Hippocampal tail volume as a predictive biomarker of antidepressant treatment outcomes in patients with major depressive disorder: a CAN-BIND report


Finding a clinically useful neuroimaging biomarker that can predict treatment response in patients with major depressive disorder (MDD) is challenging, in part because of poor reproducibility and generalizability of findings across studies. Previous work has suggested that posterior hippocampal volumes in depressed patients may be associated with antidepressant treatment outcomes. The primary purpose of this investigation was to examine further whether posterior hippocampal volumes predict remission following antidepressant treatment. Magnetic resonance imaging (MRI) scans from 196 patients with MDD and 110 healthy participants were obtained as part of the first study in the Canadian Biomarker Integration Network in Depression program (CAN-BIND 1) in which patients were treated for 16 weeks with open-label medication. Hippocampal volumes were measured using both a manual segmentation protocol and FreeSurfer 6.0. Baseline hippocampal tail (Ht) volumes were significantly smaller in patients with depression compared to healthy participants. Larger baseline Ht volumes were positively associated with remission status at weeks 8 and 16. Participants who achieved early sustained remission had significantly greater Ht volumes compared to those who did not achieve remission by week 16. Ht volume is a prognostic biomarker for antidepressant treatment outcomes in patients with MDD.

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Data availability

Data for the present analyses were accessed via exclusive permission of the CAN-BIND consortium (for data inquiries: www.canbind.ca).

Code availability

Codes used for the present analyses are available from the corresponding author, NN, upon request.


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Funding and disclosure

CAN-BIND is an Integrated Discovery Program carried out in partnership with, and financial support from, the Ontario Brain Institute (OBI), an independent non-profit corporation, funded partially by the Ontario government. The opinions, results, and conclusions are those of the authors and no endorsement by the OBI is intended or should be inferred. Additional funding is provided by the Canadian Institutes of Health Research (CIHR), Lundbeck, Bristol-Myers Squibb, Pfizer, and Servier. Funding and/or in kind support is also provided by the investigators’ universities and academic institutions. N Nogovitsyn, M Muller, R Souza, S Hassel, S Arnott, A Davis, G Hall, J Harris, J Addington, K Harkness, S Rotzinger, and N Zamyadi have no relevant or material financial disclosures or any other potential conflicts of interest. Dr. Metzak has received a Research Fellowship grant support from the CIHR. Dr. Ismail has received grants from CIHR, Brain Canada, Consortium on Neurodegeneration in Aging, Jansen; consulting honoraria from Jansen, Lundbeck, Otsuka, and Sunovion. Dr. Downar reports research grants from CIHR, the National Institute of Mental Health, Brain Canada, the Canadian Biomarker Integration Network in Depression, the OBI, the Weston Foundation, the Klarman Family Foundation, the Arrell Family Foundation, and the Buchan Family Foundation, travel stipends from Lundbeck and ANT Neuro, in-­kind equipment support for investigator­-initiated trials from MagVenture, and is an advisor for BrainCheck, TMS Neuro Solutions, and Restorative Brain Clinics. Dr. Parikh reports, in the last 36 months, consulting honoraria from Takeda, Sunovion, Assurex, and Mensante, research grants from Takeda, Assurex, OBI, Canadian Institutes of Health Research, the Ethel and James Flinn Foundation, and shares in Mensante. Dr. Soares received honoraria for ad hoc speaking or advising/consulting, or received research funds, from: Lundbeck, Merck, OBI, Ontario Research Funds—Research Excellence, Otsuka, Pfizer, Sunovion. Dr. Milev has received research funds and honoraria for speaking/consulting from: Allergan, Canadian Institutes of Health Research, Canadian Biomarker Integrated Network in Depression, Canadian Network for Mood and Anxiety Treatments, Janssen, Lundbeck, Otsuka, Pfizer, Shire, Sunovion. Dr. Frey has received research funding from Pfizer and consulting fees from Otsuka. Dr. Lam has received honoraria for ad hoc speaking or advising/consulting, or received research funds, from: Akili, Allergan, Asia-Pacific Economic Cooperation, BC Leading Edge Foundation, Canadian Institutes of Health Research, Canadian Network for Mood and Anxiety Treatments, Canadian Psychiatric Association, CME Institute, Hansoh, Healthy Minds Canada, Janssen, Lundbeck, Lundbeck Institute, Medscape, Mind.Me, MITACS, OBI, Otsuka, Pfizer, St. Jude Medical, University Health Network Foundation, and VGH-UBCH Foundation. Dr. Strother receives funding from the OBI and CIHR (MOP137097) for neuroimaging analysis in CAN-BIND and he is the Chief Scientific Officer of ADMdx, Inc., a neuroimaging consulting company. Dr. Kennedy is/or has been an advisor/consultant for: Abbott, Alkermes, Allergan, BMS, Janssen, Lundbeck, Lundbeck Institute, Otsuka, Pfizer, Servier, Sunovion; and participated in clinical trials/studies for Abbott, BMS, Janssen, Pfizer, Servier; Speaking engagements with the following organizations: BMS, Lundbeck, Pfizer, Servier, Xian-Janssen; and has received research support from: OBI, CIHR, BMS, Brain Canada, Janssen, Lundbeck, ORF, Pfizer, Servier. Dr MacQueen has received honoraria from Lundbeck, Janssen, and AllerGen in the past 36 months.

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Nogovitsyn, N., Muller, M., Souza, R. et al. Hippocampal tail volume as a predictive biomarker of antidepressant treatment outcomes in patients with major depressive disorder: a CAN-BIND report. Neuropsychopharmacol. 45, 283–291 (2020) doi:10.1038/s41386-019-0542-1

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