New Frontiers in Anxiety Research: The Translational Potential of the Bed Nucleus of the Stria Terminalis

Abstract

After decades of being overshadowed by the amygdala, new perspectives suggest that a tiny basal forebrain region known as the bed nucleus of the stria terminalis (BNST) may hold key insights into understanding and treating anxiety disorders. Converging research indicates that the amygdala and BNST play complementary but distinct functional roles during threat processing, with the BNST specializing in the detection of a potential threat to maintain hypervigilance and anxiety, while the amygdala responds to the perceived presence of an aversive stimulus (i.e., fear). Therefore, given that human anxiety is largely driven by future-oriented hypothetical threats that may never occur, studies involving the BNST stand at the forefront of essential future research with the potential to bring about profound insights for understanding and treating anxiety disorders. In this article, we present a narrative review on the BNST, summarizing its roles in anxiety and the stress response and highlighting the most recent advances in the clinical realm. Furthermore, we discuss oversights in the current state of anxiety research and identify avenues for future exploration.

Gαq protein signaling in the bed nucleus of the stria terminalis regulate the lipopolysaccharide-induced despair-like behavior in mice

“…Recently, it has been reviewed by Liu et al that the either MDD or ADs might increase the risk for the development of other disease [3] . The role of the bed nucleus of the stria terminalis (BNST) in anxiety disorders has been well investigated [4] , [5] , [6] . On the other hand, the role of BNST on the induction of MDD has not been well studied yet to date.…”

The Bed Nucleus of the Stria Terminalis as a Brain Correlate of Psychological Inflexibility in Fibromyalgia

“…The BNST-part of "the extended amygdala"-is a key nucleus in the integration of autonomic and behavioral responses to stress; however, until recently it has been relatively overlooked compared to research examining amygdala functioning [48]. BNST integrates information from several upstream sources and, via dense connections with the paraventricular nucleus of the hypothalamus (PVN) (the principal node of the hypothalamic-pituitary-adrenal axis in initiating stress-mediated cortisol responses) regulates neuroendocrine and behavioral responses to stress [49]. The ventral part of the BNST has the largest density of noradrenergic fibers in the brain [50] and most of the projections to PVN originate from this area [51].…”

Corticotropin Releasing Hormone Signaling in the Bed Nuclei of the Stria Terminalis as a Link to Maladaptive Behaviors

“…The role of the BST in sustained fear processing is not limited to rodents. Heightened levels of BST activity in humans have been demonstrated in patients with general anxiety disorder, PTSD, panic disorder, and specific phobias (for review, see Knight and Depue, 2019 ; Awasthi et al, 2020 ). While more research into the human BST is needed, there has already been success in treating certain disorders using deep brain stimulation (DBS) to the BST.…”

“…The bed nuclei of the stria terminalis (BST; also known as BNST) is a small, sexually dimorphic, heterogeneous region that in the past 20 years, has been highlighted for its role in stress and anxiety responses (for review, see Lebow and Chen, 2016 ). While traditionally BST research has focused on anxiety processing, in recent years the BST has been increasingly implicated in dysregulated signaling patterns consistent with many mental health disorders in both animal models and humans ( Gungor and Paré, 2016 ; Lebow and Chen, 2016 ; Luyten et al, 2016 ; Blomstedt et al, 2017 ; Knight and Depue, 2019 ). Given the economic and social burden of those disorders on our society today, further study of the BST is a key step in the development of more effective treatments.…”