@phdthesis{Gruendahl2023,
  author    = {Gr{\"u}ndahl, Marthe Erda},
  title     = {From Lab to Life: Investigating the Role of Social Contact for Anxiety and Related Autonomic Responses},
  doi       = {10.25972/OPUS-31685},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-316859},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2023},
  abstract  = {Social contact is an integral part of daily life. Its health-enhancing effects include reduced negative affective experiences of fear and anxiety, a phenomenon called social buffering. This dissertation studied different forms of social contact and their anxiety-buffering effects with diverse methodologies. The laboratory-based first study investigated minimal social contact in the context of pain relief learning. Results showed that the observed decreased autonomic and increased subjective fear responses following pain relief learning were independent of social influence. The minimalistic and controlled social setting may have prevented social buffering. Study 2 targeted social buffering in daily life using Ecological Momentary Assessment. We repeatedly assessed individuals' state anxiety, related cardiovascular responses, and aspects of social interactions with smartphones and portable sensors on five days. Analyses of over 1,500 social contacts revealed gender-specific effects, e.g., heart rate-reducing effects of familiarity in women, but not men. Study 3 examined anxiety, loneliness, and related social factors in the absence of social contact due to social distancing. We constructed and validated a scale measuring state and trait loneliness and isolation, and analysed its link to mental health. Results include a social buffering-like relation of lower anxiety with more trait sociability and sense of belonging. In sum, the studies showed no fear reduction by minimal social contact, but buffering effects relating to social and personal factors in more complex social situations. Anxiety responses during daily social contacts were lower with more familiar or opposite-gender interaction partners. During limited social contact, lower anxiety related to inter-individual differences in sociability, social belonging, and loneliness. By taking research from lab to life, this dissertation underlined the diverse nature of social contact and its relevance to mental health.},
  subject      = {Angst},
  language  = {en}
}
@phdthesis{Kneer2022,
  author    = {Kneer, Katharina Johanna},
  title     = {The association of three anxiety dimensions in children and adolescents: their influence on the brain and malleability by a prevention program},
  doi       = {10.25972/OPUS-25746},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-257468},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Anxiety disorders are the most prevalent group of neuropsychiatric disorders and go along with high personal suffering. They often arise during childhood and show a progression across the life span, thus making this age a specific vulnerable period during development. Still most research about these disorders is done in adults. In light of this, it seems of utmost importance to identify predictive factors of anxiety disorders in children and adolescents. Temperament or personality traits have been proclaimed as risk markers for the development of subsequent anxiety disorders, but their exact interplay is not clear. In this dissertation an effort is made to contribute to the understanding of how risk markers of early temperamental traits, in this case Trait Anxiety, Anxiety Sensitivity and Separation Anxiety are interplaying. While Trait Anxiety is regarded as a more general tendency to react anxiously to threatening situations or stimuli (Unnewehr, Joormann, Schneider, \& Margraf, 1992), Anxiety Sensitivity is the tendency to react with fear to one's own anxious sensations (Allan et al., 2014; S. Reiss, Peterson, Gursky, \& McNally, 1986), and Separation Anxiety is referring to the extent to which the child is avoiding certain situations because of the fear of being separated from primary care givers (In-Albon \& Schneider, 2011). In addition, it will be addressed how these measurements are associated with negative life events, as well as brain functioning and if they are malleable by a prevention program in children and adolescents. In study 1 the aim was to extend the knowledge about the interrelations of this anxiety dimensions and negative life events. Results indicated positive correlations of all three anxiety traits as well as with negative life events. Thus, a close connection of all three anxiety measures as well as with negative life events could be indicated. The closest association was found between Anxiety Sensitivity and Trait Anxiety and between Separation Anxiety and Anxiety Sensitivity. Furthermore, negative life events functioned as mediator