Regions In Schizophrenia Research Articles

Low-frequency BOLD fluctuations demonstrate altered thalamocortical connectivity in schizophrenia.

The thalamus plays a central and dynamic role in information transmission and processing in the brain. Multiple studies reveal increasing association between schizophrenia and dysfunction of the thalamus, in particular the medial dorsal nucleus (MDN), and its projection targets. The medial dorsal thalamic connections to the prefrontal cortex are of particular interest, and explicit in vivo evidence of this connection in healthy humans is sparse. Additionally, recent neuroimaging evidence has demonstrated disconnection among a variety of cortical regions in schizophrenia, though the MDN thalamic prefrontal cortex network has not been extensively probed in schizophrenia. To this end, we have examined thalamo-anterior cingulate cortex connectivity using detection of low-frequency blood oxygen level dependence fluctuations (LFBF) during a resting-state paradigm. Eleven schizophrenic patients and 12 healthy control participants were enrolled in a study of brain thalamocortical connectivity. Resting-state data were collected, and seed-based connectivity analysis was performed to identify the thalamocortical network. First, we have shown there is MDN thalamocortical connectivity in healthy controls, thus demonstrating that LFBF analysis is a manner to probe the thalamocortical network. Additionally, we have found there is statistically significantly reduced thalamocortical connectivity in schizophrenics compared with matched healthy controls. We did not observe any significant difference in motor networks between groups. We have shown that the thalamocortical network is observable using resting-state connectivity in healthy controls and that this network is altered in schizophrenia. These data support a disruption model of the thalamocortical network and are consistent with a disconnection hypothesis of schizophrenia.

Reduced interhemispheric connectivity in schizophrenia-tractography based segmentation of the corpus callosum

Background A reduction in interhemispheric connectivity is thought to contribute to the etiology of schizophrenia. Diffusion Tensor Imaging (DTI) measures the diffusion of water and can be used to describe the integrity of the corpus callosum white matter tracts, thereby providing information concerning possible interhemispheric connectivity abnormalities. Previous DTI studies in schizophrenia are inconsistent in reporting decreased Fractional Anisotropy (FA), a measure of anisotropic diffusion, within different portions of the corpus callosum. Moreover, none of these studies has investigated corpus callosum systematically, using anatomical subdivisions. Methods DTI and structural MRI scans were obtained from 32 chronic schizophrenic subjects and 42 controls. Corpus callosum cross sectional area and its probabilistic subdivisions were determined automatically from structural MRI scans using a model based deformable contour segmentation. These subdivisions employ a previously generated probabilistic subdivision atlas, based on fiber tractography and anatomical lobe subdivision. The structural scan was then co-registered with the DTI scan and the anatomical corpus callosum subdivisions were propagated to the associated FA map. Results Results revealed decreased FA within parts of the corpus interconnecting frontal regions in schizophrenia compared with controls, but no significant changes for callosal fibers interconnecting parietal and temporo-occipital brain regions. In addition, integrity of the anterior corpus was statistically significantly correlated with negative as well as positive symptoms, while posterior measures correlated with positive symptoms only. Conclusions This study provides quantitative evidence for a reduction of interhemispheric brain connectivity in schizophrenia, involving corpus callosum, and further points to frontal connections as possibly disrupted in schizophrenia.

31P NMR spectroscopy of phospholipid metabolites in postmortem schizophrenic brain

