The Relationship of Developmental Changes in White Matter to the Onset of Psychosis

Katherine      H. Karlsgodt; Sarah      C. Jacobson; Marc      Seal; Paolo      Fusar-Poli

Abstract

Schizophrenia is a disorder with a pronounced developmental component. Accordingly, there is a growing interest in characterizing developmental changes in the period leading up to disease onset, in an effort to develop effective preventative interventions. One of the ongoing neurodevelopmental changes known to occur in the late adolescent period that often overlaps with the prodromal phase and time of onset is white matter development and myelination. In this critical review, a disruption in the normal trajectory of white matter development could potentially play an important role in the onset of psychosis. We seek to summarize the existing state of research on white matter development in prodromal subjects, with a particular focus on diffusion tensor imaging (DTI) measures. First, we describe the physiological basis of developmental white matter changes and myelination. Next, we characterize the pattern of white matter changes associated with typical development across adolescence as measured with DTI. Then, we discuss white matter changes observed in adult patients with schizophrenia and in individuals seen in genetic and clinical high risk states. Finally, we discuss the implications of these findings for future research directions and for potential therapeutic interventions.

Keywords: Schizophrenia, white matter, high-risk, development, adolescence, myelination, diffusion tensor imaging, neuroimaging, psychosis, isotropic diffusion