A neural biomarker, the error‐related negativity, predicts the first onset of generalized anxiety disorder in a large sample of adolescent females

Meyer, Alexandria; Nelson, Brady D.; Perlman, Greg; Klein, Daniel N.; Kotov, Roman

doi:10.1111/jcpp.12922

Cited by 67 publications

(58 citation statements)

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“…Future work should establish norms for the ERN that can be used to identify who is most at risk for anxiety during different stages of development. Additionally, future studies should examine what factors may influence or shape the ERN during specific developmental periods – for example, some work suggests harsh parenting styles may increase the ERN in offspring (Brooker & Buss, 2014; Meyer et al, 2014). Moreover, given that the ERN indexes risk for anxiety, future work should examine whether the ERN may be a viable target for treatment and prevention efforts.…”

Section: Discussionmentioning

confidence: 99%

The development of the error-related negativity in large sample of adolescent females: Associations with anxiety symptoms

Meyer

Carlton

Crisler

et al. 2018

Biological Psychology

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Anxiety is the most common form of psychopathology and tends to begin early in the course of development. Given this, there is great interest in identifying developmental changes in neural systems that may delineate healthy versus anxious trajectories. A substantial amount of work has focused on the error-related negativity as a neural marker of anxiety. The ERN is a negative deflection in the event-related potential that occurs when individuals make mistakes and is increased in anxious individuals. A separate body of work has focused on normative developmental changes in the ERN - demonstrating an age-related increase in the ERN that occurs across childhood and adolescence. In the current study, we examine the ERN in relation to specific phenotypic expressions of anxiety during a core risk period in a sample of females (N = 220) ranging from 8 to 14 years old. Results from the current study suggest that error-related brain activity is related to both parent and child report of social anxiety symptoms, even when controlling for all other symptom scales. Additionally, mediation models suggest that the normative developmental increase observed in the ERN is partially mediated by increases in social anxiety symptoms. The current results are novel insofar as they identify a specific phenotypic expression of anxiety that underlies developmental increases in this neural biomarker.

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Section: Discussionmentioning

confidence: 99%

The development of the error-related negativity in large sample of adolescent females: Associations with anxiety symptoms

Meyer

Carlton

Crisler

et al. 2018

Biological Psychology

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“…This suggests that individuals at familial risk for anxiety disorders also show increased ERN amplitudes. Additional support for increased ERN as a candidate endophenotype for anxiety comes from studies suggesting that ERN magnitude could be used to predict the onset of GAD (Meyer et al, ), social anxiety (Lahat et al, ), and anxiety symptoms collapsed across different DSM categories (McDermott et al, ; Meyer et al, ; Meyer, Hajcak et al, ). Collectively, these results support the idea that increased ERN amplitudes represent a shared endophenotype for OCD and anxiety (Olvet & Hajcak, ; Riesel et al, , in press).…”

Section: Section 2: Enhanced Neural Error Signals As Endophenotype Fomentioning

confidence: 99%

“…Importantly, the clinical relevance of error‐related brain activity is supported by studies demonstrating its predictive validity for the onset of symptoms across various mental disorders (Anokhin & Golosheykin, ; Lahat et al, ; Meyer, Hajcak et al, ; Meyer et al, ). In longitudinal studies, ERN predicted the onset of anxiety symptoms in children and adolescents (Lahat et al, ; Lamm et al, ; Meyer, Hajcak et al, ; Meyer et al, ) and the development of symptoms in response to critical life events such as a natural disaster (Meyer et al, ). Further, in preschool‐aged individuals, observed hyperactive performance monitoring at the behavioral level predicted the onset of OCD and reduced ACC volume over 12 years (Gilbert, Barclay, Tillman, Barch, & Luby, ).…”

Section: Section 3: Clinical Implications and Conclusionmentioning

confidence: 99%

“…Nevertheless, even complex endophenotypes are presumably simpler than the clinical phenotype and may help to illuminate disorder mechanisms and familial environmental risk factors (Kendler & Neale, 2010). Further, the predictive validity of elevated neural error signals has not been demonstrated for OCD specifically but for anxiety symptoms and disorders more broadly (Lahat et al, 2014;Lamm et al, 2014;Meyer et al, 2017;Meyer, Hajcak, Torpey-Newman, Kujawa, & Klein, 2015;Meyer, Nelson, Perlman, Klein, & Kotov, 2018). Consistent with this, enhanced ERN amplitudes are not specific for OCD (e.g., Gillan, Fineberg, & Robbins, 2017;Riesel et al, 2017;Weinberg, Dieterich, & Riesel, 2015).…”

