Abstract
Schizophrenia is a complex neuropsychiatric syndrome with a heterogeneous genetic, neurobiological, and phenotypic profile. Currently, no objective biological measures-that is, biomarkers-are available to inform diagnostic or treatment decisions. Neuroimaging is well positioned for biomarker development in schizophrenia, as it may capture phenotypic variations in molecular and cellular disease targets, or in brain circuits. These mechanistically based biomarkers may represent a direct measure of the pathophysiological underpinnings of the disease process and thus could serve as true intermediate or surrogate endpoints. Effective biomarkers could validate new treatment targets or pathways, predict response, aid in selection of patients for therapy, determine treatment regimens, and provide a rationale for personalized treatments. In this review, the authors discuss a range of mechanistically plausible neuroimaging biomarker candidates, including dopamine hyperactivity, N-methyl-d-aspartate receptor hypofunction, hippocampal hyperactivity, immune dysregulation, dysconnectivity, and cortical gray matter volume loss. They then focus on the putative neuroimaging biomarkers for disease risk, diagnosis, target engagement, and treatment response in schizophrenia. Finally, they highlight areas of unmet need and discuss strategies to advance biomarker development.