between Anxiety Sensitivity and Trait Anxiety, indicating that a part of the association was explained by negative life events. In study 2 we extended the findings from study 1 with neurobiological parameters and examined the influence of anxiety traits on emotional brain activation by administering the "emotional face matching task". This task activated bilateral prefrontal regions as well as both hippocampi and the right amygdala. Further analyses indicated dimension-specific brain activations: Trait Anxiety was associated with a hyperactivation of the left inferior frontal gyrus (IFG) and Separation Anxiety with a lower activation bilaterally in the IFG and the right middle frontal gyrus (MFG). Furthermore, the association between Separation Anxiety and Anxiety Sensitivity was moderated by bi-hemispheric Separation-Anxiety-related IFG activation. Thus, we could identify distinct brain activation patterns for the anxiety dimensions (Trait Anxiety and Separation Anxiety) and their associations (Separation Anxiety and Anxiety Sensitivity). The aim of study 3 was to probe the selective malleability of the anxiety dimensions via a prevention program in an at-risk population. We could identify a reduction of all three anxiety traits from pre- to post-prevention-assessment and that this effect was significant in Anxiety Sensitivity and Trait Anxiety scores. Furthermore, we found that pre-intervention Separation Anxiety and Anxiety Sensitivity post-intervention were associated. In addition, pre-interventive scores were correlated with the intervention-induced change within the measure (i.e., the higher the score before the intervention the higher the prevention-induced change) and pre-intervention Anxiety Sensitivity correlated with the change in Separation Anxiety scores. All relations, seemed to be direct, as mediation/moderation analyses with negative life events did not reveal any significant effect. These results are very promising, because research about anxiety prevention in children and adolescents is still rare and our results are indicating that cognitive-behavioural-therapy based prevention is gilding significant results in an indicated sample even when samples sizes are small like in our study. In sum the present findings hint towards distinct mechanisms underlying the three different anxiety dimensions on a phenomenological and neurobiological level, though they are highly overlapping (Higa-McMillan, Francis, Rith-Najarian, \& Chorpita, 2016; Taylor, 1998). Furthermore, the closest associations were found between Anxiety Sensitivity and Trait Anxiety, as well as between Separation Anxiety and Anxiety Sensitivity. Specifically, we were able to find a neuronal manifestation of the association between Separation Anxiety and Anxiety Sensitivity (Separation Anxiety-specific IFG activation) and a predictive potential on prevention influence. The results of these studies lead to a better understanding of the etiology of anxiety disorders and the interplay between different anxiety-related temperamental traits and could lead to further valuable knowledge about the intervention as well as further prevention strategies.},
  subject      = {Pr{\"a}vention},
  language  = {en}
}
@phdthesis{Stegmann2021,
  author    = {Stegmann, Yannik},
  title     = {Electrocortical mechanisms of sustained attention during the acquisition and interaction of conditioned fear and anxiety},
  doi       = {10.25972/OPUS-23770},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-237700},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2021},
  abstract  = {Adapting defensive behavior to the characteristics of a threatening situation is a fundamental function of the brain. Particularly, threat imminence plays a major role for the organization of defensive responses. Acute threat prompts phasic physiological responses, which are usually associated with an intense feeling of fear. In contrast, diffuse and potentially threatening situations elicit a sustained state of anxious apprehension. Detection of the threatening stimulus defines the key event in this framework, initiating the transition from potential to acute threat. Consequently, attention to threat is crucial for supporting defensive behavior. The functions of attention are finely tuned to the characteristics of a threatening situation. Potential threat is associated with hypervigilance, in order to facilitate threat detection. Once a threatening stimulus has been identified, attention is selectively focused on the source of danger. Even though the concepts of selective attention and hypervigilance to threat are well established, evidence for their neural correlates remain scarce. Therefore, a major goal of this thesis is to elucidate the neural correlates of selective attention to acute threat and hypervigilance during potential threat. A second aim