@phdthesis{Gerlach2009, author = {Gerlach, Julia}, title = {Einfluss von Hypothyreose und Mukoviszidose auf das Ruhe- und Belastungs-EKG}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-40503}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2009}, abstract = {Bei Menschen, die an cystischer Fibrose oder auch an einer Hypothyreose erkrankt sind, ist die Beteiligung des Herz-Kreislauf-Systems eine bekannte Komplikation. Ziel dieser Arbeit war, m{\"o}glicherweise bislang unbekannte Auswirkungen dieser Erkrankungen auf das Belastungs-EKG von Kindern und Jugendlichen zu identifizieren und ggf. zu deuten. Dadurch sollte die Beurteilbarkeit des Belastungs-EKGs bei der Untersuchung der genannten Patientengruppen verbessert werden. Es wurden insgesamt 64 Patienten zwischen 11 und 18 Jahren zu dieser Studie herangezogen, die in drei Gruppen - n{\"a}mlich gesunde Kontrollen, hypothyreote Patienten und CF-Patienten - aufgeteilt wurden. Sowohl das Ruhe- als auch das Belastungs-EKG dieser Kinder und Jugendlichen wurden in der Extremit{\"a}ten-Ableitung II bez{\"u}glich der verschiedenen EKG-Parameter vermessen und statistisch ausgewertet. Die QT- und PQ-Dauer wurden zur Auswertung herzfrequenzkorrigiert. Bei hypothyreoten Patienten konnte sowohl in Ruhe als auch unter maximaler Belastung eine Bradykardie und eine relative Verl{\"a}ngerung der QT-Dauer festgestellt werden. In Ruhe war eine erniedrigte P-Amplitude zu erkennen. Es konnte gezeigt werden, dass unter k{\"o}rperlicher Belastung zus{\"a}tzlich eine Verl{\"a}ngerung der P-Dauer eintrat. Im Vergleich zu gesunden Probanden nahm die Dauer der P-Welle unter Belastung bei CF-Patienten weniger deutlich ab. Besonders auff{\"a}llig war die Amplitude der T-Welle, die im Gegensatz zu den Werten der Kontrollprobanden in Ruhe sehr hoch war und unter Belastung abnahm. Es ist allerdings noch unklar, warum die T-Amplitude bei Mukoviszidose-Patienten auf diese Weise reagiert. Die Hypothese, dass die hohe T-Amplitude in Ruhe bei Mukoviszidose-Patienten auf eine andere Herzachse, d. h. einen anderen Vektor zur{\"u}ckzuf{\"u}hren w{\"a}re, ließ sich nicht best{\"a}tigen. Eine m{\"o}gliche Erkl{\"a}rung ist eine Verschiebung des intra- oder parazellul{\"a}ren Elekrolythaushalts, m{\"o}glicherweise auch durch die genetische Ver{\"a}nderung des CFTR-Proteins. Dies zu kl{\"a}ren, m{\"u}sste Gegenstand weiterer Untersuchungen sein. Diese Studie hat die Bedeutung des Belastungs-EKGs f{\"u}r die Diagnose einer Rechtsherzbelastung nur indirekt durch den Vergleich von EKG-Befunden mit klinischen Daten, nicht jedoch im Vergleich zu bildgebenden Verfahren untersucht. Es ist jedoch bekannt, dass das EKG in seiner diagnostischen Wertigkeit f{\"u}r das Cor pulmonale eingeschr{\"a}nkt ist. Es m{\"u}ssen daher weitere Untersuchungsverfahren wie Herzechographie, Vektorkardiographie, Blutgasanalysen u. a. als zus{\"a}tzliche Diagnostika eingesetzt werden. Nur durch die Kombination mehrerer diagnostischer Mittel l{\"a}sst sich mit Sicherheit eine Rechtsherzbeteiligung ermitteln und ein therapeutisches Konzept gegen diese lebensbedrohliche Komplikation der zugrunde liegenden St{\"o}rung entwickeln. Zusammenfassend hat diese Studie gezeigt, dass das Belastungs-EKG von Patienten mit Hypothyreose und Mukoviszidose gegen{\"u}ber Gesunden ver{\"a}ndert ist. Das EKG kann allerdings nicht als einziges Diagnostikum bei Fragestellungen wie nach einem Cor pulmonale eingesetzt werden.}, subject = {Hypothyreose}, language = {de} } @article{RaynerColemanPurvesetal.2019, author = {Rayner, Christopher and Coleman, Jonathan R. I. and Purves, Kirstin L. and Hodsoll, John and Goldsmith, Kimberley and Alpers, Georg W. and Andersson, Evelyn and Arolt, Volker and Boberg, Julia and B{\"o}gels, Susan and Creswell, Cathy and Cooper, Peter and Curtis, Charles and Deckert, J{\"u}rgen and Domschke, Katharina and El Alaoui, Samir and Fehm, Lydia and Fydrich, Thomas and Gerlach, Alexander L. and Grocholewski, Anja and Hahlweg, Kurt and Hamm, Alfons and Hedman, Erik and Heiervang, Einar R. and Hudson, Jennifer L. and J{\"o}hren, Peter and Keers, Robert and Kircher, Tilo and Lang, Thomas and Lavebratt, Catharina and Lee, Sang-hyuck and Lester, Kathryn J. and Lindefors, Nils and Margraf, J{\"u}rgen and Nauta, Maaike and Pan{\´e}-Farr{\´e}, Christiane A. and Pauli, Paul and Rapee, Ronald M. and Reif, Andreas and Rief, Winfried and Roberts, Susanna and Schalling, Martin and Schneider, Silvia and Silverman, Wendy K. and Str{\"o}hle, Andreas and Teismann, Tobias and Thastum, Mikael and Wannem{\"u}ller, Andre and Weber, Heike and Wittchen, Hans-Ulrich and Wolf, Christiane and R{\"u}ck, Christian and Breen, Gerome and Eley, Thalia C.