Long-term Neural Embedding of Childhood Adversity in a Population-Representative Birth Cohort Followed for 5 Decades

Abstract

Background: Childhood adversity has been previously associated with alterations in brain structure, but heterogeneous designs, methods, and measures have contributed to mixed results and have impeded progress in mapping the biological embedding of childhood adversity. We sought to identify long-term differences in structural brain integrity associated with childhood adversity.

Methods: Multiple regression was used to test associations between prospectively ascertained adversity during childhood and adversity retrospectively reported in adulthood with structural magnetic resonance imaging measures of midlife global and regional cortical thickness, cortical surface area, and subcortical gray matter volume in 861 (425 female) members of the Dunedin Study, a longitudinal investigation of a population-representative birth cohort.

Results: Both prospectively ascertained childhood adversity and retrospectively reported adversity were associated with alterations in midlife structural brain integrity, but associations with prospectively ascertained childhood adversity were consistently stronger and more widely distributed than associations with retrospectively reported childhood adversity. Sensitivity analyses revealed that these associations were not driven by any particular adversity or category of adversity (i.e., threat or deprivation) or by childhood socioeconomic disadvantage. Network enrichment analyses revealed that these associations were not localized but were broadly distributed along a hierarchical cortical gradient of information processing.

Conclusions: Exposure to childhood adversity broadly is associated with widespread differences in midlife gray matter across cortical and subcortical structures, suggesting that biological embedding of childhood adversity in the brain is long lasting, but not localized. Research using retrospectively reported adversity likely underestimates the magnitude of these associations. These findings may inform future research investigating mechanisms through which adversity becomes embedded in the brain and influences mental health and cognition.

Keywords: Childhood adversity; Maltreatment; Midlife brain structure; Prospective; Retrospective.

Figure 1

Associations between childhood adversity and global brain structure. Scatterplots of associations between prospectively ascertained adverse childhood experiences (ACEs) and (A) total surface area and (B) average cortical thickness. Scatterplots of associations between retrospectively reported ACEs and (C) total surface area and (D) average cortical thickness. Forest plots of standardized effect sizes (β and 95% confidence intervals) for the associations between prospectively ascertained ACEs and retrospectively reported ACEs with (E) surface area and (F) average cortical thickness. Solid squares mark standardized effect sizes for the independent associations between prospectively ascertained and retrospectively reported ACEs and age-45 brain structure, whereas open squares mark standardized effect sizes for the associations between prospectively ascertained and retrospectively reported ACEs and age-45 brain structure when controlling for the other ACEs measure.

Figure 2

Associations between childhood adversity and parcelwise measures of cortical surface area and thickness. Parcelwise associations of (A) prospectively ascertained and (B) retrospectively reported adverse childhood experiences with surface area (p < .05, false discovery rate corrected). Parcelwise associations of (C) prospectively ascertained and (D) retrospectively reported adverse childhood experiences with cortical thickness (p < .05, false discovery rate corrected). Color bars reflect standardized effect sizes (β).

Figure 3

Associations between childhood adversity and subcortical gray matter volume. (A) The 10 subcortical structures for which gray matter volume was estimated. (B) Standardized effect sizes (β and 95% confidence intervals) for associations between prospectively ascertained adverse childhood experiences (ACEs) and retrospectively reported ACEs with average gray matter volume of 10 subcortical structures. Solid squares mark standardized effect sizes for the independent associations between prospectively ascertained and retrospectively reported ACEs and age-45 brain structure, whereas open squares mark standardized effect sizes for the associations between prospectively ascertained and retrospectively reported ACEs and age-45 brain structure when controlling for the other ACEs measure.

Figure 4

Influence of childhood socioeconomic status (SES) on associations between prospectively ascertained adversity and brain structure. Associations between prospectively ascertained adverse childhood experiences (ACEs) and age-45 brain structure are plotted with a black square, associations with SES included as ACEs are plotted with a filled blue square, and associations with SES included as a covariate are plotted with an open blue square. Forest plot shows standardized effect sizes (β and 95% confidence intervals).

Figure 5

Associations between individual forms of adversity and brain structure. Prospectively ascertained adverse childhood experiences (ACEs) scores were recalculated excluding one item at a time. Standardized effect sizes for the associations between the newly calculated leave-one-out ACEs scores and each measure of age-45 brain structure are plotted in the bar graph. Associations with all ACEs are plotted in yellow, and associations with leave-one-out ACEs scores are plotted in shades of blue.

Figure 6

Associations between threat-specific and deprivation-specific adversity and brain structure. Associations between age-45 brain structure and all adverse childhood experiences (ACEs) are plotted with a black square; threat-specific ACEs, covarying for deprivation, are plotted with an open blue square; and deprivation-specific ACEs, covarying for threat, are plotted with an open purple square. Forest plot shows standardized effect sizes (β and 95% confidence intervals).

Figure 7

Correspondence of parcelwise associations with adversity along a cortical gradient of hierarchical information processing. (A) Cortical gradient capturing the macroscale hierarchical organization of information processing from basic sensory and somatomotor (cool colors) to higher cognitive (warm colors) functions (55). Standardized effect sizes for the associations between prospectively ascertained adverse childhood experiences (ACEs) and parcelwise (B) cortical surface area and (C) cortical thickness are plotted along the gradient.