Recent research has suggested that elevated

Recent research has suggested that elevated irritability and negative emotionality early in life are significant predictors of later depression, including depression occurring during school-age, adolescence, and adulthood (Dougherty et al., 2013; Bould et al., 2014; Karevold et al., 2009). This work has also suggested that those at greatest risk for depression are likely to demonstrate persistently high or increasing levels of negative affect over the course of early childhood (Wiggins et al., 2014), a period when negative affect is typically decreasing. The current findings suggest that variations in amygdala activity may be one of the mechanisms contributing to such alterations in negative affect, and thus has the potential to significantly inform the early identification of risk for later psychiatric illness. The search for early neural markers of later psychopathology has been prioritized based on the potential to intervene more effectively during periods of relatively great OG-L002 plasticity (Insel, 2014). While the current study does not directly inform whether amygdala activity can serve as a predictor of future diagnostic status, it does raise the intriguing possibility that functional activity within the amygdala may serve as a significant biomarker that can identify children with increased- or increasing-risk for later negative affect and potential for related psychiatric disorders. However, while the current study represents an important step forward, many pragmatic as well as scientific questions will need to be answered before the potential of amygdala activity, an expensive and somewhat difficult measure to obtain, will be useful to inform earlier identification of emerging psychiatric illness. Nevertheless, while the use of neuroimaging data to directly inform psychiatric risk within a clinical setting is still an open question (Bullmore, 2012), the current findings highlight the potential of fMRI data to further clarify whether and to what extent the developmental trajectories of negative affect and amygdala function are related. Such information may prove to be important for developing clinical procedures that identify individual children exhibiting increasing risk for (or the early emergence of) psychiatric difficulties. More specifically, as our understanding of the specific relationship between negative affect and amygdala development grows, leveraging this knowledge to identify other neuropsychological and/or physiological measures that can be used effectively and potentially more affordably within clinic settings to identify emerging psychopathology and/or response to treatment may be increasingly possible (Casey et al., 2014). In line with an experimental therapeutics approach to treatment development (Insel and Gogtay, 2014), identifying specific brain-behavior relationships in health as well as disorder is considered foundational to such an effort. The current study provides one of the first pieces of evidence supporting a specific relationship between amygdala function and current as well as future negative affect in preschool age children. Future work examining this relationship and factors influencing it is now needed.
Conclusion
Conflict of interests
Acknowledgements The Klingenstein Third Generation Foundation (M.S.G.) and the Communities Healing Adolescent Depression and Suicide (CHADS) Coalition for Mental Health (J.L.L., D.M.B.) provided funding for this study. This manuscript was supported by grant K23 MH098176 (M.S.G.) from the National Institute of Mental Health (NIMH). We wish to acknowledge our child participants and their parents whose participation and cooperation made this research possible.
Adolescent development involves a complex set of interrelated biological, behavioral, psychological, and social processes. Since 1904, when G. Stanley Hall first published his two-volume magnum opus —in what is widely recognized as the beginning of the scientific focus on adolescence—the field has struggled with the sheer complexity inherent in understanding this important period of human development.