Hypovitaminosis D is associated with depression and anxiety in schizophrenia: Results from the national FACE-SZ cohort.
Introduction
Treating comorbid major depressive disorder (MDD) and anxiety disorders in SZ is clinically important due to the high prevalence of depression and suicidality in SZ and to its impact on functioning and quality of life (Andrianarisoa et al., 2017, Harvey, 2011). Hypovitaminosis D has been extensively associated with MDD in general population (for meta-analysis see (Ju et al., 2013) and for review see (Lerner et al., 2018)) and supplementing subjects with MDD has been found to improve depressive symptoms in another recent meta-analysis (Schefft et al., 2017). Patients with SZ are at higher risk of hypovitaminosis D (Belvederi Murri et al., 2013) and this association has been replicated in first episode psychosis in another recent meta-analysis (Firth et al., 2017) (for review see (Adamson et al., 2017)). Vitamin D deficiency may play a role in mediating hippocampal volume deficits, possibly through neurotrophic, neuroimmunomodulatory and glutamatergic effects (Shivakumar et al., 2015). A study has found high levels of hypovitaminosis in a monocentric sample of SZ inpatients in the south of France (Belzeaux et al., 2015) but no data is available to date in a national non-selected sample of community-dwelling SZ subjects. Studies exploring the association of vitamin D deficiency with psychotic symptomatology have yielded inconsistent findings (Akinlade et al., 2017, Cieslak et al., 2014, Nerhus et al., 2016, Yüksel et al., 2014). The association of vitamin D deficiency and depression in schizophrenia has been explored in only one study with positive results (Nerhus et al., 2016), and no study has explored the association between hypovitaminosis D and anxiety disorders in SZ subjects to date. Preliminary findings have suggested that vitamin D supplementation may improve cognition in schizophrenia (Krivoy et al., 2017), however the association of hypovitaminosis D with cognitive impairment has not been explored to date. Vitamin D insufficiency has been associated with metabolic syndrome in psychotic disorders (Yoo et al., 2018), with insulin resistance (Garbossa and Folli, 2017), with thyroid dysfunction (Kim, 2017, Wang et al., 2018) and high vitamin D blood levels have been suggested to reduce peripheral low-grade inflammation (Zhu et al., 2015). There is a current debate on the association between alcohol use disorder and vitamin D deficiency (Tardelli et al., 2017).
The objective were (i) to determine the prevalence of hypovitaminosis D and associated factors in a non-selected multicentric sample of community-dwelling SZ subjects (ii) to determine the rate of vitamin D supplementation, its effectiveness in correcting vitamin D blood levels and the associated factors. Our hypotheses were that hypovitaminosis D was associated with higher depressive and anxiety disorders, higher cognitive impairment and higher biological disturbances.
Section snippets
Study design
The FACE-SZ (FondaMental Academic Centers of Expertise for Schizophrenia) cohort is based on a French national network of 10 Schizophrenia Expert Centers (Bordeaux, Clermont-Ferrand, Colombes, Créteil, Grenoble, Lyon, Marseille, Montpellier, Strasbourg, Versailles), set up by a scientific cooperation foundation in France, the FondaMental Foundation (www.fondation-fondamental.org) and pioneered by the French Ministry of Research in order to create a platform that links thorough and systematic
Results
Overall, 140 patients have been consecutively recruited. Hypovitaminosis D has been found in 21.4% of the subjects and none of them had received vitamin D supplementation in the previous 12 months. In multivariate analysis, hypovitaminosis D has been significantly associated with respectively higher depressive symptoms (aOR = 1.18 [1.03–1.35], p = 0.02) and current anxiety disorder (aOR = 6.18 [2.15–17.75], p = 0.001), independently of age and gender. No association of hypovitaminosis D with
Discussion
Altogether, the present findings may be summarized as follows: in a national sample of community-dwelling stabilized SZ subjects mean aged 33 years, 21.4% were found with hypovitaminosis D. Hypovitaminosis D has been significantly associated with anxiety and depressive symptoms after adjustment for confounding factors, and vitamin D supplementation has been associated with lower depressive symptoms and lower rates of comorbid anxiety disorders. No association of hypovitaminosis D or vitamin D
Conclusion
The present findings suggest that hypovitaminosis D is frequent and associated with anxiety disorders and depressive symptoms in SZ subjects. As these comorbidities are under diagnosed and under treated, these results may open the path to a new precision medicine strategy in the treatment of anxiety and depression in schizophrenia. Future studies should confirm that vitamin D supplementation may be effective in alleviating depressive symptoms and anxiety disorders in SZ subjects. The
Acknowledgments and funding source
This work was funded by AP-HM (Assistance Publique des Hôpitaux de Marseille), Fondation FondaMental (RTRS Santé Mentale), by the Investissements d'Avenir program managed by the ANR under reference ANR-11-IDEX-0004-02 and ANR-10-COHO-10-01.
We express all our thanks to the nurses, and to the patients who were included in the present study. We thank Hakim Laouamri, and his team (Stéphane Beaufort, Seif Ben Salem, Karmène Souyris, Victor Barteau and Mohamed Laaidi) for the development of the
Contributors
Dr Guillaume Fond, Dr Laurent Boyer wrote the manuscript.
All authors designed the study and wrote the protocol.
Dr Guillaume Fond and Dr Ophelia Godin managed the statistical analysis.
All authors contributed to and approved the final manuscript.
Conflict of interest
The authors report no conflict of interest.
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