Editors' ChoiceMENTAL HEALTH

Painful marks of childhood abuse

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Science Translational Medicine  16 Aug 2017:
Vol. 9, Issue 403, eaao4207
DOI: 10.1126/scitranslmed.aao4207


Adverse childhood experiences epigenetically regulate expression of kappa opioid receptors.

Exposure to abuse and neglect during childhood increases the risk for psychopathology and suicide in adulthood. Although studies indicate that the opioid system controls mood-related processes and social behaviors, whether and how stressful childhood experiences impact the opioid system to increase risk for psychopathology and suicide remain unknown. Because epigenetic factors, including DNA methylation, are implicated as the pathway by which the environment can impact gene transcription and expression, Lutz and collaborators designed a study to characterize the effects of childhood abuse on expression and methylation of opioid signaling genes within limbic brain areas shown previously to be implicated in social processes and modulated by opioids. Investigators compared gene expression profiles of six opioid pathway signaling factors (proopiomelanocortin, enkephalin, dynorphin; and delta, mu, and kappa opioid receptors) in postmortem brain tissue between individuals who died by suicide with and without a history of severe childhood abuse and psychiatrically healthy controls who died suddenly from accidental causes.

Findings showed that kappa opioid receptor gene expression and methylation were significantly decreased in the anterior insula of those individuals exposed to childhood abuse compared with psychiatrically healthy controls and those who died from suicide with no history of childhood abuse. Furthermore, the authors used in vitro techniques to show that glucocorticoid receptor binding to the region where changes in methylation were observed regulated kappa opioid receptor gene expression. These data suggest that epigenetic changes in individuals exposed to childhood abuse modulate kappa opioid receptor gene expression by regulating glucocorticoid binding at this specific locus, highlighting a novel biological mechanism by which stress exposure during early life can have long-lasting impacts on the central opioid system in humans. The emergence of kappa opioid receptor as a critical signal for the encoding early life social experiences is interesting and novel, as previously data have shown more robust effects of the mu opioid receptor in social processes. Future studies are necessary to pinpoint the exact role of limbic kappa opioid receptor on socioemotional behavior and determine how exposure to early adverse events and stress signals disrupt its functions.

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