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Chapter 6 - Alcohol Use Disorders: Aetiology and Pathophysiology

Published online by Cambridge University Press:  02 November 2021

By
Nicola J. Kalk  and
Mary Thornton
Edited by
Ed Day
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Summary

The aetiology and pathophysiology of alcohol dependence are complex, derived from genetics, parenting, peer and societal norms and rules, pharmacology and mental health comorbidity. This chapter explores some of the contributing factors that make alcohol dependence a more complex phenomenon than one merely of personal choice. It explores the various aspects of family history that contribute to the heritability of alcohol use disorders, and summarises relevant social and psychological factors. It then provides a nuanced understanding of the pharmacological rationale underpinning withdrawal and relapse prevention treatment, including an understanding of the role of GABA, glutamate and opioid systems. The chapter concludes by highlighting the ways in which patients with psychiatric disorders may be at greater risk of alcohol use disorders. In doing so, consideration is given to trauma-informed principles of care in light of the high prevalence of childhood trauma in this group.

Keywords

alcoholdependencegeneticschildhood circumstancesneuropharmacologyallostasiscomorbiditytrauma
Type
Chapter
Information
Seminars in Addiction Psychiatry , pp. 111 - 127
Publisher: Cambridge University Press
Print publication year: 2021

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References

Public Health England. Estimates of alcohol dependent adults in England. 2017.Google Scholar
NHS Digital. Statistics on Alcohol, England, 2018. Office for National Statistics.Google Scholar
Ness, J., Hawton, K., Bergen, H., Cooper, J., Steeg, S., Kapur, N. et al. Alcohol use and misuse, self-harm and subsequent mortality: An epidemiological and longitudinal study from the multicentre study of self-harm in England. Emergency Medicine Journal. 2015; 32: 793–9CrossRefGoogle ScholarPubMed
Windfuhr, K., Kapur, N. Suicide and mental illness: A clinical review of 15 years’ findings from the UK National Confidential Inquiry into Suicide. British Medical Bulletin. 2011; 100 (1): 101–21.CrossRefGoogle ScholarPubMed
Holst, C., Tolstrup, J. S., Sørensen, H. J., Pisinger, V. S. C., Becker, U. Parental alcohol use disorder with and without other mental disorders and offspring alcohol use disorder. Acta Psychiatrica Scandinavica. 2019; 1–10.Google Scholar
Reilly, M. T., Noronha, A., Goldman, D., Koob, G. F. Genetic studies of alcohol dependence in the context of the addiction cycle. Neuropharmacology. 2017; 122: 3–21.CrossRefGoogle ScholarPubMed
Tawa, E. A., Hall, S. D., Lohoff, F. W. Overview of the genetics of alcohol use disorder. Alcohol and Alcoholism. 2016; 51 (5): 507–14.Google Scholar
Meque, I., Salom, C., Betts, K. S., Alati, R. Predictors of alcohol use disorders among young adults: A systematic review of longitudinal studies. Alcohol and Alcoholism. 2019; 54 (3): 310–24.Google Scholar
Kaynak, Ö., Winters, K. C., Cacciola, J., Kirby, K. C., Arria, A. M. Providing alcohol for underage youth: What messages should we be sending parents? Journal of Studies on Alcohol and Drugs. 2014; 75 (4): 590–605.CrossRefGoogle ScholarPubMed
Mattick, R. P., Clare, P. J., Aiken, A., Wadolowski, M., Hutchinson, D., Najman, J. et al. Association of parental supply of alcohol with adolescent drinking, alcohol-related harms, and alcohol use disorder symptoms: A prospective cohort study. Lancet Public Health. 2018; 3 (2): e64–71.Google Scholar
Melchior, M., Moffitt, T. E., Milne, B. J., Poulton, R., Caspi, A. Why do children from socioeconomically disadvantaged families suffer from poor health when they reach adulthood? A life-course study. American Journal of Epidemiology. 2007; 166 (8): 966–74.Google Scholar
Dom, G., De Wilde, B., Hulstijn, W., Sabbe, B. Traumatic experiences and posttraumatic stress disorders: Differences between treatment-seeking early- and late-onset alcoholic patients. Comprehensive Psychiatry. 2007; 48 (2): 178–85.Google Scholar
