Role of Vitamin D in Cognitive Dysfunction: New Molecular Concepts and Discrepancies between Animal and Human Findings.

PURPOSE OF REVIEW: increasing evidence suggests that besides the several metabolic, endocrine, and immune functions of 1alpha,25-dihydroxyvitamin D (1,25(OH)2D), the neuronal effects of 1,25(OH)2D should also be considered an essential contributor to the development of cognition in the early years and its maintenance in aging. The developmental disabilities induced by vitamin D deficiency (VDD) include neurological disorders (e.g., attention deficit hyperactivity disorder, autism spectrum disorder, schizophrenia) characterized by cognitive dysfunction. On the other hand, VDD has frequently been associated with dementia of aging and neurodegenerative diseases (e.g., Alzheimer's, Parkinson's disease). RECENT FINDINGS: various cells (i.e., neurons, astrocytes, and microglia) within the central nervous system (CNS) express vitamin D receptors (VDR). Moreover, some of them are capable of synthesizing and catabolizing 1,25(OH)2D via 25-hydroxyvitamin D 1alpha-hydroxylase (CYP27B1) and 25-hydroxyvitamin D 24-hydroxylase (CYP24A1) enzymes, respectively. Both 1,25(OH)2D and 25-hydroxyvitamin D were determined from different areas of the brain and their uneven distribution suggests that vitamin D signaling might have a paracrine or autocrine nature in the CNS. Although both cholecalciferol and 25-hydroxyvitamin D pass the blood-brain barrier, the influence of supplementation has not yet demonstrated to have a direct impact on neuronal functions. So, this review summarizes the existing evidence for the action of vitamin D on cognitive function in animal models and humans and discusses the possible pitfalls of therapeutic clinical translation.

Influence of Vitamin D Supplementation on Mental Health in Diabetic Patients: A Systematic Review.

Diabetes is associated with a number of mental health consequences, including enhanced risk of depression and anxiety, as well as decreased quality of life, and vitamin D deficiency is considered to be one of the factors that influence these outcomes in diabetic patients. The aim of the present study was to conduct a systematic review of the literature presenting the data regarding the influence of vitamin D supplementation on mental health in diabetic adults. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (Registration number CRD42020155779). A systematic search of the PubMed and Web of Science databases was performed, and the intervention studies published until September 2021 were included in the review. The human studies were included if an adult sample of diabetic individuals received vitamin D supplementation during the intervention and its effect on any mental health aspect was assessed, but studies presenting the influence of combined supplementation of multiple nutrients were excluded. After removing duplicate records, a total of 8514 publications were screened and assessed independently by two researchers, based on their title, abstract, and full text. Finally, six studies were included in the current systematic review, and the risk of bias was evaluated using the Newcastle-Ottawa Scale (NOS). The included studies analyzed the influence of a specific dose of vitamin D, or different doses of vitamin D, or compared the results of supplementation with a specific dose of vitamin D against the placebo group. The supplementation was performed for at least 12 weeks. The mental health outcomes analyzed in these studies included health-related quality of life, depression, anxiety, stress, and general mental health status of adult diabetic patients. The results of the majority of the studies confirmed the positive influence of vitamin D supplementation on the mental health of diabetic individuals. Those studies that analyzed the influence of vitamin D supplementation on depression and anxiety established the beneficial effect of the vitamin. In some studies, the influence of vitamin D supplementation on the health-related quality of life was not considered unless combined with mindfulness training. However, it must be emphasized that different dosage regimens and intervention periods were followed in the reviewed studies, and only a small number of studies were randomized against placebo, which should be considered as a limitation of the present study. The findings of the conducted systematic review demonstrated the positive influence of vitamin D supplementation on the mental health of diabetic patients, which was proved for anxiety and depression, but in the case of health-related quality of life, the positive effect was observed only when the intervention included mindfulness training. These outcomes suggest that supplementation should be recommended to improve the vitamin D status and the mental health of patients in this group.

