Abstract
It is essential to improve antidepressant treatment of major depressive disorder (MDD) and one way this could be achieved is by reducing the number of treatment steps by employing biomarkers that can predict treatment outcome. This study investigated differences between MDD patients and healthy controls in the P3 and N1 component from the event-related potential (ERP) generated in a standard two-tone oddball paradigm. Furthermore, the P3 and N1 are investigated as predictors for treatment outcome to three different antidepressants.In the international Study to Predict Optimized Treatment in Depression (iSPOT-D) - a multi-center, international, randomized, prospective practical trial - 1008 MDD participants were randomized to escitalopram, sertraline or venlafaxine-XR. The study also recruited 336 healthy controls. Treatment response and remission were established after eight weeks using the 17-item Hamilton Rating Scale for Depression. P3 and N1 latencies and amplitudes were analyzed using a peak-picking approach and further replicated by using exact low resolution tomography (eLORETA). A reduced P3 was found in MDD patients compared to controls by a peak-picking analysis. This was validated in a temporal global field power analysis. Source density analysis revealed that the difference in cortical activity originated from the posterior cingulate and parahippocampal gyrus. Male non-responders to venlafaxine-XR had significantly smaller N1 amplitudes than responders. This was demonstrated by both analytical methods. Male non-responders to venlafaxine-XR had less activity originating from the left insular cortex.The observed results are discussed from a neural network viewpoint.
| Original language | English |
|---|---|
| Pages (from-to) | 1981-1990 |
| Number of pages | 10 |
| Journal | European Neuropsychopharmacology |
| Volume | 25 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - 1 Nov 2015 |
Funding
This study was funded by the Brain Resource Company Operations Ltd. The clinical trials registration identifier is NCT00693849. Data-analyses and writing of this manuscript were unconstrained and no financial support was involved in the data-analyses and writing of this manuscript. RvD has no disclosures. MA reports research grants and options from Brain Resource Ltd. (Sydney, Australia), acted as a paid consultant for the United BioSource Corporation (UBC), Bracket, Mindmedia and Vivatech and is a co-inventor on 3 patent applications (A61B5/0402; US2007/0299323, A1; WO2010/139361 A1) related to EEG, neuromodulation and psychophysiology, but does not own these nor receives any proceeds related to these patents. KF reports research grants, options and shares from Brain Resource Ltd. PBF is supported by a NHMRC Practitioner Fellowship (606907). PBF has received equipment for research from MagVenture A/S, Medtronic Ltd, Cervel Neurotech and Brainsway Ltd and funding for research from Cervel Neurotech; CD has received support from Brain Resource, CNS response, St. Jude, Astra Zeneca, Takeda, Assurex and is a consultant for Pfizer and Genentech; EG is founder and receives income as Chief Executive Officer and Chairman for Brain Resource Ltd. He has stock options in Brain Resource Ltd. We acknowledge the iSPOT-D Investigators Group, the contributions of iSPOT-D principal investigators at each site and the central management team (global coordinator Claire Day) and Chris Spooner and Donna Palmer for support in the data-analyses. This study was funded by the Brain Resource Company Operations Ltd . The clinical trials registration identifier is NCT00693849 . Data-analyses and writing of this manuscript were unconstrained and no financial support was involved in the data-analyses and writing of this manuscript.
Keywords
- Antidepressants
- Event-Related Potential (ERP)
- Major Depressive Disorder (MDD)
- Treatment prediction
