Anxiety disorders are the most prevalent class of mental illness and are a major public health concern. There is growing evidence that sensitivity to unpredictable threat (SUT) is a core mechanism of anxiety disorders. In multiple studies using a no, predictable, or unpredictable threat (NPU-threat) task, anxiety disorders have been associated with an enhanced startle reflex in anticipation of unpredictable (but not predictable) threat. In addition, SUT has been associated with a family history (i.e., risk) of anxiety disorder, independent of concurrent anxiety. Adolescence is a critical period for the development of neural systems implicated in fear and anxiety.To date, no studies have examined SUT in relation to anxiety disorders or risk in children and adolescents. Pilot data are presented suggesting that adolescent anxiety disorders may also be characterized by a heightened startle reflex while anticipating unpredictable (but not predicable) threat. In adult studies, SUT appears to also reflect phenotypic variation in intolerance of uncertainty (IU), a personality trait indexig the degree to which individuals find uncertainty to be aversive, stressful, and threatening. Indeed, SUT has been associated with IU, but this relationship has not been established in children and adolescents. The proposed study is designed to examine the association between SUT and multiple anxiety phenotypes (disorders and symptoms, IU) in adolescent females, a demographic group at high risk for anxiety disorders. Specifically, this study will leverage resources from an ongoing R01 investigation and add the NPU-threat task and self-report measures of IU to a sample of 285 10-16 year-old adolescent females. The proposed study will also examine event-related brain potentials (ERPs) during the NPU-threat task. The startle probe itself elicits N1 and P3 responses, which measure attentional processing of the startle probe. The probe N1 and P3 are enhanced and attenuated, respectively, during unpleasant pictures, due to increased attention toward the motivationally- salient foreground stimuli. Novel pilot data are presented indicating probe N1 enhancement during the anticipation of unpredictable threat only, and probe P3 suppression during the anticipation of both predictable and unpredictable threat in adults. Startle-elicited ERPs may provide unique information about attentional correlates of SUT, and, unlike the startle reflex, may provide a measure that is specific to SUT (i.e., N1). This will be the first study to examine startle probe ERPs in relation o anxiety, IU, and risk. Overall, the proposed study will examine the association between SUT and anxiety phenotypes (disorders and symptoms, IU) (Aim 1) and maternal history of anxiety disorders (i.e., risk) in adolescent females (Aim 2). This study will also examine ERPs to assess attentional indices of SUT, and test their association with adolescent anxiety, IU, and risk (Aim 3). Finally, this study will conduct exploratory analyses examining normative changes in sensitivity to predictable and unpredictable threat over adolescence and in relation to pubertal development, which is measured in the adolescent females as part of the primary R01 investigation.

Public Health Relevance

Anxiety disorders are the most common form of mental illness and symptoms typically emerge during childhood and adolescence. However, the mechanisms that contribute to the development of anxiety disorders are largely unknown, in particular those that confer risk for anxiety disorders. The proposed study will examine sensitivity to unpredictable threat (SUT) as a potential mechanism of anxiety disorders in 285 10-16 year-old adolescent females, and test whether multiple measures of SUT (startle eye blink reflex and event-related brain potentials [ERPs]) are associated with adolescent anxiety phenotypes (anxiety disorders and symptoms, intolerance of uncertainty) and risk for anxiety (maternal history of anxiety disorders).

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Scientist Development Award - Research & Training (K01)
Project #
Application #
Study Section
Child Psychopathology and Developmental Disabilities Study Section (CPDD)
Program Officer
Sarampote, Christopher S
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
State University New York Stony Brook
Schools of Arts and Sciences
Stony Brook
United States
Zip Code