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Genome-wide analyses identify 30 loci associated with obsessive–compulsive disorder

Nature Genetics 2025年 1-13页

作者： Strom, Nora I. Gerring, Zachary F. Galimberti, Marco Yu, Dongmei Halvorsen, Matthew W. Abdellaoui, Abdel Rodriguez-Fontenla, Cristina Sealock, Julia M. Bigdeli, Tim Coleman, Jonathan R. Mahjani, Behrang Thorp, Jackson G. Bey, Katharina Burton, Christie L. Luykx, Jurjen J. Zai, Gwyneth Alemany, Silvia Andre, Christine Askland, Kathleen D. Bäckman, Julia Banaj, Nerisa Barlassina, Cristina Nissen, Judith Becker Bienvenu, O. Joseph Black, Donald Bloch, Michael H. Børte, Sigrid Bosch, Rosa Breen, Michael Brennan, Brian P. Brentani, Helena Buxbaum, Joseph D. Bybjerg-Grauholm, Jonas Byrne, Enda M. Cabana-Dominguez, Judit Camarena, Beatriz Camarena, Adrian Cappi, Carolina Carracedo, Angel Casas, Miguel Cavallini, Maria Cristina Ciullo, Valentina Cook, Edwin H. Crosby, Jesse Cullen, Bernadette A. De Schipper, Elles J. Delorme, Richard Djurovic, Srdjan Elias, Jason A. Estivill, Xavier Falkenstein, Martha J. Fundin, Bengt T. Garner, Lauryn Gironda, Christina Goes, Fernando S. Grados, Marco A. Grove, Jakob Guo, Wei Haavik, Jan Hagen, Kristen Harrington, Kelly Havdahl, Alexandra Höffler, Kira D. Hounie, Ana G. Hucks, Donald Hultman, Christina Janecka, Magdalena Jenike, Eric Karlsson, Elinor K. Kelley, Kara Klawohn, Julia Krasnow, Janice E. Krebs, Kristi Lange, Christoph Lanzagorta, Nuria Levey, Daniel Lindblad-Toh, Kerstin Macciardi, Fabio Maher, Brion Mathes, Brittany McArthur, Evonne McGregor, Nathaniel McLaughlin, Nicole C. Meier, Sandra Miguel, Euripedes C. Mulhern, Maureen Nestadt, Paul S. Nurmi, Erika L. O’Connell, Kevin S. Osiecki, Lisa Ousdal, Olga Therese Palviainen, Teemu Pedersen, Nancy L. Piras, Federica Potluri, Sriramya Rabionet, Raquel Ramirez, Alfredo Rauch, Scott Reichenberg, Abraham Riddle, Mark A. Ripke, Stephan Rosário, Maria C. Sampaio, Aline S. Schiele, Miriam A. Skogholt, Anne Heidi Sloofman, Laura G. Smit, Jan Artigas, María Soler Thomas, Laurent F. Tifft, Eric Vallada, Homero van Kirk, Nathanial Veenstra-VanderWeele, Jeremy Vulink, Nienke N. Walker, Christopher P. Wang, Ying Wendland, Jens R. Winsvold Department of Psychology Humboldt-Universität zu Berlin Berlin Germany Department of Psychiatric Phenomics and Genomics (IPPG) Ludwig-Maximilians University Munich Munich Germany Centre for Psychiatry Research Department of Clinical Neuroscience Karolinska Institutet and Stockholm Health Services Region Stockholm Stockholm Sweden Department of Biomedicine Aarhus University Aarhus Denmark University Hospital of Psychiatry and Psychotherapy University of Bern Bern Switzerland Department of Mental Health and Neuroscience Translational Neurogenomics QIMR Berghofer Medical Research Institute Brisbane QLD Australia Department of Population Health and Immunity Healthy Development and Ageing Walter and Eliza Hall Institute of Medical Research Melbourne VIC Australia Department of Psychiatry Human Genetics Yale University New Haven CT United States VA Connecticut Healthcare System West Haven CT United States Department of Center for Genomic Medicine Psychiatric and Neurodevelopmental Genetics Unit Massachusetts General Hospital Boston MA United States Stanley Center for Psychiatric Research Broad Institute of MIT and Harvard Cambridge MA United States Department of Genetics University of North Carolina at Chapel Hill Chapel Hill NC United States Department of Psychiatry Amsterdam University Medical Centers University of Amsterdam Amsterdam Netherlands Center for Research in Molecular Medicine and Chronic Diseases (CiMUS) Genomics and Bioinformatics University of Santiago de Compostela Santiago de Compostela Spain Grupo de Medicina Xenómica Genetics Instituto de Investigación Sanitaria de Santiago de Compostela (FIDIS) Santiago de Compostela Spain Vanderbilt Genetics Institute Vanderbilt University Nashville TN United States Department of Psychiatry and Behavioral Sciences SUNY Downstate Health Sciences University Brooklyn NY United States VA NY Harbor Healthcare System Brooklyn NY United States Social Genetic and Developmental Psychiatry Centre Insti

Obsessive–compulsive disorder (OCD) affects ~1% of children and adults and is partly caused by genetic factors. We conducted a genome-wide association study (GWAS) meta-analysis combining 53,660 OCD cases and 2,044,417 controls and identified 30 independent genome-wide significant loci. Gene-based approaches identified 249 potential effector genes for OCD, with 25 of these classified as the most likely causal candidates, including WDR6, DALRD3 and CTNND1 and multiple genes in the major histocompatibility complex (MHC) region. We estimated that ~11,500 genetic variants explained 90% of OCD genetic heritability. OCD genetic risk was associated with excitatory neurons in the hippocampus and the cortex, along with D₁ and D₂ type dopamine receptor-containing medium spiny neurons. OCD genetic risk was shared with 65 of 112 additional phenotypes, including all the psychiatric disorders we examined. In particular, OCD shared genetic risk with anxiety, depression, anorexia nervosa and Tourette syndrome and was negatively associated with inflammatory bowel diseases, educational attainment and body mass index. © The Author(s) 2025.

