TY - JOUR A1 - Klauke, Benedikt A1 - Winter, Bernward A1 - Gajewska, Agnes A1 - Zwanzger, Peter A1 - Reif, Andreas A1 - Herrmann, Martin J. A1 - Dlugos, Andrea A1 - Warrings, Bodo A1 - Jacob, Christian A1 - Mühlberger, Andreas A1 - Arolt, Volker A1 - Pauli, Paul A1 - Deckert, Jürgen A1 - Domschke, Katharina T1 - Affect-Modulated Startle: Interactive Influence of Catechol-O-Methyltransferase Val158Met Genotype and Childhood Trauma JF - PLoS One N2 - The etiology of emotion-related disorders such as anxiety or affective disorders is considered to be complex with an interaction of biological and environmental factors. Particular evidence has accumulated for alterations in the dopaminergic and noradrenergic system - partly conferred by catechol-O-methyltransferase (COMT) gene variation - for the adenosinergic system as well as for early life trauma to constitute risk factors for those conditions. Applying a multi-level approach, in a sample of 95 healthy adults, we investigated effects of the functional COMT Val158Met polymorphism, caffeine as an adenosine A2A receptor antagonist (300 mg in a placebo-controlled intervention design) and childhood maltreatment (CTQ) as well as their interaction on the affect-modulated startle response as a neurobiologically founded defensive reflex potentially related to fear- and distress-related disorders. COMT val/val genotype significantly increased startle magnitude in response to unpleasant stimuli, while met/met homozygotes showed a blunted startle response to aversive pictures. Furthermore, significant gene-environment interaction of COMT Val158Met genotype with CTQ was discerned with more maltreatment being associated with higher startle potentiation in val/val subjects but not in met carriers. No main effect of or interaction effects with caffeine were observed. Results indicate a main as well as a GxE effect of the COMT Val158Met variant and childhood maltreatment on the affect-modulated startle reflex, supporting a complex pathogenetic model of the affect-modulated startle reflex as a basic neurobiological defensive reflex potentially related to anxiety and affective disorders. KW - COMT VAL(158)MET polymorphism KW - serotonin transporter gene KW - life events KW - community sample KW - acoustic startle KW - prepulse inhibition KW - panic disorder KW - caffeine-induced anxiety KW - fear-potentiated startle KW - posttraumatic-stress-disorder Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-132184 VL - 7 IS - 6 ER - TY - JOUR A1 - Pauli, Paul A1 - Glotzbach-Schoon, Evelyn A1 - Andreatta, Marta A1 - Reif, Andreas A1 - Ewald, Heike A1 - Tröger, Christian A1 - Baumann, Christian A1 - Deckert, Jürgen A1 - Mühlberger, Andreas T1 - Contextual fear conditioning in virtual reality is affected by 5HTTLPR and NPSR1 polymorphisms: effects on fear-potentiated startle JF - Frontiers in Behavioral Neuroscience N2 - The serotonin (5-HT) and neuropeptide S (NPS) systems are discussed as important genetic modulators of fear and sustained anxiety contributing to the etiology of anxiety disorders. Sustained anxiety is a crucial characteristic of most anxiety disorders which likely develops through contextual fear conditioning. This study investigated if and how genetic alterations of the 5-HT and the NPS systems as well as their interaction modulate contextual fear conditioning; specifically, function polymorphic variants in the genes coding for the 5-HT transporter (5HTT) and the NPS receptor (NPSR1) were studied. A large group of healthy volunteers was therefore stratified for 5HTTLPR (S+ vs. LL carriers) and NPSR1 rs324981 (T+ vs. AA carriers) polymorphisms resulting in four genotype groups (S+/T+, S+/AA, LL/T+, LL/AA) of 20 participants each. All participants underwent contextual fear conditioning and extinction using a virtual reality (VR) paradigm. During acquisition, one virtual office room (anxiety context, CXT+) was paired with an unpredictable electric stimulus (unconditioned stimulus, US), whereas another virtual office room was not paired with any US (safety context, CXT−). During extinction no US was administered. Anxiety responses were quantified by fear-potentiated startle and ratings. Most importantly, we found a gene × gene interaction on fear-potentiated startle. Only carriers of both risk alleles (S+/T+) exhibited higher startle responses in CXT+ compared to CXT−. In contrast, anxiety ratings were only influenced by the NPSR1 polymorphism with AA carriers showing higher anxiety ratings in CXT+ as compared to CXT−. Our results speak in favor of a two level account of fear conditioning with diverging effects on implicit vs. explicit fear responses. Enhanced contextual fear conditioning as reflected in potentiated startle responses may be an endophenotype for anxiety disorders. KW - 5HTTLPR KW - NPSR1 KW - gene × gene interaction KW - contextual fear conditioning