Section: Endophenotype Conceptmentioning

confidence: 99%

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The erring brain: Error‐related negativity as an endophenotype for OCD—A review and meta‐analysis

2019

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Obsessive‐compulsive disorder (OCD) is a complex and heterogeneous disorder that is associated with high personal and societal costs. Feelings of doubt, worry, and repetitive behavior, key symptoms of OCD, have been linked to hyperactive error signals in the brain. The error‐related negativity (ERN) represents a validated marker of error processing in the ERP. Increased ERN amplitudes in OCD have been reported very robustly over the last 20 years. This article integrates results from 38 studies analyzing the ERN in OCD, using a quantitative meta‐analysis. Meta‐regressions were used to examine potential moderators such as task type, symptom severity, age, and sample size. The meta‐analysis reveals a robust increase of ERN in OCD patients compared to healthy participants in response‐conflict tasks (SMD −0.55) that is not modulated by symptom severity and age. No increase in ERN in OCD was observed in tasks that do not induce response conflict (SMD −0.10). In addition to the meta‐analysis, the current article reviews evidence supporting that increased ERN amplitudes in OCD fulfill central criteria for an endophenotype. Further, the specificity of increased ERN amplitudes for OCD and its suitability as a potential transdiagnostic endophenotype is discussed. Finally, the clinical utility and clinical applications are examined. Overall, the evidence that increased ERN amplitudes represent a promising endophenotype indicating vulnerability for OCD is compelling. Furthermore, alterations in ERN are not limited to OCD and may constitute a transdiagnostic endophenotype. Altered neural error signals might serve as a diagnostic or predictive marker and represent a promising target for interventions.

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“…The ERN is a sharp, negative deflection in the event‐related potential (ERP) waveform that occurs shortly after individuals make mistakes (Falkenstein, Hohnsbein, Hoormann, & Blanke, ; Gehring, Goss, Coles, Meyer, & Donchin, ) and is generated in the anterior cingulate cortex (ACC)—a region of the brain that integrates information about pain, threat, and punishment to modify behavioral output (Shackman et al, ). An increased ERN has been found in individuals with anxiety‐related traits (e.g., worry, punishment sensitivity) and symptoms in over 45 studies to date (see meta‐analysis: Moser, Moran, Schroder, Donnellan, & Yeung, ), and we have recently found that an increased ERN predicts the onset of new anxiety disorders in children—even when controlling for baseline anxiety symptoms and other risk factors (Meyer, Hajcak, Torpey‐Newman, Kujawa, & Klein, ; Meyer, Nelson, Perlman, Klein, & Kotov, Under Review). Considering that the ERN consistently relates to anxiety and similar traits, and has good psychometric properties across development (Meyer, Bress, & Proudfit, ), it is an important neural measure for studying the development of anxious processes.…”

Section: Introductionmentioning

confidence: 99%

Early temperamental fearfulness and the developmental trajectory of error‐related brain activity

Meyer

Hajcak

Torpey-Newman³

et al. 2018

Developmental Psychobiology

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The error-related negativity (ERN) is a negative deflection in the event-related potential waveform that occurs when an individual makes a mistake, and an increased ERN has been proposed as a biomarker for anxiety. However, previous work suggests that fearful children are characterized by a smaller ERN. We have proposed that this may reflect the changing phenomenology of anxiety across development. In the current study, we investigate this possibility using a longitudinal within- subject design. In 271 children, we completed observational measures of fear when the children were 3 years old, and then measured the ERN when the children were 6 and 9 years-old. Fearful children were characterized by a decreased ERN when they were 6-years-old; by age 9, the same children who were fearful at age 3 had increased ERNs—a pattern that closely resembles that of anxious adolescents and adults.

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A neural biomarker, the error‐related negativity, predicts the first onset of generalized anxiety disorder in a large sample of adolescent females

Abstract: This study provides evidence for the utility of the ERN as a biomarker of risk for GAD during a key developmental period.

Cited by 67 publications

References 59 publications

The development of the error-related negativity in large sample of adolescent females: Associations with anxiety symptoms

The development of the error-related negativity in large sample of adolescent females: Associations with anxiety symptoms

The erring brain: Error‐related negativity as an endophenotype for OCD—A review and meta‐analysis

Early temperamental fearfulness and the developmental trajectory of error‐related brain activity

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