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Cited by 18Stress Responses and CortisolChild Abuse and TraumaSchizophrenia research and treatment

Childhood Trauma Is Nominally Associated With Elevated Cortisol Metabolism in Severe Mental Disorder

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Aas, Monica, Ueland, Torill, Inova, Amina, Melle, Ingrid, Andreassen, Ole A., Steen, Nils Eiel·2020·Frontiers in Psychiatry
DOI 10.3389/fpsyt.2020.00391PMC PMC7247816
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Abstract

OBJECTIVE: Individuals exposed to childhood trauma display longstanding modifications of the Hypothalamic-Pituitary-Adrenal (HPA) axis, as well as cognitive impairments. Schizophrenia spectrum disorder (SZ) and bipolar disorders (BD) are characterised by higher prevalence of childhood trauma, abnormal HPA axis, and cognitive dysfunction. Elevated cortisol metabolism was recently demonstrated in both disorders. However, it is yet to be established if childhood adversity is associated with cortisol metabolism in this population, and how this may be associated with cognitive function. METHODS: One-hundred-and-fourteen participants with a DSM-IV SZ or BD diagnosis took part in the study. Diagnoses were evaluated by the Structured Clinical Interview for DSM-IV Axis I disorders (SCID-I). Estimated cortisol metabolizing activity (5α-reductase and 5β-reductase) was assessed by urinary free cortisol, and metabolites. All patients underwent cognitive assessment and completed the Childhood Trauma Questionnaire. RESULTS: Estimated 5β-reductase activity was elevated in participant with childhood physical abuse (r = 0.26, p = 0.005). After adjusting for age, sex and diagnosis, physical abuse was still nominally associated with elevated 5β-reductase. Moreover, only high 5α-reductase activity was negatively correlated with working memory and executive performance (r = -0.23, p = 0.01; r = -0.19, p = 0.05, respectively), however this disappeared after adjusting for age, sex and diagnosis. Cortisol metabolism did not mediate the association between childhood trauma and cognitive function. CONCLUSIONS: Our study indicates that childhood physical abuse is associated with elevated cortisol metabolism (5β-reductase) in adults with a SZ or BD disorder. However, our study did not support cortisol metabolism as a mediator between childhood trauma experiences and cognitive function within these disorders.

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  • A cohort study measuring cortisol metabolites revealed elevated beta reductase, a measure of cortisol turnover, in BD patients that experienced adverse childhood events such as physical abuse.

    “A cohort study measuring cortisol metabolites revealed elevated beta reductase, a measure of cortisol turnover, in BD patients that experienced adverse childhood events such as physical abuse (162).”

    From Childhood Trauma, the HPA Axis and Psychiatric Illnesses: A Targeted Literature Synthesis (2022) · cites this paper as [162]

    The Results section reports higher estimated 5β-reductase activity with childhood physical abuse, but the association was only nominal after adjustment for age, sex and diagnosis. The Methods describe a combined schizophrenia and bipolar disorder sample; the paper does not establish this finding specifically in patients with bipolar disorder. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Elevated cortisol metabolism (through urinary analysis of cortisol metabolites) was found in schizophrenia patients (n = 63) with childhood trauma compared to those without trauma.

    “Similarly, elevated cortisol metabolism (through urinary analysis of cortisol metabolites: e.g., urinary free cortisol/cortisone, allo-tetrahydrocortisol, tetrahydrocortisol, and tetrahydrocortisone) was found in schizophrenia patients (n = 63) with childhood trauma compared to those without trauma (162).”

    From Childhood Trauma, the HPA Axis and Psychiatric Illnesses: A Targeted Literature Synthesis (2022) · cites this paper as [162]

    The Methods (Subjects; Design and Cortisol Measurements) confirm urinary metabolite analysis and a group of 63 patients with schizophrenia-spectrum disorders, only 34 of whom had schizophrenia. The Results (Cortisol Metabolism and Childhood Trauma) report a nominal association between childhood physical abuse and higher 5β-reductase activity in the combined sample of 114 patients, not a trauma-versus-no-trauma finding established specifically for the 63-patient schizophrenia-spectrum group. The claim also broadens physical abuse to childhood trauma generally. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

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Research works printed but not linked: 39

