Abstract
The present study was designed to determine whether stress hormones and subjective responses to a psychological stressor were different in nonalcoholic offspring from families with a history of alcohol dependence (family history positive, FHP) than in nonalcoholic offspring without a family history of alcohol dependence (family history negative, FHN). Forty-five healthy subjects (17 FHP, 28 FHN), between the ages of 18 and 29 years, completed the Trier Social Stress Test (TSST). The TSST consisted of 5 min of public speaking followed by 5 min of mental arithmetic. Three baseline and five post-TSST blood samples were drawn. Pre- and post-TSST self-report measures of anxiety were obtained. Cortisol, adrenocorticotropin (ACTH), and prolactin significantly increased in response to the TSST in the entire study sample (F(1,187)=70.22, p<0.001, F(1,143)=33, p<0.001, and F(1,134)=14.37, p<0.001, respectively). Cortisol responses were influenced by an interaction between racial composition and family history of alcoholism (F(1,57)=4.50, p=0.038). Among Caucasian subjects, FHP subjects had greater cortisol response to the TSST compared to FHN subjects (F(1,57)=4.45, p=0.039). No family history effect was identified in African-American subjects. Adrenocorticotropin responses did not differ between FHP and FHN subjects. Adrenocorticotropin response was positively associated with baseline ACTH levels in FHN subjects (t=5.02, p=<0.001), but not in FHP subjects. Prolactin responses did not differ between FHP and FHN subjects. Anxiety response scores (post-TSST scores minus pre-TSST scores) were higher in FHP subjects compared with FHN subjects (z=−2.67, p=0.007). In addition, anxiety response scores were positively associated with cortisol response levels to the TSST in FHN subjects (t=4.52, p<0.001). In contrast, anxiety responses were negatively associated with cortisol responses in FHP subjects (t=−2.30, p=0.024). Our findings are consistent with theories that greater reactivity to stress is associated with greater risks for alcoholism. Furthermore, the findings suggest that the association between the hypothalamic–pituitary–adrenal axis hormonal response and the subjective perception of stress might be deranged in offspring of alcoholics.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Adinoff B, Iranmanesh A, Veldhuis J, Fisher L (1998). Disturbances of the stress response: the role of the HPA axis during alcohol withdrawal and abstinence. Alcohol Health Res World 22: 67–72.
Beck AT, Steer RA, Brown G (1996). Beck Depression Inventory-II Manual. San Antonio, TX.
Begleiter H, Porjesz B, Bihari B, Kissin B (1984). Event-related brain potentials in boys at risk for alcoholism. Science 225: 1493–1496.
Bennett GG, Merritt MM, Wolin KY (2004). Ethnicity, education, and the cortisol response to awakening: a preliminary investigation. Ethn Health 9: 337–347.
Blevins Jr LS, Dobs AS, Wand GS (1994). Naloxone-induced activation of the hypothalamic–pituitary–adrenal axis in suspected central adrenal insufficiency. Am J Med Sci 308: 167–170.
Brewer DD, Catalano RF, Haggerty K, Gainey RR, Fleming CB (1998). A meta-analysis of predictors of continued drug use during and after treatment for opiate addiction. Addiction 93: 73–92.
Brown SA, Vik PW, McQuaid JR, Patterson TL, Irwin MR, Grant I (1990). Severity of psychosocial stress and outcome of alcoholism treatment. J Abnorm Psychol 99: 344–348.
Bucholz KK, Cadoret R, Cloninger CR, Dinwiddie SH, Hesselbrock VM, Nurnberger Jr JI et al (1994). A new, semi-structured psychiatric interview for use in genetic linkage studies: a report on the reliability of the SSAGA. J Stud Alcohol 55: 149–158.
Cloninger CR, Bohman M, Sigvardsson S (1981). Inheritance of alcohol abuse. Cross-fostering analysis of adopted men. Arch Gen Psychiatry 38: 861–868.
Cohen S, Kamarck T, Mermelstein R (1983). A global measure of perceived stress. J Health Soc Behav 24: 385–396.
Cole G, Tucker L, Friedman GM (1990). Relationships among measures of alcohol drinking behavior, life-events and perceived stress. Psychol Rep 67: 587–591.
