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Attitudes are "the most distinctive and indispensable concept in contemporary social psychology" (Allport, 1935, p. 798). This outstanding position of the attitude concept in social cognitive research is not only reflected in the innumerous studies focusing on this concept but also in the huge number of theoretical approaches that have been put forth since then. Yet, it is still an open question, what attitudes actually are. That is, the question of how attitude objects are represented in memory cannot be unequivocally answered until now (e.g., Barsalou, 1999; Gawronski, 2007; Pratkanis, 1989, Chapter 4). In particular, researchers strongly differ with respect to their assumptions on the content, format and structural nature of attitude representations (Ferguson & Fukukura, 2012). This prevailing uncertainty on what actually constitutes our likes and dislikes is strongly dovetailed with the question of which processes result in the formation of these representations. In recent years, this issue has mainly been addressed in evaluative conditioning research (EC). In a standard EC-paradigm a neutral stimulus (conditioned stimulus, CS) is repeatedly paired with an affective stimulus (unconditioned stimulus, US). The pairing of stimuli then typically results in changes in the evaluation of the CS corresponding to the evaluative response of the US (De Houwer, Baeyens, & Field, 2005). This experimental approach on the formation of attitudes has primarily been concerned with the question of how the representations underlying our attitudes are formed. However, which processes operate on the formation of such an attitude representation is not yet understood (Jones, Olson, & Fazio, 2010; Walther, Nagengast, & Trasselli, 2005). Indeed, there are several ideas on how CS-US pairs might be encoded in memory. Notwithstanding the importance of these theoretical ideas, looking at the existing empirical work within the research area of EC (for reviews see Hofmann, De Houwer, Perugini, Baeyens, & Crombez, 2010; De Houwer, Thomas, & Baeyens, 2001) leaves one with the impression that scientists have skipped the basic processes. Basic processes hereby especially refer to the attentional processes being involved in the encoding of CSs and USs as well as the relation between them. Against the background of this huge gap in current research on attitude formation, the focus of this thesis will be to highlight the contribution of selective attention processes to a better understanding of the representation underlying our likes and dislikes. In particular, the present thesis considers the role of selective attention processes for the solution of the representation issue from three different perspectives. Before illustrating these different perspectives, Chapter 1 is meant to envision the omnipresence of the representation problem in current theoretical as well as empirical work on evaluative conditioning. Likewise, it emphasizes the critical role of selective attention processes for the representation question in classical conditioning and how this knowledge might be used to put forth the uniqueness of evaluative conditioning as compared to classical conditioning. Chapter 2 then considers the differential influence of attentional resources and goal-directed attention on attitude learning. The primary objective of the presented experiment was thereby to investigate whether attentional resources and goal-directed attention exert their influence on EC via changes in the encoding of CS-US relations in memory (i.e., contingency memory). Taking the findings from this experiment into account, Chapter 3 focuses on the selective processing of the US relative to the CS. In particular, the two experiments presented in this chapter were meant to explore the moderating influence of the selective processing of the US in its relation to the CS on EC. In Chapter 4 the important role of the encoding of the US in relation to the CS, as outlined in Chapter 3, is illuminated in the context of different retrieval processes. Against the background of the findings from the two presented experiments, the interplay between the encoding of CS-US contingencies and the moderation of EC via different retrieval processes will be discussed. Finally, a general discussion of the findings, their theoretical implications and future research lines will be outlined in Chapter 5.
The glucocorticoid (GC) cortisol, main mediator of the hypothalamic-pituitary-adrenal axis, has many implications in metabolism, stress response and the immune system. GC function is mediated mainly via the glucocorticoid receptor (GR) which binds as a transcription factor to glucocorticoid response elements (GREs). GCs are strong immunosuppressants and used to treat inflammatory and autoimmune diseases. Long-term usage can lead to several irreversible side effects which make improved understanding indispensable and warrant the adaptation of current drugs. Several large scale gene expression studies have been performed to gain insight into GC signalling. Nevertheless, studies at the proteomic level have not yet been made. The effects of cortisol on monocytes and macrophages were studied in the THP-1 cell line using 2D fluorescence difference gel electrophoresis (2D DIGE) combined with MALDI-TOF mass spectrometry. More than 50 cortisol-modulated proteins were identified which belonged to five functional groups: cytoskeleton, chaperones, immune response, metabolism, and transcription/translation. Multiple GREs were found in the promoters of their corresponding genes (+10 kb/-0.2 kb promoter regions including all alternative promoters available within the Database for Transcription Start Sites (DBTSS)). High quality GREs were observed mainly in cortisol modulated genes, corroborating the proteomics results. Differential regulation of selected immune response related proteins were confirmed by qPCR and immuno-blotting. All immune response related proteins (MX1, IFIT3, SYWC, STAT3, PMSE2, PRS7) which were induced by LPS were suppressed by cortisol and belong mainly to classical interferon target genes. Mx1 has been selected for detailed expression analysis since new isoforms have been identified by proteomics. FKBP51, known to be induced by cortisol, was identified as the strongest differentially expressed protein and contained the highest number of strict GREs. Genomic analysis of five alternative FKBP5 promoter regions suggested GC inducibility of all transcripts. 2D DIGE combined with 2D immunoblotting revealed the existence of several previously unknown FKBP51 isoforms, possibly resulting from these transcripts. Additionally multiple post-translational modifications were found, which could lead to different subcellular localization in monocytes and macrophages as seen by confocal microscopy. Similar results were obtained for the different cellular subsets of human peripheral blood mononuclear cells (PBMCs). FKBP51 was found to be constitutively phosphorylated with up to 8 phosphosites in CD19+ B lymphocytes. Differential Co-immunoprecipitation for cytoplasm and nucleus allowed us to identify new potential interaction partners. Nuclear FKBP51 was found to interact with myosin 9, whereas cytosolic FKBP51 with TRIM21 (synonym: Ro52, Sjögren`s syndrome antigen). The GR has been found to interact with THOC4 and YB1, two proteins implicated in mRNA processing and transcriptional regulation. We also applied proteomics to study rapid non-genomic effects of acute stress in a rat model. The nuclear proteome of the thymus was investigated after 15 min restraint stress and compared to the non-stressed control. Most of the identified proteins were transcriptional regulators found to be enriched in the nucleus probably to assist gene expression in an appropriate manner. The proteomic approach allowed us to further understand the cortisol mediated response in monocytes/macrophages. We identified several new target proteins, but we also found new protein variants and post-translational modifications which need further investigation. Detailed study of FKBP51 and GR indicated a complex regulation network which opened a new field of research. We identified new variants of the anti-viral response protein MX1, displaying differential expression and phosphorylation in the cellular compartments. Further, proteomics allowed us to follow the very early effects of acute stress, which happen prior to gene expression. The nuclear thymocyte proteome of restraint stressed rats revealed an active preparation for subsequent gene expression. Proteomics was successfully applied to study differential protein expression, to identify new protein variants and phosphorylation events as well as to follow translocation. New aspects for future research in the field of cortisol-mediated immune modulation have been added.
