Serum 25-hydroxyvitamin d and the onset of late-life depressive mood in older men and women: the Pro.V.A. study

Depression is a debilitating chronic condition, and its diagnosis and treatment in elderly people are often challenging. Because depressive mood seems to follow a seasonal pattern, peaking in summer and winter (1), it has recently been suggested that, through its action on the hypothalamus (which is involved in mood regulation), vitamin D might account for the link between seasonal changes in photoperiod and seasonal mood swings (2). Acting as a neurosteroid hormone, vitamin D may regulate human and animal neurotransmission, neuroprotection, and neuroimmunomodulation (3), and nuclear vitamin D receptors have been located in the human cortex and hippocampus (4). Although an association between vitamin D deficiency and depressive disorders is biologically feasible, results from clinical and epidemiological studies are still contradictory. Findings from several cross-sectional studies consistently point to hypovitaminosis D being related to mood disorders in elderly people, and serum 25-hydroxyvitamin D (25OHD) concentrations have been found lower in the depressed than in healthy controls (5–8). Very few longitudinal studies have prospectively explored the relationship between hypovitaminosis and late-life depression, however, and with conflicting results. In the InChianti population-based study, 25OHD levels less than 50 nmol/L seemed to raise the risk of developing depressive mood (9). On the other hand, Chan and coworkers (10) found no evidence of any association between 25OHD levels and incident depression in elderly people in their large Chinese prospective population-based study. Intervention studies on the effect of vitamin D supplementation on mood have been contradictory too, partly because they involved only small samples of participants and short periods of treatment, with no placebo control, and they failed to control for initial vitamin D status (11,12). Hypovitaminosis D and depression might share the same matrix because the two conditions commonly coexist in unhealthy older people. Despite this association between hypovitaminosis D and mood disorders in the elderly people, we hypothesized that low serum 25OHD concentrations might no longer be significant in predicting late-life depression after controlling for health, functional status, and physical performance. The aim of this study was thus to examine the longitudinal relationship between 25OHD levels and the onset of clinically relevant depressive symptoms over a lengthy follow-up (4.4 years) in a representative group of older men and women, controlling for functional status, physical performance, and a number of common later-life comorbidities.