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Background  Alterations of white matter integrity during adolescence/young adulthood may contribute to the neurodevelopmental pathophysiology of bipolar disorder (BD), but it remains unknown how white matter integrity changes in BD patients during this critical period of brain development. In the present study, we aimed to identify possible age-associated alterations of white matter integrity in adolescents and young adults with BD across the age range of 13–30 years.    Methods  We divided the participants into two groups by age as follows: adolescent group involving individuals of 13–21 years old (39 patients with BD and 39 healthy controls) and young adult group involving individuals of 22–30 years old (47 patients with BD and 47 healthy controls). Diffusion tensor imaging (DTI) was performed in all participants to assess white matter integrity.    Results  In the adolescent group, compared to those of healthy controls, fractional anisotropy (FA) values were significantly lower in BD patients in the left inferior longitudinal fasciculus, splenium of the corpus callosum and posterior thalamic radiation. In the young adult group, BD patients showed significantly decreased FA values in the bilateral uncinate fasciculus, genu of the corpus callosum, right anterior limb of internal capsule and fornix compared to healthy controls. White matter impairments changed from the posterior brain to the anterior brain representing a back-to-front spatiotemporal directionality in an age-related pattern.    Conclusions  Our findings provide neuroimaging evidence supporting a back-to-front spatiotemporal directionality of the altered development of white matter integrity associated with age in BD patients during adolescence/young adulthood.

Age-Related Alterations of White Matter Integrity in Adolescents and Young Adults With Bipolar Disorder