Cingulate gyrus neuroanatomy in schizophrenia subjects and their non-psychotic siblings

BACKGROUND AND METHODS: In vivo neuroimaging studies have provided evidence of decreases in the gray matter volume of the cingulate gyrus in subjects with schizophrenia as compared to healthy controls. To investigate whether these changes might be related to heritable influences, we used high-resolution magnetic resonance imaging and labeled cortical mantle distance mapping to measure gray matter volume, as well as thickness and the area of the gray/white interface, in the anterior and posterior segments of the cingulate gyrus in 28 subjects with schizophrenia and their non-psychotic siblings, and in 38 healthy control subjects and their siblings. RESULTS: There was a significant effect of group status on posterior cingulate cortex (PCC) gray matter volume (p=0.02). Subjects with schizophrenia and their non-psychotic siblings showed similar reductions of gray matter volume (~10%) in the PCC compared to healthy control subjects and their siblings. In turn, trend level effects of group status were found for thickness (p=0.08) and surface area (p=0.11) of the PCC. In the combined group of schizophrenia subjects and their siblings, a direct correlation was observed between PCC gray matter volume and negative symptoms. However, the reduction in PCC gray matter volume in schizophrenia subjects and their siblings was proportionate to an overall reduction in whole cerebral volume, i.e., the effect of group on the volume of the PCC became non-significant when cerebral volume was included as a covariate (p=0.4). There was no significant effect of group on anterior cingulate cortex volume, thickness, or area. CONCLUSIONS: Our findings suggest that decreases in the gray matter volume of the PCC occur in schizophrenia subjects and their siblings. The presence of such decreases in the non-psychotic siblings of schizophrenia subjects suggests that heritable factors may be involved in the development of cortical abnormalities in 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.     

Lack of normal gender differences of the perigenual cingulate gyrus in schizophrenia spectrum disorders

Abstract. 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.     

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.     

Morphology of the ventral frontal cortex in schizophrenia: relationship with social dysfunction.

BACKGROUND: Studies have reported premorbid as well as postonset social dysfunction in schizophrenia. This impairment has also been observed to emerge after lesions in the ventral aspect of the frontal cortex (i.e., straight gyrus and orbitofrontal cortex). METHODS: Magnetic resonance imaging scans were obtained from 45 male patients with schizophrenia and 45 matched control subjects. Cortical gray matter volume and surface area were determined for the ventral frontal cortex (VFC), subdivided into the orbitofrontal cortex (OFC) and the straight gyrus (SG). RESULTS: The global measures of gray matter volume and surface area in the VFC was not significantly different between patients and control subjects; however, there was a regional difference, with the right SG volume and surface area being smaller in patients compared with control subjects. Volume of the VFC had an inverse correlation with measurements of both premorbid and postdiagnosis social function. The smaller the gray matter in these regions, the greater the social dysfunction. There was no relationship between morphology of this brain region and any other clinical variable. CONCLUSIONS: Morphology of the VFC is directly related to abnormal social function in schizophrenia, including measures of social dysfunction that predate the onset of illness.     

Verbal learning and memory and their associations with brain morphology and illness course in schizophrenia spectrum psychoses

The California Verbal Learning Test and structural brain imaging were administered to 57 subjects with schizophrenia spectrum disorders and 94 controls in a general population sample. Cases had lower semantic cluster scores. Poorer verbal memory strategies were associated with longer duration of illness and heavier use of antipsychotic medication. After controlling for duration of illness, sex, and total gray matter, poorer verbal memory was associated with lower gray matter volume in the cingulate cortex, juxtapositional lobule, right superior temporal gyrus, and precuneus. After controlling for use of antipsychotic medication, there was an association between higher serial clustering and smaller anterior cingulate gyrus and larger intracalcarine cortex.     

