Cognitive predictors of mental health trajectories are mediated by inferior frontal and occipital development during adolescence.
Journal: Molecular psychiatry
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Affiliated Institutions:
National Clinical Research Center for Aging and Medicine at Huashan Hospital, Institute of Science and Technology for Brain-Inspired Intelligence, School of Life Sciences, Fudan University, Shanghai, , China.
SAMRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
Department of Psychiatry, University of Cambridge, Cambridge, CB SZ, UK.
Research Institute of Intelligent Complex Systems, Fudan University, Shanghai, , China.
Ministry of Education Key Laboratory of Contemporary Anthropology Fudan University, Shanghai, China.
School of Data Science, Fudan University, Shanghai, , China.
Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Square J, , Mannheim, Germany.
Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
Institute of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Square J, Mannheim, Germany.
NeuroSpin, CEA, Université Paris-Saclay, F-, Gif-sur-Yvette, France.
Departments of Psychiatry and Psychology, University of Vermont, , Burlington, VT, USA.
Sir Peter Mansfield Imaging Centre School of Physics and Astronomy, University of Nottingham, University Park, Nottingham, UK.
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.
Physikalisch-Technische Bundesanstalt (PTB), Braunschweig and Berlin, Germany.
Institut National de la Santé et de la Recherche Médicale, INSERM U A "Trajectoires développementales en psychiatrie"; Université Paris-Saclay, Ecole Normale supérieure Paris-Saclay, CNRS, Centre Borelli, Gif-sur-Yvette, France.
Institut National de la Santé et de la Recherche Médicale, INSERM U A "Trajectoires développementales en psychiatrie"; Université Paris-Saclay, Ecole Normale supérieure Paris-Saclay, CNRS, Centre Borelli, Gif-sur-Yvette; and Psychiatry Department, EPS Barthélémy Durand, Etampes, France.
Department of Psychiatry, Faculty of Medicine and Centre Hospitalier Universitaire Sainte-Justine, University of Montreal, Montreal, QC, Canada.
Department of Child and Adolescent Psychiatry, Center for Psychosocial Medicine, University Hospital Heidelberg, Heidelberg, Germany.
Department of Psychiatry and Psychotherapy, Technische Universität Dresden, Dresden, Germany.
Centre for Population Neuroscience and Stratified Medicine (PONS), Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany.
School of Psychology and Global Brain Health Institute, Trinity College Dublin, Dublin, Ireland.
National Clinical Research Center for Aging and Medicine at Huashan Hospital, Institute of Science and Technology for Brain-Inspired Intelligence, School of Life Sciences, Fudan University, Shanghai, , China. qluo@fudan.edu.cn.
Abstract summary
Laboratory studies show brain maturation involves synaptic pruning and cognitive development. Human studies suggest links between early cognitive performance and later mental health, but inconsistencies remain. It is unclear if specific brain regions mediate this relationship, and the molecular underpinnings are not well understood. Here, our longitudinal analyses in both the Adolescent Brain Cognitive Development and IMAGEN cohorts establish inverted U-shaped relationships between baseline executive function and subsequent symptom trajectories in the high-symptom individuals, whose externalizing (n = 963) or internalizing (n = 1762) symptoms exceed a clinical threshold at any point during the follow-up period, but not in the control group (n = 4291). Volumetric changes in the left lateral occipital cortex (LOC) mediated the relationship with externalizing symptoms (outwardly directed behaviors such as aggression), while changes in the right LOC and pars triangularis mediated the relationship with internalizing symptoms (inwardly directed emotional problems such as anxiety). Transcriptomic and genomic findings highlighted synaptic biology and particularly the gene ADCY1, which is implicated in synaptic pruning, as underlying both moderate executive function and its associated brain mediators. Notably, preadolescent cognitive performance predicts late-onset externalizing symptoms and remitting internalizing symptoms with high accuracies (area under the curve: 0.87 and 0.79). Our findings highlight the predictive value of cognitive performance for adolescent mental health trajectories, and indicate how this is mediated by specific brain regions, and underpinned by particular molecular pathways.
Authors & Co-authors:
Li Qingyang Q
Cao Miao M
Stein Dan J DJ
Sahakian Barbara J BJ
Jia Tianye T
Langley Christelle C
Gu Zixin Z
Hou Wenjie W
Lu Han H
Cao Luolong L
Lin Jinran J
Shi Runye R
Banaschewski Tobias T
Bokde Arun L W ALW
Desrivières Sylvane S
Flor Herta H
Grigis Antoine A
Garavan Hugh H
Gowland Penny P
Heinz Andreas A
Brühl Rüdiger R
Martinot Jean-Luc JL
Artiges Eric E
Nees Frauke F
Papadopoulos Orfanos Dimitri D
Paus Tomáš T
Poustka Luise L
Hohmann Sarah S
Baeuchl Christian C
Smolka Michael N MN
Vaidya Nilakshi N
Walter Henrik H
Whelan Robert R
Schumann Gunter G
Feng Jianfeng J
Luo Qiang Q
Study Outcome
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