Linked patterns of biological and environmental covariation with brain structure in adolescence: a population-based longitudinal study

doi:10.1038/s41380-020-0757-x

. 2021 Sep;26(9):4905-4918.

doi: 10.1038/s41380-020-0757-x. Epub 2020 May 22.

Linked patterns of biological and environmental covariation with brain structure in adolescence: a population-based longitudinal study

Amirhossein Modabbernia¹, Abraham Reichenberg^{1

2}, Alex Ing³, Dominik A Moser^{1

4}, Gaelle E Doucet¹, Eric Artiges^{5

6}, Tobias Banaschewski⁷, Gareth J Barker⁸, Andreas Becker⁹, Arun L W Bokde¹⁰, Erin Burke Quinlan¹¹, Sylvane Desrivières¹¹, Herta Flor^{12

13}, Juliane H Fröhner¹⁴, Hugh Garavan¹⁵, Penny Gowland¹⁶, Antoine Grigis¹⁷, Yvonne Grimmer⁷, Andreas Heinz¹⁸, Corinna Insensee⁹, Bernd Ittermann¹⁹, Jean-Luc Martinot²⁰, Marie-Laure Paillère Martinot^{21

22}, Sabina Millenet⁷, Frauke Nees^{7

12}, Dimitri Papadopoulos Orfanos¹⁷, Tomáš Paus²³, Jani Penttilä²⁴, Luise Poustka²⁵, Michael N Smolka¹⁴, Argyris Stringaris²⁶, Betteke M van Noort²⁷, Henrik Walter¹⁸, Robert Whelan²⁸, Gunter Schumann^{11

29

30

31}, Sophia Frangou^{32

33}; IMAGEN Consortium

Affiliations

¹ Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
² Department of Environmental Medicine & Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
³ Population Neuroscience and Precision Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
⁴ Institute of Psychology, University of Bern, Bern, Switzerland.
⁵ Institut National de la Santé et de la Recherche Médicale, INSERM Unit 1000 "Neuroimaging & Psychiatry", University Paris Saclay, University Paris Descartes - Sorbonne Paris Cité, Paris, France.
⁶ Psychiatry Department 91G16, Orsay Hospital, Orsay, France.
⁷ Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Square J5, 68159, Mannheim, Germany.
⁸ Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
⁹ Department of Child and Adolescent Psychiatry and Psychotherapy, University Medical Center, Göttingen, Germany.
¹⁰ Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
¹¹ Centre for Population Neuroscience and Precision Medicine (PONS), Institute of Psychiatry, Psychology & Neuroscience, SGDP Centre, King's College London, London, UK.
¹² Institute of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Square J5, Mannheim, Germany.
¹³ Department of Psychology, School of Social Sciences, University of Mannheim, 68131, Mannheim, Germany.
¹⁴ Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden, Germany.
¹⁵ Departments of Psychiatry and Psychology, University of Vermont, Burlington, VT, 05405, USA.
¹⁶ Sir Peter Mansfield Imaging Centre School of Physics and Astronomy, University of Nottingham, University Park, Nottingham, UK.
¹⁷ NeuroSpin, CEA, Université Paris-Saclay, 91191, Gif-sur-Yvette, France.
¹⁸ Department of Psychiatry and Psychotherapy CCM, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
¹⁹ Physikalisch-Technische Bundesanstalt (PTB), Braunschweig/Berlin, Germany.
²⁰ Institut National de la Santé et de la Recherche INSERM Unit 1000 "Neuroimaging & Paris Saclay, University Paris Descartes and Maison de Solenn, Paris, France.
²¹ Institut National de la Santé et de la Recherche Médicale, INSERM Unit 1000 "Neuroimaging & Psychiatry", University Paris Sacaly, University Paris Descartes, Paris, France.
²² AP-HP.Sorbonne Université, Department of Child and Adolescent Psychiatry, Pitié-Salpêtrière Hospital, Paris, France.
²³ Bloorview Research Institute, Holland Bloorview Kids Rehabilitation Hospital and Departments of Psychology and Psychiatry, University of Toronto, Toronto, ON, M6A 2E1, Canada.
²⁴ Department of Social and Health Care, Psychosocial Services Adolescent Outpatient Clinic Kauppakatu 14, Lahti, Finland.
²⁵ Department of Child and Adolescent Psychiatry and Psychotherapy, University Medical Centre Göttingen, von-Siebold-Str., 537075, Göttingen, Germany.
²⁶ National Institute of Mental Health/NIH, 15K North Drive, Bethesda, MD, 20892, USA.
²⁷ MSB Medical School Berlin, Hochschule für Gesundheit und Medizin, Siemens Villa, Berlin, Germany.
²⁸ School of Psychology and Global Brain Health Institute, Trinity College Dublin, Dublin, Ireland.
²⁹ PONS Research Group, Department of Psychiatry and Psychotherapy, Campus Charite Mitte, Humboldt University, Berlin, Germany.
³⁰ Leibniz Institute for Neurobiology, Magdeburg, Germany.
³¹ Institute for Science and Technology of Brain-Inspired Intelligence (ISTBI), Fudan University, Shanghai, P.R. China.
³² Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA. sophia.frangou@mssm.edu.
³³ Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada. sophia.frangou@mssm.edu.

