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Event-related potentials (ERPs) are direct measures of brain activity that can be leveraged for clinically meaningful research. They can relate robustly both to continuous measures of individual difference and to categorical diagnoses in ways that clarify similarities and distinctions between apparently related disorders and traits. ERPs can be linked to genetic risk, can act as moderators of developmental trajectories and responses to stress, and can be leveraged to identify those at greater risk for psychopathology, especially when used in combination with other neural and self-report measures. ERPs can inform models of the development of, and risk for, psychopathology. Finally, ERPs can be used as targets for existing and novel interventions and prevention efforts. We provide concrete examples for each of these possibilities by focusing on programmatic research on the error-related negativity and anxiety, and thus show that ERPs are poised to make greater contributions toward the identification, prediction, treatment, and prevention of mental disorders.

Background Multiple studies have found a reduced reward positivity (RewP) among individuals with major depressive disorder (MDD). Event-related potential studies have also reported blunted neural responses to pleasant pictures in MDD as reflected by the late positive potential (LPP). These deficits have been interpreted broadly in terms of anhedonia and decreased emotional engagement characteristic of depression. Methods In the current study, a community-based sample of 83 participants with current MDD and 45 healthy individuals performed both a guessing task and a picture viewing paradigm with neutral and pleasant pictures to assess the RewP and the LPP, respectively. Results We found that both RewP and LPP to pleasant pictures were reduced in the MDD group; moreover, RewP and LPP were both independent predictors of MDD status. Within the MDD group, a smaller RewP predicted impaired mood reactivity in younger but not older participants. Smaller LPP amplitudes were associated with increased anhedonia severity in the MDD group. Conclusions These data replicate and merge separate previous lines of research, and suggest that a blunted RewP and LPP reflect independent neural deficits in MDD – which could be used in conjunction to improve the classification of depression.

BackgroundIncreased neural error-signals have been observed in obsessive-compulsive disorder (OCD), anxiety disorders, and inconsistently in depression. Reduced neural error-signals have been observed in substance use disorders (SUD). Thus, alterations in error-monitoring are proposed as a transdiagnostic endophenotype. To strengthen this notion, data from unaffected individuals with a family history for the respective disorders are needed.MethodsThe error-related negativity (ERN) as a neural indicator of error-monitoring was measured during a flanker task from 117 OCD patients, 50 unaffected first-degree relatives of OCD patients, and 130 healthy comparison participants. Family history information indicated, that 76 healthy controls were free of a family history for psychopathology, whereas the remaining had first-degree relatives with depression (n = 28), anxiety (n = 27), and/or SUD (n = 27).ResultsIncreased ERN amplitudes were found in OCD patients and unaffected first-degree relatives of OCD patients. In addition, unaffected first-degree relatives of individuals with anxiety disorders were also characterized by increased ERN amplitudes, whereas relatives of individuals with SUD showed reduced amplitudes.ConclusionsAlterations in neural error-signals in unaffected first-degree relatives with a family history of OCD, anxiety, or SUD support the utility of the ERN as a transdiagnostic endophenotype. Reduced neural error-signals may indicate vulnerability for under-controlled behavior and risk for substance use, whereas a harm- or error-avoidant response style and vulnerability for OCD and anxiety appears to be associated with increased ERN. This adds to findings suggesting a common neurobiological substrate across psychiatric disorders involving the anterior cingulate cortex and deficits in cognitive control.