Felitti, J., Ana, R.F., Nordenberg, D., Williamson, D. F., Spitz, A. M., Edwards, V., Koss, M. P., Marks, J. S. Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults: The Adverse Childhood Experiences Study. American Journal of Preventive Medicine. 1998; 14 (4): 245–58.Google Scholar
Schwandt, M. L., Heilig, M. D., Hommer, D. W., George, M. D., Ramchandani, V. A. Childhood trauma exposure and alcohol dependence severity in adulthood: Mediation by emotional abuse severity and neuroticism. Alcoholism: Clinical and Experimental Research. 2013; 37 (6): 984–92.Google Scholar
Baer, J., Daly Martinez, C. Child maltreatment and insecure attachment: a meta-analysis. Journal of Reproductive and Infant Psychology. 2006; 24 (3): 187–97Google Scholar
Fairbairn, C. E., Briley, D. A., Kang, D., Fraley, R. C., Hankin, B. L., Ariss, T. A meta-analysis of longitudinal associations between substance use and interpersonal attachment security. Psychological Bulletin. 2018; 144 (5): 532–55.Google Scholar
Pardini, D., White, H. R., Stouthamer-Loeber, M. Early adolescent psychopathology as a predictor of alcohol use disorders by young adulthood. Drug and Alcohol Dependence. 2007; 88 (S1): S38–S49.Google Scholar
Jellinek, E. M. The Disease Concept of Alcoholism. New Haven, CT: Hillhouse Press; 1960.CrossRefGoogle Scholar
World Health Organization. Global Status Report on Alcohol and Health, 2018. Geneva: WHO; 2018.Google Scholar
Manthey, J., Shield, K. D., Rylett, M., Probst, C., Rehm, J. Global alcohol exposure between 1990 and 2017 and forecasts until 2030: A modelling study. Lancet. 2019; 393 (10190): 2893–502.Google Scholar
Kan, M., Lau, M. Comparing alcohol affordability in 65 countries worldwide. Drug and Alcohol Review. 2014; 32: 19–26.Google Scholar
Lancet. Russia’s alcohol policy: a continuing success story. Lancet [Internet]. 2019; 394 (10205): 1205.CrossRefGoogle Scholar
Farrell, S., Manning, W. G., Finch, M. D. Alcohol dependence and the price of alcoholic beverages. Journal of Health Economics. 2003; 22 (1): 117–47.Google Scholar
Khantzian, E. Understanding addictive vulnerability: an evolving psychodynamic perspective. Neuropsychoanalysis. 2013; 5 (1): 5–21.CrossRefGoogle Scholar
Schuckit, M. A., Smith, T. L., Kalmijn, J., Danko, G. P. A cross-generational comparison of alcohol challenges at about age 20 in 40 father-offspring pairs. Alcoholism: Clinical and Experimental Research. 2005; 29 (11): 1921–7.Google Scholar
Petrakis, I. L., Kerfoot, K., Pittman, B., Perrino, A., Koretski, J., Newcomb, J. et al. Subjective effects of thiopental in young adults with and without a family history of alcoholism. Journal of Addiction Research and Therapy. 2012; S7 (2): 6336–49.Google Scholar
Krystal, J. H., Staley, J., Mason, G., Petrakis, I. L., Kaufman, J., Harris, R. A. et al. γ-aminobutyric acid type A receptors and alcoholism: Intoxication, dependence, vulnerability, and treatment. Archives of General Psychiatry. 2006; 63 (9): 957–68.Google Scholar
Krystal, J. H., Petrakis, I. L., Mason, G., Trevisan, L., D’Souza, D. C. N-methyl-D-aspartate glutamate receptors and alcoholism: Reward, dependence, treatment, and vulnerability. Pharmacology and Therapeutics. 2003; 99 (1): 79–94.CrossRefGoogle ScholarPubMed
Rimondini, R., Sommer, W. H., Dall’Olio, R., Heilig, M. Long-lasting tolerance to alcohol following a history of dependence. Addiction Biology. 2008; 13 (1): 26–30.CrossRefGoogle ScholarPubMed
Heilig, M., Egli, M., Crabbe, J.C., Becker, H. C. Acute withdrawal, protracted abstinence and negative affect in alcoholism: Are they linked? Addiction Biology . 2010; 15 (2): 169–84.Google Scholar
Nutt, D. J., Besson, M., Wilson, S. J., Dawson, G. R., Lingford-Hughes, A. R. Blockade of alcohol’s amnestic activity in humans by an α5 subtype benzodiazepine receptor inverse agonist. Neuropharmacology. 2007; 53( 7): 810–20.Google Scholar
Finn, D. A., Crabbe, J. C. Exploring Alcohol Withdrawal Syndrome. Alcohol Health and Research World . 1997; 21( 1): 149–56.Google Scholar