Vitamin D Level Trajectories of Adolescent Patients with Anorexia Nervosa at Inpatient Admission, during Treatment, and at One Year Follow Up: Association with Depressive Symptoms.

(1) Background: Evidence has accumulated that patients with anorexia nervosa (AN) are at higher risk for vitamin D deficiency than healthy controls. In epidemiologic studies, low 25(OH) vitamin D (25(OH)D) levels were associated with depression. This study analyzed the relationship between 25(OH)D serum levels in adolescent patients and AN and depressive symptoms over the course of treatment. (2) Methods: 25(OH)D levels and depressive symptoms were analyzed in 93 adolescent (in-)patients with AN from the Anorexia Nervosa Day patient versus Inpatient (ANDI) multicenter trial at clinic admission, discharge, and 1 year follow up. Mixed regression models were used to analyze the relationship between 25(OH)D levels and depressive symptoms assessed by the Beck Depression Inventory (BDI-II). (3) Results: Although mean 25(OH)D levels constantly remained in recommended ranges (≥50 nmol/L) during AN treatment, levels decreased from (in)patient admission to 1 year follow up. Levels of 25(OH)D were neither cross-sectionally, prospectively, nor longitudinally associated with the BDI-II score. (4) Conclusions: This study did not confirm that 25(OH)D levels are associated with depressive symptoms in patients with AN. However, increasing risks of vitamin D deficiency over the course of AN treatment indicate that clinicians should monitor 25(OH)D levels.

Effect of Early High-Dose Vitamin D3 Repletion on Cognitive Outcomes in Critically Ill Adults.

BACKGROUND: Long-term cognitive impairment frequently occurs after critical illness; no treatments are known to improve long-term cognition. RESEARCH QUESTION: Does a single high-dose (540,000 International Units) enteral treatment of vitamin D3 given shortly after hospital admission in critically ill patients who are vitamin D deficient improve long-term global cognition or executive function? STUDY DESIGN AND METHODS: This study evaluated long-term cognitive outcomes among patients enrolled in a multicenter, blinded, randomized clinical trial comparing vitamin D3 treatment vs placebo in critically ill adults with vitamin D deficiency. Global cognition was measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Executive function was measured with a composite score derived from three Delis-Kaplan Executive Function System subscales. Outcomes were assessed at a median of 443 days (interquartile range, 390-482 days) after randomization and were compared using multivariate proportional odds regression. Adjusted ORs of > 1.0 would indicate better outcomes in the vitamin D3 group compared with the placebo group. RESULTS: Ninety-five patients were enrolled, including 47 patients randomized to vitamin D3 treatment and 48 patients randomized to placebo. The adjusted median RBANS score at follow-up was 79.6 (95% CI, 73.0-84.0) in the vitamin D3 group and 82.1 (95% CI, 74.7-84.6) in the placebo group (adjusted OR, 0.83; 95% CI, 0.50-1.38). The adjusted median executive function composite scores were 8.1 (95% CI, 6.8-9.0) and 8.7 (95% CI, 7.4-9.3), respectively (adjusted OR, 0.72; 95% CI, 0.36-1.42). INTERPRETATION: In vitamin D-deficient, critically-ill adults, a large dose of enteral vitamin D3 did not improve long-term global cognition or executive function. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03733418; URL: www.clinicaltrials.gov.

The Effects of Vitamin D-Enriched Mushrooms and Vitamin D3 on Cognitive Performance and Mood in Healthy Elderly Adults: A Randomised, Double-Blinded, Placebo-Controlled Trial.