Evidence has been accumulating that schizophrenia involves abnormalities in the composition and metabolism of cell membrane phospholipids (PLs) in the brain. In vivo 31P MRS has been used to measure the metabolic precursors and degradation products of PL metabolism in schizophrenia. Because in vivo line widths are substantially broader than in solution, only the broad phosphomonoester (PME) and phosphodiester bands, or partly resolved resonances of individual metabolites, are typically measured in vivo in the 31P spectrum. In addition to poor resolution, the relatively low signal-to-noise ratio (SNR) makes precise quantitation difficult. An alternative with substantially better resolution and precision for quantitation is high-resolution NMR spectroscopy of extracts of samples from postmortem brain. Here we determine absolute concentrations of the individual PL metabolites phosphocholine (pc), phosphoethanolamine (pe), glycerophosphocholine (gpc), and glycerophosphoethanolamine in aqueous extracts of tissue from frontal, temporal, and occipital cortex of postmortem brain for schizophrenics, controls, and patients with other mental illnesses (psychiatric controls [PC]) using high-resolution 31P NMR spectroscopy. For the complete groups, which included both males and females, there were no statistically significant differences for schizophrenics vs. controls for any of the four PL metabolites in any of the three brain regions. Trends (0.05 < P < 0.10) were noted for increased gpc in schizophrenia in all three regions. PC differed from both controls and schizophrenics in several measures. When only males were considered, gpc was significantly (P < 0.05) elevated in all three brain regions in schizophrenia.

Disrupted small-world networks in schizophrenia

The human brain has been described as a large, sparse, complex network characterized by efficient small-world properties, which assure that the brain generates and integrates information with high efficiency. Many previous neuroimaging studies have provided consistent evidence of 'dysfunctional connectivity' among the brain regions in schizophrenia; however, little is known about whether or not this dysfunctional connectivity causes disruption of the topological properties of brain functional networks. To this end, we investigated the topological properties of human brain functional networks derived from resting-state functional magnetic resonance imaging (fMRI). Data was obtained from 31 schizophrenia patients and 31 healthy subjects; then functional connectivity between 90 cortical and sub-cortical regions was estimated by partial correlation analysis and thresholded to construct a set of undirected graphs. Our findings demonstrated that the brain functional networks had efficient small-world properties in the healthy subjects; whereas these properties were disrupted in the patients with schizophrenia. Brain functional networks have efficient small-world properties which support efficient parallel information transfer at a relatively low cost. More importantly, in patients with schizophrenia the small-world topological properties are significantly altered in many brain regions in the prefrontal, parietal and temporal lobes. These findings are consistent with a hypothesis of dysfunctional integration of the brain in this illness. Specifically, we found that these altered topological measurements correlate with illness duration in schizophrenia. Detection and estimation of these alterations could prove helpful for understanding the pathophysiological mechanism as well as for evaluation of the severity of schizophrenia.

Altered resting-state functional connectivity and anatomical connectivity of hippocampus in schizophrenia

Hippocampus has been implicated in participating in the pathophysiology of schizophrenia. However, the functional and anatomical connectivities between hippocampus and other regions are rarely concurrently investigated in schizophrenia. In the present study, both functional magnetic resonance imaging (fMRI) during rest and diffusion tensor imaging (DTI) were performed on 17 patients with paranoid schizophrenia and 14 healthy subjects. Resting-state functional connectivities of the bilateral hippocampi were separately analyzed by selecting the anterior hippocampus as region of interest. The fornix body was reconstructed by diffusion tensor tractography, and the integrity of this tract was evaluated using fractional anisotropy (FA). In patients with schizophrenia, the bilateral hippocampi showed reduced functional connectivities to some regions which have been reported to be involved in episodic memory, such as posterior cingulate cortex, extrastriate cortex, medial prefrontal cortex, and parahippocampus gyrus. We speculated that these reduced connectivity may reflect the disconnectivity within a neural network related to the anterior hippocampus in schizophrenia. Meanwhile the mean FA of the fornix body was significantly reduced in patients, indicating the damage in the hippocampal anatomical connectivity in schizophrenia. The concurrence of the functional disconnectivity and damaged anatomical connectivity between the hippocampus and other regions in schizophrenia suggest that the functional–anatomical relationship need to be further investigated.

