Multilevel models from biology to psychology: mission impossible?

Systematic efforts are underway to address major flaws in the current diagnostic taxonomy of mental disorders, fostering hope that a new nosology might be based on brain biology. The National Institute of Mental Health Research Domains Criteria (RDoC) initiative aims to redefine mental illness leveraging information that spans molecular to behavioral levels of analysis. Major effort is still needed to forge multilevel conceptual and measurement models capable of representing knowledge within and across these levels. The development of such models may help refine and share complex hypotheses, and reduce the risk of replacing the current taxonomy with dimensions and/or categories that manifest little incremental biological validity. To create useful models we need to define concepts, relations among concepts, and links to supporting evidence. Some methods already enable representation of concepts and measures at the levels of behavioral and basic biological processes, but a major gap at the level of neural circuitry must be bridged to link basic biological and behavioral levels. We provide a schematic framework, using as an example the representation of selected "working memory" concepts and evidence across multiple levels of analysis as these have been described in the RDoC Workshops. This example illustrates multiple challenges and some possible solutions that may help clarify the aims of individual research projects and enable integration of diverse efforts on RDoC and related initiatives.