Kazue Nakamura

Multivariate voxel-based morphometry successfully differentiates schizophrenia patients from healthy controls

Currently available laboratory procedures might provide additional information to psychiatric diagnostic systems for more valid classifications of mental disorders. To identify the correlative pattern of gray matter distribution that best discriminates schizophrenia patients from healthy subjects, we applied discriminant function analysis techniques using the multivariate linear model and the voxel-based morphometry. The first analysis was conducted to obtain a statistical model that classified 30 male healthy subjects and 30 male schizophrenia patients diagnosed according to current operational criteria. The second analysis was performed to prospectively validate the statistical model by successfully classifying a new cohort that consisted of 16 male healthy subjects and 16 male schizophrenia patients. Inferences about the structural relevance of the gray matter distribution could be made if the individual profile of pattern expression could be linked to the specific diagnosis of each subject. The result was that 90% of the subjects were correctly classified by the eigenimage, and the Jackknife approach revealed well above chance accuracy. The pattern of the eigenimage was characterized by positive loadings indicating gray matter decline in the patients in the lateral and medial prefrontal regions, insula, lateral temporal regions, medial temporal structures, and thalamus as well as the negative loadings reflecting gray matter increase in the patients in the putamen and cerebellum. When the eigenimage derived from the original cohort was applied to classify data from the second cohort, it correctly assigned more than 80% of the healthy subjects and schizophrenia patients. These findings suggest that the characteristic distribution of gray matter changes may be of diagnostic value for 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.

Reduced white matter fractional anisotropy and clinical symptoms in schizophrenia: A voxel-based diffusion tensor imaging study

Although not consistently replicated, diffusion tensor imaging (DTI) studies in schizophrenia have revealed lower fractional anisotropy (FA) in various white matter regions, a finding consistent with the disruption of white matter integrity. In this study, we used voxel-based DTI to investigate possible whole-brain differences in the white matter FA values between 58 schizophrenia patients and 58 healthy controls. We also explored the association between FA values and clinical symptoms in schizophrenia. Compared with the controls, the schizophrenia patients showed significant FA reductions in bilateral superior longitudinal fasciculus, bilateral inferior fronto-occipital fasciculus, and genu of right internal capsule. Furthermore, in the patient group, the FA value of the anterior part of the corpus callosum was negatively correlated with the avolition score on the Scale for the Assessment of Negative Symptoms. These findings suggest widespread disruption of white matter integrity in schizophrenia, which could partly explain the severity of negative symptomatology.

A follow-up MRI study of the superior temporal subregions in schizotypal disorder and first-episode schizophrenia

While longitudinal magnetic resonance imaging (MRI) studies have demonstrated progressive gray matter reduction of the superior temporal gyrus (STG) during the early phases of schizophrenia, it remains unknown whether patients with schizotypal features exhibit similar STG changes. In this study, longitudinal MRI data were obtained from 18 patients with first-episode schizophrenia, 13 patients with schizotypal disorder, and 20 healthy controls. The volumes of the STG and its subregions [planum polare (PP), Heschl gyrus (HG), planum temporale (PT), rostral STG, and caudal STG] were measured on baseline and follow-up (mean: 2.7 years) scans and were compared across groups. At the baseline, both the schizophrenia and schizotypal patients had smaller left PT and left caudal STG than the controls. In a longitudinal comparison, the schizophrenia patients showed significant gray matter reduction of the STG over time (left: -2.8%/year; right: -1.5%/year) compared with the schizotypal patients (left: -0.6%/year; right: -0.3%/year) and controls (left: 0.0%/year; right: -0.1%/year) without a prominent effect of subregion or type of antipsychotic (typical/atypical). In the schizophrenia patients, greater annual volume reductions of the left PP and right PT were correlated with less improvement of positive psychotic symptoms. A higher cumulative dose of antipsychotics during follow-up in schizophrenia was significantly correlated with less severe gray matter reductions in the left PT and bilateral caudal STG. Our findings suggest that the left posterior STG subregions are commonly reduced in diseases of the schizophrenia spectrum; whereas, schizophrenia patients exhibit further progressive STG changes associated with overt psychosis in the early years of the illness.

