The DOI matches its Crossref record; 134 of the 134 references it cites were found in a registry or an index.
Alcohol, stress, and glucocorticoids: From risk to dependence and relapse in alcohol use disorders
Open accessAbstract
In this review, we detail the clinical evidence supporting the role of psychological and physiological stress in instrumental motivation for alcohol consumption during the development of mild to moderate alcohol use disorders (AUDs) and in the compulsive, habitual alcohol consumption seen in severe, chronic, relapsing AUDs. Traditionally, the study of AUDs has focused on the direct and indirect effects of alcohol on striatal dopaminergic pathways and their role in the reinforcing effects of alcohol. However, growing evidence also suggests that alcohol directly stimulates the hypothalamic pituitary adrenal (HPA) axis and has effects on glucocorticoid receptors in extrahypothalamic, limbic forebrain, and medial Prefrontal Cortex (PFC) circuits, which contribute to the development of AUDs and their progression in severity, chronicity, and relapse risk. Evidence indicates HPA axis, glucocorticoid, and PFC dysfunction during protracted withdrawal and under high arousal conditions in those with severe AUDs, and novel evidence is also emerging to suggest HPA axis dysfunction with binge/heavy drinking, which is associated with motivation for alcohol in non-dependent individuals. Specifically, alcohol-associated alterations in HPA axis responses to stress and alcohol cues may serve as interoceptive physiological signals and facilitate conditioning mechanisms to influence alcohol motivation. Thus, this dysfunction may serve as a potential biomarker of both risk and of relapse. Based on this emerging data, we conceptualize and present early evidence for treatment targets that may improve PFC function and/or normalize HPA axis functioning and may be beneficial in the treatment and relapse prevention of AUDs. Finally, we suggest that individual differences in alcohol-related pathophysiology in these circuits may modulate treatment and recovery response, thereby supporting the need for building personalized medicine algorithms to understand and treat AUDs. This article is part of the Special Issue entitled "Alcoholism".
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“Chronic activation of the HPA axis causes sustained cortisol to increase and altered stress responses, which is a common occurrence in substance addiction [35].”
From The Impact of Social Media & Technology on Child and Adolescent Mental Health (2025) · cites this paper as [35]
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“Both chronic stress and long-standing alcohol use promote PFC dysfunction [172].”
From Food Addiction and Psychosocial Adversity: Biological Embedding, Contextual Factors, and Public Health Implications (2020) · cites this paper as [172]
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Whiteford, H. A., Degenhardt, L., Rehm, J., Baxter, A. J., Ferrari, A. J., Erskine, H. E., Charlson, F. J., Norman, R. E., Flaxman, A. D., Johns, N., et al. (2013) · The Lancet · doi:10.1016/s0140-6736(13)61611-6 · Cited by 6,006
Stress, adaptation, and disease. Allostasis and allostatic load
McEWEN, B. S. (1998) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1998.tb09546.x · Cited by 5,092 · cited 1×
“This return to a healthy normal set-point occurs via allostatic processes, which allow the brain and body to achieve physiological stability through challenges to homeostasis by altering cellular structure and function (McEwen, 1998).”
The cognitive control of emotion
OCHSNER, K., & GROSS, J. (2005) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2005.03.010 · Cited by 4,495 · cited 2×
“…relays leads to damage via glucocorticoid -induced excitotoxicity, then self-directed behavior may be even more likely to be replaced by habit and sensory-driven automatic responding (Bechara, 2005; Ochsner and Gross, 2005; Ochsner et al., 2004; Rosenkranz and Grace, 2002; Thayer et al., 2009).”
Neural regulation of endocrine and autonomic stress responses
Ulrich-Lai, Y. M., & Herman, J. P. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2647 · Cited by 3,318 · cited 1×
“Under normal conditions, the PFC can inhibit the physiological response to stress that is related to activation of the HPA axis and the autonomic nervous system (Spencer et al., 2005; Ulrich-Lai and Herman, 2009).”
Stress signalling pathways that impair prefrontal cortex structure and function
Arnsten, A. F. T. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2648 · Cited by 3,299 · cited 2×
“…AUDs, i.e., decreases in working memory function, poor attention and flexibility, lower behavioral control, and increases in impulsive responding (Arnsten, 2009a; Bechara, 2005; Koob and Le Moal, 2005; Matikainen et al., 1986; Piazza and Le Moal, 1997; Rosenkranz and Grace, 2002; Volkow et al.,…”
Emotional processing in anterior cingulate and medial prefrontal cortex
Etkin, A., Egner, T., & Kalisch, R. (2011) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2010.11.004 · Cited by 3,059
Hasin, D. S., Stinson, F. S., Ogburn, E., & Grant, B. F. (2007) · Archives of General Psychiatry · doi:10.1001/archpsyc.64.7.830 · Cited by 2,908 · cited 1×
“…. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145 Eighteen percent of Americans suffer from an alcohol use disorder (AUD) at some point during their lifetime and up to 8% of Americans go on to develop severe AUDs (Hasin et al., 2007).”
