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date: 23 August 2017

Developmental Neurobiology of Anxiety and Related Disorders

This is an advance summary of a forthcoming article in the Oxford Research Encyclopedia of Neuroscience. Please check back later for the full article.

Recent interest in understanding the neurobiological correlates of anxiety disorders has sparked investigation of the biological state of the developing brain and the ways in which atypical structure, function, and connectivity of key frontolimbic structures are implicated in the development of anxiety disorders across childhood and adolescence. Despite the fact that abnormalities in fear learning play a central role in the etiology of anxiety disorders, behavioral studies of fear conditioning and extinction have shown mixed results when comparing anxious and non-anxious youth. Pediatric patients with anxiety disorders show alterations in the structure and function of frontolimbic circuitry. Structurally, amygdala volumes are altered in children and adolescents with anxiety. Functionally, anxious youth show increased amygdala activation in response to neutral and fear-inducing stimuli, with the magnitude of signal change in amygdala reactivity corresponding to the severity of symptomatology. Abnormalities in prefrontal cortex (PFC) and anterior cingulate cortex (ACC), and their connections with the amygdala, have also been implicated in pediatric anxiety. Anxious youth show heightened activity of the ventrolateral PFC, as well as atypical connectivity between the ventrolateral PFC and amygdala. An inverse association between prefrontal activation and the severity of anxiety symptomatology suggests that the increased activation of regulatory structures may compensate for heightened amygdala responses to threatening stimuli in anxious youth. Taken together, alterations in frontolimbic connectivity are likely to play a central role in anxiety disorders. Though findings are preliminary, pre-treatment amygdala reactivity and physiological responses during extinction have been associated with treatment outcomes among youth with anxiety disorders. These promising findings highlight future opportunities to clinically translate the emerging understanding of the neurobiological bases of pediatric anxiety disorders to optimize interventions for youth.