@article{ZannasArlothCarrilloRoaetal.2015, author = {Zannas, Anthony S. and Arloth, Janine and Carrillo-Roa, Tania and Iurato, Stella and R{\"o}h, Simone and Ressler, Kerry J. and Nemeroff, Charles B. and Smith, Alicia K. and Bradley, Bekh and Heim, Christine and Menke, Andreas and Lange, Jennifer F. and Br{\"u}ckl, Tanja and Ising, Marcus and Wray, Naomi R. and Erhardt, Angelika and Binder, Elisabeth B. and Mehta, Divya}, title = {Lifetime stress accelerates epigenetic aging in an urban, African American cohort: relevance of glucocorticoid signaling}, series = {Genome Biology}, volume = {16}, journal = {Genome Biology}, number = {266}, doi = {10.1186/s13059-015-0828-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-149865}, year = {2015}, abstract = {Background Chronic psychological stress is associated with accelerated aging and increased risk for aging-related diseases, but the underlying molecular mechanisms are unclear. Results We examined the effect of lifetime stressors on a DNA methylation-based age predictor, epigenetic clock. After controlling for blood cell-type composition and lifestyle parameters, cumulative lifetime stress, but not childhood maltreatment or current stress alone, predicted accelerated epigenetic aging in an urban, African American cohort (n = 392). This effect was primarily driven by personal life stressors, was more pronounced with advancing age, and was blunted in individuals with higher childhood abuse exposure. Hypothesizing that these epigenetic effects could be mediated by glucocorticoid signaling, we found that a high number (n = 85) of epigenetic clock CpG sites were located within glucocorticoid response elements. We further examined the functional effects of glucocorticoids on epigenetic clock CpGs in an independent sample with genome-wide DNA methylation (n = 124) and gene expression data (n = 297) before and after exposure to the glucocorticoid receptor agonist dexamethasone. Dexamethasone induced dynamic changes in methylation in 31.2 \% (110/353) of these CpGs and transcription in 81.7 \% (139/170) of genes neighboring epigenetic clock CpGs. Disease enrichment analysis of these dexamethasone-regulated genes showed enriched association for aging-related diseases, including coronary artery disease, arteriosclerosis, and leukemias. Conclusions Cumulative lifetime stress may accelerate epigenetic aging, an effect that could be driven by glucocorticoid-induced epigenetic changes. These findings contribute to our understanding of mechanisms linking chronic stress with accelerated aging and heightened disease risk.}, language = {en} } @article{ErhardtMeierDeckert2020, author = {Erhardt, Angelika and Meier, Sandra and Deckert, J{\"u}rgen}, title = {Genetik und Epigenetik von Angsterkrankungen}, series = {BIOspektrum}, volume = {26}, journal = {BIOspektrum}, issn = {0947-0867}, doi = {10.1007/s12268-020-1366-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232380}, pages = {252-254}, year = {2020}, abstract = {Anxiety disorders are the most common mental disorders. The etiology is complex involving genetic and environmental factors. The first genome-wide association studies so far implicate a number of genetic loci, genome-wide epigenetic and therapy response related genetic studies are emerging. Genetic studies of anxiety disorders — as the most recent Psychiatric Genomics Consortium (PGC) group of disorders — are at the threshold of providing findings comparable to other mental disorders.}, language = {de} } @article{WeberMaihoferJaksicetal.2022, author = {Weber, Heike and Maihofer, Adam X. and Jaksic, Nenad and Bojic, Elma Feric and Kucukalic, Sabina and Dzananovic, Emina Sabic and Uka, Aferdita Goci and Hoxha, Blerina and Haxhibeqiri, Valdete and Haxhibeqiri, Shpend and Kravic, Nermina and Umihanic, Mirnesa Muminovic and Franc, Ana Cima and Babic, Romana and Pavlovic, Marko and Mehmedbasic, Alma Bravo and Aukst-Margetic, Branka and Kucukalic, Abdulah and Marjanovic, Damir and Babic, Dragan and Jakovljevic, Miro and Sinanovic, Osman and Avidbegović, Esmina and Agani, Ferid and Warrings, Bodo and Domschke, Katharina and Nievergelt, Caroline M. and Dzubur-Kulenovic, Alma and Erhardt, Angelika}, title = {Association of polygenic risk scores, traumatic life events and coping strategies with war-related PTSD diagnosis and symptom severity in the South Eastern Europe (SEE)-PTSD cohort}, series = {Journal of Neural Transmission}, volume = {129}, journal = {Journal of Neural Transmission}, number = {5-6}, issn = {1435-1463}, doi = {10.1007/s00702-021-02446-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-268541}, pages = {661-674}, year = {2022}, abstract = {Objectives Posttraumatic stress disorder (PTSD) is triggered by extremely stressful environmental events and characterized by high emotional distress, re-experiencing of trauma, avoidance and hypervigilance. The present study uses polygenic risk scores (PRS) derived from the UK Biobank (UKBB) mega-cohort analysis as part of the PGC PTSD GWAS effort to determine the heritable basis of PTSD in the South Eastern Europe (SEE)-PTSD cohort. We further analyzed the relation between PRS and additional disease-related variables, such as number and intensity of life events, coping, sex and age at war on PTSD and CAPS as outcome variables. Methods Association of PRS, number and intensity of life events, coping, sex and age on PTSD were calculated using logistic regression in a total of 321 subjects with current and remitted PTSD and 337 controls previously subjected to traumatic events but not having PTSD. In addition, PRS and other disease-related variables were tested for association with PTSD symptom severity, measured by the Clinician Administrated PTSD Scale (CAPS) by liner regression. To assess the relationship between the main outcomes PTSD diagnosis and symptom severity, each of the examined variables was adjusted for all other PTSD related variables. Results The categorical analysis showed significant polygenic risk in patients with remitted PTSD and the total sample, whereas no effects were found on symptom severity. Intensity of life events as well as the individual coping style were significantly associated with PTSD diagnosis in both current and remitted cases. The dimensional analyses showed as association of war-related frequency of trauma with symptom severity, whereas the intensity of trauma yielded significant results independently of trauma timing in current PTSD. Conclusions The present PRS application in the SEE-PTSD cohort confirms modest but significant polygenic risk for PTSD diagnosis. Environmental factors, mainly the intensity of traumatic life events and negative coping strategies, yielded associations with PTSD both categorically and dimensionally with more significant p-values. This suggests that, at least in the present cohort of war-related trauma, the association of environmental factors and current individual coping strategies with PTSD psychopathology was stronger than the polygenic risk.