Background: The body-oriented therapeutic approach Somatic Experiencing® (SE) treats posttraumatic symptoms by changing the interoceptive and proprioceptive sensations associated with the traumatic experience. Filling a gap in the landscape of trauma treatments, SE has attracted growing interest in research and therapeutic practice, recently.
Objective: To date, there is no literature review of the effectiveness and key factors of SE. This review aims to summarize initial findings on the effectiveness of SE and to outline methodspecific key factors of SE.
Method: To gain a first overview of the literature, we conducted a scoping review including studies until 13 August 2020. We identified 83 articles of which 16 fit inclusion criteria and were systematically analysed.
Results: Findings provide preliminary evidence for positive effects of SE on PTSD-related symptoms. Moreover, initial evidence suggests that SE has a positive impact on affective and somatic symptoms and measures of well-being in both traumatized and non-traumatized
samples. Practitioners and clients identified resource-orientation and use of touch as methodspecific key factors of SE. Yet, an overall studies quality assessment as well as a Cochrane analysis of risk of bias indicate that the overall study quality is mixed.
Conclusions: The results concerning effectiveness and method-specific key factors of SE are promising; yet, require more support from unbiased RCT-research. Future research should focus on filling this gap.
Stress represents a significant problem for Western societies inducing costs as high as 3-4 % of the European gross national products, a burden that is continually increasing (WHO Briefing, EUR/04/5047810/B6). The classical stress response system is the hypothalamic-pituitary-adrenal (HPA) axis which acts to restore homeostasis after disturbances. Two major components within the HPA axis system are the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR). Cortisol, released from the adrenal glands at the end of the HPA axis, binds to MRs and with a 10 fold lower affinity to GRs. Both, impairment of the HPA axis and an imbalance in the MR/GR ratio enhances the risk for infection, inflammation and stress related psychiatric disorders. Major depressive disorder (MDD) is characterised by a variety of symptoms, however, one of the most consistent findings is the hyperactivity of the HPA axis. This may be the result of lower numbers or reduced activity of GRs and MRs. The GR gene consists of multiple alternative first exons resulting in different GR mRNA transcripts whereas for the MR only two first exons are known to date. Both, the human GR promoter 1F and the homologue rat Gr promoter 1.7 seem to be susceptible to methylation during stressful early life events resulting in lower 1F/1.7 transcript levels. It was proposed that this is due to methylation of a NGFI-A binding site in both, the rat promoter 1.7 and the human promoter 1F. The research presented in this thesis was undertaken to determine the differential expression and methylation patterns of GR and MR variants in multiple areas of the limbic brain system in the healthy and depressed human brain. Furthermore, the transcriptional control of the GR transcript 1F was investigated as expression changes of this transcript were associated with MDD, childhood abuse and early life stress. The role of NGFI-A and several other transcription factors on 1F regulation was studied in vitro and the effect of Ngfi-a overexpression on the rat Gr promoter 1.7 in vivo. The susceptibility to epigenetic programming of several GR promoters was investigated in MDD. In addition, changes in methylation levels have been determined in response to a single acute stressor in rodents. Our results showed that GR and MR first exon transcripts are differentially expressed in the human brain, but this is not due to epigenetic programming. We showed that NGFI-A has no effect on endogenous 1F/1.7 expression in vitro and in vivo. We provide evidence that the transcription factor E2F1 is a major element in the transcriptional complex necessary to drive the expression of GR 1F transcripts. In rats, highly individual methylation patterns in the paraventricular nucleus of the hypothalamus (PVN) suggest that this is not related to the stressor but can rather be interpreted as pre-existing differences. In contrast, the hippocampus showed a much more uniform epigenetic status, but still is susceptible to epigenetic modification even after a single acute stress suggesting a differential "state‟ versus "trait‟ regulation of the GR gene in different brain regions. The results of this thesis have given further insight in the complex transcriptional regulation of GR and MR first exons in health and disease. Epigenetic programming of GR promoters seems to be involved in early life stress and acute stress in adult rats; however, the susceptibility to methylation in response to stress seems to vary between brain regions.