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Correction: Obesity and brain structure in schizophrenia - ENIGMA study in 3021 individuals

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Molecular psychiatry 2024年第1期29卷 56页

作者： Sean R McWhinney Katharina Brosch Vince D Calhoun Benedicto Crespo-Facorro Nicolas A Crossley Udo Dannlowski Erin Dickie Lorielle M F Dietze Gary Donohoe Stefan Du Plessis Stefan Ehrlich Robin Emsley Petra Furstova David C Glahn Alfonso Gonzalez-Valderrama Dominik Grotegerd Laurena Holleran Tilo T J Kircher Pavel Knytl Marian Kolenic Rebekka Lencer Igor Nenadić Nils Opel Julia-Katharina Pfarr Amanda L Rodrigue Kelly Rootes-Murdy Alex J Ross Kang Sim Antonín Škoch Filip Spaniel Frederike Stein Patrik Švancer Diana Tordesillas-Gutiérrez Juan Undurraga Javier Vázquez-Bourgon Aristotle Voineskos Esther Walton Thomas W Weickert Cynthia Shannon Weickert Paul M Thompson Theo G M van Erp Jessica A Turner Tomas Hajek Department of Psychiatry Dalhousie University Halifax NS Canada. Department of Psychiatry and Psychotherapy Philipps-University Marburg Marburg Germany. Tri-institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS) Georgia State Georgia Tech Emory University Atlanta GA USA. Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM) Madrid Spain. IBiS University Hospital Virgen del Rocio Sevilla Spain. Department of Psychiatry School of Medicine University of Sevilla Sevilla Spain. Department of Psychiatry School of Medicina Pontificia Universidad Católica de Chile Santiago Chile. Department of Psychosis Studies King's College London London UK. Institute for Translational Psychiatry University of Münster Münster Germany. Centre for Addiction & Mental Health Department of Psychiatry University of Toronto Toronto ON Canada. Centre for Neuroimaging & Cognitive Genomics (NICOG) Clinical Neuroimaging Laboratory NCBES Galway Neuroscience Centre College of Medicine Nursing and Health Sciences National University of Ireland Galway Galway Ireland. Department of Psychiatry Faculty of Medicine and Health Sciences Stellenbosch University Cape Town South Africa. SAMRC Genomics of Brain Disorders Unit Cape Town South Africa. Translational Developmental Neuroscience Section Division of Psychological and Social Medicine and Developmental Neurosciences Faculty of Medicine TU Dresden Dresden Germany. National Institute of Mental Health Klecany Czech Republic. Department of Psychiatry & Behavioral Sciences Boston Children's Hospital Boston MA USA. Department of Psychiatry Harvard Medical School Boston MA USA. Olin Neuropsychiatry Research Center Institute of Living Hartford CT USA. School of Medicine Universidad Finis Terrae Santiago Chile. Early Intervention in Psychosis Program Instituto Psiquiátrico 'Dr. José Horwitz B.' Santiago Chile. Charles University Third Faculty of Medicine Prague Czech Republic. Department

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Corrigendum to "Functional maturation in visual pathways predicts attention to the eyes in infant rhesus macaques: Effects of social status" [Dev. Cogn. Neurosci., 60 C (2023): 101213]

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Developmental cognitive neuroscience 2024年 67卷 101364页

作者： Aiden Ford Zsofia A Kovacs-Balint Arick Wang Eric Feczko Eric Earl Óscar Miranda-Domínguez Longchuan Li Martin Styner Damien Fair Warren Jones Jocelyne Bachevalier Mar M Sánchez Neuroscience Program Emory University Atlanta GA USA Marcus Autism Center USA. Electronic address: aiden.l.ford@emory.edu. Emory Natl. Primate Res. Ctr. Emory Univ. Atlanta GA USA. Emory Natl. Primate Res. Ctr. Emory Univ. Atlanta GA USA Dept of Psychology Emory University Atlanta GA USA. Dept. of Pediatrics University of Minnesota Minneapolis MN USA Masonic Institute of the Developing Brain University of Minnesota Minneapolis MN USA. Data Science and Sharing Team National Institute of Mental Health NIH DHHS Bethesda MD USA. Marcus Autism Center USA Children's Healthcare of Atlanta GA USA Dept. of Pediatrics Emory University Sch. of Med. Atlanta GA USA. Dept. of Psychiatry Univ. of North Carolina Chapel Hill NC USA. Masonic Institute of the Developing Brain University of Minnesota Minneapolis MN USA Institute of Child Development University of Minnesota Minneapolis MN USA Center for Magnetic Resonance Research and Department of Radiology University of Minnesota Minneapolis MN USA. Dept. Psychiatry & Behavioral Sciences Emory Univ. Sch. of Med. Atlanta GA USA.