Despite abundant cross-sectional evidence that low vitamin D status is associated with risk of cognitive decline in ageing, interventional evidence for benefits of vitamin D supplementation is lacking. This study was a 6 month randomised, double-blinded placebo-controlled clinical trial of the effects of vitamin D3 (D3), enhanced vitamin D2 in a mushroom matrix (D2M), standard mushroom (SM) and placebo (PL) on cognition and mood in n = 436 healthy older male (49%) and female volunteers aged ≥ 60 years. Primary end points were change in serum vitamin D metabolites (25-OH-D, 25-OH-D2 and 25-OH-D3), cognitive performance, and mood over 24 weeks. Levels of total 25-OH-D and 25-OH-D3 were maintained in the D3 arm but decreased significantly (p < 0.05) in the remaining arms (D2M, SM and PL). Analysis also revealed differential changes in these metabolites depending on total vitamin D status at baseline. There were no significant effects of treatment on any of the measures of cognitive function or mood. Overall, the results show that daily supplementation of ~600 IU of vitamin D3 was sufficient to maintain 25-OH-D throughout winter months, but in contrast to existing cross-sectional studies there was no support for benefit of vitamin D supplementation for mood or cognition in healthy elderly people.

Barriers towards Sun Exposure and Strategies to Overcome These Barriers in Female Indoor Workers with Insufficient Vitamin D: A Qualitative Approach.

The prevalence of vitamin D insufficiency is significant even in tropical countries such as Malaysia. Sun exposure is the primary source of vitamin D for most people due to limited intakes of food containing vitamin D and supplements. This study explored the perception of barriers towards sun exposure and strategies to overcome these barriers among vitamin D insufficient women workers in Kuala Lumpur, Malaysia. Twenty-five female indoor workers with serum 25-hydroxyvitamin D < 50 nmol/L participated in seven focus group discussions (FGDs). Barriers towards sun exposure were lack of accurate knowledge of vitamin D, health concern towards sun exposure, time constraints, desire to have fair and beautiful skin, sedentary lifestyle, indoor workplace, weather, lack of social support, living arrangement, safety concerns, and religious or cultural practices. The improvement strategies were classified into lifestyle changes and workplace opportunity for sun exposure. Public education on safe sun exposure to produce an optimal level of vitamin D is necessary. Future studies should evaluate the effectiveness of sunlight exposure program at workplace for the high-risk vitamin D deficiency group.

Serum 25-Hydroxyvitamin D Concentrations Are Associated with Mental Health and Psychosocial Stress in Young Adults.

: We aimed to test the hypothesis that serum 25-hydroxyvitamin D3 (25(OH)D) concentration is associated with mental health and life stress measures in young adults and investigate gender and racial disparities in these associations. This study comprised 327 black and white participants. Depression, trait anxiety, perceived stress, and hostility were measured by the following validated instruments: Beck Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI), Perceived Stress Scale (PSS), and Cook-Medley Hostility Scale (CMHS). Linear regression was used to estimate correlations between serum 25(OH)D concentration and mental health measurements in the total population and in subgroups stratified by gender and race. In this sample (28.2 ± 3.1 years, 52% female, 53% black), serum 25(OH)D concentration was negatively related to BDI, STAI, PSS, total CMHS score, and the majority of CMHS subscale scores (p-values < 0.05). Stratified by gender, most of these associations remained significant only in women (p-values < 0.05). Stratified by race, higher 25(OH)D concentrations in white participants were significantly related to lower BDI, STAI, PSS, and CMHS-cynicism subscales (p-values < 0.05); 25(OH)D concentrations in the black participants were only inversely associated with CMHS and most CMHS subscales (p-values < 0.05) but not with BDI, STAI, and PSS. We present novel findings of consistent inverse relationships between serum 25(OH)D concentration and various measures of mental health and life stress. Long-term interventional studies are warranted in order to investigate the roles of vitamin D supplementation in the prevention and mitigation of depression, anxiety, and psychological stress in young adults.

On maternal Post-Partum/Natal depression. A global underrecognized problem and the need for better Treatment strategies.

