White Matter Abnormalities Related to the Risk for Schizophrenia in Infants

Young children at risk for schizophrenia can develop abnormal white matter in the hippocampal segment of left cingulum that can be detected during the first 2 years of life, according to a study published in Schizophrenia Research.

The researchers of the study recruited pregnant women with schizophrenia or schizoaffective disorder and control mothers without a history of major psychiatric illness or active substance use during pregnancy between 2003 and 2014 from the central part of North Carolina. There were a total of 240 participants (202 controls, 38 high risk) for whom data were collected from their offspring at 2 weeks, 1 year, and 2 years of age.

Magnetic resonance imaging data were collected from unsedated infants scanned during natural sleep. A weighted least-squares algorithm was used to estimate tensors. The researchers selected 18 fiber tracts segments from combined neonate and pediatric (0-2y) diffusion tensor imaging atlas that are associated with cognitive development or altered in schizophrenia for analysis. Images of every participant were deformably registered to the atlas and for group analysis, statistical diffusion profiles were generated for fractional anisotropy (FA), axial diffusivity, and radial diffusivity at equally spaced points along the length of each fiber tract.

In the high-risk group, the diffusion properties were consistently abnormal at all the 3 stages (neonatal, 1, and 2 years) in the hippocampal segment of the left cingulum (higher radial diffusivity at birth [P <.01], lower FA [P <.01] and axial diffusivity [P =.02] at 1 year, and lower FA [P =.01] at 2 year). The authors also suggested that there may be microstructure differences in the infants at high risk for schizophrenia that need further investigation. Investigators also pointed out that maternal education may also affect white matter microstructure associated with schizophrenia in early childhood. Furthermore, there was no impact of paternal age on the results of the current study.

There are some important limiting factors in the study. For example, the sample sizes of the high-risk group were much smaller than the control. The high-risk group also had children from mothers with differing conditions. The authors pointed out some technical limitations of the study as well, such as usage of different scanners and directions in the study and head motion during the scans.

Researchers conclude that the results from the current study show evidence of abnormal white matter development in infants at risk for schizophrenia, in the regions that are known to be present in adults with schizophrenia and hence support the neurodevelopmental theory of schizophrenia.

Reference
Ahn SJ, Cornea E, Murphy V, Styner M, Jarskog LF, Gilmore JH. White matter development in infants at risk for schizophrenia [published online June 8, 2019]. Schizophr Res. doi:10.1016/j.schres.2019.05.039