Middle and inferior temporal gyrus gray matter volume abnormalities in first-episode schizophrenia: an MRI study

OBJECTIVE: Magnetic resonance imaging (MRI) studies of schizophrenia reveal temporal lobe structural brain abnormalities in the superior temporal gyrus and the amygdala-hippocampal complex. However, the middle and inferior temporal gyri have received little investigation, especially in first-episode schizophrenia. METHOD: High-spatial-resolution MRI was used to measure gray matter volume in the inferior, middle, and superior temporal gyri in 20 patients with first-episode schizophrenia, 20 patients with first-episode affective psychosis, and 23 healthy comparison subjects. RESULTS: Gray matter volume in the middle temporal gyrus was smaller bilaterally in patients with first-episode schizophrenia than in comparison subjects and in patients with first-episode affective psychosis. Posterior gray matter volume in the inferior temporal gyrus was smaller bilaterally in both patient groups than in comparison subjects. Among the superior, middle, and inferior temporal gyri, the left posterior superior temporal gyrus gray matter in the schizophrenia group had the smallest volume, the greatest percentage difference, and the largest effect size in comparisons with healthy comparison subjects and with affective psychosis patients. CONCLUSIONS: Smaller gray matter volumes in the left and right middle temporal gyri and left posterior superior temporal gyrus were present in schizophrenia but not in affective psychosis at first hospitalization. In contrast, smaller bilateral posterior inferior temporal gyrus gray matter volume is present in both schizophrenia and affective psychosis at first hospitalization. These findings suggest that smaller gray matter volumes in the dorsal temporal lobe (superior and middle temporal gyri) may be specific to schizophrenia, whereas smaller posterior inferior temporal gyrus gray matter volumes may be related to pathology common to both schizophrenia and affective psychosis.     

White matter abnormalities in subjects at ultra high-risk for schizophrenia and first-episode schizophrenic patients

Schizophrenia is associated with neuroanatomical abnormalities. Gray matter decrease seems to predate first schizophrenic episode. Whether white matter abnormalities predate the onset of psychotic symptoms is unclear. We investigated this issue using voxel-based morphometry (VBM) of structural magnetic resonance images to examine individuals with prodromal symptoms who were at ultra high-risk (UHR) of developing schizophrenia and compared them to first-episode schizophrenic patients and healthy controls. White matter volume maps from high-resolution magnetic resonance T1 weighted whole brain images were analyzed in a cross-sectional study using SPM2 in 30 UHR patients, 23 first-episode schizophrenic patients and 29 healthy controls. UHR patients showed significant lower white matter volume in the right superior temporal lobe compared to healthy controls. First-episode patients with schizophrenia showed widespread smaller white matter volume bilaterally compared to UHR patients. This study provides first evidence for smaller white matter volume in the right temporal lobe of UHR patients, one of the key structures in the pathophysiology of schizophrenia. Furthermore, white matter abnormalities seem to progress after transition into schizophrenia.     

Gray and white matter brain abnormalities in first-episode schizophrenia inferred from magnetization transfer imaging

BACKGROUND: Neuroimaging studies suggest that schizophrenia is associated with gray and possibly white matter changes. It is unclear whether these changes are present at illness onset or which brain structures are selectively affected. New imaging methods such as magnetization transfer imaging may be more sensitive than conventional volumetric imaging to the subtle structural brain changes in schizophrenia. METHODS: High-resolution volumetric T1-weighted images and magnetization transfer images were acquired from 30 patients (29 with first-episode schizophrenia and 1 with schizophreniform psychoses) and 30 control subjects. Images were processed using voxel-based morphometry, which allows whole-brain analysis. RESULTS: Compared with controls, the magnetization transfer ratio (an index of signal loss derived from magnetization transfer imaging) was reduced bilaterally in the medial prefrontal cortex (right greater than left), insula (left greater than right), and white matter incorporating the fasciculus uncinatus (left greater than right) in the patient group. Analysis of the T1-weighted images did not reveal significant volumetric differences between patients and controls. CONCLUSIONS: Gray and white matter abnormalities are present in schizophrenia at illness onset. The magnetization transfer ratio is sensitive to these abnormalities, which cannot be explained by detectable atrophy in our patient group.     

Basal ganglia volumes in first-episode schizophrenia and healthy comparison subjects.

