White matter differences among adolescents reporting psychotic experiences: A population-based diffusion magnetic resonance imaging study

O'Hanlon, Erik, Leemans, A, Kelleher, Ian, Clarke, Mary C., Roddy, Sarah, Coughlan, Helen, Harley, Michelle, Amico, Francesco, Hoscheit, Matthew J., Tiedt, Lauren, Tabish, Javeria, McGettigan, Anna, Frodl, Thomas, Cannon, Mary


JAMA Psychiatry 72 (7), p. 668-677


IMPORTANCE Abnormal brain connectivity is thought to have a key role in the pathophysiology of schizophrenia and other psychotic disorders. White matter (WM) abnormalities have been reported in patients with schizophrenia and patients with prodromal syndromes. To our knowledge, no studies have yet reported on WM differences among adolescents who report psychotic experiences, a known vulnerability group for later severe psychopathology, including psychotic illness. OBJECTIVE To study WM differences using diffusion-weighted imaging (whole-brain and tractography analyses) in adolescents who report psychotic experiences. DESIGN, SETTING, AND PARTICIPANTS A population-based case-control study of 28 adolescents 13 to 16 years old who reported psychotic experiences and a matched sample of 28 adolescents who did not report psychotic experiences drawn from a sample of 212 young people recruited from primary schools in North Dublin and Kildare, Ireland. The study dates were 2008 to 2011. INTERVENTIONS High-angular resolution diffusion-weighted imaging data were used to conduct whole-brain WM analysis using tract-based spatial statistics. Based on this exploratory analysis, a tractography-based approach with constrained spherical deconvolution was performed. RESULTS Compared with control group participants, adolescents who reported psychotic experiences showed WM differences bilaterally in striatal regions in proximity to the putamen (increased fractional anisotropy, P = .01, false discovery rate corrected), and tractography identified significant WM differences bilaterally in the uncinate fasciculus (increased fractional anisotropy in the right [P = .001] and axial diffusivity in the left [P = .01] uncinate fasciculus, respectively). Similar patterns of WM differences between groups survived adjustment for other psychopathology, indicating some specificity for psychotic experiences. Exploratory along-tract analyses showed WM differences between groups in the frontal projections of the right inferior fronto-occipital fasciculus (reduced radial diffusivity in approximately 32%of the tract segment [P ≤.0001] and increased fractional anisotropy in approximately 16%of the tract segment [P ≤.0009]). CONCLUSIONS AND RELEVANCE In a population-based study of adolescents reporting psychotic experiences, we found a number of WM differences in the region of the putamen located between the inferior fronto-occipital fasciculus and the uncinate fasciculus and in the left parietal regions that include the fiber bundle of the superior longitudinal fasciculus. These findings suggest that subtle structural changes to WM microstructure are not merely a consequence of disorder but may index vulnerability to psychosis even at a very early age.