Resilience to Risk for Psychopathology: The Role of White Matter Microstructural Development in Adolescence

One major risk factor for the development of psychopathology is a family history of psychopathology (FHP). Cross-sectional studies have shown that FHP is associated with alterations in white matter microstructure in adolescents without current psychopathology; however, whether these associations persist throughout adolescence, particularly in those who remain resilient to developing psychopathology, is unclear.

Sixty-six adolescents underwent diffusion-weighted imaging at baseline (12-16 years of age) and at one or two follow-up visits (142 total scans). Adolescents' parents completed a modified Family History Assessment Module to calculate FHP density (FHPD) based on familial alcohol use, substance use, and major depressive, generalized anxiety, substance-induced mood, and antisocial personality disorders. The relationship between FHPD and white matter microstructural development was examined using multilevel modeling.

FHPD was associated with significant alterations in white matter microstructure at baseline; in the bilateral superior corona radiata and left superior longitudinal fasciculus, these effects were transient (FHPD was associated with altered white matter microstructure only in early adolescence), while effects in the posterior limb of the internal capsule were persistent. Associations between FHPD and white matter microstructure in the body of the corpus callosum emerged later in adolescence.

This prospective, longitudinal study provides novel information indicating that the association between FHP and white matter microstructure previously observed in adolescents is transient in most regions but may persist into late adolescence in other regions, despite current resilience to developing psychopathology. Future studies are necessary to determine if these persistent alterations are associated with onset of psychopathology later in life.