Correction: Genome-wide association analysis with gray matter volume as a quantitative phenotype in first-episode treatment-naive patients with schizophrenia.
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ABSTRACT:
SUBMITTER: PLOS ONE Staff
PROVIDER: S-EPMC4388674 | biostudies-literature | 2015
REPOSITORIES: biostudies-literature
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Correction: Genome-wide association analysis with gray matter volume as a quantitative phenotype in first-episode treatment-naïve patients with schizophrenia.
PloS one 20150407 4
[This corrects the article DOI: 10.1371/journal.pone.0075083.]. ...[more]
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Project description:Reduced Gray matter (GM) volume is a core feature of schizophrenia. Mapping genes that is associated with the heritable disease-related phenotypes may be conducive to elucidate the pathogenesis of schizophrenia. This study aims to identify the common genetic variants that underlie the deficits of GM volume in schizophrenia. High-resolution T1 images and whole genome genotyping data were obtained from 74 first-episode treatment-naïve patients with schizophrenia and 51 healthy controls in the Mental Health Centre of the West China Hospital, Sichuan University. All participants were scanned using a 3T MR imaging system and were genotyped using the HumanHap660 Bead Array. Reduced GM volumes in three brain areas including right hOC3v in the collateral sulcus of visual cortex (hOC3vR), left cerebellar vermis lobule 10 (vermisL10) and right cerebellar vermis lobule 10 (vermisR10) were found in patients with schizophrenia [corrected].There was a group by genotype interaction when genotypes from genome-wide scan were subsequently considered in the case-control analyses. SNPs from three genes or chromosomal regions (TBXAS1, PIK3C2G and HS3ST5) were identified to predict the changes of GM volume in hOC3vL, vermisL10 and vermisR10. These results also highlighted the usefulness of endophenotype in exploring the pathogenesis of neuropsychiatric diseases such as schizophrenia although further independent replication studies are needed in the future.
| S-EPMC3782493 | biostudies-literature
Project description:Different patterns of gray matter volume (GMV) abnormalities have been reported between chronic patients with deficit schizophrenia (DS), relative to nondeficit schizophrenia (NDS) patients. However, it is not clear whether these differences are characteristic to the pathophysiology of DS or due to the effects of medications or illness durations. To address this issue, GMV in 88 first-episode, drug-naive patients with schizophrenia (44 DS and 44 NDS), 67 of their first-degree relatives and 84 healthy controls were assessed using voxel- based morphometry (VBM) and compared between groups. Correlations between GMV and clinical symptoms in patients were also assessed. Compared to controls, DS patients displayed more severe GMV reduction in the cerebellar culmen than NDS patients. GMV reduction in culmen was also observed in the first-degree relatives of DS (but not NDS) patients, suggesting possible different genetic risk in DS and NDS. The left insula was significantly smaller in DS patients than both NDS patients and controls, and smaller GMV of this region was associated with more severe negative symptoms in patients. Our results collectively indicate that DS might represent a distinct subtype of schizophrenia from NDS and the GMV change in left insula may be a morphological signature of DS.
| S-EPMC4859347 | biostudies-literature
Project description:BackgroundOverall neocortical gray matter (NCGM) volume has not been studied in first-episode schizophrenia (FESZ) at first hospitalization or longitudinally to evaluate progression, nor has it been compared with first-episode affective psychosis (FEAFF).MethodsExpectation-maximization/atlas-based magnetic resonance imaging (MRI) tissue segmentation into gray matter, white matter (WM), or cerebrospinal fluid (CSF) at first hospitalization of 29 FESZ and 34 FEAFF, plus 36 matched healthy control subjects (HC), and, longitudinally approximately 1.5 years later, of 17 FESZ, 21 FEAFF, and 26 HC was done. Manual editing separated NCGM and its lobar parcellation, cerebral WM (CWM), lateral ventricles (LV), and sulcal CSF (SCSF).ResultsAt first hospitalization, FESZ and FEAFF showed smaller NCGM volumes and larger SCSF and LV than HC. Longitudinally, FESZ showed NCGM volume reduction (-1.7%), localized to frontal (-2.4%) and temporal (-2.6%) regions, and enlargement of SCSF (7.2%) and LV (10.4%). Poorer outcome was associated with these LV and NCGM changes. FEAFF showed longitudinal NCGM volume increases (3.6%) associated with lithium or valproate administration but without clinical correlations and regional localization.ConclusionsLongitudinal NCGM volume reduction and CSF component enlargement in FESZ are compatible with post-onset progression. Longitudinal NCGM volume increase in FEAFF may reflect neurotrophic effects of mood stabilizers.
