Stress, Hypothalamic-pituitary-adrenal (HPA) Dysfunction, and Relapse in Alcoholism
Condition: Alcohol Dependence
MeSH terms: Recurrence; Alcoholism
Study type: Observational

Summary: 
      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.
    

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.
    

Observational model: Case-Only
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Inpatient treatment facility for substance use disorders.
      
Biospecimen description: 
      serum plasma whole blood urine
    
Keywords: substance abuse; alcohol dependence; hypothalamic-pituitary-adrenal (HPA) system; cosyntropin; corticotropin-releasing Hormone (CRH); pituitary-adrenal system; stress; trauma; neurosteroids; cortisol; relapse