O10.2. EFFECTS OF ADJUVANT OMEGA-3 POLYUNSATURATED FATTY ACIDS ON WHITE MATTER IN INDIVIDUALS WITH RECENT-ONSET PSYCHOSIS TREATED CONCURRENTLY WITH RISPERIDONE

The use of omega-3 polyunsaturated fatty acids (PUFAs) as a potential therapeutic agent has generated considerable enthusiasm given their relative safety, minimal side effects, and low cost. Omega-3s have been demonstrated to play a role in the maintenance of myelin and mitigation of pro-inflammatory cascades. We examined the potential impact of adjuvant omega-3 PUFA treatment on white matter in early-phase psychosis patients treated with risperidone in the context of a double-blind placebo controlled randomized clinical trial. Thirty-seven (28M/9F) patients (mean age = 21.8) experiencing a recent-onset of psychosis were scanned at the onset of treatment and then randomly assigned to receive 16 weeks of treatment with either risperidone + omega-3 or risperidone + placebo. Thus, all participants received open-label risperidone. Of the 37 patients, 18 received follow-up MRIs at the end of the clinical trial (Omega-3, n = 10 / Placebo, n = 8). All scans were acquired on a GE 3T HDx scanner. Blood was collected prior to the baseline MR scan and after 16 weeks of treatment to determine erythrocyte levels of the omega-3 PUFAs eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and docosapentaenoic acid (DPA). We utilized an adapted tract-based spatial statistics pipeline created by the ENIGMA DTI Working Group. Free Water Imaging was used to deconstruct the diffusion signal into extracellular free water (FW) maps and a fractional anisotropy of the tissue (FA-t) maps. Between- and within-subject comparisons were conducted using nonparametric permutation-based tests with a threshold free cluster enhancement and family-wise error correction (p<0.05) controlling for age, sex, and motion. Erythrocyte omega-3 PUFA levels increased significantly in the risperidone + omega-3 group for DPA (p < .001; +72.6%), DHA (p = .002; +56.2%) and EPA (p =.001; +281.7%). Omega-3 PUFAs did not change significantly (p > .05) in patients treated with risperidone + placebo. At the onset of treatment there were robust positive correlations between FA-t with DHA and DPA among all patients. During treatment patients treated with risperidone + placebo demonstrated significant reductions in FA-t and increased FW that were either absent (i.e., FW) or largely attenuated (i.e., FA-t) among patients treated with risperidone + omega-3. Within all patients (n = 18) who were scanned at follow-up, changes in DPA, EPA and DHA blood levels were significantly correlated with changes in FW, but not FAt, over 16 weeks (p < 0.05). The baseline correlations of DPA and DHA with FA-t are in line with previous studies suggesting a perturbation in PUFA biosynthesis as a potential contributing factor to the compromised white matter often observed in psychosis. The significant positive relationship observed between changes in PUFA blood levels and changes in FW over the course of the trial lends some support to omega-3 PUFAs potentially serving a neuroprotective role by reducing pro-inflammatory responses in the brain. Our findings are also consistent with the hypothesis that adjuvant omega-3 treatment may attenuate antipsychotic treatment-related white matter alterations in patients with psychosis. We could not disentangle whether progressive alterations in white matter microstructure in the risperidone + placebo group were due to either illness progression and/or short-term antipsychotic treatment or other factors. Nevertheless, our longitudinal findings suggest that omega-3 PUFA supplementation may at least partially mitigate against such white matter changes in response to risperidone treatment.