RNA in Plasma Extracellular Vesicles of Adolescent Rhesus Macaques Reveals Immune, Bioenergetic, and Microbial Imprints of Early-Life Adversity: An Exploratory Analysis.

BACKGROUND

Exposure to early-life adversity (ELA), including childhood maltreatment, is one of the most significant risk factors for the emergence of psychosomatic disorders in adolescence and adulthood. Most investigations into biological processes that have been perturbed by ELA have profiled DNA methylation in whole blood and coalesced around perturbations of immunobiology being centrally insulted by ELA.

METHODS

To identify novel molecular signatures that are enduringly perturbed by childhood maltreatment, we isolated circulating extracellular vesicles (EVs) from plasma collected from adolescent rhesus macaques that had either experienced nurturing maternal care (n = 7; 3 female, 4 male) or maltreatment in infancy (n = 6; 3 female, 3 male). Next, we profiled the RNA found in these EVs.

RESULTS

RNA associated with genes related to translation, ATP (adenosine triphosphate) synthesis, mitochondrial function, and immune response were downregulated in circulating EVs collected from adolescent macaques that had experienced maltreatment during infancy, while those involved in ion transport, metabolism, and cell differentiation were upregulated in these EVs. Additionally, a significant proportion of EV RNA aligned to the microbiome and maltreatment during infancy altered the diversity of microbiome-associated RNA signatures found in EVs.

CONCLUSIONS

Our findings provide evidence that alterations in RNA associated with immune function, cellular energetics, and the microbiome in circulating EVs may serve as enduring biomarkers of prior exposure to ELA. As a corollary, perturbations of these RNA profiles may offer novel molecular insight into how biology can remain altered long after the shadow of ELA has passed.