Cook CJ (2002). Glucocorticoid feedback increases the sensitivity of the limbic system to stress. Physiol Behav 75: 455–464.
Costa Jr PT, McCrae RR (1992a). Normal personality assessment in clinical practice: the NEO Personality Inventory. Psychol Assess 4: 5–13.
Costa Jr PT, McCrae RR (1992b). Revised NEO Personality Inventory: Professional Manual. Odessa, FL.
Cotton NS (1979). The familial incidence of alcoholism: a review. J Stud Alcohol 40: 89–116.
Dai X, Thavundayil J, Gianoulakis C (2002). Response of the hypothalamic–pituitary–adrenal axis to stress in the absence and presence of ethanol in subjects at high and low risk of alcoholism. Neuropsychopharmacology 27: 442–452.
Dawson DA, Grant BF, Ruan WJ (2005). The association between stress and drinking: modifying effects of gender and vulnerability. Alcohol Alcohol 40: 453–460.
del Arbol JL, Munoz JR, Ojeda L, Cascales AL, Irles JR, Miranda MT et al (2000). Plasma concentrations of beta-endorphin in smokers who consume different numbers of cigarettes per day. Pharmacol Biochem Behav 67: 25–28.
Derogatis LR, Melisaratos N (1983). The brief symptom inventory: an introductory report. Psychol Med 13: 595–605.
Fahlke C, Lorenz JG, Long J, Champoux M, Suomi SJ, Higley JD (2000). Rearing experiences and stress-induced plasma cortisol as early risk factors for excessive alcohol consumption in nonhuman primates. Alcohol Clin Exp Res 24: 644–650.
Federenko IS, Nagamine M, Hellhammer DH, Wadhwa PD, Wust S (2004). The heritability of hypothalamus pituitary adrenal axis responses to psychosocial stress is context dependent. J Clin Endocrinol Metab 89: 6244–6250.
Gold PW, Chrousos GP (2002). Organization of the stress system and its dysregulation in melancholic and atypical depression: high vs low CRH/NE states. Mol Psychiatry 7: 254–275.
Goodwin DW (1984). Studies of familial alcoholism: a review. J Clin Psychiatry 45: 14–17.
Goodwin DW, Schulsinger F, Moller N, Hermansen L, Winokur G, Guze SB (1974). Drinking problems in adopted and nonadopted sons of alcoholics. Arch Gen Psychiatry 31: 164–169.
Heath AC, Bucholz KK, Madden PA, Dinwiddie SH, Slutske WS, Bierut LJ et al (1997). Genetic and environmental contributions to alcohol dependence risk in a national twin sample: consistency of findings in women and men. Psychol Med 27: 1381–1396.
Hernandez-Avila CA, Oncken C, Van Kirk J, Wand G, Kranzler HR (2002). Adrenocorticotropin and cortisol responses to a naloxone challenge and risk of alcoholism. Biol Psychiatry 51: 652–658.
Higley JD, Hasert MF, Suomi SJ, Linnoila M (1991). Nonhuman primate model of alcohol abuse: effects of early experience, personality, and stress on alcohol consumption. Proc Natl Acad Sci USA 88: 7261–7265.
Jose BS, van Oers HA, van de Mheen HD, Garretsen HF, Mackenbach JP (2000). Stressors and alcohol consumption. Alcohol Alcohol 35: 307–312.
Karlsgodt KH, Lukas SE, Elman I (2003). Psychosocial stress and the duration of cocaine use in non-treatment seeking individuals with cocaine dependence. Am J Drug Alcohol Abuse 29: 539–551.
King AC, Bernardy NC, Hauner K (2003). Stressful events, personality, and mood disturbance: gender differences in alcoholics and problem drinkers. Addict Behav 28: 171–187.
Kirschbaum C, Pirke KM, Hellhammer DH (1993). The ‘Trier Social Stress Test’—a tool for investigating psychobiological stress responses in a laboratory setting. Neuropsychobiology 28: 76–81.
Koob GF (2003). Alcoholism: allostasis and beyond. Alcohol Clin Exp Res 27: 232–243.