BACKGROUND: Previous studies suggest that dysfunction of cortico-striato-pallido-thalamic (CSPT) circuitry may be involved in the pathophysiology of schizophrenia but also show that basal ganglia structure is highly plastic and may be influenced by antipsychotic treatments. Controversy remains about whether basal ganglia pathology can be detected in vivo among treatment-na?ve patients. We conducted a magnetic resonance imaging (MRI) study to examine basal ganglia structures and the limbic forebrain in first episode schizophrenia and healthy comparison subjects. METHODS: Fifty-one patients with first-episode schizophrenia and 28 healthy comparison subjects participated in the study. A high-resolution, special contrast (white matter nulling) MRI sequence was used to measure the caudate nucleus, nucleus accumbens, putamen, and subcommissural limbic forebrain. RESULTS: Volumes of the basal ganglia regions of interest (adjusted for total brain volume and age) did not differ significantly between the groups. Age correlated significantly with caudate and putamen volumes bilaterally in the healthy comparison group, but not among patients. CONCLUSIONS: The findings suggest that there are no volumetric abnormalities in basal ganglia before treatment in first-episode schizophrenia. The lack of a negative correlation between age and striatal volume among patients may implicate illness-associated factors that alter normal age-related changes in basal ganglia size.     

Progressive decrease of left superior temporal gyrus gray matter volume in patients with first-episode schizophrenia

OBJECTIVE: Smaller temporal lobe cortical gray matter volumes, including the left superior temporal gyrus, have been reported in magnetic resonance imaging (MRI) studies of patients with chronic schizophrenia and, more recently, in patients with first-episode schizophrenia. However, it remains unknown whether there are progressive decreases in temporal lobe cortical gray matter volumes in patients with first-episode schizophrenia and whether similarly progressive volume decreases are present in patients with affective psychosis. METHOD: High-spatial-resolution MRI scans at initial hospitalization and 1.5 years later were obtained from 13 patients with first-episode schizophrenia, 15 patients with first-episode affective psychosis (mainly manic), and 14 healthy comparison subjects. MRI volumes were calculated for gray matter of superior temporal gyrus and for the amygdala-hippocampal complex. RESULTS: Patients with first-episode schizophrenia showed significant decreases in gray matter volume over time in the left superior temporal gyrus compared with patients with first-episode affective psychosis or healthy comparison subjects. This progressive decrease was more pronounced in the posterior portion of the left superior temporal gyrus (mean=9.6%) than in the anterior portions (mean=8.4%). No group differences in the rate of change over time were present in other regions. CONCLUSIONS: These findings demonstrate a progressive volume reduction of the left posterior superior temporal gyrus gray matter in patients with first-episode schizophrenia but not in patients with first-episode affective psychosis.     

Progressive decrease of left Heschl gyrus and planum temporale gray matter volume in first-episode schizophrenia: a longitudinal magnetic resonance imaging study

BACKGROUND: The Heschl gyrus and planum temporale have crucial roles in auditory perception and language processing. Our previous investigation using magnetic resonance imaging (MRI) indicated smaller gray matter volumes bilaterally in the Heschl gyrus and in left planum temporale in patients with first-episode schizophrenia but not in patients with first-episode affective psychosis. We sought to determine whether there are progressive decreases in anatomically defined MRI gray matter volumes of the Heschl gyrus and planum temporale in patients with first-episode schizophrenia and also in patients with first-episode affective psychosis. METHODS: At a private psychiatric hospital, we conducted a prospective high spatial resolution MRI study that included initial scans of 28 patients at their first hospitalization (13 with schizophrenia and 15 with affective psychosis, 13 of whom had a manic psychosis) and 22 healthy control subjects. Follow-up scans occurred, on average, 1.5 years after the initial scan. RESULTS: Patients with first-episode schizophrenia showed significant decreases in gray matter volume over time in the left Heschl gyrus (6.9%) and left planum temporale (7.2%) compared with patients with first-episode affective psychosis or control subjects. CONCLUSIONS: These findings demonstrate a left-biased progressive volume reduction in the Heschl gyrus and planum temporale gray matter in patients with first-episode schizophrenia in contrast to patients with first-episode affective psychosis and control subjects. Schizophrenia but not affective psychosis seems to be characterized by a postonset progression of neocortical gray matter volume loss in the left superior temporal gyrus and thus may not be developmentally fixed.     

