matter volume of the ACG in the patients with schizotypal disorder did not differ significantly from the values in the healthy controls or the patients with schizophrenia. However, the female patients with schizotypal disorder showed a lack of right-greater-than-left asymmetry of the ACG gray and white matter found in the female controls. These results suggest that both schizotypal and schizophrenic subjects share, at least in part, the same cerebral asymmetry abnormalities.

Perigenual cingulate gyrus volume in patients with schizophrenia: a magnetic resonance imaging study

BACKGROUND Anterior cingulate gyrus abnormalities have been suggested to be involved in the pathophysiology of schizophrenia; however, little is known about morphologic changes in the perigenual cingulate gyrus in schizophrenia patients. METHODS We investigated perigenual cingulate gyrus volume in 40 schizophrenia patients (20 men, 20 women) and 40 age- and gender-matched normal controls using magnetic resonance imaging. Volume of both gray and white matter of the perigenual cingulate gyrus was measured on consecutive axial 1-mm slices. RESULTS Total (left and right) perigenual cingulate gray matter volume was significantly reduced in female schizophrenia patients compared with female controls. There was no significant difference in the gray matter volume of the perigenual cingulate gyrus between male patients and male controls. Left perigenual cingulate white matter volume was significantly reduced in the patient compared with the control group. Furthermore, significant gender differences were found in the total gray and white matter volume of the perigenual cingulate gyrus in control subjects (women > men), although these gender differences were not significant in the patient group. CONCLUSIONS Our findings suggests volume reduction of the perigenual cingulate gyrus in schizophrenia patients, especially women and that gender differences in perigenual cingulate morphology among normal subjects are, as has been suggested for other parts of the brain, reduced in schizophrenia patients.