Biological subtyping of psychiatric syndromes as a pathway for advances in drug discovery and personalized medicine

Every common psychiatric syndrome is genetically, neurobiologically and clinically heterogeneous. This heterogeneity may reflect the dimensional variability of a single illness with common etiology, varying in severity. Alternatively, as in many areas of medicine, it may reflect different discrete types of illness leading to similar alterations of mood or behavior. Resolving uncertainty as to the nature of heterogeneity in psychiatric illness is crucial for advancing the development of novel therapeutics and improving the precision with which pharmacological interventions are chosen for specific patients. Recent work resolving illness heterogeneity has shown promise in identifying biologically distinct patient subgroups within common psychiatric syndromes. This progress offers hope for the longer-term aim of enhancing our understanding of biological alterations associated with psychiatric syndromes, so that drug development and pharmacological interventions can shift towards altering specific targeted biological processes, instead of working to change complex behavioral features that may represent the final common pathway of different biological illness mechanisms. Using approaches such as neuroimaging and peripheral immune markers, studies have identified subgroups with different patterns of biological features that provide translational targets for novel drug development programmes, and may, in the longer term, together with psychological and social perspectives, more closely link diagnostics and therapeutics in psychiatry. So far, multiple discrete subgroups have been identified, and these have been associated with clinical features. Work is now needed to improve the validity and reliability of biologically derived subtypes, and better characterize their clinical, developmental and psychosocial features. This is required to establish their clinical utility for predicting illness course and response to different therapies, and to determine how biologically distinct features of patient subgroups can guide the development of novel therapies targeting those alterations. This Review summarizes the advances in personalized medicine and drug discovery in psychiatry and suggests a framework for the development of clinically relevant biological subtypes in the field.