Altered excitatory-inhibitory balance in the NMDA-hypofunction model of schizophrenia

Schizophrenia is a common psychiatric disorder of high incidence, affecting approximately 1% of the world population. The essential neurotransmitter pathology of schizophrenia remains poorly defined, despite huge advances over the past half-century in identifying neurochemical and pathological abnormalities in the disease. The dopamine/serotonin hypothesis has originally provided much of the momentum for neurochemical research in schizophrenia. In recent years, the attention has, however, shifted to the glutamate system, the major excitatory neurotransmitter in the CNS and towards a concept of functional imbalance between excitatory and inhibitory transmission at the network level in various brain regions in schizophrenia. The evidence indicating a central role for the NMDA-receptor subtype in the aetiology of schizophrenia has led to the NMDA-hypofunction model of this disease and the use of phencyclidines as a means to induce the NMDA-hypofunction state in animal models. The purpose of this review is to discuss recent findings highlighting the importance of the NMDA-hypofunction model of schizophrenia, both from a clinical perspective, as well as in opening a line of research, which enables electrophysiological studies at the cellular and network level in vitro. In particular, changes in excitation–inhibition (E/I) balance in the NMDA-hypofunction model of the disease and the resulting changes in network behaviours, particularly in gamma frequency oscillatory activity, will be discussed.

D 2/D 3 receptor binding in striatal and extrastriatal regions in schizophrenia measured with [ 18F]fallypride PET

D 2/D 3 receptor binding in striatal and extrastriatal regions in schizophrenia measured with [ 18F]fallypride PET

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.

The neuronal pathology of schizophrenia: molecules and mechanisms

There is an accumulation of evidence for abnormalities in schizophrenia of both the major neurotransmitter systems of the brain - those of GABA (gamma-aminobutyric acid) and glutamate. Initial studies have found deficits in the putative neuronal marker, N-acetylaspartate, in a number of brain regions in schizophrenia. The animal models have provided some interesting correlates and discrepancies with these findings. The deficit in inhibitory interneurons within structures implicated in schizophrenic symptomatology may well have direct functional relevance, and can be induced by animal models of the disease such as subchronic phencyclidine administration or social isolation. Their association with these animal models suggests an environmental involvement. A loss of glutamatergic function in schizophrenia is supported by decreases in markers for the neuronal glutamate transporter in striatal structures that receive cortical glutamatergic projections. Deficits in the VGluT1 (vesicular glutamate transporter-1) in both striatal and hippocampal regions support this observation, and the association of VGluT1 density with a genetic risk factor for schizophrenia points to genetic influences on these glutamatergic deficits. Further studies differentiating neuronal loss from diminished activity and improved models allowing us to determine the temporal and causal relationships between GABAergic and glutamatergic deficits will lead to a better understanding of the processes underlying the neuronal pathology of schizophrenia.

A Diffusion Tensor Imaging Study of Fasciculi in Schizophrenia

Cognitive models propose that the symptoms and psychological impairments associated with schizophrenia arise as a consequence of impaired communication between brain regions, especially the prefrontal cortex and the temporal and parietal lobes. Functional imaging and electrophysiological data have provided evidence of functional dysconnectivity, but it is unclear whether this reflects an underlying problem with anatomical connectivity. This study used diffusion tensor imaging to examine the integrity of the major white matter fasciculi, which connects the frontal and temporal-parietal cortices, and the corpus callosum in patients with schizophrenia. A 1.5-T magnetic resonance scanner was used to acquire diffusion tensor images giving whole brain coverage at an isotropic 2.5-mm voxel size. Fractional anisotropy was measured in 33 patients with schizophrenia and 40 healthy comparison subjects with an automated voxel-based method of analysis. There was reduced fractional anisotropy in patients with schizophrenia in regions corresponding to the superior longitudinal fasciculi bilaterally and in the genu of the corpus callosum. However, within the patient group, the propensity to experience auditory hallucinations was associated with relatively increased fractional anisotropy in superior longitudinal fasciculi and in the anterior cingulum. Schizophrenia is associated with altered white matter integrity in the tracts connecting the frontal cortex with the temporal and parietal cortices and with the contralateral frontal and temporal lobes. The severity of these changes may vary with the pattern of symptoms associated with the disorder.

