Early life adversity diminishes the cortisol response to opioid blockade in women: Studies from the Family Health Patterns project

William R Lovallo, Ashley Acheson, Andrea S Vincent, Kristen H Sorocco, Andrew J Cohoon, William R Lovallo, Ashley Acheson, Andrea S Vincent, Kristen H Sorocco, Andrew J Cohoon

Abstract

Early life adversity (ELA) contributes to behavioral impulsivity along with risk for substance use disorders, both accompanied by blunted stress-axis reactivity. However, the biological contributors to blunted stress reactivity are not known. We took advantage of the fact that women have significant opioid inhibition of cortisol output by using the opioid antagonist, naltrexone, to unmask opioid interactions due to ELA. We administered 50 mg of naltrexone or placebo to 72 healthy women (23 years of age) in a double-blind crossover study and observed deviations in cortisol secretion from placebo over the next 180 minutes. ELA was assessed by reported exposure to physical and sexual abuse or neglect and low socioeconomic status and scored as Low, Medium, or High (0, 1-2, and 3+). The ELA groups all had identical placebo-day cortisol secretion, indicating normal basal regulation of the hypothalamic-pituitary-adrenocortical axis. Cortisol rises to naltrexone were largest in the Low-ELA group and strongly blunted in the High-ELA group (F = 3.51, p = 0.035), indicating a lack of opioid function in women with high degrees of ELA. The Low-ELA women reported dysphoric responses to naltrexone (F = 4.05, p = .022) indicating a mild opioid withdrawal, an effect that was absent in the High-ELA group. Women exposed to ELA have blunted cortisol responses to naltrexone, indicating reduced opioid regulation of the stress axis. Central opioid changes may be one pathway linking ELA to blunted stress reactivity in adulthood.

Conflict of interest statement

The authors have declared that no competing interest exists.

Figures

Fig 1. Saliva cortisol values in response…
Fig 1. Saliva cortisol values in response to naltrexone in women with Low (0), Medium (1–2), and High (3+) levels of Early Life Adversity.
Top panel: change in saliva cortisol from the placebo day to the naltrexone day averaged over 90–150 minutes after administration of 50 mg naltrexone or placebo. Middle panel: change in saliva cortisol on naltrexone day at each collection interval. Arrow indicates time of naltrexone or placebo administration. Bottom panel: Saliva cortisol on placebo day for the three ELA groups.

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