Maccioni, P., Colombo, G. Role of the GABAB receptor in alcohol-seeking and drinking behavior. Alcohol. 2009; 43 (7): 555–8.Google Scholar
Durant, C. F., Paterson, L. M., Turton, S., Wilson, S. J., Myers, J.F. M., Muthukumaraswamy, S. et al. Using Baclofen to explore GABA-B receptor function in alcohol dependence: Insights from pharmacokinetic and pharmacodynamic measures. Frontiers in Psychiatry. 2018; 9 (December): 1–17.Google Scholar
Kalivas, P. W., LaLumiere, R., Knackstedt, L., Shen, H. Glutamate transmission in addiction. Neuropharmacology. 2009; 56 (Suppl. 1): 169–73.CrossRefGoogle ScholarPubMed
Alasmari, F., Goodwani, S., McCullumsmith, R. E., Sari, Y. Role of glutamatergic system and mesocorticolimbic circuits in alcohol dependence. Progress in Neurobiology. 2018; 171 (May): 32–49.Google Scholar
Becker, H. C. Kindling in alcohol withdrawal. Alcohol Health and Research World. 1998; 22 (1): 25–33.Google Scholar
Quelch, D., Mick, I., McGonigle, J., Ramos, A. C., Flechais, R. C., Bolstridge, M., Rabiner, E., Wal, M. B., Newbould, R. B., Steiniger-Brach, B., van den Berg, F., Boyce, M., Østergaard Nilausen, D., Lingford-Hughes, A. A. Nalmefene reduces reward anticipation in alcohol dependence: An experimental functional magnetic resonance imaging study. Biological Psychiatry. 2017; 81 (11): 941–8.Google Scholar
Williams, T. M., Davies, S. J. C., Taylor, L. G., Daglish, M. R. C., Hammers, A., Brooks, D. J., Nutt, D. J., Lingford-Hughes, A. R. Brain opioid receptor binding in early abstinence from alcohol dependence and relationship to craving: An [11C]diprenorphine PET study. European Neuropsychopharmacology. 2009; 19 (10): 740–8.Google Scholar
Heinz, M. D., Reimold, M. D., Wrase, J., Croissant, B., Mundle, G., Dohmen, B. M., Braus, D. H., Schumann, G., Machulla, H. J., Bares, R., Mann, K. Correlation of stable elevations in striatal mu-opioid receptor availability in detoxified alcoholic patients with alcohol craving. Archives of General Psychiatry. 2005; 62( 1): 57–64.Google Scholar
Lam, M. P., Gianoulakis, C. Effects of corticotropin-releasing hormone receptor antagonists on the ethanol-induced increase of dynorphin A1-8 release in the rat central amygdala. Alcohol. 2011; 45 (7): 621–30.Google Scholar
Funk, D., Coen, K., Le, A. D. The role of kappa opioid receptors in stress-induced reinstatement of alcohol seeking in rats. Brain and Behavior. 2014; 4 (3): 356–67.Google Scholar
Walker, B. M., Koob, G. F. Pharmacological evidence for a motivational role of kappa-opioid systems in ethanol dependence. Neuropsychopharmacology. 2008; 33: 643–52.CrossRefGoogle ScholarPubMed
Soyka, M., Friede, M., Schnitker, J. Comparing nalmefene and naltrexone in alcohol dependence: Are there any differences? Results from an indirect meta-analysis. Pharmacopsychiatry. 2016; 49 (2): 66–75.Google Scholar
Ramchandani, V. A., Stangl, B. L., Blaine, S. K., Plawecki, M. H., Schwandt, M. L., Kwako, L. E. et al. Stress vulnerability and alcohol use and consequences: From human laboratory studies to clinical outcomes. Alcohol. 2018; 72: 75–88.Google Scholar
Koob, G. F., Schulkin, J. Addiction and stress: An allostatic view. Neuroscience and Biobehavorial Reviews. 2019; 106: 245–62.Google Scholar
Errico, A. L., King, A. C., Lovallo, W. R., Parsons, O. A. Cortisol dysregulation and cognitive impairment in abstinent male alcoholics. Alcoholism: Clinical and Experimental Research. 2002; 26 (8): 1198–204.Google Scholar
Besemer, F., Pereira, A. M., Smit, J. W. Alcohol-induced Cushing syndrome: Hypercortisolism caused by alcohol abuse.Netherlands Journal of Medicine. 2011; 69 (7): 318–23.Google Scholar
Junghanns, K., Horbach, R., Ehrenthal, D., Blank, S., Backhaus, J. Cortisol awakening response in abstinent alcohol-dependent patients as a marker of HPA-axis dysfunction. Psychoneuroendocrinology. 2007; 32 (8–10): 1133–7.Google Scholar
Ramchandani, V. A., Umhau, J., Pavon, F. J., Ruiz-Velasco, V., Margas, W., Sun, H. et al. A genetic determinant of the striatal dopamine response to alcohol in men. Molecular Psychiatry. 2011; 16 (8): 809–17.Google Scholar
