. 2020 Nov;25(11):2648-2671.

doi: 10.1038/s41380-020-0822-5. Epub 2020 Jun 29.

The IMAGEN study: a decade of imaging genetics in adolescents

Lea Mascarell Maričić^#¹, Henrik Walter^#¹, Annika Rosenthal¹, Stephan Ripke¹, Erin Burke Quinlan², Tobias Banaschewski³, Gareth J Barker⁴, Arun L W Bokde⁵, Uli Bromberg⁶, Christian Büchel⁷, Sylvane Desrivières², Herta Flor^{7

8}, Vincent Frouin⁹, Hugh Garavan¹⁰, Bernd Itterman¹¹, Jean-Luc Martinot¹², Marie-Laure Paillère Martinot¹³, Frauke Nees^{3

7}, Dimitri Papadopoulos Orfanos⁹, Tomáš Paus¹⁴, Luise Poustka¹⁵, Sarah Hohmann³, Michael N Smolka¹⁶, Juliane H Fröhner¹⁶, Robert Whelan¹⁷, Jakob Kaminski^{1

18}, Gunter Schumann^#², Andreas Heinz^#¹⁹; IMAGEN consortium

Collaborators, Affiliations

Collaborators

IMAGEN consortium:
Lisa Albrecht, Chris Andrew, Mercedes Arroyo, Eric Artiges, Semiha Aydin, Christine Bach, Tobias Banaschewski, Alexis Barbot, Gareth Barker, Nathalie Boddaert, Arun Bokde, Zuleima Bricaud, Uli Bromberg, Ruediger Bruehl, Christian Büchel, Arnaud Cachia, Anna Cattrell, Patricia Conrod, Patrick Constant, Jeffrey Dalley, Benjamin Decideur, Sylvane Desrivieres, Tahmine Fadai, Herta Flor, Vincent Frouin, Jürgen Gallinat, Hugh Garavan, Fanny Gollier Briand, Penny Gowland, Bert Heinrichs, Andreas Heinz, Nadja Heym, Thomas Hübner, James Ireland, Bernd Ittermann, Tianye Jia, Mark Lathrop, Dirk Lanzerath, Claire Lawrence, Hervé Lemaitre, Katharina Lüdemann, Christine Macare, Catherine Mallik, Jean-François Mangin, Karl Mann, Jean-Luc Martinot, Eva Mennigen, Fabiana Mesquita de Carvahlo, Xavier Mignon, Ruben Miranda, Kathrin Müller, Frauke Nees, Charlotte Nymberg, Marie-Laure Paillere, Tomas Paus, Zdenka Pausova, Jean-Baptiste Poline, Luise Poustka, Michael Rapp, Gabriel Robert, Jan Reuter, Marcella Rietschel, Stephan Ripke, Trevor Robbins, Sarah Rodehacke, John Rogers, Alexander Romanowski, Barbara Ruggeri, Christine Schmäl, Dirk Schmidt, Sophia Schneider, MarkGunter Schumann, Florian Schubert, Yannick Schwartz, Michael Smolka, Wolfgang Sommer, Rainer Spanagel, Claudia Speiser, Tade Spranger, Alicia Stedman, Sabina Steiner, Dai Stephens, Nicole Strache, Andreas Ströhle, Maren Struve, Naresh Subramaniam, Lauren Topper, Henrik Walter, Robert Whelan, Steve Williams, Juliana Yacubian, Monica Zilbovicius, C Peng Wong, Steven Lubbe, Lourdes Martinez-Medina, Alinda Fernandes, Amir Tahmasebi

