@article{GeigerHirtlerGottfriedetal.2017,
  author    = {Geiger, Julia and Hirtler, Daniel and Gottfried, Kristina and Rahman, Ozair and Bollache, Emilie and Barker, Alex J. and Markl, Michael and Stiller, Brigitte},
  title     = {Longitudinal Evaluation of Aortic Hemodynamics in Marfan Syndrome: New Insights from a 4D Flow Cardiovascular Magnetic Resonance Multi-Year Follow-Up Study},
  series = {Journal of Cardiovascular Magnetic Resonance},
  volume    = {19},
  journal   = {Journal of Cardiovascular Magnetic Resonance},
  number    = {33},
  doi       = {10.1186/s12968-017-0347-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-171119},
  year      = {2017},
  abstract  = {Background The aim of this 4D flow cardiovascular magnetic resonance (CMR) follow-up study was to investigate longitudinal changes in aortic hemodynamics in adolescent patients with Marfan syndrome (MFS). Methods 4D flow CMR for the assessment of in-vivo 3D blood flow with full coverage of the thoracic aorta was performed twice (baseline scan t1/follow-up scan t2) in 19 adolescent MFS patients (age at t1: 12.7 ± 3.6 years, t2: 16.2 ± 4.3 years) with a mean follow-up duration of 3.5 ± 1.2 years. Ten healthy volunteers (24 ± 3.8 years) served as a control group. Data analysis included aortic blood flow visualization by color-coded 3D pathlines, and grading of flow patterns (helices/vortices) on a 3-point scale (none, moderate, severe; blinded reading, 2 observers). Regional aortic peak systolic velocities and systolic 3D wall shear stress (WSS) along the entire aortic wall were quantified. Z-Scores of the aortic root and proximal descending aorta (DAo) were assessed. Results Regional systolic WSS was stable over the follow-up duration, except for a significant decrease in the proximal inner DAo segment (p = 0.02) between t1 and t2. MFS patients revealed significant lower mean systolic WSS in the proximal inner DAo compared with volunteers (0.78 ± 0.15 N/m\(^{2}\)) at baseline t1 (0.60 ± 0.18 N/m\(^{2}\); p = 0.01) and follow-up t2 (0.55 ± 0.16 N/m\(^{2}\); p = 0.001). There were significant relationships (p < 0.01) between the segmental WSS in the proximal inner DAo, DAo Z-scores (r = -0.64) and helix/vortex pattern grading (r = -0.55) at both t1 and t2. The interobserver agreement for secondary flow patterns assessment was excellent (Cohen's k = 0.71). Conclusions MFS patients have lower segmental WSS in the inner proximal DAo segment which correlates with increased localized aberrant vortex/helix flow patterns and an enlarged diameter at one of the most critical sites for aortic dissection. General aortic hemodynamics are stable but these subtle localized DAo changes are already present at young age and tend to be more pronounced in the course of time.},
  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}
}