Childhood trauma, HPA axis activity and antidepressant response in patients with depression

Nikkheslat, N. et al. (2020) Childhood trauma, HPA axis activity and antidepressant response in patients with depression. Brain, Behavior, and Immunity, 87, pp. 229-237. (doi: 10.1016/j.bbi.2019.11.024) (PMID:31794798) (PMCID:PMC7327513)

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Childhood trauma is among the most potent contributing risk factors for depression and is associated with poor treatment response. Hypothalamic-pituitary-adrenal (HPA) axis abnormalities have been linked to both childhood trauma and depression, but the underlying mechanisms are poorly understood. The present study aimed to investigate the link between childhood trauma, HPA axis activity and antidepressant response in patients with depression. As part of the Wellcome Trust NIMA consortium, 163 depressed patients and 55 healthy volunteers were included in this study. Adult patients meeting Structured Clinical Interview for Diagnostic and Statistical Manual Version-5 criteria for major depression were categorised into subgroups of treatment responder (n=42), treatment non-responder (n=80) and untreated depressed (n=41) based on current depressive symptom severity measured by the 17-item Hamilton Rating Scale for Depression and exposure to antidepressant medications established by Antidepressant Treatment Response Questionnaire. Childhood Trauma Questionnaire was obtained. Baseline serum C-reactive protein was measured using turbidimetric detection. Salivary cortisol was analyzed at multiple time points during the day using the ELISA technique. Glucocorticoid resistance was defined as the coexistence of hypercortisolemia and inflammation. Our results show that treatment non-responder patients had higher exposure to childhood trauma than responders. No specific HPA axis abnormalities were found in treatment non-responder depressed patients. Untreated depressed showed increased diurnal cortisol levels compared with patients on antidepressant medication, and higher prevalence of glucocorticoid resistance than medicated patients and controls. The severity of childhood trauma was associated with increased diurnal cortisol levels only in individuals with glucocorticoid resistance. Therefore, our findings suggest that the severity of childhood trauma experience contributes to a lack of response to antidepressant treatment. The effects of childhood trauma on increased cortisol levels are specifically evident in patients with glucocorticoid resistance and suggest glucocorticoid resistance as a target for the development of personalized treatment for a subgroup of depressed patients with a history of childhood trauma rather than for all patients with resistance to antidepressant treatment.

Item Type:Articles
Additional Information:This work was funded by a grant from the Wellcome Trust (Grant number: 104025/Z/14/Z) to the NIMA Consortium, which is also funded by Janssen, GlaxoSmithKline, Lundbeck and Pfizer. Recruitment of patients was supported by the National Institute of Health Research (NIHR) Clinical Research Network: Kent, Surrey and Sussex & Eastern. The work is also supported by the Medical Research Council (UK) MR/J002739/1 and the Commission of European Communities Seventh Framework Programme (Collaborative Project Grant Agreement no. 22963, Mood Inflame); and part funded by the NIHR/Wellcome Trust, King's Clinical Research Facility and the NIHR Biomedical Research Centre [and Dementia Unit] at South London and Maudsley NHS Foundation Trust and King’s College London. SRC consults for Cambridge Cognition and Shire; and his input in this project was funded by a Wellcome Trust Clinical Fellowship (110049/Z/15/Z).
Glasgow Author(s) Enlighten ID:Cavanagh, Professor Jonathan
Authors: Nikkheslat, N., McLaughlin, A. P., Hastings, C., Zajkowska, Z., Nettis, M. A., Mariani, N., Enache, D., Lombardo, G., Pointon, L., Cowen, P. J., Cavanagh, J., Harrison, N. A., Bullmore, E. T., Pariante, C. M., and Mondelli, V.
College/School:College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Mental Health and Wellbeing
Journal Name:Brain, Behavior, and Immunity
ISSN (Online):1090-2139
Published Online:30 November 2019
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in Brain, Behavior, and Immunity 87: 229-237
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
171331Consortium of Neuroimmunology of Mood Disorders and Alzheimer's DiseaseJonathan CavanaghWellcome Trust (WELLCOTR)104025/Z/14/ZHW - Mental Health and Wellbeing