Impact of childhood trauma on hypothalamus-pituitary-adrenal axis activity in alcohol-dependent patients
Abstract
AIMS: Studies in animals and humans suggest that early life stress alters hypothalamus-pituitary-adrenal (HPA) axis activity. The same alterations are related to the symptoms and course of alcohol dependence. This study examined relationships between childhood trauma and HPA axis activity in alcohol-dependent patients controlling for psychopathology and characteristics of dependence. METHODS: Thirty-eight consecutive patients (42% female) were examined at admission to detoxification (t1) and 14 days later (t2). Morning plasma levels of cortisol and adrenocorticotropin-releasing hormone (ACTH) were determined. Participants completed the Childhood Trauma Questionnaire (CTQ) and measures of anxiety, depression, and posttraumatic stress disorder. RESULTS: Sexual abuse was related to higher levels of cortisol during acute withdrawal (r = 0.38, p = 0.02). Levels of ACTH were negatively correlated with the CTQ total score (t2: r = -0.42, p < 0.01), emotional abuse (t2: r = -0.33, p = 0.04), emotional neglect (t2: r = -0.33, p = 0.04), and physical neglect (t2: r = -0.33, p = 0.05) controlling for psychopathology and characteristics of dependence. CONCLUSIONS: Our findings suggest, that childhood trauma is related to blunted ACTH and increased cortisol during withdrawal in alcohol-dependent patients. Early life stress might be a confounding variable in studies of HPA function in alcohol dependence and future studies should examine potential clinical consequences of these relationships.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
ACE and substance dependence have combined negative effects on stress reactivity in the HPA axis.
“Indeed, recent research illustrates the combined negative effects of ACE and substance dependence on stress reactivity in the HPA axis (Doan et al., in press; Gerra et al., 2014; Schäfer et al., 2010).”
From Effects of adverse childhood experiences on the association between intranasal oxytocin and social stress reactivity among individuals with cocaine dependence (2015) · cites this paper as Schäfer et al., 2010
Cites
(1970) · Cited by 24,983 · see citing works
Beck, A. T., Steer, R. A., & Brown, G. (2011) · PsycTESTS Dataset · doi:10.1037/t00742-000 · Cited by 7,535 · see citing works
The Fifth Edition of the Addiction Severity Index.
Mclellan, A., Kushner, H., Metzger, D., Peters, R., Smith, I. E., Grissom, G. R., Pettinati, H., & Argeriou, M. (1992) · Journal of Substance Abuse Treatment · doi:10.1016/0740-5472(92)90062-s · Cited by 4,279 · see citing works
Foa, E. B., Cashman, L., Jaycox, L., & Perry, K. (1997) · Psychological Assessment · doi:10.1037/1040-3590.9.4.445 · Cited by 2,709 · see citing works
Heim, C. (2000) · JAMA · doi:10.1001/jama.284.5.592 · Cited by 1,968 · see citing works
Plotsky, P. M., & Meaney, M. J. (1993) · Molecular Brain Research · doi:10.1016/0169-328x(93)90189-v · Cited by 1,638 · see citing works
Kendler, K. S., Bulik, C. M., Silberg, J., Hettema, J. M., Myers, J., & Prescott, C. A. (2000) · Archives of General Psychiatry · doi:10.1001/archpsyc.57.10.953 · Cited by 1,259 · see citing works
SÁNCHEZ, M. M., LADD, C. O., & PLOTSKY, P. M. (2001) · Development and Psychopathology · doi:10.1017/s0954579401003029 · Cited by 1,003 · see citing works
FERGUSSON, D. M., HORWOOD, L. J., & LYNSKEY, M. T. (1996) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/00004583-199610000-00024 · Cited by 826 · see citing works
Heim, C., Newport, D. J., Bonsall, R., Miller, A. H., & Nemeroff, C. B. (2001) · American Journal of Psychiatry · doi:10.1176/appi.ajp.158.4.575 · Cited by 746 · see citing works
The childhood trauma questionnaire in a community sample: Psychometric properties and normative data
