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


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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    • "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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    • "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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    • "Also in the NYU HRS, FA was higher in HR in the left subgenual ACC, the bilateral pontine tegmental white matter and the right middle frontal gyri, suggesting differences in white matter development in HR compared to controls. In the UNC HRS (which conducted imaging of neonatal HR offspring in utero), there were no differences in the diffusion properties of the genu and splenium of the CC and corticospinal tracts in offspring of mothers with SZ compared to control offspring) [Gilmore et al., 2010]. "
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