Associations between brain imaging and polygenic scores of mental health and educational attainment in children aged 9-11

Abstract

Background: Psychiatric disorders are highly heritable and polygenic, and many have their peak onset in late childhood and adolescence, a period of tremendous changes. Although the neurodevelopmental antecedents of mental illness are widely acknowledged, research in youth population cohorts is still scarce, preventing our progress towards the early characterization of these disorders. Methods: We included 7,124 children (9-11 years old) from the Adolescent Brain and Cognitive Development Study to map the associations of structural brain imaging with common genetic variants and polygenic scores for psychiatric disorders and educational attainment. We used principal component analysis to derive imaging components, and calculated their heritability. We then assessed the relationship of imaging components with genetic and clinical psychiatric risk with univariate models and Canonical correlation analysis (CCA). Results: Most imaging components had moderate heritability. Univariate models showed limited evidence and small associations of polygenic scores with brain structure at this age. CCA revealed two significant modes of covariation. The first linked higher polygenic scores for educational attainment with less externalizing problems and larger surface area. The second mode related higher polygenic scores for schizophrenia, bipolar disorder, and autism spectrum disorder to higher global cortical thickness, smaller white matter volumes of the fornix and cingulum, larger medial occipital surface area and smaller surface area of lateral and medial temporal regions. Conclusion: While cross-validation suggested limited generalizability, our results highlight the potential of multivariate models to better understand the transdiagnostic and distributed relationships between mental health and brain structure in late childhood.

Deviations from normative brain white and gray matter structure are associated with psychopathology in youth

“…We also found norm-violating behavior to be associated with L1 dev and SA dev . This is in line with a study of 7124 children aged 9-11 years from the ABCD study reporting a negative association between externalizing problems and surface area (Fernandez-Cabello et al, 2022). For SA dev we also found evidence for an association with the anxiety domain score.…”

“…While the current associations between modalities were weak, there is wide support for the benefits of combining multiple MRI modalities when studying brain development, aging, and disease (Fernandez-Cabello et al, 2022;Groves et al, 2012;Rokicki et al, 2021;Smith et al, 2020). Combining measures increases sensitivity to age and improves discrimination accuracy for common disorders of the brain (Doan et al, 2017;Rokicki et al, 2021) and has been shown to boost gene discovery for brain imaging features (van der Meer et al, 2020),.…”

Linking brain maturation and puberty during early adolescence using longitudinal brain age prediction in the ABCD cohort

“…The effect sizes were moderate and comparable to previous studies using other neuroimaging-based outcomes to study the associations between brain structure and puberty (Vijakumar et al, 2021). Brain development during adolescence is likely shaped by an interaction of genetically programmed age-related changes, biological processes, and fluctuating environmental pressures (Fernandez-Cabello et al, 2022; Ferschmann et al, 2022). Combined with previous findings, our study shows that the effects of puberty are non-negligible and should be considered an influencing factor when studying adolescent brain development.…”

“…Brain development during adolescence is characterized by a highly coordinated sequence of both progressive (cell growth and myelination) and regressive (synaptic pruning) processes (Paus et al, 2008), observable as nonlinear trajectories of cortical thinning and white matter volume increase in relation to chronological age (Blakemore & Choudhury, 2006). The neurodevelopmental progress is most likely shaped by a complex interplay of genetic factors, changes in biological processes, and new environmental pressures (Fernandez-Cabello et al, 2022; Ferschmann et al, 2022). In parallel to brain development, adolescence is a period of drastic changes in physiological processes and body composition during puberty.…”