SU89. Cortical Thickness and Gray/White Matter Contrast in Olanzapine-Treated and Unmedicated Psychosis Patients and in Healthy Controls: A Moderating Role of HDL Cholesterol

摘要

>Background: There are several indications that second-generation antipsychotics have promyelinating¹ and lipogenic effects² of importance to the therapeutic response.We examined if olanzapine (OLZ) treatment was associated with the cortical thickness or cortical gray/white matter tissue contrast changes found in psychosis patients as compared to unmedicated patients and healthy controls, and examined the potential influence of peripheral lipid levels (total, LDL, HDL, and triglycerides). >Methods: One hundred and twenty-eight subjects from the TOP study cohort, Oslo, Norway, were selected: Patients with a nonaffective psychotic disorder either on stable olanzapine monotherapy (n = 33, mean age: 31.7 y, 54.5% males) or unmedicated (n = 19, mean age: 33.7 y, 73.7% males), and healthy controls (n = 76, mean age: 32.6, 59.2% males). T1-weighted 1.5 T MR images were processed using FreeSurfer. Mean cortical thickness and gray/white matter contrast were extracted for the whole-brain surface and 8 regions in each hemisphere. Group differences were tested using ANCOVA covarying for age and sex in SPSS version 23. >Results: The OLZ group had a shorter duration of untreated psychosis, fewer positive symptoms and higher LDL levels compared to the unmedicated group (P < .05). The groups did not differ with regards to demographics, functioning, or lifestyle. The OLZ group had lower whole-brain cortical thickness compared to the unmedicated patients and controls (P < .05), with frontal and temporal regions showing regional reductions (P < .05). A group × HDL interaction indicated a differential relationship where higher HDL was associated with thicker frontotemporal and pericentral cortices within the OLZ group only (P = .001). Whole-brain mean cortical contrast did not differ significantly (P = .08). However, decreased contrast was observed in the OLZ group compared to the unmedicated group in the frontal and left temporal regions (P < .05). When lipid levels were accounted for, HDL was negatively correlated to left lateral temporal and medial temporal cortical contrast (P < .05). A group × HDL interaction in the occipital lobes indicated that higher HDL was associated with lower contrast within the OLZ group (P < .05). >Conclusion: Lower regional contrast in OLZ-treated compared to unmedicated psychosis patients may suggest higher intracortical myelin content, but direct myelin mapping methods are needed to verify this observation. Lower frontotemporal cortical thickness is not in accordance with the hypothesized neuroprotective effect. Yet, the association between HDL cholesterol and cortical thickness and contrast among olanzapine users suggest a differential serum lipid effect. Future studies should adopt longitudinal designs and new myelin mapping methods (T1/T2 mapping). Grant: Research Council of Norway, South-Eastern Norway Regional Health Authority.References1.Bartzokis. Schizophr Res. 2007.2.Steen. Eur Neuropsychopharmacol. 2016.