Interaction between CRHR1 and BDNF Genes Increases the Risk of Recurrent Major Depressive Disorder in Chinese Population

BACKGROUND: An important etiological hypothesis about depression is stress has neurotoxic effects that damage the hippocampal cells. Corticotropin-releasing hormone (CRH) regulates brain-derived neurotrophic factor (BDNF) expression through influencing cAMP and Ca2+ signaling pathways during the course. The aim of this study is to examine the single and combined effects of CRH receptor 1 (CRHR1) and BDNF genes in recurrent major depressive disorder (MDD). METHODOLOGY/PRINCIPAL FINDING: The sample consists of 181 patients with recurrent MDD and 186 healthy controls. Whether genetic variations interaction between CRHR1 and BDNF genes might be associated with increased susceptibility to recurrent MDD was studied by using a gene-based association analysis of single-nucleotide polymorphisms (SNPs). CRHR1 gene (rs1876828, rs242939 and rs242941) and BDNF gene (rs6265) were identified in the samples of patients diagnosed with recurrent MDD and matched controls. Allelic association between CRHR1 rs242939 and recurrent MDD was found in our sample (allelic: p = 0.018, genotypic: p = 0.022) with an Odds Ratio 0.454 (95% CI 0.266-0.775). A global test of these four haplotypes showed a significant difference between recurrent MDD group and control group (chi-2 = 13.117, df = 3, P = 0.016. Furthermore, BDNF and CRHR1 interactions were found in the significant 2-locus, gene-gene interaction models (p = 0.05) using a generalized multifactor dimensionality reduction (GMDR) method. CONCLUSION: Our results suggest that an interaction between CRHR1 and BDNF genes constitutes susceptibility to recurrent MDD

The Concise Guide to PHARMACOLOGY 2013/14: overview.

The Concise Guide to PHARMACOLOGY 2013/14 provides concise overviews of the key properties of over 2000 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties from the IUPHAR database. The full contents can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.12444/full. This compilation of the major pharmacological targets is divided into seven areas of focus: G protein-coupled receptors, ligand-gated ion channels, ion channels, catalytic receptors, nuclear hormone receptors, transporters and enzymes. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. A new landscape format has easy to use tables comparing related targets. It is a condensed version of material contemporary to late 2013, which is presented in greater detail and constantly updated on the website www.guidetopharmacology.org, superseding data presented in previous Guides to Receptors & Channels. It is produced in conjunction with NC-IUPHAR and provides the official IUPHAR classification and nomenclature for human drug targets, where appropriate. It consolidates information previously curated and displayed separately in IUPHAR-DB and GRAC and provides a permanent, citable, point-in-time record that will survive database updates

Estimation of the dietary requirement for vitamin D in white children aged 4–8 y: a randomized, controlled, dose-response trial

Background: Children in northern latitudes are at high risk of vitamin D deficiency during winter because of negligible dermal vitamin D3 production. However, to our knowledge, the dietary requirement for maintaining the nutritional adequacy of vitamin D in young children has not been investigated. Objective: We aimed to establish the distribution of vitamin D intakes required to maintain winter serum 25-hydroxyvitamin D [25(OH)D] concentrations above the proposed cutoffs (25, 30, 40, and 50 nmol/L) in white Danish children aged 4–8 y living at 55°N. Design: In a double-blind, randomized, controlled trial 119 children (mean age: 6.7 y) were assigned to 0 (placebo), 10, or 20 μg vitamin D3/d supplementation for 20 wk. We measured anthropometry, dietary vitamin D, and serum 25(OH)D with liquid chromatography–tandem mass spectrometry at baseline and endpoint. Results: The mean ± SD baseline serum 25(OH)D was 56.7 ± 12.3 nmol/L (range: 28.7–101.4 nmol/L). Serum 25(OH)D increased by a mean ± SE of 4.9 ± 1.3 and 17.7 ± 1.8 nmol/L in the groups receiving 10 and 20 μg vitamin D3/d, respectively, and decreased by 24.1 ± 1.2 nmol/L in the placebo group (P 30 (avoiding deficiency) and >50 nmol/L (ensuring adequacy) in 97.5% of participants were 8.3 and 19.5 μg/d, respectively, and 4.4 μg/d was required to maintain serum 25(OH)D >40 nmol/L in 50% of participants. Conclusions: Vitamin D intakes between 8 and 20 μg/d are required by white 4- to 8-y-olds during winter in northern latitudes to maintain serum 25(OH)D >30–50 nmol/L depending on chosen serum 25(OH)D threshold. This trial was registered at clinicaltrials.gov as NCT02145195

Estimation of the dietary requirement for vitamin D in white children aged 4–8 y: a randomized, controlled, dose-response trial

Background: Children in northern latitudes are at high risk of vitamin D deficiency during winter because of negligible dermal vitamin D3 production. However, to our knowledge, the dietary requirement for maintaining the nutritional adequacy of vitamin D in young children has not been investigated. Objective: We aimed to establish the distribution of vitamin D intakes required to maintain winter serum 25-hydroxyvitamin D [25(OH)D] concentrations above the proposed cutoffs (25, 30, 40, and 50 nmol/L) in white Danish children aged 4–8 y living at 55°N. Design: In a double-blind, randomized, controlled trial 119 children (mean age: 6.7 y) were assigned to 0 (placebo), 10, or 20 μg vitamin D3/d supplementation for 20 wk. We measured anthropometry, dietary vitamin D, and serum 25(OH)D with liquid chromatography–tandem mass spectrometry at baseline and endpoint. Results: The mean ± SD baseline serum 25(OH)D was 56.7 ± 12.3 nmol/L (range: 28.7–101.4 nmol/L). Serum 25(OH)D increased by a mean ± SE of 4.9 ± 1.3 and 17.7 ± 1.8 nmol/L in the groups receiving 10 and 20 μg vitamin D3/d, respectively, and decreased by 24.1 ± 1.2 nmol/L in the placebo group (P 30 (avoiding deficiency) and >50 nmol/L (ensuring adequacy) in 97.5% of participants were 8.3 and 19.5 μg/d, respectively, and 4.4 μg/d was required to maintain serum 25(OH)D >40 nmol/L in 50% of participants. Conclusions: Vitamin D intakes between 8 and 20 μg/d are required by white 4- to 8-y-olds during winter in northern latitudes to maintain serum 25(OH)D >30–50 nmol/L depending on chosen serum 25(OH)D threshold. This trial was registered at clinicaltrials.gov as NCT02145195