Methods and Challenges for Assessing Heterogeneity.

The widely acknowledged homogeneity assumption limits progress in refining clinical diagnosis, understanding mechanisms, and developing new treatments for mental health disorders. This homogeneity assumption drives both a comorbidity and a heterogeneity problem, where two different approaches tackle the problems. One, a unifying approach, tackles the comorbidity problem by assuming that a single general psychopathology factor underlies multiple disorders. Another, a multifactorial approach, tackles the heterogeneity problem by assuming that disorders comprise multiple subtypes driven by multiple discrete factors. We show how each of these approaches can make useful contributions to mental health-related research and clinical practice. For example, the unifying approach can develop a rapid assessment tool that may be clinically valuable for triaging cases. The multifactorial approach can reveal subtypes that are differentially responsive to treatments and highlight distinct mechanisms leading to similar phenotypes. Because both approaches tackle different problems, both have different limitations. We describe the statistical frameworks that incorporate and adjudicate between both approaches (e.g., the bifactor model, normative modeling, and the functional random forest). Such frameworks can identify whether sets of disorders are more affected by heterogeneity or comorbidity. Therefore, future studies that incorporate such frameworks can provide further insight into the nature of psychopathology.