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Corrigendum to "Adolescent Binge Ethanol Exposure Alters Specific Forebrain Cholinergic Cell Populations and Leads to Selective Functional Deficits in the Prefrontal Cortex" [neuroscience 361 (2017) 129-143]

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neuroscience 2018年 375卷 169页

作者： Gina M Fernandez Lisa M Savage Department of Psychology Behavioral Neuroscience Program Binghamton University State University of New York USA. Department of Psychology Behavioral Neuroscience Program Binghamton University State University of New York USA. Electronic address: lsavage@binghamton.edu.

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CRISIS AFAR: an international collaborative study of the impact of the COVID-19 pandemic on mental health and service access in youth with autism and neurodevelopmental conditions

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Molecular autism 2023年第1期14卷 7页

作者： Bethany Vibert Patricia Segura Louise Gallagher Stelios Georgiades Panagiota Pervanidou Audrey Thurm Lindsay Alexander Evdokia Anagnostou Yuta Aoki Catherine S Birken Somer L Bishop Jessica Boi Carmela Bravaccio Helena Brentani Paola Canevini Alessandra Carta Alice Charach Antonella Costantino Katherine T Cost Elaine A Cravo Jennifer Crosbie Chiara Davico Federica Donno Junya Fujino Alessandra Gabellone Cristiane T Geyer Tomoya Hirota Stephen Kanne Makiko Kawashima Elizabeth Kelley Hosanna Kim Young Shin Kim So Hyun Kim Daphne J Korczak Meng-Chuan Lai Lucia Margari Lucia Marzulli Gabriele Masi Luigi Mazzone Jane McGrath Suneeta Monga Paola Morosini Shinichiro Nakajima Antonio Narzisi Rob Nicolson Aki Nikolaidis Yoshihiro Noda Kerri Nowell Miriam Polizzi Joana Portolese Maria Pia Riccio Manabu Saito Ida Schwartz Anish K Simhal Martina Siracusano Stefano Sotgiu Jacob Stroud Fernando Sumiya Yoshiyuki Tachibana Nicole Takahashi Riina Takahashi Hiroki Tamon Raffaella Tancredi Benedetto Vitiello Alessandro Zuddas Bennett Leventhal Kathleen Merikangas Michael P Milham Adriana Di Martino Autism Center Child Mind Institute 101 E 56Th Street Third Floor New York NY USA. Department of Psychiatry School of Medicine Trinity College Dublin Dublin Ireland. Department of Psychiatry and Behavioural Neurosciences McMaster University Hamilton ON Canada. Unit of Developmental and Behavioral Pediatrics First Department of Pediatrics School of Medicine National & Kapodistrian University of Athens "Aghia Sophia" Children's Hospital Athens Greece. Neurodevelopmental and Behavioral Phenotyping Service National Institute of Mental Health Bethesda MD USA. Center for the Developing Brain Child Mind Institute New York NY USA. Autism Research Centre Bloorview Research Institute Holland Bloorview Kids Rehabilitation Hospital Toronto ON Canada. Department of Paediatrics University of Toronto Toronto ON Canada. Medical Institute of Developmental Disabilities Research Showa University Tokyo Japan. Department of Pediatrics School of Medicine University of Toronto Toronto ON Canada. Division of Paediatric Medicine Hospital for Sick Children Toronto ON Canada. Department of Psychiatry and Behavioral Sciences and Weill Institute for Neurosciences University of California San Francisco CA USA. Department of Biomedical Sciences Section of Neuroscience & Clinical Pharmacology University of Cagliari Cagliari Italy. UOSD di Neuropsichiatria Infantile - Dipartimento di Scienze Mediche Traslazionali Università Federico II di Napoli Naples Italy. Department of Psychiatry Hospital das Clinicas HCFMUSP Faculty of Medicine University of São Paulo (USP) São Paulo Brazil. Department of Health Sciences Università Degli Studi Di Milano Milan Italy. Epilepsy Center - Sleep Medicine Center Childhood and Adolescence Neuropsychiatry Unit ASST SS. Paolo E Carlo San Paolo Hospital Milan Italy. Department of Medical Surgical and Pharmacy Unit of Child Neuropsychiatry University Hospital of Sassari Sassari Italy. Department of Psychiatry Hospital for Sick Children Peter