BACKGROUND: Maternal Postpartum (PPD) or Postnatal Depression (PND) is believed to be the commonest medical complication postpartum. Evidence suggests a significantly higher prevalence of the disease compared to the often reported 10-15%. METHOD: Studies were identified by accessing several databases including PubMed/Medline, PubMed Central, EBSCO, and PsycINFO. RESULTS: Vitamin D (VD) deficiency, hormonal levels alteration (estrogen, progesterone, testosterone, oxytocin, and prolactin), thyroid dysfunction, and increased oxidative stress, play a critical role in PPD etiopathogenesis and pathophysiology. CONCLUSIONS: Treatment strategies should include an integrated approach of antidepressants and psychotherapy, melatonin, diet, sleep improvement, exercise, VD and antioxidants supplementation, and economic and social support.

Vitamin D Deficiency and Sleep Quality in Minority Pregnant Women.

PURPOSE: To examine if vitamin D deficiency was associated with poor sleep quality in a sample of African American and Hispanic pregnant women. We also examined if race moderates the relationship between serum 25(OH)D levels and sleep quality among participants in this sample. STUDY DESIGN AND METHODS: Using a cross-sectional design, a sample of 115 African American and Hispanic pregnant women were enrolled from a federally qualified health center in the Midwest. Women completed questionnaires and had blood drawn for serum 25(OH)D levels between 24- and 32 weeks gestation. The questionnaires included demographic characteristics, the Pittsburgh Sleep Quality Index, and dietary vitamin D and calcium intake. RESULTS: The overall regression model indicated that the predictors explained 17% of variance in sleep quality (F(5, 103) = 4.10, p = .002, R = 0.17). Serum 25(OH)D levels were significant predictors of sleep quality after controlling for covariates (i.e., race, maternal age, prepregnancy body mass index, gestational age at data collection). Race did not moderate the association between serum 25(OH)D levels and sleep quality among women in this sample. CLINICAL IMPLICATIONS: Pregnant women should be screened for vitamin D deficiency. Women who have vitamin D deficiency should be provided vitamin D supplementation. Vitamin D supplementation may be a simple solution to enhance sleep quality at this critical time in a woman's life.

Vitamin D supplementation compared to placebo in people with First Episode psychosis - Neuroprotection Design (DFEND): a protocol for a randomised, double-blind, placebo-controlled, parallel-group trial.

BACKGROUND: People experiencing their first episode of psychosis are often deficient in vitamin D. Observational studies have reported an association between low vitamin D concentrations and poorer subsequent health outcomes in psychosis. A vitamin D deficiency in neonates and children has been linked to a later increased risk of schizophrenia and psychotic-like experiences. This trial aims to examine the effect of high-dose vitamin D supplementation on outcomes in early psychosis. We hypothesise that vitamin D supplementation will be associated with better mental health outcomes. METHODS/DESIGN: The DFEND study is a multicentre double-blind placebo-controlled parallel-group trial of vitamin D supplementation in people with early psychosis. Patients with an ICD-10 diagnosis of functional psychosis will be randomised in a 1:1 ratio to receive either 120,000 IU/month of vitamin D (cholecalciferol) or a matched placebo for 6 months. The primary outcome is the total Positive and Negative Syndrome Scale (PANSS) score at the 6-month follow-up for all patients. Secondary outcomes include assessment of mood (Calgary Depression Scale), general function (Global Assessment of Functioning), cardiovascular risk (body mass index, waist circumference, C-reactive protein, cholesterol and HbA1c) and vitamin D levels at the 6-month follow-up. Additionally, 3- and 6-month total PANSS scores will be analysed for those with inadequate vitamin D levels at the baseline. DISCUSSION: The DFEND study is the first trial to examine whether vitamin D supplementation in early psychosis is associated with better mental health outcomes. The findings of this study may help to resolve the clinical equipoise regarding the benefits and cost-effectiveness of routine vitamin D supplementation in people with psychosis. TRIAL REGISTRATION: ISRCTN, ISRCTN12424842. Registered on 25 February 2015.

Relative D3 vitamin deficiency and consequent cognitive impairment in an animal model of Alzheimer's disease: Potential involvement of collapsin response mediator protein-2.

