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Summary Background Different subtypes of idiopathic generalized epilepsy may indicate different mechanisms and outcomes, suggesting that it is necessary to use a ‘pure sample’ of a single subtype. Methods A volumetric study, in conjunction with cognition assessments, was performed in a pure sample of patients with idiopathic generalized tonic–clonic seizures (IGE-GTCS; 15 males and 15 females) matched with normal control subjects (15 males and 17 females). The volumetric measurements were focused on the hippocampus and its surrounding structures, including the amygdala, the parahippocampal gyrus, the entorhinal cortex and the perirhinal cortex. The Wechsler Adult Intelligence Scale-Revised in China was administered to assess cognitive status. Results A volume reduction was found only in the hippocampus, with a more severe effect on the left side than the right side. The total number and frequency of seizures had significant negative correlations with multiple cognitive measures. Furthermore, the hippocampal volume reduction was significantly correlated with some aspects of cognitive impairment. Conclusion These findings suggest that compared with the other medial temporal structures, the hippocampus may be more vulnerable to the neuropathology of IGE-GTCS. The observation that cognitive deterioration was correlated with an increased frequency and total number of seizures highlights the critical importance of preventing seizures from recurrence.

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.

An enlarged volume of the pituitary gland has been reported in the schizophrenia spectrum, possibly reflecting the hypothalamic-pituitary-adrenal (HPA) hyperactivity. However, it remains largely unknown whether the pituitary size longitudinally changes in the course of the spectrum disorders. In the present study, longitudinal magnetic resonance imaging (MRI) data were obtained from 18 patients with first-episode schizophrenia, 13 patients with schizotypal disorder, and 20 healthy controls. The pituitary volume was measured at baseline and follow-up (mean, 2.7 years) scans and was compared across groups. The pituitary volume was larger in the schizophrenia patients than controls at baseline, and both patient groups had significantly larger pituitary volume than controls at follow-up. In a longitudinal comparison, both schizophrenia (3.6%/year) and schizotypal (2.7%/year) patients showed significant pituitary enlargement compared with controls (-1.8%/year). In the schizophrenia patients, greater pituitary enlargement over time was associated with less improvement of delusions and higher scores for thought disorders at the follow-up. These findings suggest that the pituitary gland exhibits ongoing volume changes during the early course of the schizophrenia spectrum as a possible marker of state-related impairments.

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.

Morphologic abnormalities of the insular cortex have been described in psychotic disorders such as schizophrenia, but it remains unclear whether these changes predate the onset of psychosis or develop progressively over the course of illness. In this study, we used magnetic resonance imaging to investigate the gray matter volume of the long and short insular cortices in 97 neuroleptic-naïve individuals at ultra-high-risk (UHR) for developing psychosis [of whom 31 (32%) later developed psychosis (UHR-P) and 66 (68%) did not (UHR-NP)] and 55 age- and gender-matched healthy comparisons. We also conducted a longitudinal comparison of the insular cortex gray matter changes in 31 UHR individuals (20 UHR-NP and 11 UHR-P) and 20 controls for whom follow-up MRI data between 1 and 4 years later were available. In the cross-sectional comparison, the UHR-P subjects had a significantly smaller insular cortex compared with the UHR-NP subjects bilaterally and with the controls on the right hemisphere, especially for the short insular region. More severe negative symptoms in UHR-P subjects at baseline were associated with smaller volumes of the right long insular cortex. In the longitudinal comparison, the UHR-P subjects showed greater gray matter reduction of insular cortex bilaterally (-5.0%/year) compared with controls (-0.4%/year) or UHR-NP subjects (-0.6%/year). Our findings suggest that insular cortex gray matter abnormalities in psychotic disorders may reflect pre-existing vulnerability, but that there are also active progressive changes of the insular cortex during the transition period into psychosis. Whether these longitudinal changes are features of the disorder or related to treatment with antipsychotic medication remains to be determined.

The present study investigated the relationship between memory strategy use and prefrontal gray/white matter volumes of healthy control subjects, patients with schizophrenia or schizotypal disorder. Gray/white matter volumes were measured for the superior, middle, inferior, ventral medial and orbital prefrontal regions, using high-resolution magnetic resonance (MR) images that were acquired from 35 patients with schizophrenia, 25 patients with schizotypal disorder and 19 healthy subjects. Participants were also administered the Japanese Verbal Learning Test (JVLT). In control subjects, larger left inferior frontal and straight gyrus's gray matter volumes were associated with higher semantic clustering rates on the JVLT, and smaller left inferior frontal gray matter volumes were associated with higher serial clustering ratio. In schizophrenic patients, smaller left orbitofrontal gray matter volumes were associated with lower semantic clustering rates on the JVLT. In schizotypal patients, smaller left inferior frontal white matter volume was associated with smaller serial clustering rates and larger semantic clustering rate. These findings suggest that semantic organization in schizophrenic patients might depend on mobilization of a memory strategy that is mediated by orbitofrontal cortex functioning. Failure to use a semantic organization strategy might be related to reduced volume in the inferior frontal gyrus. The findings for schizotypal patients suggest a compensation mechanism to remember the words using a serial processing strategy is at work when the inferior frontal gyrus cannot mediate semantic processing.

