Editors' ChoicePEDIATRICS

Childhood adversity reprograms gene expression

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Science Translational Medicine  01 Jun 2016:
Vol. 8, Issue 341, pp. 341ec87
DOI: 10.1126/scitranslmed.aag1703

Daily news reports remind us that of the nearly 5 million refugees from war-torn Syria, half are children. These highly vulnerable members of society are now at greater risk of becoming ill, malnourished, exploited, or abused. Furthermore, childhood adversity is the most commonly observed risk factor for a broad range of psychiatric disorders that emerge later in adolescence or early adulthood. The persistence and scope of this risk suggests that, even in the absence of overt psychiatric symptoms or disease, adverse conditions experienced early in life reprogram physiological responses. To probe the molecular basis of the reprogramming hypothesis, Schwaiger and colleagues examine how two factors—childhood adversity and stress—combine to alter patterns of gene expression in otherwise healthy human subjects in the 45- to 60-year age range. Only subjects who did not meet the criteria for a psychiatric disorder were included in the study.

Acute psychosocial stress, such as challenges to interpersonal or professional functioning, is one factor that is believed to precipitate the emergence of psychiatric symptoms in vulnerable individuals. In peripheral blood monocytes from control subjects and those who suffered adversity early in life, the authors performed genome-wide gene expression analyses both before and after a laboratory-based, stress-inducing public speaking challenge in order to identify stress-responsive genes whose expression changed differentially as a function of childhood adversity. They pinpointed alterations in the transcription of genes that encode proteins important for proper functioning of the immune system function (such as cytokines and cell signaling regulators). Analyses also suggested an increase in proinflammatory gene transcription in individuals with early-life adversity as well as correlations between the expression of selected genes and the release of cortisol, which serves as a peripheral marker of the stress response. The authors interpreted these findings in light of research suggesting that depression and other stress-related disorders are associated, at least in some people, with a subclinical increase in inflammation. Because the individuals studied by Schwaiger and colleagues were in mid-life and had no psychiatric diagnoses despite significant early-life adversity, these findings indicate the existence of a molecular resilience rather than a risk pathway. Likewise uncertain are the differences in transcriptional responses in the brain as related to childhood adversity and acute stress. Nonetheless, these findings provide important new information that helps ground a still-vague construct (childhood adversity) in a specific genomic response to acute psychosocial stress, thereby tying together, mechanistically, social and biological influences on human health.

M. Schwaiger et al., Altered stress-induced regulation of genes in monocytes in adults with a history of childhood adversity. Neuropsychopharmacology 10.1038/npp.2016.57 (2016). [Full Text]

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