Neuroimaging Biomarkers of New-Onset Psychiatric Disorders Following Traumatic Brain Injury

Biol Psychiatry. 2022 Mar 1;91(5):459-469. doi: 10.1016/j.biopsych.2021.06.005. Epub 2021 Jun 12.


Traumatic brain injury (TBI) has traditionally been associated with cognitive and behavioral changes during both the acute and chronic phases of injury. Because of its noninvasive nature, neuroimaging has the potential to provide unique information on underlying macroscopic and microscopic biological mechanisms that may serve as causative agents for these neuropsychiatric sequelae. This broad scoping review identifies at least 4 common macroscopic pathways that exist between TBI and new-onset psychiatric disorders, as well as several examples of how neuroimaging is currently being utilized in clinical research. The review then critically examines the strengths and limitations of neuroimaging for elucidating TBI-related microscopic pathology, such as microstructural changes, neuroinflammation, proteinopathies, blood-brain barrier damage, and disruptions in cellular signaling. A summary is then provided for how neuroimaging is currently being used to investigate TBI-related pathology in new-onset neurocognitive disorders, depression, and posttraumatic stress disorder. Identified gaps in the literature include a lack of prospective studies to definitively associate imaging findings with the development of new-onset psychiatric disorders, as well as antemortem imaging studies subsequently confirmed with postmortem correlates in the same study cohort. Although the spatial resolution and specificity of imaging biomarkers has greatly improved over the last 2 decades, we conclude that neuroimaging biomarkers do not yet exist for the definitive in vivo diagnosis of cellular pathology. This represents a necessary next step for further elucidating causal relationships between TBI and new-onset psychiatric disorders.

Keywords: Depression; Mindboggle; Neurocognitive disorders; Neuroimaging; Posttraumatic stress disorder; Traumatic brain injury.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Biomarkers
  • Brain Injuries, Traumatic* / complications
  • Brain Injuries, Traumatic* / diagnostic imaging
  • Brain Injuries, Traumatic* / psychology
  • Humans
  • Neuroimaging / methods
  • Prospective Studies
  • Stress Disorders, Post-Traumatic* / complications


  • Biomarkers