  1. [2]Church C Andreassen OA Lorentzen S Melle I Aas M Childhood Trauma and Minimization/Denial in People with and without a Severe Mental Disorder. Front Psychol (2017) 8: 1276. 10.3389/fpsyg.2017.01276 28883800 PMC5573805 · DOI
  2. [4]Anisman H Zaharia MD Meaney MJ Merali Z Do early-life events permanently alter behavioral and hormonal responses to stressors? Int J Dev Neurosci (1998) 16(3-4): 149–64. 10.1016/S0736-5748(98)00025-2 9785112 · DOI
  3. [5]Liu D Diorio J Tannenbaum B Caldji C Francis D Freedman A Maternal care, hippocampal glucocorticoid receptors, and hypothalamic-pituitary-adrenal responses to stress. Science (1997) 277(5332): 1659–62. 10.1126/science.277.5332.1659 9287218 · DOI · Paper page
  4. [6]Devylder JE Ben-David S Schobel SA Kimhy D Malaspina D Corcoran CM Temporal association of stress sensitivity and symptoms in individuals at clinical high risk for psychosis. psychol Med (2013) 43(2): 259–68. 10.1017/S0033291712001262 PMC3716006 22651857 · DOI
  5. [7]Trotman HD Holtzman CW Walker EF Addington JM Bearden CE Cadenhead KS Stress exposure and sensitivity in the clinical high-risk syndrome: initial findings from the North American Prodrome Longitudinal Study (NAPLS). Schizophr Res (2014) 160(1-3): 104–9. 10.1016/j.schres.2014.09.017 PMC4593703 25443665 · DOI
  6. [8]Veling W Counotte J Pot-Kolder R van Os J van der Gaag M Childhood trauma, psychosis liability and social stress reactivity: a virtual reality study. psychol Med (2016) 46(16): 3339–48. 10.1017/S0033291716002208 27619196 · DOI
  7. [10]Lovallo WR Farag NH Sorocco KH Cohoon AJ Vincent AS Lifetime adversity leads to blunted stress axis reactivity: studies from the Oklahoma Family Health Patterns Project. Biol Psychiatry (2012) 71(4): 344–9. 10.1016/j.biopsych.2011.10.018 PMC3264696 22112928 · DOI
  8. [11]Steen NE Methlie P Lorentzen S Dieset I Aas M Nerhus M Altered systemic cortisol metabolism in bipolar disorder and schizophrenia spectrum disorders. J Psychiatr Res (2014) 52: 57– 62. 10.1016/j.jpsychires.2014.01.017 24534618 · DOI · Paper page
  9. [12]Yehuda R McEwen BS Protective and damaging effects of the biobehavioral stress response: cognitive, systemic and clinical aspects: ISPNE XXXIV meeting summary. Psychoneuroendocrinology (2004) 29(9): 1212–22. 10.1016/j.psyneuen.2004.01.006 15219646 · DOI
  10. [13]Yehuda R Seckl J Minireview: Stress-related psychiatric disorders with low cortisol levels: a metabolic hypothesis. Endocrinology (2011) 152(12): 4496–503. 10.1210/en.2011-1218 21971152 · DOI · Paper page
  11. [14]Tseilikman V Dremencov E Maslennikova E Ishmatova A Manukhina E Downey HF Post-Traumatic Stress Disorder Chronification via Monoaminooxidase and Cortisol Metabolism. Horm Metab Res (2019) 51(9): 618–22. 10.1055/a-0975-9268 31505706 · DOI
  12. [15]Klaassens ER Giltay EJ Cuijpers P van Veen T Zitman FG Adulthood trauma and HPA-axis functioning in healthy subjects and PTSD patients: a meta-analysis. Psychoneuroendocrinology (2012) 37(3): 317–31. 10.1016/j.psyneuen.2011.07.003 21802212 · DOI
  13. [16]Steen NE Methlie P Lorentzen S Hope S Barrett EA Larsson S Increased systemic cortisol metabolism in patients with schizophrenia and bipolar disorder: a mechanism for increased stress vulnerability? J Clin Psychiatry (2011) 72(11): 1515–21. 10.4088/JCP.10m06068yel 21367348 · DOI
  14. [17]Steen NE Tesli M Kahler AK Methlie P Hope S Barrett EA SRD5A2 is associated with increased cortisol metabolism in schizophrenia spectrum disorders. Prog Neuropsychopharmacol Biol Psychiatry (2010) 34(8): 1500–6 10.1016/j.pnpbp.2010.08.013 20800085 · DOI
