Browsing by Author "Garavan, Hugh"

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    ENIGMA and the individual: Predicting factors that affect the brain in 35 countries worldwide
    (Elsevier, 2017-01-15) Thompson, Paul M.; Andreassen, Ole A.; Arias-Vasquez, Alejandro; Bearden, Carrie E.; Boedhoe, Premika S.; Brouwer, Rachel M.; Buckner, Randy L.; Buitelaar, Jan K.; Bulayeva, Kazima B.; Cannon, Dara M.; Cohen, Ronald A.; Conrod, Patricia J.; Dale, Anders M.; Deary, Ian J.; Dennis, Emily L.; de Reus, Marcel A.; Desrivieres, Sylvane; Dima, Danai; Donohoe, Gary; Fisher, Simon E.; Fouche, Jean-Paul; Francks, Clyde; Frangou, Sophia; Franke, Barbara; Ganjgahi, Habib; Garavan, Hugh; Glahn, David C.; Grabe, Hans J.; Guadalupe, Tulio; Gutman, Boris A.; Hashimoto, Ryota; Hibar, Derrek P.; Holland, Dominic; Hoogman, Martine; Pol, Hilleke E. Hulshoff; Hosten, Norbert; Jahanshad, Neda; Kelly, Sinead; Kochunov, Peter; Kremen, William S.; Lee, Phil H.; Mackey, Scott; Martin, Nicholas G.; Mazoyer, Bernard; McDonald, Colm; Medland, Sarah E.; Morey, Rajendra A.; Nichols, Thomas E.; Paus, Tomas; Pausova, Zdenka; Schmaal, Lianne; Schumann, Gunter; Shen, Li; Sisodiya, Sanjay M.; Smit, Dirk J.A.; Smoller, Jordan W.; Stein, Dan J.; Stein, Jason L.; Toro, Roberto; Turner, Jessica A.; Heuvel, Martijn P. van den; Heuvel, Odile L. van den; Erp, Theo G.M. van; Rooij, Daan van; Veltman, Dick J.; Walter, Henrik; Wang, Yalin; Wardlaw, Joanna M.; Whelan, Christopher D.; Wright, Margaret J.; Ye, Jieping; ENIGMA Consortium; Radiology and Imaging Sciences, School of Medicine
    In this review, we discuss recent work by the ENIGMA Consortium (http://enigma.ini.usc.edu) – a global alliance of over 500 scientists spread across 200 institutions in 35 countries collectively analyzing brain imaging, clinical, and genetic data. Initially formed to detect genetic influences on brain measures, ENIGMA has grown to over 30 working groups studying 12 major brain diseases by pooling and comparing brain data. In some of the largest neuroimaging studies to date – of schizophrenia and major depression – ENIGMA has found replicable disease effects on the brain that are consistent worldwide, as well as factors that modulate disease effects. In partnership with other consortia including ADNI, CHARGE, IMAGEN and others1, ENIGMA's genomic screens – now numbering over 30,000 MRI scans – have revealed at least 8 genetic loci that affect brain volumes. Downstream of gene findings, ENIGMA has revealed how these individual variants – and genetic variants in general – may affect both the brain and risk for a range of diseases. The ENIGMA consortium is discovering factors that consistently affect brain structure and function that will serve as future predictors linking individual brain scans and genomic data. It is generating vast pools of normative data on brain measures – from tens of thousands of people – that may help detect deviations from normal development or aging in specific groups of subjects. We discuss challenges and opportunities in applying these predictors to individual subjects and new cohorts, as well as lessons we have learned in ENIGMA's efforts so far.
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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.
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    Neuroanatomical Variability and Substance Use Initiation in Late Childhood and Early Adolescence
    (American Medical Association, 2024-12-02) Miller, Alex P.; Baranger, David A. A.; Paul, Sarah E.; Garavan, Hugh; Mackey, Scott; Tapert, Susan F.; LeBlanc, Kimberly H.; Agrawal, Arpana; Bogdan, Ryan; Psychiatry, School of Medicine
    Importance: The extent to which neuroanatomical variability associated with early substance involvement, which is associated with subsequent risk for substance use disorder development, reflects preexisting risk and/or consequences of substance exposure remains poorly understood. Objective: To examine neuroanatomical features associated with early substance use initiation and to what extent associations may reflect preexisting vulnerability. Design, setting, and participants: Cohort study using data from baseline through 3-year follow-up assessments of the ongoing longitudinal Adolescent Brain Cognitive Development Study. Children aged 9 to 11 years at baseline were recruited from 22 sites across the US between June 1, 2016, and October 15, 2018. Data were analyzed from February to September 2024. Exposures: Substance use initiation through 3-year follow-up (ie, age <15 years). Main outcomes and measures: Self-reported alcohol, nicotine, cannabis, and other substance use initiation and baseline magnetic resonance imaging (MRI)-derived estimates of brain structure (ie, global and regional cortical volume, thickness, surface area, sulcal depth, and subcortical volume). Covariates included family (eg, familial relationships), pregnancy (eg, prenatal exposure to substances), child (eg, sex and pubertal status), and MRI (eg, scanner model) variables. Results: Among 9804 children (mean [SD] baseline age, 9.9 [0.6] years; 5160 boys [52.6%]; 213 Asian [2.2%], 1474 Black [15.0%], 514 Hispanic/Latino [5.2%], 29 American Indian [0.3%], 10 Pacific Islander [0.1%], 7463 White [76.1%], and 75 other [0.7%]) with nonmissing baseline neuroimaging and covariate data, 3460 (35.3%) reported substance use initiation before age 15. Initiation of any substance or alcohol use was associated with thinner cortex in prefrontal regions (eg, rostral middle frontal gyrus, β = -0.03; 95% CI, -0.02 to -0.05; P = 6.99 × 10-6) but thicker cortex in all other lobes, larger globus pallidus and hippocampal volumes, as well as greater global indices of brain structure (eg, larger whole brain volume, β = 0.05; 95% CI, 0.03 to 0.06; P = 2.80 × 10-8) following Bonferroni or false discovery rate multiple testing correction. Cannabis use initiation was associated with lower right caudate volume (β = -0.03; 95% CI, -0.01 to -0.05; P = .002). Post hoc examinations restricting to postbaseline initiation suggested that the majority of associations, including thinner prefrontal cortex and greater whole brain volume, preceded initiation. Conclusions and relevance: In this cohort study of children, preexisting neuroanatomical variability was associated with substance use initiation. In addition to putative neurotoxic effects of substance exposure, brain structure variability may reflect predispositional risk for initiating substance use earlier in life with potential cascading implications for development of later problems.