Variation in fourteen brain structure volumes in schizophrenia: A comprehensive meta-analysis of 246 studies.
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ABSTRACT:
SUBMITTER: Kuo SS
PROVIDER: S-EPMC6401304 | biostudies-literature | 2019 Mar
REPOSITORIES: biostudies-literature
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Project description:Although structural brain alterations in schizophrenia have been demonstrated extensively, their quantitative distribution has not been studied over the last 14 years despite advances in neuroimaging. Moreover, a volumetric meta-analysis has not been conducted in antipsychotic-naive patients. Therefore, meta-analysis on cross-sectional volumetric brain alterations in both medicated and antipsychotic-naive patients was conducted. Three hundred seventeen studies published from September 1, 1998 to January 1, 2012 comprising over 9000 patients were selected for meta-analysis, including 33 studies in antipsychotic-naive patients. In addition to effect sizes, potential modifying factors such as duration of illness, sex composition, current antipsychotic dose, and intelligence quotient matching status of participants were extracted where available. In the sample of medicated schizophrenia patients (n = 8327), intracranial and total brain volume was significantly decreased by 2.0% (effect size d = -0.17) and 2.6% (d = -0.30), respectively. Largest effect sizes were observed for gray matter structures, with effect sizes ranging from -0.22 to -0.58. In the sample of antipsychotic-naive patients (n = 771), volume reductions in caudate nucleus (d = -0.38) and thalamus (d = -0.68) were more pronounced than in medicated patients. White matter volume was decreased to a similar extent in both groups, while gray matter loss was less extensive in antipsychotic-naive patients. Gray matter reduction was associated with longer duration of illness and higher dose of antipsychotic medication at time of scanning. Therefore, brain loss in schizophrenia is related to a combination of (early) neurodevelopmental processes-reflected in intracranial volume reduction-as well as illness progression.
| S-EPMC3756785 | biostudies-literature
Project description:CONTEXT The single-nucleotide polymorphism rs1344706 in the gene ZNF804a has been associated with schizophrenia and with quantitative phenotypic features, including brain structure volume and the core symptoms of schizophrenia. OBJECTIVE To evaluate associations of rs1344706 with brain structure and the core symptoms of schizophrenia. DESIGN Case-control analysis of covariance. SETTING University-based research hospital. PARTICIPANTS Volunteer sample of 335 individuals with schizophrenia spectrum disorders (306 with core schizophrenia) and 198 healthy volunteers. MAIN OUTCOME MEASURES Cerebral cortical gray matter and white matter (WM) volumes (total and frontal, parietal, temporal, and occipital lobes), lateral ventricular cerebrospinal fluid volume, and symptom severity from the Scale for the Assessment of Negative Symptoms and the Scale for the Assessment of Positive Symptoms divided into 3 domains: psychotic, negative, and disorganized. RESULTS The rs1344706 genotype produced significant main effects on total, frontal, and parietal lobe WM volumes (F = 3.98, P = .02; F = 4.95, P = .007; and F = 3.08, P = .05, respectively). In the schizophrenia group, rs1344706 produced significant simple effects on total (F = 3.93, P = .02) and frontal WM volumes (F = 7.16, P < .001) and on psychotic symptom severity (F = 6.07, P = .003); the pattern of effects was concordant with risk allele carriers having larger volumes and more severe symptoms of disease than nonrisk homozygotes. In the healthy volunteer group, risk allele homozygotes had increased total WM volume compared with nonrisk allele carriers (F = 4.61, P = .03), replicating a previously reported association. CONCLUSIONS A growing body of evidence suggests that the risk allele of rs1347706 is associated with a distinctive set of phenotypic features in healthy volunteers and individuals with schizophrenia. Our study supports this assertion by finding that specific genotypes of the polymorphism are associated with brain structure volumes in individuals with schizophrenia and healthy volunteers and with symptom severity in schizophrenia.
