Sulcal thickness as a vulnerability indicator for schizophrenia

University of California, Davis, Davis, California, United States
The British Journal of Psychiatry (Impact Factor: 7.99). 10/2007; 191(3):229-33. DOI: 10.1192/bjp.bp.106.034595
Source: PubMed


People with schizophrenia may demonstrate cortical abnormalities, with gyri and sulci potentially being differentially affected.
To measure frontal and temporal sulcal cortical thickness, surface area and volume in the non-psychotic relatives of patients with schizophrenia as a potential vulnerability indicator for the disorder.
An automated parcellation method was used to measure the superior frontal, inferior frontal, cingulate, superior temporal and inferior temporal sulci in the relatives of patients (n=19) and controls (n=22).
Compared with controls, relatives had reversed hemispheric asymmetry in their cingulate sulcal thickness and a bilateral reduction in their superior temporal sulcal thickness.
Cingulate and superior temporal sulcal thickness abnormalities may reflect neural abnormalities associated with the genetic liability to schizophrenia. Cortical thinning in these regions suggests that liability genes affect the dendrites, synapses or myelination process during the neurodevelopment of the cortical mantle.

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Available from: Vina M Goghari, Jan 04, 2014
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    • "Due to the putative pathogenetic neurodevelopmental mechanisms proposed to underlie schizophrenia (Rapoport et al., 2005; Weinberger, 1987) cortical thickness may be of even greater etiologic relevance than grey matter volume or density. Cortical thickness measures have been shown to be heritable (Goghari et al., 2007; Gogtay et al., 2007; Goldman et al., 2009; Winkler et al., 2010) suggesting that this aspect of cortical anatomy may represent a reliable intermediate phenotype for schizophrenia (Gottesman and Gould, 2003). "
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    ABSTRACT: Stable neuropsychological deficits may provide a reliable basis for identifying etiological subtypes of schizophrenia. The aim of this study was to identify clusters of individuals with schizophrenia based on dimensions of neuropsychological performance, and to characterize their neural correlates. We acquired neuropsychological data as well as structural and functional magnetic resonance imaging from 129 patients with schizophrenia and 165 healthy controls. We derived eight cognitive dimensions and subsequently applied a cluster analysis to identify possible schizophrenia subtypes. Analyses suggested the following four cognitive clusters of schizophrenia: (1) Diminished Verbal Fluency, (2) Diminished Verbal Memory and Poor Motor Control, (3) Diminished Face Memory and Slowed Processing, and (4) Diminished Intellectual Function. The clusters were characterized by a specific pattern of structural brain changes in areas such as Wernicke's area, lingual gyrus and occipital face area, and hippocampus as well as differences in working memory-elicited neural activity in several fronto-parietal brain regions. Separable measures of cognitive function appear to provide a method for deriving cognitive subtypes meaningfully related to brain structure and function. Because the present study identified brain-based neural correlates of the cognitive clusters, the proposed groups of individuals with schizophrenia have some external validity. Copyright © 2015. Published by Elsevier Ireland Ltd.
    Full-text · Article · Aug 2015
    • "Unaffected relatives of individuals with schizophrenia have also been shown to exhibit cortical thickness abnormalities (Goghari et al. 2007b; Gogtay et al. 2007). Healthy relatives of schizophrenia patients show reduced cingulate thickness (Goghari et al. 2007b) and sulcal thickness alterations in the cingulate sulcus and superior temporal sulcus (Goghari et al. 2007a), and young healthy siblings of schizophrenia with childhood-onset schizophrenia exhibit thinner cortices in the temporal and prefrontal regions (Gogtay et al. 2007), though these are not the consistent findings (Goldman et al. 2009). In addition, adolescents at ultra-high risk for psychosis exhibit more cortical thinning in the left middle temporal cortex than controls (Ziermans et al. 2012). "
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    ABSTRACT: Schizophrenia is a neurodevelopmental disorder associated with subtle abnormal cortical thickness and cortical surface area. However, it is unclear whether these abnormalities exist in neonates associated with genetic risk for schizophrenia. To this end, this preliminary study was conducted to identify possible abnormalities of cortical thickness and surface area in the high-genetic-risk neonates. Structural magnetic resonance images were acquired from offspring of mothers (N = 21) who had schizophrenia (N = 12) or schizoaffective disorder (N = 9), and also matched healthy neonates of mothers who were free of psychiatric illness (N = 26). Neonatal cortical surfaces were reconstructed and parcellated as regions of interest (ROIs), and cortical thickness for each vertex was computed as the shortest distance between the inner and outer surfaces. Comparisons were made for the average cortical thickness and total surface area in each of 68 cortical ROIs. After false discovery rate (FDR) correction, it was found that the female high-genetic-risk neonates had significantly thinner cortical thickness in the right lateral occipital cortex than the female control neonates. Before FDR correction, the high-genetic-risk neonates had significantly thinner cortex in the left transverse temporal gyrus, left banks of superior temporal sulcus, left lingual gyrus, right paracentral cortex, right posterior cingulate cortex, right temporal pole, and right lateral occipital cortex, compared with the control neonates. Before FDR correction, in comparison with control neonates, male high-risk neonates had significantly thicker cortex in the left frontal pole, left cuneus cortex, and left lateral occipital cortex; while female high-risk neonates had significantly thinner cortex in the bilateral paracentral, bilateral lateral occipital, left transverse temporal, left pars opercularis, right cuneus, and right posterior cingulate cortices. The high-risk neonates also had significantly smaller cortical surface area in the right pars triangularis (before FDR correction), compared with control neonates. This preliminary study provides the first evidence that early development of cortical thickness and surface area might be abnormal in the neonates at genetic risk for schizophrenia.
    No preview · Article · Nov 2014 · Brain Structure and Function
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    • "Vita and coauthors (2006) showed that morphological changes are already present in the first-episode psychosis patients. Furthermore, studies of unaffected adult first-degree relatives of schizophrenic patients demonstrated reversed hemispheric asymmetry (Goghari et al. 2007a) and reduced cortical surface area (Goghari et al. 2007b) in the cingulate and the superior temporal cortex (Schultz et al. 2009). However, several longitudinal magnetic resonance imaging (MRI) studies in the first-episode schizophrenic patients have demonstrated progressive brain changes in the years following illness onset (Gur et al. 1998, Ho et al. 2003, Kasai et al. 2003, Nakamura et al. 2007, Sun et al. 2009). "
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    ABSTRACT: Maternal deprivation (MD) leads to a variety of behavioral changes in rats which closely resemble the symptoms of schizophrenia in humans. With the aim to investigate the morphological changes which underlie the behavioral insults in this experimental paradigm we exposed 9-day-old Wistar rats to a 24 h MD. At the period of young adulthood rats were sacrificed for morphometric analysis and their brains were compared to the control group. Rats exposed to MD had a decrease in hippocampal volume (71% of the control value) as well as a decrease in the size of pyramidal (62% of the control) and granular (60% of the control) cell layers. Also, there was a decrease in the thickness of the prefrontal, retrosplenial and motor cortex compared to the control group. Analysis of the density of NeuN-immunolabeled neurons revealed a reduction in retrosplenial and prefrontal cortex (70% and 81% of the control, respectively), while there was no difference in the motor cortex. Western blot analysis confirmed a decrease in NeuN expression in the MD group compared to the control rat brain homogenates. The results of this study show that early stress in life has a long-term effect on the morphology of cognitive brain regions, most probably due to the loss of neurons during postnatal development and further contributes to our understanding of the effects of maternal separation on brain development.
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