Vitamin D deficiency is common in psychogeriatric patients, independent of diagnosis

There has been an increase in interest in vitamin D deficiency over the last 10 years. Several studies have revealed a high prevalence of vitamin D deficiency even in areas of the world that receive ample sunlight. The level of 25-hydroxyvitamin D (25(OH)D) is used to evaluate subjects’ vitamin D status. In Australia, India, and Saudi Arabia, 30-50% of children and adults have 25(OH)D levels below 50 nmol/L [1‐3]. Similarly, in Norway, more than 40% of the population have been reported to have serum 25(OH)D levels below 50 nmol/L [4]. Only a few types of food naturally contain vitamin D (e.g., salmon, mackerel, and cod liver oil); therefore, the major source of vitamin D is sunlight [5]. UVB radiation in the 290–315 nm wavelength converts 7-dehydrocholesterol in the skin to previtamin D3, which, in turn, is converted into vitamin D3. Vitamin D3 is then hydroxylated in the liver to 25(OH)D and further hydroxylated in the kidneys to its active form, 1,25 dihydroxyvitamin D (1,25(OH)₂D) [6]. Latitude and season affect the quantity and quality (wavelength) of solar radiation and thus influence the ability of sunlight to synthesize vitamin D3 in the skin [7]. For example, in Edmonton, Canada (52°N), skin exposed to sunlight from October through March produced no previtamin D3 [7]. Previous studies showed that elderly individuals produce only 25% of the cutaneous vitamin D produced by young adults [8].

There has been some debate concerning the optimal range of 25(OH)D. Serum levels of 25(OH) D below 50 nmol/L are associated with an increase in serum parathyroid hormone (PTH) levels [9] and a decrease in physical performance in older individuals [10]. It has been suggested that serum 25(OH)D levels above 50 nmol/L are sufficient to sustain bone density and calcium absorption and to prevent osteomalacia [11]. This cut-off level is now widely used in studies of vitamin D deficiency.

Several cross-sectional studies have found an association between vitamin D deficiency and depression or depressive symptoms [12‐16]. Despite some negative reports [17], Anglin et al. [18] concluded in a recent meta-analysis that low vitamin D concentration is associated with depression, but further randomized controlled trials (RCTs) of vitamin D are needed to determine whether this association is causal. There have been a few RCTs studying the effects of vitamin D on depressive symptoms, but the findings are inconsistent [19‐21]. A recently published RCT did investigate the effects of vitamin D supplementation as adjuvant treatment in patients with major depressive disorder. The results showed a significant improvement in patients being treated with an antidepressant and vitamin D as compared with patients receiving an antidepressant and placebo [22]. There are also studies reporting an association between vitamin D deficiency and cognitive impairment [23‐25] and even psychosis has been associated with vitamin D deficiency [26‐28].

Psychogeriatric patients may be at risk for vitamin D deficiency due to their age, less exposure to sunlight, and dietary factors. However, there is little knowledge regarding the actual vitamin D status in this group of patients. Therefore, one aim of this study was to compare the level of 25(OH)D in a sample of psychogeriatric patients with the level in the general elderly population from the same area. In addition, the study aimed to examine whether patients with depression differ from patients with other psychiatric diagnoses with regard to vitamin D status.

In this study, we found a high prevalence (71.6%) of vitamin D deficiency in elderly psychiatric patients compared with a control group (19.2%). We could not find any difference in vitamin D deficiency between patients in different diagnostic groups. Although this study was conducted in the northern part of Norway, vitamin D deficiency is a common problem in other parts of the world as well. Van der Wielen et al. found that among the elderly, vitamin D deficiency was more common in southern Europe than in Scandinavia [36]; therefore, our findings seem to be relevant globaly.

Our results are in line with those of other studies. In a group of psychogeriatric inpatients, Lapid et al. found no association between 25(OH)D level and psychiatric diagnosis [37], and the same findings were reported in a non-elderly group [38]. A Swedish study of adult psychiatric outpatients reported low levels of 25(OH)D (median 45 nmol/L), with slightly lower levels in patients with schizophrenia and autism compared with other diagnoses [39]. However, we are not aware of any studies that have examined the difference in levels of 25(OH)D between a control group and psychogeriatric patients with a wide range of psychiatric disorders.

There are several possible explanations for our findings. On the one hand, it is possible that older individuals with psychiatric disorders have a diet and outdoor activity pattern that may result in vitamin D deficiency, which could also be the case for different diagnostic groups, not only depressed patients. The hospital associated with this study is located at high latitude in the northern part of Norway, where there is no sun-induced production of vitamin D in the skin for more than 6 months of the year [7]. This patient group could thus be even more vulnerable to vitamin D deficiency due to a diet low in vitamin D. On the other hand, one cannot rule out the possibility that vitamin D deficiency can contribute to the development of several psychiatric disorders. It is well known that a diversity of psychiatric symptoms can occur in connection with various medical conditions. Some patients with thyrotoxicosis develop depression, others develop anxiety or psychosis, and some do not develop psychiatric disorders at all [40]. The same pattern is found in patients with hyperparathyroidism [41] and in patients with low levels of vitamin B12 [42]. These results suggests that there could be some unknown individual factors that make some people more vulnerable than others to the development of various psychiatric symptoms due to alterations in these hormones and micronutrients. Although we could not find a significant difference in serum 25(OH)D levels between different diagnostic groups, we can not rule out the possibility of a type II error, due to modest number of subjects in some of our diagnostic sub-groups.

