Escitalopram and neuroendocrine response in healthy first-degree relatives to depressed patients--a randomized placebo-controlled trial

Introduction

The mechanisms by which selective serotonin re-uptake inhibitors (SSRI) act in depressed patients remain unknown. The serotonergic neurotransmitter system and the hypothalamic-pituitary-adrenal (HPA) system may interact. The aim of the AGENDA trial was to investigate whether long-term intervention with SSRI versus placebo affects the cortisol response in the dexamethasone corticotropin-releasing hormone (DEX-CRH) test in healthy first-degree relatives to patients with major depressive disorder (MDD).

Methods

Eighty healthy first-degree relatives to patients with MDD were randomized to escitalopram 10 mg versus matching placebo daily for four weeks. The primary outcome measure was the intervention difference in the change of the total area under the curve (CorAUC_total) for plasma cortisol in the DEX-CRH test at entry to after four weeks of intervention.

Results

Change in CorAUC_total showed no statistically significant difference between the escitalopram and the placebo group, p = 0.47. There were large intra- and inter-individual differences in the results of the DEX-CRH test. There was statistically significant negative correlation between the plasma escitalopram concentration and change in CorAUC_total, rho = −0.41, p = 0.01. Post-hoc analyses showed a statistically significant interaction between age and intervention group and change in log CorAUC_total.

Conclusion

The present trial does not support an effect of escitalopram 10 mg daily compared with placebo on the HPA-axis in healthy first-degree relatives to patients with MDD. Increasing levels of escitalopram tended to decrease the HPA-response in the DEX-CRH test and this effect increased with age.

Trial Registration

ClinicalTrials.gov [{"type":"clinical-trial","attrs":{"text":"NCT00386841","term_id":"NCT00386841"}}NCT00386841     

Genetic polymorphisms in the hypothalamic pathway in relation to subsequent weight change--the DiOGenes study

Background

Single nucleotide polymorphisms (SNPs) in genes encoding the components involved in the hypothalamic pathway may influence weight gain and dietary factors may modify their effects.

Aim

We conducted a case-cohort study to investigate the associations of SNPs in candidate genes with weight change during an average of 6.8 years of follow-up and to examine the potential effect modification by glycemic index (GI) and protein intake.

Methods and Findings

Participants, aged 20–60 years at baseline, came from five European countries. Cases (‘weight gainers’) were selected from the total eligible cohort (n = 50,293) as those with the greatest unexplained annual weight gain (n = 5,584). A random subcohort (n = 6,566) was drawn with the intention to obtain an equal number of cases and noncases (n = 5,507). We genotyped 134 SNPs that captured all common genetic variation across the 15 candidate genes; 123 met the quality control criteria. Each SNP was tested for association with the risk of being a ‘weight gainer’ (logistic regression models) in the case-noncase data and with weight gain (linear regression models) in the random subcohort data. After accounting for multiple testing, none of the SNPs was significantly associated with weight change. Furthermore, we observed no significant effect modification by dietary factors, except for SNP rs7180849 in the neuromedin β gene (NMB). Carriers of the minor allele had a more pronounced weight gain at a higher GI (P = 2×10⁻⁷).

Conclusions

We found no evidence of association between SNPs in the studied hypothalamic genes with weight change. The interaction between GI and NMB SNP rs7180849 needs further confirmation.     

A comparative study of airborne pollen concentrations of three allergenic types

Airborne concentrations of pollen from Betula (birch), Poaceae (grasses) and Artemisia (mugwort) are compared during a seven year period (90–96) with respect to both quantitative and seasonal aspects, at three different sampling sites, one in Estonia (Tartu) and two in Sweden (Stockholm and Roma on the island of Gotland). All three taxa occur in the region and are well‐known causes of allergic sensitisation. The annual total and peak values of birch, grass and mugwort pollen were found to be much higher in Tartu than in Stockholm and Roma. Both the birch and the grass pollen seasons ended later in Stockholm than in Roma and Tartu. The mugwort flowering season always began earlier in Stockholm than at the other sites, and more days elapsed between start day and peak day in Stockholm than in Tartu.     

CD163 Binding to Haptoglobin-Hemoglobin Complexes Involves a Dual-point Electrostatic Receptor-Ligand Pairing

Formation of the haptoglobin (Hp)-hemoglobin (Hb) complex in human plasma leads to a high affinity recognition by the endocytic macrophage receptor CD163. A fast segregation of Hp-Hb from CD163 occurs at endosomal conditions (pH <6.5). The ligand binding site of CD163 has previously been shown to involve the scavenger receptor cysteine-rich (SRCR) domain 3. This domain and the adjacent SRCR domain 2 of CD163 contain a consensus motif for a calcium-coordinated acidic amino acid triad cluster as originally identified in the SRCR domain of the scavenger receptor MARCO. Here we show that site-directed mutagenesis in each of these acidic triads of SRCR domains 2 and 3 abrogates the high affinity binding of recombinant CD163 to Hp-Hb. In the ligand, Hp Arg-252 and Lys-262, both present in a previously identified CD163 binding loop of Hp, were revealed as essential residues for the high affinity receptor binding. These findings are in accordance with pairing of the calcium-coordinated acidic clusters in SRCR domains 2 and 3 with the two basic Arg/Lys residues in the Hp loop. Such a two-point electrostatic pairing is mechanistically similar to the pH-sensitive pairings disclosed in crystal structures of ligands in complex with tandem LDL receptor repeats or tandem CUB domains in other endocytic receptors.     

