Towards a framework to develop neuroimaging biomarkers of relapse in schizophrenia

Schizophrenia is a chronic disorder that often requires long-term relapse-prevention treatment. This treatment is effective for most individuals, yet approximately 20-30 % of them may still relapse despite confirmed adherence. Alternatively, for about 15 % it may be safe to discontinue medications over the long term, but since there are no means to identify who those individuals will be, the recommendation is that all individuals receive long-term relapse-prevention treatment with antipsychotic maintenance. Thus, the current approach to prevent relapse in schizophrenia may be suboptimal for over one third of individuals, either by being insufficient to protect against relapse, or by unnecessarily exposing them to medication side effects. There is great need to identify biomarkers of relapse in schizophrenia to stratify treatment according to the risk and develop therapeutics targeting its pathophysiology. In order to develop a line of research that meets those needs, it is necessary to create a framework by identifying the challenges to this type of study as well as potential areas for biomarker identification and development. In this manuscript we review the literature to create such a framework.