Koob, G. F. Brain stress systems in the amygdala and addiction. Brain Research. 2009; 13 (1293): 61–75.Google Scholar
Ferrari, A. J., Norman, R. E., Freedman, G., Baxter, A. J., Pirkis, J. E., Harris, M. G., Page, A., Carnahan, E., Degenhardt, L., Vos, T., Whiteford, H. A. The burden attributable to mental and substance use disorders as risk factors for suicide: Findings from the Global Burden of Disease Study 2010. PLOS ONE. 2014; 9 (4): e9136.Google Scholar
Grant, B. F., Hasin, D. S., Blanco, C., Stinson, F. S., Chou, S. P., Goldstein, R. B. The epidemiology of social anxiety disorder in the United States: Results from the National Epidemiologic Survey on Alcohol and Related Conditions. Journal of Clinical Psychiatry. 2005; 66 (1351–61).Google Scholar
Buckner, J. D., Turner, R. J. Social anxiety disorder as a risk factor for alcohol use disorders: A prospective examination of parental and peer influences. Drug and Alcohol Dependency. 2009; 100 (1–2): 128–37.CrossRefGoogle ScholarPubMed
Kessler, R.C., Crum, R. M., Warner, L. A., Nelson, C. B., Schulenberg, J., Anthony, J. C. Lifetime co-occurrence of DSM-III-R Alcohol Abuse and Dependence with other psychiatric disorders in the National Comorbidity Survey. Archives of General Psychiatry. 1997; 54 (313–21).Google Scholar
Buckner, J. D., Schmidt, N. B., Lang, A. R., Small, J., Schlauch, R. C., Lewinsohn, P. M. Specificity of social anxiety disorder as a risk factor for alcohol and cannabis dependence. Journal of Psychiatric Research. 2008; 42: 230–9.Google Scholar
Breslau, N. The epidemiology of trauma, PTSD, and other posttrauma disorders. Trauma, Violence, and Abuse. 2009; 10 (3): 198–210.Google Scholar
Sihvola, E., Rose, R. J., Dick, D. M., Pulkkinen, L., Marttunen, M., Kaprio, J. Addictive substances in adolescence: A prospective study of adolescent Finnish twins. Addiction. 2008; 103 (12): 2045–53.Google Scholar
Mackie, C. J., Castellanos-Ryan, N., Conrod, P. J. Personality moderates the longitudinal relationship between psychological symptoms and alcohol use in adolescents. Alcoholism: Clinical and Experimental Research. 2011; 35 (4): 703–16.Google Scholar
Prescott, C. A., Aggen, S. H., Kendler, K. S. Sex-specific genetic influences on the comorbidity of alcoholism and major depression in a population-based sample of U.S. Twins. The Primary Care Companion to The Journal of Clinical Psychiatry. 2000; 2 (5): 186.Google Scholar
Hunt, G. E., Malhi, G. S., Cleary, M., Lai, H. M. X., Sitharthan, T. Prevalence of comorbid bipolar and substance use disorders in clinical settings, 1990–2015: Systematic review and meta-analysis. Journal of Affective Disorders . 2016; 206: 331–49.Google Scholar
Bolton, J. M., Robinson, J., Sareen, J. Self-medication of mood disorders with alcohol and drugs in the National Epidemiologic Survey on Alcohol and Related Conditions. Journal of Affective Disorders. 2009; 115 (3): 367–75.Google Scholar
Yip, S. W., Doherty, J., Wakeley, J., Saunders, K., Tzagarakis, C., de Wit, H., Goodwin, G. M., Rogers, R. D. Ethanol Administration among young men with a broad bipolar phenotype. Neuropsychopharmacology. 2012; 37: 1808–15.Google Scholar
Mezquita, L., Bravo, A. J., Ortet, G., Pilatti, A., Pearson, M. R., Ibanez, M. I. Cross-cultural examination of different personality pathways to alcohol use and misuse in emerging adulthood. Drug and Alcohol Dependence. 2018; 192: 193–200.Google Scholar
Foulds, J. A., Boden, J. M., Newton-Howes, G. M., Mulder, R. T., Horwood, L. J. The role of novelty seeking as a predictor of substance use disorder outcomes in early adulthood. Addiction. 2017; 112 (9): 1629–37.Google Scholar
Cloninger, C. R., Sigvardsson, S., Bohman, M. Type I and type II alcoholism: An update. Alcohol Health and Research World. 1996; 20 (1): 18–23.Google Scholar
Rosenström, T., Torvik, F. A., Ystrom, E., Czajkowski, N. O., Gillespie, N. A., Aggen, S. H. et al. Prediction of alcohol use disorder using personality disorder traits: A twin study. Addiction. 2018; 113 (1): 15–24.Google Scholar

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