  15. [18]Paterson JM Holmes MC Kenyon CJ Carter R Mullins JJ Seckl JR Liver-selective transgene rescue of hypothalamic-pituitary-adrenal axis dysfunction in 11beta-hydroxysteroid dehydrogenase type 1-deficient mice. Endocrinology (2007) 148(3): 961–6. 10.1210/en.2006-0603 PMC6443039 17170103 · DOI
  16. [19]Aas M Dazzan P Mondelli V Melle I Murray RM Pariante CM A Systematic Review of Cognitive Function in First-Episode Psychosis, Including a Discussion on Childhood Trauma, Stress, and Inflammation. Front Psychiatry (2014) 4: 182. 10.3389/fpsyt.2013.00182 24409157 PMC3884147 · DOI · Paper page
  17. [20]Dauvermann MR Donohoe G The role of childhood trauma in cognitive performance in schizophrenia and bipolar disorder - A systematic review. Schizophr Res Cogn (2019) 16: 1– 11. 10.1016/j.scog.2018.11.001 30581765 PMC6293032 · DOI
  18. [21]Kay SR Fiszbein A Opler LA The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull (1987) 13(2): 261–76. 10.1093/schbul/13.2.261 3616518 · DOI · Paper page
  19. [23]Pedersen G Hagtvet KA Karterud S Generalizability studies of the Global Assessment of Functioning-Split version. Compr Psychiatry (2007) 48(1): 88– 94. 10.1016/j.comppsych.2006.03.008 17145287 · DOI
  20. [24]Lupien SJ Maheu F Tu M Fiocco A Schramek TE The effects of stress and stress hormones on human cognition: Implications for the field of brain and cognition. Brain Cogn (2007) 65(3): 209–37. 10.1016/j.bandc.2007.02.007 17466428 · DOI · Paper page
  21. [25]Perez CM Widom CS Childhood victimization and long-term intellectual and academic outcomes. Child Abuse Negl (1994) 18(8): 617–33. 10.1016/0145-2134(94)90012-4 7953902 · DOI · Paper page
  22. [26]Zanelli J Reichenberg A Morgan K Fearon P Kravariti E Dazzan P Specific and generalized neuropsychological deficits: a comparison of patients with various first-episode psychosis presentations. Am J Psychiatry (2010) 167(1): 78– 85. 10.1176/appi.ajp.2009.09010118 19952077 · DOI
  23. [27]Delis DC Kramer JH Kaplan E Ober BA California Verbal Learning Test-Second edition (CVLT-II). Norwegian Manual Supplement. Stockholm: Pearson Assessment (2004).
  24. [28]Wechsler D Wechsler Adult Intelligence Scale -Third Edition (WAIS-III) Norwegian Manual. Stockholm: Pearson Assessment (2003). 12801187
  25. [31]Bernstein DP Fink L Handelsman L Foote J Lovejoy M Wenzel K Initial reliability and validity of a new retrospective measure of child abuse and neglect. Am J Psychiatry (1994) 151(8): 1132–6. 10.1176/ajp.151.8.1132 8037246 · DOI · Paper page
  26. [32]Aas M Djurovic S Athanasiu L Steen NE Agartz I Lorentzen S Serotonin transporter gene polymorphism, childhood trauma, and cognition in patients with psychotic disorders. Schizophr Bull (2012) 38(1): 15– 22. 10.1093/schbul/sbr113 21908796 PMC3245595 · DOI
  27. [33]Ulick S Tedde R Wang JZ Defective ring A reduction of cortisol as the major metabolic error in the syndrome of apparent mineralocorticoid excess. J Clin Endocrinol Metab (1992) 74(3): 593–9. 1740492
  28. [35]Tomlinson JW Finney J Hughes BA Hughes SV Stewart PM Reduced glucocorticoid production rate, decreased 5alpha-reductase activity, and adipose tissue insulin sensitization after weight loss. Diabetes (2008) 57(6): 1536–43. 10.2337/db08-0094 PMC7611651 18340018 · DOI · Paper page
  29. [36]Sanchez P Torres JM Gavete P Ortega E Effects of swim stress on mRNA and protein levels of steroid 5alpha-reductase isozymes in prefrontal cortex of adult male rats. Neurochem Int (2008) 52(3): 426–31. 10.1016/j.neuint.2007.07.019 17826869 · DOI