Kudielka BM, Schommer NC, Hellhammer DH, Kirschbaum C (2004). Acute HPA axis responses, heart rate, and mood changes to psychosocial stress (TSST) in humans at different times of day. Psychoneuroendocrinology 29: 983–992.
Lazarus RS, Folkman S (1989). Manual Hassles And Uplifts Scales. Mind Garden: Redwood City, CA.
Marinelli M, Piazza PV (2002). Interaction between glucocorticoid hormones, stress and psychostimulant drugs. Eur J Neurosci 16: 387–394.
McBride WJ (2002). Central nucleus of the amygdala and the effects of alcohol and alcohol-drinking behavior in rodents. Pharmacol Biochem Behav 71: 509–515.
McEwen BS (1998). Protective and damaging effects of stress mediators. N Engl J Med 338: 171–179.
Mendelson JH, Sholar MB, Goletiani N, Siegel AJ, Mello NK (2005). Effects of low- and high-nicotine cigarette smoking on mood states and the HPA axis in men. Neuropsychopharmacology 30: 1751–1763.
Merikangas KR, Mehta RL, Molnar BE, Walters EE, Swendsen JD, Aguilar-Gaziola S et al (1998). Comorbidity of substance use disorders with mood and anxiety disorders: results of the International Consortium in Psychiatric Epidemiology. Addict Behav 23: 893–907.
Miller DB, O’Callaghan JP (2002). Neuroendocrine aspects of the response to stress. Metabolism 51: 5–10.
Oswald L, Zandi P, Nestadt G, Potash J, Kalaydijian A, Wand G (2006). Relationship between cortisol responses to stress and personality. Neuropsychopharmacology, 11 January [Epub ahead of print].
Pandey SC (2003). Anxiety and alcohol abuse disorders: a common role for CREB and its target, the neuropeptide Y gene. Trends Pharmacol Sci 24: 456–460.
Prescott CA, Kendler KS (1999). Genetic and environmental contributions to alcohol abuse and dependence in a population-based sample of male twins. Am J Psychiatry 156: 34–40.
Pruessner JC, Kirschbaum C, Meinlschmid G, Hellhammer DH (2003). Two formulas for computation of the area under the curve represent measures of total hormone concentration versus time-dependent change. Psychoneuroendocrinology 28: 916–931.
Rice JP, Reich T, Bucholz KK, Neuman RJ, Fishman R, Rochberg N et al (1995). Comparison of direct interview and family history diagnoses of alcohol dependence. Alcohol Clin Exp Res 19: 1018–1023.
Robison CL, Meyerhoff JL, Saviolakis GA, Chen WK, Rice KC, Lumley LA (2004). A CRH1 antagonist into the amygdala of mice prevents defeat-induced defensive behavior. Ann NY Acad Sci 1032: 324–327.
Sapolsky RM (2000). Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders. Arch Gen Psychiatry 57: 925–935.
Sarason IG, Johnson JH, Siegel JM (1978). Assessing the impact of life changes: development of the Life Experiences Survey. J Consult Clin Psychol 46: 932–946.
Schuckit MA, Gold E, Risch C (1987). Plasma cortisol levels following ethanol in sons of alcoholics and controls. Arch Gen Psychiatry 44: 942–945.
Schuckit MA, Smith TL (1996). An 8-year follow-up of 450 sons of alcoholic and control subjects. Arch Gen Psychiatry 53: 202–210.
Sherwood Brown E, Varghese FP, McEwen BS (2004). Association of depression with medical illness: does cortisol play a role? Biol Psychiatry 55: 1–9.
Sobrinho LG, Simoes M, Barbosa L, Raposo JF, Pratas S, Fernandes PL et al (2003). Cortisol, prolactin, growth hormone and neurovegetative responses to emotions elicited during an hypnoidal state. Psychoneuroendocrinology 28: 1–17.
Spielberger CD (1983). State–Trait Anxiety Inventory (STAI) Manual. Redwood City, CA.
Sussman S, Dent CW (2000). One-year prospective prediction of drug use from stress-related variables. Subst Use Misuse 35: 717–735.