PMID: 32444868
PMCID: PMC7981783
DOI: 10.1038/s41380-020-0757-x

Linked patterns of biological and environmental covariation with brain structure in adolescence: a population-based longitudinal study

Amirhossein Modabbernia et al. Mol Psychiatry. 2021 Sep.

. 2021 Sep;26(9):4905-4918.

doi: 10.1038/s41380-020-0757-x. Epub 2020 May 22.

Authors

Affiliations

¹ Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
² Department of Environmental Medicine & Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
³ Population Neuroscience and Precision Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
⁴ Institute of Psychology, University of Bern, Bern, Switzerland.
⁵ Institut National de la Santé et de la Recherche Médicale, INSERM Unit 1000 "Neuroimaging & Psychiatry", University Paris Saclay, University Paris Descartes - Sorbonne Paris Cité, Paris, France.
⁶ Psychiatry Department 91G16, Orsay Hospital, Orsay, France.
⁷ Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Square J5, 68159, Mannheim, Germany.
⁸ Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
⁹ Department of Child and Adolescent Psychiatry and Psychotherapy, University Medical Center, Göttingen, Germany.
¹⁰ Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
¹¹ Centre for Population Neuroscience and Precision Medicine (PONS), Institute of Psychiatry, Psychology & Neuroscience, SGDP Centre, King's College London, London, UK.
¹² Institute of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Square J5, Mannheim, Germany.
¹³ Department of Psychology, School of Social Sciences, University of Mannheim, 68131, Mannheim, Germany.
¹⁴ Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden, Germany.
¹⁵ Departments of Psychiatry and Psychology, University of Vermont, Burlington, VT, 05405, USA.
¹⁶ Sir Peter Mansfield Imaging Centre School of Physics and Astronomy, University of Nottingham, University Park, Nottingham, UK.
¹⁷ NeuroSpin, CEA, Université Paris-Saclay, 91191, Gif-sur-Yvette, France.
¹⁸ Department of Psychiatry and Psychotherapy CCM, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
¹⁹ Physikalisch-Technische Bundesanstalt (PTB), Braunschweig/Berlin, Germany.
²⁰ Institut National de la Santé et de la Recherche INSERM Unit 1000 "Neuroimaging & Paris Saclay, University Paris Descartes and Maison de Solenn, Paris, France.
²¹ Institut National de la Santé et de la Recherche Médicale, INSERM Unit 1000 "Neuroimaging & Psychiatry", University Paris Sacaly, University Paris Descartes, Paris, France.
²² AP-HP.Sorbonne Université, Department of Child and Adolescent Psychiatry, Pitié-Salpêtrière Hospital, Paris, France.
²³ Bloorview Research Institute, Holland Bloorview Kids Rehabilitation Hospital and Departments of Psychology and Psychiatry, University of Toronto, Toronto, ON, M6A 2E1, Canada.
²⁴ Department of Social and Health Care, Psychosocial Services Adolescent Outpatient Clinic Kauppakatu 14, Lahti, Finland.
²⁵ Department of Child and Adolescent Psychiatry and Psychotherapy, University Medical Centre Göttingen, von-Siebold-Str., 537075, Göttingen, Germany.
²⁶ National Institute of Mental Health/NIH, 15K North Drive, Bethesda, MD, 20892, USA.
²⁷ MSB Medical School Berlin, Hochschule für Gesundheit und Medizin, Siemens Villa, Berlin, Germany.
²⁸ School of Psychology and Global Brain Health Institute, Trinity College Dublin, Dublin, Ireland.
²⁹ PONS Research Group, Department of Psychiatry and Psychotherapy, Campus Charite Mitte, Humboldt University, Berlin, Germany.
³⁰ Leibniz Institute for Neurobiology, Magdeburg, Germany.
³¹ Institute for Science and Technology of Brain-Inspired Intelligence (ISTBI), Fudan University, Shanghai, P.R. China.
³² Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA. sophia.frangou@mssm.edu.
³³ Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada. sophia.frangou@mssm.edu.