Several human and animal studies have suggested possible biological explanations for the importance of vitamin D in psychiatric disorders. Vitamin D receptors and the enzyme required for its activation, 1α hydroxylase, have been identified in the human brain [43]. Active vitamin D (1,25(OH)₂D) is shown to alter cholinergic, dopaminergic, and noradrenergic neurotransmitter systems in animal models [44]. Abnormalities of these neurotransmitters have been linked to various neuropsychiatric disorders [45]. Groves et al. studied the impact of adult vitamin D deficiency in two strains of mice [46], and a small reduction in an enzyme involved in GABA synthesis (GAD65/67) was reported. Altered GABAergic neurotransmission has been linked to several psychiatric conditions, including schizophrenia [47], anxiety [48], and depression [49]. In the most neophobic strain (BALB/c mice), Groves et al. also found alterations in glutamate and glutamine levels in brain tissue, which may indicate a disruption in glutaminergic neurotransmission. NMDA receptor (glutamate receptor) dysfunction has been linked to several psychiatric conditions, including depression and schizophrenia [50, 51].

As expected, there was a significant negative correlation between serum 25(OH)D and PTH levels [9, 52]. High levels of PTH have been associated with impaired performance in cognitive tests [53] and with depression [52]. Primary hyperparathyroidism with elevated PTH and calcium can present with a variety of psychiatric symptoms [41], and we previously reported that this may be due to elevated PTH and not elevated calcium [54]. It is therefore possible that an effect of vitamin D on psychiatric symptoms could be indirectly caused by elevated PTH levels.

There was no significant difference in vitamin D levels between patients who reported taking a vitamin D supplement and patients who reported not taking a vitamin D supplement. These data are based on patients’ self-reporting and thus it is difficult to draw any firm conclusions. However, the finding could strengthen the impression that the recommended supplement dose of vitamin D in Norway (400 IE vitamin D₃) is not enough to maintain an adequate level of vitamin D in elderly individuals, and several authors have recommended 800–1000 IE vitamin D₃ as a daily supplement for the elderly [6, 55, 56].

Although the role of vitamin D in psychiatric disorders is not clear, there are also other reasons to be aware of vitamin D deficiency. A meta-analysis of 17 randomised trials demonstrated a 12% risk reduction in fractures in patient groups receiving calcium and vitamin D supplements [57]. Vitamin D deficiency can cause proximal muscle weakness and muscle pain [58]. Vitamin D supplements increase muscle strength and balance and reduce the risk of falling [59, 60]. In observational studies, vitamin D deficiency has also been associated with an increased risk of several other conditions, including cancer, diabetes, and multiple sclerosis, as well as a higher overall mortality rate and premature aging [6, 61‐63]. However, a recent review by Autier et al., found that intervention studies did not show an effect of vitamin D supplementation on non-skeletal health outcome whereas observational studies did. An exception was slightly reduced all-cause mortality [64]. The authors proposed that this difference in outcome might indicate that low 25(OH)D is a marker for ill health [64].

Our current study has some limitations. A reverse causality cannot be ruled out in this type of study design, as we do not know whether vitamin D deficiency is a contributor or a consequence of psychiatric disorders. In the control group, we did not have data to assess medical comorbidity, and therefore, we were not able to control for ill health as a possible confounder. We did not have data on the amount of time spent outdoors, use of vitamin D supplements, or psychiatric symptoms in the control group. It is unlikely, however, that elderly patients with significant mental distress participated in the population survey. Hansen et al. found that non-attendees in a survey had a 2.5-fold higher prevalence of psychiatric disorders compared with attendees [65]. In the patient group, there may also have been some recollection bias when the patients were asked about vitamin D supplementation and time spent outdoors.

Although our study did not address the issue as to whether the observed differences represent a causal relationship between vitamin D deficiency and psychiatric symptoms, the results are nonetheless important given the significance of vitamin D to overall health. We suggest that increased attention should be given to vitamin D deficiency in elderly patients with psychiatric disorders. Serum 25(OH)D assessment should be included in the set of standard blood tests performed in this patient group and treatment with vitamin D should be initiated in patients with low serum 25(OH)D. There is mounting evidence suggesting that vitamin D could have an impact on a variety of psychiatric conditions; however, more RCTs are needed to address the question of causality.