Scher, C. D., Stein, M. B., Asmundson, G. J. G., McCreary, D. R., & Forde, D. R. (2001) · Journal of Traumatic Stress · doi:10.1023/a:1013058625719 · Cited by 726 · see citing works
Anton, R. F., Moak, D. H., & Latham, P. K. (1995) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.1995.tb01475.x · Cited by 679 · see citing works
(2004) · PubMed · Cited by 567 · see citing works
Carpenter, L. L., Carvalho, J. P., Tyrka, A. R., Wier, L. M., Mello, A. F., Mello, M. F., Anderson, G. M., Wilkinson, C. W., & Price, L. H. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.05.002 · Cited by 564 · see citing works
Kokkevi, A., & Hartgers, C. (2009) · European Addiction Research · doi:10.1159/000259089 · Cited by 547 · see citing works
Hellhammer, J., Fries, E., Schweisthal, O. W., Schlotz, W., Stone, A. A., & Hagemann, D. (2007) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2006.10.005 · Cited by 540 · see citing works
Sinha, R., Garcia, M., Paliwal, P., Kreek, M. J., & Rounsaville, B. J. (2006) · Archives of General Psychiatry · doi:10.1001/archpsyc.63.3.324 · Cited by 528 · see citing works
Huot, R. L., Thrivikraman, K. V., Meaney, M. J., & Plotsky, P. M. (2001) · Psychopharmacology · doi:10.1007/s002130100701 · Cited by 506 · see citing works
Effect of previous trauma on acute plasma cortisol level following rape
(1995) · American Journal of Psychiatry · doi:10.1176/ajp.152.11.1675 · Cited by 418 · see citing works
Diminished cortisol responses to psychosocial stress associated with lifetime adverse events
Elzinga, B. M., Roelofs, K., Tollenaar, M. S., Bakvis, P., van Pelt, J., & Spinhoven, P. (2008) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2007.11.004 · Cited by 364 · see citing works
Heim, C., Mletzko, T., Purselle, D., Musselman, D. L., & Nemeroff, C. B. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.07.002 · Cited by 353 · see citing works
Childhood parental loss and adult hypothalamic-pituitary-adrenal function
Tyrka, A. R., Wier, L., Price, L. H., Ross, N., Anderson, G. M., Wilkinson, C. W., & Carpenter, L. L. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.01.011 · Cited by 250 · see citing works
Physical and sexual abuse and associated mental disorders among alcoholic inpatients
Windle, M., Windle, R. C., Scheidt, D. M., & Miller, G. (1995) · American Journal of Psychiatry · doi:10.1176/ajp.152.9.1322 · Cited by 208 · see citing works
Fox, H. C., Hong, K., Siedlarz, K. M., & Sinha, R. (2007) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301470 · Cited by 182 · see citing works
Effects of Estrogen Antagonists and Agonists on the ACTH Response to Restraint Stress in Female Rats
Young, E. A. (2001) · Neuropsychopharmacology · doi:10.1016/s0893-133x(01)00301-3 · Cited by 171 · see citing works
Impaired serum cortisol stress response is a predictor of early relapse
Junghanns, K. (2003) · Alcohol and Alcoholism · doi:10.1093/alcalc/agg052 · Cited by 166 · see citing works
Ehrenreich, H., Schuck, J., Stender, N., Pilz, J., Gefeller, O., Schilling, L., Poser, W., & Kaw, S. (1997) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.1997.tb04450.x · Cited by 160 · see citing works
McCool, B. A., & Chappell, A. M. (2008) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2008.00830.x · Cited by 160 · see citing works
Violent traumatic events and drug abuse severity
Clark, H. W., Masson, C. L., Delucchi, K., Hall, S. M., & Sees, K. L. (2001) · Journal of Substance Abuse Treatment · doi:10.1016/s0740-5472(00)00156-2 · Cited by 157 · see citing works
Fahlke, C., Lorenz, J. G., Long, J. C., Champoux, M., Suomi, S. J., & Higley, J. D. (2000) · Alcoholism Clinical and Experimental Research · doi:10.1097/00000374-200005000-00008 · Cited by 156 · see citing works
Ladd, C. O., Thrivikraman, K. V., Huot, R. L., & Plotsky, P. M. (2005) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2004.12.004 · Cited by 145 · see citing works
