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Variation in fourteen brain structure volumes in schizophrenia: A comprehensive meta-analysis of 246 studies.

ABSTRACT: Despite hundreds of structural MRI studies documenting smaller brain volumes on average in schizophrenia compared to controls, little attention has been paid to group differences in the variability of brain volumes. Examination of variability may help interpret mean group differences in brain volumes and aid in better understanding the heterogeneity of schizophrenia. Variability in 246 MRI studies was meta-analyzed for 13 structures that have shown medium to large mean effect sizes (Cohen's d?0.4): intracranial volume, total brain volume, lateral ventricles, third ventricle, total gray matter, frontal gray matter, prefrontal gray matter, temporal gray matter, superior temporal gyrus gray matter, planum temporale, hippocampus, fusiform gyrus, insula; and a control structure, caudate nucleus. No significant differences in variability in cortical/subcortical volumes were detected in schizophrenia relative to controls. In contrast, increased variability was found in schizophrenia compared to controls for intracranial and especially lateral and third ventricle volumes. These findings highlight the need for more attention to ventricles and detailed analyses of brain volume distributions to better elucidate the pathophysiology of schizophrenia.

SUBMITTER: Kuo SS

PROVIDER: S-EPMC6401304 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Variation in fourteen brain structure volumes in schizophrenia: A comprehensive meta-analysis of 246 studies.

Kuo Susan S SS Pogue-Geile Michael F MF

Neuroscience and biobehavioral reviews 20190104

Despite hundreds of structural MRI studies documenting smaller brain volumes on average in schizophrenia compared to controls, little attention has been paid to group differences in the variability of brain volumes. Examination of variability may help interpret mean group differences in brain volumes and aid in better understanding the heterogeneity of schizophrenia. Variability in 246 MRI studies was meta-analyzed for 13 structures that have shown medium to large mean effect sizes (Cohen's d≥0. ...[more]

PMID: 30615934

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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.

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.

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.

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Variation in fourteen brain structure volumes in schizophrenia: A comprehensive meta-analysis of 246 studies.

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Variation in fourteen brain structure volumes in schizophrenia: A comprehensive meta-analysis of 246 studies.

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