Browsing by Author "Gowland, Penny"

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    Chronic neuropsychiatric sequelae of SARS-CoV-2: Protocol and methods from the Alzheimer's Association Global Consortium
    (Alzheimer’s Association, 2022-09-22) de Erausquin, Gabriel A.; Snyder, Heather; Brugha, Traolach S.; Seshadri, Sudha; Carrillo, Maria; Sagar, Rajesh; Huang, Yueqin; Newton, Charles; Tartaglia, Carmela; Teunissen, Charlotte; Håkanson, Krister; Akinyemi, Rufus; Prasad, Kameshwar; D'Avossa, Giovanni; Gonzalez-Aleman, Gabriela; Hosseini, Akram; Vavougios, George D.; Sachdev, Perminder; Bankart, John; Ole Mors, Niels Peter; Lipton, Richard; Katz, Mindy; Fox, Peter T.; Katshu, Mohammad Zia; Iyengar, M. Sriram; Weinstein, Galit; Sohrabi, Hamid R.; Jenkins, Rachel; Stein, Dan J.; Hugon, Jacques; Mavreas, Venetsanos; Blangero, John; Cruchaga, Carlos; Krishna, Murali; Wadoo, Ovais; Becerra, Rodrigo; Zwir, Igor; Longstreth, William T.; Kroenenberg, Golo; Edison, Paul; Mukaetova-Ladinska, Elizabeta; Staufenberg, Ekkehart; Figueredo-Aguiar, Mariana; Yécora, Agustín; Vaca, Fabiana; Zamponi, Hernan P.; Lo Re, Vincenzina; Majid, Abdul; Sundarakumar, Jonas; Gonzalez, Hector M.; Geerlings, Mirjam I.; Skoog, Ingmar; Salmoiraghi, Alberto; Boneschi, Filippo Martinelli; Patel, Vibuthi N.; Santos, Juan M.; Arroyo, Guillermo Rivera; Moreno, Antonio Caballero; Felix, Pascal; Gallo, Carla; Arai, Hidenori; Yamada, Masahito; Iwatsubo, Takeshi; Sharma, Malveeka; Chakraborty, Nandini; Ferreccio, Catterina; Akena, Dickens; Brayne, Carol; Maestre, Gladys; Williams Blangero, Sarah; Brusco, Luis I.; Siddarth, Prabha; Hughes, Timothy M.; Ramírez Zuñiga, Alfredo; Kambeitz, Joseph; Laza, Agustin Ruiz; Allen, Norrina; Panos, Stella; Merrill, David; Ibáñez, Agustín; Tsuang, Debby; Valishvili, Nino; Shrestha, Srishti; Wang, Sophia; Padma, Vasantha; Anstey, Kaarin J.; Ravindrdanath, Vijayalakshmi; Blennow, Kaj; Mullins, Paul; Łojek, Emilia; Pria, Anand; Mosley, Thomas H.; Gowland, Penny; Girard, Timothy D.; Bowtell, Richard; Vahidy, Farhaan S.; Psychiatry, School of Medicine
    Introduction: Coronavirus disease 2019 (COVID-19) has caused >3.5 million deaths worldwide and affected >160 million people. At least twice as many have been infected but remained asymptomatic or minimally symptomatic. COVID-19 includes central nervous system manifestations mediated by inflammation and cerebrovascular, anoxic, and/or viral neurotoxicity mechanisms. More than one third of patients with COVID-19 develop neurologic problems during the acute phase of the illness, including loss of sense of smell or taste, seizures, and stroke. Damage or functional changes to the brain may result in chronic sequelae. The risk of incident cognitive and neuropsychiatric complications appears independent from the severity of the original pulmonary illness. It behooves the scientific and medical community to attempt to understand the molecular and/or systemic factors linking COVID-19 to neurologic illness, both short and long term. Methods: This article describes what is known so far in terms of links among COVID-19, the brain, neurological symptoms, and Alzheimer's disease (AD) and related dementias. We focus on risk factors and possible molecular, inflammatory, and viral mechanisms underlying neurological injury. We also provide a comprehensive description of the Alzheimer's Association Consortium on Chronic Neuropsychiatric Sequelae of SARS-CoV-2 infection (CNS SC2) harmonized methodology to address these questions using a worldwide network of researchers and institutions. Results: Successful harmonization of designs and methods was achieved through a consensus process initially fragmented by specific interest groups (epidemiology, clinical assessments, cognitive evaluation, biomarkers, and neuroimaging). Conclusions from subcommittees were presented to the whole group and discussed extensively. Presently data collection is ongoing at 19 sites in 12 countries representing Asia, Africa, the Americas, and Europe. Discussion: The Alzheimer's Association Global Consortium harmonized methodology is proposed as a model to study long-term neurocognitive sequelae of SARS-CoV-2 infection. Key points: The following review describes what is known so far in terms of molecular and epidemiological links among COVID-19, the brain, neurological symptoms, and AD and related dementias (ADRD)The primary objective of this large-scale collaboration is to clarify the pathogenesis of ADRD and to advance our understanding of the impact of a neurotropic virus on the long-term risk of cognitive decline and other CNS sequelae. No available evidence supports the notion that cognitive impairment after SARS-CoV-2 infection is a form of dementia (ADRD or otherwise). The longitudinal methodologies espoused by the consortium are intended to provide data to answer this question as clearly as possible controlling for possible confounders. Our specific hypothesis is that SARS-CoV-2 triggers ADRD-like pathology following the extended olfactory cortical network (EOCN) in older individuals with specific genetic susceptibility. The proposed harmonization strategies and flexible study designs offer the possibility to include large samples of under-represented racial and ethnic groups, creating a rich set of harmonized cohorts for future studies of the pathophysiology, determinants, long-term consequences, and trends in cognitive aging, ADRD, and vascular disease. We provide a framework for current and future studies to be carried out within the Consortium. and offers a "green paper" to the research community with a very broad, global base of support, on tools suitable for low- and middle-income countries aimed to compare and combine future longitudinal data on the topic. The Consortium proposes a combination of design and statistical methods as a means of approaching causal inference of the COVID-19 neuropsychiatric sequelae. We expect that deep phenotyping of neuropsychiatric sequelae may provide a series of candidate syndromes with phenomenological and biological characterization that can be further explored. By generating high-quality harmonized data across sites we aim to capture both descriptive and, where possible, causal associations.