of this thesis is to provide a mechanistic account for the interaction of fear and anxiety. While contemporary models view fear and anxiety as mutually exclusive, recent findings for the neural networks of fear and anxiety suggest potential interactions. In four studies, aversive cue conditioning was used to induce acute threat, while context conditioning served as a laboratory model of potential threat. To quantify neural correlates of selective attention and hypervigilance, steady-state visual evoked potentials (ssVEPs) were measured as an index of visuocortical responding. Study 1 compared visuocortical responses to acute and potential threat for high versus low trait-anxious individuals. All individuals demonstrated enhanced electrocortical responses to the central cue in the acute threat condition, suggesting evidence for the neural correlate of selective attention. However, only low anxious individuals revealed facilitated processing of the contexts in the potential threat condition, reflecting a neural correlate of hypervigilance. High anxious individuals did not discriminate among contexts. These findings contribute to the notion of aberrational processing of potential threat for high anxious individuals. Study 2 and 3 realized orthogonal combinations of cue and context conditioning to investigate potential interactions of fear and anxiety. In contrast to Study 1 and 2, Study 3 used verbal instructions to induce potentially threatening contexts. Besides ssVEPs, threat ratings and skin conductance responses (SCRs) were recorded as efferent indices of defensive responding. None of these studies found further evidence for the neural correlates of hypervigilance and selective attention. However, results for ratings and SCRs revealed additive effects of fear and anxiety, suggesting that fear and anxiety are not mutually exclusive, but interact linearly to organize and facilitate defensive behavior. Study 4 tested ssVEPs to more ecologically valid forms of context conditioning, using flickering video stimuli of virtual offices to establish context representations. Contrary to expectations, results revealed decreased visuocortical responses during sustained presentations of anxiety compared to neutral contexts. A disruption of ssVEP signals eventually suggests interferences by continuously changing video streams which are enhanced as a function of motivational relevance. In summary, this thesis provided evidence for the neural correlates of attention only for isolated forms of fear and anxiety, but not for their interaction. In contrast, an additive interaction model of fear and anxiety for measures of defensive responding offers a new perspective on the topography of defensive behavior.},
  subject      = {Furcht},
  language  = {en}
}
@phdthesis{Genheimer2020,
  author    = {Genheimer, Hannah},
  title     = {The acquisition of anxiety and the impact of transcutaneous vagus nerve stimulation on extinction learning in virtual contexts},
  doi       = {10.25972/OPUS-20639},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-206390},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {This thesis aims for a better understanding of the mechanisms underlying anxiety as well as trauma- and stressor-related disorders and the development of new therapeutic approaches. I was first interested in the associative learning mechanisms involved in the etiology of anxiety disorders. Second, I explored the therapeutic effects of transcutaneous vagus nerve stimulation (tVNS) as a promising new method to accelerate and stabilize extinction learning in humans. For these purposes, I applied differential anxiety conditioning protocols realized by the implementation of virtual reality (VR). Here, a formerly neutral virtual context (anxiety context, CTX+) is presented whereby the participants unpredictably receive mildly aversive electric stimuli (unconditioned stimulus, US). Another virtual context (safety context, CTX-) is never associated with the US. Moreover, extinction of conditioned anxiety can be modeled by presenting the same contexts without US delivery. When unannounced USs were administered after extinction, i.e. reinstatement, the strength of the "returned" conditioned anxiety can provide information on the stability of the extinction memory. In Study 1, I disentangled the role of elemental and conjunctive context representations in the acquisition of conditioned anxiety. Sequential screenshots of two virtual offices were presented like a flip-book so that I elicited the impression of walking through the contexts. Some pictures of CTX+ were paired with an US (threat elements), but not some other screenshots of the same context (non-threat elements), nor the screenshots depicting CTX- (safety elements). Higher contingency ratings for threat compared to non-threat elements revealed elemental