The report is a product of the VA/HSR&D Evidence Synthesis Program.

Neuroimaging and Neurophysiologic Biomarkers for Mental Health: An Evidence Map

Takeaway: Existing evidence gaps and limitations indicate that it may be premature to apply neuroimaging and neurophysiologic tests to evaluate and treat mental health conditions and post-acute TBI in clinical settings.

Mental health conditions and traumatic brain injury (TBI) are common among Veterans and often negatively impact them, their families, and their communities. VA allocates considerable resources to treating these conditions and improving mental healthcare and outcomes is an ongoing VA priority. For example, part of the Commander John Scott Hannon Veterans Mental Health Care Improvement Act (Section 305: “Precision Medicine for Veterans Initiative; SHA305) tasks VA with developing and implementing a precision medicine initiative focused on brain and mental health biomarkers. This evidence review was requested by the VA SHA305 Working Group to better understand characteristics of existing evidence on relationships between brain structure and functioning—and mental health conditions and TBI.

VA’s Evidence Synthesis Program (ESP) Center in Minneapolis, MN sought to provide descriptive information about the number and types of studies that address a wide range of neuroimaging and neurophysiologic assessments for diverse mental health conditions and TBI. They also highlight weaknesses and gaps in the evidence, as determined by the volume and characteristics of studies. Investigators searched MEDLINE and Embase for peer-reviewed English language articles published from January 2010 to April 2022. They also searched HSR&D’s Evidence Synthesis Program (ESP) and the Agency for Healthcare Research and Quality (AHRQ) Evidence-based Practice Center (EPC) programs to identify relevant reviews. Overall, ESP investigators identified 313 eligible primary studies and 30 eligible systematic reviews.

Summary of Findings

The majority of the identified evidence addressed depression, while fewer studies and reviews examined other conditions of interest. Most primary studies used MRI-based neuroimaging techniques and a fifth employed EEG (electroencephalogram). Two-thirds of primary studies focused on diagnoses for conditions of interest, and nearly all of those were cross-sectional. Findings include:

• Many studies evaluated the use of structural or functional MRI in diagnosis and prognosis of depression, but there were important methodological concerns:
• Nearly all diagnostic studies were cross-sectional, small in size, and included participants with variable past histories of symptoms and treatments.
• Prognostic studies focused mostly on response to antidepressants and were generally small.
• A substantial number of studies used EEG for diagnosis and prognosis of depression, but these had similar methodological issues as MRI studies.
• Fewer studies examined bipolar disorder, PTSD, post-acute TBI, substance use disorder (SUD), obsessive-compulsive disorder (OCD), and anxiety disorders. They also were focused mostly on diagnosis, and were cross-sectional and small in size.
• Fourteen studies included US Veterans, addressing PTSD, TBI, and/or SUD:
• All 11 diagnostic studies were cross-sectional, 2 prognostic studies were cohorts, and 1 was a randomized controlled trial.

Implications for VA

ESP investigators found a large number of studies, mainly using MRI-based techniques to evaluate diagnosis and prognosis for depression, but there were substantial methodological limitations. Additionally, none of the depression studies were conducted with U.S. Veterans or military service members. Given that neuroimaging tests are costly and time-consuming to conduct (and analyze), it is not clear that using such tests adds value in the clinical setting or that they could replace current standards for diagnosis of depression involving structured interviews and clinician assessments. Furthermore, no study evaluated prediction of adverse or side effects of treatments, which is often an important factor in patient and clinician decisions to stop or switch antidepressants. Thus, it is unclear how these data could be incorporated into current clinical practice to improve diagnosis or treatment selection and/or monitoring.

ESP investigators found considerably less evidence addressing other mental health conditions and post-acute TBI, and fewer studies using other neuroimaging and neurophysiologic techniques. Although there were some studies on PTSD, TBI, and SUD that included U.S. Veterans or military service members, overall these shared the same methodological limitations previously noted. Therefore, it also appears premature to implement MRI (and other neuroimaging and neurophysiologic techniques) in the clinical diagnosis and treatment of these conditions.

Future Research

ESP investigators offer the following suggestions regarding future research:

• Invest in larger studies (thousands of participants) to identify reproducible and precise associations between neuroimaging and neurophysiologic findings and mental health phenotypes.
• Conduct longitudinal studies with data on exposures, symptoms, neuroimaging, and neurophysiologic data over the lifecourse.
• Include transdiagnostic approaches for describing mental health phenotypes.
• Develop longitudinal studies with initial data that precede combat and other service-related exposures, particularly for addressing Veterans’ health and outcomes.

Ullman K, Landsteiner A, Anthony M, et al. Neuroimaging and Neurophysiologic Biomarkers for Mental Health: An Evidence Map. Washington, DC: Evidence Synthesis Program, Health Services Research and Development Service, Office of Research and Development, Department of Veterans Affairs. VA ESP Project #09-009; 2022.

To view the full report, go to https://vaww.hsrd.research.va.gov/publications/esp/neuroimaging-mh.cfm (intranet only)

ESP is currently soliciting review topics from the broader VA community. Nominations will be accepted electronically using the online Topic Submission Form. If your topic is selected for a synthesis, you will be contacted by an ESP Center to refine the questions and determine a timeline for the report.

This Management e-Brief is provided to inform you about recent HSR&D findings that may be of interest. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs. If you have any questions or comments about this Brief, please email CIDER. The Center for Information Dissemination and Education Resources (CIDER) is a VA HSR&D Resource Center charged with disseminating important HSR&D findings and information to policy makers, managers, clinicians, and researchers working to improve the health and care of Veterans.

This report is a product of VA/HSR&D's Evidence Synthesis Program (ESP), which was established to provide timely and accurate synthesis of targeted healthcare topics of particular importance to VA managers and policymakers –; and to disseminate these reports throughout VA.

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