Gabriel H Robert1,2,3,4,5, Qiang Luo6,7,8, Tao Yu9,10,11,12, Congying Chu1,4, Alex Ing1,4, Tianye Jia1,4, Dimitri Papadopoulos Orfanos13, Erin Burke-Quinlan1,4, Sylvane Desrivières1,4, Barbara Ruggeri1,4, Philip Spechler14, Bader Chaarani14, Nicole Tay1,4, Tobias Banaschewski15, Arun L W Bokde16, Uli Bromberg13, Herta Flor17,18, Vincent Frouin13, Penny Gowland19, Andreas Heinz20, Bernd Ittermann21, Jean-Luc Martinot22,23, Marie-Laure Paillère Martinot24,25, Frauke Nees18, Luise Poustka26, Michael N Smolka27, Nora C Vetter27, Henrik Walter28, Robert Whelan29, Patricia Conrod30, Ted Barker1,4, Hugh Garavan14, Gunter Schumann1,4,6,31,32. 1. Institute of Psychiatry, Psychology and Neuroscience, Centre for Population Neuroscience and Stratified Medicine (PONS), King's College London, London, United Kingdom. 2. Behavior and Basal Ganglia Unit (EA-4712), University of Rennes 1, Rennes, France. 3. Pôle Hospitalo-Universitaire de Psychiatrie Adulte, Rennes, France. 4. Social, Genetic, and Developmental Psychiatry Centre, King's College London, London, United Kingdom. 5. U1228, Empenn, Institut National de la Santé et de la Recherche Médicale & Institut National de Recherche en Informatique et Automatique, Paris, France. 6. Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China. 7. State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Institute of Brain Science, Fudan University, Shanghai, China. 8. Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Fudan University, Ministry of Education, Shanghai, China. 9. Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, Shanghai, China. 10. Shanghai Center for Women and Children's Health, Shanghai, China. 11. Shanghai Key Laboratory of Psychotic Disorders, Shanghai Institute of Mental Health, Shanghai Jiao Tong University, Shanghai, China. 12. Brain Science and Technology Research Center, Shanghai Jiao Tong University, Shanghai, China. 13. Department of Systems Neuroscience, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany. 14. Departments of Psychiatry and Psychology, University of Vermont, Burlington. 15. Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. 16. School of Medicine and Trinity College Institute of Neuroscience, Discipline of Psychiatry, Trinity College Dublin, Dublin, Ireland. 17. Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. 18. Department of Psychology, School of Social Sciences, University of Mannheim, Mannheim, Germany. 19. Sir Peter Mansfield Imaging Centre School of Physics and Astronomy, University of Nottingham, University Park, Nottingham, United Kingdom. 20. Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité, Universitätsmedizin Berlin, Berlin, Germany. 21. Physikalisch-Technische Bundesanstalt, Braunschweig and Berlin, Berlin, Germany. 22. Institut National de la Santé et de la Recherche Médicale, INSERM Unit 1000 Neuroimaging & Psychiatry, Faculté de Médecine, Université Paris-Sud, Le Kremlin-Bicêtre, Sorbonne Paris Cité, Paris, France. 23. Université Paris Descartes, Sorbonne Paris Cité, Paris, France. 24. Institut National de la Santé et de la Recherche Médicale, INSERM Unit 1000 Neuroimaging & Psychiatry, Université Paris-Sud, University Paris Descartes-Sorbonne Paris Citél, Paris, France. 25. Assistance Publique des Hôpitaux de Paris, Department of Adolescent Psychopathology and Medicine, Maison de Solenn, Cochin Hospital, Paris, France. 26. Department of Child and Adolescent Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria. 27. Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden, Germany. 28. Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité, Universitätsmedizin Berlin, Research Division of Mind and Brain Berlin, Berlin, Germany. 29. Department of Psychology, University College Dublin, Belfield, Dublin, Ireland. 30. Department of Psychiatry and Addictology, Medical Faculty, University of Montreal, Montréal, Québec, Canada. 31. PONS Research Group, Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Humboldt University, Berlin, Germany. 32. Leibniz Institute for Neurobiology, Magdeburg, Germany.