BACKGROUND:Heterogeneous mental health outcomes during the COVID-19 pandemic are documented in the general population. Such heterogeneity has not been systematically assessed in youth with autism spectrum disorder (ASD) and related neurodevelopmental disorders (NDD). To identify distinct patterns of the pandemic impact and their predictors in ASD/NDD youth, we focused on pandemic-related changes in symptoms and access to services. METHODS:Using a naturalistic observational design, we assessed parent responses on the Coronavirus Health and Impact Survey Initiative (CRISIS) Adapted For Autism and Related neurodevelopmental conditions (AFAR). Cross-sectional AFAR data were aggregated across 14 European and North American sites yielding a clinically well-characterized sample of N = 1275 individuals with ASD/NDD (age = 11.0 ± 3.6 years; n females = 277). To identify subgroups with differential outcomes, we applied hierarchical clustering across eleven variables measuring changes in symptoms and access to services. Then, random forest classification assessed the importance of socio-demographics, pre-pandemic service rates, clinical severity of ASD-associated symptoms, and COVID-19 pandemic experiences/environments in predicting the outcome subgroups. RESULTS:Clustering revealed four subgroups. One subgroup-broad symptom worsening only (20%)-included youth with worsening across a range of symptoms but with service disruptions similar to the average of the aggregate sample. The other three subgroups were, relatively, clinically stable but differed in service access: primarily modified services (23%), primarily lost services (6%), and average services/symptom changes (53%). Distinct combinations of a set of pre-pandemic services, pandemic environment (e.g., COVID-19 new cases, restrictions), experiences (e.g., COVID-19 Worries), and age predicted each outcome subgroup. LIMITATIONS:Notable limitations of the study are its cross-sectional nature and focus on the first six mont

关键词： Autism spectrum disorder behavioral problems COVID-19 pandemic Mental health outcomes Neurodevelopmental conditions Prediction Public health Risk and resilience factors Sleep

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Correction: Progressive decline in hippocampal CA1 volume in individuals at ultra-high-risk for psychosis who do not remit: findings from the longitudinal youth at risk study

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Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 2019年第12期44卷 2144页

作者： New Fei Ho Daphne J Holt Mike Cheung Juan Eugenio Iglesias Alex Goh Mingyuan Wang Joseph K W Lim Joshua de Souza Joann S Poh Yuen Mei See R Alison Adcock Stephen J Wood Michael W L Chee Jimmy Lee Juan Zhou Institute of Mental Health Singapore Singapore. new_fei_ho@imh.com.sg. Neuroscience and Behavioral Disorders Program Center for Cognitive Neuroscience Duke-National University of Singapore Graduate Medical School Singapore Singapore. new_fei_ho@imh.com.sg. Department of Psychiatry Massachusetts General Hospital and Harvard Medical School Boston MA USA. Department of Psychology National University of Singapore Singapore Singapore. University College London London UK. Institute of Mental Health Singapore Singapore. Neuroscience and Behavioral Disorders Program Center for Cognitive Neuroscience Duke-National University of Singapore Graduate Medical School Singapore Singapore. Center for Cognitive Neuroscience Duke University Durham NC USA. School of Psychology University of Birmingham Birmingham UK. Neuroscience and Behavioral Disorders Program Center for Cognitive Neuroscience Duke-National University of Singapore Graduate Medical School Singapore Singapore. helen.zhou@duke-nus.edu.sg.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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Gene expression imputation across multiple brain regions provides insights into schizophrenia risk (vol 51, pg 659, 2019)

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NATURE GENETICS 2019年第6期51卷 1068-1068页

作者： Huckins, Laura M. Dobbyn, Amanda Ruderfer, Douglas M. Hoffman, Gabriel Wang, Weiqing Pardinas, Antonio F. Rajagopal, Veera M. Als, Thomas D. Nguyen, Hoang T. Girdhar, Kiran Boocock, James Roussos, Panos Fromer, Menachem Kramer, Robin Domenici, Enrico Gamazon, Eric R. Purcell, Shaun Demontis, Ditte Borglum, Anders D. Walters, James T. R. O'Donovan, Michael C. Sullivan, Patrick Owen, Michael J. Devlin, Bernie Sieberts, Solveig K. Cox, Nancy J. Im, Hae Kyung Sklar, Pamela Stahl, Eli A. Pamela Sklar Division of Psychiatric Genomics Icahn School of Medicine at Mount Sinai New York NY USA Department of Genetics and Genomics Icahn School of Medicine at Mount Sinai New York NY USA Department of Psychiatry Icahn School of Medicine at Mount Sinai New York NY USA Icahn Institute for Genomics and Multiscale Biology Icahn School of Medicine at Mount Sinai New York NY USA Vanderbilt University Medical Center Nashville TN USA MRC Centre for Neuropsychiatric Genetics and Genomics Cardiff University Cardiff UK Department of Biomedicine Aarhus University Aarhus Denmark The Lundbeck Foundation Initiative for Integrative Psychiatric Research iPSYCH Denmark Center for Integrative Sequencing Aarhus University Aarhus Denmark Department of Human Genetics David Geffen School of Medicine University of California Los Angeles Los Angeles CA USA Human Brain Collection Core National Institute of Mental Health Bethesda MD USA Laboratory of Neurogenomic Biomarkers Centre for Integrative Biology (CIBIO) University of Trento Trento Italy Clare Hall University of Cambridge Cambridge UK University of North Carolina at Chapel Hill Chapel Hill NC USA Karolinska Institutet Stockholm Sweden Department of Psychiatry University of Pittsburgh Pittsburgh PA USA Systems Biology Sage Bionetworks Seattle WA USA Section of Genetic Medicine Department of Medicine University of Chicago Chicago IL USA Integrated Technology Research Laboratories Pharmaceutical Research Division Takeda Pharmaceutical Company Limited Fujisawa Japan Neuropsychiatry Section Department of Psychiatry Perelman School of Medicine University of Pennsylvania Philadelphia PA USA Neuropsychiatric Signaling Program Department of Psychiatry Perelman School of Medicine University of Pennsylvania Philadelphia PA USA Psychiatry JJ Peters Virginia Medical Center Bronx NY USA Department of Neuroscience Icahn School of Medicine at Mount Sinai New York New York NY USA Friedman Brain Institute

