Serum S100B: A proxy marker for grey and white matter status in the absence and presence of (increased risk of) psychotic disorder? Christine van der Leeuw1*, Sanne Peeters1,2, Ed Gronenschild1, Stijn Michielse1, Marcel Verbeek3,4, Paul Menheere5, Jim van Os1,6, Machteld Marcelis1,7, on behalf of Genetic Risk and Outcome in Psychosis (G.R.O.U.P.)¶
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OPEN ACCESS Citation: van der Leeuw C, Peeters S, Gronenschild E, Michielse S, Verbeek M, Menheere P, et al. (2017) Serum S100B: A proxy marker for grey and white matter status in the absence and presence of (increased risk of) psychotic disorder? PLoS ONE 12(3): e0174752. https://doi.org/10.1371/journal. pone.0174752 Editor: Nori Takei, United (Osaka U, Kanazawa U, Hamamatsu U Sch Med, Chiba U and Fukui U) Graduate School of Child Developmen, JAPAN Received: February 24, 2017 Accepted: March 14, 2017 Published: March 30, 2017 Copyright: © 2017 van der Leeuw et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper.
1 Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, EURON, Maastricht University Medical Centre, Maastricht, the Netherlands, 2 Faculty of Psychology and Educational Sciences, Open University of the Netherlands, Heerlen, the Netherlands, 3 Departments of Neurology and Laboratory Medicine, Radboud University Medical Centre, Nijmegen, the Netherlands, 4 Donders Institute for Brain, Cognition and Behaviour, Nijmegen, the Netherlands, 5 Central Diagnostic Laboratory, Maastricht University Medical Centre, Maastricht, the Netherlands, 6 Department of Psychosis Studies, Institute of Psychiatry, King’s College London, United Kingdom, 7 Institute for Mental Health Care Eindhoven (GGzE), Eindhoven, the Netherlands ¶ Membership of G.R.O.U.P. is provided in the Acknowledgments. * [email protected]
Abstract S100B is a protein with dose-dependent neurotrophic and neurotoxic effects. Whether S100B in psychotic disorder mirrors pathophysiological mechanisms (which elicit exacerbation of disease) or compensatory action is unclear, as is its validity as a proxy marker for brain status. Insight may be gained by examining associations between serum S100B and indices of grey (cortical thickness (CT)) and white matter (fractional anisotropy (FA)), in relation to the absence or presence of (increased risk of) psychotic disorder. Blood samples and cerebral magnetic resonance imaging (MRI) scans were acquired in 32 patients with psychotic disorder, 44 non-psychotic siblings of patients with psychotic disorder and 26 controls. Interactions between S100B and group were examined in separate models of CT and FA measures with multilevel regression analyses weighted for number of vertices and voxels (i.e. units of volume) respectively. All analyses were adjusted for sex, age, body mass index (BMI), scan sequence, handedness and highest level of education. Neither CT nor FA was associated with S100B. There were no significant S100B × group interactions (CT: χ2 = 0.044, p = 0.978; FA: χ2 = 3.672, p = 0.159). No evidence was present for S100B as a proxy marker of grey or white matter status. The association between S100B and brain measures was not moderated by psychosis risk.
Funding: This work was supported by the Geestkracht programme of the Dutch Health Research Council (ZON-MW, grant number 10000-1002), and the European Community’s Seventh Framework Programme under grant agreement No. HEALTH-F2-2009-241909 (Project EU-GEI). The sponsors had no further role in the
PLOS ONE | https://doi.org/10.1371/journal.pone.0174752 March 30, 2017
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Serum S100B: A proxy marker for grey and white matter status in the absence and presence of (increased risk of) psychotic disorder? study design; in the collection, analysis and interpretation of data; in the writing of the report, and in the decision to submit the paper for publication. Competing interests: Jim van Os is or has been an unrestricted research grant holder with, or has received financial compensation as an independent symposium speaker from, Lilly, BMS, Lundbeck, Organon, Janssen, GlaxoSmithKline, AstraZeneca, Pfizer, and Servier. Machteld Marcelis has received financial compensation as an independent symposium speaker from Lilly and Janssen. This does not alter our adherence to PLOS ONE policies on sharing data and materials. All other authors report no biomedical financial interests or potential conflicts of interest.
Introduction S100B is a protein with dose-dependent neurotrophic and neurotoxic effects. Previously, we investigated serum protein S100B as a marker of familial risk of psychotic disorder. We did not find S100B elevation in unaffected siblings of patients with psychotic disorder. Nor was S100B elevated in patients with psychotic disorder in our samples (including patients generally not in an acute stage of the disorder, with a mean illness duration