A Diffusion Tensor Imaging Study of Fasciculi in Schizophrenia

Objective: Cognitive models propose that the symptoms and psychological impairments associated with schizophrenia arise as a consequence of impaired communication between brain regions, especially the prefrontal cortex and the temporal and parietal lobes. Functional imaging and electrophysiological data have provided evidence of functional dysconnectivity, but it is unclear whether this reflects an underlying problem with anatomical connectivity. This study used diffusion tensor imaging to examine the integrity of the major white matter fasciculi, which connects the frontal and temporal-parietal cortices, and the corpus callosum in patients with schizophrenia. Method: A 1.5-T magnetic resonance scanner was used to acquire diffusion tensor images giving whole brain coverage at an isotropic 2.5-mm voxel size. Fractional anisotropy was measured in 33 patients with schizophrenia and 40 healthy comparison subjects with an automated voxel-based method of analysis. Results: There was reduced fractional anisotropy in patients with schizophrenia in regions corresponding to the superior longitudinal fasciculi bilaterally and in the genu of the corpus callosum. However, within the patient group, the propensity to experience auditory hallucinations was associated with relatively increased fractional anisotropy in superior longitudinal fasciculi and in the anterior cingulum. Conclusions: Schizophrenia is associated with altered white matter integrity in the tracts connecting the frontal cortex with the temporal and parietal cortices and with the contralateral frontal and temporal lobes. The severity of these changes may vary with the pattern of symptoms associated with the disorder.

Task-induced deactivation of midline cortical regions in schizophrenia assessed with fMRI

Task-induced deactivations (TIDs) of midline cortical regions are readily observed in fMRI studies and may reflect elements of a ‘default-mode’ of brain function associated with self-directed mental processes at rest. In this study, we examined this TID phenomenon in schizophrenia and its relevance to patients' symptoms, task performance and level of emotional awareness. Relative to control subjects, patients showed significantly greater TID of the rostral anterior cingulate (rAC)/medial prefrontal cortex (mPFC) and precuneus (PrC)/posterior cingulate cortex (PC). The magnitude of prefrontal TIDs was associated with patients' task performance and emotional awareness for others. The nature of these associations suggests a complex interchange between cognitive and emotional influences on the resting-state activity of these prefrontal ‘default mode’ regions in schizophrenia.

Volume, neuron density and total neuron number in five subcortical regions in schizophrenia

Several studies have pointed to alterations in mean volumes, neuron densities and total neuron numbers in the caudate nucleus (CN), putamen, nucleus accumbens (NA), mediodorsal nucleus of the thalamus (MDNT) and lateral nucleus of the amygdala (LNA) in schizophrenia. However, the results of these studies are conflicting and no clear pattern of alterations has yet been established in these subcortical regions, possibly due to differences in quantitative histological methods used as well as differences in the investigated case series. The present study investigates these subcortical regions in both hemispheres of the same post-mortem brains for volume, neuron density and total neuron number with high-precision design-based stereology. The analysed case series consisted of 13 post-mortem brains from male schizophrenic patients [age range: 22-64 years; mean age 51.5 +/- 3.3 years (mean +/- SEM)] and 13 age-matched male controls (age range: 25-65 years; mean age 51.9 +/- 3.1 years). A general linear model multivariate analysis of variance with diagnosis and hemisphere as fixed factors and illness duration (schizophrenic patients) or age (controls), post-mortem interval and fixation time as covariates showed a number of statistically significant alterations in the brains from schizophrenic patients compared with the controls. There was a reduced mean volume of the putamen [-5.0% on the left side (l) and -4.1% on the right side (r)] and the LNA (l: -12.1%, r: -17.6%), and a reduced mean total neuron number in the CN (l: -10.4%, r: -10.2%), putamen (l: -8.1%, r: -11.6%) and the LNA (l: -15.9%, r: -16.2%). These data show a previously unreported, distinct pattern of alterations in mean total neuron numbers in identified subcortical brain regions in a carefully selected sample of brains from schizophrenic patients. The rigorous quantitative analysis of several regions in brains from schizophrenic patients and matched controls is crucial to provide reliable information on the neuropathology of schizophrenia as well as insights about its pathogenesis.

