Extending the neurocircuitry of behavioural inhibition: a role for the bed nucleus of the stria terminalis in risk for anxiety disorders

Abstract

Behavioural inhibition is a biologically based risk factor for anxiety disorders. Children with behavioural inhibition are shy, cautious and avoidant of new situations. Much research on behavioural inhibition has focused on the amygdala as an underlying neural substrate and has identified differences in amygdala function and volume; however, amygdala findings have yet to lead to meaningful interventions for prevention or treatment of anxiety disorders. The bed nucleus of the stria terminalis (BNST) is a prime candidate to be a neural substrate of behavioural inhibition, given current evidence of BNST function and development in human research and animal models. Children with behavioural inhibition have an increased startle response to safety cues and an increased cortisol response to social evaluative situations, both of which are mediated by the BNST. In rodents, activation of the BNST underlies contextual fear responses and responses to uncertain and sustained threat. Non-human primates with anxious temperament (the macaque equivalent of behavioural inhibition) have increased BNST activity to ambiguous social situations, and activity of the BNST in anxious temperament is significantly heritable. Importantly, the BNST is sexually dimorphic and continues to develop into adulthood, paralleling the development of anxiety disorders in humans. Together, these findings suggest that further investigation of the BNST in behavioural inhibition is necessary and may lead to new avenues for the prevention and treatment of anxiety disorders.