| S-EPMC3852666 | biostudies-literature
Project description:A three-marker C-A-T dysbindin haplotype identified by Williams et al (PMID: 15066891) is associated with increased risk for schizophrenia, decreased mRNA expression, poorer cognitive performance, and early sensory processing deficits. We investigated whether this same dysbindin risk haplotype was also associated with structural variation in the gray matter volume (GMV). Using voxel-based morphometry, whole-volume analysis revealed significantly reduced GMVs in both the right dorsolateral prefrontal and left occipital cortex, corresponding to the behavioral findings of impaired spatial working memory and EEG findings of impaired visual processing already reported. These data provide important evidence of the influence of dysbindin risk variants on brain structure, and suggest a possible mechanism by which disease risk is being increased.
| S-EPMC3055383 | biostudies-literature
Project description:Patients with schizophrenia (SZ) display moderate reductions in brainstem volumes, including the midbrain, pons, superior cerebellar peduncle, and medulla oblongata. Here, we investigated alterations in brainstem volumes between SZ patients and healthy controls (HCs) stratified by sex. T1-weighted MRI brain scans were processed with FreeSurfer v6.0 in 156 SZ patients (61 males/95 females) and 205 HCs (133/72). Of the brainstem structures, pons volumes were significantly reduced, particularly in male SZ patients. The decreased pons volumes were correlated with lower levels of education but not duration of illness in male patients. These findings suggest that the reduction in pons volume in male patients might be occurred before or around the onset of the disorder.
| S-EPMC10024760 | biostudies-literature
Project description:ObjectiveThe zinc finger protein 804A (ZNF804A) gene encodes the protein 804A containing the C2H2 zinc finger structure, which plays an important role in embryonic nerve development and repair. Previous studies have shown a significant association between the ZNF804A genetic variation polymorphism rs1344706 and the risk of schizophrenia and brain structure abnormalities. However, the findings are inconsistent.Materials and methodsSeventeen studies on structural magnetic resonance imaging (sMRI), with 1,031 schizophrenia patients and 3,416 healthy controls, were included in the meta-analysis. These analyses were performed using Anisotropic Effect-Size Signed Differential Mapping (AES-SDM) software and Comprehensive Meta-Analysis (CMA) software.Resultsrs1344706 risk allele carriers of schizophrenia had increased gray matter in the brain regions including frontal lobe, temporal lobe, and other brain regions, but the carriers of healthy individuals had decreased gray matter and white matter integrity in the frontal lobe, central network, and other brain regions. The results of sensitivity analysis are stable, but publication bias exists in a few analyses of indexes.ConclusionAbnormalities of brain structure have a strong relationship with ZNF804A gene rs1344706 polymorphism, but the association may be different in healthy individuals and those with mental disorders.
| S-EPMC6432899 | biostudies-literature
Project description:BackgroundAlterations in intellectual ability and brain structure are important genetic markers for schizophrenia liability. How variations in these phenotypes interact with variance in schizophrenia liability due to genetic or environmental factors is an area of active investigation. Studying these genetic markers using a multivariate twin modeling approach can provide novel leads for (genetic) pathways of schizophrenia development.MethodsIn a sample of 70 twins discordant for schizophrenia and 130 healthy control twins, structural equation modeling was applied to quantify unique contributions of genetic and environmental factors on human brain structure (cortical thickness, cortical surface and global white matter fractional anisotropy [FA]), intellectual ability and schizophrenia liability.ResultsIn total, up to 28.1% of the genetic variance (22.8% of total variance) in schizophrenia liability was shared with intelligence quotient (IQ), global-FA, cortical thickness, and cortical surface. The strongest contributor was IQ, sharing on average 16.4% of the genetic variance in schizophrenia liability, followed by cortical thickness (6.3%), global-FA (4.7%) and cortical surface (0.5%). Furthermore, we found that up to 57.4% of the variation due to environmental factors (4.6% of total variance) in schizophrenia was shared with IQ (34.2%) and cortical surface (13.4%).ConclusionsIntellectual ability, FA and cortical thickness show significant and independent shared genetic variance with schizophrenia liability. This suggests that measuring brain-imaging phenotypes helps explain genetic variance in schizophrenia liability that is not captured by variation in IQ.
