TY - JOUR
T1 - The IMAGEN study
T2 - a decade of imaging genetics in adolescents
AU - IMAGEN consortium
AU - Mascarell Maričić, Lea
AU - Walter, Henrik
AU - Rosenthal, Annika
AU - Ripke, Stephan
AU - Quinlan, Erin Burke
AU - Banaschewski, Tobias J.
AU - Barker, Gareth J.
AU - Bokde, Arun L.W.
AU - Bromberg, Uli
AU - Büchel, Christian
AU - Desrivières, Sylvane
AU - Flor, Herta
AU - Frouin, Vincent
AU - Garavan, Hugh
AU - Itterman, Bernd
AU - Martinot, Jean Luc
AU - Martinot, Marie Laure Paillère
AU - Nees, Frauke
AU - Orfanos, Dimitri Papadopoulos
AU - Paus, Tomáš
AU - Poustka, Luise
AU - Hohmann, Sarah
AU - Smolka, Michael N.
AU - Fröhner, Juliane H.
AU - Whelan, Robert
AU - Kaminski, Jakob
AU - Schumann, Gunter
AU - Heinz, Andreas
AU - Albrecht, Lisa
AU - Andrew, Chris
AU - Arroyo, Mercedes
AU - Artiges, Eric
AU - Aydin, Semiha
AU - Bach, Christine
AU - Barbot, Alexis
AU - Boddaert, Nathalie
AU - Bricaud, Zuleima
AU - Bromberg, Uli
AU - Bruehl, Ruediger
AU - Cachia, Arnaud
AU - Cattrell, Anna
AU - Conrod, Patricia
AU - Constant, Patrick
AU - Dalley, Jeffrey
AU - Decideur, Benjamin
AU - Fadai, Tahmine
AU - Flor, Herta
AU - Frouin, Vincent
AU - Gallinat, Jürgen
AU - Lubbe, Steven
N1 - Funding Information:
Acknowlegements This work received support from the following sources: the European Union-funded FP6 Integrated Project IMAGEN (Reinforcement-related behavior in normal brain function and psychopathology) (LSHM-CT-2007-037286), the Horizon 2020 funded ERC Advanced Grant ‘STRATIFY’ (Brain network based stratification of reinforcement-related disorders) (695313), ERANID (Understanding the Interplay between Cultural, Biological and Subjective Factors in Drug Use Pathways) (PR-ST-0416-10004), BRIDGET (JPND: BRain Imaging, cognition Dementia and next generation GEnomics) (MR/N027558/1), the FP7 projects IMAGEMEND (602450; IMAgingGEnetics for MENtal Disorders) and MATRICS (603016), the Innovative Medicine Initiative Project EU-AIMS (115300-2), the Medical Research Council Grant ‘c-VEDA’ (Consortium on Vulnerability to Externalizing Disorders and Addictions) (MR/N000390/1), the Swedish Research Council FORMAS, the Medical Research Council, the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London, the Bundesmi-nisteriumfürBildung und Forschung (BMBF grants 01GS08152; 01EV0711; eMED SysAlc01ZX1311A; Forschungsnetz AERIAL 01EE1406A, 01EE1406B), the Deutsche Forschungsgemeinschaft (DFG grants SM 80/7-2, SFB 940/2, TRR 265), the Medical Research Foundation and Medical research council (grant MR/R00465X/1). Further support was provided by grants from: ANR (project AF12-NEUR0008-01—WM2NA, and ANR-12-SAMA-0004), the Fonda-tion de France, the Fondation pour la RechercheMédicale, the Mission Interministérielle de Lutte-contre-les-Drogues-et-les-Conduites-Addictives (MILDECA), the Assistance-Publique-Hôpitaux-de-Paris and INSERM (interface grant), Paris Sud University IDEX 2012; the National Institutes of Health, Science Foundation Ireland (16/ERCD/ 3797), USA (Axon, Testosterone and Mental Health during Adolescence; RO1 MH085772-01A1), and by NIH Consortium grant U54 EB020403, supported by a cross-NIH alliance that funds Big Data to Knowledge Centres of Excellence. Open access funding provided by Projekt DEAL.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/11/1
Y1 - 2020/11/1
N2 - Imaging genetics offers the possibility of detecting associations between genotype and brain structure as well as function, with effect sizes potentially exceeding correlations between genotype and behavior. However, study results are often limited due to small sample sizes and methodological differences, thus reducing the reliability of findings. The IMAGEN cohort with 2000 young adolescents assessed from the age of 14 onwards tries to eliminate some of these limitations by offering a longitudinal approach and sufficient sample size for analyzing gene-environment interactions on brain structure and function. Here, we give a systematic review of IMAGEN publications since the start of the consortium. We then focus on the specific phenotype ‘drug use’ to illustrate the potential of the IMAGEN approach. We describe findings with respect to frontocortical, limbic and striatal brain volume, functional activation elicited by reward anticipation, behavioral inhibition, and affective faces, and their respective associations with drug intake. In addition to describing its strengths, we also discuss limitations of the IMAGEN study. Because of the longitudinal design and related attrition, analyses are underpowered for (epi-) genome-wide approaches due to the limited sample size. Estimating the generalizability of results requires replications in independent samples. However, such densely phenotyped longitudinal studies are still rare and alternative internal cross-validation methods (e.g., leave-one out, split-half) are also warranted. In conclusion, the IMAGEN cohort is a unique, very well characterized longitudinal sample, which helped to elucidate neurobiological mechanisms involved in complex behavior and offers the possibility to further disentangle genotype × phenotype interactions.
AB - Imaging genetics offers the possibility of detecting associations between genotype and brain structure as well as function, with effect sizes potentially exceeding correlations between genotype and behavior. However, study results are often limited due to small sample sizes and methodological differences, thus reducing the reliability of findings. The IMAGEN cohort with 2000 young adolescents assessed from the age of 14 onwards tries to eliminate some of these limitations by offering a longitudinal approach and sufficient sample size for analyzing gene-environment interactions on brain structure and function. Here, we give a systematic review of IMAGEN publications since the start of the consortium. We then focus on the specific phenotype ‘drug use’ to illustrate the potential of the IMAGEN approach. We describe findings with respect to frontocortical, limbic and striatal brain volume, functional activation elicited by reward anticipation, behavioral inhibition, and affective faces, and their respective associations with drug intake. In addition to describing its strengths, we also discuss limitations of the IMAGEN study. Because of the longitudinal design and related attrition, analyses are underpowered for (epi-) genome-wide approaches due to the limited sample size. Estimating the generalizability of results requires replications in independent samples. However, such densely phenotyped longitudinal studies are still rare and alternative internal cross-validation methods (e.g., leave-one out, split-half) are also warranted. In conclusion, the IMAGEN cohort is a unique, very well characterized longitudinal sample, which helped to elucidate neurobiological mechanisms involved in complex behavior and offers the possibility to further disentangle genotype × phenotype interactions.
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U2 - 10.1038/s41380-020-0822-5
DO - 10.1038/s41380-020-0822-5
M3 - Review article
C2 - 32601453
AN - SCOPUS:85087116712
SN - 1359-4184
VL - 25
SP - 2648
EP - 2671
JO - Molecular Psychiatry
JF - Molecular Psychiatry
IS - 11
ER -