Alzheimer's disease (AD) starts with memory impairments that can be observed before the appearance of significant neuropathology; thus, identifying mechanisms to stop AD progression is an urgent priority. Epidemiological and clinical data show that the consequences of vitamin D deficiency are relevant to disease risk and can be observed in the progression of many diseases, especially AD, whereas higher serum levels of vitamin D are associated with better cognitive test performance. However, the potential therapeutic strategy and underlying mechanisms of vitamin D supplementation against AD still need to be further investigated. In the present study, we found that 3xTg-AD mice with vitamin D supplementation exhibited an increase in serum vitamin D concentrations and improved cognition. We measured serum vitamin D binding protein (VDBP) concentrations and found that serum VDBP levels were increased in 3xTg-AD mice compared to B6129S control mice, but there was no significant difference between control- and vitamin D-treated 3xTg-AD groups. The vitamin D-mediated memory improvement may be accompanied by the suppression of increased hippocampal collapsin response mediator protein-2 (CRMP2) phosphorylation, and the restoration of CRMP2 phosphorylation by okadaic acid (OA) could abolish the beneficial effects of vitamin D. In addition, we found that CRMP2 was associated with NR2B and PSD-95 in 3xTg-AD mice with vitamin D supplementation. This CRMP2-NR2B interaction could be disrupted by a TAT-CBD3 peptide or OA, leading to attenuated memory protection in vitamin D-treated 3xTg-AD mice. Therefore, CRMP2 may be involved in vitamin D-mediated memory improvement in AD.

The sunshine under our skin: public knowledge and practices about vitamin D deficiency in Al Ain, United Arab Emirates.

This cross-sectional study among members of public showed that people generally had good knowledge and awareness about vitamin D. However, inconsistencies between awareness and attitudes were observed. Our findings reinforce the need of educating people to improve attitude and practices toward vitamin D consumption. INTRODUCTION: Owing to its hot and dry climate, United Arab Emirates (UAE) is one of the top ranked vitamin D deficient countries. However, little is known about people's awareness surrounding this topic. METHODS: A descriptive cross-sectional survey to assess people's knowledge, awareness, and attitude toward vitamin D deficiency was conducted in Al Ain city of UAE. A 25-item validated self-administered questionnaire was used for data collection. Differences among demographic groups were analyzed using chi-square test, and simple binary logistic regressions were used to investigate the association between vitamin D awareness and other significant risk factors. RESULTS: More than 90% of the total 346 participants showed awareness toward vitamin D and its deficiency. Doctors were reported as the most common source of information. More than one-third of the participants claimed to have vitamin D deficiency with significantly more females than males. More than 70% of the sample considered sunlight as the best source of vitamin D and avoiding going out in sun as the major risk for vitamin D deficiency. Nearly half (43%) of the participants did not consume milk and only 24% claimed to be using vitamin D supplements. Females were found to be applying sunscreen and consuming vitamin supplements significantly more than their male counterparts. Participants aged 24-35 years, having bachelor degree and those who were tested for vitamin D, were found to score better for awareness questions. CONCLUSIONS: Our findings demonstrate a mismatch between knowledge and awareness, and attitude implying the need of educating people to improve their attitude toward consuming vitamin D rich food and supplements.

Vitamin D Supplementation for Premenstrual Syndrome-Related inflammation and antioxidant markers in students with vitamin D deficient: a randomized clinical trial.

Premenstrual syndrome (PMS) is a common disorder in the reproductive age that negatively significant impacts on women's quality of life. This randomized clinical trial study was undertaken to investigate the effect of vitamin D supplementation on inflammatory and antioxidant markers in 44 vitamin D deficient (25(OH)D < 20 ng/mL) students with PMS. Participants received either 50,000 IU vitamin D3 or a placebo pearl fortnightly for 4 months. At the baseline and in the last 2 months of intervention, participants were asked to complete the PMS Daily Symptoms Rating form along with taking the pearls and their blood samples were collected to assess serum levels of 25(OH)D3, Interleukin10 and 12 (IL-10, IL-12) and total antioxidant capacity (TAC). In vitamin D group, serum levels of IL-10 and IL-12 significantly decreased while TAC significantly increased post-intervention. There were significant differences regarding serum IL-12 and TAC levels between the two groups. Mean score of the total PMS symptoms showed significant improvement in 25(OH)D. Vitamin D supplementation seems to be an effective strategy to improve inflammation and antioxidant markers in vitamin D deficient women with PMS. This clinical trial was registered at Iranian Registry of Clinical Trials on 20/06/2018 (IRCT20180525039822N1).

