A biologically informed polygenic score of neuronal plasticity moderates the association between cognitive aptitudes and cortical thickness in adolescents

Research output: Contribution to journalResearch articleContributedpeer-review


  • Xavier Navarri - , University of Montreal (Author)
  • Daniel E Vosberg - , University of Montreal (Author)
  • Jean Shin - , York University Toronto (Author)
  • Louis Richer - , University of Catania (Author)
  • Gabriel Leonard - , McGill University (Author)
  • G Bruce Pike - , University of Calgary (Author)
  • Tobias Banaschewski - , National Center for Tumor Diseases (NCT) Heidelberg (Author)
  • Arun L W Bokde - , Trinity College Dublin (Author)
  • Sylvane Desrivières - , King's College Hospital NHS Foundation Trust (Author)
  • Herta Flor - , National Center for Tumor Diseases (NCT) Heidelberg (Author)
  • Antoine Grigis - , French Alternative Energies and Atomic Energy Commission (CEA) (Author)
  • Hugh Garavan - , Northern Vermont University (Author)
  • Penny Gowland - , Park University, Missouri (Author)
  • Andreas Heinz - , Charité – Universitätsmedizin Berlin (Author)
  • Rüdiger Brühl - , Physikalisch-Technische Bundesanstalt (Author)
  • Jean-Luc Martinot - , INSERM - Institut national de la santé et de la recherche médicale (Author)
  • Marie-Laure Paillère Martinot - , Université Paris-Saclay (Author)
  • Eric Artiges - , INSERM - Institut national de la santé et de la recherche médicale (Author)
  • Frauke Nees - , National Center for Tumor Diseases (NCT) Heidelberg (Author)
  • Dimitri Papadopoulos Orfanos - , French Alternative Energies and Atomic Energy Commission (CEA) (Author)
  • Luise Poustka - , University Medical Center Göttingen (Author)
  • Sarah Hohmann - , National Center for Tumor Diseases (NCT) Heidelberg (Author)
  • Juliane H Fröhner - , Department of Psychiatry and Psychotherapy (Author)
  • Michael N Smolka - , Department of Psychiatry and Psychotherapy (Author)
  • Nilakshi Vaidya - , Centre for Population Neuroscience and Precision Medicine (Author)
  • Henrik Walter - , Mental Health Institute Berlin GmbH (Author)
  • Robert Whelan - , Trinity College Dublin (Author)
  • Gunter Schumann - , Zhongshan Hospital at Fudan University (Author)
  • Zdenka Pausova - , York University Toronto (Author)
  • Tomáš Paus - , York University Toronto (Author)


Although many studies of the adolescent brain identified positive associations between cognitive abilities and cortical thickness, little is known about mechanisms underlying such brain-behavior relationships. With experience-induced plasticity playing an important role in shaping the cerebral cortex throughout life, it is likely that some of the inter-individual variations in cortical thickness could be explained by genetic variations in relevant molecular processes, as indexed by a polygenic score of neuronal plasticity (PGS-NP). Here, we studied associations between PGS-NP, cognitive abilities, and thickness of the cerebral cortex, estimated from magnetic resonance images, in the Saguenay Youth Study (SYS, 533 females, 496 males: age=15.0 ± 1.8 years of age; cross-sectional), and the IMAGEN Study (566 females, 556 males; between 14 and 19 years; longitudinal). Using Gene Ontology, we first identified 199 genes implicated in neuronal plasticity, which mapped to 155,600 single nucleotide polymorphisms (SNPs). Second, we estimated their effect sizes from an educational attainment meta-GWAS to build a PGS-NP. Third, we examined a possible moderating role of PGS-NP in the relationship between performance intelligence quotient (PIQ), and its subtests, and the thickness of 34 cortical regions. In SYS, we observed a significant interaction between PGS-NP and object assembly vis-à-vis thickness in male adolescents (p = 0.026). A median-split analysis showed that, in males with a 'high' PGS-NP, stronger associations between object assembly and thickness were found in regions with larger age-related changes in thickness (r = 0.55, p = 0.00075). Although the interaction between PIQ and PGS-NP was non-significant (p = 0.064), we performed a similar median-split analysis. Again, in the high PGS-NP males, positive associations between PIQ and thickness were observed in regions with larger age-related changes in thickness (r = 0.40, p = 0.018). In the IMAGEN cohort, we did not replicate the first set of results (interaction between PGS-NP and cognitive abilities via-a-vis cortical thickness) while we did observe the same relationship between the brain-behaviour relationship and (longitudinal) changes in cortical thickness (Matrix reasoning: r = 0.63, p = 6.5e-05). No statistically significant results were observed in female adolescents in either cohort. Overall, these cross-sectional and longitudinal results suggest that molecular mechanisms involved in neuronal plasticity may contribute to inter-individual variations of cortical thickness related to cognitive abilities during adolescence in a sex-specific manner.


Original languageEnglish
Article number101232
Pages (from-to)101232
JournalDevelopmental cognitive neuroscience
Publication statusPublished - Apr 2023

External IDs

PubMedCentral PMC10064237
Scopus 85150826683
ORCID /0000-0001-5398-5569/work/150329573
ORCID /0000-0002-8493-6396/work/150330271



  • Humans, Male, Adolescent, Female, Intelligence/physiology, Aptitude, Cross-Sectional Studies, Cognition/physiology, Cerebral Cortex, Magnetic Resonance Imaging, Neuronal Plasticity/genetics