Gray matter volume differences and the effects of smoking on gray matter in schizophrenia

OBJECTIVE: Many studies have evaluated differences in gray matter volume in schizophrenia, but have not considered the possible effects of smoking, which is extraordinarily common in people with the illness. The present study used voxel-based morphometry (VBM) to examine differences in gray matter in subjects with schizophrenia and evaluate the effects of smoking on this measure. METHODS: Thirty-two subjects with schizophrenia (14 smokers, 18 non-smokers) and 32 healthy comparison subjects participated in the study. Whole brain, voxel-wise analyses of regional gray matter volume were conducted using voxel-based morphometry (VBM). RESULTS: Reduced gray matter was observed in the schizophrenia group in the orbitofrontal cortex, bilateral insula and superior temporal gyri (STG), bilateral dorsolateral prefrontal cortices (DLPFC), medial frontal gyrus, and cingulate gyrus. Within this group, smoking subjects had greater lateral prefrontal and STG gray matter volumes relative to non-smoking subjects. CONCLUSIONS: The finding of reduced gray matter volume in prefrontal and temporal regions in schizophrenia is consistent with prior anatomical tracing and whole-brain voxel-based studies. Greater gray matter volumes in smoking relative to non-smoking subjects with schizophrenia highlight a potential experimental confound in volumetric studies and suggests that smoking may be associated with a relative preservation of lateral prefrontal and temporal gray matter in schizophrenia.     

Neuroanatomical substrates of foresight in schizophrenia

The ability to think of the long-term consequences of one's behavior and use this information to guide present and future actions, commonly referred to as foresight, is a key higher-order cognitive ability that may be deficient among persons with schizophrenia and substantially limit the degree to which such individuals experience a functional recovery from the disease. This research investigated the neuroanatomical basis of foresight in schizophrenia, in order to identify potential brain regions that may underlie impaired foresight among this population. Participants in the early course of schizophrenia or schizoaffective disorder (N=50) were assessed using structural magnetic resonance imaging and clinician-rated measures of foresight and psychopathology. Voxel-based morphometry was used to examine the relationship between foresight and regional gray matter volume in the ventromedial prefrontal, orbitofrontal and cingulate cortices. Significant positive associations were observed between foresight and gray matter volume density in the right orbitofrontal, ventromedial prefrontal, and posterior cingulate cortices, as well as the left ventromedial prefrontal and anterior cingulate cortices, after correcting for multiple comparisons. These relationships persisted after adjusting for age, gender, illness duration, and psychopathology. Better foresight was most strongly associated with increased gray matter in the right orbitofrontal/ventromedial prefrontal cortex, suggesting that reductions in gray matter volume in this region may be associated with impaired foresight in schizophrenia. Implications and directions for future research are discussed.     

Volume of the cingulate and outcome in schizophrenia

BACKGROUND: Previous studies indicated that schizophrenia patients have reduced frontal volumes in comparison with normal, but among schizophrenics, reduced volumes of the posterior (temporal, parietal and occipital) cortex were associated with poor outcome. We examined whether this pattern is seen within the anteroposterior arch of the cingulate gyrus. METHODS: MR images were acquired in 37 schizophrenia patients (Kraepelinian, n = 13; non-Kraepelinian, n = 24) and 37 controls, and CSF, gray and white matter volumes in individual Brodmann's areas (BA) of the cingulate arch (areas 25, 24, 23, 31, 30, 29) were assessed and examined in relation to outcome. RESULTS: Schizophrenia patients had significant gray matter reductions in the absolute (mm(3)) volume of Brodmann's area 24 in anterior cingulate and, when corrected for brain size, in the whole cingulate and retrosplenial (areas 29-30) cortex. White matter volumes were increased in right posterior cingulate (area 31). Schizophrenia patients also showed abnormal lateralization of white matter volumes in retrosplenial cortex (area 30) and had lower correlations between frontal and anterior cingulate regions than controls. Poor-outcome subgroup exhibited significant bilateral gray matter deficits in posterior cingulate and retrosplenial cortices compared to good-outcome patients, while no white matter increases in these areas were seen. CONCLUSIONS: Poor outcome was associated with gray matter deficits in posterior cingulate while compensatory white matter increases in dorsal posterior regions may be related to better outcome. Possible consequences of this may include thought disorder, disturbance of consciousness, treatment resistance, and cognitive decline indicative of a dementing process as a superimposed or inherent part of this schizophrenia subtype.     

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 (Heschl's 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.     