| S-EPMC4988741 | biostudies-literature
Project description:ImportanceSchizophrenia is associated with alterations in mean regional brain volumes. However, it is not known whether the clinical heterogeneity seen in the disorder is reflected at the neurobiological level, for example, in differences in the interindividual variability of these brain volumes relative to control individuals.ObjectiveTo investigate whether patients with first-episode schizophrenia exhibit greater variability of regional brain volumes in addition to mean volume differences.Data sourcesStudies that reported regional brain volumetric measures in patients and controls by using magnetic resonance imaging in the MEDLINE, EMBASE, and PsycINFO databases from inception to October 1, 2016, were examined.Study selectionCase-control studies that reported regional brain volumes in patients with first-episode schizophrenia and healthy controls by using magnetic resonance imaging were selected.Data extraction and synthesisMeans and variances (SDs) were extracted for each measure to calculate effect sizes, which were combined using multivariate meta-analysis.Main outcomes and measuresRelative variability of regional brain volumetric measurements in patients compared with control groups as indexed by the variability ratio (VR) and coefficient of variation ratio (CVR). Hedges g was used to quantify mean differences.ResultsA total of 108 studies that reported measurements from 3901 patients (1272 [32.6%] female) with first-episode schizophrenia and 4040 controls (1613 [39.9%] female) were included in the analyses. Variability of putamen (VR, 1.13; 95% CI, 1.03-1.24; P = .01), temporal lobe (VR, 1.12; 95% CI, 1.04-1.21; P = .004), thalamus (VR, 1.16; 95% CI, 1.07-1.26; P < .001), and third ventricle (VR, 1.43; 95% CI, 1.20-1.71; P < 1 × 10-5) volume was significantly greater in patients, whereas variability of anterior cingulate cortex volume was lower (VR, 0.89; 95% CI, 0.81-0.98; P = .02). These findings were robust to choice of outcome measure. There was no evidence of altered variability of caudate nucleus or frontal lobe volumes. Mean volumes of the lateral (g = 0.40; 95% CI, 0.29-0.51; P < .001) and third ventricles (g = 0.43; 95% CI, 0.26-0.59; P < .001) were greater, whereas mean volumes of the amygdala (g = -0.46; -0.65 to -0.26; P < .001), anterior cingulate cortex (g = -0.26; 95% CI, -0.43 to -0.10; P = .005), frontal lobe (g = -0.31; 95% CI, -0.44 to -0.19; P = .001), hippocampus (g = -0.66; 95% CI, -0.84 to -0.47; P < .001), temporal lobe (g = -0.22; 95% CI, -0.36 to -0.09; P = .001), and thalamus (g = -0.36; 95% CI, -0.57 to -0.15; P = .001) were lower in patients. There was no evidence of altered mean volume of caudate nucleus or putamen.Conclusions and relevanceIn addition to altered mean volume of many brain structures, schizophrenia is associated with significantly greater variability of temporal cortex, thalamus, putamen, and third ventricle volumes, consistent with biological heterogeneity in these regions, but lower variability of anterior cingulate cortex volume. This finding indicates greater homogeneity of anterior cingulate volume and, considered with the significantly lower mean volume of this region, suggests that this is a core region affected by the disorder.
| S-EPMC5669456 | biostudies-literature
Project description:Impairments in cognitive performance are common in schizophrenia, and these contribute to poor awareness of symptoms and treatment ('clinical insight'), which is an important predictor of functional outcome. Although relationships between cognitive impairment and reductions in regional brain volumes in patients are relatively well characterised, less is known about the brain structural correlates of clinical insight. To address this gap, we aimed to explore brain structural correlates of cognitive performance and clinical insight in the same sample. 108 patients with schizophrenia (SZH) and 94 age and gender-matched controls (CON) (from the Northwestern University Schizophrenia Data and Software Tool (NUSDAST) database) were included. SZH had smaller grey matter volume across most fronto-temporal regions and significantly poorer performance on all cognitive domains. Multiple regression showed that higher positive symptoms and poorer attention were significant predictors of insight in SZH; however, no significant correlations were seen between clinical insight and regional brain volumes. In contrast, symptomology did not contribute to cognitive performance, but robust positive relationships were found between regional grey matter volumes in fronto-temporal regions and cognitive performance (particularly executive function). Many of these appeared to be unique to SZH as they were not observed in CON. Findings suggest that while there exists a tight link between cognitive functioning and neuropathological processes affecting gross brain anatomy in SZH, this is not the case for clinical insight. Instead, clinical insight levels seem to be influenced by symptomology, attentional performance and other subject-specific variables.