PMID: 32444868
PMCID: PMC7981783
DOI: 10.1038/s41380-020-0757-x

Abstract

Adolescence is a period of major brain reorganization shaped by biologically timed and by environmental factors. We sought to discover linked patterns of covariation between brain structural development and a wide array of these factors by leveraging data from the IMAGEN study, a longitudinal population-based cohort of adolescents. Brain structural measures and a comprehensive array of non-imaging features (relating to demographic, anthropometric, and psychosocial characteristics) were available on 1476 IMAGEN participants aged 14 years and from a subsample reassessed at age 19 years (n = 714). We applied sparse canonical correlation analyses (sCCA) to the cross-sectional and longitudinal data to extract modes with maximum covariation between neuroimaging and non-imaging measures. Separate sCCAs for cortical thickness, cortical surface area and subcortical volumes confirmed that each imaging phenotype was correlated with non-imaging features (sCCA r range: 0.30-0.65, all P_FDR < 0.001). Total intracranial volume and global measures of cortical thickness and surface area had the highest canonical cross-loadings (|ρ| = 0.31-0.61). Age, physical growth and sex had the highest association with adolescent brain structure (|ρ| = 0.24-0.62); at baseline, further significant positive associations were noted for cognitive measures while negative associations were observed at both time points for prenatal parental smoking, life events, and negative affect and substance use in youth (|ρ| = 0.10-0.23). Sex, physical growth and age are the dominant influences on adolescent brain development. We highlight the persistent negative influences of prenatal parental smoking and youth substance use as they are modifiable and of relevance for public health initiatives.

PubMed Disclaimer

Conflict of interest statement

TB served in an advisory or consultancy role for Lundbeck, Medice, Neurim Pharmaceuticals, Oberberg GmbH, Shire. He received conference support or speaker’s fee by Lilly, Medice, Novartis and Shire. He has been involved in clinical trials conducted by Shire & Viforpharma. He received royalities from Hogrefe, Kohlhammer, CIP Medien, Oxford University Press. The present work is unrelated to the above grants and relationships. GJB has received honoraria from General Electric Healthcare for teaching on scanner programming courses. The other authors report no biomedical financial interests or potential conflicts of interest.

Figures

**Fig. 1. Sparse canonical correlation analysis (sCCA) for baseline and developmental change in cortical thickness.**
Upper panel: Baseline: a First canonical correlation coefficient. b Canonical cross-loadings for non-imaging variables. c Canonical cross-loadings for imaging variables. Lower panel: Developmental change: d First canonical correlation coefficient. e Canonical cross-loadings for non-imaging variables. f Canonical cross-loadings for imaging variables. LEQ Life Event Questionnaire, SURPS Substance Use Risk Profile Scale.

**Fig. 2. Sparse canonical correlation analysis (sCCA) for baseline and developmental change in cortical surface area.**
Upper panel: Baseline: a First canonical correlation coefficient. b Canonical cross-loadings for non-imaging variables. c Canonical cross-loadings for imaging variables. Lower panel: Developmental change: d First canonical correlation coefficient. e Canonical cross-loadings for non-imaging variables. f Canonical cross-loadings for imaging variables. LEQ Life Event Questionnaire, SURPS Substance Use Risk Profile Scale, NEO NEO-Five Factor Personality Inventory.

**Fig. 3. Sparse canonical correlation analysis (sCCA) for baseline and developmental change in subcortical volumes.**
Upper panel: Baseline: a First canonical correlation coefficient. b Canonical cross-loadings for non-imaging variables. c Canonical cross-loadings for imaging variables. Lower panel: Developmental change: d First canonical correlation coefficient. e Canonical cross-loadings for non-imaging variables. f Canonical cross-loadings for imaging variables. LEQ Life Event Questionnaire, SURPS Substance Use Risk Profile Scale, NEO NEO-Five Factor Personality Inventory.