Association between smaller left posterior superior temporal gyrus volume on magnetic resonance imaging and smaller left temporal P300 amplitude in first-episode schizophrenia

BACKGROUND: In chronic schizophrenia, the P300 is broadly reduced and shows a localized left temporal deficit specifically associated with reduced gray matter volume of the left posterior superior temporal gyrus (STG). In first-episode patients, a similar left temporal P300 deficit is present in schizophrenia, but not in affective psychosis. The present study investigated whether the left temporal P300-left posterior STG volume association is selectively present in first-episode schizophrenia. METHOD: P300 was recorded as first-episode subjects with schizophrenia (n = 15) or affective psychosis (n = 18) or control subjects (n = 18) silently counted infrequent target tones amid standard tones. High-resolution spoiled gradient-recalled acquisition magnetic resonance images provided quantitative measures of temporal lobe gray matter regions of interest. RESULTS: Patients with first-episode schizophrenia displayed a reversed P300 temporal area asymmetry (smaller on the left), while magnetic resonance imaging showed smaller gray matter volumes of left posterior STG relative to control subjects and patients with affective psychosis (15.4% and 11.0%, respectively), smaller gray matter volumes of left planum temporale (21.0% relative to both), and a smaller total Heschl's gyrus volume (14.6% and 21.1%, respectively). Left posterior STG and the left planum temporale, but not other regions of interest, were specifically and positively correlated (r>0.5) with left temporal P300 voltage in patients with schizophrenia but not in patients with affective psychosis or in control subjects. CONCLUSION: These results suggest that the left temporal P300 abnormality specifically associated with left posterior STG gray matter volume reduction is present at the first hospitalization for schizophrenia but is not present at the first hospitalization for affective psychosis.     

Cerebral gray and white matter reductions and clinical correlates in patients with early onset schizophrenia

Few magnetic resonance imaging studies of schizophrenia have investigated brain tissue volumes and their relation to clinical symptoms in patients with an early age at illness onset. The twofold purpose of the study was to investigate both gray and white matter volumes in schizophrenic men with an early age at illness onset, and to determine whether clinical features correlated with tissue volume changes, using an automated voxel-by-voxel image analysis procedure. Twenty male patients with DSM-IV diagnoses of schizophrenia, and an early age at onset (m+/-SD=19+/-2) were compared with 20 age-matched health men. Magnetic resonance (1.5-T) scans were obtained with an Inversion-Recovery prepared fast gradient echo sequence enhancing gray and white matter contrast. Statistical Parametric Mapping was used for image segmentation and comparison. Patients had significant gray matter reductions in medial frontal gyri, left insula, left parahippocampus, and left fusiform gyrus; bilateral white matter reductions in frontal lobes, and increased total cerebrospinal fluid volume were also observed. Negative symptom scores were negatively related to white matter volumes in cingulate regions, and in the right internal capsule. These findings emphasize a pattern of left-hemisphere gray matter abnormalities, and suggest that fronto-paralimbic connectivity may be altered in men with early onset 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. Received: 28 May 2002 / Accepted: 30 October 2002 Correspondence to T. Takahashi     

Reduced anterior and posterior cingulate gray matter in borderline personality disorder.

BACKGROUND: Structural abnormalities in prefrontal and cingulate gyrus regions-important in affective processing, impulse control and cognition may contribute to the psychopathology of borderline personality disorder (BPD). Previous MRI studies examining volume have reported that compared with healthy controls, BPD patients have decreases in right anterior cingulate, no differences in dorsolateral prefrontal cortex, and mixed findings for prefrontal cortex. We extended this investigation by examining gray and white matter volume of frontal and cingulate gyrus Brodmann areas (BAs) in a large group of patients and healthy controls. METHODS: MRI scans were acquired in 50 BPD patients (n = 13 with comorbid diagnosis of BPD and Schizotypal Personality Disorder (SPD) and n = 37 without SPD) and 50 healthy controls, and gray/white matter volume in cingulate gyrus and frontal lobe BAs were assessed. Normal BPD and BPD subgroup comparisons were conducted. RESULTS: Compared with controls, BPD patients showed reduced gray matter volume in BA 24 and 31 of the cingulate. BPD patients without comorbid SPD had isolated gray matter volume loss in BA 24, but were spared for BA 31 in contrast to BPD patients with SPD. There were no group differences in whole cingulate or frontal lobe volume. CONCLUSIONS: The finding of more pervasive cingulate shrinkage in the patients with BPD and SPD comorbidity resembles recent observations with the same methods in patients with schizophrenia. The pattern of reduced anterior and posterior cingulate gray matter volume in BPD patients, particularly those comorbid for SPD is consistent with the affective and attentional deficits observed in these personality disorders.     

