Considering that anxiety disorders frequently begin before adulthood and often result in chronic impairment, it is important to characterize the developmental pathways leading to the onset of clinical anxiety. Identifying neural biomarkers that can predict the onset of anxiety in childhood may increase our understanding of the etiopathogenesis of anxiety, as well as inform intervention and prevention strategies. An event-related potential (ERP), the error-related negativity (ERN) has been proposed as a biomarker of risk for anxiety and has previously been associated with concurrent anxiety in both adults and children. However, no previous study has examined whether the ERN can predict the onset of anxiety disorders. In the current study, ERPs were recorded while 236 healthy children, approximately 6 years of age, performed a Go/No-Go task to measure the ERN. Three years later, children and parents came back to the lab and completed diagnostic interviews regarding anxiety disorder status. Results indicated that enhanced error-related brain activity at age 6 predicted the onset of new anxiety disorders by age 9, even when controlling for baseline anxiety symptoms and maternal history of anxiety. Considering the potential utility of identifying early biomarkers of risk, this is a novel and important extension of previous work.

Background A number of studies have reported that depression is associated with lower relative left frontal activity in the alpha band (i.e., frontal asymmetry, or FA), as measured by electroencephalogram. FA has also been hypothesized to be a vulnerability marker for depression. If this is the case, FA should be evident in offspring of depressed mothers, a group at elevated risk for depression. However, the results of previous offspring studies have been inconsistent and none of these studies has considered whether the relationship between FA and risk changes over development in children. Method We assessed FA twice, at ages 3 and 6, in 253 never-depressed children from a community sample. Maternal history of depressive disorders was determined by a diagnostic interview completed by the mothers at the first assessment. Results There was a significant interaction between maternal depression and offspring age at assessment, indicating that FA exhibits different developmental trajectories depending on level of familial risk for depression. Offspring of depressed mothers exhibited a decreasing relative left FA over the course of early childhood, while offspring of non-depressed mothers exhibited relatively similar, symmetrical, levels of frontal alpha activity at both assessment points. Conclusions These results suggest that changes in FA from early to middle childhood distinguish those at risk for depression and that cross-sectional assessment of FA may have limited value in understanding risk. These results highlight the importance of considering development in understanding the role of FA in depression.

There is increasing interest among developmental psychopathologists in broad transdiagnostic factors that give rise to a wide array of clinical presentations (multifinality), but little is known about how these processes lead to particular psychopathological manifestations over the course of development. We examined whether individual differences in the error related negativity (ΔERN), a neural indicator of error monitoring, predicts whether early persistent irritability—a prototypical transdiagnostic construct— is associated with later internalizing versus externalizing outcomes. When children were 3 years old, mothers were interviewed about children’s persistent irritability and completed questionnaires about their children’s psychopathology. Three years later, EEG was recorded while children performed a go/no-go task to measure the ΔERN. When children were approximately 9 years old, mothers again completed questionnaires about their children’s psychopathology. Results indicated that among children who were persistently irritable at age 3, an enhanced or more negative ΔERN at age 6 predicted the development of internalizing symptoms at age 9, whereas a blunted or smaller ΔERN at age 6 predicted the development of externalizing symptoms. Our results suggest that variation in error monitoring predicts, and may even shape, the expression of persistent irritability and differentiates developmental trajectories from preschool persistent irritability to internalizing versus externalizing outcomes in middle-late childhood.

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.

Depression is characterized by low positive emotionality (PE) and high negative emotionality (NE), as well as asymmetries in resting electroencephalography (EEG) alpha power. Moreover, frontal asymmetry has itself been linked to PE, NE, and related constructs. However, little is known about associations of temperamental PE and NE with resting EEG asymmetries in young children and whether this association changes as a function of development. In a longitudinal study of 254 three-year old children, we assessed PE and NE at age 3 using a standard laboratory observation procedure. Frontal EEG asymmetries were assessed at age 3 and three years later at age 6. We observed a significant three-way interaction of preschool PE and NE and age at assessment for asymmetry at F3-F4 electrode sites, such that children with both low PE and high NE developed a pattern of increasingly lower relative left-frontal cortical activity over time. In addition, F7-F8 asymmetry was predicted by a PE by time interaction, such that the frontal asymmetry in children with high PE virtually disappeared by age 6. Overall, these findings suggest that early temperament is associated with developmental changes in frontal asymmetry, and that the combination of low PE and high NE predicts the development of the pattern of frontal symmetry that is associated with depression.