representation. Electro-cortical responses showed larger P100 and early posterior negativity amplitudes elicited by screenshots depicting CTX+ compared to CTX- and suggested conjunctive representation. These results support the dual context representation in anxiety acquisition in healthy individuals. Study 2 addressed the effects of tVNS on the stabilization of extinction learning by using a context conditioning paradigm. Potentiated startle responses as well as higher aversive ratings in CTX+ compared to CTX- indicate successful anxiety conditioning. Complete extinction was found in startle responses and valence ratings as no differentiation between CTX+ and CTX- suggested. TVNS did not affect extinction or reinstatement of anxiety which may be related to the inappropriate transferability of successful stimulation parameters from epilepsy patients to healthy participants during anxiety extinction. Therefore, in Study 3 I wanted to replicate the modulatory effects of tVNS on heart rate and pain perception by the previously used parameters. However, no effects of tVNS were observed on subjective pain ratings, on pain tolerance, or on heart rate. This led to the conclusion that the modification of stimulation parameters is necessary for a successful acceleration of anxiety extinction in humans. In Study 4, I prolonged the tVNS and, considering previous tVNS studies, I applied a cue conditioning paradigm in VR. Therefore, during acquisition a cue (CS+) presented in CTX+ predicted the US, but not another cue (CS-). Both cues were presented in a second context (CTX-) and never paired with the US. Afterward, participants received either tVNS or sham stimulation and underwent extinction learning. I found context-dependent cue conditioning only in valence ratings, which was indicated by lower valence for CS+ compared to CS- in CTX+, but no differential ratings in CTX-. Successful extinction was indicated by equal responses to CS+ and CS-. Interestingly, I found reinstatement of conditioned fear in a context-dependent manner, meaning startle response was potentiated for CS+ compared to CS- only in the anxiety context. Importantly, even the prolonged tVNS had no effect, neither on extinction nor on reinstatement of context-dependent cue conditioning. However, I found first evidence for accelerated physiological contextual extinction due to less differentiation between startles in CTX+ compared to CTX- in the tVNS than in the sham stimulated group. In sum, this thesis first confirms the dual representation of a context in an elemental and a conjunctive manner. Second, though anxiety conditioning and context-dependent cue conditioning paradigms worked well, the translation of tVNS accelerated extinction from rats to humans needs to be further developed, especially the stimulation parameters. Nevertheless, tVNS remains a very promising approach of memory enhancement, which can be particularly auspicious in clinical settings.},
  subject      = {Angst},
  language  = {en}
}
@phdthesis{Schiele2019,
  author    = {Schiele, Miriam},
  title     = {Interaction of 5-HTT/NPSR1 variants with distal and acute stress on dimensional and neuroendocrine anxiety endophenotypes - A multi-dimensional model of anxiety risk},
  doi       = {10.25972/OPUS-14860},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148600},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2019},
  abstract  = {The etiology of anxiety disorders is multifactorial with contributions from both genetic and environmental factors. Several susceptibility genes of anxiety disorders or anxiety-related intermediate phenotypes have been identified, including the serotonin transporter gene (5-HTT) and the neuropeptide S receptor gene (NPSR1), which have been shown to modulate responses to distal and acute stress experiences. For instance, gene-environment interaction (GxE) studies have provided evidence that both 5-HTT and NPSR1 interact with environmental stress, particularly traumatic experiences during childhood, in the moderation of anxiety traits, and both 5-HTT and NPSR1 have been implicated in hypothalamic-pituitary-adrenal (HPA) axis reactivity - an intermediate phenotype of mental disorders - in response to acute stress exposure. The first part of this thesis aimed to address the interplay of variations in both 5-HTT and NPSR1 genes and distal stress experiences, i.e. childhood trauma, in the moderation of anxiety-related traits, extended by investigation of the potentially protective effect of positive influences, i.e. elements of successful coping such as general self-efficacy (GSE), on a GxE risk constellation by introducing GSE as an indicator of coping ability ("C") as an additional dimension in a GxExC approach conferring - or buffering - vulnerability to anxiety. Increased anxiety was observed in 5-HTTLPR/rs25531 LALA genotype and NSPR1 