Abstract
Importance: Alcohol abuse correlates with gray matter development in adolescents, but the directionality of this association remains unknown. Objective: To investigate the directionality of the association between gray matter development and increase in frequency of drunkenness among adolescents. Design, Setting, and Participants: This cohort study analyzed participants of IMAGEN, a multicenter brain imaging study of healthy adolescents in 8 European sites in Germany (Mannheim, Dresden, Berlin, and Hamburg), the United Kingdom (London and Nottingham), Ireland (Dublin), and France (Paris). Data from the second follow-up used in the present study were acquired from January 1, 2013, to December 31, 2016, and these data were analyzed from January 1, 2016, to March 31, 2018. Analyses were controlled for sex, site, socioeconomic status, family history of alcohol dependency, puberty score, negative life events, personality, cognition, and polygenic risk scores. Personality and frequency of drunkenness were assessed at age 14 years (baseline), 16 years (first follow-up), and 19 years (second follow-up). Structural brain imaging scans were acquired at baseline and second follow-up time points. Main Outcomes and Measures: Increases in drunkenness frequency were measured by latent growth modeling, a voxelwise hierarchical linear model was used to observe gray matter volume, and tensor-based morphometry was used for gray matter development. The hypotheses were formulated before the data analyses. Results: A total of 726 adolescents (mean [SD] age at baseline, 14.4 [0.38] years; 418 [58%] female) were included. The increase in drunkenness frequency was associated with accelerated gray matter atrophy in the left posterior temporal cortex (peak: t1,710 = -5.8; familywise error (FWE)-corrected P = 7.2 × 10-5; cluster: 6297 voxels; P = 2.7 × 10-5), right posterior temporal cortex (cluster: 2070 voxels; FWE-corrected P = .01), and left prefrontal cortex (peak: t1,710 = -5.2; FWE-corrected P = 2 × 10-3; cluster: 10 624 voxels; P = 1.9 × 10-7). According to causal bayesian network analyses, 73% of the networks showed directionality from gray matter development to drunkenness increase as confirmed by accelerated gray matter atrophy in late bingers compared with sober controls (n = 20 vs 60; β = 1.25; 95% CI, -2.15 to -0.46; t1,70 = 0.3; P = .004), the association of drunkenness increase with gray matter volume at age 14 years (β = 0.23; 95% CI, 0.01-0.46; t1,584 = 2; P = .04), the association between gray matter atrophy and alcohol drinking units (β = -0.0033; 95% CI, -6 × 10-3 to -5 × 10-4; t1,509 = -2.4; P = .02) and drunkenness frequency at age 23 years (β = -0.16; 95% CI, -0.28 to -0.03; t1,533 = -2.5; P = .01), and the linear exposure-response curve stratified by gray matter atrophy and not by increase in frequency of drunkenness. Conclusions and Relevance: This study found that gray matter development and impulsivity were associated with increased frequency of drunkenness by sex. These results suggest that neurotoxicity-related gray matter atrophy should be interpreted with caution.
