Symptom clustering of major depression in a national telehealth sample

Background: Major depressive disorder (MDD) is a heterogeneous disorder whose possible symptom combinations have not been well delineated. The aim of this study was to explore the heterogeneity of symptoms experienced by those with MDD to characterize phenotypic presentations.Methods: Cross-sectional data (N = 10,158) from a large telemental health platform were used to identify subtypes of MDD. Symptom data, gathered from both clinically-validated surveys and intake questions, were analyzed via polychoric correlations, principal component analysis, and cluster analysis.Results: Principal components analysis (PCA) of baseline symptom data revealed 5 components, including anxious distress, core emotional, agitation/irritability, insomnia, and anergic/apathy components. PCA-based cluster analysis resulted in four MDD phenotypes, the largest of which was characterized by a prominent elevation on the anergic/apathy component, but also core emotional. The four clusters differed on demographic and clinical characteristics. Limitations: The primary limitation of this study is that the phenotypes uncovered are limited by the questions asked. These phenotypes will need to be cross validated with other samples, potentially expanded to include biological/genetic variables, and followed longitudinally.Conclusions: The heterogeneity in MDD, as illustrated by the phenotypes in this sample, may explain the heterogeneity of treatment response in large-scale treatment trials. These phenotypes can be used to study varying rates of recovery following treatment and to develop clinical decision support tools and artificial intelligence algorithms. Strengths of this study include its size, breadth of included symptoms, and novel use of a telehealth platform.