Prefrontal abnormalities in patients with simple schizophrenia: structural and functional brain-imaging studies in five cases.

Simple schizophrenia is an uncommon disorder with unknown pathophysiology, and its position in the current diagnostic system is ambiguous. Brain-imaging studies may help to elucidate its pathophysiology. Five patients fulfilling both ICD-10 criteria for simple schizophrenia and DSM-IV criteria for simple deteriorative disorder underwent computed tomography, magnetic resonance imaging, and single photon emission computed tomography. These scans were assessed individually by visual inspection as well as automatically by comparison with scans in normal controls or other schizophrenia subtype patients using voxel-based image analyses. Three of the five simple schizophrenia patients had findings of atrophy and reduced cerebral perfusion in the frontal areas. Voxel-based analyses also showed prefrontal grey matter deficits and hypoperfusion in simple schizophrenia patients compared with the controls. Although this study is limited by the small number of patients with simple schizophrenia, the results suggest that simple schizophrenia, or at least this subpopulation, may have rather homogeneous morphological and functional deficits in the prefrontal cortex. It is also suggested that simple schizophrenia may occupy an extreme position of the schizophrenic continuum where the prefrontal deficits and negative symptoms are most purely manifested.

Volumetric MRI study of the short and long insular cortices in schizophrenia spectrum disorders.

We have previously reported volume reductions of the insular cortex in schizophrenia, but it is still not clear whether insular cortex volume loss preferentially involves the anterior (short insular cortex) or posterior (long insular cortex) portion. On the other hand, no volumetric studies of the brain have examined changes in insular cortex volume in subjects with schizotypal features. In this study, we separately investigated the volumes of the short and long insular cortex portions using magnetic resonance imaging in 37 schizotypal disorder patients (24 males, 13 females), 62 schizophrenia patients (32 males, 30 females), and 69 healthy controls (35 males, 34 females). While the volumes of the short and long insular cortex were significantly reduced in schizophrenia patients compared with schizotypal disorder patients and control subjects, there was no difference between schizotypal disorder patients and control subjects. These results suggest that the volume reduction of the insular cortex may be specific to overt schizophrenia without topographically specific localization.

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.

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

Brain 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.

Bilateral volume reduction of the insular cortex in patients with schizophrenia: a volumetric MRI study.

The morphologic changes of the insular cortex have been described in schizophrenia, but with inconsistencies between reports. We investigated the insular cortex volume by magnetic resonance imaging in 59 schizophrenia patients (31 males, 28 females) and 62 age- and gender-matched healthy controls (31 males, 31 females). The insular cortex volume was measured on consecutive coronal 1-mm slices. Volumes of the left and right insular cortex were significantly reduced in schizophrenia patients compared with control subjects. There were no effects of gender on the insular cortex volume in the patient group or control subjects. Bilateral insular cortex volumes were correlated negatively with illness duration in the patient group. The findings of this study suggest that there is a possible progressive loss of the gray matter volume of the bilateral insular cortices subsequent to the onset of schizophrenia.

Lack of normal gender differences of the perigenual cingulate gyrus in schizophrenia spectrum disorders. A magnetic resonance imaging study.

We have previously reported a lack of normal gender differences of the perigenual cingulate gyrus in patients with schizophrenia. The purpose of this study was to examine the perigenual cingulate gyrus morphology in patients with schizotypal disorder. We investigated volume of the gray and white matter of the perigenual cingulate gyrus in 26 patients with schizotypal disorder (14 males, 12 females) in comparison with 61 age- and gender-matched healthy controls (30 males, 31 females) and 58 schizophrenia patients (31 males, 27 females) using magnetic resonance imaging. The volumetric measures of the perigenual cingulate gyrus were compared among the three groups that were entered into the same multiple analysis of variance model. The gray and white matter volume of the perigenual cingulate gyrus in the schizotypal patients did not differ significantly from the values in the healthy controls or the schizophrenia patients. Similar to schizophrenia, however, the schizotypal patients showed a lack of normal gender differences of the perigenual cingulate gray matter seen in the healthy controls (females > males). These results suggest that both schizotypal and schizophrenia patients may share the same disruption of the normal pattern of gender differences of the perigenual cingulate gyrus.

Volume reduction of the right anterior limb of the internal capsule in patients with schizotypal disorder.

