Neurobiological mechanisms of early life adversity, blunted stress reactivity and risk for addiction

Mustafa al'Absi, Annie T. Ginty, William R. Lovallo

Research output: Contribution to journalReview articlepeer-review

10 Scopus citations


Blunted stress reactivity resulting from early exposure to stress during childhood and adolescence may increase vulnerability to addiction. Early life adversity (ELA) affects brain structure and function and results in blunted stress axis reactivity. In this review, we focus on the underlying neurobiological mechanisms associated with a blunted response to stress, ELA, and risk for addictive disorders. ELA and blunted reactivity are accompanied by unstable mood regulation, impulsive behaviors, and reduced cognitive function. Neuroimaging studies reveal cortical and subcortical changes in persons exposed to ELA and those who have a genetic disposition for addiction. We propose a model in which blunted stress reactivity may be a marker of risk for addiction through an altered motivational and behavioral reactivity to stress that contribute to disinhibited behavioral reactivity and impulsivity leading in turn to increased vulnerability for substance use. Evidence supporting this hypothesis in the context of substance use initiation, maintenance, and risk for relapse is presented. The effects of ELA on persons at risk for addiction may lead to early experimentation with drugs of abuse. Early adoption of drug intake may alter neuroregulation in such vulnerable persons leading to a permanent dysregulation of motivational responses consistent with dependence. This article is part of the special issue on 'Vulnerabilities to Substance Abuse'.

Original languageEnglish (US)
Article number108519
StatePublished - May 1 2021

Bibliographical note

Funding Information:
This paper was supported in part by grants from the National Institutes of Health : R01DA016351 and R01DA027232 (MA), K01HL145021 (ATG); the US Department of Veterans Affairs , CX000252 , and the National Institutes of Health , AA12207 (WRL).

Publisher Copyright:
© 2021


  • Addiction risk
  • Early life adversity
  • HPA axis
  • Neurobiological mechanisms
  • Stress reactivity

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review


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