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Visualizing Microglia with a Fluorescence Turn‐On Ugt1a7c Substrate

Angewandte Chemie 2019年第24期131卷

作者： Beomsue Kim Masahiro Fukuda Jung‐Yeol Lee Dongdong Su Srikanta Sanu Aymeric Silvin Audrey T. T. Khoo Taejoon Kwon Xiao Liu Weijie Chi Xiaogang Liu Sejong Choi Diana S. Y. Wan Sung‐Jin Park Jin‐Soo Kim Florent Ginhoux H. Shawn Je Young‐Tae Chang Singapore Bioimaging Consortium Agency for Science Technology and Research (A*STAR) Singapore 138667 Singapore Program in Neuroscience and Behavioral Disorders Duke-NUS Medical School Singapore 169857 Singapore Department of Chemistry Pohang University of Science and Technology Pohang 37673 Korea Present address: New drug discovery center DGMIF Daegu 41061 Korea Singapore Immunology Network A*STAR Singapore 138648 Singapore Department of Biomedical Engineering Ulsan National Institute of Science and Technology Ulsan 44919 Korea Center for Self-assembly and Complexity Institute for Basic Science (IBS) Pohang 37673 Korea Singapore University of Technology and Design Singapore 487372 Singapore Department of Chemistry Seoul National University Seoul 08826 Korea Center for Genome Engineering IBS Daejeon 34047 Korea

Microglia, the brain‐resident macrophage, are involved in brain development and contribute to the progression of neural disorders. Despite the importance of microglia, imaging of live microglia at a cellular resoluti... 详细信息

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The eleven-item Alcohol, Smoking and Substance Involvement Screening Test (ASSIST-11): Cross-cultural psychometric evaluation across 42 countries

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Journal of Psychiatric Research 2023年第1期165卷 16-27页

作者： Lee, Chih-Ting Lin, Chung-Ying Koós, Mónika Nagy, Léna Kraus, Shane W. Demetrovics, Zsolt Potenza, Marc N. Ballester-Arnal, Rafael Batthyány, Dominik Bergeron, Sophie Billieux, Joël Burkauskas, Julius Cárdenas-López, Georgina Carvalho, Joana Castro-Calvo, Jesús Chen, Lijun Ciocca, Giacomo Corazza, Ornella Csako, Rita I. Fernandez, David P. Fernandez, Elaine F. Fujiwara, Hironobu Fuss, Johannes Gabrhelík, Roman Gewirtz-Meydan, Ateret Gjoneska, Biljana Gola, Mateusz Grubbs, Joshua B. Hashim, Hashim T. Islam, Md. Saiful Ismail, Mustafa Jiménez-Martínez, Martha Jurin, Tanja Kalina, Ondrej Klein, Verena Költő, András Lee, Sang-Kyu Lewczuk, Karol Lochner, Christine López-Alvarado, Silvia Lukavská, Kateřina Mayta-Tristán, Percy Milea, Ionut Miller, Dan J. Orosová, Oľga Orosz, Gábor Ponce, Fernando P. Quintana, Gonzalo R. Garzola, Gabriel C.Quintero Ramos-Diaz, Jano Rigaud, Kévin Rousseau, Ann Scanavino, Marco De Tubino Schulmeyer, Marion K. Sharan, Pratap Shibata, Mami Shoib, Sheikh Sigre-Leirós, Vera Sniewski, Luke Spasovski, Ognen Steibliene, Vesta Stein, Dan J. Strizek, Julian Ünsal, Berk C. Vaillancourt-Morel, Marie-Pier Van Hout, Marie Claire Bőthe, Beáta Department of Family Medicine National Cheng Kung University Hospital College of Medicine National Cheng Kung University Tainan Taiwan Institute of Allied Health Sciences College of Medicine National Cheng Kung University Tainan Taiwan Biostatistics Consulting Center National Cheng Kung University Hospital College of Medicine National Cheng Kung University Tainan Taiwan Doctoral School of Psychology ELTE Eötvös Loránd University Budapest Hungary Institute of Psychology ELTE Eötvös Loránd University Budapest Hungary Department of Psychology University of Nevada Las Vegas Las Vegas NV United States Centre of Excellence in Responsible Gaming University of Gibraltar Gibraltar Gibraltar Yale University School of Medicine New Haven CT United States Connecticut Council on Problem Gambling Wethersfield CT United States Departmento de Psicología Básica Clínica y Psicobiología University Jaume I of Castellón Spain Institute for Behavioural Addictions Sigmund Freud University Vienna Austria Département de Psychologie Université de Montréal Montréal Canada Institute of Psychology University of Lausanne Lausanne Switzerland Center for Excessive Gambling Addiction Medicine Lausanne University Hospitals (CHUV) Lausanne Switzerland Laboratory of Behavioral Medicine Neuroscience Institute Lithuanian University of Health Sciences Lithuania Virtual Teaching and Cyberpsychology Laboratory School of Psychology National Autonomous University of Mexico Mexico William James Center for Research Departamento de Educação e Psicologia Universidade de Aveiro CPUP: Center for Psychology at Porto University Aveiro Portugal Department of Personality Assessment and Psychological Treatments University of Valencia Spain Department of Psychology College of Humanity and Social Science Fuzhou University China Section of Sexual Psychopathology Department of Dynamic and Clinical Psychology and Health Studies Sapienza University of Rome Rome Italy Department of Clinical Pharmaceuti

The Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) is an instrument to screen substance-use-related health risks. However, little is known whether the ASSIST could be further shortened while remain... 详细信息

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Frontispiece: Visualizing Microglia with a Fluorescence Turn-On Ugt1a7c Substrate

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Angewandte Chemie International Edition 2019年第24期58卷

作者： Dr. Beomsue Kim Dr. Masahiro Fukuda Dr. Jung-Yeol Lee Dr. Dongdong Su Dr. Srikanta Sanu Dr. Aymeric Silvin Audrey T. T. Khoo Prof. Taejoon Kwon Xiao Liu Dr. Weijie Chi Prof. Xiaogang Liu Sejong Choi Diana S. Y. Wan Dr. Sung-Jin Park Prof. Jin-Soo Kim Prof. Florent Ginhoux Prof. H. Shawn Je Prof. Young-Tae Chang Singapore Bioimaging Consortium Agency for Science Technology and Research (A*STAR) Singapore 138667 Singapore Program in Neuroscience and Behavioral Disorders Duke-NUS Medical School Singapore 169857 Singapore Department of Chemistry Pohang University of Science and Technology Pohang 37673 Korea Present address: New drug discovery center DGMIF Daegu 41061 Korea Singapore Immunology Network A*STAR Singapore 138648 Singapore Department of Biomedical Engineering Ulsan National Institute of Science and Technology Ulsan 44919 Korea Center for Self-assembly and Complexity Institute for Basic Science (IBS) Pohang 37673 Korea Singapore University of Technology and Design Singapore 487372 Singapore Department of Chemistry Seoul National University Seoul 08826 Korea Center for Genome Engineering IBS Daejeon 34047 Korea

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Author Correction: The type II RAF inhibitor tovorafenib in relapsed/refractory pediatric low-grade glioma: the phase 2 FIREFLY-1 trial

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Nature medicine 2025年 2025 Apr 16页

作者： Lindsay B Kilburn Dong-Anh Khuong-Quang Jordan R Hansford Daniel Landi Jasper van der Lugt Sarah E S Leary Pablo Hernáiz Driever Simon Bailey Sébastien Perreault Geoffrey McCowage Angela J Waanders David S Ziegler Olaf Witt Patricia A Baxter Hyoung Jin Kang Timothy E Hassall Jung Woo Han Darren Hargrave Andrea T Franson Michal Yalon Oren Helen Toledano Valérie Larouche Cassie Kline Mohamed S Abdelbaki Nada Jabado Nicholas G Gottardo Nicolas U Gerber Nicholas S Whipple Devorah Segal Susan N Chi Liat Oren Enrica E K Tan Sabine Mueller Izzy Cornelio Lisa McLeod Xin Zhao Ashley Walter Daniel Da Costa Peter Manley Samuel C Blackman Roger J Packer Karsten Nysom Children's National Hospital Washington DC USA. lkilburn@***. Children's Cancer Centre Royal Children's Hospital Melbourne Melbourne Victoria Australia. Michael Rice Centre for Hematology and Oncology Women's and Children's Hospital Adelaide South Australia Australia. South Australia Health and Medical Research Institute Adelaide Australia South Australian Immunogenomics Cancer Institute University of Adelaide Adelaide South Australia Australia. Duke University Durham NC USA. Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands. Cancer and Blood Disorders Center Seattle Children's Seattle WA USA. Charité Universitätsmedizin Berlin corporate member of Freie Universität Berlin and Humboldt-Universität Berlin German HIT-LOGGIC-Registry for LGG in Children and Adolescents Berlin Germany. Great North Children's Hospital and Newcastle University Centre for Cancer Newcastle-upon-Tyne UK. CHU Sainte-Justine Université de Montréal Montréal Quebec Canada. Sydney Children's Hospitals Network Westmead New South Wales Australia. Ann & Robert H. Lurie Children's Hospital Chicago IL USA. Kids Cancer Centre Sydney Children's Hospital Randwick New South Wales Australia. Children's Cancer Institute Lowy Cancer Research Centre University of New South Wales Sydney New South Wales Australia. School of Clinical Medicine University of New South Wales Sydney New South Wales Australia. Hopp Children's Cancer Center Heidelberg (KiTZ) Heidelberg Germany. Clinical Cooperation Unit Pediatric Oncology German Cancer Research Center (DKFZ) Heidelberg Germany. Department of Pediatric Oncology Hematology Immunology and Pulmonology Heidelberg University Hospital Heidelberg Germany. German Cancer Consortium (DKTK) Heidelberg Germany. National Center for Tumor Diseases (NCT) Heidelberg Germany. Texas Children's Cancer Center Texas Children's Hospital Baylor College of Medicine Houston TX USA. Department of Pediatrics Seoul National University College of Medi

