Article
Psychiatry
Beatriz Cantieri Almeida, Emanuella Dutra Goncalves, Maria Helena de Sousa, Maria Jose Martins Duarte Osis, Marilia Jesus Batista de Brito Mota, Aline Cristiane Planello
Summary: Brazilian psychiatrists have some familiarity with PGx but express concerns regarding education, test requests and interpretation, cost-effectiveness, and ethical issues. Age, practice setting, and gender are associated with varying perceptions and competency in PGx. Education and training resources are needed to improve the clinical implementation of PGx in psychiatry.
PSYCHIATRY RESEARCH
(2021)
Article
Health Care Sciences & Services
Savannah Collett, Amanda Massmann, Natasha J. J. Petry, Joel Van Heukelom, April Schultz, Tadd Hellwig, Jordan F. F. Baye
Summary: This study aimed to evaluate adverse effects such as bradycardia, hypotension, and syncope in patients who are expected to have absent CYP2D6 enzyme activity due to drug-drug or drug-gene interactions. The study found that CYP2D6 poor metabolizers taking metoprolol had an increased risk of bradycardia. This study further supports the role of genetic testing in precision medicine.
JOURNAL OF PERSONALIZED MEDICINE
(2023)
Article
Chemistry, Medicinal
Frederique Rodieux, Flavia Storelli, Francois Curtin, Sergio Manzano, Alain Gervaix, Klara M. Posfay-Barbe, Jules Desmeules, Youssef Daali, Caroline F. Samer
Summary: The study aimed to evaluate pupillometry as a phenotyping method for assessing CYP2D6 activity in children treated with tramadol. The results showed that tramadol affected pupillary parameters in children, but a correlation between pupillometry measurements and CYP2D6 activity could not be identified.
Article
Oncology
Natalie Reizine, Keith Danahey, Emily Schierer, Ping Liu, Merisa Middlestadt, Jenna Ludwig, Tien M. Truong, Xander M. R. van Wijk, Kiang-Teck J. Yeo, Monica Malec, Mark J. Ratain, Peter H. O'Donnell
Summary: This study analyzed the opioid exposures of 61,572 adult oncology patients and found that patients with abnormal CYP2D6 metabolizer status may experience inadequate pain control with common first-line opioids, resulting in increased pain-related hospitalizations. Preemptive genotyping could serve as a prospective evaluation tool to improve oncology pain management strategies.
Article
Oncology
Elze R. Timmers, Torsten Plosch, Marenka Smit, Ingrid H. Hof, Rikst Nynke Verkaik-Schakel, Marina A. J. Tijssen, Tom J. de Koning, Klary E. Niezen-Koning
Summary: This study found differences in the percentage of methylation of the gene encoding for the serotonin reuptake transporter between dystonia patients and healthy controls. Methylation levels were also associated with the severity of anxiety and presence of a depressive disorder. These findings suggest that there may be alterations in the serotonin metabolism in dystonia patients, which could contribute to their non-motor symptoms.
CLINICAL EPIGENETICS
(2022)
Article
Psychiatry
Frances Adiukwu, Olufisayo Adesokun, Emmanuel Essien, Nadir Yalcin, Ramdas Ransing, Sachin Nagendrappa, Chonnakarn Jatchavala, Ayotunde Bolatito Olakunke, Faisal A. Nawaz, Nagina Khan
Summary: Pharmacogenetic studies the impact of inherited traits on medication, while pharmacogenomics examines the entire genome's role in medication response. Despite their inconsistent distinction and interchangeable use, pharmacogenomics shows potential in psychiatry but has limited clinical utility and research diversity in pharmacogenetics. This article provides an overview of pharmacogenetics in psychiatry, explores challenges, and offers recommendations to enhance its applicability and clinical utility.
ASIAN JOURNAL OF PSYCHIATRY
(2023)
Article
Genetics & Heredity
Malcolm Forbes, Mal Hopwood, Chad A. Bousman
Summary: Pharmacogenomic testing for antidepressant medication selection and dosing is gaining attention in Australia. This study evaluated the coverage of CYP2D6 and CYP2C19 variants in commercial antidepressant PGx testing panels in Victoria. The findings suggest that current PGx tests may not be suitable for all individuals due to limited coverage of CYP2D6 variants.