Deficits in parvalbumin and calbindin immunoreactive cells in the hippocampus of isolation reared rats

Post-mortem studies have provided evidence for abnormalities of the gamma-aminobutyric acid (GABA)-ergic system in schizophrenia. The calcium-binding proteins (CBPs), parvalbumin (PV), calbindin (CB) and calretinin (CR) can be used as markers for specific subpopulations of GABAergic neurons in the brain. Isolation rearing of rats is a non-pharmacological, non-lesion manipulation that leads to deficits in prepulse inhibition of the startle reflex (PPI) and other behavioural and neurochemical alterations reminiscent of schizophrenia. Female rats were reared in social housing (groups of three) or singly for 11 weeks post weaning and PPI was measured. Brains were removed and hippocampal CBP- containing neurons determined following immunocytochemical staining. Compared to socially housed rats, isolated rats exhibited PPI deficits and reductions in PV and CB-immunoreactive cells in the hippocampus, with no significant change in CR. These findings demonstrate selective abnormalities of sub-populations of GABAergic interneurons in the hippocampus of isolation reared rats, which resemble the neuronal deficits seen in this region in schizophrenia.

Association study between the TNXB locus and schizophrenia in a Japanese population

The chromosome 6p21-24 region, which contains the human leukocyte antigen (HLA) region, has been suggested as an important locus for a susceptibility gene for schizophrenia. Recently, a significant association between schizophrenia and the TNXB locus, located immediately telomeric of the NOTCH4 locus in the HLA region, was observed. Few studies have further investigated the region in schizophrenia. In the present study, we investigated the region in a Japanese population. Subjects included 241 patients with schizophrenia and 290 controls. Twenty-six single nucleotide polymorphisms (SNPs) and the corresponding haplotypes were analyzed. As a result, exactly the same SNPs in the TNXB locus (rs1009382 and rs204887) as in the previous study were associated with schizophrenia (P = 0.034 and 0.034, respectively, uncorrected). A SNP (rs2071287) in the NOTCH4 locus and haplotype around it were also suggested to associate with the disease, consistent with another previous study (P = 0.041 and permutation P = 0.024, respectively, uncorrected). Although these associations became insignificant after Bonferroni correction, the findings might provide support for the association of the TNXB locus or its adjacent region of the NOTCH4 locus with schizophrenia.

Volumetric analysis of septal region in schizophrenia and affective disorder

MRI and post-mortem studies indicate an increased prevalence of cavum septi pellucidi (CSP) in schizophrenia and affective disorder. The aim of this study was to characterize the CSP and the septal tissue among patients with schizophrenia, patients with affective disorder, and control subjects. The volumes of CSP and septal tissue were measured in post-mortem brains in 42 patients with schizophrenia, 14 patients with affective disorder, and 17 normal control cases by planimetry of serial sections. Enlargements of CSP (>100 mm(3)) were found in eight of the 42 (19%) patients with schizophrenia. There were no significant differences in CSP volumes between patients with affective disorder and controls. Enlarged CSP in schizophrenia were not associated with reduced septal tissue volumes. By contrast, a significant positive correlation between volumes of CSP and septal tissue volumes in patients with schizophrenia (P = 0.03) and in control cases (P < 0.01) was found, but not in patients with affective disorder (P = 0.53). The finding of enlarged CSP in schizophrenia strongly supports the hypothesis of an early developmental abnormality in this key structure of the limbic system.