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Global cross-cultural validation of a brief measure for identifying potential suicide risk in 42 countries

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Public Health 2024年 229卷 13-23页

作者： Gewirtz-Meydan, A. Koós, M. Nagy, L. Kraus, S.W. Demetrovics, Z. Potenza, M.N. Ballester-Arnal, R. Batthyány, D. Bergeron, S. Billieux, J. Burkauskas, J. Cárdenas-López, G. Carvalho, J. Castro-Calvo, J. Chen, L. Ciocca, G. Corazza, O. Csako, R. Fernandez, D.P. Fujiwara, H. Fernandez, E.F. Fuss, J. Gabrhelík, R. Gjoneska, B. Gola, M. Grubbs, J.B. Hashim, H.T. Islam, M.S. Ismail, M. Jiménez-Martínez, M.C. Jurin, T. Kalina, O. Klein, V. Költő, A. Lee, S.-K. Lewczuk, K. Lin, C.-Y. Lochner, C. López-Alvarado, S. Lukavská, K. Mayta-Tristán, P. Miller, D.J. Orosová, O. Orosz, G. Ponce, F.P. Quintana, G.R. Quintero Garzola, G.C. Ramos-Diaz, J. Rigaud, K. Rousseau, A. De Tubino Scanavino, M. Schulmeyer, M.K. Sharan, P. Shibata, M. Shoib, S. Sigre-Leirós, V. Sniewski, L. Spasovski, O. Steibliene, V. Stein, D.J. Strong, C. Ünsal, B.C. Vaillancourt-Morel, M.-P. Van Hout, M.C. Bőthe, B. School of Social Work Faculty of Social Welfare and Health Sciences University of Haifa Israel Institute of Psychology ELTE Eötvös Loránd University Budapest Hungary Institute of Forensic Psychiatry and Sex Research University of Duisburg-Essen Essen Germany Doctoral School of Psychology ELTE Eötvös Loránd University Budapest Hungary Department of Psychology University of Nevada Las Vegas Las Vegas NV United States Centre of Excellence in Responsible Gaming University of Gibraltar Gibraltar Gibraltar Yale University School of Medicine New Haven CT United States Connecticut Council on Problem Gambling Wethersfield CT United States Departmento de Psicología Básica Clínica y Psicobiología University Jaume I of Castellón Spain Institute for Behavioural Addictions Sigmund Freud University Vienna Austria Département de Psychologie Université de Montréal Montréal Canada Institute of Psychology University of Lausanne Lausanne Switzerland Center for Excessive Gambling Addiction Medicine Lausanne University Hospitals (CHUV) Lausanne Switzerland Laboratory of Behavioral Medicine Neuroscience Institute Lithuanian University of Health Sciences Lithuania Virtual Teaching and Cyberpsychology Laboratory School of Psychology National Autonomous University of Mexico Mexico William James Center for Research Departamento de Educação e Psicologia Universidade de Aveiro Aveiro Portugal Department of Personality Assessment and Psychological Treatments University of Valencia Spain Department of Psychology College of Humanity and Social Science Fuzhou University China Section of Sexual Psychopathology Department of Dynamic and Clinical Psychology and Health Studies Sapienza University of Rome Rome Italy Department of Clinical Pharmaceutical and Biological Sciences University of Hertfordshire United Kingdom Department of Psychology and Cognitive Science University of Trento Italy Department of Psychology and Neuroscience Auckland University of Technology Auckland New Z