Article
Psychiatry
Beatriz Carvalho Henriques, Avery Buchner, Xiuying Hu, Yabing Wang, Vasyl Yavorskyy, Keanna Wallace, Rachael Dong, Kristina Martens, Michael S. Carr, Bahareh Behroozi Asl, Joshua Hague, Sudhakar Sivapalan, Wolfgang Maier, Mojca Z. Dernovsek, Neven Henigsberg, Joanna Hauser, Daniel Souery, Annamaria Cattaneo, Ole Mors, Marcella Rietschel, Gerald Pfeffer, Stacey Hume, Katherine J. Aitchison
Summary: This study aimed to cross-validate various technologies for genotyping CYP2D6 and CYP2C19, providing a wide range of assay options, automated haplotype translation, and workflow optimization to enhance feasibility for clinical implementation of these genetic profiles.
TRANSLATIONAL PSYCHIATRY
(2021)
Article
Cell Biology
Colby E. Witt, Sergio Mena, Lauren E. Honan, Lauren Batey, Victoria Salem, Yangguang Ou, Parastoo Hashemi
Summary: This study used fast-scan controlled-adsorption voltammetry (FSCAV) to measure low-periodicity fluctuations in serotonin levels in mouse hippocampi. Correlation analyses revealed that these oscillations were present in vivo but not in vitro, and were not significantly different under different conditions (sex and stress paradigm). The administration of a selective serotonin reuptake inhibitor resulted in a shift in the frequency of the oscillations, suggesting regulation by transporter proteins. Additionally, the experimental parameters of FSCAV were optimized for higher temporal resolution, leading to more pronounced shifts in oscillation frequency and decreased amplitude.
Article
Cell Biology
Huangfei Yu, Tianyin Qu, Jinlan Yang, Qing Dai
Summary: In this study, it is reported that serotonin transporter (SERT) transports serotonin into colorectal cancer cells, enhancing Yes-associated protein (YAP) expression and promoting colon cancer cell growth. The transglutaminase 2 (TG2) mediates RhoA serotonylation and activates RhoA-ROCK1/2 signaling to upregulate YAP expression. Blocking SERT with citalopram reverses serotonin-induced YAP expression and cell proliferation. In addition, SERT expression is correlated with YAP in human colorectal cancer samples and the levels of serotonin are significant in patients with colorectal cancer. Therefore, targeting the serotonin-SERT-YAP axis may be a potential therapeutic strategy for colorectal cancer.
CELL COMMUNICATION AND SIGNALING
(2023)
Review
Psychiatry
David E. Nichols
Summary: At first glance, the molecular structures of MDMA and MDA seem similar, but their activity stereochemistry differs. MDMA is distinct from classical hallucinogenic phenethylamines in structure and psychopharmacology. It promotes affiliative social behavior, has acute anxiolytic effects, and induces introspection and personal reflection. Its mechanism of action involves the transport and release of neuronal serotonin.
FRONTIERS IN PSYCHIATRY
(2022)
Review
Genetics & Heredity
Adam Jameson, Beth Fylan, Greg C. Bristow, Gurdeep S. Sagoo, Caroline Dalton, Alastair Cardno, Jaspreet Sohal, Samantha L. McLean
Summary: The use of pharmacogenetics (PGx) in psychiatry aims to personalize medication selection, but its implementation in mental health settings in the UK has been slow. Barriers to implementation include cost, workflow integration concerns, and limited knowledge about PGx, while enablers include optimism for precision medicine, reducing ADRs, and becoming a routine part of psychiatric care. Overcoming these barriers and capitalizing on the enablers are crucial for the uptake of PGx in NHS psychiatric care settings.
