Candidate biomarkers in psychiatric disorders: state of the field

Author:

Abi‐Dargham Anissa1,Moeller Scott J.1,Ali Farzana1,DeLorenzo Christine1,Domschke Katharina23,Horga Guillermo45,Jutla Amandeep45,Kotov Roman1,Paulus Martin P.6,Rubio Jose M.789,Sanacora Gerard10,Veenstra‐VanderWeele Jeremy45,Krystal John H.10

Affiliation:

1. Renaissance School of Medicine at Stony Brook University Stony Brook NY USA

2. Department of Psychiatry and Psychotherapy, Faculty of Medicine University of Freiburg Freiburg Germany

3. Centre for Basics in Neuromodulation, Faculty of Medicine University of Freiburg Freiburg Germany

4. Department of Psychiatry Columbia University New York NY USA

5. New York State Psychiatric Institute New York NY USA

6. Laureate Institute for Brain Research Tulsa OK USA

7. Zucker School of Medicine at Hofstra‐Northwell Hempstead NY USA

8. Feinstein Institute for Medical Research ‐ Northwell Manhasset NY USA

9. Zucker Hillside Hospital ‐ Northwell Health Glen Oaks NY USA

10. Department of Psychiatry Yale School of Medicine New Haven CT USA

Abstract

The field of psychiatry is hampered by a lack of robust, reliable and valid biomarkers that can aid in objectively diagnosing patients and providing individualized treatment recommendations. Here we review and critically evaluate the evidence for the most promising biomarkers in the psychiatric neuroscience literature for autism spectrum disorder, schizophrenia, anxiety disorders and post‐traumatic stress disorder, major depression and bipolar disorder, and substance use disorders. Candidate biomarkers reviewed include various neuroimaging, genetic, molecular and peripheral assays, for the purposes of determining susceptibility or presence of illness, and predicting treatment response or safety. This review highlights a critical gap in the biomarker validation process. An enormous societal investment over the past 50 years has identified numerous candidate biomarkers. However, to date, the overwhelming majority of these measures have not been proven sufficiently reliable, valid and useful to be adopted clinically. It is time to consider whether strategic investments might break this impasse, focusing on a limited number of promising candidates to advance through a process of definitive testing for a specific indication. Some promising candidates for definitive testing include the N170 signal, an event‐related brain potential measured using electroencephalography, for subgroup identification within autism spectrum disorder; striatal resting‐state functional magnetic resonance imaging (fMRI) measures, such as the striatal connectivity index (SCI) and the functional striatal abnormalities (FSA) index, for prediction of treatment response in schizophrenia; error‐related negativity (ERN), an electrophysiological index, for prediction of first onset of generalized anxiety disorder, and resting‐state and structural brain connectomic measures for prediction of treatment response in social anxiety disorder. Alternate forms of classification may be useful for conceptualizing and testing potential biomarkers. Collaborative efforts allowing the inclusion of biosystems beyond genetics and neuroimaging are needed, and online remote acquisition of selected measures in a naturalistic setting using mobile health tools may significantly advance the field. Setting specific benchmarks for well‐defined target application, along with development of appropriate funding and partnership mechanisms, would also be crucial. Finally, it should never be forgotten that, for a biomarker to be actionable, it will need to be clinically predictive at the individual level and viable in clinical settings.

Publisher

Wiley

Subject

Psychiatry and Mental health,Pshychiatric Mental Health

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