RESUMEN
Over the last half century, a body of convergent evidence has accumulated linking disruption of early brain development with an increased risk of mental disorders, including schizophrenia. The orderly cascade of brain development may be disrupted by exposure to suboptimal concentrations of a range of biological substrates and micronutrients. We hypothesized that those exposed to vitamin D deficiency during early life, have an increased risk of neurodevelopmental disorders, including schizophrenia. The hypothesis was based on the link between an increased risk of schizophrenia in (a) those born in winter and spring, when vitamin D deficiency is more prevalent, and (b) the offspring of dark-skinned migrants living in cold climates, who have a markedly increased risk of vitamin D deficiency. In this review, we summarize evidence from analytic epidemiology related to this hypothesis. Two case-control studies based on Danish neonatal dried blood spots have found that neonatal vitamin deficiency is associated with an increased risk of schizophrenia. However, recent genetic analyses have also suggested that common variants linked to schizophrenia may lead to lower vitamin D concentrations (possibly mediated via reduced outdoor activity). We summarize limitations of the current evidence and outline suggestions that can guide future research. Based on currently available data, there is insufficient evidence to support public health recommendations related to this topic. However, we cannot reject the hypothesis that the provision of vitamin D supplementation to pregnant women and/or offspring in groups vulnerable to vitamin D deficiency may subsequently reduce the incidence of schizophrenia in the offspring.
Asunto(s)
Esquizofrenia , Deficiencia de Vitamina D , Femenino , Humanos , Recién Nacido , Micronutrientes , Embarazo , Estaciones del Año , Vitamina D , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/epidemiologíaRESUMEN
The aim of the present study was to describe vitamin D status and seasonal variation in the general Danish population. In this study, 3092 persons aged 2 to 69 years (2565 adults, 527 children) had blood drawn twice (spring and autumn) between 2012 and 2014. A sub-sample of participants had blood samples taken monthly over a year. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were measured by liquid chromatography mass spectrometry, and information on supplement use was assessed from questionnaires. Seasonal variations in 25(OH)D concentrations were evaluated graphically and descriptively, and status according to age, sex, and supplement use was described. It was found that 86% of both adults and children were vitamin D-sufficient in either spring and or/autumn; however, many had a spring concentration below 50 nmol/L. A wide range of 25(OH)D concentrations were found in spring and autumn, with very low and very high values in both seasons. Among adults, women in general had higher median 25(OH)D concentrations than men. Furthermore, vitamin D supplement use was substantial and affected the median concentrations markedly, more so during spring than autumn. Seasonal variation was thus found to be substantial, and bi-seasonal measurements are vital in order to capture the sizable fluctuations in vitamin D status in this Nordic population.
Asunto(s)
Estaciones del Año , Deficiencia de Vitamina D/epidemiología , Vitamina D/análogos & derivados , Adolescente , Adulto , Anciano , Niño , Preescolar , Dinamarca/epidemiología , Suplementos Dietéticos , Escolaridad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios , Vitamina D/administración & dosificación , Vitamina D/sangre , Deficiencia de Vitamina D/sangreRESUMEN
Objective: Several genetic polymorphisms determine vitamin D status. We aimed to estimate the strength of association of established 25-hydroyxvitamin D (25OHD)-associated variants in the mother and in the fetus, with 25OHD concentration in newborn umbilical cord plasma. Methods: We randomly selected 578 mother and child dyads from the prospective Norwegian Mother and Child Cohort study. 25OHD was assayed in maternal samples taken shortly after delivery and in cord samples. We genotyped the mother and child for single nucleotide polymorphisms in or near GC, DHCR7, CYP2R1, and CYP24A1, previously confirmed to be associated with 25OHD, and computed genetic risk score (GRS). The genetic associations were replicated in an independent sample of 594 subjects. Results: Although both fetal and maternal GRS were associated with cord 25OHD, only fetal GRS remained significantly associated with cord 25OHD in a regression model with maternal and fetal GRS simultaneously (1.6 nmol/L per fetal 25OHD-increasing allele; 95% confidence interval, 0.6 to 2.5, P = 0.0001). Two fetal single nucleotide polymorphisms in the GC gene (rs2282679 and rs222040) were the strongest genetic predictors of cord 25OHD [4.0 (2.1 to 5.9) and 3.0 (1.3 to 4.8) nmol/L per fetal allele, P < 0.001], followed by rs12785878 in DHCR7 [2.0 (0.1 to 3.8) nmol/L, P = 0.037]. The independent replication sample gave similar results. With fetal genotype included in a regression model with environmental factors, R2 for cord 25OHD was 0.28. Conclusions: We show that fetal 25OHD-modifying genotype was a stronger predictor of cord 25OHD than corresponding maternal genotype. This raises interesting questions about fetal acquisition and placental transfer of 25OHD.
Asunto(s)
Estado Nutricional/genética , Polimorfismo de Nucleótido Simple , Deficiencia de Vitamina D/congénito , Deficiencia de Vitamina D/genética , Vitamina D/sangre , Adulto , Estudios de Cohortes , Suplementos Dietéticos , Femenino , Feto/metabolismo , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Recién Nacido , Intercambio Materno-Fetal/genética , Madres , Embarazo , Atención Prenatal , Fenómenos Fisiologicos de la Nutrición Prenatal/genética , Vitamina D/administración & dosificación , Deficiencia de Vitamina D/sangre , Adulto JovenRESUMEN
AIMS/HYPOTHESIS: The aim of this work was to assess whether neonatal levels of 25-hydroxyvitamin D (25(OH)D) are associated with risk of developing type 1 diabetes before the age of 18 years. METHODS: Two large-scale studies with different designs-a case-cohort and a case-control-were conducted using Danish national register data and biobank material. Weighted Cox regression and conditional logistic regression were used to calculate HRs and ORs, respectively. The concentration of 25(OH)D was assessed from neonatal dried blood spots using highly sensitive liquid chromatography-tandem mass spectrometry. Quintiles of 25(OH)D3 were used in the main analyses. RESULTS: The case-cohort study included 912 type 1 diabetes cases and 2866 individuals without type 1 diabetes born in Denmark between 1981 and 2002 and followed up until the end of 2012. The case-control study included 527 matched case-control pairs born between 1981 and 1999 and followed up until May 2004. Both studies found no association between 25(OH)D3 levels and later risk of developing type 1 diabetes. The neonatal total 25(OH)D levels in the studies were low: 46% (case-cohort study) and 51% (case-control study) of individuals had 25(OH)D levels <25 nmol/l. CONCLUSIONS/INTERPRETATION: Our two large-scale national studies showed that 25(OH)D3 levels around the time of birth were not associated with later type 1 diabetes risk. Whether higher levels of 25(OH)D3 during pregnancy, acquired by higher doses of supplementation than are recommended today in most countries, could protect the offspring against type 1 diabetes cannot be ruled out by the present studies.