Effects of fingolimod, a sphingosine-1-phosphate (S1P) receptor agonist, on white matter microstructure, cognition and s
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ORIGINAL RESEARCH
Effects of fingolimod, a sphingosine-1-phosphate (S1P) receptor agonist, on white matter microstructure, cognition and symptoms in schizophrenia Michael M. Francis 1,2 & Tom A. Hummer 1 & Emily Liffick 1,2 & Jenifer L. Vohs 1,2 & Nikki F. Mehdiyoun 1,2 & Andrew C. Visco 1,2 & Ziyi Yang 3 & Richard J. Kovacs 4 & Ying Zhang 3 & Alan Breier 1,2
# Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Several lines of evidence have implicated white matter (WM) deficits in schizophrenia, including microstructural alterations from diffusion tensor (DTI) brain imaging studies. It has been proposed that dysregulated inflammatory processes, including heightened activity of circulating lymphocytes, may contribute to WM pathology in this illness. Fingolimod is a sphingosine-1phosphate (S1P) receptor agonist that is approved for the treatment of relapsing multiple sclerosis (MS). Fingolimod robustly decreases the number of circulating lymphocytes through sequestration of these cells in lymph tissue. In addition, this agent improved WM microstructure as shown by increases in DTI fractional anisotropy (FA). In this pilot study, we assessed the effects of fingolimod on WM microstructure, cognition and symptoms in an eight-week, double-blind trial. Forty subjects with schizophrenia or schizoaffective disorder were randomized 1:1 to fingolimod (0.5 mg/day) and placebo. Fingolimod caused significant reductions in circulating lymphocytes (p < .001). In addition, there was a statistically non-significant association (p = .089) between DTI-FA change in the WM skeleton and fingolimod. There were significant relationships between the degree of lymphocyte reductions and increases in FA in the corpus collosum (p = .004) and right superior longitudinal fasciculus ( p = .02), and a non-significant correlation with the WM skeleton. There were no significant fingolimod versus placebo interactions on cognitive or symptom measures. There were no serious adverse events related to fingolimod treatment. Future studies with larger samples and treatment durations are needed to further establish fingolimod’s potential therapeutic effects in schizophrenia. Keywords fingolimod . DTI . White matter . Schizophrenia
Background
* Michael M. Francis [email protected] 1
Department of Psychiatry, Indiana University School of Medicine, 355 W. 16th St., Suite 4800, Indianapolis, IN 46202, USA
2
Prevention and Recovery Center for Early Psychosis, Outpatient Care Center, Eskenazi Health Midtown Community Mental Health Center, 720 Eskenazi Ave, Outpatient Care Center, Lower Level, Indianapolis, IN 46202, USA
3
Department of Biostatistics, Richard M. Fairbanks School of Public Health, Indiana University, 410 W. Tenth St., Suite 3000, 46202 Indianapolis, IN, USA
4
Krannert Institute of Cardiology, Indiana University School of Medicine, 1801 N. Senate Blvd, Indianapolis, IN 46202, USA
Schizophrenia is a severe brain disorder that begins during the late teens or early adult years and typically progresses to a lifelon
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