Regional deficits in brain volume in schizophrenia: A meta-analysis of voxel-based morphometry studies
ABSTRACT Voxel-based morphometry is a method for detecting group differences in the density or volume of brain matter. The authors reviewed the literature on use of voxel-based morphometry in schizophrenia imaging research to examine the capabilities of this method for clearly identifying specific structural differences in patients with schizophrenia, compared with healthy subjects. The authors looked for consistently reported results of relative deficits in gray and white matter in schizophrenia and evaluated voxel-based morphometry methods in order to propose a future strategy for using voxel-based morphometry in schizophrenia research.
The authors reviewed all voxel-based morphometry studies of schizophrenia that were published to May 2004 (15 studies). The studies included a total of 390 patients with a diagnosis of schizophrenia and 364 healthy volunteers.
Gray and white matter deficits in patients with schizophrenia, relative to healthy comparison subjects, were reported in a total of 50 brain regions. Deficits were reported in two of the 50 regions in more than 50% of the studies and in nine of the 50 regions in one study only. The most consistent findings were of relative deficits in the left superior temporal gyrus and the left medial temporal lobe. Use of a smaller smoothing kernel (4-8 mm) led to detection of a greater number of regions implicated in schizophrenia.
This review implicates the left superior temporal gyrus and the left medial temporal lobe as key regions of structural difference in patients with schizophrenia, compared to healthy subjects. The diversity of regions reported in voxel-based morphometry studies is in part related to the choice of variables in the automated process, such as smoothing kernel size and linear versus affine transformation, as well as to differences in patient groups. Voxel-based morphometry can be used as an exploratory whole-brain approach to identify abnormal brain regions in schizophrenia, which should then be validated by using region-of-interest analyses.
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ABSTRACT: Schizophrenia is a complex mental disorder that displays behavioral deficits such as decreased sensory gating, reduced social interaction and working memory deficits. The neurodevelopmental model is one of the widely accepted hypotheses of the etiology of schizophrenia. Subtle developmental abnormalities of the brain which stated long before the onset of clinical symptoms are thought to lead to the emergence of illness. Schizophrenia has strong genetic components but its underlying molecular pathogenesis is still poorly understood. Genetic linkage and association studies have identified several genes involved in neuronal migrations as candidate susceptibility genes for schizophrenia, although their effect size is small. Recent progress in copy number variation studies also has identified much higher risk loci such as 22q11. Based on these genetic findings, we are now able to utilize genetically-defined animal models. Here we summarize the results of neurodevelopmental and behavioral analysis of genetically-defined animal models. Furthermore, animal model experiments have demonstrated that embryonic and perinatal neurodevelopmental insults in neurogenesis and neuronal migrations cause neuronal functional and behavioral deficits in affected adult animals, which are similar to those of schizophrenic patients. However, these findings do not establish causative relationship. Genetically-defined animal models are a critical approach to explore the relationship between neuronal migration abnormalities and behavioral abnormalities relevant to schizophrenia.Frontiers in Neuroscience 03/2015; 9:74. DOI:10.3389/fnins.2015.00074
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ABSTRACT: The notion that schizophrenia patients' (SZ) sense of being detached from external reality is a core feature of the disorder has existed since the early days of its recognition and is still largely emphasized in first person accounts of SZs; however, its etiology, neurophysiological mechanism, and significance for clinical symptoms are unclear. Mind-wandering is a ubiquitous experience of being detached from reality, the underlying neural mechanism of which closely resembles the brain in a resting-state. The resting-state functional magnetic resonance imaging data of 33 SZs and 33 matched healthy controls (CNT) were acquired. All subjects answered the mind-wandering subscale of the Imaginal Processing Inventory Questionnaire. Functional connectivity maps were constructed using 82 regions of interest comprising default-mode, salience, and frontoparietal networks. SZs exhibit significantly higher mind-wandering frequency relative to CNT. The elevated mind-wandering frequency in SZs significantly correlated with positive and general symptom severity. The mind-wandering frequency was inversely correlated with connectivity degree in the right ventromedial prefrontal cortex, the brain region involved in self-experience in SZs. Our results suggest that self-disturbances in SZs can explain SZs' disconnection to the external world, leading to the manifestation of positive psychotic symptoms. This study demonstrates strong preliminary evidence that contributes significantly to resolve the complex relationship between self, world, and the brain of SZs, which may lie at the "core" of psychotic experiences. Copyright © 2015 Elsevier B.V. All rights reserved.Schizophrenia Research 04/2015; DOI:10.1016/j.schres.2015.03.021 · 4.43 Impact Factor