A classifier driven approach to find biomarkers for affective disorders from transcription profiles in blood

Gene expression profiles in blood are increasingly being used to identify biomarkers for different affective disorders. We have selected a set of 29 genes to generate expression profiles for healthy control subjects as well as for patients diagnosed with acute post-traumatic stress disorder (PTSD) and with borderline personality disorder (BPD). Measurements were performed by quantitative polymerase chain reaction (qPCR). Using the actual data in an anonym-ous form we constructed a series of artificial data sets with known gene expression profiles. These sets were used to test 14 classification algorithms and feature selection methods for their ability to identify the correct expression patterns. Application of the three most effective algorithms to the actual expression data showed that control subjects can be dis-tinguished from BPD patients based on differential expression levels of the gene transcripts Gi2, GR and MAPK14, targets that may have links to stress related diseases. Controls can also be distinguished from acute PTSD patients by differential expression levels of the transcripts for ERK2 and RGS2 that are known to be associated with mood disord-ers and social anxiety. We conclude that it is possible to identify informative transcription profiles in blood samples from individuals with affective disorders

Personality, war trauma, PTSD and depression

Psychobiology of PTS

GR gene BclI polymorphysm changes the path, but not the level, of dexamethasone-induced cortisol suppression

Background: The hypothalamo-pituitary-adrenocortical (HPA) axis self-regulation is achieved via cortisol binding to mineralocorticoid (MR) and glucocorticoid receptors (GR). It is often disturbed in mental disorders, particularly in those where traumatic stress has been implicated, such as posttraumatic stress disorder and depression. Although dexamethasone suppression test (DST) is often used as diagnostic aid, the findings still vary. In search of the factors influencing the DST outcome, we examined the glucocorticoicl receptor (GR) gene Bell polymorphism. Methods: A total of 229 male subjects were classified into three Bell groups: two groups with homozygous carriers (of the G allele, N=108, and of the C allele, N=26), and one with heterozygous carriers (N=95). Multiple hierarchical linear regression analysis was clone, where the dependent variable was the clexamethasone-inclucecl cortisol suppression, and predictors included receptor variables. The interactions of the count of `G's with the predictors were introduced to single out the effects of the G allele. Results: The means of all studied variables, including suppression, are statistically the same in the three groups. However, the mechanism of suppression involves MRs only in the G allele carriers. Limitations: The subjects were selected by criteria suited for the aim of the large project whose part is this study, hence the relatively small number of CC carriers. Also, we did not assess MR functional properties that would probably sharpen the results. Conclusion: Our finding that MRs participate in cortisol suppression in the G allele carriers suggests that research aimed at refining HPA axis-based therapy might require its adjustment for such patients., (C) 2014 Elsevier By. All rights reserved.European Commission {[}INCO-CT-2004-509213]; Ministry of Science, Serbia {[}179018, 41009

Posttraumatic and depressive symptoms in beta-endorphin dynamics

A disturbed beta-endorphin system can be a part of the post-traumatic stress disorder (PTSD) and depression allostasis. Study subjects (N=392) included those with PTSD and/or (stress-induced) depression, and healthy controls with and without traumas. The aim of the study was to examine the network of relations centered around plasma beta-endorphin. The network included anxiety (as a personality trait), traumatic events, pain, aggressiveness, depressive symptoms, and three clusters of PTSD symptoms: intrusions, avoidance, and hyperarousal. Beta-endorphin was represented by individual mean from 13 time points (BEmean), reflecting the total amount of the peripherally secreted hormone, and the coefficient of variation (BEvar), calculated as the ratio of standard deviation to the mean, reflecting the hormone's dynamics. BEvar correlated with all other variables, BEmean had no correlations. Structural equation modeling (SEM) was used to examine all interrelations (including their directions) of BEvar and the state/trait variables in the context of their entirety. The model revealed that hyperarousal and anxiety were the only direct agents of peripheral beta-endorphin fluctuations, mediating the effects of other variables. Traumatic events and intrusions act on BEvar via hyperarousal, while depressive symptoms, avoidance, and pain act via anxiety. Hyperarousal should be emphasized as the main agent not only because its effect on BEvar is larger than that of anxiety, but also because it increases anxiety itself (via avoidance and pain). All influences on BEvar are positive and they indicate long-term (sensitizing) effects (as opposed to direct stimulation, for example, by acute pain, anger, etc.). Relations apart from beta-endorphin are also discussed. (C) 2015 Elsevier B.V. All rights reserved,European Commission, via Sixth Framework Programme {[}INCO-CT-2004-509213]; Ministry of Science, Serbia {[}179018, 41009

The fungistatic activity of organic selenium and its application to the production of cultivated mushrooms Agaricus bisporus and Pleurotus spp.

