Abstract
Although the cost of poor treatment outcomes of depression is staggering, we do not yet have clinically useful methods for selecting the most effective antidepressant for each depressed person. Emotional brain activation is altered in major depressive disorder (MDD) and implicated in treatment response. Identifying which aspects of emotional brain activation are predictive of general and specific responses to antidepressants may help clinicians and patients when making treatment decisions. We examined whether amygdala activation probed by emotion stimuli is a general or differential predictor of response to three commonly prescribed antidepressants, using functional magnetic resonance imaging (fMRI). A test–retest design was used to assess patients with MDD in an academic setting as part of the International Study to Predict Optimized Treatment in Depression. A total of 80 MDD outpatients were scanned prior to treatment and 8 weeks after randomization to the selective serotonin reuptake inhibitors escitalopram and sertraline and the serotonin–norepinephrine reuptake inhibitor, venlafaxine-extended release (XR). A total of 34 matched controls were scanned at the same timepoints. We quantified the blood oxygen level-dependent signal of the amygdala during subliminal and supraliminal viewing of facial expressions of emotion. Response to treatment was defined by ⩾50% symptom improvement on the 17-item Hamilton Depression Rating Scale. Pre-treatment amygdala hypo-reactivity to subliminal happy and threat was a general predictor of treatment response, regardless of medication type (Cohen’s d effect size 0.63 to 0.77; classification accuracy, 75%). Responders showed hypo-reactivity compared to controls at baseline, and an increase toward ‘normalization’ post-treatment. Pre-treatment amygdala reactivity to subliminal sadness was a differential moderator of non-response to venlafaxine-XR (Cohen’s d effect size 1.5; classification accuracy, 81%). Non-responders to venlafaxine-XR showed pre-treatment hyper-reactivity, which progressed to hypo-reactivity rather than normalization post-treatment, and hypo-reactivity post-treatment was abnormal compared to controls. Impaired amygdala activation has not previously been highlighted in the general vs differential prediction of antidepressant outcomes. Amygdala hypo-reactivity to emotions signaling reward and threat predicts the general capacity to respond to antidepressants. Amygdala hyper-reactivity to sad emotion is involved in a specific non-response to a serotonin–norepinephrine reuptake inhibitor. The findings suggest amygdala probes may help inform the personal selection of antidepressant treatments.
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Acknowledgements
LMW takes responsibility for the integrity of the data and the accuracy of the data analysis and was the Academic PI for iSPOT-D from 2008-2013. Dr Claire V.A. Day was the Global Trial Coordinator for iSPOT-D. Brain Resource was involved in the design of the study, managed the central coordination of the study, and provided the executive structure for a publication committee to manage the preparation of manuscripts. Brain Resource was not involved in the acquisition, analysis, or interpretation of the data. We gratefully acknowledge the contributions of the co-investigators and at the Sydney site where imaging data were acquired, and the Westmead Hospital MRI personnel at the Sydney site (Lavier Gomes, FRACR; Sheryl Foster). We gratefully acknowledge the editorial support of Jon Kilner (Pittsburgh, PA, USA). Clinical trials registration details are as follows: Trial registration: International Study to Predict Optimized Treatment in Depression (iSPOT-D); registry name: ClinicalTrials.gov; URL: http://www.clinicaltrials.gov/ct2/show/NCT00693849?term=iSPOT-D&rank=1; Registration number: NCT00693849. iSPOT-D is sponsored by the Brain Resource Company Operations.
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Williams, L., Korgaonkar, M., Song, Y. et al. Amygdala Reactivity to Emotional Faces in the Prediction of General and Medication-Specific Responses to Antidepressant Treatment in the Randomized iSPOT-D Trial. Neuropsychopharmacol 40, 2398–2408 (2015). https://doi.org/10.1038/npp.2015.89
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DOI: https://doi.org/10.1038/npp.2015.89
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