rs324981 AA genotype carriers, respectively, with a history of childhood maltreatment but only in the absence of a person's ability to cope with adversity, whereas a dose-dependent effect on anxiety traits as a function of maltreatment experiences irrespective of coping characteristics was observed in the presence of at least one 5-HTT S/LG or NSPR1 T allele, respectively. The second part of this thesis addressed the respective impact of 5-HTT and NPSR1 variants on the neuroendocrine, i.e. salivary cortisol response to acute psychosocial stress by applying the Maastricht Acute Stress Test (MAST). A direct effect of NPSR1 - but not 5-HTT - on the modulation of acute stress reactivity could be discerned, with carriers of the more active NPSR1 T allele Summary III displaying significantly higher overall salivary cortisol levels in response to the MAST compared to AA genotype carriers. In summary, study 1 observed a moderating effect of GSE in interaction with childhood maltreatment and 5-HTT and NPSR1, respectively, in an extended GxExC model of anxiety risk, which may serve to inform targeted preventive interventions mitigating GxE risk constellations and to improve therapeutic interventions by strengthening coping ability as a protective mechanism to promote resilient functioning. In study 2, a modulation of HPA axis function, considered to be an endophenotype of stress-related mental disorders, by NPSR1 gene variation could be discerned, suggesting neuroendocrine stress reactivity as an important potential intermediate phenotype of anxiety given findings linking NPSR1 to dimensional and categorical anxiety. Results from both studies may converge within the framework of a multi-level model of anxiety risk, integrating neurobiological, neuroendocrine, environmental, and psychological factors that act together in a highly complex manner towards increasing or decreasing anxiety risk.},
  subject      = {Angst},
  language  = {en}
}
@phdthesis{Aboagye2019,
  author    = {Aboagye, Benjamin},
  title     = {Behavioral and physiologic consequences of inducible inactivation of the \(Tryptophan\) \(hydroxylase\) 2 gene in interaction with early-life adversity},
  doi       = {10.25972/OPUS-17358},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-173581},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2019},
  abstract  = {Disruptions in brain serotonin (5-hydroxytryptamine, 5-HT) signaling pathways have been associated with etiology and pathogenesis of various neuropsychiatric disorders, but specific neural mechanisms of 5-HT function are yet to be fully elucidated. Tryptophan hydroxylase 2 (TPH2) is the rate-limiting enzyme for brain 5-HT synthesis. Therefore, in this study a tamoxifen (Tam)-inducible cre-mediated conditional gene (Tph2) knockout in adult mouse brain (Tph2icKO) has been established to decipher the specific role of brain 5-HT in the regulation of behavior in adulthood. Immunohistochemistry and high-performance liquid chromatography (HPLC) were used first to test the efficacy of Tam-inducible inactivation of Tph2 and consequential reduction of 5-HT in adult mouse brain. Tam treatment resulted in ≥90\% reduction in the number of 5-HT immuno-reactive cells in the anterior raphe nuclei. HPLC revealed a significant reduction in concentration of 5-HT and its metabolite 5-hydroxyindole acetic acid (5-HIAA) in selected brain regions of Tph2icKO, indicating the effectiveness of the protocol used. Second, standard behavioral tests were used to assess whether reduced brain 5-HT concentrations could alter anxiety-, fear- and depressive-like behavior in mice. No altered anxiety- and depressive-like behaviors were observed in Tph2icKO compared to control mice (Tph2CON) in all indices measured, but Tph2icKO mice exhibited intense and sustained freezing during context-dependent fear memory retrieval. Tph2icKO mice also exhibited locomotor hyperactivity in the aversive environments, such as the open field, and consumed more food and fluid than Tph2CON mice. Lastly, the combined effect of maternal separation (MS) stress and adult brain 5-HT depletion on behavior was assessed in male and female mice. Here, MS stress, 5-HT depletion and their interaction elicited anxiety-like behavior in a sex-dependent manner. MS reduced exploratory behavior in both male and female mice. Reduced 5-HT enhanced anxiety in female, but not in male mice. Furthermore, expression of genes related to the 5-HT system and emotionality (Tph2, Htr1a, Htr2a, Maoa and Avpr1a) was assessed by performing a quantitative real-time PCR. In Tph2icKO mice there was a reduction in expression of Tph2 in the raphe nuclei of both male and female mice. Interaction between MS stress and 5-HT deficiency was detected showing increased Htr2a and Maoa expression in raphe and hippocampus respectively of female mice. In male mice, MS stress and 5-HT depletion interaction effects reduced Avpr1a expression in raphe, while the expression of Htr1a, Htr2a and Maoa was differentially altered by 5-HT depletion and MS in various brain regions.},