Transcriptomic imputation approaches combine eQTL reference panels with large-scale genotype data in order to test associations between disease and gene expression. These genic associations could elucidate signals in complex genome-wide association study (GWAS) loci and may disentangle the role of different tissues in disease development. We used the largest eQTL reference panel for the dorso-lateral prefrontal cortex (DLPFC) to create a set of gene expression predictors and demonstrate their utility. We applied DLPFC and 12 GTEx-brain predictors to 40,299 schizophrenia cases and 65,264 matched controls for a large transcriptomic imputation study of schizophrenia. We identified 413 genic associations across 13 brain regions. Stepwise conditioning identified 67 non-MHC genes, of which 14 did not fall within previous GWAS loci. We identified 36 significantly enriched pathways, including hexosaminidase-A deficiency, and multiple porphyric disorder pathways. We investigated developmental expression patterns among the 67 non-MHC genes and identified specific groups of pre- and postnatal expression.

关键词： Gene expression Genome-wide association studies Schizophrenia Transcriptomics

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Global, regional, and national incidence of six major immune-mediated inflammatory diseases: findings from the global burden of disease study 2019

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eClinicalMedicine 2023年 64卷 102193-102193页

作者： Wu, Dongze Jin, Yingzhao Xing, Yuhan Abate, Melsew Dagne Abbasian, Mohammadreza Abbasi-Kangevari, Mohsen Abbasi-Kangevari, Zeinab Abd-Allah, Foad Abdelmasseh, Michael Abdollahifar, Mohammad-Amin Abdulah, Deldar Morad Abedi, Aidin Abedi, Vida Abidi, Hassan Aboagye, Richard Gyan Abolhassani, Hassan Abuabara, Katrina Abyadeh, Morteza Addo, Isaac Yeboah Adeniji, Kayode Nelson Adepoju, Abiola Victor Adesina, Miracle Ayomikun Adnani, Qorinah Estiningtyas Sakilah Afarideh, Mohsen Aghamiri, Shahin Agodi, Antonella Agrawal, Anurag Arriagada, Constanza Elizabeth Aguilera Ahmad, Aqeel Ahmad, Danish Ahmad, Sohail Ahmadi, Ali Ahmed, Ayman Aithala, Janardhana P. Ajadi, Abdullateef Abiodun Ajami, Marjan Akbarzadeh-Khiavi, Mostafa Alahdab, Fares AlBataineh, Mohammad T. Alemi, Sharifullah Al-Gheethi, Adel Ali Saeed Ali, Liaqat Alif, Sheikh Mohammad Almazan, Joseph Uy Almustanyir, Sami Alqahtani, Jaber S. Alqasmi, Ibrahim Altaf, Ihsan Ullah Khan Alvis-Guzman, Nelson Alvis-Zakzuk, Nelson J. Al-Worafi, Yaser Mohammed Aly, Hany Amani, Reza Amu, Hubert Amusa, Ganiyu Adeniyi Andrei, Catalina Liliana Ansar, Adnan Ansariniya, Hossein Anyasodor, Anayochukwu Edward Arabloo, Jalal Arefnezhad, Reza Arulappan, Judie Asghari-Jafarabadi, Mohammad Ashraf, Tahira Atata, Jamila Abdulhamid Athari, Seyyed Shamsadin Atlaw, Daniel Atout, Maha Moh'd Wahbi Aujayeb, Avinash Awan, Asma Tahir Ayatollahi, Haleh Azadnajafabad, Sina Azzam, Ahmed Y. Badawi, Alaa Badiye, Ashish D. Bagherieh, Sara Baig, Atif Amin Bantie, Berihun Bantie Barchitta, Martina Bardhan, Mainak Barker-Collo, Suzanne Lyn Barone-Adesi, Francesco Batra, Kavita Bayileyegn, Nebiyou Simegnew Behnoush, Amir Hossein Belgaumi, Uzma Iqbal Bemanalizadeh, Maryam Bensenor, Isabela M. Beyene, Kebede A. Bhagavathula, Akshaya Srikanth Bhardwaj, Pankaj Bhaskar, Sonu Bhat, Ajay Nagesh Bitaraf, Saeid Bitra, Veera R. Boloor, Archith Bora, Kaustubh Botelho, João Silva Buchbinder, Rachelle Calina, Daniela Cámera, Luis Alberto Carvalho, Andre F. Chan, Jeffrey Shi Kai Chattu, Vijay Kumar Abebe, Endeshaw Chekol Department of Rheumatology and Immunology Sichuan Provincial People's Hospital School of Medicine University of Electronic Science and Technology of China China Department of Medicine & Therapeutics The Chinese University of Hong Kong Hong Kong Department of Paediatrics The Chinese University of Hong Kong Hong Kong School of Pharmacy The Chinese University of Hong Kong Hong Kong Jockey Club School of Public Health and Primary Care The Chinese University of Hong Kong Hong Kong Department of Nursing Woldia University Woldia Ethiopia Department of Orthopedic Surgery Harvard University Boston MA United States Postgraduate Medical Education Harvard University Boston MA United States Maternal Fetal Care Center Harvard University Boston MA United States Department of Health Policy and Oral Epidemiology Harvard University Boston MA United States Division of General Internal Medicine Harvard University Boston MA United States Department of Orthopaedic Surgery Shahid Beheshti University of Medical Sciences Tehran Iran Social Determinants of Health Research Center Shahid Beheshti University of Medical Sciences Tehran Iran Department of Biotechnology Shahid Beheshti University of Medical Sciences Tehran Iran Department of Epidemiology Shahid Beheshti University of Medical Sciences Tehran Iran National Nutrition and Food Technology Research Institute Shahid Beheshti University of Medical Sciences Tehran Iran Department of Immunology Shahid Beheshti University of Medical Sciences Tehran Iran Department of Neurology Shahid Beheshti University of Medical Sciences Tehran Iran Department of Medical Genetics Shahid Beheshti University of Medical Sciences Tehran Iran Center for Comprehensive Genetic Services Shahid Beheshti University of Medical Sciences Tehran Iran Cancer Research Center Shahid Beheshti University of Medical Sciences Tehran Iran Department of Health Economics and Statistics Shahid Beheshti University of Medical Sciences Tehran Iran Functional Neuro

