Altered white matter integrity in pediatric bipolar disorder and the potential role of psychotic symptoms revealed by free water elimination corrected and superficial white matter DTI analyses.

Little is known about the relationship of white matter (WM) fasciculi abnormalities with pathologies of pediatric bipolar disorder (PBD). The aim of the present study was to investigate the abnormalities of WM integrity, characterized by free water elimination (FWE) corrected and superficial WM (SWM) diffusion tensor imaging (DTI) metrics in patients with PBD, and in particular, stratifying groups by psychotic symptoms. DTI data for 27 PBD patients with psychotic symptoms (P-PBD), 25 PBD patients without psychotic symptoms (NP-PBD), and 19 healthy controls (HCs) were examined. The commonly used DTI metrics (FA: fractional anisotropy, MD: mean diffusivity, RD: radial diffusivity, and AD: axial diffusivity), derived using a classical DTI model, a FWE model, and a SWM model, respectively, were computed. The differences in DTI metrics were explored among three groups using tract-based spatial statistics, as well as between-group differences, in regions of interest. In addition, support vector machine (SVM) analyses with leave-one-out cross-validation were applied to verify the capacity of altered WM indices in distinguishing these study groups. Analyses of covariance revealed significant FW-FA differences in three clusters located at the left parietal lobe, left occipital lobe, and right frontal lobe, as well as significant SWM-FA differences in four clusters located at the bilateral occipital lobe, left parietal lobe, and right frontal lobe. As compared with HCs, both groups of PBD patients showed decreased FW-FA and SWM-FA values in aforementioned regions, respectively. Notably, the P-PBD group further exhibited decreased FW-FA and SWM-FA values mainly distributed in the left middle occipital gyrus (MOG) containing fibers from the superior longitudinal fasciculus, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, and forceps major when compared to the NP-PBD group. Brain regions with altered FW-FA and SWM-FA could effectively discriminate PBD patients from HCs in each SVM analysis. The present study suggested that disrupted WM integrity in the frontal-parietal-occipital regions might be involved in the pathologies of PBD and further WM damage in the left MOG might contribute to the development of psychotic symptoms in PBD.