KW - fear-potentiated startle Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96516 ER - TY - JOUR A1 - Weber, Heike A1 - Scholz, Claus Jürgen A1 - Domschke, Katharina A1 - Baumann, Christian A1 - Klauke, Benedikt A1 - Jacob, Christian P. A1 - Maier, Wolfgang A1 - Fritze, Jürgen A1 - Bandelow, Borwin A1 - Zwanzger, Peter Michael A1 - Lang, Thomas A1 - Fehm, Lydia A1 - Ströhle, Andreas A1 - Hamm, Alfons A1 - Gerlach, Alexander L. A1 - Alpers, Georg W. A1 - Kircher, Tilo A1 - Wittchen, Hans-Ulrich A1 - Arolt, Volker A1 - Pauli, Paul A1 - Deckert, Jürgen A1 - Reif, Andreas T1 - Gender Differences in Associations of Glutamate Decarboxylase 1 Gene (GAD1) Variants with Panic Disorder N2 - Background: Panic disorder is common (5% prevalence) and females are twice as likely to be affected as males. The heritable component of panic disorder is estimated at 48%. Glutamic acid dehydrogenase GAD1, the key enzyme for the synthesis of the inhibitory and anxiolytic neurotransmitter GABA, is supposed to influence various mental disorders, including mood and anxiety disorders. In a recent association study in depression, which is highly comorbid with panic disorder, GAD1 risk allele associations were restricted to females. Methodology/Principal Findings: Nineteen single nucleotide polymorphisms (SNPs) tagging the common variation in GAD1 were genotyped in two independent gender and age matched case-control samples (discovery sample n = 478; replication sample n = 584). Thirteen SNPs passed quality control and were examined for gender-specific enrichment of risk alleles associated with panic disorder by using logistic regression including a genotype6gender interaction term. The latter was found to be nominally significant for four SNPs (rs1978340, rs3762555, rs3749034, rs2241165) in the discovery sample; of note, the respective minor/risk alleles were associated with panic disorder only in females. These findings were not confirmed in the replication sample; however, the genotype6gender interaction of rs3749034 remained significant in the combined sample. Furthermore, this polymorphism showed a nominally significant association with the Agoraphobic Cognitions Questionnaire sum score. Conclusions/Significance: The present study represents the first systematic evaluation of gender-specific enrichment of risk alleles of the common SNP variation in the panic disorder candidate gene GAD1. Our tentative results provide a possible explanation for the higher susceptibility of females to panic disorder. KW - Medizin Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75830 ER - TY - JOUR A1 - Rayner, Christopher A1 - Coleman, Jonathan R. I. A1 - Purves, Kirstin L. A1 - Hodsoll, John A1 - Goldsmith, Kimberley A1 - Alpers, Georg W. A1 - Andersson, Evelyn A1 - Arolt, Volker A1 - Boberg, Julia A1 - Bögels, Susan A1 - Creswell, Cathy A1 - Cooper, Peter A1 - Curtis, Charles A1 - Deckert, Jürgen A1 - Domschke, Katharina A1 - El Alaoui, Samir A1 - Fehm, Lydia A1 - Fydrich, Thomas A1 - Gerlach, Alexander L. A1 - Grocholewski, Anja A1 - Hahlweg, Kurt A1 - Hamm, Alfons A1 - Hedman, Erik A1 - Heiervang, Einar R. A1 - Hudson, Jennifer L. A1 - Jöhren, Peter A1 - Keers, Robert A1 - Kircher, Tilo A1 - Lang, Thomas A1 - Lavebratt, Catharina A1 - Lee, Sang-hyuck A1 - Lester, Kathryn J. A1 - Lindefors, Nils A1 - Margraf, Jürgen A1 - Nauta, Maaike A1 - Pané-Farré, Christiane A. A1 - Pauli, Paul A1 - Rapee, Ronald M. A1 - Reif, Andreas A1 - Rief, Winfried A1 - Roberts, Susanna A1 - Schalling, Martin A1 - Schneider, Silvia A1 - Silverman, Wendy K. A1 - Ströhle, Andreas A1 - Teismann, Tobias A1 - Thastum, Mikael A1 - Wannemüller, Andre A1 - Weber, Heike A1 - Wittchen, Hans-Ulrich A1 - Wolf, Christiane A1 - Rück, Christian A1 - Breen, Gerome A1 - Eley, Thalia C. T1 - A genome-wide association meta-analysis of prognostic outcomes following cognitive behavioural therapy in individuals with anxiety and depressive disorders JF - Translational Psychiatry N2 - Major depressive disorder and the anxiety disorders are highly prevalent, disabling and moderately heritable. Depression and anxiety are also highly comorbid and have a strong genetic correlation (r(g) approximate to 1). Cognitive behavioural therapy is a leading evidence-based treatment but has variable outcomes. Currently, there are no strong predictors of outcome. Therapygenetics research aims to identify genetic predictors of prognosis following therapy. We performed genome-wide association meta-analyses of symptoms following cognitive behavioural therapy in adults with anxiety disorders (n = 972), adults with major depressive disorder (n = 832) and children with anxiety disorders (n = 920; meta-analysis n = 2724). We (h(SNP)(2)) and polygenic scoring was used to examine genetic associations between therapy outcomes and psychopathology, personality and estimated the variance in therapy outcomes