Costa, A. C., Bono, G., Martignoni, E., Merlo, P., Sances, G., & Nappi, G. (1996) · Psychoneuroendocrinology · doi:10.1016/0306-4530(96)00001-7 · Cited by 114 · see citing works
Physical and sexual abuse, depression and alcohol use disorders in adolescents: onsets and outcomes
Clark, D. B. (2003) · Drug and Alcohol Dependence · doi:10.1016/s0376-8716(02)00254-5 · Cited by 114 · see citing works
Male-female differences in effects of parental absence on glucocorticoid stress response
Flinn, M. V., Quinlan, R. J., Decker, S. A., Turner, M. T., & England, B. G. (1996) · Human Nature · doi:10.1007/bf02692108 · Cited by 111 · see citing works
Roman, E., & Nylander, I. (2005) · Stress · doi:10.1080/10253890500188666 · Cited by 92 · see citing works
Physical and sexual abuse history and addiction treatment outcomes
Rosen, C. S., Ouimette, P. C., Sheikh, J. I., Gregg, J. A., & Moos, R. H. (2002) · Journal of Studies on Alcohol · doi:10.15288/jsa.2002.63.683 · Cited by 86 · see citing works
Shalev, U., Finnie, P. S. B., Quinn, T. L., Tobin, S. W., & Wahi, P. (2006) · Psychopharmacology · doi:10.1007/s00213-006-0427-y · Cited by 62 · see citing works
Gerra, G., Leonardi, C., Cortese, E., Zaimovic, A., Dell’Agnello, G., Manfredini, M., Somaini, L., Petracca, F., Caretti, V., Baroni, C. M., et al. (2008) · Addiction Biology · doi:10.1111/j.1369-1600.2007.00086.x · Cited by 45 · see citing works
Watson, S., Owen, B. M., Gallagher, P., Hearn, A. J., Young, A. H., & Ferrier, I. N. (2007) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.a939 · Cited by 42 · see citing works
Zimmermann, U., Hundt, W., Spring, K., Grabner, A., & Holsboer, F. (2002) · Biological Psychiatry · doi:10.1016/s0006-3223(02)01444-0 · Cited by 27 · see citing works
Urinary free cortisol and childhood trauma in cocaine dependent adults
Roy, A. (2002) · Journal of Psychiatric Research · doi:10.1016/s0022-3956(02)00002-x · Cited by 25 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Stress and the HPA axis: role of glucocorticoids in alcohol dependence
Stephens, M. (2012) · Alcohol Research: Current Reviews · doi:10.35946/arcr.v34.4.11 · Cited by 571 · see citing works
Adverse childhood experiences: towards a clear conceptual meaning
Kalmakis, K. A., & Chandler, G. E. (2014) · Journal of Advanced Nursing · doi:10.1111/jan.12329 · Cited by 390 · see citing works
Effect of childhood physical abuse on cortisol stress response
Carpenter, L. L., Shattuck, T. T., Tyrka, A. R., Geracioti, T. D., & Price, L. H. (2011) · Psychopharmacology · doi:10.1007/s00213-010-2007-4 · Cited by 307 · see citing works
Sex hormone activity in alcohol addiction: Integrating organizational and activational effects
Lenz, B., Müller, C. P., Stoessel, C., Sperling, W., Biermann, T., Hillemacher, T., Bleich, S., & Kornhuber, J. (2011) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2011.11.001 · Cited by 136 · see citing works
Huang, M., Schwandt, M. L., Ramchandani, V. A., George, D. T., & Heilig, M. (2012) · Alcoholism: Clinical and Experimental Research · doi:10.1111/j.1530-0277.2011.01695.x · Cited by 116 · see citing works
Walsh, K., Galea, S., & Koenen, K. C. (2012) · Clinical Psychology Science and Practice · doi:10.1111/cpsp.12004 · Cited by 87 · see citing works
Zhang, S., Lin, X., Liu, J., Pan, Y., Zeng, X., Chen, F., & Wu, J. (2020) · Psychiatry Research · doi:10.1016/j.psychres.2020.113524 · Cited by 83 · see citing works
Early life stress and substance use disorders: The critical role of adolescent substance use
Kirsch, D. E., & Lippard, E. (2022) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2022.173360 · Cited by 76 · see citing works
