Hirofumi Hagino

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.

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.

Morphologic alterations of the parcellated superior temporal gyrus in schizophrenia spectrum.

Morphologic abnormalities of the superior temporal gyrus (STG) as well as its sub-regions such as Heschls gyrus (HG) or planum temporale (PT) have been reported in schizophrenia patients, but have not been extensively studied in schizotypal subjects. In the present study, magnetic resonance images were acquired from 65 schizophrenia patients, 39 schizotypal disorder patients, and 72 healthy controls. Volumetric analyses were performed using consecutive 1-mm coronal slices on the temporal pole (TP) and superior temporal sub-regions [planum polare (PP), HG, PT, rostral STG, and caudal STG]. The HG was significantly smaller in schizophrenia patients compared with controls but not in schizotypal patients, while volume reductions of the left PT and bilateral caudal STG were common to both disorders. The TP gray matter was larger in female schizotypal patients compared with female schizophrenia patients. There were no significant group differences in the PP and rostral STG volume. In the subgroup of early phase schizophrenia patients (illness duration <1.0 year), smaller volumes for the left PP and rostral STG were correlated with hallucinations and delusions. Our findings suggest that morphologic changes in the posterior regions of the STG are common to the schizophrenia spectrum, whereas less involvement of the HG, and possibly the PP and rostral STG might be related to the sparing of schizotypal patients from developing overt psychosis.

Parietal lobe volume deficits in schizophrenia spectrum disorders

There has been little attention given to whether parietal lobe structural deficits are present in patients with schizophrenia and related personality disorders. The current study was designed to examine parietal volume alterations between schizophrenia and schizotypal personality disorder. Twenty-five patients with schizotypal disorder, 53 patients with schizophrenia, and 59 healthy volunteers were scanned using high-resolution magnetic resonance imaging (MRI). Volume measurements of the postcentral gyrus (PoCG), precuneus, superior parietal gyrus (SuPG), supramarginal gyrus (SMG), and angular gyrus (AGG) were performed on consecutive 1-mm coronal slices. Gray matter volumes were reduced in all parietal subregions in patients with schizophrenia compared with healthy controls. White matter volumes were also reduced in the SuPG and PoCG. In contrast, the schizotypal subjects had gray matter reductions only in the PoCG, while other regions were not affected. In addition, there was a lack of normal significant-leftward asymmetry in the SMG in schizophrenia. These findings demonstrate that volume reductions in the somatosensory cortices are common morphological characteristics in schizophrenia spectrum disorders. The additional volume alterations in schizophrenia may support the notion that a deficit in the posterior parietal region is critical for the manifestation of overt psychotic symptoms.

Volume reduction of the left planum temporale gray matter associated with long duration of untreated psychosis in schizophrenia: A preliminary report

A longer duration of untreated psychosis (DUP) in schizophrenia is reported to lead to a poorer clinical outcome, possibly reflecting a neurodegenerative process after the onset of overt psychosis. However, the effect of DUP on brain morphology in schizophrenia is still poorly understood. In this study, we used magnetic resonance imaging to investigate the relation between DUP and volumetric measurements for the superior temporal sub-regions (Heschls gyrus, planum temporale, and caudal superior temporal gyrus), the medial temporal lobe structures (hippocampus and amygdala), and the frontal lobe regions (prefrontal area and anterior cingulate gyrus) in a sample of 38 schizophrenia patients (20 males and 18 females) whose illness duration was less than five years. We found a significant negative correlation between DUP and the volume of gray matter in the left planum temporale even after controlling for age, age at illness onset, and duration and dosage of neuroleptic medication. There was no such correlation for the other brain regions including each sub-region of the prefrontal cortex (the superior frontal gyrus, middle frontal gyrus, inferior frontal gyrus, ventral medial prefrontal cortex, orbitofrontal cortex, and straight gyrus). When subjects were divided into two groups around the median DUP, the long-DUP group had a significantly smaller planum temporale gray matter than the short-DUP group. These findings may reflect a progressive pathological process in the gray matter of the left planum temporale during the initial untreated phase of schizophrenia, whereas abnormalities in the medial temporal regions might be, as has been suggested from previous longitudinal findings, relatively static at least during the early course of the illness.