that could be explained by common genetic variants learning. No single nucleotide polymorphisms were strongly associated with treatment outcomes. No significant estimate of h(SNP)(2) could be obtained, suggesting the heritability of therapy outcome is smaller than our analysis was powered to detect. Polygenic scoring failed to detect genetic overlap between therapy outcome and psychopathology, personality or learning. This study is the largest therapygenetics study to date. Results are consistent with previous, similarly powered genome-wide association studies of complex traits. KW - Human behaviour KW - Personalized medicine KW - Prognostic markers KW - Psychiatric disorders Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225048 VL - 9 IS - 150 ER - TY - JOUR A1 - Peters, Marcell K. A1 - Hemp, Andreas A1 - Appelhans, Tim A1 - Behler, Christina A1 - Classen, Alice A1 - Detsch, Florian A1 - Ensslin, Andreas A1 - Ferger, Stefan W. A1 - Frederiksen, Sara B. A1 - Gebert, Frederike A1 - Haas, Michael A1 - Helbig-Bonitz, Maria A1 - Hemp, Claudia A1 - Kindeketa, William J. A1 - Mwangomo, Ephraim A1 - Ngereza, Christine A1 - Otte, Insa A1 - Röder, Juliane A1 - Rutten, Gemma A1 - Costa, David Schellenberger A1 - Tardanico, Joseph A1 - Zancolli, Giulia A1 - Deckert, Jürgen A1 - Eardley, Connal D. A1 - Peters, Ralph S. A1 - Rödel, Mark-Oliver A1 - Schleuning, Matthias A1 - Ssymank, Axel A1 - Kakengi, Victor A1 - Zhang, Jie A1 - Böhning-Gaese, Katrin A1 - Brandl, Roland A1 - Kalko, Elisabeth K.V. A1 - Kleyer, Michael A1 - Nauss, Thomas A1 - Tschapka, Marco A1 - Fischer, Markus A1 - Steffan-Dewenter, Ingolf T1 - Predictors of elevational biodiversity gradients change from single taxa to the multi-taxa community level JF - Nature Communications N2 - The factors determining gradients of biodiversity are a fundamental yet unresolved topic in ecology. While diversity gradients have been analysed for numerous single taxa, progress towards general explanatory models has been hampered by limitations in the phylogenetic coverage of past studies. By parallel sampling of 25 major plant and animal taxa along a 3.7 km elevational gradient on Mt. Kilimanjaro, we quantify cross-taxon consensus in diversity gradients and evaluate predictors of diversity from single taxa to a multi-taxa community level. While single taxa show complex distribution patterns and respond to different environmental factors, scaling up diversity to the community level leads to an unambiguous support for temperature as the main predictor of species richness in both plants and animals. Our findings illuminate the influence of taxonomic coverage for models of diversity gradients and point to the importance of temperature for diversification and species coexistence in plant and animal communities. KW - community ecology KW - macroecology KW - tropical ecology KW - biodiversity Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-169374 VL - 7 ER - TY - JOUR A1 - Kingslake, Jonathan A1 - Dias, Rebecca A1 - Dawson, Gerard R. A1 - Simon, Judit A1 - Goodwin, Guy M. A1 - Harmer, Catherine J. A1 - Morriss, Richard A1 - Brown, Susan A1 - Guo, Boliang A1 - Dourish, Colin T. A1 - Ruhé, Henricus G. A1 - Lever, Anne G. A1 - Veltman, Dick J. A1 - van Schaik, Anneke A1 - Deckert, Jürgen A1 - Reif, Andreas A1 - Stäblein, Michael A1 - Menke, Andreas A1 - Gorwood, Philip A1 - Voegeli, Géraldine A1 - Perez, Victor A1 - Browning, Michael T1 - The effects of using the PReDicT Test to guide the antidepressant treatment of depressed patients: study protocol for a randomised controlled trial JF - Trials N2 - Background Antidepressant medication is commonly used to treat depression. However, many patients do not respond to the first medication prescribed and improvements in symptoms are generally only detectable by clinicians 4–6 weeks after the medication has been initiated. As a result, there is often a long delay between the decision to initiate an antidepressant medication and the identification of an effective treatment regimen. Previous work has demonstrated that antidepressant medications alter subtle measures of affective cognition in depressed patients, such as the appraisal of facial expression. Furthermore, these cognitive effects of antidepressants are apparent early in the course of treatment and can also predict later clinical response. This trial will assess whether an electronic test of affective cognition and symptoms (the Predicting Response to Depression Treatment Test; PReDicT Test) can be used to guide antidepressant treatment in depressed patients and, therefore, hasten treatment response compared to a control group of patients treated as usual. Methods/design The study is a randomised, two-arm, multi-centre, open-label, clinical investigation of a medical device, the PReDicT Test. It will be conducted in five European countries (UK, France, Spain, Germany