Neuroimaging Biomarkers in Schizophrenia

Nina V. Kraguljac, William M. McDonald, Alik S. Widge, Carolyn I. Rodriguez, Mauricio Tohen, Charles B. Nemeroff

Research output: Contribution to journalReview articlepeer-review

17 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)509-521
Number of pages13
JournalThe American journal of psychiatry
Issue number6
StatePublished - Jun 1 2021


  • Biomarker
  • Neuroimaging
  • Schizophrenia Spectrum and Other Psychotic Disorders
  • Work Group on Biomarkers and Novel Treatments of the APA Council of Research

ASJC Scopus subject areas

  • Psychiatry and Mental health


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