Affiliations

¹ Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany.
² Department of Social Genetic & Developmental Psychiatry, Institute of Psychiatry, King's College London, London, UK.
³ Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Square J5, 68159, Mannheim, Germany.
⁴ Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
⁵ Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
⁶ University Medical Centre Hamburg-Eppendorf, House W34, 3.OG, Martinistr. 52, 20246, Hamburg, Germany.
⁷ Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Square J5, Mannheim, Germany.
⁸ Department of Psychology, School of Social Sciences, University of Mannheim, 68131, Mannheim, Germany.
⁹ NeuroSpin, CEA, Université Paris-Saclay, F-91191, Gif-sur-Yvette, France.
¹⁰ Departments of Psychiatry and Psychology, University of Vermont, Burlington, VT, 05405, USA.
¹¹ Physikalisch-Technische Bundesanstalt (PTB), Abbestr. 2-12, Berlin, Germany.
¹² Institut National de la Santé et de la Recherche Médicale, INSERM Unit 1000 "Neuroimaging& Psychiatry", University Paris Sud, University Paris Descartes-Sorbonne Paris Cité, and Maison de Solenn, Paris, France.
¹³ Institut National de la Santé et de la Recherche Médicale, INSERM Unit 1000 "Neuroimaging & Psychiatry", University Paris Sud, University Paris Descartes, Sorbonne Université, and AP-HP, Department of Child and Adolescent Psychiatry, Pitié-Salpêtrière Hospital, Paris, France.
¹⁴ Rotman Research Institute, Baycrest and Departments of Psychology and Psychiatry, University of Toronto, Toronto, ON, M6A 2E1, Canada.
¹⁵ Department of Child and Adolescent Psychiatry and Psychotherapy, University Medical Centre Göttingen, von-Siebold-Str. 5, 37075, Göttingen, Germany.
¹⁶ Department of Psychiatry and Neuroimaging Center, TechnischeUniversität Dresden, Dresden, Germany.
¹⁷ School of Psychology and Global Brain Health Institute, Trinity College Dublin, Dublin, Ireland.
¹⁸ Berlin Institute of Health, Berlin, Germany.
¹⁹ Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany. andreas.heinz@charite.de.

^# Contributed equally.

PMID: 32601453
PMCID: PMC7577859
DOI: 10.1038/s41380-020-0822-5

The IMAGEN study: a decade of imaging genetics in adolescents

Lea Mascarell Maričić et al. Mol Psychiatry. 2020 Nov.

. 2020 Nov;25(11):2648-2671.

doi: 10.1038/s41380-020-0822-5. Epub 2020 Jun 29.

Authors

Collaborators

IMAGEN consortium:
Lisa Albrecht, Chris Andrew, Mercedes Arroyo, Eric Artiges, Semiha Aydin, Christine Bach, Tobias Banaschewski, Alexis Barbot, Gareth Barker, Nathalie Boddaert, Arun Bokde, Zuleima Bricaud, Uli Bromberg, Ruediger Bruehl, Christian Büchel, Arnaud Cachia, Anna Cattrell, Patricia Conrod, Patrick Constant, Jeffrey Dalley, Benjamin Decideur, Sylvane Desrivieres, Tahmine Fadai, Herta Flor, Vincent Frouin, Jürgen Gallinat, Hugh Garavan, Fanny Gollier Briand, Penny Gowland, Bert Heinrichs, Andreas Heinz, Nadja Heym, Thomas Hübner, James Ireland, Bernd Ittermann, Tianye Jia, Mark Lathrop, Dirk Lanzerath, Claire Lawrence, Hervé Lemaitre, Katharina Lüdemann, Christine Macare, Catherine Mallik, Jean-François Mangin, Karl Mann, Jean-Luc Martinot, Eva Mennigen, Fabiana Mesquita de Carvahlo, Xavier Mignon, Ruben Miranda, Kathrin Müller, Frauke Nees, Charlotte Nymberg, Marie-Laure Paillere, Tomas Paus, Zdenka Pausova, Jean-Baptiste Poline, Luise Poustka, Michael Rapp, Gabriel Robert, Jan Reuter, Marcella Rietschel, Stephan Ripke, Trevor Robbins, Sarah Rodehacke, John Rogers, Alexander Romanowski, Barbara Ruggeri, Christine Schmäl, Dirk Schmidt, Sophia Schneider, MarkGunter Schumann, Florian Schubert, Yannick Schwartz, Michael Smolka, Wolfgang Sommer, Rainer Spanagel, Claudia Speiser, Tade Spranger, Alicia Stedman, Sabina Steiner, Dai Stephens, Nicole Strache, Andreas Ströhle, Maren Struve, Naresh Subramaniam, Lauren Topper, Henrik Walter, Robert Whelan, Steve Williams, Juliana Yacubian, Monica Zilbovicius, C Peng Wong, Steven Lubbe, Lourdes Martinez-Medina, Alinda Fernandes, Amir Tahmasebi