  subject      = {Anxiety},
  language  = {en}
}
@phdthesis{Raab2018,
  author    = {Raab, Annette},
  title     = {The role of Rgs2 in animal models of affective disorders},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-152550},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2018},
  abstract  = {Anxiety and depressive disorders result from a complex interplay of genetic and environmental factors and are common mutual comorbidities. On the level of cellular signaling, regulator of G protein signaling 2 (Rgs2) has been implicated in human and rodent anxiety as well as rodent depression. Rgs2 negatively regulates G protein-coupled receptor (GPCR) signaling by acting as a GTPase accelerating protein towards the Gα subunit. The present study investigates, whether mice with a homozygous Rgs2 deletion (Rgs2-/-) show behavioral alterations as well as an increased susceptibility to stressful life events related to human anxiety and depressive disorders and tries to elucidate molecular underlying's of these changes. To this end, Rgs2-/- mice were characterized in an aversive-associative learning paradigm to evaluate learned fear as a model for the etiology of human anxiety disorders. Spatial learning and reward motivated spatial learning were evaluated to control for learning in non-aversive paradigms. Rgs2 deletion enhanced learning in all three paradigms, rendering increased learning upon deletion of Rgs2 not specific for aversive learning. These data support reports indicating increased long-term potentiation in Rgs2-/- mice and may predict treatment response to conditioning based behavior therapy in patients with polymorphisms associated with reduced RGS2 expression. Previous reports of increased innate anxiety were corroborated in three tests based on the approach-avoidance conflict. Interestingly, Rgs2-/- mice showed novelty-induced hypo-locomotion suggesting neophobia, which may translate to the clinical picture of agoraphobia in humans and reduced RGS2 expression in humans was associated with a higher incidence of panic disorder with agoraphobia. Depression-like behavior was more distinctive in female Rgs2-/- mice. Stress resilience, tested in an acute and a chronic stress paradigm, was also more distinctive in female Rgs2-/- mice, suggesting Rgs2 to contribute to sex specific effects of anxiety disorders and depression. Rgs2 deletion was associated with GPCR expression changes of the adrenergic, serotonergic, dopaminergic and neuropeptide Y systems in the brain and heart as well as reduced monoaminergic neurotransmitter levels. Furthermore, the expression of two stress-related microRNAs was increased upon Rgs2 deletion. The aversive-associative learning paradigm induced a dynamic Rgs2 expression change. The observed molecular changes may contribute to the anxious and depressed phenotype as well as promote altered stress reactivity, while reflecting an alter basal stress level and a disrupted sympathetic tone. Dynamic Rgs2 expression may mediate changes in GPCR signaling duration during memory formation. Taken together, Rgs2 deletion promotes increased anxiety-like and depression-like behavior, altered stress reactivity as well as increased cognitive function.},
  subject      = {Angst},
  language  = {en}
}
@phdthesis{Ziegler2016,
  author    = {Ziegler, Christiane},
  title     = {Epigenetic Mechanisms in the Pathogenesis and Therapy of Anxiety Disorders},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146815},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2016},
  abstract  = {Anxiety disorders (AD) are common, disabling mental disorders, which constitute the most prevalent mental health condition conveying a high individual and socioeconomic burden. Social anxiety disorder (SAD), i.e. fear in social situations particularly when subjectively scrutinized by others, is the second most common anxiety disorder with a life time prevalence of 10\%. Panic disorder (PD) has a life time prevalence of 2-5\% and is characterized by recurrent and abrupt surges of intense fear and anticipatory anxiety, i.e. panic attacks, occurring suddenly and unexpected without an apparent cue. In recent years, psychiatric research increasingly focused on epigenetic mechanisms such as DNA methylation as a possible solution for the problem of the so-called "hidden heritability", which conceptualizes the fact that the genetic risk variants identified so far only explain a small part of the estimated heritability of mental disorders. In the first part of this thesis, oxytocin receptor (OXTR) gene methylation was investigated regarding its role in the pathogenesis of social anxiety disorder. In