Biomarkers for Antidepressant Selection: iSPOT-D Study

Abstract

The International Study to Predict Optimized Treatment in Depression (iSPOT-D) is a randomized clinical trial conducted at 22 sites across 5 countries, looking at biomarkers of improvement in depressive symptoms to treatment with SSRIs escitalopram and sertraline, and the SNRI venlafaxine-XR. It is the first to take an integrative neuroscience approach to biomarker discovery, looking across the disciplines of structural and functional MRI, EEG, cognitive performance, and genomics, all in the same patients. The initial biomarkers from within each of these disciplines have now been reported. Symptom improvement has been found to be predicted by markers relating to greater structural connectivity in the cingulate and less connectivity in hippocampal and amygdala axonal projections, along with less amygdala engagement in processing facial emotion. Non-remission has additionally been predicted by markers relating to less attention and cognitive control, including less engagement of the dorsolateral prefrontal cortex during inhibitory control and smaller medial frontal volume, greater frontal EEG theta activity, and poorer cognitive performance. Specific biomarkers of response to SSRIs have been identified that include the rs10245483 SNP major allele and better performance on the cognitive assessment, and in females, more left lateralized resting brain activity. Symptom improvement to the SNRI has been found to be predicted by rs10245483 SNP minor allele, less amygdala engagement to sad facial expressions and less frontal EEG theta. The next step in this study will be to integrate these findings across disciplines so as to explore how this integration can enhance prediction accuracy and improve our understanding of the key drivers underlying these relationships, and whether integration into a single biomarker or a more stepwise approach is a more feasible approach from a real-world clinical perspective. The replicability of these biomarkers will also be evaluated in a new sample of patients. Registry Name: ClinicalTrials.gov Registration Number: NCT00693849 URL: http://www.clinicaltrials.gov/ct2/show/NCT00693849?term=ispot-D&rank=1