| S-EPMC2782514 | biostudies-literature
Project description:The catechol-O-methyltransferase (COMT) gene is a schizophrenia susceptibility gene. A common functional polymorphism of this gene, Val158/158Met, has been proposed to influence gray matter volume (GMV). However, the effects of this polymorphism on cortical thickness/surface area in schizophrenic patients are less clear. In this study, we explored the relationship between the Val158Met polymorphism of the COMT gene and the GMV/cortical thickness/cortical surface area in 150 first-episode treatment-naïve patients with schizophrenia and 100 healthy controls. Main effects of diagnosis were found for GMV in the cerebellum and the visual, medial temporal, parietal, and middle frontal cortex. Patients with schizophrenia showed reduced GMVs in these regions. And main effects of genotype were detected for GMV in the left superior frontal gyrus. Moreover, a diagnosis × genotype interaction was found for the GMV of the left precuneus, and the effect of the COMT gene on GMV was due mainly to cortical thickness rather than cortical surface area. In addition, a pattern of increased GMV in the precuneus with increasing Met dose found in healthy controls was lost in patients with schizophrenia. These findings suggest that the COMTMet variant is associated with the disruption of dopaminergic influence on gray matter in schizophrenia, and the effect of the COMT gene on GMV in schizophrenia is mainly due to changes in cortical thickness rather than in cortical surface area.
| S-EPMC5562642 | biostudies-other
Project description:Major depressive disorder (MDD) has been linked to differences in the volume of certain areas of the brain and to variants in the piccolo presynaptic cytomatrix protein (PCLO), but the relationship between PCLO and brain morphology has not been studied. A single-nucleotide polymorphism (SNP) in PCLO, rs2522833, is thought to affect protein stability and the activity of the hypothalamic-pituitary-adrenal axis. We investigated the relationship between cortical volume and this SNP in first-episode, drug-naive patients with MDD or healthy control subjects. Seventy-eight participants, including 30 patients with MDD and 48 healthy control subjects, were recruited via interview. PCLO rs2522833 genotyping and plasma cortisol assays were performed, and gray matter volume was estimated using structural magnetic resonance images. Among the individuals carrying the C-allele of PCLO rs2522833, the volume of the left temporal pole was significantly smaller in those with MDD than in healthy controls (family-wise error-corrected, P=0.003). No differences were detected in other brain regions. In addition, the C-carriers showed a larger volume reduction in the left temporal pole than those in the individuals with A/A genotype (P=0.0099). Plasma cortisol levels were significantly higher in MDD-affected C-carriers than in the healthy control C-carriers (12.76±6.10 vs 9.31±3.60?nm, P=0.045). We conclude that PCLO SNP rs2522833 is associated with a gray matter volume reduction in the left temporal pole in drug-naive, first-episode patients with MDD carrying the C-allele.
