Effects of adrenal sensitivity, stress- and cue-induced craving, and anxiety on subsequent alcohol relapse and treatment outcomes

Arch Gen Psychiatry. 2011 Sep;68(9):942-52. doi: 10.1001/archgenpsychiatry.2011.49. Epub 2011 May 2.


Context: Alcoholism is a chronic, relapsing illness in which stress and alcohol cues contribute significantly to relapse risk. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, increased anxiety, and high alcohol craving have been documented during early alcohol recovery, but their influence on relapse risk has not been well studied.

Objectives: To investigate these responses in treatment-engaged, 1-month-abstinent, recovering alcohol-dependent patients relative to matched controls (study 1) and to assess whether HPA axis function, anxiety, and craving responses are predictive of subsequent alcohol relapse and treatment outcome (study 2).

Design: Experimental exposure to stress, alcohol cues, and neutral, relaxing context to provoke alcohol craving, anxiety, and HPA axis responses (corticotropin and cortisol levels and cortisol to corticotropin ratio) and a prospective 90-day follow-up outcome design to assess alcohol relapse and aftercare treatment outcomes.

Setting: Inpatient treatment in a community mental health center and hospital-based research unit.

Participants: Treatment-engaged alcohol-dependent individuals and healthy controls.

Main outcome measures: Time to alcohol relapse and to heavy drinking relapse.

Results: Significant HPA axis dysregulation, marked by higher basal corticotropin level and lack of stress- and cue-induced corticotropin and cortisol responses, higher anxiety, and greater stress- and cue-induced alcohol craving, was seen in the alcohol-dependent patients vs the control group. Stress- and cue-induced anxiety and stress-induced alcohol craving were associated with fewer days in aftercare alcohol treatment. High provoked alcohol craving to both stress and to cues and greater neutral, relaxed-state cortisol to corticotropin ratio (adrenal sensitivity) were each predictive of shorter time to alcohol relapse.

Conclusions: These results identify a significant effect of high adrenal sensitivity, anxiety, and increased stress- and cue-induced alcohol craving on subsequent alcohol relapse and treatment outcomes. Findings suggest that new treatments that decrease adrenal sensitivity, stress- and cue-induced alcohol craving, and anxiety could be beneficial in improving alcohol relapse outcomes.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adrenal Glands / physiopathology*
  • Adrenocorticotropic Hormone / blood
  • Adult
  • Alcoholism / complications
  • Alcoholism / physiopathology
  • Alcoholism / psychology*
  • Alcoholism / therapy
  • Anxiety / complications
  • Anxiety / psychology*
  • Behavior, Addictive / complications
  • Behavior, Addictive / metabolism*
  • Behavior, Addictive / physiopathology
  • Behavior, Addictive / psychology*
  • Behavior, Addictive / therapy
  • Case-Control Studies
  • Cues
  • Female
  • Humans
  • Hydrocortisone / blood
  • Hypothalamo-Hypophyseal System / physiopathology
  • Male
  • Middle Aged
  • Pituitary-Adrenal System / physiopathology
  • Psychotherapy / methods
  • Recurrence
  • Relaxation Therapy / methods
  • Stress, Psychological / complications
  • Stress, Psychological / psychology*


  • Adrenocorticotropic Hormone
  • Hydrocortisone