Meta-Analysis of Gray Matter Anomalies in Schizophrenia: Application of Anatomic Likelihood Estimation and Network Analysis

Department of Psychiatry, University of Texas Health Science Center, San Antonio, Texas 78229-3900, USA.
Biological psychiatry (Impact Factor: 10.26). 06/2008; 64(9):774-81. DOI: 10.1016/j.biopsych.2008.03.031
Source: PubMed


Although structural neuroimaging methods have been widely used to study brain morphology in schizophrenia, synthesizing this literature has been difficult. With the increasing popularity of voxel-based morphometric (VBM) methods in which group differences are reported in standardized coordinates, it is possible to apply powerful meta-analytic techniques initially designed for functional neuroimaging. In this study, we performed a voxelwise, coordinate-based meta-analysis to better conceptualize the neuroanatomic correlates of schizophrenia.
Thirty-one peer-reviewed articles, with a total of 1195 patients with schizophrenia contrasted with 1262 healthy volunteers, were included in the meta-analysis. Coordinates from each article were used to create a statistical map that estimated the likelihood of between-group gray matter density differences at every brain voxel. These results were subsequently entered into a network analysis.
Patients had reduced gray matter density relative to control subjects in a distributed network of regions, including bilateral insular cortex, anterior cingulate, left parahippocampal gyrus, left middle frontal gyrus, postcentral gyrus, and thalamus. Network analysis grouped these regions into four distinct networks that potentially represent different pathologic processes. Patients had increased gray matter density in striatal regions.
This study expands on previous meta-analyses of the neuroanatomy of schizophrenia by elucidating a series of brain networks disrupted by the illness. Because it is possible that these networks are influenced by independent etiologic factors, this work should foster more detailed neural models of the illness and focus research designed to discover the mechanisms of gray matter reduction in schizophrenia.

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    • "Neuroanatomical traits derived from magnetic resonance imaging (MRI) are logical endophenotypes as their selection can be informed by a large body of the literature in clinical samples, and they are likely to be biologically intermediate between genes' functions and their more remote effects on behavioral phenotypes [Glahn et al., 2007]. Despite marked clinical and methodological heterogeneity, multiple meta-analyses of voxel-based morphometry studies in schizophrenia have identified the insula and the medial prefrontal cortex (mPFC) as the neuroanatomical regions most consistently associated with schizophrenia across all published case-control studies [Glahn et al., 2008; Fornito et al., 2009; Bora et al., 2011; Palaniyappan et al., 2012; Shepherd et al., 2012]. "
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    ABSTRACT: The insula and medial prefrontal cortex (mPFC) share functional , histological, transcriptional, and developmental characteristics , and they serve higher cognitive functions of theoretical relevance to schizophrenia and related disorders. Meta-analyses and multivariate analysis of structural magnetic resonance imaging (MRI) scans indicate that gray matter density and volume reductions in schizophrenia are the most consistent and pronounced in a network primarily composed of the insula and mPFC. We used source-based morphometry, a multivariate technique optimized for structural MRI, in a large sample of randomly ascertained pedigrees (N ¼ 887) to derive an insula– mPFC component and to investigate its genetic determinants. Firstly, we replicated the insula–mPFC gray matter component as an independent source of gray matter variation in the general population, and verified its relevance to schizophrenia in an
    American Journal of Medical Genetics Part B Neuropsychiatric Genetics 10/2015; DOI:10.1002/ajmg.b.32360 · 3.42 Impact Factor
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    • "The current finding is in line with previous reports of frontotemporal and insular gray matter reductions in SZ (Glahn et al., 2008; Nesvag et al., 2008; Rimol et al., 2010; Schultz et al., 2012b; Shepherd et al., 2012), which may reflect alterations at the neuronal and synaptic level, with consequences for cognitive networks and processing. Evidence from DTI studies suggests disruptions of fronto-temporal white matter bundles in SZ, including the uncinate fasciculus (Kubicki et al., 2002; Samartzis et al., 2014). "
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    ABSTRACT: Schizophrenia (SZ) is a psychotic disorder with significant cognitive dysfunction. Abnormal brain activation during cognitive processing has been reported, both in task-positive and task-negative networks. Further, structural cortical and subcortical brain abnormalities have been documented, but little is known about how task-related brain activation is associated with brain anatomy in SZ compared to healthy controls (HC). Utilizing linked independent component analysis (LICA), a data-driven multimodal analysis approach, we investigated structure–function associations in a large sample of SZ (n = 96) and HC (n = 142). We tested for associations between task-positive (fronto-parietal) and task-negative (default-mode) brain networks derived from fMRI activation during an n-back working memory task, and brain structural measures of surface area, cortical thickness, and gray matter volume, and to what extent these associations differed in SZ compared to HC. A significant association (p b .05, corrected for multiple comparisons) was found between a component reflecting the task-positive fronto-parietal network and another component reflecting cortical thickness in fronto-temporal brain regions in SZ, indicating increased activation with increased thickness. Other structure–function associations across, between and within groups were generally moderate and significant at a nominal p-level only, with more numerous and stronger associations in SZ compared to HC. These results indicate a complex pattern of moderate associations between brain activation during cognitive processing and brain morphometry, and extend previous findings of fronto-temporal brain abnormalities in SZ by suggesting a coupling between cortical thickness of these brain regions and working memory-related brain activation.
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    • "Neuroimaging techniques have been extensively studied over the past years, and there is now a considerable number of studies including structural and functional magnetic resonance imaging that aim to develop new diagnostic markers for schizophrenia. Relevant findings of neuroimaging studies in patients with schizophrenia include gray (Glahn et al., 2008) and white (Takayanagi et al., 2013; Bracht et al., 2014) matter abnormalities. Nevertheless, at the present moment it is difficult to draw firm conclusions regarding the Contents lists available at ScienceDirect journal homepage: "
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    ABSTRACT: Optical coherence tomography (OCT) has been recently used to investigate neuropsychiatric disorders. We aimed to study retinal OCT measures of patients with schizophrenia with respect to healthy controls, and to evaluate possible differences between recent illness episode (RIE) and non-recent illness episode (NRIE) patients. Thirty schizophrenia patients were classified as RIE (n=10) or NRIE (n=20), and compared with 30 matched controls. Statistical analyses included linear mixed-effects models to study the association between OCT measures and group membership. Multivariate models were used to control for potential confounders. In the adjusted linear mixed-effects regression model, patients had a significantly thinner retinal nerve fiber layer (RNFL) in overall measurements, and in the nasal, superior and inferior quadrants. Macular inner ring thickness and macular volume were also significantly smaller in patients than controls. Compared with controls, in the adjusted model only NRIE (but not RIE) patients had significantly reduced RNFL overall measures, superior RNFL, nasal RNFL, macular volume, and macular inner ring thickness. No significant correlation was found between illness duration and retinal measurements after controlling for age. In conclusion, retinal parameters observed using OCT in schizophrenia patients could be related to clinical status and merit attention as potential state biomarkers of the disorder. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    07/2015; 229(1-2). DOI:10.1016/j.psychres.2015.07.028
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