The activity of organic selenium against pathogenic molds and its use as a potential selenium source in the production of enriched mushrooms were examined. The effect of commercial selenized yeast on mycelia growth was examined using a method with mycelia disks and a well diffusion method. For mushroom enrichment, different concentrations of selenium were added to a growth substrate. The results presented in this paper suggest that the most suitable concentration of selenized yeast that inhibits the growth of the mycopathogenic molds is 70-100 mg/kg of selenium. With the addition of this concentration to the substrate, mushroom fruit bodies will uptake a high level of selenium, about 100 μg/g for Pleurotus spp., and 200 μg/g for Agaricus bisporus in dry weight of the mushroom. Thereby a double effect in the cultivation of mushrooms is achieved

Satureja horvatii essential oil: In vitro antimicrobial and antiradical properties and in situ control of Listeria monocytogenes in pork meat

The dominant compounds in Satureja horvatii oil were p-cymene (33.14\%), thymol (26.11\%) and thymol methyl ether (15.08\%). The minimum inhibitory concentration (MIC) varied from 0.03 to 0.57 mg/mL for bacteria, and from 0.56 to 2.23 mg/mL for yeast strains, while minimum bactericidal/yeast-cidal concentration (MBC/MYC) varied from 0.07 to 1.15 mg/mL and 1.11 to 5.57 mg/mL for bacteria and yeasts, respectively. The antiradical potential of the essential oil was evaluated using hydroxyl radical (center dot OH) generated in Fenton reaction. The meat preserving potential of essential oil from Satureja horvatii was investigated against L monocytogenes. Essential oil successfully inhibited development of L monocytogenes in pork meat. Sensorial evaluation on flavor and color of meat was performed. The color and flavor of meat treated with essential oil improved after 4 days of storage. S. horvatii essential oil can act as a potent inhibitor of food spoiling microorganisms, in meat products and also can be a useful source of natural antioxidants. (C) 2013 Elsevier Ltd. All rights reserved.Ministry of Education and Science of Serbia {[}173029, 173032, 173040]; Department of Agricultural and Food Sciences, Alma Mater Studiorum, University of Bologna, Italy; Erasmus Mundus fellowship under EMEC

Lymphocyte glucocorticoid receptor expression level and hormone-binding properties differ between war trauma-exposed men with and without PTSD

<p>Objective: Posttraumatic stress disorder (PTSD) has been shown to be associated with altered glucocorticoid receptor (GR) activity. We studied the expression and functional properties of the receptor in peripheral blood mononuclear cells (PBMCs) from non-traumatized healthy individuals (healthy controls; n = 85), and war trauma-exposed individuals with current PTSD (n = 113), with life-time PTSD (n = 61) and without PTSD (trauma controls; n = 88). The aim of the study was to distinguish the receptor alterations related to PTSD from those related to trauma itself or to resilience to PTSD.</p><p>Methods: Functional status of the receptor was assessed by radioligand binding and lysozyme synthesis inhibition assays. The level of GR gene expression was measured by quantitative PCR and immunoblotting.</p><p>Results: Current PTSD patients had the lowest, while trauma controls had the highest number of glucocorticoid binding sites (B-max) in PBMCs. Hormone-binding potential (B-max/K-D ratio) of the receptor was diminished in the current PTSD group in comparison to all other study groups. Correlation between B-max and K-D that normally exists in healthy individuals was decreased in the current PTSD group. Contrasting B-max data, GR protein level was lower in trauma controls than in participants with current or life-time PTSD.</p><p>Conclusions: Current PTSD is characterized by reduced lymphocyte GR hormone-binding potential and by disturbed compensation between B-max and hormone-binding affinity. Resilience to PTSD is associated with enlarged fraction of the receptor molecules capable of hormone binding, within the total receptor molecule population in PBMCs. (C) 2013 Elsevier Inc. All rights reserved.</p>

Mineralocorticoid receptor and heat shock protein expression levels in peripheral lymphocytes from war trauma-exposed men with and without PTSD

Alterations in the number and functional status of mineralocorticoid (MR) and glucocorticoid receptors (GR) may contribute to vulnerability to posttraumatic stress disorder (PTSD). Corticosteroid receptors are chaperoned by heat shock proteins Hsp90 and Hsp70. We examined relations between corticosteroid receptor and heat shock protein expression levels, and related them with war trauma exposure, PTSD and resilience to PTSD. Relative levels of MR. Hsp90 and Hsp70 were determined by immunoblotting in lymphocytes from war trauma-exposed men with current PTSD (current PTSD group, n=113), with lifetime PTSD (life-time PTSD group, n=61) and without PTSD (trauma control group, n=88), and from non-traumatized healthy controls (healthy control group, n=85). Between-group differences in MR, Hsp90 and Hsp70 levels and in MR/GR ratio were not observed. The level of MR was correlated with both Hsp90 and Hsp70 levels in trauma control and healthy control groups. On the other hand, GR level was correlated only with Hsp90 level, and this correlation was evident in current PTSD and trauma control groups. In conclusion, PTSD and exposure to trauma are not related to changes in lymphocyte MR, Hsp90 or Hsp70 levels, but may be associated with disturbances in corticosteroid receptors interaction with heat shock proteins. (C) 2013 Elsevier Ireland Ltd. All rights reserved.European Commision {[}INCO-CT-2004-509213]; Ministry of Education, Science and Technological Development of the Republic of Serbia {[}41009, 179018