The Map Is Not the Territory: Redefining the Diagnosis and Treatment of Neuropsychiatric Conditions in the 21st Century

How we conceptualize disease informs how we treat it, as exemplified by approaches to treating diseases of the mind. More than a century ago, Edward Colwes wrote about the importance of steady progress towards a truth, informed by understanding clinical symptoms and the course of disease. The aspiration of using mechanistic insights of disease to guide development of novel therapeutics for neuropsychiatric conditions has been elusive. The neuropharmacological revolution in treating serious mental illnesses occurred in the absence - not because of - scientific advances into the understanding of the brain. Serendipity-based drug discovery helped to transform patient care and left a legacy of important medicines; however, these successes contributed to the codification of categorical diagnoses which were reinforced by the descriptors of drug classes. The field of psychiatry came to view the “map as the territory.” That is, the representation of mental illnesses became ‘ground truths’ to be further refined into ever more precise definitions, without the benefit of biological underpinnings to define this reality. Categorical definitions limited the generation of mechanistic insights and, absent a model for scientific innovation, large pharma exited or significantly scaled back investments in neuroscience therapeutics development. Yet, today, not only are more neuroscience companies forming, but a high proportion of these companies cite ‘precision neuroscience’ as a core part of their strategy. What does this mean for the field and where will we go from here? This presentation reviews the rationale and need for a new conceptual framework for neuropsychiatric research and drug development. By leveraging recent advances in brain imaging, data science and the tools of precision medicine, the field of neuropsychiatry is positioned to evolve a classification system from categorical CNS conditions to biologically informed diseases which could transform diagnostics and therapeutics development for the next century.