See this image and copyright information in PMC

Cited by

Prenatal Tobacco Exposure, Brain Subcortical Volumes, and Gray-White Matter Contrast.
Puga TB, Doucet GE, Thiel GE, Theye E, Dai HD. Puga TB, et al. JAMA Netw Open. 2024 Dec 2;7(12):e2451786. doi: 10.1001/jamanetworkopen.2024.51786. JAMA Netw Open. 2024. PMID: 39699892 Free PMC article.
Association of Maternal Smoking during Pregnancy with Neurophysiological and ADHD-Related Outcomes in School-Aged Children.
Jansone K, Eichler A, Fasching PA, Kornhuber J, Kaiser A, Millenet S, Banaschewski T, Nees F, On Behalf Of The Imac-Mind Consortium. Jansone K, et al. Int J Environ Res Public Health. 2023 Mar 7;20(6):4716. doi: 10.3390/ijerph20064716. Int J Environ Res Public Health. 2023. PMID: 36981624 Free PMC article.
Multivariate Patterns of Brain-Behavior-Environment Associations in the Adolescent Brain and Cognitive Development Study.
Modabbernia A, Janiri D, Doucet GE, Reichenberg A, Frangou S. Modabbernia A, et al. Biol Psychiatry. 2021 Mar 1;89(5):510-520. doi: 10.1016/j.biopsych.2020.08.014. Epub 2020 Aug 24. Biol Psychiatry. 2021. PMID: 33109338 Free PMC article.
A Shared Multivariate Brain-Behavior Relationship in a Transdiagnostic Sample of Adolescents.
Bashford-Largo J, Nakua H, Blair RJR, Dominguez A, Hatch M, Blair KS, Dobbertin M, Ameis S, Bajaj S. Bashford-Largo J, et al. Biol Psychiatry Cogn Neurosci Neuroimaging. 2024 Apr;9(4):377-386. doi: 10.1016/j.bpsc.2023.07.015. Epub 2023 Aug 11. Biol Psychiatry Cogn Neurosci Neuroimaging. 2024. PMID: 37572936 Free PMC article.
Examining attachment, cortisol secretion, and cognitive neurodevelopment in preschoolers and its predictive value for telomere length at age seven.
de Mendonça Filho EJ, Frechette A, Pokhvisneva I, Arcego DM, Barth B, Tejada CV, Sassi R, Wazana A, Atkinson L, Meaney MJ, Silveira PP. de Mendonça Filho EJ, et al. Front Behav Neurosci. 2022 Oct 13;16:954977. doi: 10.3389/fnbeh.2022.954977. eCollection 2022. Front Behav Neurosci. 2022. PMID: 36311861 Free PMC article.

See all "Cited by" articles

References

1. Demetriou A, Christou C, Spanoudis G, Platsidou M. The development of mental processing: efficiency, working memory, and thinking. Monogr Soc Res Child Dev. 2002;67:i–viii. - PubMed
1. Blakemore SJ, Burnett S, Dahl RE. The role of puberty in the developing adolescent brain. Hum Brain Mapp. 2010;31:926–33. - PMC - PubMed
1. Blakemore SJ, Choudhury S. Development of the adolescent brain: implications for executive function and social cognition. J Child Psychol Psychiatry. 2006;47:296–312. - PubMed
1. Paus T, Keshavan M, Giedd JN. Why do many psychiatric disorders emerge during adolescence? Nat Rev Neurosci. 2008;9:947–57. - PMC - PubMed
1. Andersen SL. Trajectories of brain development: point of vulnerability or window of opportunity? Neurosci Biobehav Rev. 2003;27:3–18. - PubMed

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Grants and funding

LinkOut - more resources

Full Text Sources
Medical
- MedlinePlus Health Information
Research Materials
- NCI CPTC Antibody Characterization Program

[1] Demetriou A, Christou C, Spanoudis G, Platsidou M. The development of mental processing: efficiency, working memory, and thinking. Monogr Soc Res Child Dev. 2002;67:i–viii. - PubMed

[2] Demetriou A, Christou C, Spanoudis G, Platsidou M. The development of mental processing: efficiency, working memory, and thinking. Monogr Soc Res Child Dev. 2002;67:i–viii. - PubMed

[3] Blakemore SJ, Burnett S, Dahl RE. The role of puberty in the developing adolescent brain. Hum Brain Mapp. 2010;31:926–33. - PMC - PubMed

[4] Blakemore SJ, Burnett S, Dahl RE. The role of puberty in the developing adolescent brain. Hum Brain Mapp. 2010;31:926–33. - PMC - PubMed

[5] Blakemore SJ, Choudhury S. Development of the adolescent brain: implications for executive function and social cognition. J Child Psychol Psychiatry. 2006;47:296–312. - PubMed

[6] Blakemore SJ, Choudhury S. Development of the adolescent brain: implications for executive function and social cognition. J Child Psychol Psychiatry. 2006;47:296–312. - PubMed

[7] Paus T, Keshavan M, Giedd JN. Why do many psychiatric disorders emerge during adolescence? Nat Rev Neurosci. 2008;9:947–57. - PMC - PubMed

[8] Paus T, Keshavan M, Giedd JN. Why do many psychiatric disorders emerge during adolescence? Nat Rev Neurosci. 2008;9:947–57. - PMC - PubMed

[9] Andersen SL. Trajectories of brain development: point of vulnerability or window of opportunity? Neurosci Biobehav Rev. 2003;27:3–18. - PubMed

[10] Andersen SL. Trajectories of brain development: point of vulnerability or window of opportunity? Neurosci Biobehav Rev. 2003;27:3–18. - PubMed

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

Linked patterns of biological and environmental covariation with brain structure in adolescence: a population-based longitudinal study

Affiliations

Linked patterns of biological and environmental covariation with brain structure in adolescence: a population-based longitudinal study

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

Similar articles

Cited by

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Research Materials