Stress, Hypothalamic-pituitary-adrenal (HPA) Dysfunction, and Relapse in Alcoholism

This study has been completed.
Dallas VA Medical Center
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Information provided by (Responsible Party):
Bryon H Adinoff, University of Texas Southwestern Medical Center Identifier:
First received: June 19, 2008
Last updated: January 2, 2013
Last verified: January 2013

This proposal is part of the INIA Stress Consortium. This study will

  1. explore the contributions of lifetime trauma, recent stress, and alcohol use on stress-hormone axis disruption in treatment seeking, one-month abstinent, alcohol-dependent subjects
  2. assess the combined contributions of stress-hormone axis disruption and episodic stress on the risk of prospective drinking following treatment
  3. determine the role of neurosteroids in alcohol use.

Alcohol Dependence

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Cross-Sectional
Official Title: Stress, HPA Dysfunction, and Relapse in Alcoholism

Resource links provided by NLM:

Further study details as provided by University of Texas Southwestern Medical Center:

Primary Outcome Measures:
  • Examine the contributions of previous trauma, recent stress, and chronic alcohol use to the stress-hormone axis reactivity in one-month abstinent alcohol-dependent subjects. [ Time Frame: one month ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Assess the ability of stress-hormone axis reactivity and ongoing stress to predict subsequent drinking behavior following treatment discharge. [ Time Frame: Six months ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA
serum plasma whole blood urine

Enrollment: 75
Study Start Date: August 2007
Study Completion Date: March 2012
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
alcohol dependence
Alcohol-dependent subjects currently being treated in an inpatient treatment facility.

Detailed Description:

The hypothalamic-pituitary-adrenal (HPA) system is suggested as a key biologic link in stress-induced relapse. The HPA axis provides a regulatory feedback network between the brain and the body's behavioral and physiologic responses to stress, recovery, and adaptation. Both trauma and chronic alcohol use produce persistent disturbances in the HPA response to stress. The chronic use of alcohol may also impair the stress-induced release of neurosteroids, compounds that directly modulate central nervous system activity. Thus, altered cortisol and neurosteroid responsiveness during abstinence may impair the central nervous system's ability to mount an appropriate response to environmental stressors, heightening the probability of relapse. However, the relationship between stress, relapse, and HPA axis disturbances remains tentative. In the proposed study, the investigators will assess the contribution of trauma, stress, and alcohol use upon pituitary-adrenocortical functioning in alcohol dependence. The relative contribution of adrenocortical disruption and episodic stress to prospective drinking behaviors will then be determined.

Hypothesis: We hypothesize (1) that lifetime trauma, recent stress, and chronic alcohol use will additively contribute to HPA axis disruption, (2) alterations in glucocorticoid and neurosteroid release as well as episodic stress will predict a return to drinking.

Methods: One hundred treatment-seeking, one-month abstinent, alcohol-dependent subjects will be studied. Standardized assessments will be used to assess childhood and adult trauma as well as recent (six months) stress. Pituitary-adrenal (including ACTH (adrenocorticotropin), cortisol, and neurosteroids) responses to both neuroendocrine [ovine corticotropin releasing hormone (oCRH), cosyntropin, and dexamethasone] and experiential (public speaking) challenges will be measured. Drinking behavior and episodic stress will be prospectively assessed for six months following neuroendocrine assessment.

Significance: If our hypotheses are supported, a definitive connection between previous trauma, biological stress response mechanisms, and ongoing stress upon prospective drinking behavior will be demonstrated. The identification of a specific biologic mechanism that underlies this association will provide a fertile framework for the development of targeted pharmacological interventions to decrease relapse in this vulnerable population. In addition, elucidating the concurrent contributions of stress-response biologic systems and externals stressors will provide the therapist and patient with a constellation of specific risk factors for focused treatment.


Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Inpatient treatment facility for substance use disorders.

Inclusion Criteria:

  • Diagnosis of alcohol dependence

Exclusion Criteria:

  • Medical or psychiatric disorders that may effect stress-hormone axis functioning.
  • Medications that may effect stress-hormone axis functioning.
  • English speaking.
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Please refer to this study by its identifier: NCT00744588

United States, Texas
UT Southwestern Medical Center at Dallas
Dallas, Texas, United States, 75390-8564
Sponsors and Collaborators
University of Texas Southwestern Medical Center
Dallas VA Medical Center
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Principal Investigator: Bryon Adinoff, MD UT Southwestern Medical Center at Dallas and VA North Texas Health Care System
  More Information

Additional Information:
No publications provided

Responsible Party: Bryon H Adinoff, Professor, University of Texas Southwestern Medical Center Identifier: NCT00744588     History of Changes
Other Study ID Numbers: AA016668, U01AA016668
Study First Received: June 19, 2008
Last Updated: January 2, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Texas Southwestern Medical Center:
substance abuse
alcohol dependence
hypothalamic-pituitary-adrenal (HPA) system
corticotropin-releasing Hormone (CRH)
pituitary-adrenal system

Additional relevant MeSH terms:
Alcohol-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Substance-Related Disorders processed this record on November 27, 2015