Psychotropic medications target glycogen synthase kinase 3β (GSK3β), but the functional integration with other factors relevant for drug efficacy is poorly understood. We discovered that the ...suggested psychiatric risk factor FK506 binding protein 51 (FKBP51) increases phosphorylation of GSK3β at serine 9 (pGSK3β(S9)). FKBP51 associates with GSK3β mainly through its FK1 domain; furthermore, it also changes GSK3β's heterocomplex assembly by associating with the phosphatase PP2A and the kinase cyclin-dependent kinase 5. FKBP51 acts through GSK3β on the downstream targets Tau, β-catenin and T-cell factor/lymphoid enhancing factor (TCF/LEF). Lithium and the antidepressant (AD) paroxetine (PAR) functionally synergize with FKBP51, as revealed by reporter gene and protein association analyses. Deletion of FKBP51 blunted the PAR- or lithium-induced increase in pGSK3β(S9) in cells and mice and attenuated the behavioral effects of lithium treatment. Clinical improvement in depressive patients was predicted by baseline GSK3β pathway activity and by pGSK3β(S9) reactivity to ex vivo treatment of peripheral blood mononuclear lymphocytes with lithium or PAR. In sum, FKBP51-directed GSK3β activity contributes to the action of psychotropic medications. Components of the FKBP51-GSK3β pathway may be useful as biomarkers predicting AD response and as targets for the development of novel ADs.
Abstract Depression has frequently been reported to be associated with other physical diseases and changes in the cytokine system. We aimed to investigate associations between a medical history of ...depression, its comorbidities and cytokine plasma levels in the Bavarian Nutrition Survey II (BVS II) study sample and in patients suffering from an acute depressive episode. The BVS II is a representative study of the Bavarian population aged 13–80 years. The disease history of its 1050 participants was assessed through face-to-face interviews. A sub-sample of 568 subjects and 62 additional acutely depressed inpatients of the Max Planck Institute of Psychiatry participated in anthropometric measurements and blood sampling. Tumor necrosis factor-α (TNF-α) and soluble TNF receptor (sTNF-R) p55 and sTNF-R p75 plasma levels were measured using enzyme-linked immunosorbent assays. A history of depression was associated with a higher incidence of high blood pressure, peptic ulcer, dyslipoproteinemia, osteoporosis, allergic skin rash, atopic eczema and thyroid disease. Within the BVS II sample, participants with a history of depression differed from subjects who had never had depression with regard to sTNF-R p55 and sTNF-R p75 levels even when controlling for age, BMI and smoking status. Acutely depressed inpatients showed even higher levels of sTNF-R p55 and sTNF-R p75 than subjects in the normal population. TNF-α levels were also significantly elevated in acutely depressed patients. These results confirm earlier studies regarding the comorbidities of depression and support the hypothesis that activation of the TNF-α system may contribute to the development of a depressive disorder.
Although previous investigations have demonstrated reliable empirical relationships between satellite data and nearly contemporaneous ground observations, satellite imagery has not been incorporated ...into routine lake monitoring programs. This paper focuses on key issues involved in applying satellite imagery to the regional assessment of lake clarity. Ten Landsat Thematic Mapper (TM) images and four Multispectral Scanner (MSS) images of the Twin Cities Metropolitan Area (TCMA) spanning 25 years (1973–1998) were analyzed. Based on this analysis, recommendations are made for a Landsat-based procedure for water clarity assessment. Closeness of fit (
r
2 values) of regression models between satellite brightness data and measured Secchi disk transparency (SDT) decreased with increasing size of the time window between image collection and ground observation of SDT. Use of SDT data collected within ±1 day of the image date is recommended, but where SDT data are limited, windows up to ±7 days yield reasonable results, especially in late summer when water clarity is relatively constant. Average brightness data from at least nine pixels in the deep open area of a lake should be used to predict lake clarity, but the accuracy of predicted SDT did not improve much as the number of pixels in the area of interest (AOI) increased above this value. A three-coefficient regression model using the TM1/TM3 ratio and TM1 was a consistent and reliable predictor of SDT (
r
2 values of .7–.8). A similar relationship involving the MSS1/MSS2 ratio and MSS1 was a reasonable predictor of SDT for MSS data. Efforts to produce a standard prediction equation for SDT applicable to images collected on different dates were not successful, but a simple regression procedure to account for differences in atmospheric conditions among image collection dates substantially decreased the range of coefficients in the regression model.
Abstract We analyzed the association of sleep quality and glucose metabolism in women after gestational diabetes (pGDM) and in women after normoglycemic pregnancy (controls). Data during pregnancy ...and a visit within the first 15 months after delivery were collected from 61 pGDM and 30 controls in a prospective cohort study. This included a medical history, physical examination, questionnaires (Pittsburgh Sleep Quality Index (PSQI), and Perceived Stress Scale (PSS)), and 5-point oral glucose tolerance test with insulin measurements to determine indices of insulin sensitivity and insulin secretion. We used Spearman correlation coefficients and multivariate regression models for analysis.9.3 ± 3.2 months after delivery, pGDM had significantly higher fasting and 2 h glucose levels and lower insulin sensitivity than controls. There was no significant difference in age, BMI and sleep quality as assessed with the PSQI between the two groups. The PSQI score correlated with the ogtt-2 h plasma glucose in pGDM (δ = 0.41; p = 0.0012), but not in controls. This association was confirmed with a multivariate linear regression model with adjustment for age, BMI and months post-delivery. Perceived stress was an independent risk factor (OR 1.12; 95% CI 1.02–1.23) for impaired sleep. Our findings suggest that post-delivery sleep quality significantly influences glucose tolerance in women after GDM and that impaired sleep is associated with increased stress perception. Measures to improve of sleep quality and reduce perceived stress should therefore be tested as additional strategies to prevent progression to type 2 diabetes after GDM.
