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Background Growth differentiation factor (GDF)-15 is linked to inflammation, cancer, and atherosclerosis. GDF-15 is expressed in most tissues but is extremely induced under pathological conditions. Elevated serum levels are suggested as a risk factor and a marker for cardiovascular diseases. However, the cellular sources and the effects of GDF-15 on the cardiovascular system have not been completely elucidated including progression, and morphology of atherosclerotic plaques. Thus, this work aimed to characterize the influence of GDF-15 deficiency on the morphology of atherosclerotic plaques in blood vessels with low-oxygen blood and low blood pressure as the pulmonary trunk (PT), in hypercholesterolemic ApoE−/− mice. Methods GDF-15−/− ApoE−/− mice were generated by crossbreeding of ApoE−/−- and GDF-15−/− mice. After feeding a cholesterol-enriched diet (CED) for 20 weeks, samples of the brachiocephalic trunk (BT) and PT were dissected and lumen stenosis (LS) was measured. Furthermore, changes in the cellularity of the PT, amounts of apoptosis-, autophagy-, inflammation- and proliferation-relevant proteins were immunohisto-morphometrically analyzed. Additionally, we examined an atherosclerotic plaque in a human post mortem sample of the pulmonary artery. Results After CED the body weight of GDF-15−/−ApoE−/− was 22.9% higher than ApoE−/−. Double knockout mice showed also an 35.3% increase of plasma triglyceride levels, whereas plasma cholesterol was similar in both genotypes. LS in the BT and PT of GDF-15−/−ApoE−/− mice was significantly reduced by 19.0% and by 6.7% compared to ApoE−/−. Comparing LS in PT and BT of the same genotype revealed a significant 38.8% (ApoE−/−) or 26.4% (GDF-15−/−ApoE−/−) lower LS in the PT. Immunohistomorphometry of atherosclerotic lesions in PT of GDF-15−/−ApoE−/− revealed significantly increased levels (39.8% and 7.3%) of CD68 + macrophages (MΦ) and α-actin + smooth muscle cells than in ApoE−/−. The density of TUNEL + , apoptotic cells was significantly (32.9%) higher in plaques of PT of GDF-15−/−ApoE−/− than in ApoE−/−. Analysis of atherosclerotic lesion of a human pulmonary artery showed sm-α-actin, CD68+, TUNEL+, Ki67+, and APG5L/ATG+ cells as observed in PT. COX-2+ and IL-6+ immunoreactivities were predominantly located in endothelial cells and subendothelial space. In BT and PT of GDF15−/−ApoE−/− mice the necrotic area was 10% and 6.5% lower than in ApoE−/−. In BT and PT of GDF15−/−ApoE−/− we found 40% and 57% less unstable plaques than ApoE−/− mice. Conclusions Atherosclerotic lesions occur in both, BT and PT, however, the size is smaller in PT, possibly due to the effect of the low-oxygen blood and/or lower blood pressure. GDF-15 is involved in atherosclerotic processes in BT and PT, although different mechanisms (e.g. apoptosis) in these two vessels seem to exist.

Background With a lack of experimental designs that explore which therapeutic style is helpful for which patient, the aim of this study was to test the feasibility of experimentally varying the therapeutic style under realistic conditions and to investigate how this affects alliance ratings by clients and counselors. Methods We defined two manualized therapeutic styles (neutral/distant relational style vs. high affiliation relational style) based on the interpersonal circumplex. In a randomized two-group design, 64 healthy university students (70% female, Mage = 23.78, SDage = 2.81) received a single psychological counseling session on interpersonal conflicts by one of four counselors and in one of the two styles. We checked the manipulation success using observer-rated degree of affiliation and ratings of counselors’ interpersonal behavior with the Interpersonal Message Inventory (IMI-R). A series of linear regression models analyzed whether the style predicted working alliance, assessed via the Working Alliance Inventory (WAI). Results In accordance with the hypotheses, significant differences in the rated degree of affiliation (p ≤ .001) and IMI-R ratings (p ≤ .001 in friendly, p = .003 in hostile dimension) were found between the two groups. Overall, alliance ratings were high across groups and raters (WAI overall scores ranging from 3.76 to 4.07). The style did not predict clients’ alliance ratings. Conclusion The experimental variation of the therapeutic style proved feasible under realistic conditions with high overall alliance ratings. The novel experimental design may provide a basis for further research.

