Stress and Anxiety Impact Maturation of Adolescent Neural Circuitry Involved in Emotion and Reward Processing

Background and Purpose: Adolescence is an important period for neurodevelopment related to stress regulation, emotional processing, and reward, and a time of increased vulnerability for psychiatric symptoms and diagnoses. Understanding how these neural circuits develop and are influenced by environmental factors such as stress is crucial in developing novel prevention and intervention strategies to provide adequate treatment for disadvantaged adolescents at increased risk for psychiatric problems. Our study aimed to examine the impact of stress and anxiety on adolescent neurodevelopment and hypothesized that age and anxiety would be significantly associated with atypical development of neural circuits involved in stress regulation, emotion, and reward.

Methods: We recruited 36 typically developing adolescents from the community to participate in clinical interviews and a functional neuroimaging protocol. All participants were scanned using a 3T GE MRI scanner and completed the Montreal Imaging Stress Task (MIST). The MIST task employs challenging mental math with negative social feedback to induce performance and social evaluative stress in participants. The State-Trait Anxiety Inventory–Child version (STAI-C) was administered to all participants to measure anxiety. FMRIB Software Library (FSL) was used to analyze fMRI data and perform covariate analyses. All covariate analyses were corrected using a familywise error (FWE) at z>2.3 (p<.01 cluster thresholded).

Results: Our data revealed that stress blocks significantly activated a network of cortical regions involved in emotion regulation including the insula, frontal operculum, and paracingulate regions. Results showed deactivation of the nucleus accumbens (NA) under stress.  Covariate analyses revealed significant age-dependent maturational changes in stress activation in fronto-limbic circuitry. Analyses also indicate significant correlations between trait anxiety scores and stress-induced activation in ventromedial prefrontal regions and ventral anterior cingulate. Finally, deactivation of the NA was moderately correlated with increased activation of the insula under stress conditions.

Conclusion and Implications:  Our study reveals the novel finding that the neural circuits of stress response and regulation show significant age-dependent maturation during adolescence and significant covariation with trait anxiety. This suggests that age-dependent and anxiety-sensitive neural nodes may play key roles in the emergence of psychiatric disorders during adolescence. Further, our results indicate the NA, a brain area involved in reward processing and anticipation of pleasure, becomes temporarily deactivated during acute stress, which may potentially provide a link between the brain’s experience of stress and negative symptoms such as anhedonia. Future research is needed to replicate these findings in a larger sample and to examine the duration of the decreased reward response. Ultimately, further investigation of the link between these regions, their clinical correlates, and how this may develop in individuals with chronic stress or trauma history could provide important information for the development of preventative screening and secondary prevention initiatives to identify adolescents at increased neurodevelopmental risk for specific psychiatric symptoms and late onset psychiatric disorders.