FRONTIERS IN GENETICS
(2021)
Article
Neurosciences
Nikita Deo, Gregory Redpath
Summary: This article examines the important role of endocytosis in the cellular basis of depression and anxiety. It provides a detailed explanation of the endocytic regulation of 5-HT receptors and SERT, and explores how SSRIs and hallucinogenic compounds modulate serotonin signaling through endocytosis.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Health Care Sciences & Services
Pritmohinder S. Gill, Amanda L. Elchynski, Patricia A. Porter-Gill, Bradley G. Goodson, Mary Ann Scott, Damon Lipinski, Amy Seay, Christina Kehn, Tonya Balmakund, G. Bradley Schaefer
Summary: This pilot study highlights the value of a multidisciplinary treatment approach in delivering precision healthcare and improving physician clinical decisions. It also demonstrates the feasibility of implementing pharmacogenetic testing in neurodevelopmental and neurobehavioral disorders.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Immunology
Johannes Hoch, Niklas Burkhard, Shanshan Zhang, Marina Rieder, Timoteo Marchini, Vincent Geest, Krystin Krauel, Timm Zahn, Nicolas Schommer, Muataz Ali Hamad, Carolina Bauer, Nadine Gauchel, Daniela Stallmann, Claus Normann, Dennis Wolf, Ruediger Eberhard Scharf, Daniel Duerschmied, Nancy Schanze
Summary: This study found that deficiency of the serotonin transporter (SERT) is associated with metabolic derangements in mice. High-fat diet feeding in SERT-deficient mice resulted in enhanced insulin resistance, liver steatosis, and adipose tissue inflammation. These findings suggest that SERT deficiency may contribute to altered inflammatory processes.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Allergy
Sascha Hein, Marie-Luise Herrlein, Ines Mhedhbi, Daniela Bender, Vanessa Haberger, Nuka Benz, Jonathan Eisert, Julia Stingl, Michael Dreher, Doris Oberle, Jessica Schulze, Christin Mache, Matthias Budt, Christoph Hildt, Thorsten Wolff, Eberhard Hildt
Summary: The study revealed differences in titer, neutralizing capacity, and affinity of antibodies between sera elicited by BNT162b2 and CVnCoV vaccines, which could potentially contribute to the observed differences in vaccine efficacy. BNT162b2-elicited sera and convalescent sera showed higher levels of spike-RBD-specific antibodies and neutralizing antibodies compared to CVnCoV-elicited sera, with a reduction in binding and neutralizing antibodies for the B.1.351 variant of concern.
Article
Pharmacology & Pharmacy
Sabrina Yamoune, Katharina Wintz, Christian Niederau, Rogerio B. Craveiro, Michael Wolf, Julia Stingl
Summary: The study found that genetic polymorphism in the CYP2C8 gene may be associated with disturbed periodontal remodeling in periodontal fibroblasts, potentially contributing to the risk of side effects of antiresorptive bone treatment.
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
(2022)
Article
Medical Informatics
Cynthia Huber, Tim Friede, Julia Stingl, Norbert Benda
Summary: A systematic classification of biomarker-drug pairs is proposed, categorizing them into five ascending categories based on the evidence of the biomarker's predictive nature in relation to a specific drug. This classification will support regulatory decision-making and drug development by indicating the usefulness of biomarker-related subgrouping.
THERAPEUTIC INNOVATION & REGULATORY SCIENCE
(2022)
Article
Gastroenterology & Hepatology
Thomas Seufferlein, Thomas J. Ettrich, Stefan Menzler, Helmut Messmann, Gerhard Kleber, Alexander Zipprich, Stefanie Frank-Gleich, Hana Alguel, Klaus Metter, Frank Odemar, Theodor Heuer, Ulrich Huegle, Ruediger Behrens, Andreas W. Berger, Catharina Scholl, Katharina L. Schneider, Lukas Perkhofer, Friederike Rohlmann, Rainer Muche, Julia C. Stingl
Summary: The study suggests that green tea extract (GTE) and its active component epigallocatechingallate (EGCG) may have potential antitumor effects in the colorectum. However, a randomized trial did not find a significant difference in adenoma rate between the GTE and placebo groups.
AMERICAN JOURNAL OF GASTROENTEROLOGY
(2022)
Review
Pharmacology & Pharmacy
Immaculate M. Langmia, Katja S. Just, Sabrina Yamoune, Julian Peter Mueller, Julia C. Stingl
Summary: The long-term use of ketamine and esketamine as antidepressants requires further research to improve safety, dosing, and identification of individuals at risk of drug-drug interactions.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2022)
Article
Respiratory System
Ingmar Bergs, Katja S. Just, Annegret Mueller, Julia C. Stingl, Michael Dreher
Summary: The study found that 41% of COPD patients in the emergency department received therapy that was underdosed according to current guidelines. Dyspnea was the most common symptom in this group and occurred more frequently in patients who received underdosed inhalation therapy.
INTERNATIONAL JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE
(2022)
Article
Genetics & Heredity
Carina M. Mathey, Carlo Maj, Annika B. Scheer, Julia Fazaal, Bettina Wedi, Dorothea Wieczorek, Philipp M. Amann, Harald Loffler, Lukas Koch, Clemens Schoffl, Heinrich Dickel, Nomun Ganjuur, Thorsten Hornung, Susann Forkel, Jens Greve, Gerda Wurpts, Par Hallberg, Anette Bygum, Christian Von Buchwald, Malgorzata Karawajczyk, Michael Steffens, Julia Stingl, Per Hoffmann, Stefanie Heilmann-Heimbach, Elisabeth Mangold, Kerstin U. Ludwig, Eva R. Rasmussen, Mia Wadelius, Bernhardt Sachs, Markus M. Nothen, Andreas J. Forstner
Summary: This study investigated the possible association between ACEi/ARB-induced angioedema and HAE genes through molecular genetic screening. The results suggest that HAE-associated mutations are, at best, a rare cause of ACEi/ARB-induced angioedema, and there was no significant association found between ACEi/ARB-induced angioedema and other variants in the investigated genes.