Huang, M., Schwandt, M. L., Chester, J. A., Kirchhoff, A. M., Kao, C., Liang, T., Tapocik, J. D., Ramchandani, V. A., George, D. T., Hodgkinson, C. A., et al. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2014.55 · Cited by 59 · see citing works
Flanagan, J. C., Baker, N. L., McRae-Clark, A. L., Brady, K. T., & Moran-Santa Maria, M. M. (2015) · Psychiatry Research · doi:10.1016/j.psychres.2015.07.064 · Cited by 56 · see citing works
Braquehais, M. D., Picouto, M. D., Casas, M., & Sher, L. (2012) · World Journal of Pediatrics · doi:10.1007/s12519-012-0358-0 · Cited by 51 · see citing works
Desire Thinking across the Continuum of Drinking Behaviour
Caselli, G., Ferla, M., Mezzaluna, C., Rovetto, F. M., & Spada, M. M. (2011) · European Addiction Research · doi:10.1159/000333601 · Cited by 51 · see citing works
Montagud‐Romero, S., Núñez, C., Blanco-Gandía, M. C., Laorden, E. M., Aguilar, M. A., Navarro‐Zaragoza, J., Almela, P., Milanés, M. V., Laorden, M. L., Miñarro, J., et al. (2017) · Psychopharmacology · doi:10.1007/s00213-017-4612-y · Cited by 48 · see citing works
Francke, I. D., Viola, T. W., Tractenberg, S. G., & Grassi‐Oliveira, R. (2013) · Child Abuse & Neglect · doi:10.1016/j.chiabu.2013.04.008 · Cited by 42 · see citing works
Khat Use and Trait Anger: Effects on Affect Regulation during an Acute Stressful Challenge
Bongard, S., Al’Absi, M., Khalil, N. S., & Habori, M. A. (2011) · European Addiction Research · doi:10.1159/000330317 · Cited by 39 · see citing works
Gerra, G., Somaini, L., Manfredini, M., Raggi, M. A., Saracino, M. A., Amore, M., Leonardi, C., Cortese, E., & Donnini, C. (2014) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2013.10.011 · Cited by 37 · see citing works
Waes, V. V., Darnaudéry, M., Marrocco, J., Gruber, S. H. M., Talavera, E., Mairesse, J., Camp, G. V., Casolla, B., Nicoletti, F., Mathé, A. A., et al. (2011) · Behavioural Brain Research · doi:10.1016/j.bbr.2011.02.033 · Cited by 30 · see citing works
Gerra, M. L., Gerra, M. C., Tadonio, L., Pellegrini, P., Marchesi, C., Mattfeld, E., Gerra, G., & Ossola, P. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.09.052 · Cited by 31 · see citing works
Madden, R. A., Atkinson, K., Shen, X., Green, C., Hillary, R. F., Hawkins, E. L., Såge, E., Sandu, A., Waiter, G. D., McNeil, C. J., et al. (2023) · European Psychiatry · doi:10.1192/j.eurpsy.2022.2347 · Cited by 26 · see citing works
Muehlhan, M., Höcker, A., Miller, R. E., Trautmann, S., Wiedemann, K., Lotzin, A., Barnow, S., & Schäfer, I. (2018) · Addiction Biology · doi:10.1111/adb.12681 · Cited by 25 · see citing works
Schäfer, I., Pawils, S., Drießen, M., Härter, M. C., Hillemacher, T., Klein, M., Muehlhan, M., Ravens‐Sieberer, U., Schäfer, M., Scherbaum, N., et al. (2017) · European Journal of Psychotraumatology · doi:10.1080/20008198.2017.1304114 · Cited by 24 · see citing works
Gerber, H., Borgwardt, S., Schmid, O., Gerhard, U., Jöechle, W., Riecher‐Rössler, A., Wiesbeck, G. A., & Walter, M. (2012) · European Addiction Research · doi:10.1159/000334411 · Cited by 20 · see citing works
Odenwald, M. G., & Semrau, P. (2011) · European Addiction Research · doi:10.1159/000333336 · Cited by 19 · see citing works
Trautmann, S., Muehlhan, M., Kirschbaum, C., Wïttchen, H., Höfler, M., Tobias Stalder, A., & Steudte‐Schmiedgen, S. (2017) · Addiction Biology · doi:10.1111/adb.12487 · Cited by 18 · see citing works
Substanzbezogene Störungen als Ursache und als Folge früher Gewalt
CANSAS Study Group, Schäfer, I., Barnow, S., & Pawils, S. (2015) · Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz · doi:10.1007/s00103-015-2264-9 · Cited by 15 · see citing works
The Potential Role of Glucocorticoids and the HPA Axis in Alcohol Dependence
Stephens, M. A. C., McCaul, M. E., & Wand, G. S. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-405941-2.00021-3 · Cited by 16 · see citing works
Substance use in youth adopted from foster care: Developmental mechanisms of risk
