Analysis of Features Selected by a Deep Learning Model for Differential Treatment Selection in Depression

Background: Deep learning has utility in predicting differential antidepressant treatment response among patients with major depressive disorder, yet there remains a paucity of research describing how to interpret deep learning models in a clinically or etiologically meaningful way. In this paper, we describe methods for analyzing deep learning models of clinical and demographic psychiatric data, using our recent work on a deep learning model of STAR*D and CO-MED remission prediction. Methods: Our deep learning analysis with STAR*D and CO-MED yielded four models that predicted response to the four treatments used across the two datasets. Here, we use classical statistics and simple data representations to improve interpretability of the features output by our deep learning model and provide finer grained understanding of their clinical and etiological significance. Specifically, we use representations derived from our model to yield features predicting both treatment non-response and differential treatment response to four standard antidepressants, and use linear regression and t-tests to address questions about the contribution of trauma, education, and somatic symptoms to our models. Results: Traditional statistics were able to probe the input features of our deep learning models, reproducing results from previous research, while providing novel insights into depression causes and treatments. We found that specific features were predictive of treatment response, and were able to break these down by treatment and non-response categories; that specific trauma indices were differentially predictive of baseline depression severity; that somatic symptoms were significantly different between males and females, and that education and low income proved important psycho-social stressors associated with depression. Conclusion: Traditional statistics can augment interpretation of deep learning models. Such interpretation can lend us new hypotheses about depression and contribute to building causal models of etiology and prognosis. We discuss dataset-specific effects and ideal clinical samples for machine learning analysis aimed at improving tools to assist in optimizing treatment.