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Depression 1.9 X more likely in Japanese women 5 years after having low vitamin D - March 2023


Low plasma 25-hydroxyvitamin D levels are associated with an increased risk of depressive symptoms in community-dwelling Japanese people aged between 40 and 74 years: The Murakami cohort study

Journal of Affective Disorders Volume 325, 15 March 2023, Pages 48-54 https://doi.org/10.1016/j.jad.2022.12.104
Aya Hinata a, Kaori Kitamura a, Yumi Watanabe a, Keiko Kabasawa b, Toshiko Saito c, Akemi Takahashi d, Ribeka Takachi e, Ryosaku Kobayashi d, Rieko Oshiki d, Masayuki Iki f, Shoichiro Tsugane g, Ayako Sasaki h, Kei Watanabe i, Kazutoshi Nakamura a

Background
Association between vitamin D levels and the occurrence of depression are not always consistent. The present cohort study aimed to determine this association in older adults, using a method for measuring vitamin D levels which is more accurate than those used in previous studies.

Methods
Participants were 3447 individuals aged 40–74 years without depressive symptoms at baseline who participated in the 5-year follow-up survey. The baseline investigation, including a self-administered questionnaire survey and blood collection, was conducted in 2011–2013. Plasma 25-hydroxyvitamin D (25OHD) levels were measured, and divided into overall quartiles summed up by sub-quartiles and stratified by age, sex, and season. The outcome was depressive symptoms determined by the CES-D (11-item, cut-off score of 6/7) 5 years later. Covariates were demographics, lifestyles, baseline CES-D score, and disease history.

Results
Mean plasma 25(OH)D levels were 58.0 nmol/L in men and 45.7 in women (P < 0.0001), and cumulative incidences of depressive symptoms were 249/1577 (15.8 %) in men and 313/1870 (16.7 %) in women (P = 0.4526). The lower 25(OH)D quartile group had higher adjusted ORs in men and women combined (P for trend = 0.0107) and women (P for trend = 0.0003), but not in men. Adjusted ORs of the lowest quartile group were significantly higher than the highest group in men and women combined (OR = 1.39, 95 % CI: 1.06–1.81) and women (OR = 1.89, 95 % CI: 1.31–2.72).

Limitation
Depressive symptoms were self-reported.

Conclusions
Low vitamin D levels were associated with a high risk of depressive symptoms, especially in women. Women are thus considered a major target for preventing vitamin D deficiency to address depression.

Introduction
Depression is a common mental disorder that affects 322 million people worldwide, corresponding to roughly 4.4 % of the global population in 2015 (World Health Organization, 2017). The total estimated number of people living with depression increased by 18 % between 2005 and 2015 (GBD 2015 DALYs and HALE Collaborators, 2016). Depression is widely known as a major risk factor for suicide (Moitra et al., 2021). Furthermore, late-life depression is associated with a higher risk of all-cause mortality among community-dwelling older people (Wei et al., 2019). For these reasons, prevention of depression is a high-priority public health issue.

Vitamin D is a fat-soluble vitamin synthesized in the skin by sunlight and/or supplied from vitamin D-containing food. Levels of vitamin D are inversely associated with the risk of non-communicable chronic diseases, such as cancer (Han et al., 2019), cardiovascular diseases (Zhang et al., 2017), and diabetes (Lucato et al., 2017). Moreover, vitamin D is reportedly associated with mental health, consistent with the expression of vitamin D receptors and vitamin D metabolizing enzymes in the central nervous system (Humble, 2010). Recent evidence suggests that vitamin D is associated with the occurrence of depression. For instance, Li et al. (2019) conducted a meta-analysis of six cohort studies and concluded that vitamin D levels are inversely and dose-dependently associated with depression in older adults. However, relatively few published cohort studies have examined the association between vitamin D and depression, and results of the six cohort studies were not necessarily consistent with each other (Li et al., 2019). Results from two other recently published cohort studies on this theme were also conflicting (Briggs et al., 2019; Sahasrabudhe et al., 2020). Moreover, sex-dependent differences in the association between vitamin D levels and depression have been reported (Milaneschi et al., 2010; Rhee et al., 2020), but were not in mutual agreement.

