Lu LH, Zhou XJ, Fitzgerald J, Keedy SK, Reilly JL, Passarotti AM, Sweeney JA, Pavuluri M. Microstructural abnormalities of white matter differentiate pediatric and adult onset bipolar disorder. Bipolar Disord 2012: 14: 597–606. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S.Objectives:  White‐matter microstructure, known to undergo significant developmental transformation, is abnormal in bipolar disorder (BD). Available evidence suggests that white‐matter deviation may be more pronounced in pediatric than adult‐onset BD. The present study aimed to examine how white‐matter microstructure deviates from a typical maturational trajectory in BD.Methods:  Fractional anisotropy (FA) was measured in 35 individuals presenting with first episode BD (type I) and 46 healthy controls (HC) (aged 9–42) using diffusion tensor imaging (DTI). Patients were medication free and close to illness onset at the time of the DTI scans. Tract‐based spatial statistics were used to examine the center of white‐matter tracts, and FA was extracted from nine tracts of interest. Axial, radial, and mean diffusivity were examined in post‐hoc analyses.Results:  The left anterior limb of the internal capsule (ALIC) showed significantly lower FA in pediatric than adult‐onset BD. The lower FA in BD was due primarily to greater radial, rather than decreased axial, diffusivity.Conclusions:  The ALIC connects the frontal lobes with archistriatum, thalamus, and medial temporal regions, and alteration in these pathways may contribute to mood dysregulation in BD. Abnormalities in this pathway appear to be associated with an earlier onset of illness and thus may reflect a greater susceptibility to illness.