and the Netherlands) in depressed patients who are commencing antidepressant medication. Patients will be randomised to treatment guided by the PReDicT Test (PReDicT arm) or to Treatment as Usual (TaU arm). Patients in the TaU arm will be treated as per current standard guidelines in their particular country. Patients in the PReDicT arm will complete the PReDicT Test after 1 (and if necessary, 2) weeks of treatment. If the test indicates non-response to the treatment, physicians will be advised to immediately alter the patient’s antidepressant therapy by dose escalation or switching to another compound. The primary outcome of the study is the proportion of patients showing a clinical response (defined as 50% or greater decrease in baseline scores of depressionmeasured using the Quick Inventory of Depressive Symptoms – Self-Rated questionnaire) at week 8. Health economic and acceptability data will also be collected and analysed. Discussion This trial will test the clinical efficacy, cost-effectiveness and acceptability of using the novel PReDicT Test to guide antidepressant treatment selection in depressed patients. Trial registration ClinicalTrials.gov, ID: NCT02790970. Registered on 30 March 2016. KW - psychiatry KW - depression KW - prediction KW - treatment KW - antidepressant KW - primary care Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173012 VL - 18 ER - TY - JOUR A1 - Gottschalk, Michael G. A1 - Richter, Jan A1 - Ziegler, Christiane A1 - Schiele, Miriam A. A1 - Mann, Julia A1 - Geiger, Maximilian J. A1 - Schartner, Christoph A1 - Homola, György A. A1 - Alpers, Georg W. A1 - Büchel, Christian A1 - Fehm, Lydia A1 - Fydrich, Thomas A1 - Gerlach, Alexander L. A1 - Gloster, Andrew T. A1 - Helbig-Lang, Sylvia A1 - Kalisch, Raffael A1 - Kircher, Tilo A1 - Lang, Thomas A1 - Lonsdorf, Tina B. A1 - Pané-Farré, Christiane A. A1 - Ströhle, Andreas A1 - Weber, Heike A1 - Zwanzger, Peter A1 - Arolt, Volker A1 - Romanos, Marcel A1 - Wittchen, Hans-Ulrich A1 - Hamm, Alfons A1 - Pauli, Paul A1 - Reif, Andreas A1 - Deckert, Jürgen A1 - Neufang, Susanne A1 - Höfler, Michael A1 - Domschke, Katharina T1 - Orexin in the anxiety spectrum: association of a HCRTR1 polymorphism with panic disorder/agoraphobia, CBT treatment response and fear-related intermediate phenotypes JF - Translational Psychiatry N2 - Preclinical studies point to a pivotal role of the orexin 1 (OX1) receptor in arousal and fear learning and therefore suggest the HCRTR1 gene as a prime candidate in panic disorder (PD) with/without agoraphobia (AG), PD/AG treatment response, and PD/AG-related intermediate phenotypes. Here, a multilevel approach was applied to test the non-synonymous HCRTR1 C/T Ile408Val gene variant (rs2271933) for association with PD/AG in two independent case-control samples (total n = 613 cases, 1839 healthy subjects), as an outcome predictor of a six-weeks exposure-based cognitive behavioral therapy (CBT) in PD/AG patients (n = 189), as well as with respect to agoraphobic cognitions (ACQ) (n = 483 patients, n = 2382 healthy subjects), fMRI alerting network activation in healthy subjects (n = 94), and a behavioral avoidance task in PD/AG pre- and post-CBT (n = 271). The HCRTR1 rs2271933 T allele was associated with PD/AG in both samples independently, and in their meta-analysis (p = 4.2 × 10−7), particularly in the female subsample (p = 9.8 × 10−9). T allele carriers displayed a significantly poorer CBT outcome (e.g., Hamilton anxiety rating scale: p = 7.5 × 10−4). The T allele count was linked to higher ACQ sores in PD/AG and healthy subjects, decreased inferior frontal gyrus and increased locus coeruleus activation in the alerting network. Finally, the T allele count was associated with increased pre-CBT exposure avoidance and autonomic arousal as well as decreased post-CBT improvement. In sum, the present results provide converging evidence for an involvement of HCRTR1 gene variation in the etiology of PD/AG and PD/AG-related traits as well as treatment response to CBT, supporting future therapeutic approaches targeting the orexin-related arousal system. KW - human behaviour KW - molecular neuroscience KW - personalized medicine KW - predictive markers KW - psychiatric disorders Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227479 VL - 9 ER - TY - JOUR A1 - Biehl, Stefanie C. A1 - Dresler, Thomas A1 - Reif, Andreas A1 - Scheuerpflug, Peter A1 - Deckert, Jürgen A1 - Herrmann, Martin J. T1 - Dopamine Transporter (DAT1) and Dopamine Receptor D4 (DRD4) Genotypes Differentially Impact on Electrophysiological Correlates of Error Processing JF - PLoS One N2 - Recent studies as well as theoretical models of error processing assign fundamental importance to the brain's dopaminergic system. Research about how the electrophysiological correlates of error processing—the error-related negativity (ERN) and the error positivity (Pe)—are influenced by variations of common dopaminergic genes, however, is still relatively scarce. In the present study, we therefore investigated whether polymorphisms in the DAT1 gene and in the DRD4 gene, respectively, lead to interindividual differences in these error processing correlates. One hundred sixty participants completed a version of the Eriksen Flanker Task while a 26-channel EEG was recorded. The task was slightly modified in order to increase error rates. During data analysis, participants were split into two groups depending on their DAT1 and their DRD4 genotypes, respectively. ERN and Pe amplitudes after correct responses and after errors as well as difference amplitudes between errors and correct responses were analyzed. We found a differential effect of DAT1 genotype on the Pe difference amplitude but not on the ERN difference amplitude, while the reverse was true for DRD4 genotype. These findings are in line with predictions from theoretical models of dopaminergic transmission in the brain. They furthermore tie results from clinical investigations of disorders impacting on the dopamine system to genetic variations known to be at-risk genotypes. KW - haplotypes KW - electroencephalography KW - basal ganglia KW - reaction time KW - dopaminergics KW - dopamine KW - ADHD KW - research errors Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-137930 VL - 6 IS - 12 ER - TY - JOUR A1 - Manish, Asthana A1 - Nueckel, Katharina A1 - Mühlberger, Andreas A1 - Neueder, Dorothea A1 - Polak, Thomas A1 - Domschke, Katharina A1 - Deckert, Jürgen A1 - Herrmann, Martin J. T1 - Effects of transcranial direct current stimulation on consolidation of fear memory JF - Frontiers in Neuropsychiatric Imaging and Stimulation N2 - It has been shown that applying transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) influences declarative memory processes. This study investigates the efficacy of tDCS on emotional memory consolidation, especially experimental fear conditioning. We applied an auditory fear-conditioning paradigm, in which two differently colored squares (blue and yellow) were presented as conditioned stimuli (CS) and an auditory stimulus as unconditioned stimulus (UCS). Sixty-nine participants were randomly assigned into three groups: anodal, cathodal, and sham stimulation. The participants of the two active groups (i.e., anodal and cathodal) received tDCS over the left DLPFC for 12 min after fear conditioning. The effect of fear conditioning and consolidation (24 h later) was measured by assessing the skin conductance response (SCR) to the CS. The results provide evidence that cathodal stimulation of the left DLPFC leads to an inhibitory effect on fear memory consolidation compared to anodal and sham stimulation, as indicated by decreased SCRs to CS+ presentation during extinction training at day 2. In conclusion, current work suggests that cathodal stimulation interferes with processes of fear memory consolidation. KW - transcranial direct current stimulation KW - dorsolateral prefrontal cortex KW - fear conditioning KW - fear memory consolidation Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-97294 ER - TY - JOUR A1 - Pittig, Andre A1 - Heinig, Ingmar A1 - Goerigk, Stephan A1 - Thiel, Freya A1 - Hummel, Katrin A1 - Scholl, Lucie A1 - Deckert, Jürgen A1 - Pauli, Paul A1 - Domschke, Katharina A1 - Lueken, Ulrike A1 - Fydrich, Thomas A1 - Fehm, Lydia A1 - Plag, Jens A1 - Ströhle, Andreas A1 - Kircher, Tilo A1 - Straube, Benjamin A1 - Rief, Winfried A1 - Koelkebeck, Katja A1 - Arolt, Volker A1 - Dannlowski, Udo A1 - Margraf, Jürgen A1 - Totzeck, Christina A1 - Schneider, Silvia A1 - Neudeck, Peter A1 - Craske, Michelle G. A1 - Hollandt, Maike A1 - Richter, Jan A1 - Hamm, Alfons A1 - Wittchen, Hans-Ulrich T1 - Efficacy of temporally intensified exposure for anxiety disorders: A multicenter randomized clinical trial JF - Depression and Anxiety N2 - Background The need to optimize exposure treatments for anxiety disorders may be addressed by temporally intensified exposure sessions. Effects on symptom reduction and public health benefits should be examined across different anxiety disorders with comorbid conditions. Methods This multicenter randomized controlled trial compared two variants of prediction error-based exposure therapy (PeEx) in various anxiety disorders (both 12 sessions + 2 booster sessions, 100 min/session): temporally intensified exposure (PeEx-I) with exposure sessions condensed to 2 weeks (n = 358) and standard nonintensified exposure (PeEx-S) with weekly exposure sessions (n = 368). Primary outcomes were anxiety symptoms (pre, post, and 6-months follow-up). Secondary outcomes were global severity (across sessions), quality of life, disability days, and comorbid depression. Results Both treatments resulted in substantial improvements at post (PeEx-I: d\(_{within}\) = 