Objectives: This study aimed to examine the psychometric properties of the P4 suicide screener in a multinational sample. The primary goal was to evaluate the reliability and validity of the scale and investigate its ... 详细信息

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Heterogeneity analysis provides evidence for a genetically homogeneous subtype of bipolar-disorder

arXiv

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arXiv 2024年

作者： McGrouther, Caroline C. Rangan, Aaditya V. Florio, Arianna Di Elman, Jeremy A. Schork, Nicholas J. Kelsoe, John Stahl, Eli A. Breen, Gerome Forstner, Andreas J. McQuillin, Andrew Ripke, Stephan Trubetskoy, Vassily Mattheisen, Manuel Wang, Yunpeng Coleman, Jonathan R.I. Gaspar, Héléna A. de Leeuw, Christiaan A. Steinberg, Stacy Whitehead Pavlides, Jennifer M. Trzaskowski, Maciej Byrne, Enda M. Pers, Tune H. Holmans, Peter A. Richards, Alexander L. Abbott, Liam Agerbo, Esben Akil, Huda Albani, Diego Alliey-Rodriguez, Ney Als, Thomas D. Anjorin, Adebayo Antilla, Verneri Awasthi, Swapnil Badner, Judith A. Bækvad-Hansen, Marie Barchas, Jack D. Bass, Nicholas Bauer, Michael Belliveau, Richard Bergen, Sarah E. Pedersen, Carsten Bøcker Bøen, Erlend Boks, Marco P. Boocock, James Budde, Monika Bunney, William Burmeister, Margit Bybjerg-Grauholm, Jonas Byerley, William Casas, Miquel Cerrato, Felecia Cervantes, Pablo Chambert, Kimberly Charney, Alexander W. Chen, Danfeng Churchhouse, Claire Clarke, Toni-Kim Coryell, William Craig, David W. Cruceanu, Cristiana Curtis, David Czerski, Piotr M. Dale, Anders M. de Jong, Simone Degenhardt, Franziska Del-Favero, Jurgen DePaulo, J. Raymond Djurovic, Srdjan Dobbyn, Amanda L. Dumont, Ashley Elvsåshagen, Torbjørn Escott-Price, Valentina Fan, Chun Chieh Fischer, Sascha B. Flickinger, Matthew Foroud, Tatiana M. Forty, Liz Frank, Josef Fraser, Christine Freimer, Nelson B. Frisén, Louise Gade, Katrin Gage, Diane Garnham, Julie Giambartolomei, Claudia Pedersen, Marianne Giørtz Goldstein, Jaqueline Gordon, Scott D. Gordon-Smith, Katherine Green, Elaine K. Green, Melissa J. Greenwood, Tiffany A. Grove, Jakob Guan, Weihua Guzman-Parra, José Hamshere, Marian L. Hautzinger, Martin Heilbronner, Urs Herms, Stefan Hipolito, Maria Hoffmann, Per Holland, Dominic Huckins, Laura Jamain, Stéphane Johnson, Jessica S. Kandaswamy, Radhika Karlsson, Robert Kennedy, James L. Kittel-Schneider, Sarah Knowles, James A. Kogevinas, Manolis Koller, Anna C. Kupka, Ralph Lavebratt, Catharina Lawrence, Jacob Lawson, Courant Institute of Mathematical Sciences New York University New YorkNY United States School of Medicine Division of Psychological Medicine and Clinical Neurosciences Cardiff University Cardiff United Kingdom Department of Psychiatry University of California San Diego San DiegoCA United States The Translational Genomics Research Institute Quantitative Medicine and Systems Biology PhoenixAZ United States Department of Psychiatry University of California San Diego La Jolla CA United States Department of Genetics and Genomic Sciences Icahn School of Medicine at Mount Sinai New YorkNY United States Department of Psychiatry Icahn School of Medicine at Mount Sinai New YorkNY United States Medical and Population Genetics Broad Institute CambridgeMA United States MRC Social Genetic and Developmental Psychiatry Centre King’s College London London United Kingdom NIHR BRC for Mental Health King’s College London London United Kingdom University of Basel Basel Switzerland Institute of Human Genetics University of Bonn School of Medicine University Hospital Bonn DE Bonn Germany Centre for Human Genetics University of Marburg DE Marburg Germany Institute of Medical Genetics and Pathology University Hospital Basel Basel Switzerland Division of Psychiatry University College London London United Kingdom Stanley Center for Psychiatric Research Broad Institute CambridgeMA United States Department of Psychiatry and Psychotherapy Charité - Universitätsmedizin Berlin Germany Analytic and Translational Genetics Unit Massachusetts General Hospital BostonMA United States iSEQ Center for Integrative Sequencing Aarhus University DK Aarhus Denmark Department of Biomedicine - Human Genetics Aarhus University DK Aarhus Denmark Department of Clinical Neuroscience Centre for Psychiatry Research Karolinska Institutet Stockholm Sweden Department of Psychiatry Psychosomatics and Psychotherapy Center of Mental Health University Hospital Würzburg DE Würzburg Ge

