Allostatic load as a mediator of childhood maltreatment and adulthood depressive symptoms: A longitudinal analysis

O'Shields, Jay; Mowbray, Orion; Patel, Dipali

doi:10.1016/j.psyneuen.2022.105839

Cited by 3 publications

(2 citation statements)

References 53 publications

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“…We found that AL partly mediated the longitudinal association between exposomic burden and youth psychopathology at age 12 (parent-reported). This finding aligns with previous works showing the mediating role of AL on the path from specific exposures, childhood physical and sexual abuse 95,96 and neighborhood poverty, 97,98 to mental health burden in older adolescents and adults. Our results also indicate that AL mediates the relationship between genetic susceptibility and mental health burden.…”

Section: Discussionsupporting

confidence: 92%

Allostatic load in early adolescence: gene / environment contributions and relevance for mental health

Hoffman,

Tran,

Moore

et al. 2023

Preprint

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Background. Allostatic load is the cumulative 'wear and tear' on the body due to chronic adversity. We aimed to test poly-environmental (exposomic) and polygenic contributions to allostatic load and their combined contribution to early adolescent mental health. Methods. We analyzed data on N = 5,035 diverse youth (mean age 12) from the Adolescent Brain Cognitive Development Study (ABCD). Using dimensionality reduction method, we calculated and overall allostatic load score (AL) using body mass index [BMI], waist circumference, blood pressure, blood glycemia, blood cholesterol, and salivary DHEA. Childhood exposomic risk was quantified using multi-level environmental exposures before age 11. Genetic risk was quantified using polygenic risk scores (PRS) for metabolic system susceptibility (type 2 diabetes [T2D]) and stress-related psychiatric disease (major depressive disorder [MDD]). We used linear mixed effects models to test main, additive, and interactive effects of exposomic and polygenic risk (independent variables) on AL (dependent variable). Mediation models tested the mediating role of AL on the pathway from exposomic and polygenic risk to youth mental health. Models adjusted for demographics and genetic principal components. Results. We observed disparities in AL with non-Hispanic White youth having significantly lower AL compared to Hispanic and Non-Hispanic Black youth. In the diverse sample, childhood exposomic burden was associated with AL in adolescence (beta=0.25, 95%CI 0.22-0.29, P<.001). In European ancestry participants (n=2,928), polygenic risk of both T2D and depression was associated with AL (T2D-PRS beta=0.11, 95%CI 0.07-0.14, P<.001; MDD-PRS beta=0.05, 95%CI 0.02-0.09, P=.003). Both polygenic scores showed significant interaction with exposomic risk such that, with greater polygenic risk, the association between exposome and AL was stronger. AL partly mediated the pathway to youth mental health from exposomic risk and from MDD-PRS, and fully mediated the pathway from T2D-PRS. Conclusions. AL can be quantified in youth using anthropometric and biological measures and is mapped to exposomic and polygenic risk. Main and interactive environmental and genetic effects support a diathesis-stress model. Findings suggest that both environmental and genetic risk be considered when modeling stress-related health conditions.

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Section: Discussionsupporting

confidence: 92%

Allostatic load in early adolescence: gene / environment contributions and relevance for mental health

Hoffman,

Tran,

Moore

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Chronic social defeat in rodents has been shown to trigger inflammation and impact immune function (Niraula & Sheridan, 2019; Powell et al, 2013). Compromised immune function and associated inflammation have also been discussed as strong mediators of the pathological influences of childhood maltreatment (Baldwin et al, 2018; Coelho et al, 2014; Cohen-Woods et al, 2018; Danese et al, 2007; do Prado et al, 2017; Gonzalez, 2013; Osborn & Widom, 2020; O’Shields et al, 2022). A more stringent analysis of our data using DGE also pointed to immune function as a biological process that was perturbed after maltreatment.…”

Section: Discussionmentioning

confidence: 99%

RNA in extracellular vesicles during adolescence reveal immune, energetic and microbial imprints of early life adversity

Korobkova

Morin

Aoued³

et al. 2023

Preprint

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Exposure to early life adversity (ELA), including childhood maltreatment, is one of the most significant risk factors for the emergence of neuropsychiatric disorders in adolescence and adulthood. Despite this relationship being well established, the underlying mechanisms remain unclear. One way to achieve this understanding is to identify molecular pathways and processes that are perturbed as a consequence of childhood maltreatment. Ideally, these perturbations would be evident as changes in DNA, RNA or protein profiles in easily accessible biological samples collected in the shadow of childhood maltreatment. In this study, we isolated circulating extracellular vesicles (EVs) from plasma collected from adolescent rhesus macaques that had either experienced nurturing maternal care (CONT) or maternal maltreatment (MALT) in infancy. RNA sequencing of RNA in plasma EVs and gene enrichment analysis revealed that genes related to translation, ATP synthesis, mitochondrial function and immune response were downregulated in MALT samples, while genes involved in ion transport, metabolism and cell differentiation were upregulated. Interestingly, we found that a significant proportion of EV RNA aligned to the microbiome and that MALT altered the diversity of microbiome-associated RNA signatures found in EVs. Part of this altered diversity suggested differences in prevalence of bacterial species in CONT and MALT animals noted in the RNA signatures of the circulating EVs. Our findings provide evidence that immune function, cellular energetics and the microbiome may be important conduits via which infant maltreatment exerts effects on physiology and behavior in adolescence and adulthood. As a corollary, perturbations of RNA profiles related to immune function, cellular energetics and the microbiome may serve as biomarkers of responsiveness to ELA. Our results demonstrate that RNA profiles in EVs can serve as a powerful proxy to identify biological processes that might be perturbed by ELA and that may contribute to the etiology of neuropsychiatric disorders in the aftermath of ELA.

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Exposomic and polygenic contributions to allostatic load in early adolescence

Hoffman,

Tran,

Moore

et al. 2024

Nat. Mental Health

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Allostatic load as a mediator of childhood maltreatment and adulthood depressive symptoms: A longitudinal analysis

Cited by 3 publications

References 53 publications

Allostatic load in early adolescence: gene / environment contributions and relevance for mental health

Allostatic load in early adolescence: gene / environment contributions and relevance for mental health

RNA in extracellular vesicles during adolescence reveal immune, energetic and microbial imprints of early life adversity

Exposomic and polygenic contributions to allostatic load in early adolescence

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