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Article Prenatal and Neonatal Brain Structure and White Matter Maturation in Children at High Risk for Schizophrenia

Department of Psychiatry, Columbia University, New York, New York, United States
American Journal of Psychiatry (Impact Factor: 12.3). 09/2010; 167(9):1083-91. DOI: 10.1176/appi.ajp.2010.09101492
Source: PubMed

ABSTRACT

Schizophrenia is a neurodevelopmental disorder associated with abnormalities of brain structure and white matter, although little is known about when these abnormalities arise. This study was conducted to identify structural brain abnormalities in the prenatal and neonatal periods associated with genetic risk for schizophrenia.
Prenatal ultrasound scans and neonatal structural magnetic resonance imaging (MRI) and diffusion tensor imaging were prospectively obtained in the offspring of mothers with schizophrenia or schizoaffective disorder (N=26) and matched comparison mothers without psychiatric illness (N=26). Comparisons were made for prenatal lateral ventricle width and head circumference, for neonatal intracranial, CSF, gray matter, white matter, and lateral ventricle volumes, and for neonatal diffusion properties of the genu and splenium of the corpus callosum and corticospinal tracts.
Relative to the matched comparison subjects, the offspring of mothers with schizophrenia did not differ in prenatal lateral ventricle width or head circumference. Overall, the high-risk neonates had nonsignificantly larger intracranial, CSF, and lateral ventricle volumes. Subgroup analysis revealed that male high-risk infants had significantly larger intracranial, CSF, total gray matter, and lateral ventricle volumes; the female high-risk neonates were similar to the female comparison subjects. There were no group differences in white matter diffusion tensor properties.
Male neonates at genetic risk for schizophrenia had several larger than normal brain volumes, while females did not. To the authors' knowledge, this study provides the first evidence, in the context of its limitations, that early neonatal brain development may be abnormal in males at genetic risk for schizophrenia.

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    • "Recent MR imaging studies of neonates at high genetic risk for schizophrenia have revealed structural abnormalities in the lateral ventricle, total gray matter (GM), cerebrospinal fluid, and intracranial volumes in male neonates (Gilmore et al. 2010a). Altered brain structural network was also found in high-risk neonates (Shi 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.
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    • "Thousands of diffusion MRI (dMRI) datasets are collected every day across the world in studies of autism (Wolff et al., 2012), schizophrenia (Gilmore et al., 2010), Huntington's disease (Dumas et al., 2012), Alzheimer's disease (Rose et al., 2000), Parkinson's disease, substance abuse (Parnell et al., 2009; Coleman et al., 2012) and many other conditions. White matter (WM) degeneration is often identified as a crucial biomarker for all these diseases. "
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    ABSTRACT: In the last decade, diffusion MRI (dMRI) studies of the human and animal brain have been used to investigate a multitude of pathologies and drug-related effects in neuroscience research. Study after study identifies white matter (WM) degeneration as a crucial biomarker for all these diseases. The tool of choice for studying WM is dMRI. However, dMRI has inherently low signal-to-noise ratio and its acquisition requires a relatively long scan time; in fact, the high loads required occasionally stress scanner hardware past the point of physical failure. As a result, many types of artifacts implicate the quality of diffusion imagery. Using these complex scans containing artifacts without quality control (QC) can result in considerable error and bias in the subsequent analysis, negatively affecting the results of research studies using them. However, dMRI QC remains an under-recognized issue in the dMRI community as there are no user-friendly tools commonly available to comprehensively address the issue of dMRI QC. As a result, current dMRI studies often perform a poor job at dMRI QC. Thorough QC of dMRI will reduce measurement noise and improve reproducibility, and sensitivity in neuroimaging studies; this will allow researchers to more fully exploit the power of the dMRI technique and will ultimately advance neuroscience. Therefore, in this manuscript, we present our open-source software, DTIPrep, as a unified, user friendly platform for thorough QC of dMRI data. These include artifacts caused by eddy-currents, head motion, bed vibration and pulsation, venetian blind artifacts, as well as slice-wise and gradient-wise intensity inconsistencies. This paper summarizes a basic set of features of DTIPrep described earlier and focuses on newly added capabilities related to directional artifacts and bias analysis.
    Full-text · Article · Jan 2014 · Frontiers in Neuroinformatics
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    • "There is very little literature looking at infants or toddlers who subsequently develop schizophrenia, given the methodological complexities of such a study. That being said, offspring of mothers with schizophrenia were found on average to have larger intracranial volumes, greater volumes of CSF, and greater gray matter volume on structural MRI in male neonates, compared to controls, although controlling for total intracranial volume resulted in all differences being non-significant (27). "
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    ABSTRACT: Background: Autism spectrum disorder (ASD) and childhood onset schizophrenia (COS) are pediatric neurodevelopmental disorders associated with significant morbidity. Both conditions are thought to share an underlying genetic architecture. A comparison of neuroimaging findings across ASD and COS with a focus on altered neurodevelopmental trajectories can shed light on potential clinical biomarkers and may highlight an underlying etiopathogenesis. Methods: A comprehensive review of the medical literature was conducted to summarize neuroimaging data with respect to both conditions in terms of structural imaging (including volumetric analysis, cortical thickness and morphology, and region of interest studies), white matter analysis (include volumetric analysis and diffusion tensor imaging) and functional connectivity. Results: In ASD, a pattern of early brain overgrowth in the first few years of life is followed by dysmaturation in adolescence. Functional analyses have suggested impaired long-range connectivity as well as increased local and/or subcortical connectivity in this condition. In COS, deficits in cerebral volume, cortical thickness, and white matter maturation seem most pronounced in childhood and adolescence, and may level off in adulthood. Deficits in local connectivity, with increased long-range connectivity have been proposed, in keeping with exaggerated cortical thinning. Conclusion: The neuroimaging literature supports a neurodevelopmental origin of both ASD and COS and provides evidence for dynamic changes in both conditions that vary across space and time in the developing brain. Looking forward, imaging studies which capture the early post natal period, which are longitudinal and prospective, and which maximize the signal to noise ratio across heterogeneous conditions will be required to translate research findings into a clinical environment.
    Full-text · Article · Dec 2013 · Frontiers in Psychiatry
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