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Abstract
BackgroundElectroconvulsive therapy (ECT) is the most effective treatment option for major depressive disorder, so understanding whether its clinical effect relates to structural brain changes is vital for current and future antidepressant research. ObjectiveTo determine whether clinical response to ECT is related to structural volumetric changes in the brain as measured by structural magnetic resonance imaging (MRI) and, if so, which regions are related to this clinical effect. We also determine whether a similar model can be used to identify regions associated with electrode placement (unilateral versus bilateral ECT). MethodsLongitudinal MRI and clinical data (Hamilton Depression Rating Scale) was collected from 10 sites as part of the Global ECT-MRI research collaboration (GEMRIC). From 192 subjects, relative changes in 80 (sub)cortical areas were used as potential features for classifying treatment response. We used recursive feature elimination to extract relevant features, which were subsequently used to train a linear classifier. As a validation, the same was done for electrode placement. We report accuracy as well as the structural coefficients of regions included in the discriminative spatial patterns obtained. ResultsA pattern of structural changes in cortical midline, striatal and lateral prefrontal areas discriminates responders from non-responders (75% accuracy, p < 0.001) while left-sided mediotemporal changes discriminate unilateral from bilateral electrode placement (81% accuracy, p < 0.001). ConclusionsThe identification of a multivariate discriminative pattern shows that structural change is relevant for clinical response to ECT, but this pattern does not include mediotemporal regions that have been the focus of electroconvulsive therapy research so far.
Highlights
Major depressive disorder is a leading cause of disability worldwide and one of the biggest challenges the field of mental health faces today [1]
In a recent Global ECT-MRI Research Collaboration (GEMRIC) mega-analysis this increase in hippocampal volume after Electroconvulsive therapy (ECT) was again related to both electrode placement and number of ECT sessions administered [16], but while translational and human studies have suggested a link between hippocampal volume and behavioral changes [17e21], no relation to treatment outcome was established
We dissociate regions related to treatment response from those related to site of electrical stimulation by showing that the type of ECT used can be identified by a discriminative map that incorporates unilateral medial temporal regions that are known to be affected by ECT [46]
Summary
Major depressive disorder is a leading cause of disability worldwide and one of the biggest challenges the field of mental health faces today [1]. Understanding the mechanisms through which ECT achieves its remarkably strong clinical effect could provide critical biological markers to advance both established and emerging antidepressant therapies To this end, the Global ECT-MRI Research Collaboration (GEMRIC) was founded to pool data from multiple sites to increase power and enable analyses that cannot be performed on smaller samples [4]. Stimulated by translational studies on neurotrophic effects of ECT, medial temporal lobe structures including the hippocampus and amygdala have been subject to a number of investigations [7,11e13] Most these studies report significant volume increases after ECT, which has been confirmed through meta-analyses [14,15]. Electroconvulsive therapy (ECT) is the most effective treatment option for major depressive disorder, so understanding whether its clinical effect relates to structural brain changes is vital for current and future antidepressant research. We used recursive feature elimination to extract relevant features, which were subsequently used to train a linear
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