| S-EPMC5534936 | biostudies-literature
Project description:Region of Interest (ROI) longitudinal studies have detected progressive gray matter (GM) volume reductions in patients with first-episode schizophrenia (FESZ). However, there are only a few longitudinal voxel-based morphometry (VBM) studies, and these have been limited in ability to detect relationships between volume loss and symptoms, perhaps because of methodologic issues. Nor have previous studies compared and validated VBM results with manual Region of Interest (ROI) analysis. In the present VBM study, high-dimensional warping and individualized baseline-rescan templates were used to evaluate longitudinal volume changes within subjects and compared with longitudinal manual ROI analysis on the same subjects. VBM evaluated thirty-three FESZ and thirty-six matched healthy control subjects (HC) at baseline (cross-sectionally) and longitudinally evaluated 21 FESZ and 23 HC after an average of 1.5 years from baseline scans. Correlation analyses detected the relationship between changes in regional GM volumes in FESZ and clinical symptoms derived from the Brief Psychiatric Rating Scale, as well as cognitive function as assessed by the Mini-Mental State Examination. At baseline, patients with FESZ had significantly smaller GM volume compared to HC in some regions including the left superior temporal gyrus (STG). On rescan after 1.5 years, patients showed significant GM volume reductions compared with HC in the left STG including Heschl's gyrus, and in widespread brain neocortical regions of frontal, parietal, and limbic regions including the cingulate gyrus. FESZ showed an association of positive symptoms and volume loss in temporal (especially STG) and frontal regions, and negative symptoms and volume loss in STG and frontal regions. Worse cognitive function was linked to widespread volume reduction, in frontal, temporal and parietal regions. The validation VBM analyses showed results similar to our previous ROI findings for STG and cingulate gyrus. We conclude FESZ show widespread, progressive GM volume reductions in many brain regions. Importantly, these reductions are directly associated with a worse clinical course. Congruence with ROI analyses suggests the promise of this longitudinal VBM methodology.
| S-EPMC3230661 | biostudies-other
Project description:Studies comparing gray matter (GM) volume of schizophrenic patients with or without auditory verbal hallucinations (AVHs) to that of normal controls remain controversial. This project aims to investigate changes of GM volumes of drug-naïve schizophrenic patients with and without AVHs. Eighteen first episode schizophrenic (FES) patients with AVHs, 18 FES patients without AVHs, and 18 healthy controls were scanned using structural MRI. Voxel-based morphometry (VBM) analysis was conducted to investigate changes of GM volume among the three groups. Patients with and without AVHs exhibited reduced GM volumes relative to normal controls in the left superior temporal gyrus, frontal regions, cerebellum and caudate. Further analysis of the GM of subcortical structures found that patients with AVHs had reduced thalamic volume than healthy controls. No significant difference was found between patients with and without AVHs. Significant correlation was found between the total scores of the Positive and Negative Syndrome Scale and bilateral thalamic volume. ROC analysis of thalamic volumes of the patients with AVHs and normal controls showed that the area under the curve was 0.698 (P = 0.043). The decreased thalamic volumes might serve as a biomarker for discriminating FES AVHs patients from normals.
| S-EPMC4585923 | biostudies-other
Project description:Background: The findings of many neuroimaging studies in patients with first-episode major depressive disorder (MDD), and even those of previous meta-analysis, are divergent. To quantitatively integrate these studies, we performed a meta-analysis of gray matter volumes using voxel-based morphometry (VBM). Methods: We performed a comprehensive literature search for relevant studies and traced the references up to May 1, 2021 to select the VBM studies between first-episode MDD and healthy controls (HC). A quantitative meta-analysis of VBM studies on first-episode MDD was performed using the Seed-based d Mapping with Permutation of Subject Images (SDM-PSI) method, which allows a familywise error rate (FWE) correction for multiple comparisons of the results. Meta-regression was used to explore the effects of demographics and clinical characteristics. Results: Nineteen studies, with 22 datasets comprising 619 first-episode MDD and 707 HC, were included. The pooled and subgroup meta-analysis showed robust gray matter reductions in the left insula, the bilateral parahippocampal gyrus extending into the bilateral hippocampus, the right gyrus rectus extending into the right striatum, the right superior frontal gyrus (dorsolateral part), the left superior frontal gyrus (medial part) and the left superior parietal gyrus. Meta-regression analyses showed that higher HDRS scores were significantly more likely to present reduced gray matter volumes in the right amygdala, and the mean age of MDD patients in each study was negatively correlated with reduced gray matter in the left insula. Conclusions: The present meta-analysis revealed that structural abnormalities in the fronto-striatal-limbic and fronto-parietal networks are essential characteristics in first-episode MDD patients, which may become a potential target for clinical intervention.