We used magnetic resonance imaging to investigate the prevalence and length of the adhesio interthalamica (AI) in 72 schizophrenia patients, 47 schizotypal disorder patients, and 81 healthy controls. The AI was more often absent and shorter in both disorders than in controls, possibly reflecting common neurodevelopmental abnormalities in the schizophrenia spectrum.

Abnormal neurodevelopment in midline structures such as the adhesio interthalamica (AI), as well as in the medial temporal lobe structures has been implicated in schizophrenia, while its genetic mechanism is unknown. This magnetic resonance imaging study investigated the effect of the genotypic combination of the dopamine D3 receptor (DRD3) Ser9Gly and brain-derived neurotrophic factor (BDNF) Val66Met polymorphisms on the AI length and volumetric measures of the medial temporal lobe structures (amygdala, hippocampus, and parahippocampal gyrus) in 33 schizophrenia patients and 29 healthy controls. The subjects with a combination of the Ser/Ser genotype of DRD3 and Met-containing genotypes of BDNF (high-risk combination) had a shorter AI than those without it in the healthy controls, but not in the schizophrenia patients. The subjects carrying the high-risk combination had a smaller posterior hippocampus than those without it for both diagnostic groups. These genotypic combination effects on brain morphology were not explained by the independent effect of each polymorphism. These findings suggest the effect of gene-gene interaction between the DRD3 and BDNF variations on brain morphology in midline and medial temporal lobe structures, but do not support its specific role in the pathogenesis of schizophrenia.

Abnormal neurodevelopment in midline structures such as the adhesio interthalamica (AI) has been reported in schizophrenia, but not consistently replicated. We investigated the prevalence and anterior-posterior length of the AI in 62 schizophrenia patients (32 males, 30 females) and 63 healthy controls (35 males, 28 females) using magnetic resonance imaging. We also explored the relation between the AI and volumetric measurements for the third ventricle, medial temporal structures (amygdala, hippocampus, and parahippocampal gyrus), superior temporal sub-regions, and frontal lobe regions (prefrontal area and anterior cingulate gyrus). The AI was absent in 24.2% (15/62) of the schizophrenia patients and in 9.5% (6/63) of the controls, showing a significant group difference. For the length of the AI, schizophrenia patients had a shorter AI than controls, and males had a shorter AI than females. The subjects without an AI had a significantly larger third ventricle and smaller parahippocampal gyrus than the subjects with an AI for both groups. We found a significant diagnosis-by-AI interaction for the amygdala. The schizophrenia patients without an AI had a smaller bilateral amygdala than those with an AI, whereas the AI was not associated with the volume of the amygdala in the control subjects. These findings suggest that the absence of AI in schizophrenia could be a marker of developmental abnormalities in the neural network including the thalamus and connected amygdaloid regions, which may play an important role in the pathogenesis of schizophrenia.

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.

Background. Schneider's first-rank symptoms involve an alienated feature of the sense of one's own mental or physical activity. To clarify the brain morphological basis for the production of these symptoms, volumes of the frontal and medial temporal regions and their clinical correlates were examined in patients with schizophrenia.Method. Twenty-two patients with schizophrenia and 44 age- and gender-matched healthy control subjects were included. All patients were in their psychotic episodes with definite Schneiderian symptoms, rated by using the Scale for Assessment of Positive Symptoms. Volumetric measurements of high-resolution magnetic resonance imaging were performed in the prefrontal area, cingulate gyrus, and precentral gyrus, and the medial temporal structures such as the amygdala, hippocampus, and parahippocampal gyrus.Results. Patients had significantly decreased volumes in the cingulate gray matter and the amygdala compared to controls. In the patient group, Schneiderian symptom severity showed significant inverse correlations with volumes of the right posterior cingulate gray matter and of the left anterior parahippocampal gyrus.Conclusions. Schneiderian symptoms may be associated with morphological abnormalities in the limbic-paralimbic regions such as the cingulate gyrus and parahippocampal gyrus, which possibly serve the self-monitoring function and the coherent storage and reactivation of information.