Drug abuse: hedonic homeostatic dysregulation
Koob, G. F., & Moal, M. L. (1997) · Science · doi:10.1126/science.278.5335.52 · Cited by 2,535 · cited 2×
“…consumption results in larger-scale adaptations and wear and tear (allostatic overload) to the reward and neuroendocrine regulation circuits (Koob and Le Moal, 2005; Sinha, 2001); these adaptations may represent the pathophysiology underlying the transition from controlled to compulsive…”
Dopamine in motivational control: rewarding, aversive, and alerting
Bromberg-Martin, E. S., Matsumoto, M., & Hikosaka, O. (2010) · Neuron · doi:10.1016/j.neuron.2010.11.022 · Cited by 2,396 · cited 1×
“A wealth of preclinical and clinical data indicates that acute stressors may play a role in the motivation for alcohol consumption in those with and without AUDs (Chaplin et al., 2008; Goeders, 2004; Sinha, 2001; Uhart and Wand, 2009).”
Decision making, impulse control and loss of willpower to resist drugs: a neurocognitive perspective
Bechara, A. (2005) · Nature Neuroscience · doi:10.1038/nn1584 · Cited by 2,149 · cited 3×
“…relays leads to damage via glucocorticoid -induced excitotoxicity, then self-directed behavior may be even more likely to be replaced by habit and sensory-driven automatic responding (Bechara, 2005; Ochsner and Gross, 2005; Ochsner et al., 2004; Rosenkranz and Grace, 2002; Thayer et al., 2009).”
Research works printed but not linked: 8
- Arnsten, 2009, Stress signalling pathways that impair prefrontal cortex structure and function, Nat. Rev. Neurosci., 10, 410, 10.1038/nrn2648 · DOI · Paper page
- D’Sa, 2012, Alterations in serum cytokines, chemokines, interferons, growth factors and C-Reactive protein in alcohol-dependent individuals compared with social drinkers, Alcohol. Clin. Exp. Res., 36
- Glassman, 1993, Clinical trials and therapeutics smokng vulnerabi lity to, Clini. Pharmaco. Ther., 54
- Seo, 2014, Neurobiol. alcohol craving relapse Handb. Clin. Neurosci., 125, 355
- Sinha, 2012, Pharmacotherapy development to target dysfunction of stress and craving regulation in alcohol dependence, Alcohol. Clin. Exp. Res., S234, 36
- Sinha R, Fox H, Tuit K, Morgan P (2011a) Chronic alcohol related adaptations in stress arousal: Effects on Relapse Susceptibility and Treatment Outcome. Presented at the Stress and Alcoholism: New Approaches to Treatment Conference, Volterra, Italy, May 3–6. Alcohol Supplement S57.
- Sinha, 2009, Enhanced negative emotion and alcohol craving, and altered physiological responses following stress and cue exposure in alcohol dependent individuals. Neuropsychopharmacology, Official Publ. Am. Coll. Neuropsychopharmacol., 34, 1198, 10.1038/npp.2008.78 · DOI · Paper page
- Sinha, 2013, Alcohol effects on neuroendocrine and metabolic responses to stress and motivation for alcohol intake, Alcohol. Clin. Exp. Res., 254A
Cited by
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Stress and Obesity: Are There More Susceptible Individuals?
van der Valk, E. S., Savas, M., & van Rossum, E. F. C. (2018) · Current Obesity Reports · doi:10.1007/s13679-018-0306-y · Cited by 402
Alcohol use disorder relapse factors: A systematic review.
Sliedrecht, W., de Waart, R., Witkiewitz, K., & Roozen, H. G. (2019) · Psychiatry Research · doi:10.1016/j.psychres.2019.05.038 · Cited by 358
Diseases, Disorders, and Comorbidities of Interoception
Bonaz, B., Lane, R. D., Oshinsky, M. L., Kenny, P. J., Sinha, R., Mayer, E. A., & Critchley, H. D. (2021) · Trends in Neurosciences · doi:10.1016/j.tins.2020.09.009 · Cited by 260
Sex Differences in the Neurobiology of Alcohol Use Disorder
Flores‐Bonilla, A. (2020) · Alcohol research · doi:10.35946/arcr.v40.2.04 · Cited by 218
Guinle, M. I. B. (2020) · Alcohol research · doi:10.35946/arcr.v40.2.05 · Cited by 211
Metadata
- Authors
- Blaine, S. K., & Sinha, R.
- Affiliations
- Yale University (US)
- Corresponding author
- Sinha, Rajita
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2017-08
- Volume
- 122
- Pages
- 136-147
- ISSN
- 0028-3908 (ISSN-L)
- PMC
- PMC5479733
- OpenAlex
- W2583762848
- Cited by
- 257
- References
- 133
- Citations by year
- 2026: 21 · 2025: 20 · 2024: 25 · 2023: 35 · 2022: 38 · 2021: 30 · 2020: 39 · 2019: 13 · 2018: 29 · 2017: 7
- FWCI
- 3.19
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Neuropharmacology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Alcoholism (R01-AA13892, R01-AA020504)
- Alcohol Abuse at the National Institutes of Health (R21-AA025277)
- Topics
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- alcoholism, stress, glucocorticoids, hypothalamic-pituitary-adrenal axis, relapse, drinking motives, binge drinking, prefrontal cortex, alcohol withdrawal, alcohol cue reactivity, interoception, conditioning, biomarkers, personalized medicine, treatment goals
- MeSH terms
- Alcohol Drinking, Alcoholism, Animals, Brain, Glucocorticoids, Humans, Hypothalamo-Hypophyseal System, Pituitary-Adrenal System, Recurrence, Stress, Physiological, Stress, Psychological, Prefrontal Cortex
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