}, title = {A genome-wide association meta-analysis of prognostic outcomes following cognitive behavioural therapy in individuals with anxiety and depressive disorders}, series = {Translational Psychiatry}, volume = {9}, journal = {Translational Psychiatry}, number = {150}, doi = {10.1038/s41398-019-0481-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-225048}, pages = {1-13}, year = {2019}, abstract = {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.}, language = {en} } @article{WeselekKeinerFauseretal.2020, author = {Weselek, Grit and Keiner, Silke and Fauser, Mareike and Wagenf{\"u}hr, Lisa and M{\"u}ller, Julia and Kaltschmidt, Barbara and Brandt, Moritz D. and Gerlach, Manfred and Redecker, Christoph and Hermann, Andreas and Storch, Alexander}, title = {Norepinephrine is a negative regulator of the adult periventricular neural stem cell niche}, series = {Stem Cells}, volume = {38}, journal = {Stem Cells}, number = {9}, doi = {10.1002/stem.3232}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218250}, pages = {1188 -- 1201}, year = {2020}, abstract = {The limited proliferative capacity of neuroprogenitor cells (NPCs) within the periventricular germinal niches (PGNs) located caudal of the subventricular zone (SVZ) of the lateral ventricles together with their high proliferation capacity after isolation strongly implicates cell-extrinsic humoral factors restricting NPC proliferation in the hypothalamic and midbrain PGNs. We comparatively examined the effects of norepinephrine (NE) as an endogenous candidate regulator of PGN neurogenesis in the SVZ as well as the periventricular hypothalamus and the periaqueductal midbrain. Histological and neurochemical analyses revealed that the pattern of NE innervation of the adult PGNs is inversely associated with their in vivo NPC proliferation capacity with low NE levels coupled to high NPC proliferation in the SVZ but high NE levels coupled to low NPC proliferation in hypothalamic and midbrain PGNs. Intraventricular infusion of NE decreased NPC proliferation and neurogenesis in the SVZ-olfactory bulb system, while pharmacological NE inhibition increased NPC proliferation and early neurogenesis events in the caudal PGNs. Neurotoxic ablation of NE neurons using the Dsp4-fluoxetine protocol confirmed its inhibitory effects on NPC proliferation. Contrarily, NE depletion largely impairs NPC proliferation within the hippocampus in the same animals. Our data indicate that norepinephrine has opposite effects on the two fundamental neurogenic niches of the adult brain with norepinephrine being a negative regulator of adult periventricular neurogenesis. This knowledge might ultimately lead to new therapeutic approaches to influence neurogenesis in hypothalamus-related metabolic diseases or to stimulate endogenous regenerative potential in neurodegenerative processes such as Parkinson's disease.}, language = {en} } @article{FroehlichSassenrathNadjiOhletal.2022, author = {Fr{\"o}hlich, Ellen and Sassenrath, Claudia and Nadji-Ohl, Minou and Unteroberd{\"o}rster, Meike and R{\"u}ckriegel, Stefan and Brelie, Christian von der and Roder, Constantin and Forster, Marie-Therese and Schommer, Stephan and L{\"o}hr, Mario and Pala, Andrej and Goebel, Simone and Mielke, Dorothee and Gerlach, R{\"u}diger and Renovanz, Mirjam and Wirtz, Christian Rainer and Onken, Julia and Czabanka, Marcus and Tatagiba, Marcos Soares and Rohde, Veit and Ernestus, Ralf-Ingo and Vajkoczy, Peter and Gansland, Oliver and Coburger, Jan}, title = {Resilience in lower grade glioma patients}, series = {Cancers}, volume = {14}, journal = {Cancers}, number = {21}, issn = {2072-6694}, doi = {10.3390/cancers14215410}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-297518}, year = {2022}, abstract = {Current data show that resilience is an important factor in cancer patients' well-being. We aim to explore the resilience of patients with lower grade glioma (LGG) and the potentially influencing factors. We performed a cross-sectional assessment of adult patients with LGG who were enrolled in the LoG-Glio registry. By phone interview, we administered the following measures: Resilience Scale (RS-13), distress thermometer, Montreal Cognitive Assessment Test for visually impaired patients (MoCA-Blind), internalized stigmatization by brain tumor (ISBI), Eastern Cooperative Oncological Group performance status (ECOG), patients' perspective questionnaire (PPQ) and typical clinical parameters. We calculated correlations and