Candidate biomarkers in psychiatric disorders: state of the field

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.

Biomarkers for clinical use in psychiatry: where are we and will we ever get there?

“…Given these challenges, will we ever see biomarkers that are relevant for clinical use in psychiatry? Abi‐Dargham et al 2 offer some suggestions for advancing biomarker discovery, such as focussing on promising biomarker candidates identified in their review, designing studies with an explicit goal of discovering biomarkers for a particular indication, embracing alternate forms of classification for testing potential biomarkers in subgroups of patients based on neurobiological features, adequately powered epi/genetic studies of mega‐samples well characterized in clinical course and treatment response, and a priori stratification approaches to test preventive and therapeutic approaches. These are all useful avenues to pursue for biomarker research.…”

“…ADNI began in 2004 with substantial public‐private partnership funding that allowed academic centers internationally to standardize data collection and pool data, which led to discovery of biomarkers for AD. Similar initiatives in psychiatry, such as the Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care for Depression (EMBARC) project, the Canadian Biomarker Integration Network in Depression (CAN‐BIND), the Personalized Prognostic Tools for Early Psychosis Management (PRONIA) Consortium, and the planned longitudinal cohort study by the recently launched BD 2 Integrated Network 7 , are clearly steps in the right direction.…”

“…Given the urgent and pressing need for biomarkers to transform psychiatric practice, the state of the field review of candidate biomarkers in psychiatry by Abi‐Dargham et al 2 is most timely. They correctly point out that the “litmus test for biomarkers in psychiatric disorders is their ability to change clinical practice”.…”

Balancing the beautiful and the good in pursuit of biomarkers for depression

“…The overview by Abi‐Dargham et al 1 offers a perspective on psychiatric biomarker development primarily based on the classical forward translational model. This approach, currently prioritized by the US National Institute of Mental Health, postulates a linear path from first identifying a biological pathological process through to development of an intervention that both engages the pathophysiologic target and leads to clinical improvement.…”

The time is now to start evaluating biomarkers in the clinic

“…Yet, there may be opportunities to evaluate biomarkers in the clinic, and potentially change clinical practice and care. Abi‐Dargham et al 1 provide a comprehensive account of the current state of candidate biomarkers in psychiatric disorders. Their effort is wide‐reaching and impressive, describing promising candidates and gaps in autism spectrum disorder, schizophrenia, anxiety, post‐traumatic stress disorder, mood disorders, and substance use disorders.…”