| S-EPMC9261092 | biostudies-literature
Project description:Background and hypothesisSchizophrenia is highly heritable, with a polygenic effect of many genes conferring risk. Evidence on whether cumulative risk also predicts alterations in brain morphology and function is inconsistent. This systematic review examined evidence for schizophrenia polygenic risk score (sczPRS) associations with commonly used magnetic resonance imaging (MRI) measures. We expected consistent evidence to emerge for significant sczPRS associations with variation in structure and function, specifically in frontal, temporal, and insula cortices that are commonly implicated in schizophrenia pathophysiology.Study designIn accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched MEDLINE, Embase, and PsycINFO for peer-reviewed studies published between January 2013 and March 2022. Studies were screened against predetermined criteria and National Institutes of Health (NIH) quality assessment tools.Study resultsIn total, 57 studies of T1-weighted structural, diffusion, and functional MRI were included (age range = 9-80 years, Nrange = 64-76 644). We observed moderate, albeit preliminary, evidence for higher sczPRS predicting global reductions in cortical thickness and widespread variation in functional connectivity, and to a lesser extent, region-specific reductions in frontal and temporal volume and thickness. Conversely, sczPRS does not predict whole-brain surface area or gray/white matter volume. Limited evidence emerged for sczPRS associations with diffusion tensor measures of white matter microstructure in a large community sample and smaller cohorts of children and young adults. These findings were broadly consistent across community and clinical populations.ConclusionsOur review supports the hypothesis that schizophrenia is a disorder of disrupted within and between-region brain connectivity, and points to specific whole-brain and regional MRI metrics that may provide useful intermediate phenotypes.
| S-EPMC10754175 | biostudies-literature
Project description:Changed synapse density has been suggested to be involved in the altered brain connectivity underlying schizophrenia (SCZ) pathology. However, postmortem studies addressing this topic are heterogeneous and it is not known whether changes are restricted to specific brain regions. Using meta-analysis, we systematically and quantitatively reviewed literature on the density of postsynaptic elements in postmortem brain tissue of patients with SCZ compared to healthy controls. We included 3 outcome measurements for postsynaptic elements: dendritic spine density (DSD), postsynaptic density (PSD) number, and PSD protein expression levels. Random-effects meta-analysis (31 studies) revealed an overall decrease in density of postsynaptic elements in SCZ (Hedges's g: -0.33; 95% CI: -0.60 to -0.05; P = .020). Subgroup analyses showed reduction of postsynaptic elements in cortical but not subcortical tissues (Hedges's g: -0.44; 95% CI: -0.76 to -0.12; P = .008, Hedges's g: -0.11; 95% CI: -0.54 to 0.35; P = .671) and specifically a decrease for the outcome measure DSD (Hedges's g: -0.81; 95% CI: -1.37 to -0.26; P = .004). Further exploratory analyses showed a significant decrease of postsynaptic elements in the prefrontal cortex and cortical layer 3. In all analyses, substantial heterogeneity was present. Meta-regression analyses showed no influence of age, sex, postmortem interval, or brain bank on the effect size. This meta-analysis shows a region-specific decrease in the density of postsynaptic elements in SCZ. This phenotype provides an important cellular hallmark for future preclinical and neuropathological research in order to increase our understanding of brain dysconnectivity in SCZ.
| S-EPMC7442385 | biostudies-literature