We still don't know that our children need vitamin D daily: a study of parents' understanding of vitamin D requirements in children aged 0-2 years.

BACKGROUND: Vitamin D deficiency has been highlighted as a serious public health problem in the United Kingdom. One in four toddlers are not achieving the recommended intake for their healthy development. This study uses quantitative and qualitative methods to explore parents' perceptions, awareness and behaviours around vitamin D intake, and the acceptability of and factors affecting purchasing of food and drink fortified with Vitamin D in children aged 0-2 years old. METHODS: One hundred and ninety-four parents completed an online questionnaire, advertised to parents with one child aged up to 2 years on popular social media websites. The majority of participants were mothers, White-British ethnic background, aged 25-44 years. Participants provided an email address if they wanted to be contacted about the focus groups. Recruitment posters advertising the focus groups were placed in community centres. Eighteen participated in 5 focus groups (13 parents), and 5 individual interviews. A thematic analysis methodology was applied. RESULTS: Fifty-seven percent (n = 110) of parents reported receiving information about vitamin D during pregnancy and 52% (n = 100) after the birth of their child. Parents reported a low level of satisfaction with vitamin D information: many thought it was limited and recommendations on supplements were unclear. Parents wanted more information about vitamin D requirements for their child (80%, n = 153 out of 192 respondents, 2 non-response), about vitamin D and breastfeeding (56%, n = 108) and vitamin D and pregnancy (49%, n = 94). The recommendations were for simpler, easier to read, with specific and clearer guidelines; delivered regularly during routine appointments, at timely stages throughout pregnancy and after the birth. 23% (n = 45, out of 194 respondents) of parents did not know why vitamin D is important for health. Only 26% (n = 49, out of 192 respondents) of parents reported giving their youngest child a vitamin D supplement on most days of the week. The majority of parents (interview/focus group) wanted more information about foods/drinks fortified with vitamin D. CONCLUSION: Parents were generally not aware of the importance of vitamin D, dietary requirements including supplementation and the availability of vitamin D fortified foods. Major improvements are required for the effective promotion of vitamin D information to parents.

Is Vitamin D Supplementation Useful for Weight Loss Programs? A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background and Objectives: The controversy about the impact of vitamin D supplementation on weight loss treatment was observed in several randomized controlled trials (RCTs). This meta-analysis investigates the effects of vitamin D supplementation (cholecalciferol or ergocalciferol) on weight loss through holistic measurements of Body Mass Index (BMI), weight and waist circumference. Materials and Methods: Google Scholar, WOS, PubMed and Scopus were explored to collect relevant studies. The selected articles focused on vitamin D supplementation in overweight and obese individuals with different conditions. Eleven RCTs were included into this meta-analysis with a total of 947 subjects, with a mean of the follow-up from 1 to 12 months and different vitamin D interventions (from 25,000 to 600,000 IU/monthly of cholecalciferol). Results: The meta-analyzed mean differences for random effects showed that cholecalciferol supplementation deceases the BMI by -0.32 kg/m2 (CI95% -0.52, -0.12 kg/m2, p = 0.002) and the waist circumference by -1.42 cm (CI95% -2.41, -0.42 cm, p = 0.005), but does not statistically affect weight loss -0.43 kg (CI95% -1.05, +0.19 kg, p = 0.17). Conclusions: This meta-analysis lays the foundation for defining the potential clinical efficacy of vitamin D supplementation as a potential therapeutic option for weight loss programs, but further studies are needed to confirm the validity of these findings and delineate potential underlying mechanisms.