Affiliations

¹ Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany.
² Department of Social Genetic & Developmental Psychiatry, Institute of Psychiatry, King's College London, London, UK.
³ Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Square J5, 68159, Mannheim, Germany.
⁴ Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
⁵ Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
⁶ University Medical Centre Hamburg-Eppendorf, House W34, 3.OG, Martinistr. 52, 20246, Hamburg, Germany.
⁷ Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Square J5, Mannheim, Germany.
⁸ Department of Psychology, School of Social Sciences, University of Mannheim, 68131, Mannheim, Germany.
⁹ NeuroSpin, CEA, Université Paris-Saclay, F-91191, Gif-sur-Yvette, France.
¹⁰ Departments of Psychiatry and Psychology, University of Vermont, Burlington, VT, 05405, USA.
¹¹ Physikalisch-Technische Bundesanstalt (PTB), Abbestr. 2-12, Berlin, Germany.
¹² Institut National de la Santé et de la Recherche Médicale, INSERM Unit 1000 "Neuroimaging& Psychiatry", University Paris Sud, University Paris Descartes-Sorbonne Paris Cité, and Maison de Solenn, Paris, France.
¹³ Institut National de la Santé et de la Recherche Médicale, INSERM Unit 1000 "Neuroimaging & Psychiatry", University Paris Sud, University Paris Descartes, Sorbonne Université, and AP-HP, Department of Child and Adolescent Psychiatry, Pitié-Salpêtrière Hospital, Paris, France.
¹⁴ Rotman Research Institute, Baycrest and Departments of Psychology and Psychiatry, University of Toronto, Toronto, ON, M6A 2E1, Canada.
¹⁵ Department of Child and Adolescent Psychiatry and Psychotherapy, University Medical Centre Göttingen, von-Siebold-Str. 5, 37075, Göttingen, Germany.
¹⁶ Department of Psychiatry and Neuroimaging Center, TechnischeUniversität Dresden, Dresden, Germany.
¹⁷ School of Psychology and Global Brain Health Institute, Trinity College Dublin, Dublin, Ireland.
¹⁸ Berlin Institute of Health, Berlin, Germany.
¹⁹ Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany. andreas.heinz@charite.de.

^# Contributed equally.

PMID: 32601453
PMCID: PMC7577859
DOI: 10.1038/s41380-020-0822-5

Abstract

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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Conflict of interest statement

TB has served as an advisor or consultant to Bristol-Myers Squibb, DesitinArzneimittel, Eli Lilly, Medice, Novartis, Pfizer, Shire, UCB, and Vifor Pharma; he has received conference attendance support, conference support, or speaking fees from Eli Lilly, Janssen McNeil, Medice, Novartis, Shire, and UCB; and he is involved in clinical trials conducted by Eli Lilly, Novartis, and Shire; the present work is unrelated to these relationships. GB has received honoraria from General Electric Healthcare for teaching on scanner programming courses and acts as a consultant for IXICO. The other authors report no biomedical financial interests or potential conflicts of interest.

Figures

**Fig. 1. Selection process.**
Flow-chart of selection process of identified publications.

**Fig. 2. Effect of genetic variations on brain structure, function and behavior.**
Genes and epigenetic modifications associated with brain structure (hippocampus and putamen volume), functional activation (reward anticipation and feedback as elicited by the MID task; SST task) and behavior (alcohol consumption, nicotine and cannabis consumption).

See this image and copyright information in PMC

References

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The IMAGEN study: a decade of imaging genetics in adolescents

Collaborators

Affiliations

The IMAGEN study: a decade of imaging genetics in adolescents

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Figures

References

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Grants and funding

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Medical