Uncinate fasciculus findings in schizophrenia: a magnetic resonance diffusion tensor imaging study

OBJECTIVE: Disruptions in connectivity between the frontal and temporal lobes may explain some of the symptoms observed in schizophrenia. Conventional magnetic resonance imaging (MRI) studies, however, have not shown compelling evidence for white matter abnormalities, because white matter fiber tracts cannot be visualized by conventional MRI. Diffusion tensor imaging is a relatively new technique that can detect subtle white matter abnormalities in vivo by assessing the degree to which directionally organized fibers have lost their normal integrity. The first three diffusion tensor imaging studies in schizophrenia showed lower anisotropic diffusion, relative to comparison subjects, in whole-brain white matter, prefrontal and temporal white matter, and the corpus callosum, respectively. Here the authors focus on fiber tracts forming temporal-frontal connections. METHOD: Anisotropic diffusion was assessed in the uncinate fasciculus, the most prominent white matter tract connecting temporal and frontal brain regions, in 15 patients with chronic schizophrenia and 18 normal comparison subjects. A 1.5-T GE Echospeed system was used to acquire 4-mm-thick coronal line-scan diffusion tensor images. Maps of the fractional anisotropy were generated to quantify the water diffusion within the uncinate fasciculus. RESULTS: Findings revealed a group-by-side interaction for fractional anisotropy and for uncinate fasciculus area, derived from automatic segmentation. The patients with schizophrenia showed a lack of normal left-greater-than-right asymmetry seen in the comparison subjects. CONCLUSIONS: These findings demonstrate the importance of investigating white matter tracts in vivo in schizophrenia and support the hypothesis of a disruption in the normal pattern of connectivity between temporal and frontal brain regions in schizophrenia.     

Superior temporal gyrus differences in childhood-onset schizophrenia

The posterior superior temporal gyrus (STG) is the approximate site of Wernicke's area, a language region, which in previous studies has been reported to be abnormal in adults with schizophrenia. The present study assesses volumetric differences in the superior temporal gyrus of subjects with childhood-onset schizophrenia (COS). MRI scans of 18 subjects diagnosed with childhood-onset schizophrenia and 16 age- and sex-matched normals were analyzed to assess possible volume differences. The COS subjects displayed significant enlargement of the right posterior superior temporal gyrus, showing white matter increases bilaterally in this region. Our findings are consistent with studies that have found increased volumes in temporal lobe regions in COS and may provide a possible neural correlate for the language impairment observed in COS patients.     

A follow-up MRI study of the fusiform gyrus and middle and inferior temporal gyri in schizophrenia spectrum

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.     

Magnetic resonance imaging correlates of first-episode psychosis in young adult male patients: combined analysis of grey and white matter

Background: Several patterns of grey and white matter changes have been separately described in young adults with first-episode psychosis. Concomitant investigation of grey and white matter densities in patients with first-episode psychosis without other psychiatric comorbidities that include all relevant imaging markers could provide clues to the neurodevelopmental hypothesis in schizophrenia. Methods: We recruited patients with first-episode psychosis diagnosed according to the DSM-IV-TR and matched controls. All participants underwent magnetic resonance imaging (MRI). Voxel-based morphometry (VBM) analysis and mean diffusivity voxel-based analysis (VBA) were used for grey matter data. Fractional anisotropy and axial, radial and mean diffusivity were analyzed using tract-based spatial statistics (TBSS) for white matter data. Results: We included 15 patients and 16 controls. The mean diffusivity VBA showed significantly greater mean diffusivity in the first-episode psychosis than in the control group in the lingual gyrus bilaterally, the occipital fusiform gyrus bilaterally, the right lateral occipital gyrus and the right inferior temporal gyrus. Moreover, the TBSS analysis revealed a lower fractional anisotropy in the first-episode psychosis than in the control group in the genu of the corpus callosum, minor forceps, corticospinal tract, right superior longitudinal fasciculus, left middle cerebellar peduncle, left inferior longitudinal fasciculus and the posterior part of the fronto-occipital fasciculus. This analysis also revealed greater radial diffusivity in the first-episode psychosis than in the control group in the right corticospinal tract, right superior longitudinal fasciculus and left middle cerebellar peduncle. Limitations: The modest sample size and the absence of women in our series could limit the impact of our results. Conclusion: Our results highlight the structural vulnerability of grey matter in posterior areas of the brain among young adult male patients with first-episode psychosis. Moreover, the concomitant greater radial diffusivity within several regions already revealed by the fractional anisotropy analysis supports the idea of a late myelination in patients with first-episode psychosis.     