Background: The causes for immune-mediated inflammatory diseases (IMIDs) are diverse and the incidence trends of IMIDs from specific causes are rarely studied. The study aims to investigate the pattern and trend of IMIDs from 1990 to 2019. Methods: We collected detailed information on six major causes of IMIDs, including asthma, inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, psoriasis, and atopic dermatitis, between 1990 and 2019, derived from the Global Burden of Disease study in 2019. The average annual percent change (AAPC) in number of incidents and age standardized incidence rate (ASR) on IMIDs, by sex, age, region, and causes, were calculated to quantify the temporal trends. Findings: In 2019, rheumatoid arthritis, atopic dermatitis, asthma, multiple sclerosis, psoriasis, inflammatory bowel disease accounted 1.59%, 36.17%, 54.71%, 0.09%, 6.84%, 0.60% of overall new IMIDs cases, respectively. The ASR of IMIDs showed substantial regional and global variation with the highest in High SDI region, High-income North America, and United States of America. Throughout human lifespan, the age distribution of incident cases from six IMIDs was quite different. Globally, incident cases of IMIDs increased with an AAPC of 0.68 and the ASR decreased with an AAPC of −0.34 from 1990 to 2019. The incident cases increased across six IMIDs, the ASR of rheumatoid arthritis increased (0.21, 95% CI 0.18, 0.25), while the ASR of asthma (AAPC = −0.41), inflammatory bowel disease (AAPC = −0.72), multiple sclerosis (AAPC = −0.26), psoriasis (AAPC = −0.77), and atopic dermatitis (AAPC = −0.15) decreased. The ASR of overall and six individual IMID increased with SDI at regional and global level. Countries with higher ASR in 1990 experienced a more rapid decrease in ASR. Interpretation: The incidence patterns of IMIDs varied considerably across the world. Innovative prevention and integrative management strategy are urgently needed to mitigate the increasing ASR of rh

关键词： Global burden of disease study Immune-mediated inflammatory disease Incidence Trend

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Lithium response in bipolar disorder is associated with focal adhesion and PI3K-Akt networks: a multi-omics replication study

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Translational psychiatry 2024年第1期14卷 109页