Background: Several meta-analyses highlight pronounced problems in general Theory of Mind (ToM), the ability to infer other persons' mental states, in patients with psychosis in comparison to non-clinical controls. In addition, first studies suggest associations between Hyper-ToM, an exaggerated inference of mental states to others, and delusions. Research on different ToM subtypes (Cognitive ToM, Affective ToM, and Hyper-ToM) and symptom clusters of psychosis (positive, negative, and disorganized symptoms) have gathered conflicting findings. Thus, the present study examined group differences between patients with psychosis and non-clinical controls concerning Cognitive ToM/Affective ToM and Hyper-ToM. Further, the association between ToM subtypes and symptom clusters (positive, negative, and disorganized symptoms) were examined.Methods: Patients with psychotic disorders (n = 64, 1/3 with present delusions indicated by a minimum score of four in the PANSS P1 item) and non-clinical controls (n = 21) were examined with assessments of Cognitive ToM and Affective ToM abilities and Hyper-ToM errors using the Frith-Happé animations. Psychopathology was assessed using the Positive and Negative Syndrome Scale.Results: Patients with psychosis presented more pronounced problems in Cognitive and Affective ToM in comparison to non-clinical controls, whereas there were no group differences with regard to Hyper-ToM errors. Furthermore, deficits in Cognitive ToM were associated with general delusions, whereas problems in Affective ToM were associated with negative and disorganized symptoms. In addition, there was no association between Hyper-ToM errors and any symptoms when controlling for years of education.Conclusions: Our findings suggest that deficits in ToM subtypes might not be directly related to delusions and positive symptoms and are in line with more recently developed cognitive models of delusions. In addition, our results support the well-established finding of associations between ToM alterations and negative or disorganized symptoms. Our results shed light on the role of different dimensions of ToM in specific symptoms of psychosis.

Objective: Little is known about the specific psychological features that differentiate persistent depressive disorder (PDD) and episodic depression (ED). Thus, the present study aimed to investigate differences in social cognition and interpersonal problems between these two forms of depression and healthy controls. In addition, we aimed to examine childhood maltreatment (CM) as a possible origin of these alterations.Methods: In a cross-sectional study, adult patients with a current PDD (n = 34) or in a current episode of ED (n = 38), and healthy controls (n = 39) completed questionnaires about depression severity, empathy, interpersonal problems, and CM, as well as tests of affective theory of mind and facial emotion recognition.Results: Patients with PDD reported higher empathic distress than patients with ED and healthy controls. Both depressive groups recognized angry faces with higher accuracy and reported more interpersonal problems, with no differences between PDD and ED. Empathic distress and interpersonal problems mediated the link between CM and depression in the combined sample.Limitations: Patient groups were not drug-naïve and antidepressant intake might have influenced social-cognitive functions. Self-report measures of empathy and interpersonal problems are vulnerable to bias. The cross-sectional design does not allow causal conclusions.Conclusion: Depressed patients may not show deficits in decoding the affective states of others and in feeling with others. However, depressed individuals—in particular patients with PDD—may feel easily overwhelmed by emotionally tense situations, resulting in empathic distress and avoidant/submissive interpersonal behavior. Exposure to CM might be an origin of alterations in social cognition and interpersonal problems.

Objective: In psychotherapy process research, there is a lack of experimental designs that specifically explore which therapeutic style is helpful for which patient. Thus, the aim of this study was to test the feasibility of experimentally varying the therapeutic style under realistic conditions and how this affects alliance. Method: We defined two therapeutic styles (relationship-focused vs. problem-focused) based on the interpersonal circumplex. In a randomized two-group design, 64 healthy university students (70% female, Mage=23.78 years old, SDage=2.81) were assigned to one of the styles and received a single psychological counseling session on interpersonal conflicts. We checked the manipulation success using an adherence rating and counselors’ interpersonal impressions via the Interpersonal Message Inventory (IMI-R). Primary outcome was alliance (Working Alliance Inventory, WAI). Symptom severity (Symptom Checklist, SCL-K-9) was also assessed. Results: Analyses of adherence (p< .001) and IMI-R ratings (p< .001 in friendly dimension, p=.003 in hostile dimension) were hypotheses-conform to the proposed therapeutic styles. Alliance was highly rated in both conditions and by all raters. While clients did not show any group differences, counselor and observer ratings were significantly higher in the relationship-focused than in the problem-focused condition (p=.040; p=.003). In both groups, symptom severity decreased significantly after the session (p=.020).Conclusions: The experimental variation of the therapeutic style is feasible under realistic conditions with high overall alliance ratings. The novel experimental design may provide a basis for further process research. Mediator and moderator analyses could yield more detailed information on differential relationship forming and thus an individualized therapeutic style.