Association between Depressive Symptoms and Vitamin D Deficiency. among Recently Admitted Nursing Home Patients

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Association between Depressive Symptoms and Vitamin D Deficiency among Recently Admitted Nursing Home Patients Gotaro Kojima, MD 1 ; Marianne Tanabe, MD 2 ; Kamal Masaki, MD 3 ; G. Webster Ross, MD 4 ; Anna Tamai, MD 5 ; Helen Petrovitch, MD 4 ; Gregory Gatchell, DO 2 ; Daryl Fujii, PhD 2. 1 Japan Green Medical Centre, London, UK; 2 Community Living Center, Veterans Affairs Pacific Islands Health Care System, Hawaii, USA; 3 The John A. Hartford Foundation Center of Excellence in Geriatrics, Department of Geriatric Medicine, John A. Burns School of Medicine, University of Hawaii, Hawaii, USA; 4 Pacific Health Research and Education Institute, Veterans Affairs Pacific Islands Health Care System, Honolulu, Hawaii, USA; 5 Center for Home Care Medicine, Faculty of Medicine, The University of Tokyo, Tokyo, Japan. Corresponding Author: Gotaro Kojima, MD Japan Green Medical Centre 10 Throgmorton Avenue London EC2N 2DL UK Email: gotarokojima@yahoo.co.jp Phone: +44(0)20-7330-1750 Fax: +44(0)20-7330-1751 1

Alternate Corresponding Author: Marianne Tanabe, MD Community Living Center Veterans Affairs Pacific Islands Health Care System 459 Patterson Road, Honolulu HI 96819 Email: Marianne.Tanabe@va.gov Phone: (808)433-0239 Fax: (808)433-0281 Acknowledgment: This material is the result of work supported with resources and the use of facilities of the VAPIHCS, Honolulu, HI. The contents do not necessarily represent the views of the Department of Veterans Affairs or the United States Government. Funding: none 2

The prevalence of depression or depressive symptoms at the time of nursing home admission has been reported up to 80%. 1 Depressive symptoms have been shown to be associated with multiple negative health outcomes. 2 A possible risk factor for depression is vitamin D deficiency. A recently published meta-analyses showed that lower vitamin D levels were significantly associated with higher risk of depression among non-institutionalized populations. 3 Vitamin D deficiency has been observed in 40% or more of community dwelling elders 4 and up to 100% of nursing home residents in some studies. 5 Although nursing home residents are at high risk for both depression and vitamin D deficiency, to our knowledge, there has been only one study investigating the association of vitamin D and depression in the nursing home with marginal findings. 6 This study examines the association of prevalent depressive symptoms with vitamin D deficiency among recently admitted nursing home residents. METHODS This cross-sectional study involved male veterans admitted between 2011 and 2012 to the Veterans Affairs Pacific Islands Health Care System Community Living Center for rehabilitation, skilled-nursing, intermediate, and respite care and was approved by the Institutional Review Board. The 15-item GDS 7 was used to assess depressive symptoms. Patients with GDS >5 were considered to have prevalent depressive symptoms. Total serum 25-hydroxyvitamin D (25(OH)D) levels were measured. Vitamin D deficiency was defined as 25(OH)D level<20 ng/ml. 4 Demographic data collected included age, ethnicity, body mass index (BMI), reasons for 3

admission, setting prior to admission, smoking, alcohol use, vitamin D supplementation and antidepressant use. The cohort was divided into vitamin D deficient and the non-deficient groups and compared in demographic variables, GDS, and prevalent depressive symptoms using t-tests and chi-square tests for continuous and categorical variables, respectively. We used univariate and multivariate logistic regression models to calculate odds ratios (OR) with 95% confidence intervals (CI) of prevalent depressive symptoms for vitamin D deficiency and vitamin D levels, adjusted for covariates. RESULTS Of 302 male veterans admitted, those without 25(OH)D levels (n=61) or GDS (n=123) and on antidepressants (n=27) or vitamin D supplementation (n=27) were excluded, the latter two to control for potential effects on psychological and vitamin D status, leaving 64. (21.2%). Mean 25(OH)D level was 20.9 ng/ml and the prevalence of vitamin D deficiency was 51.6%. Mean age was 67.8 years and mean BMI was 27.3. Half of the cohort was White (50.0%) and Asian/ Pacific Islander was 42.2%. Mean GDS score was 3.1, and 23.4% had >5 points. Patients with vitamin D deficiency were significantly likelier to be younger and have higher BMI. Vitamin D deficiency and 25(OH)D were used in multivariate logistic regression models as independent variables in two models, respectively, both adjusted for age, BMI, and ethnicity. While 25(OH)D was not associated with prevalent depressive symptoms, vitamin D deficiency was significantly and independently associated with prevalent depressive symptoms (OR=9.05, 4

