White Matter and Youth Psychopathology: Case Closed?

Psychiatric problems in children (and adults) are reflected in brain networks. Remarkable advances in functional magnetic resonance imaging continue to evince a bidirectional relation between the functional flow of activation across the brain and the etiology of psychiatric disorders. This work is analogous to that of a city engineer surveying traffic to understand flow patterns, efficiency, congestion, and even the influence of city-wide conditions (eg, snowfall). Yet, the engineer further considers a factor long neglected in human neuroscience-the roads. Functional connectivity does not take place across the intercellular ether, but across a nexus of millions of interconnected axonal pathways or white matter (WM), so named for the color given by the fatty myelin surrounding the axons. Insight into the role of these tracts in the pathology of psychiatric illness continues to be limited, in contrast to the functional connectivity they support. WM tracts are among the last components of the brain to reach maturity, and their malleability in youth may play a key role in the manifestation of psychopathology in children. An emerging body of research suggests that pediatric psychopathology may be caused in part by WM alterations at both the global and the regional levels. Yet, these findings are almost exclusively derived from cross-sectional studies, which cannot model developmental course, and small sample sizes, which limit the ability to draw firm conclusions.