Importance: Alcohol abuse correlates with gray matter development in adolescents, but the directionality of this association remains unknown. Objective: To investigate the directionality of the association between gray matter development and increase in frequency of drunkenness among adolescents. Design, Setting, and Participants: This cohort study analyzed participants of IMAGEN, a multicenter brain imaging study of healthy adolescents in 8 European sites in Germany (Mannheim, Dresden, Berlin, and Hamburg), the United Kingdom (London and Nottingham), Ireland (Dublin), and France (Paris). Data from the second follow-up used in the present study were acquired from January 1, 2013, to December 31, 2016, and these data were analyzed from January 1, 2016, to March 31, 2018. Analyses were controlled for sex, site, socioeconomic status, family history of alcohol dependency, puberty score, negative life events, personality, cognition, and polygenic risk scores. Personality and frequency of drunkenness were assessed at age 14 years (baseline), 16 years (first follow-up), and 19 years (second follow-up). Structural brain imaging scans were acquired at baseline and second follow-up time points. Main Outcomes and Measures: Increases in drunkenness frequency were measured by latent growth modeling, a voxelwise hierarchical linear model was used to observe gray matter volume, and tensor-based morphometry was used for gray matter development. The hypotheses were formulated before the data analyses. Results: A total of 726 adolescents (mean [SD] age at baseline, 14.4 [0.38] years; 418 [58%] female) were included. The increase in drunkenness frequency was associated with accelerated gray matter atrophy in the left posterior temporal cortex (peak: t1,710 = -5.8; familywise error (FWE)-corrected P = 7.2 × 10-5; cluster: 6297 voxels; P = 2.7 × 10-5), right posterior temporal cortex (cluster: 2070 voxels; FWE-corrected P = .01), and left prefrontal cortex (peak: t1,710 = -5.2; FWE-corrected P = 2 × 10-3; cluster: 10 624 voxels; P = 1.9 × 10-7). According to causal bayesian network analyses, 73% of the networks showed directionality from gray matter development to drunkenness increase as confirmed by accelerated gray matter atrophy in late bingers compared with sober controls (n = 20 vs 60; β = 1.25; 95% CI, -2.15 to -0.46; t1,70 = 0.3; P = .004), the association of drunkenness increase with gray matter volume at age 14 years (β = 0.23; 95% CI, 0.01-0.46; t1,584 = 2; P = .04), the association between gray matter atrophy and alcohol drinking units (β = -0.0033; 95% CI, -6 × 10-3 to -5 × 10-4; t1,509 = -2.4; P = .02) and drunkenness frequency at age 23 years (β = -0.16; 95% CI, -0.28 to -0.03; t1,533 = -2.5; P = .01), and the linear exposure-response curve stratified by gray matter atrophy and not by increase in frequency of drunkenness. Conclusions and Relevance: This study found that gray matter development and impulsivity were associated with increased frequency of drunkenness by sex. These results suggest that neurotoxicity-related gray matter atrophy should be interpreted with caution.
Authors: Roshan Prakash Rane; Evert Ferdinand de Man; JiHoon Kim; Kai Görgen; Mira Tschorn; Michael A Rapp; Tobias Banaschewski; Arun L W Bokde; Sylvane Desrivieres; Herta Flor; Antoine Grigis; Hugh Garavan; Penny A Gowland; Rüdiger Brühl; Jean-Luc Martinot; Marie-Laure Paillere Martinot; Eric Artiges; Frauke Nees; Dimitri Papadopoulos Orfanos; Herve Lemaitre; Tomas Paus; Luise Poustka; Juliane Fröhner; Lauren Robinson; Michael N Smolka; Jeanne Winterer; Robert Whelan; Gunter Schumann; Henrik Walter; Andreas Heinz; Kerstin Ritter Journal: Elife Date: 2022-05-26 Impact factor: 8.713
Authors: Max M Owens; Matthew D Albaugh; Nicholas Allgaier; Dekang Yuan; Gabriel Robert; Renata B Cupertino; Philip A Spechler; Anthony Juliano; Sage Hahn; Tobias Banaschewski; Arun L W Bokde; Sylvane Desrivières; Herta Flor; Antoine Grigis; Penny Gowland; Andreas Heinz; Rüdiger Brühl; Jean-Luc Martinot; Marie-Laure Paillère Martinot; Eric Artiges; Frauke Nees; Dimitri Papadopoulos Orfanos; Herve Lemaitre; Tomáš Paus; Luise Poustka; Sabina Millenet; Juliane H Fröhner; Michael N Smolka; Henrik Walter; Robert Whelan; Scott Mackey; Gunter Schumann; Hugh Garavan Journal: Transl Psychiatry Date: 2022-05-06 Impact factor: 7.989
Authors: Elise E DeVito; Andrea H Weinberger; Raina D Pang; Nicole Petersen; Tessa Fagle; Alicia M Allen Journal: Curr Behav Neurosci Rep Date: 2020-07-15