Identifying biological markers for improved precision medicine in psychiatry

Erin Burke Quinlan¹, Tobias Banaschewski², Gareth J Barker³, Arun L W Bokde⁴, Uli Bromberg⁵, Christian Büchel⁵, Sylvane Desrivières⁶, Herta Flor^{7

8}, Vincent Frouin⁹, Hugh Garavan¹⁰, Andreas Heinz¹¹, Rüdiger Brühl¹², Jean-Luc Martinot¹³, Marie-Laure Paillère Martinot¹⁴, Frauke Nees^{2

5}, Dimitri Papadopoulos Orfanos⁹, Tomáš Paus¹⁵, Luise Poustka¹⁶, Sarah Hohmann², Michael N Smolka¹⁷, Juliane H Fröhner¹⁷, Henrik Walter¹¹, Robert Whelan¹⁸, Gunter Schumann^{19

20}; IMAGEN Consortium

Affiliations

¹ Centre for Population Neuroscience and Precision Medicine (PONS), Institute of Psychiatry, Psychology & Neuroscience, SGDP Centre, King's College London, London, UK. erin.quinlan@kcl.ac.uk.
² Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Square J5, 68159, Mannheim, Germany.
³ Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
⁴ Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
⁵ University Medical Centre Hamburg-Eppendorf, House W34, 3.OG, Martinistr. 52, 20246, Hamburg, Germany.
⁶ Centre for Population Neuroscience and Precision Medicine (PONS), Institute of Psychiatry, Psychology & Neuroscience, SGDP Centre, King's College London, London, UK.
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 Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité, Universitätsmedizin Berlin, Charitéplatz 1, Berlin, Germany.
¹² Physikalisch-Technische Bundesanstalt (PTB), Braunschweig and Berlin, Germany [or depending on journal requirements can be: Physikalisch-Technische Bundesanstalt (PTB), Abbestr. 2 - 12, Berlin, Germany.
¹³ Institut National de la Santé et de la Recherche Médicale, INSERM Unit 1000 "Neuroimaging & Psychiatry", University Paris Saclay, University Paris Descartes - Sorbonne Paris Cité; Maison de Solenn, Paris, France.
¹⁴ Institut National de la Santé et de la Recherche Médicale, INSERM Unit 1000 "Neuroimaging & Psychiatry", University Paris Sud - Paris Saclay, University Paris Descartes; and AP-HP.Sorbonne Université, Department of Child and Adolescent Psychiatry, Pitié-Salpêtrière Hospital, Paris, France.
¹⁵ Bloorview Research Institute, Holland Bloorview Kids Rehabilitation, Departments of Psychology and Psychiatry, University of Toronto, Toronto, ON, M6A 2E1, Canada.
¹⁶ Department of Child and Adolescent Psychiatry and Psychotherapy, University Medical Centre Göttingen, von-Siebold-Str. 5, 37075, Göttingen, Germany.
¹⁷ Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden, Germany.
¹⁸ School of Psychology and Global Brain Health Institute, Trinity College, Dublin, Ireland.
¹⁹ PONS Research Group, Department of Psychiatry and Psychotherapy, Campus Charite Mitte, Humboldt University, Berlin and Leibniz Institute for Neurobiology, Magdeburg, Germany.
²⁰ Institute for Science and Technology of Brain-inspired Intelligence (ISTBI), Fudan University, Shanghai, PR China.

PMID: 31676814
PMCID: PMC6978138
DOI: 10.1038/s41380-019-0555-5

Review

Identifying biological markers for improved precision medicine in psychiatry

Erin Burke Quinlan et al. Mol Psychiatry. 2020 Feb.

. 2020 Feb;25(2):243-253.

doi: 10.1038/s41380-019-0555-5. Epub 2019 Nov 1.

Authors

Affiliations

¹ Centre for Population Neuroscience and Precision Medicine (PONS), Institute of Psychiatry, Psychology & Neuroscience, SGDP Centre, King's College London, London, UK. erin.quinlan@kcl.ac.uk.
² Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Square J5, 68159, Mannheim, Germany.
³ Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
⁴ Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
⁵ University Medical Centre Hamburg-Eppendorf, House W34, 3.OG, Martinistr. 52, 20246, Hamburg, Germany.
⁶ Centre for Population Neuroscience and Precision Medicine (PONS), Institute of Psychiatry, Psychology & Neuroscience, SGDP Centre, King's College London, London, UK.
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 Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité, Universitätsmedizin Berlin, Charitéplatz 1, Berlin, Germany.
¹² Physikalisch-Technische Bundesanstalt (PTB), Braunschweig and Berlin, Germany [or depending on journal requirements can be: Physikalisch-Technische Bundesanstalt (PTB), Abbestr. 2 - 12, Berlin, Germany.
¹³ Institut National de la Santé et de la Recherche Médicale, INSERM Unit 1000 "Neuroimaging & Psychiatry", University Paris Saclay, University Paris Descartes - Sorbonne Paris Cité; Maison de Solenn, Paris, France.
¹⁴ Institut National de la Santé et de la Recherche Médicale, INSERM Unit 1000 "Neuroimaging & Psychiatry", University Paris Sud - Paris Saclay, University Paris Descartes; and AP-HP.Sorbonne Université, Department of Child and Adolescent Psychiatry, Pitié-Salpêtrière Hospital, Paris, France.
¹⁵ Bloorview Research Institute, Holland Bloorview Kids Rehabilitation, Departments of Psychology and Psychiatry, University of Toronto, Toronto, ON, M6A 2E1, Canada.
¹⁶ Department of Child and Adolescent Psychiatry and Psychotherapy, University Medical Centre Göttingen, von-Siebold-Str. 5, 37075, Göttingen, Germany.
¹⁷ Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden, Germany.
¹⁸ School of Psychology and Global Brain Health Institute, Trinity College, Dublin, Ireland.
¹⁹ PONS Research Group, Department of Psychiatry and Psychotherapy, Campus Charite Mitte, Humboldt University, Berlin and Leibniz Institute for Neurobiology, Magdeburg, Germany.
²⁰ Institute for Science and Technology of Brain-inspired Intelligence (ISTBI), Fudan University, Shanghai, PR China.