Volumetric analysis of sulci/gyri-defined in vivo frontal lobe regions in schizophrenia: Precentral gyrus, cingulate gyrus, and prefrontal region

Methodological limitations in most previous magnetic resonance imaging (MRI)-based volumetric studies might have contributed to the inconsistent results regarding the frontal lobe regions of schizophrenia. Thus, applying the largest sample to date among those that have fully taken account of the intrinsic anatomical landmarks, this study aimed at clarifying the volumetric alterations of the frontal lobe and its subregions in schizophrenia. Participants comprised 59 patients with schizophrenia and 58 healthy controls. Measurements were performed on consecutive 1-mm-thick coronal slices reformatted from three-dimensional 1.5-T MR images. The whole frontal lobe was demarcated and then subdivided into the precentral gyrus (PCG), anterior cingulate, and posterior cingulate, and the remainder temporarily as the prefrontal region. Patients with schizophrenia had significant cortical volume reductions in the bilateral whole frontal lobe, prefrontal region, PCG, posterior cingulate, and right anterior cingulate. This study has confirmed that patients with schizophrenia do have cortical volume reductions in the whole frontal lobe and its subregions. Volume reduction in the PCG suggests that the primary motor cortex might contribute to the mechanisms of schizophrenia, considering its important role in the processing of multiple motor-related cognitive functioning suggested by the recent literature.

The Disrupted-in-Schizophrenia-1 Ser704Cys polymorphism and brain morphology in schizophrenia

The Disrupted-in-Schizophrenia-1 (DISC1) polymorphism is a strong candidate for a schizophrenia-susceptibility gene as it is widely expressed in cortical and limbic regions, but the effect of its genotype variation on brain morphology in schizophrenia is not well known. This study examined the association between the DISC1 Ser704Cys polymorphism and volumetric measurements for a broad range of fronto-parietal, temporal, and limbic-paralimbic regions using magnetic resonance imaging in a Japanese sample of 33 schizophrenia patients and 29 healthy comparison subjects. The Cys carriers had significantly larger volumes of the medial superior frontal gyrus and short insular cortex than the Ser homozygotes only for healthy comparison subjects. The Cys carriers tended to have a smaller supramarginal gyrus than the Ser homozygotes in schizophrenia patients, but not in healthy comparison subjects. The right medial superior frontal gyrus volume was significantly correlated with daily dosage of antipsychotic medication in Ser homozygote schizophrenia patients. These different genotype effects of the DISC1 Ser704Cys polymorphism on the brain morphology in schizophrenia patients and healthy comparison subjects suggest that variation in the DISC1 gene might be, at least partly, involved in the neurobiology of schizophrenia. Our findings also suggest that the DISC1 genotype variation might have some relevance to the medication effect on brain morphology in schizophrenia.

Volume reduction of the amygdala in patients with schizophrenia: a magnetic resonance imaging study

The amygdala is known to be involved in the pathology of schizophrenia. While only a limited number of studies in schizophrenia have measured the amygdala as a single structure. The aim of this study was to examine the hypothesis that patients with schizophrenia would show reduced volumes in the amygdala compared with normal controls. We investigated amygdala volume in 40 patients with schizophrenia (20 males, 20 females) and 40 age- and gender-matched normal controls using three-dimensional magnetic resonance imaging (MRI). Whole volumes of both the amygdala and the temporal lobe were measured on consecutive coronal 1-mm slices. The amygdala volume was significantly smaller in schizophrenia patients than in controls. Considering gender differences, male patients had significantly smaller volumes in the bilateral amygdala than male controls; female patients had a significantly reduced right amygdala compared with female controls. Furthermore, a significant left-smaller-than-right volumetric asymmetry of the amygdala was detected in male patients with schizophrenia. The results may be important for understanding the role of the amygdala in the pathophysiology of schizophrenia and the anatomical substrates of gender difference in the expressions of the illness.