Risperidone in first-episode psychosis: a longitudinal, exploratory voxel-based morphometric study

Previous studies have provided evidence supporting a neuroplastic effect of atypical antipsychotics. The present investigation explores the short-term effects of risperidone on brain parenchyma by performing voxel-based morphometry on baseline and 6-week follow-up MRI scans obtained from 15 neuroleptic-na?ve individuals with first-episode psychosis treated with risperidone and 15 healthy controls. The risperidone-treated subjects demonstrated changes in grey matter and white matter in several brain regions, including superior temporal gyrus. No areas of change were found in controls. The results of this exploratory investigation support the possibility that risperidone has short-term effects on brain parenchyma in individuals with first-episode psychosis.     

Cerebral grey, white matter and csf in never-medicated, first-episode schizophrenia

We report the first voxel-based morphometric (VBM) study to examine cerebral grey and white matter and cerebrospinal fluid (CSF) using computational morphometry in never-medicated, first-episode psychosis (FEP). Region-of-interest (ROI) analysis was also performed blind to group membership. 26 never-medicated individuals with FEP (23 with DSM-IV schizophrenia) and 38 healthy controls had MRI brain scans. Groups were balanced for age, sex, handedness, ethnicity, paternal socio-economic status, and height. Healthy controls were recruited from the local community by advertisement. Grey matter, white matter, and CSF: global brain volume ratios were significantly smaller in patients. Patients had significantly less grey matter volume in L and R caudate nuclei, cingulate gyri, parahippocampal gyri, superior temporal gyri, cerebellum and R thalamus, prefrontal cortex. They also had significantly less white matter volume in the R anterior limb of the internal capsule fronto-occipital fasciculus and L and R fornices, and significantly greater CSF volume especially in the R lateral ventricle. Excluding the 3 subjects with brief psychotic disorder did not alter our results. Our data suggest that fronto-temporal and subcortical-limbic circuits are morphologically abnormal in never-medicated, schizophrenia. ROI analysis comparing the schizophrenia group (n=23) with the healthy controls (n=38) confirmed caudate volumes were significantly smaller bilaterally by 11%, and lateral ventricular volume was significantly larger on the right by 26% in the patients. Caudate nuclei and lateral ventricular volume measurements were uncorrelated (Pearson correlation coefficient 0.30, p=0.10), ruling out the possibility of segmentation artefact. Ratio of lateral ventricle to caudate volume was bilaterally significantly increased (p<0.005, 2-tailed), which could represent an early biomarker in first-episode, never-medicated schizophrenia.     

Optimized voxel-based morphometry of gray matter volume in first-episode, antipsychotic-naive schizophrenia

This study examined gray matter (GM) volume abnormalities in first-episode, antipsychotic-na?ve Indian schizophrenia patients. Magnetic resonance images of 18 schizophrenia patients and 18 matched healthy comparison subjects were analyzed by optimized voxel-based morphometry. Schizophrenia patients had significantly smaller global GM and greater global CSF volumes and smaller regional GM volume in superior frontal, inferior frontal, cingulate, post-central, superior temporal and parahippocampal gyri, inferior parietal lobule, insula, caudate nuclei, thalamus and cerebellum. Findings suggest limbic, heteromodal cortical, striatal, thalamic and cerebellar abnormalities in schizophrenia.     

Differences and similarities in insular and temporal pole MRI gray matter volume abnormalities in first-episode schizophrenia and affective psychosis