Background: Bipolar Disorder (BD) is a complex disease. It is heterogeneous, both at the phenotypic and genetic level, although the extent and impact of this heterogeneity is not fully understood. One way to assess th... 详细信息

Background: Bipolar Disorder (BD) is a complex disease. It is heterogeneous, both at the phenotypic and genetic level, although the extent and impact of this heterogeneity is not fully understood. One way to assess this heterogeneity is to look for patterns in the subphenotype data. Because of the variability in how phenotypic data was collected by the various BD studies over the years, homogenizing this subphenotypic data is a challenging task, and so is replication. An alternative methodology, taken here, is to set aside the intricacies of subphenotype and allow the genetic data itself to determine which subjects define a homogeneous genetic subgroup (termed ‘bicluster’ below). Results: In this paper, we leverage recent advances in heterogeneity analysis to look for genetically-driven subgroups (i.e., biclusters) within the broad phenotype of Bipolar Disorder. We first apply this covariate-corrected biclustering algorithm to a cohort of 2524 BD cases and 4106 controls from the Bipolar Disease Research Network (BDRN) within the Psychiatric Genomics Consortium (PGC). We find evidence of genetic heterogeneity delineating a statistically significant bicluster comprising a subset of BD cases which exhibits a disease-specific pattern of differential-expression across a subset of SNPs. This disease-specific genetic pattern (i.e., ‘genetic subgroup’) replicates across the remaining data-sets collected by the PGC containing 5781/8289, 3581/7591, and 6825/9752 cases/controls, respectively. This genetic subgroup (discovered without using any BD subtype information) was more prevalent in Bipolar type-I than in Bipolar type-II. Conclusions: Our methodology has successfully identified a replicable homogeneous genetic subgroup of bipolar disorder. This subgroup may represent a collection of correlated genetic risk-factors for BDI. By investigating the subgroup’s bicluster-informed polygenic-risk-scoring (PRS), we find that the disease-specific pattern highlighted by the bicluste

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Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder

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Molecular psychiatry 2023年第12期28卷 5251-5261页