Marten space use and habitat selection in managed coniferous boreal forests of eastern Canada

Effects of habitat loss and fragmentation on the behavior of individual organisms may have direct consequences on population viability in altered forest ecosystems. The American marten (Martes americana) is a forest specialist considered as one of the most sensitive species to human-induced disturbances. As some studies have shown that martens cannot tolerate >30–40% clear-cuts within their home range, we investigated marten space use (home range size and overlap) and habitat selection in landscapes fragmented by 2 different patterns of timber harvesting in the black spruce boreal forest: dispersed-cut landscapes (10–80 ha cut-blocks) and clustered-cut landscapes (50–200 ha cut-blocks). We installed radio-collars on female martens and determined 20 winter home ranges (100% minimum convex polygons and 60–90% kernels) in dispersed-cut (n = 8) and clustered-cut (n = 12) landscapes. Home range size was not related to the proportion of clear-cuts (i.e., habitat loss), but rather to the proportion of mixedwood stands 70–120 years old. However, female body condition was correlated to habitat condition inside their home ranges (i.e., amount of residual forest and recent clear-cuts). At the home range scale, we determined that mixedwood forests were also among the most used forest stands and the least used were recent clear-cuts and forested bogs, using resource selection functions. At the landscape scale, home ranges included more mixedwood forests than random polygons and marten high activity zones were composed of more residual forest and less human-induced disturbances (clear-cuts, edges, and roads). These results suggest that mixedwood forests, which occupy approximately 10% of the study area, play a critical role for martens in this conifer-dominated boreal landscape. We recommend permanent retention or special management considerations for these isolated stands, as harvesting mixedwood often leads to forest composition conversion that would reduce the availability of this highly used habitat. © The Wildlife Society, 2013     

Effect of ultraviolet-B radiation in laboratory on morphological and ultrastructural characteristics and physiological parameters of selected cultivar of Oryza sativa L.

Ultraviolet-B radiation (UVBR) affects plants in many important ways, including reduction of growth rate and primary productivity, and changes in ultrastructures. Rice (Oryza sativa) is one of the most cultivated cereals in the world, along with corn and wheat, representing over 50 % of agricultural production. In this study, we examined O. sativa plants exposed to ambient outdoor radiation and laboratory-controlled photosynthetically active radiation (PAR) and PAR + UVBR conditions for 2 h/day during 30 days of cultivation. The samples were studied for morphological and ultrastructural characteristics, and physiological parameters. PAR + UVBR caused changes in the ultrastructure of leaf of O. sativa and leaf morphology (leaf index, leaf area and specific leaf area, trichomes, and papillae), plant biomass (dry and fresh weight), photosynthetic pigments, phenolic compounds, and protein content. As a photoprotective acclimation strategy against PAR + UVBR damage, an increase of 66.24 % in phenolic compounds was observed. Furthermore, PAR + UVBR treatment altering the levels of chlorophylls a and b, and total chlorophyll. In addition, total carotenoid contents decreased after PAR + UVBR treatment. The results strongly suggested that PAR + UVBR negatively affects the ultrastructure, morphology, photosynthetic pigments, and growth rates of leaf of O. sativa and, in the long term, it could affect the viability of this economically important plant.     

A new species of Goera Stephens, 1829 (Goeridae: Trichoptera) from the Solomon Islands

Male and female of Goera pitisopai sp. nov. from the Solomon Islands are illustrated and described based on recently collected material. This is the first species of the family Goeridae reported from the Solomon Islands, and the sixth from the Australasian region.     

The diet of polar bears (Ursus maritimus) from Svalbard, Norway, inferred from scat analysis

Polar bears (Ursus maritimus) are heavily dependent on marine prey, in particular ice-associated seals, which they hunt on landfast sea ice or free-floating pack ice. Dramatic current (and predicted) losses of sea ice habitat make it increasingly important to gain more knowledge of the relative use by bears of all types of prey from the marine food web as well as from terrestrial sources. This study uses frequency of occurrence of food items in 119 polar bear scats sampled on the sea ice as well as on shore in coastal areas in the Svalbard Archipelago, mainly in spring, between 2003 and 2010 to explore the diet of bears in the region. Ringed seals (Pusa hispida) occurred in 62.2 % (CI 52.8–70.9 %) of the scat samples examined. Various terrestrial plants (32.8 %, CI 24.4–42.0 %) and marine algae (21.8 %, CI 14.8–30.4 %) also occurred frequently in the scats; the significance of this high occurrence of plants and algae is not clear. Bearded seals (Erignathus barbatus) and various bird species constituted only minor components of the diet, while Svalbard reindeer (Rangifer tarandus platyrhynchus) occurred in 9.2 % (CI 4.7–15.9 %) of the scats, indicating that this species may play a more important role than previously reported. The novel combination of genetic analyses of material in the fecal samples along with detailed exploration of the physical–structural properties of prey hairs and plant parts provided a much fuller picture of the diet of polar bears than would have been possible from observational studies of polar bear predation behavior alone. This approach may provide an important tool for monitoring the responses of polar bears to ongoing ecosystem changes that will result from continued warming in the Arctic.