CONTEXT: Whether psychoses associated with schizophrenia and affective disorder represent manifestations of different disorders or the same disorder is an important but unresolved question in psychiatry. Results of previous volumetric magnetic resonance imaging investigations indicate that gray matter volume reductions in neocortical regions may be specific to schizophrenia. OBJECTIVE: To simultaneously evaluate multiple olfactocentric paralimbic regions, which play crucial roles in human emotion and motivation, in first-episode patients with schizophrenia and affective psychosis. DESIGN: A cross-sectional study using high-spatial resolution magnetic resonance imaging in patients with schizophrenia and affective psychosis at their first hospitalization. SETTING: Inpatient units at a private psychiatric hospital. PARTICIPANTS: Fifty-three first-episode patients, 27 with schizophrenia and 26 with affective (mainly manic) psychosis, and 29 control subjects. MAIN OUTCOME MEASURES: Using high-spatial resolution magnetic resonance imaging, the gray matter volumes of 2 olfactocentric paralimbic regions of interest, the insular cortex and the temporal pole, were evaluated. RESULTS: A bilateral volume reduction in insular cortex gray matter was specific to first-episode patients with schizophrenia. In contrast, both first-episode psychosis groups showed a volume reduction in left temporal pole gray matter and an absence of normal left-greater-than-right asymmetry. Region of interest correlations showed that only patients with schizophrenia lacked a positive correlation between left temporal pole and left anterior amygdala-hippocampal complex gray matter volumes, whereas both psychosis groups were similar in lacking normal positive correlations between left temporal pole and left anterior superior temporal gyrus gray matter volumes. CONCLUSIONS: These partially different and partially similar patterns of structural abnormalities in olfactocentric paralimbic regions and their associated abnormalities in other temporolimbic regions may be important factors in the differential and common manifestations of the 2 psychoses.     

Abnormalities of myelination in schizophrenia detected in vivo with MRI,and post-mortem with analysis of oligodendrocyte proteins

Schizophrenia unfolds during the late period of brain maturation, while myelination is still continuing. In the present study, we used MRI and T2 relaxation analysis to measure the myelin water fraction in schizophrenia. In schizophrenia (n=30) compared with healthy subjects (n=27), overall white matter showed 12% lower myelin water fraction (P=0.031), with the most prominent effects on the left genu of the corpus callosum (36% lower, P=0.002). The left anterior genu was affected in both first-episode (P=0.035) and chronic patients (P=0.011). In healthy subjects, myelin water fraction in total white matter and in frontal white matter increased with age, and with years of education, indicating ongoing maturation. In patients with schizophrenia, neither relation was statistically significant. Post-mortem studies of anterior frontal cortex demonstrated less immunoreactivity of two oligodendrocyte-associated proteins in schizophrenia (2',3'-cyclic nucleotide 3'-phosphodiesterase by 33%, P=0.05; myelin-associated glycoprotein by 27%, P=0.14). Impaired myelination in schizophrenia could contribute to abnormalities of neural connectivity and persistent functional impairment in the illness.     

Diagnosis-related regional gray matter loss over two years in first episode schizophrenia and bipolar disorder.

BACKGROUND: We examined gray- and white-matter brain volumes in first episode psychosis (FEP) at initial presentation and at two-year follow-up. We predicted that FEP subjects would show longitudinal reductions in fronto-temporal gray- and white-matter volumes compared with controls. Furthermore, we expected groups to be differentiated by diagnosis-related reductions. METHODS: Twenty-five schizophrenia and 8 bipolar disorder FEP patients underwent a structural MRI scan at first presentation and 2 years later. Matched healthy subjects (n = 22) underwent a single identical scan. RESULTS: At initial presentation FEP subjects had significantly less gray- and white-matter than healthy subjects. Diagnostic dissociations were revealed both at first presentation and at follow-up. In schizophrenia patients, gray-matter deficits were observed in lateral and medial frontal regions and in bilateral posterior temporal lobe regions, with additional extensive losses over time in lateral fronto-temporal regions and left anterior cingulate gyrus. By contrast, gray matter deficit in bipolar patients was localized to bilateral inferior temporal gyri with additional loss over time observed only in the anterior cingulate cortex. CONCLUSIONS: The results are consistent with a dual process model of psychosis, in which the diagnosis-related gray matter loss is determined by neurodevelopmental gray-matter volumetric differences which predate symptom onset, and diagnosis-related neurodegenerative gray-matter loss over time.     

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.     

