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High-Dose Testosterone Treatment Increases Serotonin Transporter Binding in Transgender People

Georg S. Kranz, Wolfgang Wadsak, Ulrike Kaufmann, Markus Savli, Pia Baldinger, Gregor Gryglewski, Daniela Haeusler, Marie Spies, Markus Mitterhauser, Siegfried Kasper, Rupert Lanzenberger
2015 Biological Psychiatry  
BACKGROUND: Women are two times more likely to be diagnosed with depression than men. Sex hormones modulating serotonergic transmission are proposed to partly underlie these epidemiologic findings. Here, we used the cross-sex steroid hormone treatment of transsexuals seeking sex reassignment as a model to investigate acute and chronic effects of testosterone and estradiol on serotonin reuptake transporter (SERT) binding in female-to-male and male-to-female transsexuals. METHODS: Thirty-three
more » ... nssexuals underwent [ 11 C]DASB positron emission tomography before start of treatment, a subset of which underwent a second scan 4 weeks and a third scan 4 months after treatment start. SERT nondisplaceable binding potential was quantified in 12 regions of interest. Treatment effects were analyzed using linear mixed models. Changes of hormone plasma levels were correlated with changes in regional SERT nondisplaceable binding potential. RESULTS: One and 4 months of androgen treatment in female-to-male transsexuals increased SERT binding in amygdala, caudate, putamen, and median raphe nucleus. SERT binding increases correlated with treatment-induced increases in testosterone levels, suggesting that testosterone increases SERT expression on the cell surface. Conversely, 4 months of antiandrogen and estrogen treatment in male-to-female transsexuals led to decreases in SERT binding in insula, anterior, and mid-cingulate cortex. Increases in estradiol levels correlated negatively with decreases in regional SERT binding , indicating a protective effect of estradiol against SERT loss. CONCLUSIONS: Given the central role of the SERT in the treatment of depression and anxiety disorders, these findings may lead to new treatment modalities and expand our understanding of the mechanism of action of antidepressant treatment properties.
doi:10.1016/j.biopsych.2014.09.010 pmid:25497691 pmcid:PMC4585531 fatcat:xmtun33g5re5bbwofnjlscghzy

Normative database of the serotonergic system in healthy subjects using multi-tracer PET

Markus Savli, Andreas Bauer, Markus Mitterhauser, Yu-Shin Ding, Andreas Hahn, Tina Kroll, Alexander Neumeister, Daniela Haeusler, Johanna Ungersboeck, Shannan Henry, Sanaz Attaripour Isfahani, Frank Rattay (+3 others)
2012 NeuroImage  
Database 5-HT1A 5-HT2A 5-HT1B 5-HTT The highly diverse serotonergic system with at least 16 different receptor subtypes is implicated in the pathophysiology of most neuropsychiatric disorders including affective and anxiety disorders, obsessive compulsive disorder, post-traumatic stress disorder, eating disorders, sleep disturbance, attention deficit/ hyperactivity disorder, drug addiction, suicidal behavior, schizophrenia, Alzheimer, etc. Alterations of the interplay between various pre-and
more » ... tsynaptic receptor subtypes might be involved in the pathogenesis of these disorders. However, there is a lack of comprehensive in vivo values using standardized procedures. In the current PET study we quantified 3 receptor subtypes, including the major inhibitory (5-HT 1A and 5-HT 1B ) and excitatory (5-HT 2A ) receptors, and the transporter (5-HTT) in the brain of healthy human subjects to provide a database of standard values. PET scans were performed on 95 healthy subjects (age=28.0±6.9 years; 59% males) using the selective radioligands [carbonyl-11 C]WAY-100635, [ 11 C]P943, [ 18 F]altanserin and [ 11 C]DASB, respectively. A standard template in MNI stereotactic space served for region of interest delineation. This template follows two anatomical parcellation schemes: 1) Brodmann areas including 41 regions and 2) AAL (automated anatomical labeling) including 52 regions. Standard values (mean, SD, and range) for each receptor and region are presented. Mean cortical and subcortical binding potential (BP) values were in good agreement with previously published human in vivo and post-mortem data. By means of linear equations, PET binding potentials were translated to post-mortem binding (provided in pmol/g), yielding 5.89 pmol/g (5-HT 1A ), 23.5 pmol/g (5-HT 1B ), 31.44 pmol/g (5-HT 2A ), and 11.33 pmol/g (5-HTT) being equivalent to the BP of 1, respectively. Furthermore, we computed individual voxel-wise maps with BP values and generated average tracer-specific whole-brain binding maps. This knowledge might improve our interpretation of the alterations taking place in the serotonergic system during neuropsychiatric disorders.
doi:10.1016/j.neuroimage.2012.07.001 pmid:22789740 fatcat:b2pwlthdjbeinjvhuosmhyhzu4

