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Increased hippocampal tail volume predicts depression status and remission to anti-depressant medications in major depression

Molecular Psychiatry volume 23, pages 1737–1744 (2018)Cite this article

Abstract

Studies of patients with major depressive disorder (MDD) have consistently reported reduced hippocampal volumes; however, the exact pattern of these volume changes in specific anatomical subfields and their functional significance is unclear. We sought to clarify the relationship between hippocampal tail volumes and (i) a diagnosis of MDD, and (ii) clinical remission to anti-depressant medications (ADMs). Outpatients with nonpsychotic MDD (n=202) based on DSM-IV criteria and a 17-item Hamilton Rating Scale for Depression (HRSD17) score ⩾16 underwent pretreatment magnetic resonance imaging as part of the international Study to Predict Optimized Treatment for Depression (iSPOT-D). Gender-matched healthy controls (n=68) also underwent MRI scanning. An automated pipeline was used to objectively measure hippocampal subfield and whole brain volumes. Remission was defined as an HRSD17 of ⩽7 following 8 weeks of randomized open-label treatment ADMs: escitalopram, sertraline or venlafaxine-extended release. After controlling for age and total brain volume, hippocampal tail volume was larger in the MDD cohort compared to control subjects. Larger hippocampal tail volume was positively related to clinical remission, independent of total hippocampal volume, total brain volume and age. These data provide convergent evidence of the importance of the hippocampus in the development or treatment of MDD. Hippocampal tail volume is proposed as a potentially useful biomarker of sensitivity to ADM treatment.

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Acknowledgments

We thank all the patients and volunteers who agreed to participate in this study, and the staff of the MRI facility at the Westmead Hospital, NSW, Australia. Professor Evian Gordon and Lea Williams are acknowledged for their contribution to the instigation and leadership of this project. Dr Mayuresh Korgoankar is thanked for his contribution to data collection and patient recruitment. We acknowledge Brain Resource as the sponsor for the iSPOT-D study (NCT00693849). Claire Day and Catherine King (Global Study Co-ordinators) are thanked as is the iSPOT-D Publication Team for their valuable input into this manuscript and to the study overall. We acknowledge the hard work of the Brain Dynamics Centre iSPOT-D team at the Sydney site for their help with data collection of the presented cohort. Dr Anthony Harris is thanked for his role in clinical supervision of clinical imaging evaluations (as PI for the Sydney site), and Dr Tim Usherwood for his role in overseeing the partnership with primary care practitioners and recruitment of patients from these primary care settings (as co-PI for the Sydney site). Dr Lavier Gomes, Ms Sheryl Foster and the Department of Radiology at Westmead are thanked for their substantial contributions to MRI data acquisition. SMG acknowledges the support of the Sydney Medical School, the Heart Research Institute, the Frecker Family Trust and the Parker-Hughes Bequest.

Brain Resource Ltd is the sponsor for the iSPOT-D study (NCT00693849).

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Authors and Affiliations

  1. Sydney Translational Imaging Laboratory, Heart Research Institute, Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia

    J J Maller, K Broadhouse & S M Grieve

  2. Sydney Medical School, The University of Sydney, Sydney, NSW, Australia

    J J Maller, K Broadhouse & S M Grieve

  3. General Electric Healthcare, Richmond, VIC, Australia

    J J Maller

  4. Duke-National University of Singapore, Singapore, Singapore

    A J Rush

  5. Brain Resource Ltd, Sydney, NSW, Australia

    E Gordon

  6. Brain Resource Ltd, San Francisco, CA, USA

    E Gordon

  7. Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, FL, USA

    S Koslow

  8. The Brain Dynamics Centre, Westmead Institute for Medical Research, University of Sydney, Sydney, NSW, Australia

    S M Grieve

  9. Department of Radiology, Royal Prince Alfred Hospital, Camperdown, Sydney, NSW, Australia

    S M Grieve

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Correspondence to J J Maller.

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Conflict of Interest

EG is the CEO of Brain Resource Ltd and has significant equity and stock options in the company. AJR has received consulting fees from Brain Resource Ltd, Duke-NUS, Eli Lilly, Emmes Corp, Liva-Nova Inc., Medavante Inc., Otsuka Pharmaceuticals USA, Santium Inc., Sunovion, Takeda USA, University of Texas Southwestern Med Cntr.; royalties from Guilford Publications and the University of Texas Southwestern Medical Center at Dallas. SK serves on the Board of Directors of MyBrainSolutions and receive compensation in cash and stock options; serve as a private consultant for grant mentoring and preparation to staff at the University of Miami, Miller School of Medicine, Miami, Florida, and Louisiana State University Health Science Center; serves as a Director for the BRAINnet Database. SMG has previously received fees as a consultant for Brain Resource Ltd. The remaining authors declare no conflict of interest.

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Maller, J.J., Broadhouse, K., Rush, A.J. et al. Increased hippocampal tail volume predicts depression status and remission to anti-depressant medications in major depression. Mol Psychiatry 23, 1737–1744 (2018). https://doi.org/10.1038/mp.2017.224

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