PMID: 31676814
PMCID: PMC6978138
DOI: 10.1038/s41380-019-0555-5

Abstract

Mental disorders represent an increasing personal and financial burden and yet treatment development has stagnated in recent decades. Current disease classifications do not reflect psychobiological mechanisms of psychopathology, nor the complex interplay of genetic and environmental factors, likely contributing to this stagnation. Ten years ago, the longitudinal IMAGEN study was designed to comprehensively incorporate neuroimaging, genetics, and environmental factors to investigate the neural basis of reinforcement-related behavior in normal adolescent development and psychopathology. In this article, we describe how insights into the psychobiological mechanisms of clinically relevant symptoms obtained by innovative integrative methodologies applied in IMAGEN have informed our current and future research aims. These aims include the identification of symptom groups that are based on shared psychobiological mechanisms and the development of markers that predict disease course and treatment response in clinical groups. These improvements in precision medicine will be achieved, in part, by employing novel methodological tools that refine the biological systems we target. We will also implement our approach in low- and medium-income countries to understand how distinct environmental, socioeconomic, and cultural conditions influence the development of psychopathology. Together, IMAGEN and related initiatives strive to reduce the burden of mental disorders by developing precision medicine approaches globally.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest

Dr. Banaschewski has served as an advisor or consultant to Actelion, Hexal Pharma,Bristol-Myers Squibb, Desitin Arzneimittel, Eli Lilly, Lundbeck, Medice, Neurim Pharmaceuticals, Novartis, Pfizer, and Shire, UCB, and Vifor Pharma; he has received conference attendance support, conference support, or speaking fees from Eli Lilly, Janssen McNeil, Medice, Novartis, and Shire, and UCB; and he is involved in clinical trials conducted by Eli Lilly, Novartis, and Shire and Viforpharma; he received royalities from Hogrefe, Kohlhammer, CIP Medien, Oxford University Press; the present work is unrelated to these relationships. Dr. Barker 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

**Figure 1**
Classification accuracy of variables from six domains predicting age 16 binge drinking using data from age 14. Position on the x-axis represents the correlation between each variable and binge drinking. Based on data from Whelan *et a*l 2014 . CANTAB = Cambridge Neuropsychological Test Automated Battery; ESPAD = European School Survey Project on Alcohol and Other Drugs; GMV = gray matter volume; LEQ = Life Events Questionnaire; MID = fMRI Monetary Incentive Delay task; NEO = NEO Personality Inventory; PBQ = Pregnancy and Birth Questionnaire; RT = reaction time; SURPS = Substance Use Risk Profile Scale; SST = fMRI Stop Signal Task; SWM = Spatial Working Memory; TCI = Temperament and Character Inventory.

See this image and copyright information in PMC

References

1. Whiteford HA, Degenhardt L, Rehm J, Baxter AJ, Ferrari AJ, Erskine HE, et al. Global burden of disease attributable to mental and substance use disorders: findings from the Global Burden of Disease Study 2010. Lancet. 2013;382(9904):1575–1586. - PubMed
1. Gustavsson A, Svensson M, Jacobi F, Allgulander C, Alonso J, Beghi E, et al. Cost of disorders of the brain in Europe 2010. Eur Neuropsychopharmacol. 2011;21(10):718–779. - PubMed
1. Trautmann S, Rehm J, Wittchen HU. The economic costs of mental disorders: Do our societies react appropriately to the burden of mental disorders? EMBO Rep. 2016;17(9):1245–1249. - PMC - PubMed
1. Pangalos MN, Schechter LE, Hurko O. Drug development for CNS disorders: strategies for balancing risk and reducing attrition. Nat Rev Drug Discov. 2007;6(7):521–532. - PubMed
1. Perry CJ, Lawrence AJ. Hurdles in Basic Science Translation. Front Pharmacol. 2017;8:478. - PMC - PubMed

Publication types

Actions
Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Identifying biological markers for improved precision medicine in psychiatry

Affiliations

Identifying biological markers for improved precision medicine in psychiatry

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Medical