95%CI=1.61-50.71, p=0.01) (Table 1). DISCUSSION Our findings support an association between depressive symptoms and vitamin D deficiency in nursing home residents. Vitamin D deficiency was independently and significantly associated with prevalent depressive symptoms in the multivariate logistic regression model among 64 veterans at the time of nursing home admission. Enigmatically, in our study, BMI appears to have a complex confounding effect that may be unique to the elderly and merit further investigation. Although obesity is associated with higher mortality in general populations, higher BMI has been shown to have a survival benefit in older adults known as obesity paradox. 8 In our cohort, higher BMI was associated with both higher levels of vitamin D deficiency and less depressive whereas in the literature obesity is known to be a risk factor for both vitamin D deficiency 9 and depression 10 in younger adults. The obesity-vitamin D deficiency link has been attributed to excess adipose tissues acting as storage of fat soluble vitamin D leading to lower bioavailability or lower exposure to sunlight due to impaired mobility or disability. 9 In elderly residing in nursing homes, malnutrition and weight loss can be highly prevalent, and low BMI can be associated with depression. In the elderly, low BMI may thus be a surrogate marker of poor overall health status leading possibly to depressed symptoms. Potential limitations of this study include cross-sectional study design; small subject size; cohort 5

of male veterans; inherent sampling bias with the exclusion of veterans as described above; and although validated to be a reliable screening tool use of GDS scores as opposed to psychiatric interviews. In this study, Vitamin D deficiency was significantly associated with prevalent depressive symptoms among recently admitted nursing home residents after adjusting for covariates. This important association merits further investigation and clarification. ACKNOWLEDGMENT Author Contributions Study concept and design: GK, MT, KM, GWR, AT, and HP. Acquisition of data: GK and AT. Analysis and interpretation of data: GK, MT, KM, GWR, AT, HP, GG, and DF. Drafting the article: GK. Revising the article critically for important intellectual content: GK, MT, KM, GWR, AT, HP, GG, and DF. Final approval of the version to be published: GK, MT, KM, GWR, AT, HP, GG, and DF. Sponsor s Role None. 6

REFERENCES 1. Hoover DR, Siegel M, Lucas J, et al. Depression in the first year of stay for elderly long-term nursing home residents in the USA. Int Psychogeriatr 2010;22:1161-1171. 2. Seitz D, Purandare N, Conn D. Prevalence of psychiatric disorders among older adults in long-term care homes: a systematic review. Int Psychogeriatr 2010;22:1025-1039. 3. Anglin RE, Samaan Z, Walter SD, et al. Vitamin D deficiency and depression in adults: systematic review and meta-analysis. Br J Psychiatry 2013;202:100-107. 4. Holick MF. Vitamin D deficiency. N Engl J Med 2007;357:266-281. 5. Rolland Y, de Souto Barreto P, Abellan Van Kan G, et al. Vitamin D supplementation in older adults: searching for specific guidelines in nursing homes. J Nutr Health Aging 2013;17:402-412. 6. Verhoeven V, Vanpuyenbroeck K, Lopez-Hartmann M, et al. Walk on the sunny side of life--epidemiology of hypovitaminosis D and mental health in elderly nursing home residents. J Nutr Health Aging 2012;16:417-420. 7. Sheikh JI, Yesavage JA. Geriatric Depression Scale (GDS). Recent evidence and development of a shorter version.: The Haworth Press, Inc; 1986. 8. Oreopoulos A, Kalantar-Zadeh K, Sharma AM, et al. The obesity paradox in the elderly: potential mechanisms and clinical implications. Clin Geriatr Med 2009;25:643-659, viii. 9. Lagunova Z, Porojnicu AC, Lindberg F, et al. The dependency of vitamin D status on body mass index, gender, age and season. Anticancer Res 2009;29:3713-3720. 10. Singh M. Mood, food, and obesity. Front Psychol 2014;5:925. 7

Table 1. Odds ratios of prevalent depressive symptoms* for vitamin D status using multivariate logistic regression models. Model 1 Model 2 Factors Odds Ratio (95%CI ) p value Odds Ratio (95%CI) p value vitamin D deficiency 9.05 (1.61-50.71) 0.01 - - vitamin D level - - 0.94 (0.86-1.01) 0.11 age 1.06 (0.98-1.14) 0.15 1.04 (0.97-1.11) 0.24 body mass index 0.84 (0.72-0.97) 0.02 0.85 (0.74-0.98) 0.03 White ref - ref - Asian/Pacific islander 0.47 (0.10-2.15) 0.33 0.39 (0.09-1.68) 0.20 Black 0.51 (0.03-7.47) 0.62 0.76 (0.06-10.19) 0.84 * Prevalent depressive symptoms: Defined as Geriatric Depression Scale score of five or more. Model 1: Outcome variable is vitamin D deficiency defined as serum 25-hydroxyvitamin D level <20ng/mL. Model 2: Outcome variable is serum 25-hydroxyvitamin D level. Both adjusted for age, body mass index, and ethnicity. CI: Confidence interval. Vitamin D deficiency: Defined as serum 25-hydroxyvitamin D level <20ng/mL. 8