The bed nucleus of the stria terminalis (BNST), also referred to as the BST, is fast becoming a relevant region of interest with regard to human stress-related psychiatric disease. This is due to its established role in sustained fear states, and social attachment behaviors, which comprise aggressive behaviors, initiation of mating and offspring and parental bonding but additionally due to its diverse anatomy, connectivity and receptor subpopulations. Human stress-related psychiatric diseases such as anxiety, posttraumatic stress disorder (PTSD) and social dysfunctions all display long-term changes in mood, arousal, sleep, appetite and interest in social interactions.

The BNST processes information and readiness for response to a threat, by maintaining online information from a vast connectivity network. Mood state and arousal are processed via connections to the amygdala, dorsal raphe, ventral tegmental area (VTA) and medial prefrontal cortex (mPFC). The BNST’s projections to the hypothalamus allow monitoring of feeding, drinking and fluid maintenance via brainstem connections.16 Connections to the lateral septum17 and medial amygdala (MeA) allow coordination of reproductive behaviors as part of the social behavioral network. Since anatomically, the BNST is sexually dimorphic, it may explain the gender disparity in the prevalence and treatment of stress-related psychiatric diseases and as such should be investigated as a possible target for treatments. Indeed, drug targets already involve subpopulations of receptors abundant in the BNST such as serotonin. While research into the BNST’s role in sustained fear is well-established and critical in the treatment of human anxiety, the BNST has further promise in understanding other human-related psychiatric diseases.

This is the first review to incorporate several roles of this region in both rodent and human data to promote a united view of the BNST. This is essential in the study of psychiatric diseases such as anxiety, which are part of a larger umbrella of long-term anxiety disorders such as generalized anxiety disorder (GAD), PTSD, social anxiety and anti-social behaviors. This review outlines the complex anatomy of the BNST together with its diversity and interconnectivity. It then discusses the role of the BNST in stress-related psychiatric disease. It concludes with a discussion on the importance of gender disparities in these psychiatric disorders and the possible role of the BNST. These topics aim to help the reader gauge the profound promise of the BNST as a potential target for the treatment of stress-related psychiatric diseases.

Molecular Psychiatry (2016) 21, 450–463

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EXPERT REVIEW Overshadowed by the amygdala: the bed nucleus of the stria terminalis emerges as key to psychiatric disorders MA Lebow and A Chen