The relationship between Vitamin D and depressive disorders.

Studies have suggested a relationship between low circulating levels of Vitamin D and depression. Vitamin D deficiency may be a consequence of depression-related factors, such as reduced sun exposure, decreased outdoor activity, and dietary changes, but it can also play a role in the pathophysiology of depressive conditions through a range of molecular mechanisms. In the present manuscript, findings related to prospective longitudinal studies on the relationship between Vitamin D levels and depressive symptoms and to randomized controlled trials on Vitamin D supplementation for depressive disorders are reviewed.

The prevalence of depressive symptoms in Chinese longevous persons and its correlation with vitamin D status.

BACKGROUND: Hypovitaminosis D and depressive syndromes are common conditions in old adults. However, little is known about the relationship between vitamin D and depression in exceptional aged people. The objective of this study is to evaluate the relationship between vitamin D levels and depressive symptoms in Chinese longevous persons. METHODS: We used a dataset from a cross-sectional survey of a sample of Chinese longevous people with self-reported age 100 or older, including 175 men and 765 women, was conducted from June 2014 to December 2016 in Hainan Province, China. Data on demographics, lifestyle characteristics and health conditions were collected using a structured questionnaire. Anthropometrics and blood samples were obtained following the standard procedure. Depressive symptoms of the participants were assessed using a shortened version of the Geriatric Depression Scale (GDS-15). Serum vitamin D levels were measured using an automated radioimmunoassay. RESULTS: The prevalence of longevous persons with depressive symptoms among the sample was 32.2% (95% confidence interval: 29.7-34.7%). Serum vitamin D levels were lower in participants with depressive symptoms than in those without (20.8 ± 8.7 vs. 23.7 ± 9.7, ng/mL). Vitamin D deficiency was an independent risk factor for depression after controlling for the potential covariates (Odds ratio = 1.47, 95% Confidence interval = 1.08-2.00; p = 0.014). A negative relationship between serum vitamin D levels and depressive symptoms was also detected, and the relationship remained significant after adjusting for a wide range of other covariates. The multivariate adjusted odds ratio of depressive symptoms for the lowest versus highest quartiles of vitamin D levels was 1.73 (95% confidence interval: 1.10-2.72), and the adjusted odds ratio with a 5 ng/mL decrement of serum 25OHD levels was 1.10 (95% confidence interval: 1.01-1.19). CONCLUSIONS: This study showed an inverse association between vitamin D levels and depressive symptoms among Chinese longevous persons. Depressive symptoms should be screened in longevous persons who had vitamin D deficiency. Further studies on vitamin D supplement and prevention along with treatment of depression are needed among very old population.

Vitamin D as potential antidepressant in outpatients with musculoskeletal pain
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OBJECTIVE: To determine the incidence of vitamin D deficiency, anxiety, and depression disorders in an outpatient population with musculoskeletal pain (MSP), and to evaluate the effects of correcting a vitamin D deficiency on MSP and psychological symptoms. MATERIALS AND METHODS: A total of 261 outpatients with MSP and 100 controls were involved. The Hospital Anxiety and Depression Scale (HADS) was used to assess psychological symptoms. Serum vitamin D was measured. Outpatients with vitamin D insufficiency and deficiency received oral vitamin D supplementation. Pain severity and psychological symptoms were evaluated before and after vitamin D supplementation plus dairy products. RESULTS: Vitamin D deficiency was found in 88.7% of participants in the MSP group and 69% of controls. Clinical anxiety was reported by 38.3% of participants in the MSP group and 9% of controls, while clinical depression was reported by 31.8% of participants in the MSP group and 2% of controls. Multisite pain was significantly and positively associated with anxiety, depression, and pain severity, and was inversely associated with daily calcium intake. Anxiety was inversely associated with vitamin D level, daily calcium intake, and age. A similar pattern was observed for depression. MSP was the most significant independent predictor of anxiety (OR = 7.84) and depression (OR = 5.89). Relative to baseline, all measured outcome parameters significantly improved after vitamin D supplementation plus increased intake of dairy products. CONCLUSION: Low serum vitamin D is associated with MSP along with low calcium intake, depression, and anxiety. Supplementation with vitamin D improved MSP and associated disorders.
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Vitamin D deficiency and depressive symptoms in the perinatal period.

