White matter fractional anisotropy over two time points in early onset schizophrenia and adolescent cannabis use disorder: A naturalistic diffusion tensor imaging study

Recurrent exposure to cannabis in adolescence increases the risk for later development of psychosis, but there are sparse data regarding the impact of cannabis use on brain structure during adolescence. This pilot study investigated the effect of cannabis use disorder (CUD) upon white matter fractional anisotropy (WM FA) values in non-psychotic treatment-seeking adolescents relative to adolescents with early onset schizophrenia-spectrum disorders (EOSS) and to healthy control (HC) participants. Diffusion tensor imaging (DTI) and tractography methods were used to examine fractional anisotropy (FA) of the cingulum bundle, superior longitudinal fasciculus (SLF), corticospinal tract (CST), inferior longitudinal fasciculus (ILF), inferior fronto-occipital fasciculus (IFOF) and uncinate fasciculus in adolescents with EOSS (. n=34), CUD (. n=19) and HC (. n=29). Participants received DTI and substance use assessments at baseline and at 18-month follow-up. Using multivariate analysis of variance, a significant main effect of diagnostic group was observed. Post-hoc testing revealed that adolescents with CUD showed an altered change in FA values in the left ILF and in the left IFOF (trend level) compared with HC adolescents. Greater consumption of cannabis during the inter-scan interval predicted a greater decrease in left ILF FA in CUD. These preliminary longitudinal data suggest that heavy cannabis use during adolescence, or some factor associated with cannabis use, is associated with an altered change in WM FA values in a fiber bundle that has been implicated in the pathophysiology of EOSS (i.e., the left ILF). Additional studies are needed to clarify the clinical significance of these findings.