The Anatomy of First Episode and Chronic Schizophrenia: An ALE Meta-analysis

University of Cambridge, Cambridge, England, United Kingdom
American Journal of Psychiatry (Impact Factor: 12.3). 05/2008; 165(8):1015-23. DOI: 10.1176/appi.ajp.2008.07101562
Source: PubMed


The authors sought to map gray matter changes in first-episode schizophrenia and to compare these with the changes in chronic schizophrenia. They postulated that the data would show a progression of changes from hippocampal deficits in first-episode schizophrenia to include volume reductions in the amygdala and cortical gray matter in chronic schizophrenia.
A systematic search was conducted for voxel-based structural MRI studies of patients with first-episode schizophrenia and chronic schizophrenia in relation to comparison groups. Meta-analyses of the coordinates of gray matter differences were carried out using anatomical likelihood estimation. Maps of gray matter changes were constructed, and subtraction meta-analysis was used to compare them.
A total of 27 articles were identified for inclusion in the meta-analyses. A marked correspondence was observed in regions affected by both first-episode schizophrenia and chronic schizophrenia, including gray matter decreases in the thalamus, the left uncus/amygdala region, the insula bilaterally, and the anterior cingulate. In the comparison of first-episode schizophrenia and chronic schizophrenia, decreases in gray matter volume were detected in first-episode schizophrenia but not in chronic schizophrenia in the caudate head bilaterally; decreases were more widespread in cortical regions in chronic schizophrenia.
Anatomical changes in first-episode schizophrenia broadly coincide with a basal ganglia-thalamocortical circuit. These changes include bilateral reductions in caudate head gray matter, which are absent in chronic schizophrenia. Comparing first-episode schizophrenia and chronic schizophrenia, the authors did not find evidence for the temporolimbic progression of pathology from hippocampus to amygdala, but there was evidence for progression of cortical changes.

    • "These features can then be compared at subject level for their functional implications. Under this strategy, biomarkers have been consistently identified from both healthy and diseased human brains, characterizing neural development , ageing, Alzheimer's disease, schizophrenia, and so on [Ellison-Wright et al., 2008; Frisoni et al., 2010; Giedd and Rapoport, 2010; Raz and Rodrigue, 2006]. More importantly, many attributes of brain structure, including both global and regional traits, are confirmed to be genetically influenced in twin studies, with heritability estimated around 40–90% [Peper et al., 2007; Thompson et al., 2001; Winkler et al., 2010]. "
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    ABSTRACT: While detecting genetic variations underlying brain structures helps reveal mechanisms of neural disorders, high data dimensionality poses a major challenge for imaging genomic association studies. In this work, we present the application of a recently proposed approach, parallel independent component analysis with reference (pICA-R), to investigate genomic factors potentially regulating gray matter variation in a healthy population. This approach simultaneously assesses many variables for an aggregate effect and helps to elicit particular features in the data. We applied pICA-R to analyze gray matter density (GMD) images (274,131 voxels) in conjunction with single nucleotide polymorphism (SNP) data (666,019 markers) collected from 1,256 healthy individuals of the Brain Imaging Genetics (BIG) study. Guided by a genetic reference derived from the gene GNA14, pICA-R identified a significant SNP-GMD association (r = -0.16, P = 2.34 × 10(-8) ), implying that subjects with specific genotypes have lower localized GMD. The identified components were then projected to an independent dataset from the Mind Clinical Imaging Consortium (MCIC) including 89 healthy individuals, and the obtained loadings again yielded a significant SNP-GMD association (r = -0.25, P = 0.02). The imaging component reflected GMD variations in frontal, precuneus, and cingulate regions. The SNP component was enriched in genes with neuronal functions, including synaptic plasticity, axon guidance, molecular signal transduction via PKA and CREB, highlighting the GRM1, PRKCH, GNA12, and CAMK2B genes. Collectively, our findings suggest that GNA12 and GNA14 play a key role in the genetic architecture underlying normal GMD variation in frontal and parietal regions. Hum Brain Mapp, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
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    • "Schizophrenia is a devastating and disabling neuropsychiatric disorder. The neural mechanisms of this disorder have been attributed to structural and functional abnormalities of the brain [1] [2] [3] [4] [5]. Schizophrenia patients have exhibited functional changes in both task-evoked activation and spontaneous brain activity [6] [7]. "
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    ABSTRACT: Altered spontaneous brain activity as measured by ALFF, fALFF, and ReHo has been reported in schizophrenia, but no consensus has been reached on alternations of these indexes in the disorder. We aimed to clarify the regional alterations in ALFF, fALFF, and ReHo in schizophrenia using a meta-analysis and a large-sample validation. A meta-analysis of activation likelihood estimation was conducted based on the abnormal foci of ten studies. A large sample of 86 schizophrenia patients and 89 healthy controls was compared to verify the results of the meta-analysis. Meta-analysis demonstrated that the alternations in ALFF and ReHo had similar distribution in schizophrenia patients. The foci with decreased ALFF/fALFF and ReHo in schizophrenia were mainly located in the somatosensory cortex, posterior parietal cortex, and occipital cortex; however, foci with increased ALFF/fALFF and ReHo were mainly located in the bilateral striatum, medial temporal cortex, and medial prefrontal cortex. The large-sample study showed consistent findings with the meta-analysis. These findings may expound the pathophysiological hypothesis and guide future research.
    Full-text · Article · Jul 2015
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    • "The confounding effect of statistically significant mean age difference between two groups on neuroimaging could not be ruled out. Researches have shown age related volumetric differences in brain structures in the vicinity of CSP (Ellison-Wright et al., 2008;Meisenzahl et al., 2008;Trzesniak et al., 2011). Hence, whether enlarged CSP in study group was due to age related or due to neurodevelopmental disease process could not be established. "
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    ABSTRACT: Like prevalence of abnormal cavum septum pellucidum in patients of schizophrenia remains controversial, its role in clinical outcome, duration of illness and effect on treatment remains less understood as well. Our study examined clinical correlates of enlarged cavum septum pellucidum in schizophrenia. A total of 139 patients diagnosed with schizophrenia during the year 2012 and 2013 were taken for the study. We compared them in respect to the presence and absence of enlarged cavum septum pellucidum. We found 16 patients with enlarged cavum septum pellucidum and were compared with those without enlarged cavum septum pellucidum for socio-demographic and clinical variables. We also correlated these clinical variables with dimension of cavum septum pellucidum. We found statistically significant increased current age and duration of illness in patients with enlarged cavum septum pellucidum. The implications of these findings are discussed with possible confounding effect of current age on neuroimaging. No meaningful correlation was found. No difference in clinical variables was found. Retrospective design and use of computed tomography were limitation of our study. Copyright © 2015 Elsevier B.V. All rights reserved.
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