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State-dependent changes in hippocampal grey matter in depression

Molecular Psychiatry volume 18, pages 1265–1272 (2013)Cite this article

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Abstract

Reduced hippocampal volume has been reported in depression and may be involved in the aetiology of depressive symptoms and vulnerability to depressive relapse. Neuroplasticity following antidepressant drug treatment in the hippocampus has been demonstrated in animal models but adaptive changes after such treatment have not been shown in humans. In this study, we determined whether grey matter loss in the hippocampus in depression (1) is present in medication-free depressed (2) changes in response to antidepressant treatment and (3) is present as a stable trait in medication-free remitted patients. Sixty-four medication-free unipolar depressed patients: 39 currently depressed and 25 in remission, and 66 healthy controls (HC) underwent structural magnetic resonance imaging in a cross-sectional and longitudinal design. Thirty-two currently depressed participants were then treated with the antidepressant citalopram for 8 weeks. Adherence to treatment was evaluated by measuring plasma citalopram concentration. We measured regional variation in grey matter concentration by using voxel-based morphometry-Diffeomorphic Anatomical Registration Through Exponentiated Lie algebra. Patients with current depression had bilaterally reduced grey matter in the hippocampus compared with HC and untreated patients in stable remission with the latter groups not differing. An increase in grey matter was observed in the hippocampus following treatment with citalopram in currently depressed patients. Grey matter reduction in the hippocampus appears specific to the depressed state and is a potential biomarker for a depressive episode.

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Acknowledgements

We thank all the participants, without their interest in our research this study would not have been possible. We are grateful to the Manchester Wellcome Trust Clinical Research Facility for help in recruiting, screening and scanning of volunteers, to staff at the Neuroscience and Psychiatry Unit (Dr Diana Chase, Kathryn Lloyd-Williams, Dr Karen Lythe, Dr Ivan Koychev and Christine Holliday) and to the Mental Health Research Network (MHRN, Moira Winters, Isabel Adeyemi, Vicky Bell, Humera Hussain and Martina Witter) for their assistance in recruitment and data acquisition. Prof. Anderson had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. This study was funded by the NEWMOOD EU Integrated Programme LSHM-CT-2004-503474 and the Medical Research Council UK (REMEDi) G0601526. The NIHR Manchester Biomedical Research Centre provided additional financial support and the REMEDi study was adopted as a portfolio study by the UK Clinical Research Network (UKCRN).

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  1. D Arnone

    Present address: 4Current address: Affective Disorders Research Group, Department of Psychological Medicine, Institute of Psychiatry, London SE5 8AF.,

  2. D Arnone and S McKie: These authors contributed equally to the work.

Authors and Affiliations

  1. Neuroscience and Psychiatry Unit, University of Manchester, Manchester, UK

    D Arnone, S McKie, R Elliott, G Juhasz, E J Thomas, J F W Deakin & I M Anderson

  2. Department of Pharmacodynamics, Semmelweis University, Budapest, Hungary

    G Juhasz

  3. Department of Imaging Science and Biomedical Engineering, University of Manchester, Manchester, UK

    D Downey & S Williams

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  1. D Arnone
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Correspondence to D Arnone.

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Competing interests

Prof. Deakin has carried out consultancy and speaking engagements for Bristol Myers Squibb, AstraZeneca, Eli Lilly, Schering Plough, Janssen-Cilag and Servier. All fees are paid to the University of Manchester to reimburse them for the time taken. He has share options in P1vital. Prof. Anderson has received grant support from AstraZeneca and Servier; consultancy fees/honoraria for speaking/support to attend conferences from Wyeth, Servier, Eli Lilly and Lundbeck; Prof Williams receives grant funding from AstraZeneca and has had research grant support from Pfizer and Servier in recent years. Dr Elliott has received consultancy fees from Cambridge Cognition. Dr Arnone has received travel grants from Servier and Jannsen-Cilag. The remaining authors declare no conflict of interest.

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Arnone, D., McKie, S., Elliott, R. et al. State-dependent changes in hippocampal grey matter in depression. Mol Psychiatry 18, 1265–1272 (2013). https://doi.org/10.1038/mp.2012.150

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