Classification of First-Episode Schizophrenia Patients and Healthy Subjects by Automated MRI Measures of Regional Brain Volume and Cortical Thickness

Background Although structural magnetic resonance imaging (MRI) studies have repeatedly demonstrated regional brain structural abnormalities in patients with schizophrenia, relatively few MRI-based studies have attempted to distinguish between patients with first-episode schizophrenia and healthy controls. Method Three-dimensional MR images were acquired from 52 (29 males, 23 females) first-episode schizophrenia patients and 40 (22 males, 18 females) healthy subjects. Multiple brain measures (regional brain volume and cortical thickness) were calculated by a fully automated procedure and were used for group comparison and classification by linear discriminant function analysis. Results Schizophrenia patients showed gray matter volume reductions and cortical thinning in various brain regions predominantly in prefrontal and temporal cortices compared with controls. The classifiers obtained from 66 subjects of the first group successfully assigned 26 subjects of the second group with accuracy above 80%. Conclusion Our results showed that combinations of automated brain measures successfully differentiated first-episode schizophrenia patients from healthy controls. Such neuroimaging approaches may provide objective biological information adjunct to clinical diagnosis of early schizophrenia.

Volume reduction and altered sulco-gyral pattern of the orbitofrontal cortex in first-episode schizophrenia

BACKGROUND 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. METHOD 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. RESULTS 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. CONCLUSION 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.

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.

Differentiation of first-episode schizophrenia patients from healthy controls using ROI-based multiple structural brain variables

BACKGROUND Brain morphometric measures from magnetic resonance imaging (MRI) have not been used to discriminate between first-episode patients with schizophrenia and healthy subjects. METHODS Magnetic resonance images were acquired from 34 (17 males, 17 females) first-episode schizophrenia patients and 48 (24 males, 24 females) age- and parental socio-economic status-matched healthy subjects. Twenty-nine regions of interest (ROI) were measured on 1-mm-thick coronal slices from the prefrontal and central parts of the brain. Linear discriminant function analysis was conducted using standardized z scores of the volumes of each ROI. RESULTS Discriminant function analysis with cross-validation procedures revealed that brain anatomical variables correctly classified 75.6% of male subjects and 82.9% of female subjects, respectively. The results of the volumetric comparisons of each ROI between patients and controls were generally consistent with those of the previous literature. CONCLUSIONS To our knowledge, this study provides the first evidence of MRI-based successful classification between first-episode patients with schizophrenia and healthy controls. The potential of these methods for early detection of schizophrenia should be further explored.

Increased pituitary volume in schizophrenia spectrum disorders

While hypothalamic-pituitary-adrenal (HPA) axis hyperactivity has been implicated in psychotic disorders, previous magnetic resonance imaging (MRI) studies of the pituitary gland volume in schizophrenia have yielded controversial results. It is also unknown whether patients with schizophrenia spectrum such as schizotypal disorder exhibit pituitary volume changes. In this study, we investigated the pituitary volume using MRI in 47 schizotypal disorder patients (29 males, mean age=25.0 years), 72 schizophrenia patients (38 males, mean age=26.2 years), and 81 age and gender matched healthy controls (46 males, mean age=24.5 years). Both patient groups had a larger pituitary volume compared with controls, but no difference was found between the schizophrenia and schizotypal patients. The pituitary volume was larger in females than in males for all diagnostic groups. There was no association between the pituitary volume and type (typical versus atypical), daily dosage, or duration of antipsychotic medication in either patient group. These findings are consistent with a stress-diathesis model of schizophrenia and further suggest that the schizotypal patients share HPA axis hyperactivity with young established schizophrenia patients reflecting a common vulnerability to stress within the schizophrenia spectrum.