Early-life stress exposure and intracortical myelination in childhood: a population-based neuroimaging study

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Abstract
Objective: Early life stress (ELS) is a known risk factor for psychopathology later in life, yet the neural mechanisms underpinning this relationship remain unclear. This study aimed to explore associations between ELS and intracortical myelination (ICM) – a structural marker of brain maturation – at a pivotal neurodevelopmental period in childhood.
Methods: Prospective data from 2,285 pre-adolescents within the Generation R Study were used to construct cumulative measures of prenatal (in utero) and postnatal (birth to age 10) ELS spanning multiple risk domains. Whole-brain, surface-based, vertex-wise linear regression analyses were conducted to map associations between pre- and postnatal stress and grey-/white matter contrast (GWC), a proxy for ICM, at age 10.
Results: Negative associations with GWC were observed for both prenatal (mean β = -0.31) and postnatal (mean β = -0.29) ELS, indicative of greater ICM. Spatial clusters were located primarily in early maturing sensorimotor regions (e.g., somatosensory cortex) and some late maturing multimodal association areas (e.g., prefrontal cortex). Exploratory analyses revealed that 14% of the significant vertices detected exhibited shared associations between prenatal and postnatal stress, while 52% demonstrated unique associations with prenatal stress. Of all ELS domains examined, only contextual risk (i.e., socioeconomic disadvantage) was independently linked to ICM. All findings can be explored and visualized flexibly on our interactive web application.
Conclusion: ELS exposure was associated with greater ICM in both early and late maturing cortical regions at age 10, suggestive of accelerated neurodevelopment. Risk factors relating to socioeconomic disadvantage appear to be a driving force in this relationship.