White matter development in infants at risk for schizophrenia.

backgroundSchizophrenia is considered a neurodevelopmental disorder with a pathophysiology that likely begins long before the onset of clinical symptoms. White matter abnormalities have been observed in schizophrenia and we hypothesized that the first 2 years of life is a period in which white matter abnormalities associated with schizophrenia risk may emerge.

methods38 infants at high risk for schizophrenia and 202 healthy controls underwent diffusion tensor MRIs after birth and at 1 and 2 years of age. Quantitative tractography was used to determine diffusion properties (fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD)) of 18 white matter tracts and a general linear model was used to analyze group differences at each age.

resultsAdjusting gestational age at birth, postnatal age at MRI, gender, MRI scanner type, and maternal education, neonates at high risk had significantly lower FA (p = 0.02) and AD (p = 0.03) in the superior segment of the left cingulate, and higher RD in the hippocampal segment of the left cingulate (p = 0.04). High risk one year olds had significantly lower FA (p < 0.01) and AD (p = 0.02) in the hippocampal segment of the left cingulate. High risk two year olds had significantly lower FA in the left prefrontal cortico-thalamic tract (p = 0.04) and higher RD in the right uncinate fasciculus (p = 0.04). None of the tract differences remained significant after correction for multiple comparisons.

conclusionsThere is evidence of abnormal white matter development in young children at risk for schizophrenia, especially in the hippocampal segment of left cingulum. These results support the neurodevelopmental theory of schizophrenia and indicate that impaired white matter may be present in early childhood.