作者： Azmeraw T Amare Anbupalam Thalamuthu Klaus Oliver Schubert Janice M Fullerton Muktar Ahmed Simon Hartmann Sergi Papiol Urs Heilbronner Franziska Degenhardt Fasil Tekola-Ayele Liping Hou Yi-Hsiang Hsu Tatyana Shekhtman Mazda Adli Nirmala Akula Kazufumi Akiyama Raffaella Ardau Bárbara Arias Jean-Michel Aubry Roland Hasler Hélène Richard-Lepouriel Nader Perroud Lena Backlund Abesh Kumar Bhattacharjee Frank Bellivier Antonio Benabarre Susanne Bengesser Joanna M Biernacka Armin Birner Cynthia Marie-Claire Pablo Cervantes Hsi-Chung Chen Caterina Chillotti Sven Cichon Cristiana Cruceanu Piotr M Czerski Nina Dalkner Maria Del Zompo J Raymond DePaulo Bruno Étain Stephane Jamain Peter Falkai Andreas J Forstner Louise Frisen Mark A Frye Sébastien Gard Julie S Garnham Fernando S Goes Maria Grigoroiu-Serbanescu Andreas J Fallgatter Sophia Stegmaier Thomas Ethofer Silvia Biere Kristiyana Petrova Ceylan Schuster Kristina Adorjan Monika Budde Maria Heilbronner Janos L Kalman Mojtaba Oraki Kohshour Daniela Reich-Erkelenz Sabrina K Schaupp Eva C Schulte Fanny Senner Thomas Vogl Ion-George Anghelescu Volker Arolt Udo Dannlowski Detlef Dietrich Christian Figge Markus Jäger Fabian U Lang Georg Juckel Carsten Konrad Jens Reimer Max Schmauß Andrea Schmitt Carsten Spitzer Martin von Hagen Jens Wiltfang Jörg Zimmermann Till F M Andlauer Andre Fischer Felix Bermpohl Philipp Ritter Silke Matura Anna Gryaznova Irina Falkenberg Cüneyt Yildiz Tilo Kircher Julia Schmidt Marius Koch Kathrin Gade Sarah Trost Ida S Haussleiter Martin Lambert Anja C Rohenkohl Vivien Kraft Paul Grof Ryota Hashimoto Joanna Hauser Stefan Herms Per Hoffmann Esther Jiménez Jean-Pierre Kahn Layla Kassem Po-Hsiu Kuo Tadafumi Kato John Kelsoe Sarah Kittel-Schneider Ewa Ferensztajn-Rochowiak Barbara König Ichiro Kusumi Gonzalo Laje Mikael Landén Catharina Lavebratt Marion Leboyer Susan G Leckband Alfonso Tortorella Mirko Manchia Lina Martinsson Michael J McCarthy Susan McElroy Francesc Colom Vincent Millischer Marina Mitjans Francis M Mondimore Palmiero Monteleone Caroline Discipline of Psychiatry School of Medicine University of Adelaide Adelaide SA Australia. azmeraw.amare@adelaide.edu.au. Centre for Healthy Brain Ageing (CHeBA) Discipline of Psychiatry and Mental Health UNSW Medicine & Health University of New South Wales Sydney Australia. Discipline of Psychiatry School of Medicine University of Adelaide Adelaide SA Australia. Northern Adelaide Local Health Network Mental Health Services Adelaide SA Australia. Neuroscience Research Australia Sydney NSW Australia. School of Medical Sciences University of New South Wales Sydney NSW Australia. Institute of Psychiatric Phenomics and Genomics (IPPG) University Hospital LMU Munich Munich Germany. Department of Psychiatry and Psychotherapy University Hospital Ludwig-Maximilian-University Munich Munich Germany. Institute of Human Genetics University of Bonn School of Medicine & University Hospital Bonn Bonn Germany. Department of Child and Adolescent Psychiatry Psychosomatics and Psychotherapy LVR Klinikum Essen University of Duisburg-Essen Rheinische Kliniken Essen Germany. Epidemiology Branch Division of Population Health Research Division of Intramural Research Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health Bethesda MD USA. Intramural Research Program National Institute of Mental Health National Institutes of Health US Department of Health & Human Services Bethesda MD USA. HSL Institute for Aging Research Harvard Medical School Boston MA USA. Program for Quantitative Genomics Harvard School of Public Health Boston MA USA. Department of Psychiatry University of California San Diego San Diego CA USA. Department of Psychiatry and Psychotherapy Charité - Universitätsmedizin Berlin Campus Charité Mitte Berlin Germany. Department of Biological Psychiatry and Neuroscience Dokkyo Medical University School of Medicine Mibu Tochigi Japan. Unit of Clinical Pharmacology Hospital University Agency of Caglia

Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental health disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistentl...

Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental health disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li was developed in the International Consortium of Lithium Genetics cohort (ConLiGen: N = 2367) and replicated in the combined PsyCourse (N = 89) and BipoLife (N = 102) studies. The associations of Li and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P < 0.05. Li was positively associated with lithium treatment response in the ConLiGen cohort, in both the categorical (P = 9.8 × 10, R = 1.9%) and continuous (P = 6.4 × 10, R = 2.6%) outcomes. Compared to bipolar patients in the 1 decile of the risk distribution, individuals in the 10 decile had 3.47-fold (95%CI: 2.22-5.47) higher odds of responding favorably to lithium. The results were replicated in the independent cohorts for the categorical treatment outcome (P = 3.9 × 10, R = 0.9%), but not for the continuous outcome (P = 0.13). Gene-based analyses revealed 36 candidate genes that are enriched in biological pathways controlled by glutamate and acetylcholine. Li may be useful in the development of pharmacog

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Midlife proteome-wide analysis identifies plasma biomarkers for 25-year dementia risk linked to diverse pathophysiology

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Alzheimer's & Dementia 2022年第S6期18卷