The Norepinephrine Transporter in Attention-Deficit/Hyperactivity Disorder Investigated With Positron Emission Tomography

Thomas Vanicek, Marie Spies, Christina Rami-Mark, Markus Savli, Anna Höflich, Georg S. Kranz, Andreas Hahn, Alexandra Kutzelnigg, Tatjana Traub-Weidinger, Markus Mitterhauser, Wolfgang Wadsak, Marcus Hacker (+3 others)
2014 JAMA psychiatry  
IMPORTANCE Attention-deficit/hyperactivity disorder (ADHD) research has long focused on the dopaminergic system's contribution to pathogenesis, although the results have been inconclusive. However, a case has been made for the involvement of the noradrenergic system, which modulates cognitive processes, such as arousal, working memory, and response inhibition, all of which are typically affected in ADHD. Furthermore, the norepinephrine transporter (NET) is an important target for frequently
more » ... cribed medication in ADHD. Therefore, the NET is suggested to play a critical role in ADHD. OBJECTIVE To explore the differences in NET nondisplaceable binding potential (NET BP ND ) using positron emission tomography and the highly selective radioligand (S,S)- between adults with ADHD and healthy volunteers serving as controls. DESIGN, SETTING, AND PARTICIPANTS Twenty-two medication-free patients with ADHD (mean [SD] age, 30.7 [10.4] years; 15 [68%] men) without psychiatric comorbidities and 22 age-and sex-matched healthy controls (30.9 [10.6] years; 15 [68%] men) underwent positron emission tomography once. A linear mixed model was used to compare NET BP ND between groups. MAIN OUTCOMES AND MEASURES The NET BP ND in selected regions of interest relevant for ADHD, including the hippocampus, putamen, pallidum, thalamus, midbrain with pons (comprising a region of interest that includes the locus coeruleus), and cerebellum. In addition, the NET BP ND was evaluated in thalamic subnuclei (13 atlas-based regions of interest). RESULTS We found no significant differences in NET availability or regional distribution between patients with ADHD and healthy controls in all investigated brain regions (F 1,41 < 0.01; P = .96). Furthermore, we identified no significant association between ADHD symptom severity and regional NET availability. Neither sex nor smoking status influenced NET availability. We determined a significant negative correlation between age and NET availability in the thalamus (R 2 = 0.29; P < .01 corrected) and midbrain with pons, including the locus coeruleus (R 2 = 0.18; P < .01 corrected), which corroborates prior findings of a decrease in NET availability with aging in the human brain. CONCLUSIONS AND RELEVANCE Our results do not indicate involvement of changes in brain NET availability or distribution in the pathogenesis of ADHD. However, the noradrenergic transmitter system may be affected on a different level, such as in cortical regions, which cannot be reliably quantified with this positron emission tomography ligand. Alternatively, different key proteins of noradrenergic neurotransmission might be affected. and from the local community via advertisement. Patients had not received psychopharmacologic treatment for at least 6 months before the screening visit; all control participants were naive to all psychopharmacologic treatment. Of the original 51 study participants, 2 (4%) were excluded because of substance abuse, 2 (4%) because of somatic disorders, and 3 (6%) because of radiosynthesis difficulties.
doi:10.1001/jamapsychiatry.2014.1226 pmid:25338091 pmcid:PMC4699255 fatcat:6dodlic3gvfy5fkygwi3y33zue

[18F]FE@SUPPY: a suitable PET tracer for the adenosine A3 receptor? An in vivo study in rodents

