Vitamin D deficiency in first episode psychosis: A case–control study

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Abstract

Background

Vitamin D deficiency is seen in a high proportion of people with established psychotic disorders, but it is not known if this is present at onset of the illness. We set out to examine vitamin D levels in people with their first episode of psychosis (FEP).

Method

We conducted a matched case–control study to examine vitamin D levels and rates of vitamin D deficiency in sixty nine patients presenting with their FEP and sixty nine controls matched for age, sex and ethnicity. Differences between groups were tested using student's-t tests, paired t-tests and odds ratios for further analysis.

Results

Vitamin D levels were significantly lower in cases than in controls (p < 0.001). The odds ratio of being vitamin D deficient was 2.99 in the FEP group relative to the control group. There was no correlation between vitamin D levels and length of hospitalisation in the patient group (r =  0.027, p = 0.827).

Conclusions

We found higher rates of vitamin D deficiency in people with FEP compared to matched controls. Given that vitamin D is neuroprotective; that developmental vitamin D deficiency may be a risk factor for psychosis, and that incipient psychosis may affect lifestyle factors and diet, future studies are required to examine this association further. In the meantime, there is a need for more widespread testing of vitamin D levels in FEP and for the development of appropriate management strategies.

Introduction

Low levels of vitamin D have traditionally been associated with musculoskeletal consequences (Wharton and Bishop, 2003, Boonen et al., 2006). In recent years, however, the importance of this essential nutrient across a range of conditions has become apparent. It is increasingly recognised, for example, that low vitamin D levels are seen in cardiovascular disease (Wang et al., 2008), diabetes (Holick, 2008) and multiple sclerosis (Orton et al., 2011) (Wood, 2012) and influence the body's ability to mount immune responses (Hewison, 2011).

Vitamin D levels in the general population are higher in men than in women and decrease with increasing age (Zadshir et al., 2005). There is also a relationship between low vitamin D levels and obesity (Wortsman et al., 2000, Vimaleswaran et al., 2013) and with smoking (Brot et al., 1999, Cutillas-Marco et al., 2012). It has been postulated that those with increased adipose tissue stores (in which vitamin D, being fat soluble, is stored), due to obesity, have lower circulating levels of vitamin D due to this increased storage capacity (Wortsman et al., 2000). Cigarette smoking has been associated with altered vitamin D metabolism, with increased hepatic cytochrome enzyme activity (Hermann et al., 2000) suggested as the mechanism of deranged vitamin D metabolism.

In humans, skin exposure to ultraviolet B sunlight is the major primary source of vitamin D (Holick, 2004), with diet contributing a maximum of 20% (Fuller and Casparian, 2001). Vitamin D levels thus vary seasonally, with levels in late winter and early spring around half of those in the autumn reflecting ambient levels of sunlight (Hypponen and Power, 2007). People with more pigmented skin need more sunlight to produce vitamin D, so are particularly affected by limited sun exposure, with lower levels of vitamin D consistently observed in Black and Asian populations (Ford et al., 2006, Looker et al., 2008, Mithal et al., 2009).

Vitamin D is involved in a number of brain processes including neurodevelopment, neurotransmitter expression, neurotrophic and growth factor regulation and is thought to be neuroprotective (Eyles et al., 2013). There is a growing interest in the relationship between vitamin D and mental health (Berk et al., 2008, Berg et al., 2010, Menkes et al., 2012) and it has been proposed that developmental deficiency of vitamin D may contribute to the aetiology of schizophrenia (McGrath, 1999, McGrath et al., 2004, McGrath et al., 2010b).

All previous reports of vitamin D deficiency in psychosis have been in those with established disorder, and therefore could be due to prolonged hospitalisation, poor nutrition, or to the prescription of anticonvulsant medications (Pack et al., 2004). To our knowledge, no data exists on vitamin D levels at first onset of the disorder. We therefore tested the hypothesis that vitamin D levels in patients with their first episode of psychosis (FEP) are lower than those in their peers in the general population.

Section snippets

Method

The study population comprised 69 adults with a first episode of psychosis. All participants met the ICD-10 criteria for psychosis (codes F20-29 and F30-33) and had been admitted to psychiatric inpatient units in London and South-East England. Participants provided written informed consent. The project was approved by the Research Ethics Committee of The Joint South London and Maudsley and The Institute of Psychiatry NHS Research Ethics Committee.

The patients were matched for gender, age (plus

Results

The mean age of the cases was 31.0, (SD = 10.9; range 18–58); and of controls 30.7, (SD = 11.1; range 18–59). Twenty seven participants (39%) in each group were male. Within each group, 39 subjects were white (56%), 20 were black (29%) and 10 of Asian ethnicity (14%).

Mean serum vitamin D level was significantly lower in cases (36.5 nmol/L (SD = 23.0)) than in controls (53.8 nmol/L (SD = 33.0)) (t =  4.064, df = 68, p < 0.001). Vitamin D deficiency was present in 36.2% (n = 25) of cases and 15.9% (n = 11) of

Discussion

This study shows for the first time that vitamin D levels are low at the onset of a first psychotic episode. In our sample, one third of people were vitamin D deficient at the time of their first episode of illness. The similar prevalence of vitamin D insufficiency between controls and cases suggests a shift in the curve to the left in FEP.

Three factors may underlie this. The first relates to the long prodromal phase in some patients with schizophrenia, lasting up to five years (White et al.,

Conclusion

We examined vitamin D levels in people at the first onset of psychotic illness and found them lower than those reported in the population with established psychotic illnesses (Lally et al., 2013) and, lower than matched controls. Further work is needed to see whether this line of work may yield strategies to prevent or modify the course of the disease or improve longevity in the disorder.

These risks highlight the need for practical guidelines to help this group access appropriate and equitable

Disclaimer

This paper summarises independent research funded by the National Institute for Health Research (NIHR) under its IMPACT Programme (Grant Reference Number RP-PG-0606-1049). The views expressed are those of the author(s) and not necessarily those of the National Health Service (NHS), the NIHR or the Department of Health.

Role of funding source

Details of the role of the study sponsors Program grant for research: all researchers have remained independent from the funders in the completion and submission of this work.

Trial registration details (registry and number) — ISRCTN number is ISRCTN58667926.

Contributors

Authors M Crews and J Lally contributed equally to the study design, data analysis, the paper construction and writing and should be acknowledged as equal first authors. All of the other authors contributed to reviews of the manuscript and the original research design and the analysis of data.

Conflict of interest

All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (and currently in the possession of the corresponding author) and declare: this is a National Institute of Health Research (NIHR) funded study (grant number: RP-PG-0606-1049); This study was also partially funded by a Medical Research Council (UK) grant to Dr Howes (grant number: MC-A656-5QD30).

RMM has received payment for lectures including service on speakers' bureaus for BMS, Janssen, and AZ.

FG

Acknowledgement

There are no acknowledgments to make.

This paper summarises independent research funded by the National Institute for Health Research (NIHR) under its IMPACT Programme (Grant Reference Number RP-PG-0606-1049). The views expressed are those of the author(s) and not necessarily those of the National Health Service (NHS), the NIHR or the Department of Health.

(This is included in the declaration of competing interests section).

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    Both authors contributed equally to this work and should be acknowledged as equal first authors.

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