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Altered Relationship between Cortisol Response to Social Stress and Mediotemporal Function during Fear Processing in People at Clinical High Risk for Psychosis: A Preliminary Report

Research output: Contribution to journalArticlepeer-review

Original languageEnglish
JournalEuropean Archives Of Psychiatry And Clinical Neuroscience
Early online date4 Sep 2021
Accepted/In press11 Aug 2021
E-pub ahead of print4 Sep 2021

Bibliographical note

Funding Information: This study was supported by Grant MR/J012149/1 from the Medical Research Council (MRC). SB was supported by National Institute for Health Research (NIHR) Clinician Scientist Award NIHR CS-11-001 when this work was carried out. This study represents independent research supported by the NIHR-Wellcome King’s Clinical Research Facility and the NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. EAK was supported by the NIHR Collaboration for Leadership in Applied Health Research and Care South London at King’s College Hospital NHS Foundation Trust when this work was carried out. The views expressed are those of the authors and not necessarily those of the NHS, NIHR or the Department of Health and Social Care. MGB was supported by a Veni fellowship from the Netherlands Organization for Scientific Research. RM has received honoraria from giving lectures/seminars at meetings supported by Janssen, Sunovian, Otsuka Pharmaceutical and Lundbeck. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. Publisher Copyright: © 2021, The Author(s).


King's Authors


Evidence suggests that people at Clinical High Risk for Psychosis (CHR) have a blunted cortisol response to stress and altered mediotemporal activation during fear processing, which may be neuroendocrine–neuronal signatures of maladaptive threat responses. However, whether these facets are associated with each other and how this relationship is affected by cannabidiol treatment is unknown. We examined the relationship between cortisol response to social stress and mediotemporal function during fear processing in healthy people and in CHR patients. In exploratory analyses, we investigated whether treatment with cannabidiol in CHR individuals could normalise any putative alterations in cortisol-mediotemporal coupling. 33 CHR patients were randomised to 600 mg cannabidiol or placebo treatment. Healthy controls (n = 19) did not receive any drug. Mediotemporal function was assessed using a fearful face-processing functional magnetic resonance imaging paradigm. Serum cortisol and anxiety were measured immediately following the Trier Social Stress Test. The relationship between cortisol and mediotemporal blood-oxygen-level-dependent haemodynamic response was investigated using linear regression. In healthy controls, there was a significant negative relationship between cortisol and parahippocampal activation (p = 0.023), such that the higher the cortisol levels induced by social stress, the lower the parahippocampal activation (greater deactivation) during fear processing. This relationship differed significantly between the control and placebo groups (p = 0.033), but not between the placebo and cannabidiol groups (p = 0.67). Our preliminary findings suggest that the parahippocampal response to fear processing may be associated with the neuroendocrine (cortisol) response to experimentally induced social stress, and that this relationship may be altered in patients at clinical high risk for psychosis.

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