White Matter Microstructure in Early-Onset Schizophrenia: A Systematic Review of Diffusion Tensor Imaging Studies

Abstract

Objective: Neurodevelopmental processes and neural connectivity are thought to play pivotal roles in schizophrenia. This article reviews diffusion tensor imaging (DTI) studies of brain white matter connections and microstructure and their development in patients with early-onset schizophrenia (EOS), that is, schizophrenia with an age of onset before 18 years.

Method: A systematic literature search revealed 21 original case-control DTI studies of children and/or adolescents with EOS.

Results: Nearly all studies report significantly lower regional fractional anisotropy (FA) in patients with EOS than in healthy control participants. However, the anatomical locations and extent of these differences are highly variable across studies. Furthermore, consistent evidence for associations between DTI indices and age of onset, medication variables, and measures of symptomatology and cognition in EOS is lacking. Only 3 available studies have investigated cross-sectional age-related differences or longitudinal changes in DTI measures in adolescents with EOS. The results are mixed, with different studies indicating diverging, converging, or parallel developmental FA trajectories between patients and controls.

Conclusion: The study of brain structural connectivity, as inferred from DTI, and its development in EOS may inform us on the origin and ontogeny of schizophrenia. We suggest some directions for future research in this field and argue for increased focus on developmental questions. Specifically, further investigations of age of onset effects and multimethod longitudinal studies of structural and functional connectivity development before, at, and after onset of schizophrenia and related syndromes in children and adolescents are called for.

Keywords: brain development; diffusion tensor imaging; early-onset; schizophrenia; white matter.