Longitudinal associations of structural and functional brain connectivity with dimensions of psychopathology in adolescence

Lucy Vanes¹, Divyangana Rakesh², Tobias Banaschewski³, Arun L W Bodke⁴, Sylvane Desrivières⁵, Herta Flor⁶, Hugh Garavan⁷, Penny Gowland⁸, Antoine Grigis⁹, Andreas Heinz¹⁰, Herve Lemaitre¹¹, Jean-Luc Martinot¹², Marie-Laure Paillère Martinot¹³, Eric Artiges¹⁴, Frauke Nees¹⁵, Dimitri Papadopoulos Orfanos¹⁶, Luise Poustka¹⁷, Michael N Smolka¹⁸, Sarah Hohmann³, Nathalie Holz³, Nilakshi Vaidya¹⁹, Henrik Walter²⁰, Robert Whelan²¹, Gunter Schumann²², Gareth J Barker²; IMAGEN Consortium

Collaborators, Affiliations

Collaborators

IMAGEN Consortium:
Michael Rapp, Eric Artiges, Christine Bach, Tomas Paus, Alexis Barbot, Gareth Barker, Arun Bokde, Nora Vetter, Christian Büchel, Anna Cattrell, Penny Gowland, Hans Crombag, Katharina Czech, Jeffrey Dalley, Benjamin Decideur, Tade Spranger, Tamzin Ripley, Nadja Heym, Herta Flor, Wolfgang Sommer, Birgit Fuchs, Jürgen Gallinat, Hugh Garavan, Rainer Spanagel, Mehri Kaviani, Bert Heinrichs, Andreas Heinz, Naresh Subramaniam, Tianye Jia, Albrecht Ihlenfeld, Bernd Ittermann, Tobias Banaschewski, Jennifer Jones, Arno Klaassen, Christophe Lalanne, Dirk Lanzerath, Claire Lawrence, Hervé Lemaitre, Sylvane Desrivieres, Catherine Mallik, Karl Mann, Adam Mar, Lourdes Martinez-Medina, Jean-Luc Martinot, Fabiana Mesquita de Carvahlo, Yannick Schwartz, Ruediger Bruehl, Kathrin Müller, Frauke Nees, Charlotte Nymberg, Mark Lathrop, Trevor Robbins, Zdenka Pausova, Jani Pentilla, Francesca Biondo, Jean-Baptiste Poline, Sarah Hohmann, Luise Poustka, Sabina Millenet, Michael Smolka, Juliane Fröhner, Maren Struve, Steve Williams, Thomas Hübner, Uli Bromberg, Semiha Aydin, John Rogers, Alexander Romanowski, Christine Schmäl, Dirk Schmidt, Stephan Ripke, Mercedes Arroyo, Florian Schubert, Yolanda Pena-Oliver, Mira Fauth-Bühler, Xavier Mignon, Robert Whelan, Claudia Speiser, Tahmine Fadai, Dai Stephens, Andreas Ströhle, Marie-Laure Paillere, Nicole Strache, David Theobald, Sarah Jurk, Helene Vulser, Ruben Miranda, Juliana Yacubilin, Vincent Frouin, Alexander Genauck, Caroline Parchetka, Isabel Gemmeke, Johann Kruschwitz, Katharina WeiB, Henrik Walter, Jianfeng Feng, Dimitri Papadopoulos, Irina Filippi, Alex Ing, Barbara Ruggeri, Bing Xu, Christine Macare, Congying Chu, Eanna Hanratty, Erin Burke Quinlan, Gabriel Robert, Gunter Schumann, Tao Yu, Veronika Ziesch, Alicia Stedman