One reason for the variability observed in the association between vitamin D levels and risk of depression is that vitamin D levels, evaluated by measuring blood 25-hydroxyvitamin D (25OHD), are influenced significantly by demographic and environmental factors, such as age, sex, and season (Nakamura et al., 2015). To investigate the longitudinal association between blood 25(OH)D levels and diseases in community-dwelling individuals, we established a cohort study (Nakamura et al., 2018) which classified 8497 blood samples into quartile groups of 25(OH)D levels, stratified by age, sex, and season. This allowed us to determine accurately the vitamin D status by adjusting for its major correlates. The present study aimed to determine the longitudinal association between vitamin D levels and depressive symptoms over a 5-year follow-up period in middle-aged and older Japanese adults.

Section snippets
Participants
All 34,802 residents of the Murakami region aged between 40 and 74 years were invited to participate in the study. Of these, 14,364 (41.3 %) participated in the baseline questionnaire survey of the Murakami cohort study conducted in Niigata Prefecture, Japan, and 8497 of the 14,364 participants provided blood samples. The baseline survey determined that 5588 of these participants were eligible. Data from the 3447 people who participated in the 5-year follow-up survey and who had no missing data . . . .

Results
The mean age of participants was 60.5 years (SD, 8.5). Mean crude plasma 25(OH)D levels were 58.0 nmol/L (SD, 18.0) in men and 45.7 nmol/L (SD, 16.1) in women (P < 0.0001). By age group, mean 25(OH)D levels were 43.8 nmol/L (SD, 18.1) for participants in their 40s, 48.3 nmol/L (SD, 17.8) for those in their 50s, 54.1 nmol/L (SD, 17.8) for those in their 60s, and 55.2 nmol/L (SD, 16.7) for those in their 70s (P for trend<0.0001). Incidences of depressive symptoms were 249/1577 (15.8 %) in men and . . . . .

Discussion
The present 5-year cohort study, which targeted community-dwelling people aged between 40 and 74 years, demonstrated that 1) low vitamin D levels were associated with a high risk of developing depressive symptoms, 2) this association was robust in women but not observed in men, and 3) this association was likely to be more robust in older people than in younger people. . . . .

A meta-analysis published in 2019 (Li et al., 2019) reported that higher serum 25(OH)D levels are associated with a lower risk . . . .

CRediT authorship contribution statement
AH and KN conceived the study. AH, KK, YW, KKa, MI, ST, and KN designed the study. KKi, TS, AT, RT, RK, RO, AS, and KN conducted the research. AH and KN analyzed data and wrote the initial draft of the manuscript. RT, MI, ST, and KW critically reviewed and revised the manuscript. KN had primary responsibility for the final content. All authors read and approved the final manuscript.

Conflict of interest
None of the authors had conflicts of interest.

Acknowledgements
We thank Kyowa Medex Co., Ltd. and DiaSorin Inc. for providing the plasma 25(OH)D assay. We also thank the following institutions for their help in blood collection: Murakami City Government, Sekikawa Village Government, Awashimaura Village Government, the Medical Association of Murakami City and Iwafune District, Murakami General Hospital, Niigata Prefectural Sakamachi Hospital, Sampoku Tokushukai Hospital, Murakami Memorial Hospital, Senami Hospital, Sakanamachi Hospital, Aoki Clinic, Arakawa

Supporting sources
Kyowa Medex Co., Ltd. and DiaSorin Inc. provided the plasma 25(OH)D assay. The supporting sources had no involvement in or restrictions regarding publication.

Funding
This work was supported by JSPS KAKENHI Grants (JP23249035, JP40339958, and JP15H04782) and a National Cancer Center Research and Development Fund (23-A31toku) (since 2010).

Role of the funding source
The funding sources had no involvement in or restrictions regarding publication.

32 References online


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