}, language = {en} } @article{HampfScherfClavelWeissetal.2023, author = {Hampf, Chantal and Scherf-Clavel, Maike and Weiß, Carolin and Kl{\"u}pfel, Catherina and Stonawski, Saskia and Hommers, Leif and Lichter, Katharina and Erhardt-Lehmann, Angelika and Unterecker, Stefan and Domschke, Katharina and Kittel-Schneider, Sarah and Menke, Andreas and Deckert, J{\"u}rgen and Weber, Heike}, title = {Effects of anxious depression on antidepressant treatment response}, series = {International Journal of Molecular Sciences}, volume = {24}, journal = {International Journal of Molecular Sciences}, number = {24}, issn = {1422-0067}, doi = {10.3390/ijms242417128}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-355801}, year = {2023}, abstract = {Anxious depression represents a subtype of major depressive disorder and is associated with increased suicidality, severity, chronicity and lower treatment response. Only a few studies have investigated the differences between anxious depressed (aMDD) and non-anxious depressed (naMDD) patients regarding treatment dosage, serum-concentration and drug-specific treatment response. In our naturalistic and prospective study, we investigated whether the effectiveness of therapy including antidepressants (SSRI, SNRI, NaSSA, tricyclics and combinations) in aMDD patients differs significantly from that in naMDD patients. In a sample of 346 patients, we calculated the anxiety somatization factor (ASF) and defined treatment response as a reduction (≥50\%) in the Hamilton Depression Rating Scale (HDRS)-21 score after 7 weeks of pharmacological treatment. We did not observe an association between therapy response and the baseline ASF-scores, or differences in therapy outcomes between aMDD and naMDD patients. However, non-responders had higher ASF-scores, and at week 7 aMDD patients displayed a worse therapy outcome than naMDD patients. In subgroup analyses for different antidepressant drugs, venlafaxine-treated aMDD patients showed a significantly worse outcome at week 7. Future prospective, randomized-controlled studies should address the question of a worse therapy outcome in aMDD patients for different psychopharmaceuticals individually.}, language = {en} } @article{BellingerWehrmannRohdeetal.2023, author = {Bellinger, Daniel and Wehrmann, Kristin and Rohde, Anna and Schuppert, Maria and St{\"o}rk, Stefan and Flohr-Jost, Michael and Gall, Dominik and Pauli, Paul and Deckert, J{\"u}rgen and Herrmann, Martin J. and Erhardt-Lehmann, Angelika}, title = {The application of virtual reality exposure versus relaxation training in music performance anxiety: a randomized controlled study}, series = {BMC Psychiatry}, volume = {23}, journal = {BMC Psychiatry}, doi = {10.1186/s12888-023-05040-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357833}, year = {2023}, abstract = {Background Performance anxiety is the most frequently reported anxiety disorder among professional musicians. Typical symptoms are - on a physical level - the consequences of an increase in sympathetic tone with cardiac stress, such as acceleration of heartbeat, increase in blood pressure, increased respiratory rate and tremor up to nausea or flush reactions. These symptoms can cause emotional distress, a reduced musical and artistical performance up to an impaired functioning. While anxiety disorders are preferably treated using cognitive-behavioral therapy with exposure, this approach is rather difficult for treating music performance anxiety since the presence of a public or professional jury is required and not easily available. The use of virtual reality (VR) could therefore display an alternative. So far, no therapy studies on music performance anxiety applying virtual reality exposure therapy have investigated the therapy outcome including cardiovascular changes as outcome parameters. Methods This mono-center, prospective, randomized and controlled clinical trial has a pre-post design with a follow-up period of 6 months. 46 professional and semi-professional musicians will be recruited and allocated randomly to an VR exposure group or a control group receiving progressive muscle relaxation training. Both groups will be treated over 4 single sessions. Music performance anxiety will be diagnosed based on a clinical interview using ICD-10 and DSM-5 criteria for specific phobia or social anxiety. A behavioral assessment test is conducted three times (pre, post, follow-up) in VR through an audition in a concert hall. Primary outcomes are the changes in music performance anxiety measured by the German B{\"u}hnenangstfragebogen and the cardiovascular reactivity reflected by heart rate variability (HRV). Secondary outcomes are changes in blood pressure, stress parameters such as cortisol in the blood and saliva, neuropeptides, and DNA-methylation. Discussion The trial investigates the effect of VR exposure in musicians with performance anxiety compared to a relaxation technique on anxiety symptoms and corresponding cardiovascular parameters. We expect a reduction of anxiety but also a consecutive improvement of HRV with cardiovascular protective effects. Trial registration This study was registered on clinicaltrials.gov. (ClinicalTrials.gov Number: NCT05735860)}, language = {en} }