Affiliations

¹ Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom. Electronic address: lucy.vanes@kcl.ac.uk.
² Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.
³ Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Square J5, 68159 Mannheim, Germany; German Center for Mental Health (DZPG), partner site Mannheim-Heidelberg-Ulm.
⁴ Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
⁵ Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.
⁶ Institute of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Square J5, Mannheim, Germany; Department of Psychology, School of Social Sciences, University of Mannheim, 68131 Mannheim, Germany.
⁷ Departments of Psychiatry and Psychology, University of Vermont, 05405 Burlington, Vermont, USA.
⁸ Sir Peter Mansfield Imaging Centre School of Physics and Astronomy, University of Nottingham, University Park, Nottingham, United Kingdom.
⁹ NeuroSpin, CEA, Université Paris-Saclay, F-91191 Gif-sur-Yvette, France.
¹⁰ Department of Psychiatry and Psychotherapy, University of Tübingen, Germany; German Center for Mental Health (DZPG), Site Tübingen, Germany.
¹¹ NeuroSpin, CEA, Université Paris-Saclay, F-91191 Gif-sur-Yvette, France; Institut des Maladies Neurodégénératives, UMR 5293, CNRS, CEA, Université de Bordeaux, 33076 Bordeaux, France.
¹² Institut National de la Santé et de la Recherce Médicale, INSERM U A10 "Trajectoires développementales & psychiatrie", University Paris-Saclay, Ecole Normale Supérieure Paris-Saclay, CNRS; Centre Borelli, Gif-sur-Yvette, France.
¹³ Institut National de la Santé et de la Recherce Médicale, INSERM U A10 "Trajectoires développementales & psychiatrie", University Paris-Saclay, Ecole Normale Supérieure Paris-Saclay, CNRS; Centre Borelli, Gif-sur-Yvette, France; AP-HP. Sorbonne Université, Department of Child and Adolescent Psychiatry, Pitié-Salpêtrière Hospital, Paris, France.
¹⁴ Institut National de la Santé et de la Recherce Médicale, INSERM U A10 "Trajectoires développementales & psychiatrie", University Paris-Saclay, Ecole Normale Supérieure Paris-Saclay, CNRS; Centre Borelli, Gif-sur-Yvette, France; Psychiatry Department, EPS Barthélémy Durand, Etampes, France.
¹⁵ Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Square J5, 68159 Mannheim, Germany; German Center for Mental Health (DZPG), partner site Mannheim-Heidelberg-Ulm; Institute of Medical Psychology and Medical Sociology, University Medical Center Schleswig Holstein, Kiel University, Kiel, Germany.
¹⁶ Department of Psychology, School of Social Sciences, University of Mannheim, 68131 Mannheim, Germany.
¹⁷ Department of Child and Adolescent Psychiatry, Center for Psychosocial Medicine, University Hospital Heidelberg, Heidelberg, Germany.
¹⁸ Department of Psychiatry and Psychotherapy, Technische Universität Dresden, Dresden, Germany.
¹⁹ Centre for Population Neuroscience and Stratified Medicine (PONS), Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Germany.
²⁰ 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.
²¹ School of Psychology and Global Brain Health Institute, Trinity College Dublin, Ireland.
²² Centre for Population Neuroscience and Stratified Medicine (PONS), Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Germany; Centre for Population Neuroscience and Precision Medicine (PONS), Institute for Science and Technology of Brain-inspired Intelligence (ISTBI), Fudan University, Shanghai, China.

PMID: 41005664
DOI: 10.1016/j.bpsc.2025.09.015

Free article

Longitudinal associations of structural and functional brain connectivity with dimensions of psychopathology in adolescence

Lucy Vanes et al. Biol Psychiatry Cogn Neurosci Neuroimaging. 2025.

Free article

. 2025 Sep 24:S2451-9022(25)00293-9.

doi: 10.1016/j.bpsc.2025.09.015. Online ahead of print.

