Gerdina H. M. Pijnenborg, Frederike Jörg, Frits A. J. Muskiet, Eva Corpeleijn, Richard Bruggeman, Jojanneke Bruins, E. R. van den Heuvel, Agna A. Bartels-Velthuis, Reproductive Origins of Adult Health and Disease (ROAHD), Lifestyle Medicine (LM), Clinical Psychology and Experimental Psychopathology, Perceptual and Cognitive Neuroscience (PCN), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Stochastic Operations Research, and Statistics
People with psychotic disorders have an increased metabolic riskand their mean life expectancy is reduced with circa 28 years (Olfsonet al., 2015).Predictors of this increased metabolic risk are genetic predisposition (Liu et al., 2013), lifestyle factors such as unhealthy diet,physical inactivity and smoking (Bobes et al., 2010), and the side effectsof antipsychotic medication (Werner and Coveñas, 2014;Chadda et al.,2013). Low vitamin D status might also contribute to an increased metabolicrisk (Ginde et al., 2009;Kendrick et al., 2009;Kilkkinen et al.,2009;Ford et al., 2009) and all-cause mortality by promoting atherosclerosis,hypertension, inflammation and activation of the renin-angiotensinsystem (Wang et al., 2012;Garland et al., 2014;Lee et al., 2008). Also,one review demonstrated cardiovascular mortality rates in the generalpopulation were higher during winter than in summer (Zittermann etal., 2005).Vitamin D interacts with dopaminergic, cholinergic and noradrenergicneurotransmitter systems, which have all been implicated inSchizophrenia Research 195 (2018) 513–518⁎ Corresponding author at: University Medical Center Groningen, University Center for Psychiatry, Rob Giel Research center, P.O. Box 30.001 (CC72), 9700 RB Groningen, The Netherlands.E-mail addresses: j.bruins@lentis.nl (J. Bruins), f.jorg@umcg.nl (F. Jörg),e.r.v.d.heuvel@tue.nl (E.R. van den Heuvel), a.a.bartels@umcg.nl (A.A. Bartels-Velthuis),e.corpeleijn@umcg.nl (E. Corpeleijn), f.a.j.muskiet@umcg.nl (F.A.J. Muskiet),g.h.m.pijnenborg@rug.nl (G.H.M. Pijnenborg), r.bruggeman@umcg.nl (R. Bruggeman).experiencing psychotic symptoms (Eyles et al., 2013). When vitaminD is low, dopamine signalling in the brain appears to decrease (Eyleset al., 2013;Cui et al., 2015;Cui et al., 2013;Groves et al., 2014), whichin its turn could lead to more severe negative symptoms of psychosis(Buchanan et al., 2007). Indeed, several studies found that vitamin D insufficiencywas strongly associated with negative symptoms of psychosis(Graham et al., 2015;Yüksel et al., 2014;Cieslak et al., 2014;OttesenBerg et al., 2010).Vitamin D is thus associated with both metabolic risk and negativesymptom severity. Negative symptoms have also been shown to interferewith patients' ability to be physically active and make healthy lifestylechoices, which can increase their metabolic risk (Bergqvist et al.,2013). Negative symptom severity may therefore mediate the associationbetween low vitamin D and increased metabolic risk in peoplewith a psychotic disorder.Vitamin D is mostly produced in the skin by exposure to ultravioletBradiation in sunlight (Brown et al., 1999;Holick, 2007). Absorption ofvitamin D and levels of circulation differ among individuals and can beinfluenced by determinants such as latitude, season, time of day, skincolor (Holick et al., 2011), bodyweight, age, calcium intake(Zittermann et al., 2014), diet and genetics (Mazahery and von Hurst,2015).Vitamin D shows a natural fluctuation throughout the year, with vitaminD insufficiency more likely to occur during winter than in summer(Rosecrans and Dohnal, 2014). A recent study suggestsseasonality may also affect clinical symptoms of schizophrenia, althoughthe underlying mechanism is unknown (Byrne et al., 2015).In this study we aim to investigate whether vitamin D levels are associatedwith metabolic risk in people with psychotic disorders andwhether this effect was mediated by negative symptoms. We hypothesizethat vitamin D levels may influence the severity of metabolic disturbancesand negative symptoms. As vitamin D levels naturally fluctuatethroughout the seasons (Rosecrans and Dohnal, 2014), we examinewhether metabolic risk and negative symptom severity follow a similarseasonal fluctuation pattern. Furthermore, we investigate whether thehttp://dx.doi.org/10.1016/j.schres.2017.08.0590920-9964/© 2017 Elsevier B.V. All rights reserved.Contents lists available at ScienceDirectSchizophrenia Researchjournal homepage: www.elsevier.com/locate/schresseverity of metabolic risk and negative symptoms differ between patientsusing and patients not using vitamin D supplementation. In thiscross-sectional study, seasonal patterns and differences with regard tosupplementation may indicate an interdependent and potentially causalconnection between vitamin D, metabolic risk and negative symptomseverity