Elsevier

Psychiatry Research

Volume 270, December 2018, Pages 104-110
Psychiatry Research

Hypovitaminosis D is associated with depression and anxiety in schizophrenia: Results from the national FACE-SZ cohort.

https://doi.org/10.1016/j.psychres.2018.09.024Get rights and content

Highlights

  • Beyond its role in bone metabolism, vitamin D has been shown to have multiple functions including a role in depression and cognitive impairment in general population.

  • Vitamin D has been associated with increased risk of schizophrenia onset, but its role in illness characteristics remains unclear.

  • In this study, vitamin D has been found to be frequent in a national sample of outpatients with schizophrenia, and associated with anxiety and depression.

  • Vitamin D supplementation has been associated with lower rates of anxiety and depression but remains insufficiently prescribed.

Abstract

Objective

Hypovitaminosis D has been associated with respectively major depressive disorder, schizophrenia (SZ) and cognitive disorders in the general population, and with positive and negative symptoms and metabolic syndrome in schizophrenia. The objectives were (i) to determine the prevalence of hypovitaminosis D and associated factors (with a focus on depression and cognition) in a national non-selected multicentric sample of community-dwelling SZ subjects (ii) to determine the rate of SZ patients being administered vitamin D supplementation and associated factors.

Methods

A comprehensive 2 daylong clinical and neuropsychological battery was administered in 140 SZ subjects included between 2015 and 2017 in the national FondaMental Expert Center (FACE-SZ) Cohort. Hypovitaminosis D was defined by blood vitamin D level <25 nM. Depressive symptoms were assessed by the Positive and Negative Syndrome Scale depressive subscore and current anxiety disorder by the Structured Clinical Interview for Mental Disorders.

Results

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 respectively positive and negative symptoms, cognitive scores or other biological variables has been found (all p > 0.05), however, a trend toward significance has been found for metabolic syndrome (p = 0.06). Vitamin D supplementation has been administered during the previous 12 months in only 8.5% of the subjects but was associated with lower depressive symptoms (aOR = 0.67 [0.46–0.98], p = 0.04) and lower rate of current anxiety disorder (aOR = 0.06 [0.01–0.66], p = 0.02) compared to patients with hypovitaminosis D.

Conclusion

Hypovitaminosis D is frequent and associated with depressive symptoms and anxiety disorders in schizophrenia. Vitamin D supplementation is associated with lower depressive and anxiety symptoms, however patients with hypovitaminosis D remain insufficiently treated.

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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