Alterations in brain development may contribute to chronic mental disorders. Novel treatments targeted toward the early-childhood manifestations of such chronic disorders may provide unique therapeutic opportunities. However, attempts to develop and deliver novel treatments face many challenges. Work on pediatric anxiety disorders illustrates both the inherent challenges as well as the unusual opportunities for therapeutic advances. The present review summarizes three aspects of translational research on pediatric anxiety disorders as the work informs efforts to develop novel interventions. First, the review summarizes data on developmental conceptualizations of anxiety from both basic neuroscience and clinical perspectives. This summary is integrated with a discussion of the two best-established treatments, cognitive behavioral therapy and selective serotonin reuptake inhibitors. Second, the review summarizes work on attention bias to threat, considering implications for both novel treatments and translational research on neural circuitry functional development. This illustrates the manner in which clinical findings inform basic systems neuroscience research. Finally, the review summarizes work in basic science on fear learning, as studied in fear conditioning, consolidation, and extinction paradigms. This summary ends by describing potential novel treatments, illustrating the manner in which basic neuroscience informs therapeutics.

The present study compared blood oxygen level dependent (BOLD) response in behaviorally inhibited and behaviorally non-inhibited adolescents to positive and negative feedback following their choice in a reward task. Previous data in these same subjects showed enhanced activation in striatal areas in behaviorally inhibited subjects to cues predicting gain or a loss. However, no analyses had examined responses following actual gains or losses. Relative to non-inhibited subjects, behaviorally inhibited subjects in the current study showed enhanced caudate response to negative but not positive feedback, indicating that striatal sensitivity to feedback may be specific to aversive information. In addition, compared to non-inhibited subjects, behaviorally inhibited subjects exhibited reduced differentiation between positive and negative feedback in ventromedial prefrontal cortex (vmPFC). This suggests a perturbed ability to encode reward value.

Previous research has implicated a large network of brain regions in the processing of risk during decision making. However, it has not yet been determined if activity in these regions is predictive of choices on future risky decisions. Here, we examined functional MRI data from a large sample of healthy subjects performing a naturalistic risk-taking task and used a classification analysis approach to predict whether individuals would choose risky or safe options on upcoming trials. We were able to predict choice category successfully in 71.8% of cases. Searchlight analysis revealed a network of brain regions where activity patterns were reliably predictive of subsequent risk-taking behavior, including a number of regions known to play a role in control processes. Searchlights with significant predictive accuracy were primarily located in regions more active when preparing to avoid a risk than when preparing to engage in one, suggesting that risk taking may be due, in part, to a failure of the control systems necessary to initiate a safe choice. Additional analyses revealed that subject choice can be successfully predicted with minimal decrements in accuracy using highly condensed data, suggesting that information relevant for risky choice behavior is encoded in coarse global patterns of activation as well as within highly local activation within searchlights.fMRI | machine learning | decision-making

Anxious individuals show an attention bias towards threatening information. However, under conditions of sustained environmental threat this otherwise-present attention bias disappears. It remains unclear whether this suppression of attention bias can be caused by a transient activation of the fear system. In the present experiment, high socially-anxious and low socially-anxious individuals (HSA group, n = 12; LSA group, n = 12) performed a modified dot-probe task in which they were shown either a neutral or socially threatening prime word prior to each trial. EEG was collected and ERP components to the prime and faces displays were computed. The behavioral results indicated that HSA individuals show an attention bias to threat after a neutral prime, but no attention bias after a threatening prime, demonstrating that suppression of attention bias can occur after a transient activation of the fear system. Low Socially Anxious individuals showed an opposite pattern: no evidence of a bias to threat with neutral primes but induction of an attention bias to threat following threat primes. ERP results suggested differential processing of the primes and faces displays by HSA and LSA individuals. However, no group by prime interaction was found for any of ERP components.

Objective Behaviorally inhibited children face increased risk for anxiety disorders, although factors that predict which children develop a disorder remain poorly specified. The current study examines whether the startle reflex response may be used to differentiate between behaviorally inhibited adolescents with and without a history of anxiety. Method Participants were assessed for behavioral inhibition during toddlerhood and early childhood. They returned to the laboratory as adolescents and completed a fear-potentiated startle paradigm and a clinical diagnostic interview (Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version). Magnitude of the startle reflex was examined at baseline and during cues associated with safety and threat. Results Only adolescents who showed high levels of behavioral inhibition and had a lifetime occurrence of anxiety disorders showed increased startle reactivity in the presence of safety cues. Neither behavioral inhibition nor diagnosis was related to startle reactivity during threat cues. Conclusions These results suggest that neurobiological measures, such as the startle reflex, may be a potential risk marker for the development of anxiety disorders among behaviorally inhibited adolescents. These methods may enhance our ability to identify vulnerable individuals before the development of anxious psychopathology.