Blake, A. J., Tung, I., Langley, A. K., & Waterman, J. (2018) · Children and Youth Services Review · doi:10.1016/j.childyouth.2018.01.005 · Cited by 14 · see citing works
Goodyear‐Brown, P., Fath, A., & Myers, L. (2011) · Wiley eBooks · doi:10.1002/9781118094822.ch1 · Cited by 14 · see citing works
Hopf, F. W., Sparta, D. R., & Bonci, A. (2011) · ILAR Journal · doi:10.1093/ilar.52.3.239 · Cited by 11 · see citing works
Zhang, A., Price, J. L., Leonard, D. S., North, C. S., Surís, A., Javors, M. A., & Adinoff, B. H. (2020) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.14334 · Cited by 8 · see citing works
Stability of trauma-related symptoms during acute substance use treatment
Herzog, E., Odenwald, M. G., Proescholdt, M. G., Haubold, A., Bohnacker, I., Flögel, M., Linde, A., Müller, S., Wiesbeck, G. A., Lang, U. E., et al. (2015) · Journal of Addictive Diseases · doi:10.1080/10550887.2015.1127718 · Cited by 6 · see citing works
Schäfer, I., Barnow, S., & Pawils, S. (2016) · Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz · Cited by 6 · see citing works
Ghogare, A. S., Patil, P. S., & Vankar, G. K. (2021) · Annals of Indian Psychiatry · doi:10.4103/aip.aip_54_21 · Cited by 6 · see citing works
Vulnerability to alcohol use disorders following early sexual abuse: The role of effortful control
Klanecky, A. K., & McChargue, D. E. (2012) · Addiction Research & Theory · doi:10.3109/16066359.2012.703269 · Cited by 5 · see citing works
Substanzbezogene Störungen und traumatische Erfahrungen in der Kindheit
Wieland, N., & Klein, M. C. (2018) · Suchttherapie · doi:10.1055/a-0582-1751 · Cited by 4 · see citing works
Prevalence of Childhood Victimization Experiences in Psychiatric Patients: a Systematic Review
Mesquita, C. D. S., Basto-Pereira, M., & Maia, Â. (2016) · International Journal of Mental Health and Addiction · doi:10.1007/s11469-016-9697-8 · Cited by 4 · see citing works
Early Life Adversity as a Risk Factor for Alcohol Use Disorder
Schwandt, M. L. (2023) · Springer eBooks · doi:10.1007/978-3-031-32483-3_34 · Cited by 3 · see citing works
Sperry, S. H., & Lippard, E. (2025) · FOCUS The Journal of Lifelong Learning in Psychiatry · doi:10.1176/appi.focus.20240044 · Cited by 1 · see citing works
Wood, E. K., Aston, S. A., O'Connell, P., Hafen, E., Skowbo, A. N., Schwandt, M. L., Lindell, S. G., Smith, E., Johnson, M., Baron, Z., et al. (2024) · Stress · doi:10.1080/10253890.2024.2377272
- Authors
- Schäfer, I., Teske, L., Schulze-Thüsing, J., Homann, K., Reimer, J., Haasen, C., Hissbach, J., & Wiedemann, K.
- Affiliations
- University Medical Center Hamburg-Eppendorf (DE)
- Klinik und Poliklinik für Psychiatrie und Psychotherapie (DE)
- Venue
- European Addiction Research
- Publisher
- S. Karger AG
- Published
- 2010
- Volume
- 16
- Issue
- 2
- Pages
- 108-114
- ISSN
- 1022-6877 (ISSN-L)
- 1421-9891
- OpenAlex
- W2082141301
- Cited by
- 41
- References
- 41
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 2 · 2018: 3 · 2017: 3 · 2016: 2 · 2015: 3 · 2014: 2 · 2013: 4 · 2012: 7
- FWCI
- 2.62
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Addiction Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- childhood trauma, hypothalamic-pituitary-adrenal axis, alcoholism, cortisol, alcohol withdrawal, early life stress, sexual abuse, emotional abuse, emotional neglect, physical neglect, post-traumatic stress disorder, anxiety, depression
- MeSH terms
- Adolescent, Adult, Alcoholism, Child, Child Abuse, Psychology, Child, Female, Humans, Hydrocortisone, Hypothalamo-Hypophyseal System, Life Change Events, Longitudinal Studies, Male, Pituitary-Adrenal System, Psychometrics, Stress, Psychological, Chi-Square Distribution, Case-Control Studies, Adult Survivors of Child Abuse
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
