Increased Error-Related Brain Activity Distinguishes Generalized Anxiety Disorder With and Without Comorbid Major Depressive Disorder

Generalized anxiety disorder (GAD) and major depressive disorder (MDD) are so frequently comorbid that some have suggested that the 2 should be collapsed into a single overarching distress disorder. Yet there is also increasing evidence that the 2 categories are not redundant. Neurobehavioral markers that differentiate GAD and MDD would be helpful in ongoing efforts to refine classification schemes based on neurobiological measures. The error-related negativity (ERN) may be one such marker. The ERN is an event-related potential component presenting as a negative deflection approximately 50 ms following an erroneous response and reflects activity of the anterior cingulate cortex. There is evidence for an enhanced ERN in individuals with GAD, but the literature in MDD is mixed. The present study measured the ERN in 26 GAD, 23 comorbid GAD and MDD, and 36 control participants, all of whom were female and medication-free. Consistent with previous research, the GAD group was characterized by a larger ERN and an increased difference between error and correct trials than controls. No such enhancement was evident in the comorbid group, suggesting comorbid depression may moderate the relationship between the ERN and anxiety. The present study further suggests that the ERN is a potentially useful neurobiological marker for future studies that consider the pathophysiology of multiple disorders in order to construct or refine neurobiologically based diagnostic phenotypes.