Identify depressive phenotypes by applying RDOC domains to the PHQ-9.

Major depression consists of multiple phenotypic traits. Our objective was to characterize depressive phenotypes in the patient health questionnaire (PHQ)-9 using the Research Domain Criteria (RDoC) research framework. Cross-sectional data were examined from the 2013-2014 (N = 5397) and 2015-2016 (N = 5164) National Health and Nutrition Examination Survey, a large, nationally representative U.S. sample. Using both factor analysis and qualitative analysis in mapping scale items along RDoC domains, a four factor model was found to be theoretically appropriate and had an excellent model fit for the PHQ-9. The factor structure consisted of phenotypes describing Negative Valence Systems and Externalizing (anhedonia and depression), Negative Valence Systems and Internalizing (depression, guilt and self-harm), Arousal and Regulatory Systems (sleep, fatigue and appetite) and Cognitive and Sensorimotor Systems (concentration and psychomotor). High correlation between these phenotypes did indicate screening and monitoring for depression study population using a single depression score is likely useful in most circumstances. In multiple indicator multiple cause analysis, differences in the means of the phenotypic traits were found by age, race/ethnicity, sex, and number of comorbidities. Future research should explore whether phenotype expression derived from readily available self-rated depression scales can help to inform more personalized care.

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Declaration of Competing Interest Author DG reports a book royalty agreement with Taylor Francis Publishing. Author MS has received grant support from Otsuka, Alkermes, Janssen, the National Institutes of Health, the Centers for Disease Control and Prevention and the International Society for Bipolar Disorders. She has served as a consultant to Bracket, Otsuka, Janssen, Alkermes, Neurocrine and Health Analytics and receives royalties from Springer Press, Johns Hopkins University Press, Oxford Press, and UpToDate. All other authors declare no conflicts of interest with the research or writing of this paper.