Daniela Haeusler, Claudia Kuntner, Lukas Nics, Markus Savli, Markus Zeilinger, Thomas Wanek, Panagiotis Karagiannis, Rupert R. Lanzenberger, Oliver Langer, Karem Shanab, Helmut Spreitzer, Wolfgang Wadsak (+2 others)
2015 European Journal of Nuclear Medicine and Molecular Imaging  
the strategy of evaluating [ 18 F]FE@SUPPY in "humanized animal models". In conclusion, preclinical evaluation points to the suitability of [ 18 F]FE@SUPPY as an A3R PET tracer in humans.
doi:10.1007/s00259-014-2976-3 pmid:25601336 pmcid:PMC4349960 fatcat:lsgbwk2djbfbrmtdhicaxdcuoa

Cortisol plasma levels in social anxiety disorder patients correlate with serotonin-1A receptor binding in limbic brain regions

Rupert Lanzenberger, Wolfgang Wadsak, Christoph Spindelegger, Markus Mitterhauser, Elena Akimova, Leonhard-Key Mien, Martin Fink, Ulrike Moser, Markus Savli, Georg S. Kranz, Andreas Hahn, Kurt Kletter (+1 others)
2010 International Journal of Neuropsychopharmacology  
Dysregulation of the hypothalamic-pituitary-adrenocortical axis with deficient glucocorticoid feedback and alterations in the serotonergic system have been identified as biological correlates of mood disorders. Close examination of the interaction between these systems may offer insights into the pathophysiology of anxiety disorders and depression to understand how stress and these disorders are related. In this study, we investigated the relationship between plasma levels of cortisol and the
more » ... minant inhibitory serotonergic receptor, serotonin-1A (5-HT 1A ). Using positron emission tomography (PET) and the radioligand [carbonyl-11 C]WAY-100635, we quantified the 5-HT 1A receptor binding. Data from 12 male patients with social phobia and 18 matched control subjects were analysed. Seven brain regions were investigated : the anterior and posterior cingulate cortices, hippocampus, amygdala, medial orbitofrontal and retrosplenial cortices, and dorsal raphe nucleus. Partial correlation analysis, controlled for age and radiochemical variables, was performed to demonstrate the association between cortisol plasma levels and 5-HT 1A receptor binding. Cortisol plasma levels were significantly lower in patients with social phobia compared to healthy controls. Moreover, we found strong negative correlations between cortisol plasma levels and 5-HT 1A binding in the amygdala (r=x0.93, p=0.0004), hippocampus (r=x0.80, p=0.009), and retrosplenial cortex (r=x0.48, p=0.04) in patients with social phobia. Within the former two regions, these associations were significantly higher in patients than in healthy controls. This PET study confirms a negative association between plasma cortisol levels and the 5-HT 1A receptor distribution consistent with studies in rodents and non-human primates. Dysregulation of the cortisol level might increase the vulnerability for mood disorders by altering limbic 5-HT 1A receptors.
doi:10.1017/s1461145710000581 pmid:20519060 fatcat:q3chaznat5birj22yvs32eie3a

The Saliva of Probands Sucking an Iota-Carrageenan Containing Lozenge Inhibits Viral Binding and Replication of the Most Predominant Common Cold Viruses and SARS-CoV-2

Martina Morokutti-Kurz, Nicole Unger-Manhart, Philipp Graf, Pia Rauch, Julia Kodnar, Maximilian Große, Christian Setz, Markus Savli, Friedrich Ehrenreich, Andreas Grassauer, Eva Prieschl-Grassauer, Ulrich Schubert
2021 International Journal of General Medicine  
Markus Savli reports personal fees from Marinomed Biotech AG.  ... 
doi:10.2147/ijgm.s325861 pmid:34526804 pmcid:PMC8437468 fatcat:j6npoaohxvambngklwmoy3k2uu

The Aeolus Data Innovation and Science Cluster

Isabell Krisch, Oliver Reitebuch, Jonas Von Bismarck, Tommaso Parrinello, Michael Rennie, Fabian Weiler, Dorit Huber, Jos De Kloe, Alain Dabas, Anne Grete Straume-Lindner, Saleh Abdalla, Stefano Aprile (+35 others)
2021 2021 IEEE International Geoscience and Remote Sensing Symposium IGARSS  
doi:10.1109/igarss47720.2021.9553634 fatcat:2ixwbrmy25ge5bjy67gk6ijawu

Challenges in the differentiation of midbrain raphe nuclei in neuroimaging research

