Structural neurodevelopment at the individual level - a life-course investigation using ABCD, IMAGEN and UK Biobank data

Abstract

Adolescents exhibit remarkable heterogeneity in the structural architecture of brain development. However, due to the lack of large-scale longitudinal neuroimaging studies, existing research has largely focused on population averages and the neurobiological basis underlying individual heterogeneity remains poorly understood. Using structural magnetic resonance imaging from the IMAGEN cohort (n=1,543), we show that adolescents can be clustered into three groups defined by distinct developmental patterns of whole-brain gray matter volume (GMV). Genetic and epigenetic determinants of group clustering and long-term impacts of neurodevelopment in mid-to-late adulthood were investigated using data from the Adolescent Brain Cognitive Development (ABCD), IMAGEN and UK Biobank cohorts. Group 1, characterized by continuously decreasing GMV, showed generally the best neurocognitive performances during adolescence. Compared to Group 1, Group 2 exhibited a slower rate of GMV decrease and worsened neurocognitive development, which was associated with epigenetic changes and greater environmental burden. Further, Group 3 showed increasing GMV and delayed neurocognitive development during adolescence due to a genetic variation, while these disadvantages were attenuated in mid-to-late adulthood. In summary, our study revealed novel clusters of adolescent structural neurodevelopment and suggested that genetically-predicted delayed neurodevelopment has limited long-term effects on mental well-being and socio-economic outcomes later in life. Our results could inform future research on policy interventions aimed at reducing the financial and emotional burden of mental illness.

Population clustering of structural brain aging and its association with brain development

“…This approach enabled robust investigation of the association between genetic susceptibility of neuropsychiatric disorders and brain imaging phenotypes. PRS for major neuro-developmental disorders including attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASD), neurodegenerative diseases including Alzheimer's disease (AD) and Parkinson's disease (PD), neuropsychiatric disorders including bipolar disorder (BIP), major depressive disorder (MDD), and schizophrenia (SCZ), and delayed structural brain development (GWAS from an unpublished longitudinal neuroimaging study) 23 were calculated for each participant using multiple P value thresholds (from 0.005 to 0.5 at intervals of 0.005) and results were then averaged over all thresholds (Fig. 5).…”

“…Parkinson's Disease (PD), bipolar disorder (BIP), major depressive disorder (MDD), schizophrenia (SCZ) and delayed brain development using GWAS summary statistics 23 at multiple P value thresholds (from 0.005 to 0.5 at intervals of 0.005, and 1), with higher P value thresholds incorporating larger number of independent SNPs. After quality control of genotype and imaging data, PRSs were generated for 25,861 participants on UK Biobank genotyping data.…”