Sex-specific patterns of white matter microstructure are associated with emerging depression during adolescence

Prior research has demonstrated associations between adolescent depression and alterations in the white matter microstructure of fiber tracts implicated in emotion regulation. Using diffusion tensor imaging, this study explored premorbid, sex-specific white matter microstructural features that related to future emergence of major depressive disorder (MDD) during adolescence and young adulthood. Adolescents from the National Consortium on Alcohol and Neurodevelopment in Adolescence study, who were 12-21 years old at study entry and had not experienced major depression as of the baseline assessment, were selected for inclusion (N = 462, n = 223 female adolescents). Over five years of annual follow-up, 63 participants developed a diagnosis of MDD, as determined by the Computerized Semi-Structured Assessment for the Genetics of Alcoholism (n = 39 female adolescents). A whole-brain multivariate modeling approach was used to examine the relationship between fractional anisotropy (FA) at baseline and emergence into MDD, as a function of sex, controlling for age at baseline. Among female adolescents, those who developed MDD had significantly lower baseline FA in a portion of left precentral gyrus white matter, while male adolescents exhibited the opposite pattern. These results may serve as indirect microstructural markers of risk and targets for the prevention of depression during adolescence.