The relation of vitamin D, metabolic risk and negative symptom severity in people with psychotic disorders

Abstract

People with psychotic disorders have an increased metabolic risk and their mean life expectancy is reduced with circa 28 years (Olfson et 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 effects of antipsychotic medication (Werner and Covenas, 2014;Chadda et al., 2013). Low vitamin D status might also contribute to an increased metabolic risk (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-angiotensin system (Wang et al., 2012;Garland et al., 2014;Lee et al., 2008). Also, one review demonstrated cardiovascular mortality rates in the general population were higher during winter than in summer (Zittermann et al., 2005). Vitamin D interacts with dopaminergic, cholinergic and noradrenergic neurotransmitter systems, which have all been implicated in Schizophrenia 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. Jorg), 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 vitamin D is low, dopamine signalling in the brain appears to decrease (Eyles et al., 2013;Cui et al., 2015;Cui et al., 2013;Groves et al., 2014), which in its turn could lead to more severe negative symptoms of psychosis (Buchanan et al., 2007). Indeed, several studies found that vitamin D insufficiency was strongly associated with negative symptoms of psychosis (Graham et al., 2015;Yuksel et al., 2014;Cieslak et al., 2014;Ottesen Berg et al., 2010). Vitamin D is thus associated with both metabolic risk and negative symptom severity. Negative symptoms have also been shown to interfere with patients' ability to be physically active and make healthy lifestyle choices, which can increase their metabolic risk (Bergqvist et al., 2013). Negative symptom severity may therefore mediate the association between low vitamin D and increased metabolic risk in people with a psychotic disorder. Vitamin D is mostly produced in the skin by exposure to ultravioletB radiation in sunlight (Brown et al., 1999;Holick, 2007). Absorption of vitamin D and levels of circulation differ among individuals and can be influenced by determinants such as latitude, season, time of day, skin color (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 vitamin D insufficiency more likely to occur during winter than in summer (Rosecrans and Dohnal, 2014). A recent study suggests seasonality may also affect clinical symptoms of schizophrenia, although the underlying mechanism is unknown (Byrne et al., 2015). In this study we aim to investigate whether vitamin D levels are associated with metabolic risk in people with psychotic disorders and whether this effect was mediated by negative symptoms. We hypothesize that vitamin D levels may influence the severity of metabolic disturbances and negative symptoms. As vitamin D levels naturally fluctuate throughout the seasons (Rosecrans and Dohnal, 2014), we examine whether metabolic risk and negative symptom severity follow a similar seasonal fluctuation pattern. Furthermore, we investigate whether the http://dx.doi.org/10.1016/j.schres.2017.08.059 0920-9964/© 2017 Elsevier B.V. All rights reserved. Contents lists available at ScienceDirect Schizophrenia Research journal homepage: www.elsevier.com/locate/schres severity of metabolic risk and negative symptoms differ between patients using and patients not using vitamin D supplementation. In this cross-sectional study, seasonal patterns and differences with regard to supplementation may indicate an interdependent and potentially causal connection between vitamin D, metabolic risk and negative symptom severity