作者： Keenan A Walker Jingsha Chen Liu Shi Yunju Yang Myriam Fornage Linda Zhou Pascal Schlosser Aditya Surapaneni Morgan E Grams Michael R Duggan Zhongsheng Peng Gabriela Gomez Adrienne Tin Ron C Hoogeveen Kevin J Sullivan Peter Ganz Joni V Lindbohm Mika Kivimaki Alejo J Nevado-Holgado Noel Buckley Rebecca F Gottesman Thomas H Mosley Eric Boerwinkle Christie M Ballantyne Josef Coresh Laboratory of Behavioral Neuroscience National Institute on Aging Intramural Research Program Baltimore MD USA Johns Hopkins Bloomberg School of Public Health Baltimore MD USA Department of Psychiatry University of Oxford Oxford United Kingdom The University of Texas Health Science Center at Houston Houston TX USA Department of Epidemiology Johns Hopkins Bloomberg School of Public Health Baltimore MD USA Division of Nephrology Department of Medicine Johns Hopkins University School of MedicineDivision of Nephrology Department of Medicine Johns Hopkins University School of MedicineDivision of Nephrology Department of Medicine Johns Hopkins University Baltimore MD USA Department of Neurology Johns Hopkins University School of Medicine Baltimore MD USA University of Mississippi Medical Center Jackson MS USA Baylor College of Medicine Houston TX USA UCSF Medical Center San Francisco CA USA Department of Epidemiology and Public Health University College London London United Kingdom University College London London United Kingdom National Institute of Neurological Disorders and Stroke Intramural Research Program Bethesda MD USA MIND Center University of Mississippi Medical Center Jackson MS USA Johns Hopkins University Baltimore MD USA

Background A diverse set of biological processes have been implicated in the pathophysiology of Alzheimer’s disease (AD). However, there is limited understanding of the biological pathways mechanistically relevant in...

Background A diverse set of biological processes have been implicated in the pathophysiology of Alzheimer’s disease (AD). However, there is limited understanding of the biological pathways mechanistically relevant in the earliest phase of disease and a lack of protein biomarkers available to capture the biological systems involved. Method To discover early biomarkers and further understand on a molecular level the systemic factors that may promote neurodegeneration, we used a large-scale proteomic platform to relate 4,877 plasma proteins measured in middle-aged adults to dementia risk over a 25-year period ( n =10,981; 1,874 incident dementia cases) in the Atherosclerosis Risk in Communities (ARIC) study ( Figure 1 ). Associated proteins were related to 20-year cognitive decline in the Whitehall II study, and to AD risk and CSF biomarkers in the European Medical Information Framework-AD (EMIF-AD) study. Result Proteome-wide associations in ARIC discovered 32 dementia-associated plasma proteins involved in proteostasis, immunity, synaptic function, and extracellular matrix organization ( Figure 2 ). We replicated the relationship between 15 candidate proteins and neurocognitive outcomes in Whitehall or EMIF-AD, and demonstrated that dementia-associated plasma proteins are associated with cerebrospinal fluid markers of Aß42, p-tau181, neurodegeneration, and neuroinflammation ( Figure 3 ). We found many of the protein biomarkers were abnormally expressed in AD brain tissue, though some of the strongest midlife dementia-associated proteins (e.g., GDF-15) were not detected in brain. Using network analyses, we found an evolving plasma protein signature for dementia risk suggesting a dysregulation of specific immune pathways and disrupted proteostasis/autophagy and extracellular matrix organization in midlife ∼20 years before dementia onset, and abnormal coagulation/complement signaling ∼10 years before dementia onset ( Figure 4 ). We used two-sample Mendelian randomizatio

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Midlife plasma proteome-wide analysis identifies peripheral immune networks associated with 25-year dementia risk

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Alzheimer's & Dementia 2022年第S6期18卷