  30. [37]Mondelli V Dazzan P Hepgul N Di FM Aas M D’Albenzio A Abnormal cortisol levels during the day and cortisol awakening response in first-episode psychosis: the role of stress and of antipsychotic treatment. Schizophr Res (2010) 116(2-3): 234–42. 10.1016/j.schres.2009.08.013 PMC3513410 19751968 · DOI · Paper page
  31. [38]Aas M Henry C Andreassen OA Bellivier F Melle I Etain B The role of childhood trauma in bipolar disorders. Int J Bipolar Disord (2016) 4(1): 2. 10.1186/s40345-015-0042-0 26763504 PMC4712184 · DOI
  32. [39]Raven PW Taylor NF 11Beta-HSD and 17beta-HSD as biological markers of depression: sex differences and correlation with symptom severity. Endocr Res (1998) 24(3-4): 659–62. 10.3109/07435809809032666 9888556 · DOI
  33. [40]Poór V Juricskay S Gáti A Osváth P Tényi T Urinary steroid metabolites and 11beta-hydroxysteroid dehydrogenase activity in patients with unipolar recurrent major depression. J Affect Disord (2004) 81(1): 55–9. 10.1016/S0165-0327(03)00199-X 15183600 · DOI
  34. [42]Pruessner JC Dedovic K Pruessner M Lord C Buss C Collins L Stress regulation in the central nervous system: evidence from structural and functional neuroimaging studies in human populations - 2008 Curt Richter Award Winner. Psychoneuroendocrinology (2010) 35(1): 179–91. 10.1016/j.psyneuen.2009.02.016 19362426 · DOI · Paper page
  35. [43]Anacker C Hen R Adult hippocampal neurogenesis and cognitive flexibility - linking memory and mood. Nat Rev Neurosci (2017) 18(6): 335–46 10.1038/nrn.2017.45 PMC6261347 28469276 · DOI · Paper page
  36. [44]Sapolsky RM Krey LC McEwen BS The neuroendocrinology of stress and aging: the glucocorticoid cascade hypothesis. Endocr Rev (1986) 7(3): 284– 301. 10.1210/edrv-7-3-284 3527687 · DOI · Paper page
  37. [45]Sapolsky RM The possibility of neurotoxicity in the hippocampus in major depression: a primer on neuron death. Biol Psychiatry (2000) 48(8): 755–65. 10.1016/S0006-3223(00)00971-9 11063972 · DOI · Paper page
  38. [46]Aas M Henry C Bellivier F Lajnef M Gard S Kahn JP Affective lability mediates the association between childhood trauma and suicide attempts, mixed episodes and co-morbid anxiety disorders in bipolar disorders. Psychol Med (2017) 47(5): 902–12. 10.1017/S0033291716003081 27894372 · DOI
  39. [48]Tajima EA Herrenkohl TI Huang B Whitney SD Measuring child maltreatment: a comparison of prospective parent reports and retrospective adolescent reports. Am J Orthopsychiatry (2004) 74(4): 424–35. 10.1037/0002-9432.74.4.424 15554804 · DOI

Cited by

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Authors
Aas, M., Ueland, T., Inova, A., Melle, I., Andreassen, O. A., & Steen, N. E.
Affiliations
Oslo University Hospital (NO)
Corresponding author
Aas, Monica
ORCID
Venue
Frontiers in Psychiatry
Publisher
Frontiers Media SA
Published
2020-05-14
Volume
11
Pages
391-391
ISSN
1664-0640 (ISSN-L)
DOI
10.3389/fpsyt.2020.00391
PMC
PMC7247816
OpenAlex
W3025500123
Cited by
18
References
7
Citations by year
2026: 4 · 2025: 4 · 2024: 2 · 2023: 3 · 2022: 3 · 2021: 1 · 2020: 1
FWCI
1.16
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Psychiatry (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research Portal (King's College London) (publishedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • NORA - Norwegian Open Research Archives (submittedVersion, cc-by)
Funders
Norges Forskningsråd (22 327)
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Keywords
childhood trauma, child physical abuse, cortisol metabolism, 5beta-reductase, 5α-reductase, hypothalamic-pituitary-adrenal axis, schizophrenia spectrum disorders, bipolar disorder, cognitive function, working memory, executive function, urinary free cortisol

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