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Original Investigation
June 17, 2020

Assessment of Neurobiological Mechanisms of Cortical Thinning During Childhood and Adolescence and Their Implications for Psychiatric Disorders

Author Affiliations
  • 1Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada
  • 2Bloorview Research Institute, Toronto, Ontario, Canada
  • 3National Institute of Developmental Psychiatry for Children and Adolescents, Sao Paulo, Brazil
  • 4Interdisciplinary Lab for Clinical Neurosciences, Federal University of Sao Paulo, Sao Paulo, Brazil
  • 5Department of Psychiatry, Federal University of Sao Paulo, Sao Paulo, Brazil
  • 6Department of Psychiatry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil
  • 7The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
  • 8Department of Psychology and Psychiatry, University of Toronto, Toronto, Ontario, Canada
JAMA Psychiatry. Published online June 17, 2020. doi:10.1001/jamapsychiatry.2020.1495
Key Points

Question  What are the neurobiological mechanisms of cortical thinning during childhood and adolescence, and do these mechanisms have implications for psychiatric disorders?

Findings  In this cohort study of 3596 individuals aged 9 to 21 years, interregional profiles of age-associated cortical thinning correlated with transcriptomic profiles of genes involved in myelin and dendritic architecture. These genes (and their coexpression networks) were enriched among genes associated with a number of psychiatric disorders that emerge during the first 2 decades of life.

Meaning  This study found genetic similarity between interregional variation in cortical thinning during maturation and multiple psychiatric disorders, which suggests specific cellular and molecular pathways that may modify susceptibility to these disorders.

Abstract

Importance  Many psychiatric disorders can be conceptualized as disorders of brain maturation during childhood and adolescence. Discovering the neurobiological underpinnings of brain maturation may elucidate molecular pathways of vulnerability and resilience to such disorders.

Objective  To investigate the underlying neurobiological mechanisms of age-associated cortical thinning during maturation and their implications for psychiatric disorders.

Design, Setting, and Participants  This multicohort analysis used data from 3 community-based studies. The Saguenay Youth Study provided data from 1024 adolescents who were recruited at a single site in Quebec, Canada. The IMAGEN cohort provided data from 1823 participants who were recruited in 8 European cities. The Brazil High Risk Cohort Study for the Development of Childhood Psychiatric Disorders provided data from 815 participants who were recruited in 2 Brazilian cities. Cortical thickness was estimated from the results of magnetic resonance imaging (MRI) scans, and age-associated cortical thinning was estimated in 34 cortical regions. Gene expression from the Allen Human Brain Atlas was aligned with the same regions. Similarities in the interregional profiles of gene expression and the profiles of age-associated cortical thinning were measured. The involvement of dendrites, dendritic spines, and myelin was tested using 3 gene panels. Enrichment for genes associated with psychiatric disorders was tested among the genes associated with thinning and their coexpression networks. Data analysis was conducted between March and October 2019.

Main Outcomes and Measures  MRI-derived estimates of age-associated cortical thinning and gene expression in 34 cortical regions.

Results  A total of 3596 individuals aged 9 to 21 years were included in this study. Of those, 1803 participants (50.1%) were female, and the mean (SD) age was 15.2 (2.6) years. Interregional profiles of age-associated cortical thinning were associated with interregional gradients in the expression of genes associated with dendrites, dendritic spines, and myelin; the variance in thinning explained by the gene panels across different points ranged from 0.45% to 10.55% for the dendrite panel, 0.00% to 9.98% for the spine panel, and 0.19% to 26.39% for the myelin panel. These genes and their coexpression networks were enriched for genes associated with several psychiatric disorders.

Conclusions and Relevance  In this study, genetic similarity between interregional variation in cortical thinning during maturation and multiple psychiatric disorders suggests overlapping molecular underpinnings. This finding adds to the understanding of the neurodevelopmental mechanisms of psychiatric disorders.

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