FRONTIERS IN GENETICS
(2022)
Article
Medicine, Research & Experimental
David Bruecken, Jenny Unterkofler, Sophie Pauge, Jonas Bienzeisler, Christian Huebel, Sebastian Zechbauer, Rolf Rossaint, Wolfgang Greiner, Birthe Aufenberg, Rainer Roehrig, Leo Cornelius Bollheimer, Joerg Christian Brokmann
Summary: This study aims to improve the healthcare gap for nursing home residents by implementing an intersectoral telemedicine approach, reducing unnecessary hospitalizations. By combining telemedicine with standard care, the goal is to provide timely medical consultation and optimize resource allocation to meet individual medical needs.
Article
Pharmacology & Pharmacy
Ingmar Bergs, Katja S. Just, Catharina Scholl, Michael Dreher, Julia C. Stingl
Summary: This study aimed to analyze the association between inhaled therapy and adverse drug reactions (ADRs) in COPD patients, with a focus on the impact of overdose. The results showed that overdose of inhaled therapies led to severe ADRs and affected emergency room presentations. These ADRs are rarely associated with inhaled therapy by healthcare professionals or patients. Due to the high volume of prescriptions for inhaled drugs, greater attention should be paid to pharmacovigilance and patient education in COPD patients.
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Article
Pediatrics
Sarah Leitzen, Diana Dubrall, Irmgard Toni, Julia Stingl, Patrick Christ, Ursula Koberle, Matthias Schmid, Antje Neubert, Bernhardt Sachs
Summary: The study compares the differences between ADRs reported in the KiDSafe project and the spontaneous ADR reports sent to EudraVigilance. The results show underreporting of ADRs in the spontaneous reports compared to the systematically collected KiDSafe reports. The two approaches yield different results in terms of reported drugs, ADRs, and medication errors.
Article
Pharmacology & Pharmacy
Julia Carolin Stingl, Jason Radermacher, Justyna Wozniak, Roberto Viviani
Summary: Pharmacogenetic variability in drug metabolism can affect patient vulnerability to side effects and therapeutic failure. This study introduces a systematic statistical methodology to estimate quantitative dose adjustments based on pharmacokinetic differences in pharmacogenetic subgroups. The methodology addresses the challenges of sparse data, incomplete information on phenotypic groups, and heterogeneity of study design. The results demonstrate the effectiveness of the modeling approach in predicting dose adjustments and considering uncertainty.
Meeting Abstract
Obstetrics & Gynecology
F. Heitz, K. Weber-Lassalle, C. Ernst, K. Moellenhoff, N. De Gregorio, J. Hauke, D. Dietrich, J. Borde, C. Jackisch, T-W Park-Simon, L. C. Hanker, E. Pohl-Rescigno, K. Prieske, S. Kommoss, F. Marme, J. C. Stingl, S. Rita, P. Harter, E. Hahnen
GEBURTSHILFE UND FRAUENHEILKUNDE
(2022)
Meeting Abstract
Respiratory System
I Bergs, S. K. Just, J. Stingl, M. Dreher
Meeting Abstract
Respiratory System
I Bergs, S. K. Just, J. Stingl, M. Dreher
Article
Virology
Marie-Luise Herrlein, Paul Schmanke, Fabian Elgner, Catarina Sabino, Sami Akhras, Daniela Bender, Mirco Glitscher, Denna Tabari, Catharina Scholl, Julia Stingl, Eberhard Hildt
Summary: In this study, the authors investigate the interaction between Zika virus (ZIKV) and the cellular protein tetherin (THN). They find that although THN expression is strongly induced during ZIKV infection, the protein level of THN is actually reduced due to enhanced lysosomal degradation. They also show that enrichment of THN inhibits ZIKV release and spread, indicating THN's capacity to restrict ZIKV. This study provides valuable insights into the virus-host interaction and the strategies employed by ZIKV to escape restriction.
JOURNAL OF VIROLOGY
(2022)