Developing Psychiatric Biomarkers: a Review Focusing on the Error-Related Negativity as a Biomarker for Anxiety

Abstract

Efforts to identify psychiatric biomarkers that confer clinical utility have not yet been as successful as other areas of medicine. The current review evaluates one promising psychiatric biomarker (the error-related negativity (ERN)—a neural index of error processing) in an attempt to outline a roadmap for the development of future biological markers of risk for psychopathology. Integrating suggestions from the Biomarkers Definition Working Group into a framework of psychopathology, with an emphasis on a developmental perspective, we demonstrate that the ERN relates to diagnoses and dimensional anxiety symptoms concurrently—and can predict new onset disorders prospectively. The ERN appears related to a clinically relevant transdiagnostic phenotype (i.e., the tendency to engage in checking behaviors)—and also differentiates anxiety from highly comorbid conditions such as depression. We emphasize the importance of evaluating the psychometric properties of psychiatric biomarkers, in adults and children, pointing out that the ERN displays excellent internal and test-retest reliability across development. Furthermore, we discuss the diagnostic utility of the ERN as well as animal models of error processing that may pave the way for the development of pharmacological interventions. Finally, we raise the possibility that a psychiatric biomarker can serve as a target of treatment, thereby encouraging the development of novel intervention strategies. In the case of the ERN, we discuss the use of attentional training, parenting interventions, and neurostimulation as potential avenues of intervention to alleviate or prevent the onset of anxiety disorders.