Regional Deficits in Brain Volume in Schizophrenia: A Meta-Analysis of Voxel-Based Morphometry Studies

Department of Experimental Psychology, University of Oxford, Oxford, England, United Kingdom
American Journal of Psychiatry (Impact Factor: 12.3). 01/2006; 162(12):2233-45. DOI: 10.1176/appi.ajp.162.12.2233
Source: PubMed


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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    • "In modulated images, the total volume of gray matter is the same as in the original images as modulation scales by the same amount of expansion or contraction that is applied during normalization. The modulated gray matter volumes were smoothed with a Gaussian kernel of 8 mm full width at half maximum (FWHM), which is the optimal kernel for detecting morphometric differences in small as well as larger neural structures (Honea et al., 2005; White et al., 2001). No outliers were identified via a homogeneity check, thus the normalized, modulated, and smoothed gray matter segments of all 125 subjects were included in the statistical analyses. "
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    ABSTRACT: Alexithymia, a deficit in emotional self-awareness, and deficits in empathy, which encompasses the awareness of other's emotions, are related constructs that are both associated with a range of psychopathological disorders. Neuroimaging studies suggest that there is overlap between the neural bases of alexithymia and empathy, but no systematic comparison has been conducted so far. The aim of this structural magnetic resonance imaging study was to disentangle the overlap and differences between the morphological profiles of the cognitive and affective dimensions of alexithymia and empathy, and to find out to what extent these differ between women and men. High-resolution T1 anatomical images were obtained from 125 healthy right-handers (18 - 42 years), 70 women and 55 men. By means of voxel-based morphometry, region of interest (ROI) analyses were performed on gray matter volumes of several anatomically defined a-priori regions previously linked to alexithymia and empathy. Partial correlations were conducted within the female and male group using ROI parameter estimates as dependent variables and the cognitive and affective dimensions of alexithymia and empathy, respectively, as predictors, controlling for age. Results were considered significant if they survived Holm-Bonferroni correction for multiple comparisons. The left amygdala was identified as a key substrate of both alexithymia and empathy. This association was characterized by an opposite pattern: The cognitive alexithymia dimension was linked to smaller, the two empathy dimensions to larger left amygdala volume. While sex-specific effects were not observed for empathy, they were evident for the affective alexithymia dimension: Men - but not women - with difficulty fantasizing had smaller gray matter volume in the middle cingulate cortex. Moreover, structural covariance patterns between the left amygdala and other emotion-related brain regions differed markedly between alexithymia and empathy. These differences may underlie the complex patterns of deficits in emotional self- and other-awareness observed across a range of psychopathological conditions. Copyright © 2015. Published by Elsevier Inc.
    NeuroImage 08/2015; 122. DOI:10.1016/j.neuroimage.2015.08.014 · 6.36 Impact Factor
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    • "While the handful of previous fMRI studies of facial emotion perception in relatives did not report abnormalities in these regions, an fMRI study of language processing in schizophrenia and relatives reported reduced fusiform activation in both groups compared to controls (Li et al., 2007). Moreover, structural MRI studies indicate that both patients (Honea et al., 2005) and relatives (Goghari et al., 2011) have reduced fusiform grey matter volumes, particularly for the left hemisphere. Our finding of left hemisphere hypoactivation converges with these findings, and provides additional evidence that temporo-occipital lobe abnormalities in schizophrenia are associated with the genetic liability to the disorder. "
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    ABSTRACT: Deficits in facial emotion perception in schizophrenia may be a marker of disorder liability. Previous functional magnetic resonance imaging (fMRI) studies investigating these deficits have been limited by task demands that may recruit other impaired cognitive processes in schizophrenia. We used a family study design along with a passive viewing task during fMRI to investigate brain activation abnormalities underlying facial emotion perception in schizophrenia and examine whether such abnormalities are associated with the genetic liability to the disorder. Twenty-eight schizophrenia patients, 27 nonpsychotic relatives, and 27 community controls passively viewed images of facial emotions during an fMRI scan. Analyses revealed hypoactivation in face processing areas for both patients and relatives compared to controls, and hyperactivation in relatives compared to both patients and controls for frontal regions implicated in emotion processing. Results suggest that activation abnormalities during facial emotion perception are manifestations of the genetic liability to schizophrenia, and may be accompanied by compensatory mechanisms in relatives. Studying mechanisms in nonpsychotic relatives is a valuable way to examine effects of the unexpressed genetic liability to schizophrenia on the brain and behaviour. Copyright © 2015 Elsevier B.V. All rights reserved.
    Schizophrenia Research 07/2015; 168(1). DOI:10.1016/j.schres.2015.07.012 · 3.92 Impact Factor
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    • "In addition, not only do the current results agree with that of prior research in finding deficiencies in facial expressions of emotion specific to negative emotions in schizophrenia, but there is evidence of the brain-based nature of this deficit. Neuroanatomical anomalies are consistently reported in schizophrenia, and some of the more focal neuroanatomical anomalies tend to occur in frontal and temporal structures (Honea et al., 2005; Torres et al., 2013) implicated in facial emotion recognition (Nakamura et al., 2014), and deficient facial emotion recognition in schizophrenia has been linked to anomalous activation of these areas (Baird et al., 1999). While the nature of these findings may vary with disorder subtype (Pinkham et al., 2015), several studies have found hypoactivation specifically in response to the negatively valenced emotions (Ji et al., 2015; Phillips et al., 1999) measured behaviorally in the current study. "
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    ABSTRACT: Facial emotion recognition has been found to be impaired in schizophrenia, although overall results have been inconclusive. A new set of facial emotion stimuli with Chinese faces was developed, using static and dynamic avatars, the identification of which were subsequently validated in 562 healthy control subjects. This test was then used to identify facial emotion recognition accuracy in 44 patients with schizophrenia and 41 healthy controls. Overall, patients identified facial emotions significantly worse than healthy controls (p = 0.018) with a significant main effect for type of emotion (p = 0.016). Patients performed significantly worse in fear (p = 0.029) and sadness (p = 0.037), and marginally worse in anger (p = 0.052). No significant differences were evident in contempt (p = 0.254) or happiness (p = 0.943). Regarding error rates of misattribution, patients overidentified contempt (p = 0.035) and sadness (p = 0.01), but not anger, fear, or happiness. Conclusion, patients of Chinese ethnicity with schizophrenia may have significantly greater difficulties identifying negative, but not positive emotions.
    The Journal of nervous and mental disease 07/2015; 203(9). DOI:10.1097/NMD.0000000000000358 · 1.69 Impact Factor
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