Automated ROI-based brain parcellation analysis of frontal and temporal brain volumes in schizophrenia

Structural MRI studies of schizophrenia have yielded a diversity of findings. To help characterize regional gray matter changes in schizophrenia, we used an automated region of interest (ROI)-based approach that targeted frontal and temporal regions in schizophrenia patients. The sample compromised 43 schizophrenia patients (21 chronic patients, 22 unmedicated first episode patients), 20 first episode non-schizophrenia psychosis patients and 47 comparison subjects. Automated regional volume measurement was performed in 22 ROIs, including frontal and temporal cortical subregions and hippocampus. Correlations between volume measures, duration of illness and clinical scores were evaluated. Chronic schizophrenia patients showed gray matter volume differences in left dorsolateral prefrontal cortex (DLPFC) and right supplementary motor area (SMA). First episode psychosis patients presented smaller right anterior cingulate cortex (ACC) and left DLPFC than comparison subjects. Disorganization scores and duration of illness correlated negatively with gray matter volume of DLPFC and SMA in chronic schizophrenia patients. Using an automated ROI-based method, we found volume reductions in lateral and medial frontal regions in both first episode and chronic schizophrenia. The automated ROI-based method can be used as a valid and efficient tool for quantification of regional gray matter volume in schizophrenia in multiple ROIs across the brains of large numbers of subjects.     

Correlations between MRI-assessed volumes of the thalamus and cortical Brodmann's areas in schizophrenia

BACKGROUND: We compared the thalamic-cortical volumetric correlational patterns in patients with schizophrenia and normal comparison subjects, and evaluated their relations to outcome. METHODS: High-resolution MR images were acquired in patients with schizophrenia (n=106) and normal comparison subjects (n=42). Patients were divided into good-outcome (n=52) and poor-outcome (Kraepelinian, n=54) subtypes based on their ability for self-care. Correlations between the relative gray and white matter volumes of the individual cortical Brodmann's areas and five dorsoventral levels of the thalamus were assessed. RESULTS: Compared to normal subjects, schizophrenia patients lacked significant thalamic gray matter volume correlations with the prefrontal and medial temporal cortical regions in the right hemisphere, and with frontal, cingulate, posterior parietal and occipital regions in the left hemisphere, while normal white matter volume cortical-thalamic correlations along the cingulate gyrus and in the temporal lobe were not found in schizophrenia patients in both hemispheres. In contrast to both normal comparison subjects and good-outcome group, schizophrenia patients with poor outcomes showed significant bilateral gray matter volume correlations between the dorsal thalamus and ventral prefrontal cortex, while the group differences in the white matter volume correlations were mostly restricted to the cingulate arch. CONCLUSIONS: Whereas patients with schizophrenia exhibit deficiencies in cortical-thalamic correlational patterns, poor outcome is associated with abnormal interregional correlations not observed in either normal subjects or patients with good outcomes. This latter finding may be explained by a core neurodevelopmental disturbance that results in aberrant cortical-thalamic connectivity in poor-outcome schizophrenia.     

Reduced left angular gyrus volume in first-episode schizophrenia

OBJECTIVE: Research suggests that the normal left-greater-than-right angular gyrus volume asymmetry is reversed in chronic schizophrenia. The authors examined whether angular gyrus volume and asymmetry were abnormal in patients with first-episode schizophrenia. METHOD: Magnetic resonance imaging scans were obtained from 14 inpatients at their first hospitalization for psychosis and 14 normal comparison subjects. Manual editing was undertaken to delineate postcentral, supramarginal, and angular gyri gray matter volumes. RESULTS: Group comparisons revealed that the left angular gyrus gray matter volume in patients was 14.8% less than that of the normal subjects. None of the other regions measured showed significant group volume or asymmetry differences. CONCLUSIONS: Patients with new-onset schizophrenia showed smaller left angular gyrus volumes than normal subjects, consistent with other studies showing parietal lobe volume abnormalities in schizophrenia. Angular gyrus pathology in first-episode patients suggests that the angular gyrus may be a neuroanatomical substrate for the expression of schizophrenia.     

