T95. FREE WATER IMAGING REVEALS DIFFERENTIAL PATTERNS OF WHITE MATTER ALTERATIONS IN INDIVIDUALS WITH ADOLESCENT-ONSET SCHIZOPHRENIA AND BIPOLAR DISORDER.

Background Recent studies using an advanced diffusion model, Free Water Imaging (FWI), have demonstrated that fractional anisotropy (FA) reductions in schizophrenia (SZ) patients were mostly associated with increases in extracellular free-water (FW) in the early stages of the illness, while patients with chronic SZ predominantly showed decreases in FA of the tissue (FAt). Conversely, a study comparing patients with chronic bipolar disorder (BP) and healthy individuals (HC) reported that FW was increased in BP subjects suggesting a different trajectory compared to the one found in SZ patients. The present study is the first to investigate WM properties in adolescent-onset SZ and BP together. Utilizing conventional diffusion tensor imaging and FWI, we aim to identify imaging biomarkers that could help differentiate the biological nature of these two disorders. Methods Forty-eight (20F/28M) SZ patients (mean age: 16.28), 15 (7F/8M) BP patients (mean age: 15.52) and 35 (18F/17M) HCs (mean age: 15.65) were included in the study. The mean duration of psychosis (DOP) was 0.97 years in BP subjects and 1.84 years in SZ subjects. All participants underwent diffusion MRI scanning (1.5 T Siemens Magnetom Sonata, 60 gradient directions with b = 1000 m/s2 and 5 images with b = 0 m/s2). Each scan was repeated three times to increase the signal-to-noise ratio and was subsequently corrected for motion and eddy currents before getting averaged. FA, FAt and FW maps were calculated and then skeletonized using Tract-Based Spatial Statistics (TBSS). Voxel-wise, non-parametric statistics were conducted with 5000 permutations and threshold-free cluster enhancement controlling for age, sex and motion. Statistical maps were family-wise error corrected at a significance level of p < 0.05. Results Significant ANOVA effects were explained by pairwise post-hoc t-tests revealing the expected global FA decrease in SZ and BP subjects comparing to HCs. Further, lower FA restricted to the corpus callosum was found in BP comparing to SZ individuals. Applying FWI, BP subjects had both spatially limited decreased FAt and widespread increased FW comparing with HCs, while SZ subjects had extensively decreased FAt but not increased FW. Comparing between the BP and SZ groups, there was no difference in FAt, but significantly higher FW in BP in most regions of the WM skeleton. Discussion Our results are in line with previous studies suggesting a perturbation of WM health in individuals suffering from BP and SZ. The use of FWI in the present study allows for the further clarification of the biological nature of FA reductions: while SZ patients showed only reductions in FAt compared to HCs, the BP group also had marked increases in FW both compared to HCs and the SZ group. These increases in FW spatially overlapped with FA decreases, suggesting that an extra-cellular pathology is driving the observed FA reductions. The present alterations of WM properties in adolescent-onset BP are similar to those previously described in chronic BP and indicate that FW increases might be a biomarker of BP disorder. Interestingly, the adolescent SZ group, unlike recent-onset or first episode adult SZ cohorts, show no FW alterations, but instead FAt reductions similar to those previously reported in chronic SZ subjects. This could be explained by the longer illness duration, or different disease trajectories between adult and adolescent-onset psychosis. Taken together, we show differential patterns of WM aberrations in adolescent-onset SZ and BP, which lend support to the presence of distinct pathologies underlying the neurobiological development and manifestation of these disorders. [ABSTRACT FROM AUTHOR]