M81. Atypical Antipsychotic Dose-Dependent Effects on Fractional Anisotropy in a Cohort of Chronic Schizophrenia Patients

• Published in: Schizophrenia bulletin 2017-03, Vol.43 (suppl_1), p.S240-S240
• Main Authors: Lang, Donna, Kim, David, Woodward, Melissa, Procyshyn, Ric, Thornton, Allen, O’Connor, Tiffany, Goghari, Vina, White, Randall, Leonova, Olga, Su, Wayne, Rauscher, Alexander, Warburton, Darren, Vertinsky, Talia, Smith, Geoff, Honer, William
• Format: Article
• Language: English
• Subjects: Abstracts
• ISSN: 0586-7614; 1745-1701
• DOI: 10.1093/schbul/sbx022.076

Background: The neurotoxic and/or neuroprotective effects of individual antipsychotics remain controversial, with equivocal reports emerging from the animal and human literature, particularly in cognitively critical fronto-temporal areas. We investigated the relationship between antipsychotic dose and frontal white matter fractional anisotropy (FA) to determine potential neurotoxicity of atypical antipsychotics and the relationships between white matter FA, symptom severity and cognition. Methods: 3T diffusion imaging was performed in 10 chronic DSM-V schizoaffective and 9 schizophrenia patients (mean age 30.6 yr: 6 F, 13 M). Symptom severity was assessed with the PANSS (mean score = 96.1). Cognitive measures included Trails A & B, the Hopkins Verbal Learning Test and the Symbol Digit Modalities Test. Patients were being treated with a mix of one or more atypical medications (aripriprazole, clozapine, olanzapine, quetiapine, palliperidone, risperidone). Fractional anisotropy (FA) of the major frontal tracts (genu, fornix, bilateral anterior limb internal capsule, bilateral superior longitudinal fasciculus—SLF) was extracted with FSLv5.3 FMRIB and co-registered to the JHU DTI atlas prior to FreeSurfer 5.0 segmentation. Exploratory linear regressions were used to probe regions prior to specific region-of-interest analysis of variance. Bonferroni correction was applied at the .01 level. Results: One dataset was omitted due to poor imaging quality. Mean chlorpromazine equivalent (CPZE) dose was 680.2 mg/d. Mean duration of illness = 10.1 years. Strong inverse relationships were observed between FA in the left SLF ( r  = −.654, F (17,1) = 12.7, P  = .0024) and the fornix body ( r  = −.651, F (17,1) = 12.5, P  = .0025) and CPZE dose. These relationships were not associated with age, PANSS scores or cognitive measures ( P > .05). FA values in all other regions of interest were not significantly correlated to any other measures of interest. Conclusion: In vitro investigations suggested that atypical neuroleptics, particularly clozapine, may be associated with increased cerebral cell death The inverse association of reduced FA signal in the SLF and the fornix with antipsychotic dose suggests a dose-dependent alteration in axonal permeability in patients receiving atypical medications, however, this change in FA signal is not necessarily a direct measure of neuronal pathology.