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Review
. 2012;34(4):468-83.

Stress and the HPA axis: role of glucocorticoids in alcohol dependence

Mary Ann C Stephens  1 , Gary Wand
Affiliations
Review

Stress and the HPA axis: role of glucocorticoids in alcohol dependence

Mary Ann C Stephens et al. Alcohol Res. 2012.

Abstract

Stress has long been suggested to be an important correlate of uncontrolled drinking and relapse. An important hormonal response system to stress-the hypothalamic-pituitary-adrenal (HPA) axis-may be involved in this process, particularly stress hormones known as glucocorticoids and primarily cortisol. The actions of this hormone system normally are tightly regulated to ensure that the body can respond quickly to stressful events and return to a normal state just as rapidly. The main determinants of HPA axis activity are genetic background, early-life environment, and current life stress. Alterations in HPA axis regulation are associated with problematic alcohol use and dependence; however, the nature of this dysregulation appears to vary with respect to stage of alcohol dependence. Much of this research has focused specifically on the role of cortisol in the risk for, development of, and relapse to chronic alcohol use. These studies found that cortisol can interact with the brain's reward system, which may contribute to alcohol's reinforcing effects. Cortisol also can influence a person's cognitive processes, promoting habit-based learning, which may contribute to habit formation and risk of relapse. Finally, cortisol levels during abstinence may be useful clinical indicators of relapse vulnerability in alcohol-dependent people.

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Figures

Figure 1
Figure 1
The major components of the stress response mediated by the hypothalamic–pituitary–adrenal (HPA) axis. Both alcohol and stress can induce nerve cells in one brain region (i.e., the hypothalamus) to produce and release corticotropin-releasing factor (CRF). Within the hypothalamus, CRF stimulates the release of a hormone that produces morphine-like effects (i.e., β-endorphin). CRF also is transported to a key endocrine gland, the anterior pituitary gland. There, CRF stimulates production of a protein proopiomelanocortin (POMC). POMC serves as the basis for a number of stress-related hormones, including adrenocorticotropic hormone (ACTH), β-lipotropin (β-LPH), and β-endorphin. ACTH stimulates cells of the adrenal glands to produce and release the stress hormone cortisol. When cortisol levels reach a certain level, CRF and ACTH release diminishes. Other neurons releasing serotonin (5-HT), norepin ephrine (NE), γ-aminobutyric acid (GABA), or endogenous opioids also regulate CRH release. NOTE: = ⊕ excites; ⊖ = inhibits.
Figure 2
Figure 2
Summary of the activity of the hypothalamic–pituitary–adrenal (HPA) axis during different stages of alcoholism development and their potential consequences. NOTE: *Low level of response (LR) to alcohol is a phenotype that predicts higher risk for alcohol-related problems (Hu et al. 2005); currently, there are no data characterizing HPA axis response to mental stress in this high-risk group. Posttraumatic stress disorder (PTSD) is a complicated disorder with multiple subtypes and comorbidities; the HPA axis profile of individuals with PTSD symptomatology generally is not thought to react to mental stress with enhanced responsivity and therefore does not fit the model depicted above for other high-risk social drinkers.
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References

    1. Aardal-Eriksson E, Eriksson TE, Thorell LH. Salivary cortisol, posttraumatic stress symptoms, and general health in the acute phase and during 9-month follow-up. Biological Psychiatry. 2001;50(12):986–993. - PubMed
    1. Adinoff B, Best SE, Ye W, et al. Adrenocortical and pituitary glucocorticoid feedback in abstinent alcohol-dependent women. Alcoholism: Clinical and Experimental Research. 2010;34(5):915–924. - PMC - PubMed
    1. Adinoff B, Iranmanesh A, Veldhuis J, Fisher L. Disturbances of the stress response: The role of the HPA axis during alcohol withdrawal and abstinence. Alcohol Health & Research World. 1998;22(1):67–72. - PMC - PubMed
    1. Adinoff B, Junghanns K, Kiefer F, Krishnan-Sarin S. Suppression of the HPA axis stress-response: Implications for relapse. Alcoholism: Clinical and Experimental Research. 2005a;29(7):1351–1355. - PMC - PubMed
    1. Adinoff B, Krebaum SR, Chandler PA, et al. Dissection of hypothalamic-pituitary-adrenal axis pathology in 1-month-abstinent alcohol-dependent men, part 2: Response to ovine corticotropin-releasing factor and naloxone. Alcoholism: Clinical and Experimental Research. 2005b;29(4):528–537. - PMC - PubMed

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