1.50, PeEx-S: d\(_{within}\) = 1.78) and follow-up (PeEx-I: d\(_{within}\) = 2.34; PeEx-S: d\(_{within}\) = 2.03). Both groups showed formally equivalent symptom reduction at post and follow-up. However, time until response during treatment was 32% shorter in PeEx-I (median = 68 days) than PeEx-S (108 days; TR\(_{PeEx-I}\)-I = 0.68). Interestingly, drop-out rates were lower during intensified exposure. PeEx-I was also superior in reducing disability days and improving quality of life at follow-up without increasing relapse. Conclusions Both treatment variants focusing on the transdiagnostic exposure-based violation of threat beliefs were effective in reducing symptom severity and disability in severe anxiety disorders. Temporally intensified exposure resulted in faster treatment response with substantial public health benefits and lower drop-out during the exposure phase, without higher relapse. Clinicians can expect better or at least comparable outcomes when delivering exposure in a temporally intensified manner. KW - randomized controlled trial KW - anxiety disorders KW - exposure therapy KW - intensified treatment KW - public health Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-257331 VL - 38 IS - 11 ER - TY - JOUR A1 - Schiele, Miriam A. A1 - Ziegler, Christiane A1 - Kollert, Leonie A1 - Katzorke, Andrea A1 - Schartner, Christoph A1 - Busch, Yasmin A1 - Gromer, Daniel A1 - Reif, Andreas A1 - Pauli, Paul A1 - Deckert, Jürgen A1 - Herrmann, Martin J. A1 - Domschke, Katharina T1 - Plasticity of Functional MAOA Gene Methylation in Acrophobia JF - International Journal of Neuropsychopharmacology N2 - Epigenetic mechanisms have been proposed to mediate fear extinction in animal models. Here, MAOA methylation was analyzed via direct sequencing of sodium bisulfite-treated DNA extracted from blood cells before and after a 2-week exposure therapy in a sample of n = 28 female patients with acrophobia as well as in n = 28 matched healthy female controls. Clinical response was measured using the Acrophobia Questionnaire and the Attitude Towards Heights Questionnaire. The functional relevance of altered MAOA methylation was investigated by luciferase-based reporter gene assays. MAOA methylation was found to be significantly decreased in patients with acrophobia compared with healthy controls. Furthermore, MAOA methylation levels were shown to significantly increase after treatment and correlate with treatment response as reflected by decreasing Acrophobia Questionnaire/Attitude Towards Heights Questionnaire scores. Functional analyses revealed decreased reporter gene activity in presence of methylated compared with unmethylated pCpGfree_MAOA reporter gene vector constructs. The present proof-of-concept psychotherapy-epigenetic study for the first time suggests functional MAOA methylation changes as a potential epigenetic correlate of treatment response in acrophobia and fosters further investigation into the notion of epigenetic mechanisms underlying fear extinction. KW - monoamine oxidase A KW - anxiety KW - extinction KW - epigenetics KW - DNA methylation Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-228571 VL - 21 IS - 9 ER - TY - JOUR A1 - Katzorke, Andrea A1 - Zeller, Julia B. M. A1 - Müller, Laura D. A1 - Lauer, Martin A1 - Polak, Thomas A1 - Reif, Andreas A1 - Deckert, Jürgen A1 - Herrmann, Martin J. T1 - Reduced activity in the right inferior frontal gyrus in elderly APOE-E4 carriers during a verbal fluency task JF - Frontiers in Human Neuroscience N2 - Apolipoprotein-E4 (APOE-E4) is a major genetic risk factor for developing Alzheimer’s disease (AD). The verbal fluency task (VFT), especially the subtask category fluency, has shown to provide a good discrimination between cognitively normal controls and subjects with AD. Interestingly, APOE-E4 seems to have no effect on the behavioral performance during a VFT in healthy elderly. Thus, the purpose of the present study was to reveal possible compensation mechanisms by investigating the effect of APOE-E4 on the hemodynamic response in non-demented elderly during a VFT by using functional near-infrared spectroscopy (fNIRS). We compared performance and hemodynamic response of high risk APOE-E4/E4, -E3/E4 carriers with neutral APOE-E3/E3 non-demented subjects (N = 288; 70–77 years). No difference in performance was found. APOE-E4/E4, -E3/E4 carriers had a decreased hemodynamic response in the right inferior frontal junction (IFJ) with a corresponding higher response in the left middle frontal gyrus (MFG) during category fluency. Performance was correlated with the hemodynamic response in the MFG. We assume a compensation of decreased IFJ brain activation by utilizing the MFG during category fluency and thus resulting in no behavioral differences between APOE-groups during the performance of a VFT. KW - psychiatry KW - near-infrared spectroscopy