Features of structural brain abnormality detected in first-episode psychosis

OBJECTIVE: Structural magnetic resonance imaging (MRI) studies that focus on first-episode psychosis avoid some common confounds, such as chronicity of illness, treatment effects, and long-term substance abuse. However, such studies may select subjects with poor short-term treatment response or outcome. In this study, the authors focus on structural brain abnormalities in never or minimally treated patients who underwent MRI scanning early in their first episode of psychosis. METHOD: The authors examined 37 patients (13 medication naive, 24 previously treated) who were experiencing their first episode of psychosis; the mean duration of symptoms was short (31 weeks). These patients were comparable in age, gender, handedness, ethnicity, and parental socioeconomic status to a group of 25 healthy comparison subjects. A three-dimensional, inversion recovery prepared, fast spoiled gradient/recall in the steady state scan of the whole brain that used 1.5-mm contiguous sections was performed to acquire a T(1)-weighted data set. Human ratings of volumetric measurement of brain structures were performed with stereological techniques on three-dimensional reconstructed MRIs. RESULTS: The patient group had significant deficits in cortical gray matter, temporal lobe gray matter, and whole brain volume as well as significant enlargement of the lateral and third ventricles. Structural deviations were found in both treatment-naive and minimally treated subjects. No relationships were found between any brain matter volumes and positive or negative symptoms. CONCLUSIONS: Structural brain abnormalities were distributed throughout the cortex with particular decrement evident in gray matter. This feature is consistent with altered cell structure and disturbed neuronal connectivity, which accounts for the functional abnormality of psychosis.     

Abnormal Causal Connectivity by Structural Deficits in First-Episode,Drug-Naive Schizophrenia at Rest

Anatomical deficits and resting-state functional connectivity (FC) alterations in prefrontal-thalamic-cerebellar circuit have been implicated in the neurobiology of schizophrenia. However, the effect of structural deficits in schizophrenia on causal connectivity of this circuit remains unclear. This study was conducted to examine the causal connectivity biased by structural deficits in first-episode, drug-naive schizophrenia patients. Structural and resting-state functional magnetic resonance imaging (fMRI) data were obtained from 49 first-episode, drug-naive schizophrenia patients and 50 healthy controls. Data were analyzed by voxel-based morphometry and Granger causality analysis. The causal connectivity of the integrated prefrontal-thalamic (limbic)-cerebellar (sensorimotor) circuit was partly affected by structural deficits in first-episode, drug-naive schizophrenia as follows: (1) unilateral prefrontal-sensorimotor connectivity abnormalities (increased driving effect from the left medial prefrontal cortex [MPFC] to the sensorimotor regions); (2) bilateral limbic-sensorimotor connectivity abnormalities (increased driving effect from the right anterior cingulate cortex [ACC] to the sensorimotor regions and decreased feedback from the sensorimotor regions to the right ACC); and (3) bilateral increased and decreased causal connectivities among the sensorimotor regions. Some correlations between the gray matter volume of the seeds, along with their causal effects and clinical variables (duration of untreated psychosis and symptom severity), were also observed in the patients. The findings indicated the partial effects of structural deficits in first-episode, drug-naive schizophrenia on the prefrontal-thalamic (limbic)-cerebellar (sensorimotor) circuit. Schizophrenia may reinforce the driving connectivities from the left MPFC or right ACC to the sensorimotor regions and may disrupt bilateral causal connectivities among the sensorimotor regions.Key words: first-episode schizophrenia, causal effect, structural deficits, voxel-based morphometry, Granger causality analysis     

A volumetric MRI and magnetization transfer imaging follow-up study of patients with first-episode schizophrenia

Conventional MRI studies have not provided definitive evidence of progressive loss of brain volume in the early stages of schizophrenia, although more subtle changes may have gone undetected. We have looked for such subtle changes using volumetric MRI and magnetization transfer imaging (MTI), an advanced MRI technique sensitive to subtle neuropathological abnormalities. Magnetization transfer images and high-resolution volumetric T1-weighted images were acquired from 16 patients with first-episode schizophrenia at the start of the study and 3.7 years later. A group of 12 healthy controls were also scanned on two occasions. Images were processed using a voxel-based approach that allows whole-brain analysis. There was a group difference with a significant volume loss in the patients' white matter adjacent to the lateral ventricles in the right and left temporal lobes, in medial temporal gyrus, and in the white matter in and around the right middle frontal gyrus. No cortical differences were detected between the groups using MTI or volumetric MRI. The absence of any time-by-group interaction suggests that these abnormalities do not progress in the early stages of the disease. The results of the study need to be interpreted in the light of the small sample size and of the limitations of current image analysis methods.