We have previously reported bilateral volume reductions in the anterior limb of the internal capsule (ALIC) in patients with schizophrenia. The purpose of this study was to extend the volumetric measurements of ALIC to subjects with schizotypal features to explore the neurobiology underlying schizophrenia-spectrum disorders in view of the fronto-thalamic connectivity. Three-dimensional magnetic resonance images were acquired from 24 patients with schizotypal disorder (ICD-10) and 47 healthy volunteers matched for age, gender, handedness, and parental education. Volumetric analyses of the ALIC and anterior parts of the caudate and lentiform nuclei were conducted using consecutive 1-mm thick coronal slices rostral to the anterior commissure. Compared with the comparison subjects, the schizotypal patients had significantly decreased volume in the right ALIC, but there was no significant group difference in the left ALIC volume. Volumes of the anterior part of the caudate or lentiform nucleus did not differ between groups. Volume deficit confined to the right ALIC suggests that limited involvement of the fronto-thalamic connectivity may have some relevance to the sparing of schizotypal patients from the development of overt psychosis.

Effect of orthography on the verbal fluency performance in schizophrenia: examination using Japanese patients.

Letter fluency performance is less impaired than the category fluency performance in alphabetical-language speakers with schizophrenia. The purpose of this study was to determine whether the same pattern in the performance on the two verbal fluency tasks exists in subjects using a non-alphabetical language. In the Japanese orthography, there is one-to-one correspondence between sound (syllable) and graphemes ("kana" script), in contrast to one-to-many associations in alphabetical languages (e.g. English, French). The category fluency task (ANIMAL, FRUIT) and the letter fluency task ("KA", "TA" in "kana" script) were administered on 38 patients with schizophrenia and the equal number of normal controls. In order to examine the influence of psychotic symptoms on the verbal fluency performance, the Scale for the Assessment of Positive Symptoms (SAPS) and the Scale for the Assessment of Negative Symptoms (SANS) were administered. The patients performed significantly worse both in the letter- and category fluency tasks compared with control subjects. However, performance on the letter fluency task and category fluency task was similarly impaired in Japanese patients with schizophrenia, unlike the results in previous studies with alphabetical-language speakers. On the other hand, Alogia symptoms, as assessed by SANS, was a significant predictive variable in the regression model for the category fluency task score (ANIMAL), whereas the factor of the other domains of negative symptoms as a whole was a significant predictive variable in the model for the letter fluency task score (TA), which confirmed the findings in previous studies with alphabetical-language subjects. These results suggest that the pattern of impairment in the verbal fluency performance in schizophrenia is dependent on the specific language systems used by the patients although the degradation of the verbal fluency performance is influenced by some types of negative symptoms irrespective of the language system.

Bilateral volume reduction of the insular cortex in patients with schizophrenia: a volumetric MRI Study.

The morphologic changes of the insular cortex have been described in schizophrenia, but with inconsistencies between reports. We investigated the insular cortex volume by magnetic resonance imaging in 59 schizophrenia patients (31 males, 28 females) and 62 age- and gender-matched healthy controls (31 males, 31 females). The insular cortex volume was measured on consecutive coronal 1-mm slices. Volumes of the left and right insular cortex were significantly reduced in schizophrenia patients compared with control subjects. There were no effects of gender on the insular cortex volume in the patient group or control subjects. Bilateral insular cortex volumes were correlated negatively with illness duration in the patient group. The findings of this study suggest that there is a possible progressive loss of the gray matter volume of the bilateral insular cortices subsequent to the onset of schizophrenia.

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.

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.

Proton magnetic resonance spectroscopy of the inferior frontal gyrus and thalamus and its relationship to verbal learning task performance in patients with schizophrenia: a preliminary report.

Previous research has found frontal lobe involvement in memory impairment in schizophrenia. In the present study, proton magnetic resonance spectroscopy was performed in 13 young patients with schizophrenia and 13 normal control subjects. Spectra were obtained from a voxel of 2 x 2 x 1.5 cm(3) in the bilateral inferior frontal gyrus and thalamus. Subjects were given a verbal learning task and stimulus category repetition (SCR) was calculated from the performance of the task. Significantly reduced N-acetylaspartate (NAA)/choline-containing compounds ratios were found in the left inferior frontal cortex of patients compared with controls. The total number of words recalled by patients was significantly lower than that recalled by controls. In all subjects, SCR scores were positively correlated with NAA/phosphocreatine ratios of the left inferior frontal cortex, which showed a trend towards a decrease in patients. These results support the notion of metabolic abnormalities in the left inferior frontal region related to verbal memory deficits in patients with 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.

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

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.