| S-EPMC8282212 | biostudies-literature
Project description:BACKGROUND:Enlarged ventricles and reduced hippocampal volume are consistently found in patients with first-episode schizophrenia. Studies investigating brain structure in antipsychotic-naive patients have generally focused on the striatum. In this study, we examined whether ventricular enlargement and hippocampal and caudate volume reductions are morphological traits of antipsychotic-naive first-episode schizophrenia. METHODS:We obtained high-resolution 3-dimensional T1-weighted magnetic resonance imaging scans for 38 antipsychotic-naive first-episode schizophrenia patients and 43 matched healthy controls by use of a 3-T scanner. We warped the brain images to each other by use of a high-dimensional intersubject registration algorithm. We performed voxel-wise group comparisons with permutation tests. We performed small volume correction for the hippocampus, caudate and ventricles by use of a false discovery rate correction (p < 0.05) to control for multiple comparisons. We derived and analyzed estimates of brain structure volumes. We grouped patients as those with (n = 9) or without (n = 29) any lifetime substance abuse to examine the possible effects of substance abuse. RESULTS:We found that hippocampal and caudate volumes were decreased in patients with first-episode schizophrenia. We found no ventricular enlargement, differences in global volume or significant associations between tissue volume and duration of untreated illness or psychopathology. The hippocampal volume reductions appeared to be influenced by a history of substance abuse. Exploratory analyses indicated reduced volume of the nucleus accumbens in patients with first-episode schizophrenia. LIMITATIONS:This study was not a priori designed to test for differences between schizophrenia patients with or without lifetime substance abuse, and this subgroup was small. CONCLUSION:Reductions in hippocampal and caudate volume may constitute morphological traits in antipsychotic-naive first-episode schizophrenia patients. However, the clinical implications of these findings are unclear. Moreover, past substance abuse may accentuate hippocampal volume reduction. Magnetic resonance imaging studies addressing the potential effects of substance abuse in antipsychotic-naive first-episode schizophrenia patients are warranted.
| S-EPMC2834791 | biostudies-literature
Project description:CONTEXT:Previous magnetic resonance imaging (MRI) findings have demonstrated psychopathological symptom-related smaller gray matter volumes in various cingulate gyrus subregions in schizophrenia and bipolar disorder. However, it is unclear whether these gray matter abnormalities show a subregional specificity to either disorder and whether they show postonset progression. OBJECTIVE:To determine whether there are initial and progressive gray matter volume deficits in cingulate gyrus subregions in patients with first-episode schizophrenia (FESZ) and patients with first-episode affective psychosis (FEAFF, mainly manic) and their specificity to FESZ or FEAFF. DESIGN:A naturalistic cross-sectional study at first hospitalization for psychosis and a longitudinal follow-up approximately 1(1/2) years later. SETTING AND PARTICIPANTS:Patients were from a private psychiatric hospital. Thirty-nine patients with FESZ and 41 with FEAFF at first hospitalization for psychosis and 40 healthy control subjects (HCs) recruited from the community underwent high-spatial-resolution MRI, with follow-up scans in 17 FESZ patients, 18 FEAFF patients, and 18 HCs. Individual subjects were matched for age, sex, parental socioeconomic status, and handedness. MAIN OUTCOME MEASURES:Cingulate gyrus gray matter volumes in 3 anterior subregions (subgenual, affective, and cognitive) and 1 posterior subregion, and whether there was a paracingulate sulcus. RESULTS:At first hospitalization, patients with FESZ showed significantly smaller left subgenual (P = .03), left (P = .03) and right (P = .005) affective, right cognitive (P = .04), and right posterior (P = .003) cingulate gyrus gray matter subregions compared with HCs. Moreover, at the 1(1/2)-year follow-up, patients with FESZ showed progressive gray matter volume decreases in the subgenual (P = .002), affective (P < .001), cognitive (P < .001), and posterior (P = .02) cingulate subregions compared with HCs. In contrast, patients with FEAFF showed only initial (left, P < .001; right, P = .002) and progressive subgenual subregion abnormalities (P < .001). Finally, patients with FESZ showed a less asymmetric paracingulate pattern than HCs (P = .02). CONCLUSIONS:Patients with FEAFF and FESZ showed differences in initial gray matter volumes and in their progression. Initial and progressive changes in patients with FEAFF were confined to the subgenual cingulate, a region strongly associated with affective disorder, whereas patients with FESZ evinced widespread initial and progressively smaller volumes.
| S-EPMC2793338 | biostudies-literature