KW - verbal fluency task KW - apolipoprotein-E4 KW - Alzheimer's disease KW - elderly Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-171892 VL - 11 ER - TY - JOUR A1 - Schiele, Miriam A. A1 - Reinhard, Julia A1 - Reif, Andreas A1 - Domschke, Katharina A1 - Romanos, Marcel A1 - Deckert, Jürgen A1 - Pauli, Paul T1 - Developmental aspects of fear: Comparing the acquisition and generalization of conditioned fear in children and adults JF - Developmental Psychobiology N2 - Most research on human fear conditioning and its generalization has focused on adults whereas only little is known about these processes in children. Direct comparisons between child and adult populations are needed to determine developmental risk markers of fear and anxiety. We compared 267 children and 285 adults in a differential fear conditioning paradigm and generalization test. Skin conductance responses (SCR) and ratings of valence and arousal were obtained to indicate fear learning. Both groups displayed robust and similar differential conditioning on subjective and physiological levels. However, children showed heightened fear generalization compared to adults as indexed by higher arousal ratings and SCR to the generalization stimuli. Results indicate overgeneralization of conditioned fear as a developmental correlate of fear learning. The developmental change from a shallow to a steeper generalization gradient is likely related to the maturation of brain structures that modulate efficient discrimination between danger and (ambiguous) safety cues. KW - fear conditioning KW - fear generalization KW - development KW - skin conductance KW - maturation Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-189488 VL - 58 IS - 4 ER - TY - JOUR A1 - Ziegler, Alice A1 - Meyer, Hanna A1 - Otte, Insa A1 - Peters, Marcell K. A1 - Appelhans, Tim A1 - Behler, Christina A1 - Böhning-Gaese, Katrin A1 - Classen, Alice A1 - Detsch, Florian A1 - Deckert, Jürgen A1 - Eardley, Connal D. A1 - Ferger, Stefan W. A1 - Fischer, Markus A1 - Gebert, Friederike A1 - Haas, Michael A1 - Helbig-Bonitz, Maria A1 - Hemp, Andreas A1 - Hemp, Claudia A1 - Kakengi, Victor A1 - Mayr, Antonia V. A1 - Ngereza, Christine A1 - Reudenbach, Christoph A1 - Röder, Juliane A1 - Rutten, Gemma A1 - Schellenberger Costa, David A1 - Schleuning, Matthias A1 - Ssymank, Axel A1 - Steffan-Dewenter, Ingolf A1 - Tardanico, Joseph A1 - Tschapka, Marco A1 - Vollstädt, Maximilian G. R. A1 - Wöllauer, Stephan A1 - Zhang, Jie A1 - Brandl, Roland A1 - Nauss, Thomas T1 - Potential of airborne LiDAR derived vegetation structure for the prediction of animal species richness at Mount Kilimanjaro JF - Remote Sensing N2 - The monitoring of species and functional diversity is of increasing relevance for the development of strategies for the conservation and management of biodiversity. Therefore, reliable estimates of the performance of monitoring techniques across taxa become important. Using a unique dataset, this study investigates the potential of airborne LiDAR-derived variables characterizing vegetation structure as predictors for animal species richness at the southern slopes of Mount Kilimanjaro. To disentangle the structural LiDAR information from co-factors related to elevational vegetation zones, LiDAR-based models were compared to the predictive power of elevation models. 17 taxa and 4 feeding guilds were modeled and the standardized study design allowed for a comparison across the assemblages. Results show that most taxa (14) and feeding guilds (3) can be predicted best by elevation with normalized RMSE values but only for three of those taxa and two of those feeding guilds the difference to other models is significant. Generally, modeling performances between different models vary only slightly for each assemblage. For the remaining, structural information at most showed little additional contribution to the performance. In summary, LiDAR observations can be used for animal species prediction. However, the effort and cost of aerial surveys are not always in proportion with the prediction quality, especially when the species distribution follows zonal patterns, and elevation information yields similar results. KW - biodiversity KW - species richness KW - LiDAR KW - elevation KW - partial least square regression KW - arthropods KW - birds KW - bats KW - predictive modeling Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-262251 SN - 2072-4292 VL - 14 IS - 3 ER - TY - JOUR A1 - Kuhn, Manuel A1 - Scharfenort, Robert A1 - Schümann, Dirk A1 - Schiele, Miriam A. A1 - Münsterkötter, Anna L. A1 - Deckert, Jürgen A1 - Domschke, Katharina A1 - Haaker, Jan A1 - Kalisch, Raffael A1 - Pauli, Paul A1 - Reif, Andreas A1 - Romanos, Marcel A1 - Zwanzger, Peter A1 - Lonsdorf, Tina B. T1 - Mismatch or allostatic load? Timing of life adversity differentially shapes gray matter volume and anxious