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Childhood trauma, HPA axis activity and antidepressant response in patients with depression.
Nikkheslat, Naghmeh; McLaughlin, Anna P; Hastings, Caitlin; Zajkowska, Zuzanna; Nettis, Maria A; Mariani, Nicole; Enache, Daniela; Lombardo, Giulia; Pointon, Linda; Cowen, Philip J; Cavanagh, Jonathan; Harrison, Neil A; Bullmore, Edward T; Pariante, Carmine M; Mondelli, Valeria.
Affiliation
  • Nikkheslat N; Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, Kings College London, UK. Electronic address: naghmeh.nikkheslat@kcl.ac.uk.
  • McLaughlin AP; Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, Kings College London, UK.
  • Hastings C; Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, Kings College London, UK.
  • Zajkowska Z; Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, Kings College London, UK.
  • Nettis MA; Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, Kings College London, UK.
  • Mariani N; Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, Kings College London, UK.
  • Enache D; Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, Kings College London, UK.
  • Lombardo G; Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, Kings College London, UK.
  • Pointon L; Department of Psychiatry, Behavioural and Clinical Neurosciences Institute, University of Cambridge, UK.
  • Cowen PJ; University Department of Psychiatry, Warneford Hospital, Oxford, UK.
  • Cavanagh J; Mental Health and Wellbeing, Sackler Institute, Neurology Block, Queen Elizabeth University Hospital, Glasgow, UK.
  • Harrison NA; Department of Neuroscience, Brighton & Sussex Medical School, University of Sussex, Brighton, UK.
  • Bullmore ET; Department of Psychiatry, Behavioural and Clinical Neurosciences Institute, University of Cambridge, UK; GlaxoSmithKline R&D, Stevenage UK, Cambridgeshire & Peterborough NHS Foundation Trust, Cambridge UK.
  • Pariante CM; Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, Kings College London, UK; National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London, UK.
  • Mondelli V; Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, Kings College London, UK; National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London, UK.
Brain Behav Immun ; 87: 229-237, 2020 07.
Article in En | MEDLINE | ID: mdl-31794798
ABSTRACT
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Depression / Hypothalamo-Hypophyseal System Type of study: Guideline / Qualitative_research / Risk_factors_studies Limits: Adult / Child / Humans Language: En Journal: Brain Behav Immun Journal subject: ALERGIA E IMUNOLOGIA / CEREBRO / PSICOFISIOLOGIA Year: 2020 Type: Article

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Depression / Hypothalamo-Hypophyseal System Type of study: Guideline / Qualitative_research / Risk_factors_studies Limits: Adult / Child / Humans Language: En Journal: Brain Behav Immun Journal subject: ALERGIA E IMUNOLOGIA / CEREBRO / PSICOFISIOLOGIA Year: 2020 Type: Article