summary, OXTR methylation patterns were implicated in different phenotypes of social anxiety disorder on a categorical, neuropsychological, neuroendocrinological as well as on a neural network level. The results point towards a multilevel role of OXTR gene hypomethylation particularly at one CpG site (CpG3, Chr3: 8 809 437) within the protein coding region of the gene in SAD. The second part of the thesis investigated monoamine oxidase A (MAOA) gene methylation regarding its role in the pathogenesis of panic disorder as well as - applying a psychotherapy-epigenetic approach - its dynamic regulation during the course of cognitive behavioural therapy (CBT) in PD patients. First, MAOA hypomethylation was shown to be associated with panic disorder as well as with panic disorder severity. Second, in patients responding to treatment MAOA hypomethylation was shown to be reversible up to the level of methylation in healthy controls after the course of CBT. This increase in MAOA methylation along with successful psychotherapeutic treatment was furthermore shown to be associated with symptom improvement regarding agoraphobic avoidance in an independent replication sample of non-medicated patients with PD. Taken together, in the future the presently identified epigenetic patterns might contribute to establishing targeted preventive interventions and personalized treatment options for social anxiety disorder or panic disorder, respectively.},
  subject      = {Angst},
  language  = {en}
}
@phdthesis{Kastner2015,
  author    = {Kastner, Anna Katharina},
  title     = {Attention mechanisms in contextual anxiety and cued fear and their influence on processing of social cues},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-123747},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2015},
  abstract  = {Anxiety is an affective state characterized by a sustained, long-lasting defensive response, induced by unpredictable, diffuse threat. In comparison, fear is a phasic response to predictable threat. Fear can be experimentally modeled with the help of cue conditioning. Context conditioning, in which the context serves as the best predictor of a threat due to the absence of any conditioned cues, is seen as an operationalization of sustained anxiety. This thesis used a differential context conditioning paradigm to examine sustained attention processes in a threat context compared to a safety context for the first time. In three studies, the attention mechanisms during the processing of contextual anxiety were examined by measuring heart rate responses and steady-state-visually evoked potentials (ssVEPs). An additional focus was set on the processing of social cues (i.e. faces) and the influence of contextual information on these cues. In a last step, the correlates of sustained anxiety were compared to evoked responses by phasic fear, which was realized in a previously established paradigm combining predictable and unpredictable threat. In the first study, a contextual stimulus was associated with an aversive loud noise, while a second context remained unpaired. This conditioning paradigm created an anxiety context (CTX+) and a safety context (CTX-). After acquisition, a social agent vs. an object was presented as a distractor in both contexts. Heart rate and cortical responses, with ssVEPs by using frequency tagging, to the contexts and the distractors were assessed. Results revealed enhanced ssVEP amplitudes for the CTX+ compared to the CTX- during acquisition and during presentation of distractor stimuli. Additionally, the heart rate was accelerated in the acquisition phase, followed by a heart rate deceleration as a psychophysiological marker of contextual anxiety. Study 2 used the same context conditioning paradigm as Study 1. In contrast to the first study, persons with different emotional facial expressions were presented in the anxiety and safety contexts in order to compare the differential processing of these cues within periods of threat and safety. A similar anxiety response was found in the second study, although only participants who Abstract VIII were aware of the contingency between contexts and aversive event showed a sensory amplification of the threat context, indicated by heart rate response and ssVEP activation. All faces irrespective of their emotional expression received increased attentional resources when presented within the anxiety context, which suggests a general hypervigilance in anxiety contexts. In the third study, the differentiation of predictable and unpredictable threat as an operationalization of fear and anxiety was examined on a cortical and physiological level. In the predictable condition, a social cue was paired with an aversive event, while in the unpredictable condition the aversive event remained unpaired with the respective cue. A fear response to the predictable