Developmental Differences in a Hippocampal-Cingulate Pathway Involved in Learned Safety Following Interpersonal Trauma Exposure.

Objective: Nearly 65% of youth experience trauma, and up to one-third of youth with trauma exposure face profound mental health sequelae. There remains a need to elucidate factors that contribute to psychopathology following trauma exposure, and to optimize interventions for youth who do not benefit sufficiently from existing treatments. Here, we probe safety signal learning (SSL), which is a mechanism of fear reduction that leverages learned safety to inhibit fear in the presence of threat-associated stimuli and has been shown to attenuate fear via a hippocampal-cingulate--specifically, a dorsal anterior cingulate cortex (dACC)--pathway.

Hippocampal Involvement in Safety Signal Learning Varies With Anxiety Among Healthy Adults.

Background: Safety signal learning (SSL), based on conditioned inhibition of fear in the presence of learned safety, can effectively attenuate threat responses in animal models and humans. Difficulty regulating threat responses is a core feature of anxiety disorders, suggesting that SSL may provide a novel mechanism for fear reduction. Cross-species evidence suggests that SSL involves functional connectivity between the anterior hippocampus and the dorsal anterior cingulate cortex.

Responding to threat: Associations between neural reactivity to and behavioral avoidance of threat in pediatric anxiety.

Background: Despite broad recognition of the central role of avoidance in anxiety, a lack of specificity in its operationalization has hindered progress in understanding this clinically significant construct. The current study uses a multimodal approach to investigate how specific measures of avoidance relate to neural reactivity to threat in youth with anxiety disorders.

Methods: Children with anxiety disorders (ages 6-12 years; n = 65 for primary analyses) completed laboratory task- and clinician-based measures of avoidance, as well as a functional magnetic resonance imaging task probing neural reactivity to threat.

Multivariate links between the developmental timing of adversity exposure and white matter tract integrity in adulthood.

Early-life adversity is pervasive worldwide and represents a potent risk factor for increased mental health burden across the lifespan. However, there is substantial individual heterogeneity in associations between adversity exposure, neurobiological changes, and mental health problems. Accounting for key features of adversity such as the developmental timing of exposure may clarify associations between adversity, neurodevelopment, and mental health.

Extinction Learning Across Development: Neurodevelopmental Changes and Implications for Pediatric Anxiety Disorders.

Alterations in extinction learning relate to the development and maintenance of anxiety disorders across the lifespan. While exposure therapy, based on principles of extinction, can be highly effective for treating anxiety, many patients do not show sufficient improvement following treatment. In particular, evidence suggests that exposure therapy does not work sufficiently for up to 40% of children who receive this evidence-based treatment.