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Cognitive predictors of mental health trajectories are mediated by inferior frontal and occipital development during adolescence

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 unde...

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Main Authors: Li, Qingyang (Author) , Cao, Miao (Author) , Stein, Dan J. (Author) , Sahakian, Barbara J. (Author) , Jia, Tianye (Author) , Langley, Christelle (Author) , Gu, Zixin (Author) , Hou, Wenjie (Author) , Lu, Han (Author) , Cao, Luolong (Author) , Lin, Jinran (Author) , Shi, Runye (Author) , Banaschewski, Tobias (Author) , Bokde, Arun L. W. (Author) , Desrivières, Sylvane (Author) , Flor, Herta (Author) , Grigis, Antoine (Author) , Garavan, Hugh (Author) , Gowland, Penny (Author) , Heinz, Andreas (Author) , Brühl, Rüdiger (Author) , Martinot, JeanLuc (Author) , Artiges, Eric (Author) , Nees, Frauke (Author) , Papadopoulos Orfanos, Dimitri (Author) , Paus, Tomáš (Author) , Poustka, Luise (Author) , Hohmann, Sarah (Author) , Baeuchl, Christian (Author) , Smolka, Michael (Author) , Vaidya, Nilakshi (Author) , Walter, Henrik (Author) , Whelan, Robert (Author) , Schumann, Gunter (Author) , Feng, Jianfeng (Author) , Luo, Qiang (Author)
Format: Article (Journal)
Language:English
Published: 01 February 2025
In: Molecular psychiatry
Year: 2025, Volume: 30, Issue: 7, Pages: 30553068
ISSN:14765578
DOI:10.1038/s41380-025-02912-6
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/s41380-025-02912-6
Verlag, lizenzpflichtig, Volltext: http://www.nature.com/articles/s41380-025-02912-6
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Author Notes:Qingyang Li, Miao Cao, Dan J. Stein, Barbara J. Sahakian, Tianye Jia, Christelle Langley, Zixin Gu, Wenjie Hou, Han Lu, Luolong Cao, Jinran Lin, Runye Shi, Tobias Banaschewski, Arun L.W. Bokde, Sylvane Desrivières, Herta Flor, Antoine Grigis, Hugh Garavan, Penny Gowland, Andreas Heinz, Rüdiger Brühl, Jean-Luc Martinot, Eric Artiges, Frauke Nees, Dimitri Papadopoulos Orfanos, Tomáš Paus, Luise Poustka, Sarah Hohmann, Christian Baeuchl, Michael N. Smolka, Nilakshi Vaidya, Henrik Walter, Robert Whelan, Gunter Schumann, Jianfeng Feng, Qiang Luo and IMAGEN Consortium
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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.
Item Description:Mitglieder des IMAGEN CONSORTIUM: Tobias Banaschewski, Arun L.W. Bokde, Sylvane Desrivières, Herta Flor, Antoine Grigis, Hugh Garavan, Penny Gowland, Andreas Heinz, Rüdiger Brühl, Jean-Luc Martinot, Eric Artiges, Frauke Nees, Dimitri Papadopoulos Orfanos, Tomáš Paus, Luise Poustka, Sarah Hohmann, Christian Baeuchl, Michael N. Smolka, Nilakshi Vaidya, Henrik Walter, Robert Whelan and Gunter Schumann
Gesehen am 15.07.2025
Physical Description:Online Resource
ISSN:14765578
DOI:10.1038/s41380-025-02912-6

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