Discovering biomarkers for antidepressant response: protocol from the Canadian biomarker integration network in depression (CAN-BIND) and clinical characteristics of the first patient cohort

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. Discussion 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.

Neural signals of “Intensity” but not “Wanting” or “Liking” of rewards may be trait markers for depression

We have shown previously that particpants “at risk” of depression have decreased neural processing of reward suggesting this might be a neural biomarker for depression. However, how the neural signal related to subjective experiences of reward (wanting, liking, intensity) might differ as trait markers for depression, is as yet unknown. Using SPM8 parametric modulation analysis the neural signal related to the subjective report of wanting, liking and intensity was compared between 25 young people with a biological parent with depression (FH) and 25 age/gender matched controls. In a second study the neural signal related to the subjective report of wanting, liking and intensity was compared between 13 unmedicated recovered depressed (RD) patients and 14 healthy age/gender matched controls. The analysis revealed differences in the neural signal for wanting, liking and intensity ratings in the ventral striatum, dmPFC and caudate respectively in the RD group compared to controls . Despite no differences in the FH groups neural signal for wanting and liking there was a difference in the neural signal for intensity ratings in the dACC and anterior insula compared to controls. These results suggest that the neural substrates tracking the intensity but not the wanting or liking for rewards and punishers might be a trait marker for depression.