G. S. Kranz, A. Hahn, M. Savli, R. Lanzenberger
2012 Proceedings of the National Academy of Sciences of the United States of America  
Kranz, Andreas Hahn, Markus Savli, and Rupert Lanzenberger 1 Department of Psychiatry and Psychotherapy, Medical University of Vienna, 1090 Vienna, Austria Fig. 1 . 1 (A) Delineation of DRN (green) and  ... 
doi:10.1073/pnas.1206247109 pmid:22711836 pmcid:PMC3406805 fatcat:g266mguupffopdwplm5plbxhsq

Page 572 of Journal of Clinical Oncology Vol. 26, Issue SUPPLEMENT [page]

2008 Journal of Clinical Oncology  
Savli, Hakan 20688 18018, 18022, 18024 Savulescu, Julian 6533 Savwvides, Panayiotis 6069, 6072, 13533, 15076 Savwides, Panos 6071 Sawa, Toshiyuki 19039 Sawada, Jun-ichi 14504 Sawada, Junichi 8034 Sawada  ...  8092 Schuchter, Lynn 9020, 9059 Schuchter, M. 6071 Schueller, Johannes 4586 Schuette, Kerstin 15595 Schuette, W. 7541 Schuetze, Scott M. 10501, 10531, 10537, 10580 Schiler, Julia 14519, 22050 Schuler, Markus  ... 

Research needs in allergy: an EAACI position paper, in collaboration with EFA

Nikolaos G Papadopoulos, Ioana Agache, Sevim Bavbek, Beatrice M Bilo, Fulvio Braido, Victoria Cardona, Adnan Custovic, Jan deMonchy, Pascal Demoly, Philippe Eigenmann, Jacques Gayraud, Clive Grattan (+124 others)
2012 Clinical and Translational Allergy  
In less than half a century, allergy, originally perceived as a rare disease, has become a major public health threat, today affecting the lives of more than 60 million people in Europe, and probably close to one billion worldwide, thereby heavily impacting the budgets of public health systems. More disturbingly, its prevalence and impact are on the rise, a development that has been associated with environmental and lifestyle changes accompanying the (Continued on next page) continuous process
more » ... f urbanization and globalization. Therefore, there is an urgent need to prioritize and concert research efforts in the field of allergy, in order to achieve sustainable results on prevention, diagnosis and treatment of this most prevalent chronic disease of the 21 st century. The European Academy of Allergy and Clinical Immunology (EAACI) is the leading professional organization in the field of allergy, promoting excellence in clinical care, education, training and basic and translational research, all with the ultimate goal of improving the health of allergic patients. The European Federation of Allergy and Airways Diseases Patients' Associations (EFA) is a non-profit network of allergy, asthma and Chronic Obstructive Pulmonary Disorder (COPD) patients' organizations. In support of their missions, the present EAACI Position Paper, in collaboration with EFA, highlights the most important research needs in the field of allergy to serve as key recommendations for future research funding at the national and European levels. Although allergies may involve almost every organ of the body and an array of diverse external factors act as triggers, there are several common themes that need to be prioritized in research efforts. As in many other chronic diseases, effective prevention, curative treatment and accurate, rapid diagnosis represent major unmet needs. Detailed phenotyping/endotyping stands out as widely required in order to arrange or re-categorize clinical syndromes into more coherent, uniform and treatment-responsive groups. Research efforts to unveil the basic pathophysiologic pathways and mechanisms, thus leading to the comprehension and resolution of the pathophysiologic complexity of allergies will allow for the design of novel patient-oriented diagnostic and treatment protocols. Several allergic diseases require well-controlled epidemiological description and surveillance, using disease registries, pharmacoeconomic evaluation, as well as large biobanks. Additionally, there is a need for extensive studies to bring promising new biotechnological innovations, such as biological agents, vaccines of modified allergen molecules and engineered components for allergy diagnosis, closer to clinical practice. Finally, particular attention should be paid to the difficult-to-manage, precarious and costly severe disease forms and/or exacerbations. Nonetheless, currently arising treatments, mainly in the fields of immunotherapy and biologicals, hold great promise for targeted and causal management of allergic conditions. Active involvement of all stakeholders, including Patient Organizations and policy makers are necessary to achieve the aims emphasized herein.
doi:10.1186/2045-7022-2-21 pmid:23121771 pmcid:PMC3539924 fatcat:hiw53rbabvgtdp5hmumpkhshni