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.

To clarify the developmental brain changes during adolescence, brain morphology was compared between healthy younger adolescent and elder adolescent subjects using both voxel-based morphometry (VBM) and volumetric region-of-interest (ROI) analysis of magnetic resonance imaging (MRI). High-resolution three-dimensional MRI scans were acquired in 23 (10 males and 13 females) younger adolescent subjects (13-14 years) and 30 (15 males and 15 females) elder adolescent subjects (19-21 years). Whole-brain analysis by VBM revealed that the elder adolescent subjects had significantly more gray matter in the left medial temporal regions than the younger adolescent subjects and significantly less gray matter in the left medial frontal region (Brodmann area 6). In the volumetric analysis, significantly less cerebral gray matter volume and significantly greater cerebral white matter volume were found in elder adolescents compared with younger adolescents. The volume of the hippocampus was significantly larger in male elder adolescents than in male younger adolescents. The volume of the parahippocampal gyrus did not differ between younger and elder adolescent subjects. These results suggest a robust maturational process ongoing in the human hippocampus during adolescence, especially in males. The possible relevance of these findings to progress in myelination and implications in psychiatric disorders were discussed.

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.

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 (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.

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 largely unknown whether other temporal lobe structures also exhibit similar progressive changes and whether these changes, if present, are specific to schizophrenia among the spectrum disorders. In this longitudinal MRI study, the gray matter volumes of the fusiform, middle temporal, and inferior temporal gyri were measured at baseline and follow-up scans (mean inter-scan interval=2.7 years) in 18 patients with first-episode schizophrenia, 13 patients with schizotypal disorder, and 20 healthy controls. Both schizophrenia and schizotypal patients had a smaller fusiform gyrus than controls bilaterally at both time points, whereas no group difference was found in the middle and inferior temporal gyri. In the longitudinal comparison, the schizophrenia patients showed significant fusiform gyrus reduction (left, -2.6%/year; right, -2.3%/year) compared with schizotypal patients (left: -0.4%/year; right: -0.2%/year) and controls (left: 0.1%/year; right: 0.0%/year). However, the middle and inferior temporal gyri did not exhibit significant progressive gray matter change in all diagnostic groups. In the schizophrenia patients, a higher cumulative dose of antipsychotics during follow-up was significantly correlated with less severe gray matter reduction in the left fusiform gyrus. The annual gray matter loss of the fusiform gyrus did not correlate with that of the STG previously reported in the same subjects. Our findings suggest regional specificity of the progressive gray matter reduction in the temporal lobe structures, which might be specific to overt schizophrenia within the schizophrenia spectrum.

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.

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.

Magnetic resonance imaging was used to investigate the relation between the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and volumetric measurements for the medial temporal lobe structures (amygdala, hippocampus, and parahippocampal gyrus) and prefrontal sub-regions (the superior frontal gyrus, middle frontal gyrus, inferior frontal gyrus, ventral medial prefrontal cortex, orbitofrontal cortex, and straight gyrus) in a Japanese sample of 33 schizophrenia patients and 29 healthy subjects. For the controls, the Met carriers had significantly smaller parahippocampal and left superior frontal gyri than the Val homozygotes. The schizophrenia patients carrying the Met allele had a significantly smaller right parahippocampal gyrus than those with the Val/Val genotype, but the genotype did not affect the prefrontal regions in schizophrenia patients. These findings might reflect different genotypic effects of BDNF on brain morphology in schizophrenia patients and healthy controls, implicating the possible role of the brain morphology as an endophenotype for future genetic studies in schizophrenia.

Magnetic resonance imaging was used to evaluate the prevalence of the cavum septi pellucidi (CSP) in 154 schizophrenia patients, 47 schizotypal disorder patients, and 163 healthy controls. We also explored the relation of a large CSP (≥ 6 mm) with medial temporal lobe structures. No significant difference was found in the prevalence of the CSP (76.0% of the schizophrenia patients, 81.6% of the controls, and 85.1% of the schizotypal patients) or the large CSP (6.5% of the schizophrenia patients, 7.4% of the controls, and 10.6% of the schizotypal patients) among the groups, but patients with a large CSP (10 schizophrenia and 5 schizotypal patients) had smaller volumes of bilateral amygdala and left posterior parahippocampal gyrus than patients without it. In the control subjects, the large CSP did not affect the volumes of the medial temporal lobe structures. These findings might reflect neurodevelopmental abnormalities in midline and associated limbic structures of the brain in schizophrenia spectrum.

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.

Morphologic abnormalities of the superior temporal gyrus (STG) as well as its sub-regions such as Heschl's 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

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.

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.

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 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.