作者： Anna H Ou Sara B Rosenthal Mazda Adli Kazufumi Akiyama Nirmala Akula Martin Alda Azmeraw T Amare Raffaella Ardau Bárbara Arias Jean-Michel Aubry Lena Backlund Michael Bauer Bernhard T Baune Frank Bellivier Antonio Benabarre Susanne Bengesser Abesh Kumar Bhattacharjee Joanna M Biernacka Pablo Cervantes Guo-Bo Chen Hsi-Chung Chen Caterina Chillotti Sven Cichon Scott R Clark Francesc Colom David A Cousins Cristiana Cruceanu Piotr M Czerski Clarissa R Dantas Alexandre Dayer Maria Del Zompo Franziska Degenhardt J Raymond DePaulo Bruno Étain Peter Falkai Frederike Tabea Fellendorf Ewa Ferensztajn-Rochowiak Andreas J Forstner Louise Frisén Mark A Frye Janice M Fullerton Sébastien Gard Julie S Garnham Fernando S Goes Maria Grigoroiu-Serbanescu Paul Grof Oliver Gruber Ryota Hashimoto Joanna Hauser Urs Heilbronner Stefan Herms Per Hoffmann Andrea Hofmann Liping Hou Stephane Jamain Esther Jiménez Jean-Pierre Kahn Layla Kassem Tadafumi Kato Sarah Kittel-Schneider Barbara König Po-Hsiu Kuo Ichiro Kusumi Nina Lackner Gonzalo Laje Mikael Landén Catharina Lavebratt Marion Leboyer Susan G Leckband Carlos A López Jaramillo Glenda MacQueen Mario Maj Mirko Manchia Cynthia Marie-Claire Lina Martinsson Manuel Mattheisen Michael J McCarthy Susan L McElroy Francis J McMahon Philip B Mitchell Marina Mitjans Francis M Mondimore Palmiero Monteleone Caroline M Nievergelt Markus M Nöthen Tomas Novák Urban Ösby Norio Ozaki Sergi Papiol Roy H Perlis Claudia Pisanu James B Potash Andrea Pfennig Daniela Reich-Erkelenz Andreas Reif Eva Z Reininghaus Marcella Rietschel Guy A Rouleau Janusz K Rybakowski Martin Schalling Peter R Schofield K Oliver Schubert Thomas G Schulze Barbara W Schweizer Florian Seemüller Giovanni Severino Tatyana Shekhtman Paul D Shilling Kazutaka Shimoda Christian Simhandl Claire M Slaney Alessio Squassina Thomas Stamm Pavla Stopkova Sarah K Tighe Alfonso Tortorella Gustavo Turecki Eduard Vieta Julia Volkert Stephanie Witt Naomi R Wray Adam Wright L Trevor Young Peter P Zandi John R Kelsoe Department of Psychiatry University of California San Diego La Jolla CA USA. Center for Computational Biology and Bioinformatics Department of Medicine University of California San Diego La Jolla CA USA. Department of Psychiatry and Psychotherapy Charité- Universitätsmedizin Berlin Campus Charité Mitte Berlin Germany. Fliedner Klinik Berlin Center for Psychiatry Psychotherapy and Psychosomatic Medicine Berlin Germany. Department of Biological Psychiatry and Neuroscience Dokkyo Medical University School of Medicine Mibu Japan. Intramural Research Program National Institute of Mental Health National Institutes of Health US Department of Health & Human Services Bethesda MD USA. Department of Psychiatry Dalhousie University Halifax NS Canada. National Institute of Mental Health Klecany Czech Republic. Discipline of Psychiatry University of Adelaide Adelaide SA Australia. Unit of Clinical Pharmacology Hospital University Agency of Cagliari Cagliari Italy. Department of Evolutive Biology Ecology and Environmental Sciences Facultat de Biologia and Institut de Biomedicina (IBUB) Universitat de Barcelona Barcelona Spain. CIBER de Salud Mental ISCIII Madrid Barcelona Catalonia Spain. Department of Mental Health and Psychiatry Mood Disorders Unit-Geneva University Hospitals Geneva Switzerland. Department of Molecular Medicine and Surgery Karolinska Institutet and Center for Molecular Medicine Karolinska University Hospital Stockholm Sweden. Department of Psychiatry and Psychotherapy University Hospital Carl Gustav Carus Medical Faculty Technische Universität Dresden Dresden Germany. Department of Psychiatry University of Münster Münster Germany. INSERM UMR-S 1144-Université Paris Cité Département de Psychiatrie et de Médecine Addictologique AP-HP Groupe Hospitalier Lariboisière-F Widal Paris France. Bipolar and Depressive Disorders Unit Institute of Neuroscience Hospital Clinic University of Barcelona IDIBAPS CIBERSAM ISCIII Barcelona Catalonia Spa

Lithium is the gold standard treatment for bipolar disorder (BD). However, its mechanism of action is incompletely understood, and prediction of treatment outcomes is limited. In our previous multi-omics study of the Pharmacogenomics of Bipolar Disorder (PGBD) sample combining transcriptomic and genomic data, we found that focal adhesion, the extracellular matrix (ECM), and PI3K-Akt signaling networks were associated with response to lithium. In this study, we replicated the results of our previous study using network propagation methods in a genome-wide association study of an independent sample of 2039 patients from the International Consortium on Lithium Genetics (ConLiGen) study. We identified functional enrichment in focal adhesion and PI3K-Akt pathways, but we did not find an association with the ECM pathway. Our results suggest that deficits in the neuronal growth cone and PI3K-Akt signaling, but not in ECM proteins, may influence response to lithium in BD.

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An International Adult Guideline for Making Clozapine Titration Safer by Using Six Ancestry-Based Personalized Dosing Titrations, CRP, and Clozapine Levels

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Pharmacopsychiatry 2021年第2期55卷 73-86页

