Prenatal and neonatal brain structure and white matter maturation in children at high risk for schizophrenia

Abstract

Objective: 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.

Method: 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.

Results: 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.

Conclusions: 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.

Figures

FIGURE 1. Representative MRI Images and Image Analysis of Brain Structure in Infants at High Genetic Risk for Schizophreniaa

aPart A is a T2-weighted image with tissue segmented into CSF (yellow), gray matter (blue), unmyelinated white matter (green), and myelinated white matter (red). Part B displays the regional parcellation; see text for details. Part C is a fractional anisotropy image. Part D displays the white matter tractography involving the genu of the corpus callosum (G), splenium of the corpus callosum (S), and corticospinal tract (CS).