Anterior cingulate, gyrus rectus, and orbitofrontal abnormalities in elderly depressed patients: an MRI-based parcellation of the prefrontal cortex

OBJECTIVE: To examine structural abnormalities in subregions of the prefrontal cortex in elderly patients with depression, the authors explored differences in gray matter, white matter, and CSF volumes by applying a parcellation method based on magnetic resonance imaging (MRI). METHOD: Twenty-four elderly patients with major depression and 19 group-matched comparison subjects were studied with high-resolution MRI. Cortical surface extraction, tissue segmentation, and cortical parcellation methods were applied to obtain volume measures of gray matter, white matter, and CSF in seven prefrontal subregions: the anterior cingulate, gyrus rectus, orbitofrontal cortex, precentral gyrus, superior frontal cortex, middle frontal cortex, and inferior frontal cortex. RESULTS: Highly significant bilateral volume reductions in gray matter were observed in the anterior cingulate, the gyrus rectus, and the orbitofrontal cortex. Depressed patients also exhibited significant bilateral white matter volume reductions and significant CSF volume increases in the anterior cingulate and the gyrus rectus. Finally, the depressed group showed significant CSF volume reductions in the orbitofrontal cortex relative to the comparison subjects. None of the other regions examined revealed significant structural abnormalities. CONCLUSIONS: The prominent bilateral gray matter deficits in the anterior cingulate and the gyrus rectus as well as the orbitofrontal cortex may reflect disease-specific modifications of elderly depression. The differential pattern of abnormalities detected in the white matter and CSF compartments imply that distinct etiopathological mechanisms might underlie the structural cortical changes in these regions.     

Localized volume reduction in prefrontal, temporolimbic, and paralimbic regions in schizophrenia: an MRI parcellation study

Functional and structural abnormalities of the anterior cingulate gyrus (ACG) in patients with schizophrenia have been repeatedly reported. However, one remaining issue is whether gray matter volume reduction in ACG exists to an extent comparable with, or even in excess of, that in other prefrontal and temporolimbic regions. High-spatial-resolution magnetic resonance imaging was performed on patients with schizophrenia (n=27) and on age-, gender-, and parental socioeconomic-status-matched healthy control subjects (n=27). After the gray and white matter were semiautomatically segmented, whole prefrontal and temporal lobes were manually parceled into 15 subregions-by-two hemispheres (30 regions of interest) constituting seven prefrontal gray matter regions, six temporal gray matter regions, the prefrontal white matter, and the temporal white matter. Compared with healthy subjects, schizophrenic patients showed significant gray matter volume reduction in the bilateral ACG, this being the largest effect size (left, 0.84; right, 0.56) among all the regions examined. There were also significant gray matter volume reductions in the bilateral posterior STG, bilateral inferior frontal gyrus, left posterior amygdala-hippocampal complex (mostly hippocampus), and the left insula. These results suggest that gray matter volume reductions in the ACG are prominent among prefrontal and temporolimbic regions in patients with schizophrenia. These findings indicate the importance of ACG abnormalities in the pathophysiology of schizophrenia.     

Prefrontal-thalamic-cerebellar gray matter networks and executive functioning in schizophrenia

OBJECTIVE: Poor executive functioning is a core deficit in schizophrenia and has been linked to frontal lobe alterations. We aimed to identify (1) prefrontal cerebral areas in which decreased volume is linked to executive dysfunction in schizophrenia; and (2) areas throughout the brain that are volumetrically related to the prefrontal area identified in the first analysis, thus detecting more extended volumetric networks associated with executive functioning. METHOD: Fifty-three outpatients with schizophrenia and 62 healthy controls, matched for age, gender and handedness, were recruited. High-resolution images were acquired on a 1.5 tesla scanner and regional gray and white matter volumes were analyzed by voxel-based morphometry within SPM5 (statistical parametric mapping, University College London, UK). Executive functioning was assessed using the Wisconsin Card Sorting Test (WCST). RESULTS: Twenty-one patients with poor executive functioning showed reduced dorsolateral prefrontal and anterior cingulate gray matter volume as compared to 30 patients with high WCST performance, with a maximum effect in the left dorsolateral prefrontal cortex. Left dorsolateral prefrontal gray matter volume predicted WCST performance after controlling for possible confounding effects of global cognitive functioning, verbal attention span, negative symptoms, illness duration and education. In this area, both patient groups had less gray matter than healthy controls. Left dorsolateral prefrontal gray matter volume was positively related to dorsal prefrontal, anterior cingulate and parietal gray matter volume; and negatively related to thalamic, cerebellar, pontine and right parahippocampal gray matter volume. CONCLUSIONS: Volumetric alterations in prefrontal-thalamic-cerebellar gray matter networks may lead to executive dysfunction in schizophrenia.