multivariate regression models. Of 74 patients who were assessed, 38\% of those showed a low level of resilience. Our results revealed significant correlations of resilience with distress (p < 0.001, -0.49), MOCA (p = 0.003, 0.342), ECOG (p < 0.001, -0.602), stigmatization (p < 0.001, -0.558), pain (p < 0.001, -0.524), and occupation (p = 0.007, 0.329). In multivariate analyses, resilience was negatively associated with elevated ECOG (p = 0.020, β = -0.383) and stigmatization levels (p = 0.008, β = -0.350). Occupation showed a tendency towards a significant association with resilience (p = 0.088, β = -0.254). Overall, low resilience affected more than one third of our cohort. Low functional status is a specific risk factor for low resilience. The relevant influence of stigmatization on resilience is a novel finding for patients suffering from a glioma and should be routinely identified and targeted in clinical routine.}, language = {en} } @article{FeketeKulpokTaurinesetal.2023, author = {Fekete, Stefanie and Kulpok, Christine and Taurines, Regina and Egberts, Karin and Geissler, Julia and Gerlach, Manfred and Malonga Makosi, Doroth{\´e}e and K{\"o}nig, Jochem and Urschitz, Michael S. and Toni, Irmgard and Neubert, Antje and Romanos, Marcel}, title = {Value of a web-based pediatric drug information system to prevent serious adverse drug reactions in child and adolescent psychiatry}, series = {Journal of Neural Transmission}, volume = {130}, journal = {Journal of Neural Transmission}, number = {1}, doi = {10.1007/s00702-022-02563-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324817}, pages = {53-63}, year = {2023}, abstract = {Psychotropic drugs are frequently prescribed 'off-label' to children and adolescents and carry the risk of serious adverse drug reactions (sADR). We examined the frequency of sADRs of psychotropic drugs in pediatric inpatients and explored their potential preventability through following the recommendations of a web-based pediatric drug information system (PDIS). The potential socio-economic impacts of using this online system is also addressed. Routine clinical data from all inpatients treated in a child and adolescent psychiatry department between January 2017 and December 2018 were retrospectively examined for the occurrence of sADRs as defined by the European Medicines Agency. The preventability of the sADRs was assessed based on the information of the PDIS. Furthermore, the expected prolongation of the hospital stay due to sADRs was calculated as well as the associated treatment costs. The study was supported by the Innovation Fund of the Joint Federal Committee, grant number 01NVF16021. In total, 1036 patients were screened of whom 658 (63.5\%) received psychopharmacological treatment. In 53 (8.1\%) of these patients 54 sADRs were documented, of which 37 sADRs were identified as potentially preventable through PDIS. Mitigating sADR through PDIS would likely have prevented prolonged hospital stays and conferred considerable savings for health insurance companies. PDIS provides systematic and evidence-based information about pediatric psychopharmacotherapy and helps to prevent prescribing errors. Therefore, PDIS is a useful tool to increase drug therapy safety in child and adolescent psychiatry. Further prospective studies are needed to confirm the results.}, language = {en} } @article{GottschalkRichterZiegleretal.2019, author = {Gottschalk, Michael G. and Richter, Jan and Ziegler, Christiane and Schiele, Miriam A. and Mann, Julia and Geiger, Maximilian J. and Schartner, Christoph and Homola, Gy{\"o}rgy A. and Alpers, Georg W. and B{\"u}chel, Christian and Fehm, Lydia and Fydrich, Thomas and Gerlach, Alexander L. and Gloster, Andrew T. and Helbig-Lang, Sylvia and Kalisch, Raffael and Kircher, Tilo and Lang, Thomas and Lonsdorf, Tina B. and Pan{\´e}-Farr{\´e}, Christiane A. and Str{\"o}hle, Andreas and Weber, Heike and Zwanzger, Peter and Arolt, Volker and Romanos, Marcel and Wittchen, Hans-Ulrich and Hamm, Alfons and Pauli, Paul and Reif, Andreas and Deckert, J{\"u}rgen and Neufang, Susanne and H{\"o}fler, Michael and Domschke, Katharina}, title = {Orexin in the anxiety spectrum: association of a HCRTR1 polymorphism with panic disorder/agoraphobia, CBT treatment response and fear-related intermediate phenotypes}, series = {Translational Psychiatry}, volume = {9}, journal = {Translational Psychiatry}, doi = {10.1038/s41398-019-0415-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227479}, year = {2019}, abstract = {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.}, language = {en} }