Neuroanatomic substrates of sex differences in language dysfunction in schizophrenia: A pilot study

Objective This pilot study investigated whether our previous findings of disrupted normal sexual brain dimorphisms in language-associated regions in schizophrenia were linked with our previously reported sex differences in language dysfunction in schizophrenia. Method Nineteen adults with schizophrenia and 15 normal comparisons were tested on phonology, semantics and grammar and underwent structural MRI. Results Among males, left hippocampal and left planum temporale (PT) abnormalities were associated with phonological, semantic and grammar deficits, accounting for 17–52% and 27–33%, respectively, of variance in diagnostic group differences. Anterior cingulate gyrus was significantly associated with semantics. Among females, right Heschl's Gyrus (HG) and left PT were significantly associated with phonology, right HG with semantics and grammar and right hippocampus with semantics. Conclusions These preliminary findings suggest disrupted sexual brain dimorphisms in schizophrenia are associated with sex-specific language deficits, and left hippocampal abnormalities, in particular, contribute to language dysfunction among men. Abnormalities in right cortical temporal regions showed stronger associations with language dysfunction among females.

Linkage disequilibrium analysis of the CHRNA7 gene and its partially duplicated region in schizophrenia

Several previous studies have reported a significant linkage between markers in the alpha 7 nicotinic cholinergic receptor subunit ( CHRNA7) gene and either schizophrenia or the P50 sensory gating deficit, a schizophrenia endophenotype. However, CHRFAM7A, a partially duplicated gene 1.6 Mb upstream of the CHRNA7 gene, has complicated further genetic analysis. We genotyped 14 polymorphic markers throughout the full-length CHRNA7 gene and the duplicated region in 188 unrelated Han Chinese patients with schizophrenia and 188 controls. The duplicated regions were assessed by genotyping up- and down-stream polymorphic markers in the vicinity of each region and analyzing the linkage disequilibrium (LD) between each pair of markers. No evidence of risk variants for schizophrenia in either the CHRNA7 gene or the partially duplicated region was found in the LD analysis. A significant deviation from the Hardy–Weinberg equilibrium (HWE) was found only in the genotypic distribution of SNP9 (IVS4-1912) in patients ( p = 0.00829), but not in controls. In conclusion, our LD analysis did not reveal any association between schizophrenia in our Han Chinese population and the CHRNA7 gene or its partially duplicated region. However, we could not exclude the possibility of a weak genetic effect due to the small sample size. Analyses of larger samples and higher-density markers, particularly around SNP9 (IVS4-1912), are still needed.

The Human Homolog of the QKI Gene Affected in the Severe Dysmyelination “Quaking” Mouse Phenotype: Downregulated in Multiple Brain Regions in Schizophrenia

The authors sought to understand the origins of oligodendrocyte/myelin gene expression abnormalities in the brains of persons with schizophrenia. Twelve cortical regions (Brodmann's areas 8, 10, 44, 46, 23/31, 24/32, 20, 21, 22, 36/28, 7, and 17) and three noncortical regions (caudate, hippocampus, and putamen) of 16 elderly schizophrenia patients and 14 matched comparison subjects were examined using 450 separate microarrays. The mRNA levels of QKI and its isoforms were then measured in a larger cohort by using quantitative real-time polymerase chain reaction (qPCR) in the cingulate cortex of schizophrenia subjects and matched comparison subjects. Expression of QKI mRNA was decreased in seven cortical regions and the hippocampus in the schizophrenia subjects. QKI gene expression deficits detected by microarray were validated by qPCR in the cingulate cortex, where the expression of isoforms QKI-5, QKI-6, and QKI-7 were profoundly perturbed in schizophrenia. Since QKI plays a fundamental role in oligodendrocyte differentiation and in myelination, its underexpression may be pivotal to, and upstream of, other myelin-associated gene expression abnormalities in schizophrenia. Given the role of QKI in determination of oligodendrocyte fate, these results not only confirm oligodendrocyte-related gene expression abnormalities in schizophrenia but suggest that the physiology of glial progenitor cells may be altered in schizophrenia.

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.