title: Discovering biomarkers for antidepressant response: protocol from the Canadian biomarker integration network in depression (CAN-BIND) and clinical characteristics of the first patient cohort.
abstract: BACKGROUND
  Major Depressive Disorder (MDD) is among the most prevalent and disabling medical conditions worldwide. Identification of clinical and biological markers ("biomarkers") of treatment response could personalize clinical decisions and lead to better outcomes. This paper describes the aims, design, and methods of a discovery study of biomarkers in antidepressant treatment response, conducted by the Canadian Biomarker Integration Network in Depression (CAN-BIND). The CAN-BIND research program investigates and identifies biomarkers that help to predict outcomes in patients with MDD treated with antidepressant medication. The primary objective of this initial study (known as CAN-BIND-1) is to identify individual and integrated neuroimaging, electrophysiological, molecular, and clinical predictors of response to sequential antidepressant monotherapy and adjunctive therapy in MDD.
  
  
  METHODS
  CAN-BIND-1 is a multisite initiative involving 6 academic health centres working collaboratively with other universities and research centres. In the 16-week protocol, patients with MDD are treated with a first-line antidepressant (escitalopram 10-20 mg/d) that, if clinically warranted after eight weeks, is augmented with an evidence-based, add-on medication (aripiprazole 2-10 mg/d). Comprehensive datasets are obtained using clinical rating scales; behavioural, dimensional, and functioning/quality of life measures; neurocognitive testing; genomic, genetic, and proteomic profiling from blood samples; combined structural and functional magnetic resonance imaging; and electroencephalography. De-identified data from all sites are aggregated within a secure neuroinformatics platform for data integration, management, storage, and analyses. Statistical analyses will include multivariate and machine-learning techniques to identify predictors, moderators, and mediators of treatment response.
  
  
  CONCLUSIONS
  From June 2013 to February 2015, a cohort of 134 participants (85 outpatients with MDD and 49 healthy participants) has been evaluated at baseline. The clinical characteristics of this cohort are similar to other studies of MDD. Recruitment at all sites is ongoing to a target sample of 290 participants. CAN-BIND will identify biomarkers of treatment response in MDD through extensive clinical, molecular, and imaging assessments, in order to improve treatment practice and clinical outcomes. It will also create an innovative, robust platform and database for future research.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier NCT01655706 . Registered July 27, 2012.
authors.affiliation: University of British Columbia and Vancouver Coastal Health Authority, 2255 Wesbrook Mall, Vancouver, BC, V6T 2A1, Canada.
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authors.affiliation: Department of Psychiatry, University of Toronto, 250 College Street, 8th floor, Toronto, ON, M5T 1R8, Canada.|Centre for Addiction and Mental Health, 1001 Queen St. W, Toronto, ON, M6J 1A8, Canada.
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authors.affiliation: University Health Network, 399 Bathurst Street, Toronto, ON, M5T 2S8, Canada.
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authors.affiliation: Department of Psychiatry, University of Toronto, 250 College Street, 8th floor, Toronto, ON, M5T 1R8, Canada.|Centre for Addiction and Mental Health, 1001 Queen St. W, Toronto, ON, M6J 1A8, Canada.
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authors.affiliation: Department of Psychiatry, University of Toronto, 250 College Street, 8th floor, Toronto, ON, M5T 1R8, Canada.|Centre for Addiction and Mental Health, 1001 Queen St. W, Toronto, ON, M6J 1A8, Canada.
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authors.affiliation: University Health Network, 399 Bathurst Street, Toronto, ON, M5T 2S8, Canada. sidney.kennedy@uhn.ca.|Department of Psychiatry, University of Toronto, 250 College Street, 8th floor, Toronto, ON, M5T 1R8, Canada. sidney.kennedy@uhn.ca.|St. Michael's Hospital, 193 Yonge St, Toronto, ON, M5B 1M4, Canada. sidney.kennedy@uhn.ca.
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mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002170:Canada; D015283:Citalopram / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000097:blood* / Q000188:drug therapy*; D004569:Electroencephalography; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D040901:Proteomics; D011788:Quality of Life; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D015415:Biomarkers; D015283:Citalopram