cue was found, indicated by increased oscillatory response and accelerated heart rate. Both predictable and unpredictable threat yielded increased ssVEP amplitudes evoked by the context stimuli, while the response in the unpredictable context showed longer-lasting ssVEP activation to the threat context. To sum up, all three studies endorsed anxiety as a long-lasting defensive response. Due to the unpredictability of the aversive events, the individuals reacted with hypervigilance in the anxiety context, reflected in a facilitated processing of sensory information and an orienting response. This hypervigilance had an impact on the processing of novel cues, which appeared in the anxiety context. Considering the compared stimuli categories, the stimuli perceived in a state of anxiety received increased attentional resources, irrespective of the emotional arousal conveyed by the facial expression. Both predictable and unpredictable threat elicited sensory amplification of the contexts, while the response in the unpredictable context showed longer-lasting sensory facilitation of the threat context.},
  subject      = {Angst},
  language  = {en}
}
@article{LadwigLederbogenAlbusetal.2014,
  author    = {Ladwig, Karl-Heinz and Lederbogen, Florian and Albus, Christian and Angermann, Christiane and Borggrefe, Martin and Fischer, Denise and Fritzsche, Kurt and Haass, Markus and Jordan, Jochen and J{\"u}nger, Jana and Kindermann, Ingrid and K{\"o}llner, Volker and Kuhn, Bernhard and Scherer, Martin and Seyfarth, Melchior and V{\"o}ller, Heinz and Waller, Christiane and Herrmann-Lingen, Christoph},
  title     = {Position paper on the importance of psychosocial factors in cardiology: Update 2013},
  series = {GMS German Medical Science},
  volume    = {12},
  journal   = {GMS German Medical Science},
  doi       = {10.3205/000194},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121196},
  year      = {2014},
  abstract  = {Background: The rapid progress of psychosomatic research in cardiology and also the increasing impact of psychosocial issues in the clinical daily routine have prompted the Clinical Commission of the German Heart Society (DGK) to agree to an update of the first state of the art paper on this issue which was originally released in 2008. Methods: The circle of experts was increased, general aspects were implemented and the state of the art was updated. Particular emphasis was dedicated to coronary heart diseases (CHD), heart rhythm diseases and heart failure because to date the evidence-based clinical knowledge is most advanced in these particular areas. Differences between men and women and over the life span were considered in the recommendations as were influences of cognitive capability and the interactive and synergistic impact of classical somatic risk factors on the affective comorbidity in heart disease patients. Results: A IA recommendation (recommendation grade I and evidence grade A) was given for the need to consider psychosocial risk factors in the estimation of coronary risks as etiological and prognostic risk factors. Furthermore, for the recommendation to routinely integrate psychosocial patient management into the care of heart surgery patients because in these patients, comorbid affective disorders (e.g. depression, anxiety and post-traumatic stress disorder) are highly prevalent and often have a malignant prognosis. A IB recommendation was given for the treatment of psychosocial risk factors aiming to prevent the onset of CHD, particularly if the psychosocial risk factor is harmful in itself (e.g. depression) or constrains the treatment of the somatic risk factors. Patients with acute and chronic CHD should be offered anti-depressive medication if these patients suffer from medium to severe states of depression and in this case medication with selective reuptake inhibitors should be given. In the long-term course of treatment with implanted cardioverter defibrillators (ICDs) a subjective health technology assessment is warranted. In particular, the likelihood of affective comorbidities and the onset of psychological crises should be carefully considered. Conclusions: The present state of the art paper presents an update of current empirical evidence in psychocardiology. The paper provides evidence-based recommendations for the integration of psychosocial factors into cardiological practice and highlights areas of high priority. The evidence for estimating the efficiency for psychotherapeutic and psychopharmacological interventions has increased substantially since the first release of the policy document but is, however, still weak. There remains an urgent need to establish curricula for physician competence in psychodiagnosis, communication and referral to ensure that current psychocardiac knowledge is translated into the daily routine.},
  language  = {en}
}