Reliable set-up for in-loop 11C-carboxylations using Grignard reactions for the preparation of [carbonyl-11C]WAY-100635 and [11C]-(+)-PHNO

Christina Rami-Mark, Johanna Ungersboeck, Daniela Haeusler, Lukas Nics, Cecile Philippe, Markus Mitterhauser, Matthaeus Willeit, Rupert Lanzenberger, Georgios Karanikas, Wolfgang Wadsak
2013 Applied Radiation and Isotopes  
Peter Ergoth and Markus Zeilinger are gratefully acknowledged for their initial support.  ...  WAY-100635 which is still in use in our facility in various clinical studies dealing with the (patho-)physiological distribution of serotonin 5HT 1A receptor, e.g. basic neuroscience investigations Savli  ... 
doi:10.1016/j.apradiso.2013.07.023 pmid:23974301 pmcid:PMC3842501 fatcat:bj3yojisdne7rbi5wkknst5smq

[18F]FMeNER-D2: Reliable fully-automated synthesis for visualization of the norepinephrine transporter

Christina Rami-Mark, Ming-Rong Zhang, Markus Mitterhauser, Rupert Lanzenberger, Marcus Hacker, Wolfgang Wadsak
2013 Nuclear Medicine and Biology  
Acknowledgments We thank Markus Savli, PhD and Andreas Hahn, PhD for analyzing the PET data and providing Fig. 5 . This work was supported by a grant of the Austrian Science Fund (FWF P22981) to R.  ... 
doi:10.1016/j.nucmedbio.2013.08.007 pmid:24100201 pmcid:PMC3919152 fatcat:olukanorkrct3nqfh2zqnz35qu

BARNABA İNCİLİ VE YAZMALARININ DEĞERİ ÜZERİNE BİR ARAŞTIRMA

Ahmet Güç, Emine MEYDAN
2019 Celal Bayar Üniversitesi Sosyal Bilimler Dergisi  
Mehmet Reşat Şavlı: Barnabas İncili'nde Hz.  ...  Bazı kaynaklara göre V. yüzyılda Juhannes Markus tarafından yazıldığı düşünülen, Barnaba'nın İşleri ve Havari Barnaba'nın Methiyesi adlarıyla bilinen ve içerik olarak da Kıbrıs geleneğini yansıtan iki  ... 
doi:10.18026/cbayarsos.496950 fatcat:6b7aprt7yzc25neh7fxcjchfmy

The 5-HTTLPR Polymorphism Affects Network-Based Functional Connectivity in the Visual-Limbic System in Healthy Adults

Hengyi Cao, Anais Harneit, Henrik Walter, Susanne Erk, Urs Braun, Carolin Moessnang, Lena S Geiger, Zhenxiang Zang, Sebastian Mohnke, Andreas Heinz, Nina Romanczuk-Seiferth, Thomas Mühleisen (+7 others)
2017 Neuropsychopharmacology  
suppression scores a Regions with 5-HTT expression in postmortem human brain (Kish et al, 2005; Varnas et al, 2004 ). b Regions with 5-HTT expression in humans as implicated by positron emission tomography (Savli  ... 
doi:10.1038/npp.2017.121 pmid:28589968 fatcat:2trnn577wzggfg6yl3suokyysm

Table of Contents

2021 2021 IEEE International Geoscience and Remote Sensing Symposium IGARSS  
Germany; Sander Niemeijer, S[&]T, Netherlands; Ines Nikolaus, Physics Solutions, Germany; Gaetan Perron, ABB, Canada; Bas Pijnacker-Hordijk, S[&]T, Netherlands; Katja Reissig, IB Reissig, Germany; Matic Savli  ...  Irena Hajnsek, German Aerospace Center (DLR) / ETH Zürich, Germany; Alberto Moreira, Manfred Zink, Stefan Buckreuss, Thomas Kraus, Markus Bachmann, Thomas Busche, German Aerospace Center (DLR), Germany  ... 
doi:10.1109/igarss47720.2021.9553380 fatcat:zm7sioez6vgblpj25frkkxtfc4
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