Authors

Collaborators

IMAGEN Consortium:
Michael Rapp, Eric Artiges, Christine Bach, Tomas Paus, Alexis Barbot, Gareth Barker, Arun Bokde, Nora Vetter, Christian Büchel, Anna Cattrell, Penny Gowland, Hans Crombag, Katharina Czech, Jeffrey Dalley, Benjamin Decideur, Tade Spranger, Tamzin Ripley, Nadja Heym, Herta Flor, Wolfgang Sommer, Birgit Fuchs, Jürgen Gallinat, Hugh Garavan, Rainer Spanagel, Mehri Kaviani, Bert Heinrichs, Andreas Heinz, Naresh Subramaniam, Tianye Jia, Albrecht Ihlenfeld, Bernd Ittermann, Tobias Banaschewski, Jennifer Jones, Arno Klaassen, Christophe Lalanne, Dirk Lanzerath, Claire Lawrence, Hervé Lemaitre, Sylvane Desrivieres, Catherine Mallik, Karl Mann, Adam Mar, Lourdes Martinez-Medina, Jean-Luc Martinot, Fabiana Mesquita de Carvahlo, Yannick Schwartz, Ruediger Bruehl, Kathrin Müller, Frauke Nees, Charlotte Nymberg, Mark Lathrop, Trevor Robbins, Zdenka Pausova, Jani Pentilla, Francesca Biondo, Jean-Baptiste Poline, Sarah Hohmann, Luise Poustka, Sabina Millenet, Michael Smolka, Juliane Fröhner, Maren Struve, Steve Williams, Thomas Hübner, Uli Bromberg, Semiha Aydin, John Rogers, Alexander Romanowski, Christine Schmäl, Dirk Schmidt, Stephan Ripke, Mercedes Arroyo, Florian Schubert, Yolanda Pena-Oliver, Mira Fauth-Bühler, Xavier Mignon, Robert Whelan, Claudia Speiser, Tahmine Fadai, Dai Stephens, Andreas Ströhle, Marie-Laure Paillere, Nicole Strache, David Theobald, Sarah Jurk, Helene Vulser, Ruben Miranda, Juliana Yacubilin, Vincent Frouin, Alexander Genauck, Caroline Parchetka, Isabel Gemmeke, Johann Kruschwitz, Katharina WeiB, Henrik Walter, Jianfeng Feng, Dimitri Papadopoulos, Irina Filippi, Alex Ing, Barbara Ruggeri, Bing Xu, Christine Macare, Congying Chu, Eanna Hanratty, Erin Burke Quinlan, Gabriel Robert, Gunter Schumann, Tao Yu, Veronika Ziesch, Alicia Stedman