Gene–PUFA interactions and obesity risk Jourdan, C.; Kloiber, S.; Nieters, A. ...
British journal of nutrition,
10/2011, Letnik:
106, Številka:
8
Journal Article
Recenzirano
Odprti dostop
Although there are indications for modulatory effects of PUFA on associations between SNP and obesity risk, scientific evidence in human subjects is still scarce. The present analyses investigated ...interaction effects between SNP in candidate genes for obesity and PUFA in erythrocyte membranes on obesity risk. Within the second Bavarian Food Consumption Survey (cross-sectional, population-based), 568 adults provided blood samples. Fatty acid composition of erythrocyte membranes was analysed by means of GC. Genotyping was performed for twenty-one genes, including cytokines, adipokines, neurotransmitters and transcription factors. In addition, plasma IL-6 concentrations were analysed. For the statistical analysis, a logistic regression model assuming additive genetic effects was chosen. About 20 % of the study participants were classified as obese (BMI ≥ 30 kg/m2). Several significant gene–PUFA interactions were found, indicating regulatory effects of PUFA by gene variants of IL-2, IL-6, IL-18, TNF receptor family member 1B and 21, leptin receptor and adiponectin on obesity risk. After stratification by genotype, the strongest effects were found for rs2069779 (IL-2) and all tested PUFA as well as for rs1800795 (IL-6) and linoleic or arachidonic acid. The obesity risk of minor allele carriers significantly decreased with increasing fatty acid content. The genetic PUFA–IL-6 interaction was also reflected in plasma IL-6 concentrations. If replicated in a prospective study with sufficient statistical power, the results would indicate a beneficial effect of high PUFA supply for a substantial proportion of the population with respect to obesity risk.
Major depressive disorder (MDD) is one of the leading causes of global disability. It is a risk factor for noncompliance with medical treatment, with about 40% of patients not responding to currently ...used antidepressant drugs. The identification and clinical implementation of biomarkers that can indicate the likelihood of treatment response are needed in order to predict which patients will benefit from an antidepressant drug. While analyzing the blood plasma proteome collected from MDD patients before the initiation of antidepressant medication, we observed different fibrinogen alpha (FGA) levels between drug responders and nonresponders. These results were replicated in a second set of patients. Our findings lend further support to a recently identified association between MDD and fibrinogen levels from a large-scale study.
Major depression and the metabolic syndrome (MetS) are interacting clinical conditions influenced by genetic susceptibility. For both disorders, impaired serotonergic neurotransmission in specific ...brain areas has been suggested. This led us to investigate whether variants in the gene coding for tryptophan hydroxylase 2 (TPH2), the brain-specific and rate-limiting enzyme for serotonin biosynthesis, might be predictive for an increased liability for the development of MetS in depressed patients. In a case-control study consisting of 988 patients with recurrent unipolar depression (RUD) and 1023 psychiatric healthy controls, MetS components were ascertained according to the International Diabetes Foundation criteria. A total of 41 single nucleotide polymorphisms fully covering the TPH2 gene region were genotyped in stage 1 (300 patients/300 controls), resulting in significant genetic associations of polymorphisms located in exon 7 and intron 8 of TPH2 and the occurrence of MetS in depressed patients after correction for age, gender and multiple testing (51 RUD-MetS/179 RUD-non-MetS). We were able to confirm the significant association of rs17110690 in stage 2 (688 patients/723 controls; 110 RUD-MetS/549 RUD-non-MetS) and to link risk-genotypes and risk-haplotypes for MetS to lower TPH2 mRNA expression and to lower 5-hydroxyindoleacetic acid levels in cerebrospinal fluid previously reported in functional studies. Our findings suggest that TPH2 polymorphisms characterize a subgroup of depressed patients who are especially prone to develop metabolic disorders induced by a genotype-dependent impairment of serotonergic neurotransmission. Identifying depressed patients at high risk for MetS using genetic variants could have direct clinical impact on individualized disease management and prevention strategies.
A procedure that uses Landsat imagery to estimate Secchi disk transparency (SDT) of lakes was developed and applied to ∼500 lakes with surface areas >10
ha in the seven-county metropolitan area of ...Minneapolis and St. Paul, MN, USA, to assess spatial patterns and temporal trends in lake clarity. Thirteen Landsat MSS and TM images over the period 1973–1998 were used for the analysis. Satellite brightness values from lake surfaces were calibrated against available historical data on SDT (
n=∼20–40) measured nearly contemporaneously with the acquisition date of each image. Calibration regression equations for the late-summer TM images had a range of
r
2 from 0.72 to 0.93. Regression analysis for three late-summer MSS images yielded
r
2 values ranging from 0.60 to 0.79. Results indicate that a single late-summer image yields a reliable estimate of regional lake clarity and reasonably accurate estimates of SDT for individual lakes. An analysis of seasonal patterns on a large lake water-quality database was used to develop a model that adjusts synoptic satellite SDT estimates from different dates to a common reference, making them more comparable from year-to-year. Analysis of long-term trends shows that in spite of the large land-use changes within the region over the study period, only 49 (about 10%) of assessed lakes in the region showed significant temporal trends in SDT over the period, and more lakes had increasing SDT (34) than decreasing SDT (15).
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