作者： Jose de Leon Georgios Schoretsanitis Robert L. Smith Espen Molden Anssi Solismaa Niko Seppälä Miloslav Kopeček Patrik Švancer Ismael Olmos Carina Ricciardi Celso Iglesias-Garcia Ana Iglesias-Alonso Edoardo Spina Can-Jun Ruan Chuan-Yue Wang Gang Wang Yi-Lang Tang Shih-Ku Lin Hsien-Yuan Lane Yong Sik Kim Se Hyun Kim Anto P. Rajkumar Dinora F. González-Esquivel Helgi Jung-Cook Trino Baptista Christopher Rohde Jimmi Nielsen Hélène Verdoux Clelia Quiles Emilio J. Sanz Carlos De Las Cuevas Dan Cohen Peter F.J. Schulte Aygün Ertuğrul A. Elif Anıl Yağcıoğlu Nitin Chopra Betsy McCollum Charles Shelton Robert O. Cotes Arun R. Kaithi John M. Kane Saeed Farooq Chee H. Ng John Bilbily Christoph Hiemke Carlos López-Jaramillo Ian McGrane Fernando Lana Chin B. Eap Manuel Arrojo-Romero Flavian Ş. Rădulescu Erich Seifritz Susanna Every-Palmer Chad A. Bousman Emmanuel Bebawi Rahul Bhattacharya Deanna L. Kelly Yuji Otsuka Judit Lazary Rafael Torres Agustin Yecora Mariano Motuca Sherry K.W. Chan Monica Zolezzi Sami Ouanes Domenico De Berardis Sandeep Grover Ric M. Procyshyn Richard A. Adebayo Oleg O. Kirilochev Andrey Soloviev Konstantinos N. Fountoulakis Alina Wilkowska Wiesław J. Cubała Muhammad Ayub Alzira Silva Raphael M. Bonelli José M. Villagrán-Moreno Benedicto Crespo-Facorro Henk Temmingh Eric Decloedt Maria R. Pedro Hiroyoshi Takeuchi Masaru Tsukahara Gerhard Gründer Marina Sagud Andreja Celofiga Dragana Ignjatovic Ristic Bruno B. Ortiz Helio Elkis António J. Pacheco Palha Adrián LLerena Emilio Fernandez-Egea Dan Siskind Abraham Weizman Rim Masmoudi Shamin Mohd Saffian Jonathan G. Leung Peter F. Buckley Stephen R. Marder Leslie Citrome Oliver Freudenreich Christoph U. Correll Daniel J. Müller Mental Health Research Center Eastern State Hospital Lexington KY USA Department of Psychiatry University of Kentucky Lexington KY USA Psychiatry and Neurosciences Research Group (CTS-549) Institute of Neurosciences University of Granada Granada Spain Biomedical Research Centre in Mental Health Net (CIBERSAM) Santiago Apostol Hospital University of the Basque Country Vitoria Spain Department of Psychiatry Psychotherapy and Psychosomatics Psychiatric Hospital University of Zürich Zürich Switzerland The Zucker Hillside Hospital Psychiatry Research Northwell Health Glen Oaks New York USA Center for Psychopharmacology Diakonhjemmet Hospital Oslo Norway Section for Pharmacology and Pharmaceutical Biosciences Department of Pharmacy University of Oslo Oslo Norway Faculty of Medicine and Health Technology Tampere University Tampere Finland Department of Psychiatry Tampere University Hospital Tampere Finland Department of Psychiatry Satasairaala Finland National Institute of Mental Health Klecany Czech Republic Department of Psychiatry Charles University Third Faculty of Medicine Prague Czech Republic Clinical Pharmacology Unit and Pharmacy Department Vilardebó Hospital Administración de Servicios de Salud Montevideo Uruguay Clinical Pharmacology Unit and Outpatient Clinic Vilardebó Hospital Administración de Servicios de Salud Montevideo Uruguay Universidad de Oviedo. CIBERSAM. INEUROPA. ISPA-FIMBA Oviedo Spain Hospital Valle del Nalón Langreo Spain Hospital Universitario Central de Asturias Oviedo Spain Department of Clinical and Experimental Medicine University of Messina Messina Italy Laboratory of Clinical Psychopharmacology Beijing Anding Hospital Capital Medical University Beijing China The National Clinical Research Centre for Mental Disorders & Beijing Key Lab of Mental Disorders Beijing Anding Hospital Capital Medical University Beijing China Department of Psychiatry Beijing Anding Hospital Capital Medical University Beijing China Depart

This international guideline proposes improving clozapine package inserts worldwide by using ancestry-based dosing and titration. Adverse drug reaction (ADR) databases suggest that clozapine is the third most toxic drug in the United States (US), and it produces four times higher worldwide pneumonia mortality than that by agranulocytosis or myocarditis. For trough steady-state clozapine serum concentrations, the therapeutic reference range is narrow, from 350 to 600 ng/mL with the potential for toxicity and ADRs as concentrations increase. Clozapine is mainly metabolized by CYP1A2 (female non-smokers, the lowest dose; male smokers, the highest dose). Poor metabolizer status through phenotypic conversion is associated with co-prescription of inhibitors (including oral contraceptives and valproate), obesity, or inflammation with C-reactive protein (CRP) elevations. The Asian population (Pakistan to Japan) or the Americas’ original inhabitants have lower CYP1A2 activity and require lower clozapine doses to reach concentrations of 350 ng/mL. In the US, daily doses of 300–600 mg/day are recommended. Slow personalized titration may prevent early ADRs (including syncope, myocarditis, and pneumonia). This guideline defines six personalized titration schedules for inpatients: 1) ancestry from Asia or the original people from the Americas with lower metabolism (obesity or valproate) needing minimum therapeutic dosages of 75–150 mg/day, 2) ancestry from Asia or the original people from the Americas with average metabolism needing 175–300 mg/day, 3) European/Western Asian ancestry with lower metabolism (obesity or valproate) needing 100–200 mg/day, 4) European/Western Asian ancestry with average metabolism needing 250–400 mg/day, 5) in the US with ancestries other than from Asia or the original people from the Americas with lower clozapine metabolism (obesity or valproate) needing 150–300 mg/day, and 6) in the US with ancestries other than from Asia or the original people from

关键词： Native American continental ancestry group Asian continental ancestry group clozapine/adverse effects clozapine/blood clozapine/metabolism clozapine/therapeutic use clozapine/toxicity CYP1A2 drug labeling European continental ancestry group infection inflammation mortality/drug effects sex smoking.

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