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    Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes: findings from the ENIGMA Epigenetics Working Group
    (Springer Nature, 2021) Jia, Tianye; Chu, Congying; Liu, Yun; Van Dongen, Jenny; Papastergios, Evangelos; Armstrong, Nicola J.; Bastin, Mark E.; Carrillo-Roa, Tania; den Braber, Anouk; Harris, Mathew; Jansen, Rick; Liu, Jingyu; Luciano, Michelle; Ori, Anil P.S.; Santiañez, Roberto Roiz; Ruggeri, Barbara; Sarkisyan, Daniil; Shin, Jean; Sungeun, Kim; Tordesillas Gutiérrez, Diana; van't Ent, Dennis; Ames, David; Artiges, Eric; Bakalkin, Georgy; Banaschewski, Tobias; Bokde, Arun L.W.; Brodaty, Henry; Bromberg, Uli; Brouwer, Rachel; Büchel, Christian; Burke Quinlan, Erin; Cahn, Wiepke; de Zubicaray, Greig I.; Ehrlich, Stefan; Ekström, Tomas J.; Flor, Herta; Fröhner, Juliane H.; Frouin, Vincent; Garavan, Hugh; Gowland, Penny; Heinz, Andreas; Hoare, Jacqueline; Ittermann, Bernd; Jahanshad, Neda; Jiang, Jiyang; Kwok, John B.; Martin, Nicholas G.; Martinot, Jean-Luc; Mather, Karen A.; McMahon, Katie L.; McRae, Allan F.; Nees, Frauke; Orfanos, Dimitri Papadopoulos; Paus, Tomáš; Poustka, Luise; Sämann, Philipp G.; Schofield, Peter R.; Smolka, Michael N.; Stein, Dan J.; Strike, Lachlan T.; Teeuw, Jalmar; Thalamuthu, Anbupalam; Trollor, Julian; Walter, Henrik; Wardlaw, Joanna M.; Wen, Wei; Whelan, Robert; Apostolova, Liana G.; Binder, Elisabeth B.; Boomsma, Dorret I.; Calhoun, Vince; Crespo-Facorro, Benedicto; Deary, Ian J.; Hulshoff Pol, Hilleke; Ophoff, Roel A.; Pausova, Zdenka; Sachdev, Perminder S.; Saykin, Andrew; Wright, Margaret J.; Thompson, Paul M.; Schumann, Gunter; Desrivières, Sylvane; Radiology and Imaging Sciences, School of Medicine
    DNA methylation, which is modulated by both genetic factors and environmental exposures, may offer a unique opportunity to discover novel biomarkers of disease-related brain phenotypes, even when measured in other tissues than brain, such as blood. A few studies of small sample sizes have revealed associations between blood DNA methylation and neuropsychopathology, however, large-scale epigenome-wide association studies (EWAS) are needed to investigate the utility of DNA methylation profiling as a peripheral marker for the brain. Here, in an analysis of eleven international cohorts, totalling 3337 individuals, we report epigenome-wide meta-analyses of blood DNA methylation with volumes of the hippocampus, thalamus and nucleus accumbens (NAcc)—three subcortical regions selected for their associations with disease and heritability and volumetric variability. Analyses of individual CpGs revealed genome-wide significant associations with hippocampal volume at two loci. No significant associations were found for analyses of thalamus and nucleus accumbens volumes. Cluster-based analyses revealed additional differentially methylated regions (DMRs) associated with hippocampal volume. DNA methylation at these loci affected expression of proximal genes involved in learning and memory, stem cell maintenance and differentiation, fatty acid metabolism and type-2 diabetes. These DNA methylation marks, their interaction with genetic variants and their impact on gene expression offer new insights into the relationship between epigenetic variation and brain structure and may provide the basis for biomarker discovery in neurodegeneration and neuropsychiatric conditions.