Tsigos C, Chrousos GP (2002). Hypothalamic–pituitary–adrenal axis, neuroendocrine factors and stress. J Psychosom Res 53: 865–871.
Uhart M, McCaul ME, Oswald LM, Choi L, Wand GS (2004). GABRA6 gene polymorphism and an attenuated stress response. Mol Psychiatry 9: 998–1006.
Van de Kar LD, Blair ML (1999). Forebrain pathways mediating stress-induced hormone secretion. Front Neuroendocrinol 20: 1–48.
Waltman C, McCaul ME, Wand GS (1994). Adrenocorticotropin responses following administration of ethanol and ovine corticotropin-releasing hormone in the sons of alcoholics and control subjects. Alcohol Clin Exp Res 18: 826–830.
Wand G, McCaul ME, Gotjen D, Reynolds J, Lee S (2001). Confirmation that offspring from families with alcohol-dependent individuals have greater hypothalamic–pituitary–adrenal axis activation induced by naloxone compared with offspring without a family history of alcohol dependence. Alcohol Clin Exp Res 25: 1134–1139.
Wand GS, Mangold D, Ali M (1999a). Adrenocorticotropin responses to naloxone in sons of alcohol-dependent men. J Clin Endocrinol Metab 84: 64–68.
Wand GS, Mangold D, Ali M, Giggey P (1999b). Adrenocortical responses and family history of alcoholism. Alcohol Clin Exp Res 23: 1185–1190.
Wand GS, Mangold D, El Deiry S, McCaul ME, Hoover D (1998). Family history of alcoholism and hypothalamic opioidergic activity. Arch Gen Psychiatry 55: 1114–1119.
Wand GS, Waltman C, Martin CS, McCaul ME, Levine MA, Wolfgang D (1994). Differential expression of guanosine triphosphate binding proteins in men at high and low risk for the future development of alcoholism. J Clin Invest 94: 1004–1011.
Yanovski JA, Yanovski SZ, Boyle AJ, Gold PW, Sovik KN, Sebring NG et al (2000). Hypothalamic–pituitary–adrenal axis activity during exercise in African American and Caucasian women. J Clin Endocrinol Metab 85: 2660–2663.
Yanovski JA, Yanovski SZ, Friedman TC, Loh YP, Jayasvasti V, Cutler Jr GB et al (1996). Etiology of the differences in corticotropin-releasing hormone-induced adrenocorticotropin secretion of black and white women. J Clin Endocrinol Metab 81: 3307–3311.
Zimmermann U, Spring K, Kunz-Ebrecht SR, Uhr M, Wittchen HU, Holsboer F (2004). Effect of ethanol on hypothalamic—pituitary–adrenal system response to psychosocial stress in sons of alcohol-dependent fathers. Neuropsychopharmacology 29: 1156–1165.
Zonnevylle-Bender MJ, van Goozen SH, Cohen-Kettenis PT, Jansen LM, van Elburg A, Engeland H (2005). Adolescent anorexia nervosa patients have a discrepancy between neurophysiological responses and self-reported emotional arousal to psychosocial stress. Psychiatry Res 135: 45–52.
Acknowledgements
This work was supported by NIH Grants AA 10158 (GSW), AA 12303 (GSW), and AA 12837 (MEM), a gift from the Kenneth A Lattman Foundation (GSW), and Grant M01 RR00052 (GCRC). We thank Lisa Yanek (MPH) for her technical advice in this manuscript.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Uhart, M., Oswald, L., McCaul, M. et al. Hormonal Responses to Psychological Stress and Family History of Alcoholism. Neuropsychopharmacol 31, 2255–2263 (2006). https://doi.org/10.1038/sj.npp.1301063
Received:
Revised:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/sj.npp.1301063
Keywords
This article is cited by
-
Hypothalamic-Pituitary-Adrenal Reactivity to Acute Stress: an Investigation into the Roles of Perceived Stress and Family Resources
Prevention Science (2017)
-
The effects of repeated corticosterone exposure on the interoceptive effects of alcohol in rats
Psychopharmacology (2012)
-
Neural Circuitry Associated with Risk for Alcohol Use Disorders
Neuropsychology Review (2010)