作者： Keenan A Walker Jingsha Chen Liu Shi Yunju Yang Myriam Fornage Linda Zhou Pascal Schlosser Aditya Surapaneni Morgan E Grams Michael R Duggan Zhongsheng Peng Gabriela Gomez Adrienne Tin Ron C Hoogeveen Kevin J Sullivan Peter Ganz Joni V Lindbohm Mika Kivimaki Alejo J Nevado-Holgado Noel Buckley Rebecca F Gottesman Thomas H Mosley Eric Boerwinkle Christie M Ballantyne Josef Coresh Laboratory of Behavioral Neuroscience National Institute on Aging Intramural Research Program Baltimore MD USA Johns Hopkins Bloomberg School of Public Health Baltimore MD USA Department of Psychiatry University of Oxford Oxford United Kingdom The University of Texas Health Science Center at Houston Houston TX USA Department of Epidemiology Johns Hopkins Bloomberg School of Public Health Baltimore MD USA Division of Nephrology Department of Medicine Johns Hopkins University School of MedicineDivision of Nephrology Department of Medicine Johns Hopkins University School of MedicineDivision of Nephrology Department of Medicine Johns Hopkins University Baltimore MD USA Department of Neurology Johns Hopkins University School of Medicine Baltimore MD USA University of Mississippi Medical Center Jackson MS USA Baylor College of Medicine Houston TX USA UCSF Medical Center San Francisco CA USA Department of Epidemiology and Public Health University College London London United Kingdom University College London London United Kingdom National Institute of Neurological Disorders and Stroke Intramural Research Program Bethesda MD USA MIND Center University of Mississippi Medical Center Jackson MS USA Johns Hopkins University Baltimore MD USA

Background A diverse set of biological processes have been implicated in the pathophysiology of Alzheimer’s disease (AD) and related dementias. However, there is limited understanding of the biological pathways mecha...

Background A diverse set of biological processes have been implicated in the pathophysiology of Alzheimer’s disease (AD) and related dementias. However, there is limited understanding of the biological pathways mechanistically relevant in the earliest phase of disease and a lack of protein biomarkers available to capture the biological systems involved. Method To discover early biomarkers and further understand on a molecular level the systemic factors that may promote neurodegeneration, we used a large-scale proteomic platform to relate 4,877 plasma proteins measured in middle-aged adults to dementia risk over a 25-year period ( n =10,981; 1,874 incident dementia cases) in the Atherosclerosis Risk in Communities (ARIC) study ( Figure 1 ). Dementia-associated proteins were related to 20-year cognitive decline in the Whitehall II study, and to AD risk and CSF biomarkers European Medical Information Framework-AD study. Result Proteome-wide association study in ARIC discovered 32 midlife dementia-associated plasma proteins, the majority of which were involved in either immune function, proteostasis/autophagy, or extracellular matrix organization ( Figure 2 ). We replicated the relationship between candidate proteins and neurocognitive outcomes in multiple independent cohorts and demonstrated a relationship between dementia-associated plasma proteins and cerebrospinal fluid markers of Aß42, p-tau181, neurodegeneration, and neuroinflammation ( Figure 3 ). Using network analysis, we identified 19 co-expressed protein modules, 4 of which were strongly associated with either short-term and long-term dementia risk ( Figure 4 ). Pathway analyses conducted for the dementia-associated protein modules suggested dysregulation of specific immune pathways (e.g., JAK-STAT signaling, Toll-like receptor activation) and disrupted proteostasis/autophagy and extracellular matrix organization during midlife ∼20 years before dementia onset, and abnormal coagulation/complement signaling ∼10

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Corrigendum to "Associations of circulating cell-free DNA, C-reactive protein, and cardiometabolic risk among low-active smokers with elevated depressive symptoms" [Brain Behav. Immun. - Health 25 (2022) 100519]

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Brain, behavior, & immunity - health 2023年 27卷 100583页

作者： Teresa E Daniels Emily K Zitkovsky Zachary J Kunicki Destiny J Price Abigail L Peterson Phyllis A Dennery Hung-Teh Kao Lawrence H Price Audrey R Tyrka Ana M Abrantes Mood Disorders Research Program and Laboratory for Clinical and Translational Neuroscience Butler Hospital 345 Blackstone Boulevard Providence RI 02906 USA. Department of Psychiatry and Human Behavior Warren Alpert Medical School of Brown University 345 Blackstone Boulevard Providence RI 02906 USA. Initiative on Stress Trauma and Resilience (STAR) Department of Psychiatry and Human Behavior Warren Alpert Medical School Brown University Providence RI USA. Warren Alpert Medical School of Brown University Providence RI USA. Department of Psychiatry New York State Psychiatric Institute and Columbia University Irving Medical Center 1051 Riverside Dr New York NY 10032 USA. Department of Molecular Biology Cell Biology and Biochemistry Brown University Providence RI USA. Department of Pediatrics Warren Alpert Medical School of Brown University 593 Eddy St Providence RI 02903 USA. Behavioral Medicine and Addictions Research Department Butler Hospital 345 Blackstone Boulevard Providence RI 02906 USA.

[This corrects the article DOI: 10.1016/***.2022.100519.].

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