Affiliations

¹ Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom. Electronic address: lucy.vanes@kcl.ac.uk.
² Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.
³ Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Square J5, 68159 Mannheim, Germany; German Center for Mental Health (DZPG), partner site Mannheim-Heidelberg-Ulm.
⁴ Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
⁵ Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.
⁶ Institute of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Square J5, Mannheim, Germany; Department of Psychology, School of Social Sciences, University of Mannheim, 68131 Mannheim, Germany.
⁷ Departments of Psychiatry and Psychology, University of Vermont, 05405 Burlington, Vermont, USA.
⁸ Sir Peter Mansfield Imaging Centre School of Physics and Astronomy, University of Nottingham, University Park, Nottingham, United Kingdom.
⁹ NeuroSpin, CEA, Université Paris-Saclay, F-91191 Gif-sur-Yvette, France.
¹⁰ Department of Psychiatry and Psychotherapy, University of Tübingen, Germany; German Center for Mental Health (DZPG), Site Tübingen, Germany.
¹¹ NeuroSpin, CEA, Université Paris-Saclay, F-91191 Gif-sur-Yvette, France; Institut des Maladies Neurodégénératives, UMR 5293, CNRS, CEA, Université de Bordeaux, 33076 Bordeaux, France.
¹² Institut National de la Santé et de la Recherce Médicale, INSERM U A10 "Trajectoires développementales & psychiatrie", University Paris-Saclay, Ecole Normale Supérieure Paris-Saclay, CNRS; Centre Borelli, Gif-sur-Yvette, France.
¹³ Institut National de la Santé et de la Recherce Médicale, INSERM U A10 "Trajectoires développementales & psychiatrie", University Paris-Saclay, Ecole Normale Supérieure Paris-Saclay, CNRS; Centre Borelli, Gif-sur-Yvette, France; AP-HP. Sorbonne Université, Department of Child and Adolescent Psychiatry, Pitié-Salpêtrière Hospital, Paris, France.
¹⁴ Institut National de la Santé et de la Recherce Médicale, INSERM U A10 "Trajectoires développementales & psychiatrie", University Paris-Saclay, Ecole Normale Supérieure Paris-Saclay, CNRS; Centre Borelli, Gif-sur-Yvette, France; Psychiatry Department, EPS Barthélémy Durand, Etampes, France.
¹⁵ Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Square J5, 68159 Mannheim, Germany; German Center for Mental Health (DZPG), partner site Mannheim-Heidelberg-Ulm; Institute of Medical Psychology and Medical Sociology, University Medical Center Schleswig Holstein, Kiel University, Kiel, Germany.
¹⁶ Department of Psychology, School of Social Sciences, University of Mannheim, 68131 Mannheim, Germany.
¹⁷ Department of Child and Adolescent Psychiatry, Center for Psychosocial Medicine, University Hospital Heidelberg, Heidelberg, Germany.
¹⁸ Department of Psychiatry and Psychotherapy, Technische Universität Dresden, Dresden, Germany.
¹⁹ Centre for Population Neuroscience and Stratified Medicine (PONS), Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Germany.
²⁰ 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.
²¹ School of Psychology and Global Brain Health Institute, Trinity College Dublin, Ireland.
²² Centre for Population Neuroscience and Stratified Medicine (PONS), Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Germany; Centre for Population Neuroscience and Precision Medicine (PONS), Institute for Science and Technology of Brain-inspired Intelligence (ISTBI), Fudan University, Shanghai, China.

PMID: 41005664
DOI: 10.1016/j.bpsc.2025.09.015

Abstract

Background: Adolescence is a critical period of neurodevelopment marked by ongoing maturation of structural and functional brain connectivity. Simultaneously, this period is associated with an increase in mental health problems, spanning from subclinical symptoms to diagnosable disorders.

Methods: This study investigates longitudinal associations between psychopathology dimensions and voxelwise brain measures related to connectivity across three time points (ages 14, 19, and 23) in over 1500 individuals using the IMAGEN dataset. White matter microstructure was indexed using diffusion metrics quantified along the white matter (WM) skeleton (N = 1736), while functional connectivity was captured as voxelwise degree centrality (DC) derived from resting-state functional imaging (N = 1510).

Results: Development of WM microstructure was selectively linked to externalising (but not internalising) symptomatology. Here, higher externalising symptoms were associated with widespread reductions in fractional anisotropy (FA) across the WM skeleton, as well as accelerated decreases in FA in the corticospinal tract over time. In contrast, functional DC was developmentally associated with general, rather than specific, psychopathology in frontal and temporal regions. An increase in total difficulties over time was associated with developmental decrease in DC in bilateral superior frontal gyri. In addition, a positive association between total difficulties and DC in left inferior temporal gyrus was observed in younger, but not older, adolescents or young adults.

Conclusions: These findings highlight the dynamic interplay between brain connectivity development and psychopathology in adolescence, with potential implications for identifying neural markers of risk and resilience during sensitive windows of development.

Keywords: Internalising; adolescence; externalising; functional connectivity; structural connectivity.

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Longitudinal associations of structural and functional brain connectivity with dimensions of psychopathology in adolescence

Collaborators

Affiliations

Longitudinal associations of structural and functional brain connectivity with dimensions of psychopathology in adolescence

Authors

Collaborators

Affiliations

Abstract

LinkOut - more resources

Full Text Sources