temperament JF - Social Cognitive and Affective Neuroscience N2 - Traditionally, adversity was defined as the accumulation of environmental events (allostatic load). Recently however, a mismatch between the early and the later (adult) environment (mismatch) has been hypothesized to be critical for disease development, a hypothesis that has not yet been tested explicitly in humans. We explored the impact of timing of life adversity (childhood and past year) on anxiety and depression levels (N = 833) and brain morphology (N = 129). Both remote (childhood) and proximal (recent) adversities were differentially mirrored in morphometric changes in areas critically involved in emotional processing (i.e. amygdala/hippocampus, dorsal anterior cingulate cortex, respectively). The effect of adversity on affect acted in an additive way with no evidence for interactions (mismatch). Structural equation modeling demonstrated a direct effect of adversity on morphometric estimates and anxiety/depression without evidence of brain morphology functioning as a mediator. Our results highlight that adversity manifests as pronounced changes in brain morphometric and affective temperament even though these seem to represent distinct mechanistic pathways. A major goal of future studies should be to define critical time periods for the impact of adversity and strategies for intervening to prevent or reverse the effects of adverse childhood life experiences. KW - VBM KW - childhood maltreatment KW - adversity KW - stressful life events KW - mismatch KW - allostatic load Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-189645 VL - 11 IS - 4 ER - TY - JOUR A1 - Tanoey, Justine A1 - Baechle, Christina A1 - Brenner, Hermann A1 - Deckert, Andreas A1 - Fricke, Julia A1 - Günther, Kathrin A1 - Karch, André A1 - Keil, Thomas A1 - Kluttig, Alexander A1 - Leitzmann, Michael A1 - Mikolajczyk, Rafael A1 - Obi, Nadia A1 - Pischon, Tobias A1 - Schikowski, Tamara A1 - Schipf, Sabine M. A1 - Schulze, Matthias B. A1 - Sedlmeier, Anja A1 - Moreno Velásquez, Ilais A1 - Weber, Katharina S. A1 - Völzke, Henry A1 - Ahrens, Wolfgang A1 - Gastell, Sylvia A1 - Holleczek, Bernd A1 - Jöckel, Karl-Heinz A1 - Katzke, Verena A1 - Lieb, Wolfgang A1 - Michels, Karin B. A1 - Schmidt, Börge A1 - Teismann, Henning A1 - Becher, Heiko T1 - Birth order, Caesarean section, or daycare attendance in relation to child- and adult-onset type 1 diabetes: results from the German National Cohort JF - International Journal of Environmental Research and Public Health N2 - (1) Background: Global incidence of type 1 diabetes (T1D) is rising and nearly half occurred in adults. However, it is unclear if certain early-life childhood T1D risk factors were also associated with adult-onset T1D. This study aimed to assess associations between birth order, delivery mode or daycare attendance and type 1 diabetes (T1D) risk in a population-based cohort and whether these were similar for childhood- and adult-onset T1D (cut-off age 15); (2) Methods: Data were obtained from the German National Cohort (NAKO Gesundheitsstudie) baseline assessment. Self-reported diabetes was classified as T1D if: diagnosis age ≤ 40 years and has been receiving insulin treatment since less than one year after diagnosis. Cox regression was applied for T1D risk analysis; (3) Results: Analyses included 101,411 participants (100 childhood- and 271 adult-onset T1D cases). Compared to “only-children”, HRs for second- or later-born individuals were 0.70 (95% CI = 0.50–0.96) and 0.65 (95% CI = 0.45–0.94), respectively, regardless of parental diabetes, migration background, birth year and perinatal factors. In further analyses, higher birth order reduced T1D risk in children and adults born in recent decades. Caesarean section and daycare attendance showed no clear associations with T1D risk; (4) Conclusions: Birth order should be considered in both children and adults’ T1D risk assessment for early detection. KW - perinatal KW - adult-onset KW - late-onset KW - autoimmune KW - delivery mode KW - sex KW - offspring KW - NAKO Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-286216 SN - 1660-4601 VL - 19 IS - 17 ER - TY - JOUR A1 - Hampf, Chantal A1 - Scherf-Clavel, Maike A1 - Weiß, Carolin A1 - Klüpfel, Catherina A1 - Stonawski, Saskia A1 - Hommers, Leif A1 - Lichter, Katharina A1 - Erhardt-Lehmann, Angelika A1 - Unterecker, Stefan A1 - Domschke, Katharina A1 - Kittel-Schneider, Sarah A1 - Menke, Andreas A1 - Deckert, Jürgen A1 - Weber, Heike T1 - Effects of anxious depression on antidepressant treatment response JF - International Journal of Molecular Sciences N2 - 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. KW - pharmacotherapy KW - depressive disorder KW - anxious depression KW - anxiety KW - therapy response Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-355801 SN - 1422-0067 VL - 24 IS - 24 ER -