Neural mechanisms of acute stress and trait anxiety in adolescents

Adolescence is a critical period of heightened stress sensitivity and elevated vulnerability for developing mental illness, suggesting a possible association between stress exposure and the etiology of psychiatric disorders. In adults, aberrant neurobiological responses to acute stress relate to anxiety symptoms, yet less is known about the neural stress response in adolescents and how it relates to biological and psychological variables. Here we characterize the neurobiology of stress response in adolescents using multiple modalities, including neuroimaging, subjective stress ratings, heart rate, and cortisol data. We evaluated stress response in adolescents using the Montreal Imaging Stress Task (MIST), an acute psychosocial stressor commonly administered in adult functional magnetic resonance imaging (fMRI) studies but not previously utilized with this population. FMRI data were acquired from 101 adolescents (44 female; 9-16 years) exhibiting varied trait anxiety severity. The MIST elicited decreased high-frequency heart rate variability and increased heart rate, subjective stress and cortisol. Whole-brain analyses comparing fMRI activity during experimental versus control MIST conditions revealed stress-related activation in regions including the anterior insula, dorsal anterior cingulate cortex, and dorsolateral prefrontal cortex and deactivations in the hippocampus, ventral striatum, and putamen. Region of Interest analyses found that during acute stress (a) hippocampal deactivation corresponded to heightened cortisol release, (b) trait anxiety was associated with increased hippocampal and ventral striatum activation and decreased putamen activity, and (c) males exhibited greater putamen deactivation than females. These results provide novel evidence that the MIST is an effective stressor for adolescents. Associations between the neural acute stress response, other biological factors, and trait anxiety highlight the importance of these neurobiological mechanisms in understanding anxiety disorders.