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Greater age-related changes in white matter morphometry following early life stress: Associations with internalizing problems in adolescence.

ABSTRACT: Early life stress (ELS) is associated with increased risk for internalizing disorders and variations in gray matter development. It is unclear, however, whether ELS affects normative age-related changes in white matter (WM) morphology, and if such maturational differences are associated with risk for internalizing psychopathology. We conducted comprehensive interviews in a cross-sectional sample of young adolescents (N = 156; 89 F; Ages 9-14) to assess lifetime exposure to stress and objective cumulative ELS severity. We used diffusion-weighted imaging to measure WM fixel-based morphometry and tested the effects of age and ELS on WM fiber density and cross-section (FDC), and associations between WM FDC and internalizing problems. Age was positively associated with FDC in all WM tracts; greater ELS severity was related to stronger age-WM associations in several association tracts connecting the frontal lobes with limbic, parietal, and occipital regions, including bilateral superior and inferior longitudinal and uncinate fasciculi (UF). Among older adolescents with greater ELS severity, a higher UF FDC was associated with fewer internalizing problems. Greater ELS severity predicted more mature WM morphometry in tracts implicated in emotion regulation and cognitive processing. More phenotypically mature UF WM may be adaptive against internalizing psychopathology in adolescents exposed to ELS.

SUBMITTER: Chahal R

PROVIDER: S-EPMC7750321 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Greater age-related changes in white matter morphometry following early life stress: Associations with internalizing problems in adolescence.

Chahal Rajpreet R Kirshenbaum Jaclyn S JS Ho Tiffany C TC Mastrovito Dana D Gotlib Ian H IH

Developmental cognitive neuroscience 20201208

Early life stress (ELS) is associated with increased risk for internalizing disorders and variations in gray matter development. It is unclear, however, whether ELS affects normative age-related changes in white matter (WM) morphology, and if such maturational differences are associated with risk for internalizing psychopathology. We conducted comprehensive interviews in a cross-sectional sample of young adolescents (N = 156; 89 F; Ages 9-14) to assess lifetime exposure to stress and objective c ...[more]

PMID: 33340790

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Project description:Importance:Although multiple cross-sectional and longitudinal studies have established that sleep problems and behavioral difficulties are associated in children, the directionality of this association and whether sleep problems are differentially associated with different types of childhood behavioral difficulties are unclear. Understanding these associations will inform the focus and timing of interventions. Objective:To determine whether longitudinal and reciprocal associations exist between child sleep problems and externalizing, internalizing, or both behavioral difficulties. Design, Setting, and Participants:Prospective cohort study using nationally representative data from the first 5 waves (2004, 2006, 2008, 2010, and 2012) of the kindergarten cohort (4983 children aged 4-5 years in 2004) collected for the Longitudinal Study of Australian Children. Associations were evaluated using cross-lagged structural equation model analyses performed from May 25, 2016, to September 20, 2017. Main Outcomes and Measures:Child sleep problems and internalizing and externalizing behavioral difficulties. Sleep problems were defined using parent-reported child sleep problem severity and specific difficulties (ie, difficulty getting to sleep at night, not happy sleeping alone, waking during the night, and restless sleep) on 4 or more nights of the week. Child behavioral difficulties were defined using the parent-reported Strengths and Difficulties Questionnaire for externalizing difficulties (conduct problems and hyperactivity/inattention subscales) and internalizing difficulties (emotional problems subscale). Results:The 4983 children enrolled in 2004 had a mean (SD) age of 4.7 (0.2) years and comprised a similar percentage of boys (2536 [50.9%]) and girls. In 2012, 3956 children (79.4%) aged 12 to 13 years were retained. Significant bidirectional associations were detected between sleep problems and externalizing difficulties during the elementary school transition period, with greater sleep problems associated with later externalizing behavior and vice versa (cross-lagged path coefficient, 0.04 [95% CI, 0.01-0.08] to 0.09 [95% CI, 0.06-0.13]). Although sleep was a significant driver of later internalizing difficulties (coefficient, 0.10 [95% CI, 0.07-0.14] to 0.16 [95% CI, 0.12-0.19]), the reverse association was not significant. In the final model that included all 3 constructs, the associations were attenuated but remained significant over time. Conclusions and Relevance:These results suggest that future studies should investigate whether implementing sleep problem intervention decreases the occurrence of both externalizing and internalizing difficulties. Interventions targeting externalizing, but not internalizing, difficulties may benefit childhood sleep.

Project description:BackgroundAdolescence is a critical time for brain development. Findings from previous studies have been inconsistent, failing to distinguish the influence of pubertal status and aging on brain maturation. The current study sought to address these inconsistencies, addressing the trajectories of pubertal development and aging by longitudinally tracking structural brain development during adolescence.MethodsTwo cohorts of healthy children were recruited (cohort 1: 9-10 years old; cohort 2: 12-13 years old at baseline). MRI data were acquired for gray matter volume and white matter tract measures. To determine whether age, pubertal status, both or their interaction best modelled longitudinal data, we compared four multi-level linear regression models to the null model (general brain growth indexed by total segmented volume) using Bayesian model selection.ResultsData were collected at baseline (n = 116), 12 months (n = 97) and 24 months (n = 84) after baseline. Findings demonstrated that the development of most regional gray matter volume, and white matter tract measures, were best modelled by age. Interestingly, precentral and paracentral regions of the cortex, as well as the accumbens demonstrated significant preference for the pubertal status model. None of the white matter tract measures were better modelled by pubertal status.LimitationsThe major limitation of this study is the two-cohort recruitment. Although this allowed a faster coverage of the age span, a complete per person trajectory over 6 years of development (9-15 years) could not be investigated.ConclusionsComparing the impact of age and pubertal status on regional gray matter volume and white matter tract measures, we found age to best predict longitudinal changes. Further longitudinal studies investigating the differential influence of puberty status and age on brain development in more diverse samples are needed to replicate the present results and address mechanisms underlying norm-variants in brain development.

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Greater age-related changes in white matter morphometry following early life stress: Associations with internalizing problems in adolescence.

Publications

Greater age-related changes in white matter morphometry following early life stress: Associations with internalizing problems in adolescence.

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