Depression affects 1 in 7 women during the perinatal period. Women with vitamin D deficiency may be at an increased risk for depression. This study investigated the relationship between maternal and cord blood 25-hydroxyvitamin D (25OHD) and maternal depressive symptoms over the perinatal period. Study objectives were to examine variations and relationships between maternal and cord blood vitamin D levels and maternal depressive symptoms over the perinatal period. At a large medical center in southern California, pregnant women (N = 126) were recruited for this longitudinal cohort study. Depressive symptoms (Edinburgh Postnatal Depression Screen, EPDS) and vitamin D status (25OHD) were measured at three time points in the perinatal period: time 1 (T1; N = 125) EPDS and 25OHD were collected in early pregnancy; time 2 (T2; N = 96) EPDS was conducted in the third trimester with blood collected at time of delivery; and time 3 (T3; N = 88) was collected postpartum. A significant inverse relationship between vitamin D status and depressive symptoms was observed between 25OHD and EPDS scores at all time points in this sample (T1 = - 0.18, P = 0.024; T2 = - 0.27, P = 0.009; T3 = - 0.22, P = 0.019). This association remained after controlling for confounders. Low cord blood 25OHD levels were inversely associated with higher EPDS scores in the third trimester (r = - 0.22, P = 0.02). Clinicians may want to consider screening women diagnosed with vitamin D deficiency for depression and vice versa. Vitamin D may represent an important biomarker for pregnant and postpartum women diagnosed with depression. Further studies examining underlying mechanisms and supplementation are needed.

Effect of an vitamin D deficiency on depressive symptoms in child and adolescent psychiatric patients - a randomized controlled trial: study protocol.

BACKGROUND: Depression is a significant health and economic burden worldwide affecting not only adults but also children and adolescents. Current treatment options for this group are scarce and show moderate effect sizes. There is emerging evidence that dietary patterns and specific nutritional components might play a role in the risk for developing depression. This study protocol focusses on the role of vitamin D which is for long known to be relevant for calcium and phosphorous homeostasis and bone health but might also impact on mental health. However, the assessment of the vitamin D status of depressed juvenile patients, or supplementation of vitamin D is currently not part of routine treatment. Controlled intervention studies are indispensable to prove whether a vitamin D deficiency ameliorates depressive symptoms. METHODS/DESIGN: This double blinded, randomized controlled trial will enroll 200 inpatients from a child and adolescent psychiatric department with a vitamin D deficiency defined by a 25(OH)-vitamin D-level < 30 nmol/l (12 ng/ml) and a Beck Depressions Inventory (BDI-II) score > 13 (indicating at least: mild depression). Upon referral, all patients will be screened, checked for inclusion criteria, and those eligible will be randomized after written consent into a supplementation or placebo group. Both study-arms will receive treatment-as-usual for their psychiatric disorder according to established clinical guidelines. The participants of the vitamin D supplementation group will receive 2640 I.E. vitamin D3 q.d. for 28 days in accordance with best practice in pediatric endocrinology. We hypothesize that delaying supplementation of vitamin D in the placebo arm will affect the treatment success of the depressive symptomatology in comparison to the vitamin D supplementation group. Patients will be enrolled for a period of 28 days based on the mean length of hospitalization of juveniles with depression. DISCUSSION: Randomized controlled trials in children and adolescents with depression are needed to elucidate the role of a vitamin D deficiency for mental disorders and to investigate the relevance of a routine assessment and supplementation of vitamin D deficits. TRIAL REGISTRATION: DRKS00009758, 16/06/2016 (retrospectively registered).