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The bed nucleus: a future hot spot in obsessive compulsive disorder research?

In a recent Molecular Psychiatry article, Lebow and Chen1 review the importance and significance of the bed nucleus of the stria terminalis (BNST) in the field of neuropsychiatric disorders. The authors ascribe the role of ‘valence surveillance’ to the BNST and conclude that the BNST keeps most significant information on mood and basic needs readily available, whereas it processes contextual information, and assesses threat and reward.1 We agree with the authors that the role of the BNST in neuropsychiatry has been underestimated for a long period of time. Although the authors emphasize the role of the BNST in anxiety and post-traumatic stress disorder, they do not specify its potential role in obsessive compulsive disorder (OCD).

In the review by Lebow and Chen, as well as in the original articles, the authors refer to the commonly described role of the BNST in the symptom domains anxiety, sustained fear, threat and reward. All of the four have crucial roles in the clinical picture of OCD, too. In the current Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5), OCD was removed from its old classification of anxiety disorders in the DSM-III and DSM-IV, and included in an own chapter with related disorders. However, anxiety has a crucial role in the development and maintenance of OCD symptoms, as obsessions are usually accompanied by high levels of anxiety and exposure to threatening stimuli commonly causes panic-like responses in OCD.2 Compulsions are then carried out in order to relieve the anxiety and aversive emotions built up by the obsessions. Further, in the currently dominating cognitive model of OCD, dysfunctional beliefs are thought to cause obsessions and compulsions. Among others, one very common belief is the tendency to overestimate threats.3 And last, OCD is related to dysfunctional reward anticipation and reward processing, for example apparent in decision-making.4

Switching the focus from the phenotype to the pathophysiology of OCD, a common hypothesis is that dysfunctions in the cortico-striato-thalamo-cortical network cause intrusive thoughts and repetitive behaviors in OCD, with special emphasis on the involvement of the orbitofrontal cortex, the anterior cingulated cortex (ACC) and the striatum, including the nucleus accumbens (NAcc).5 Therefore the NAcc has been in the focus of OCD research for a long time and has been used as target for deep brain stimulation (DBS) for otherwise treatment-resistant OCD.6 Interestingly, an Italian DBS research group of the University of Milan recently compared the effects of NAcc stimulation and BNST stimulation in a group of eight treatment-resistant and severely affected OCD patients, and reported that DBS of the BNST is more effective compared with NAcc stimulation.7 Similar observations have been made by Luyten et al.8 from Leuven University. They report in Molecular Psychiatry that DBS for severe OCD is in retrospect more effective if the electrical field around the electrode captures the BNST instead of the anterior limb of the capsula interna, which is just as the NAcc, a prominent target for DBS in OCD.8 Although the involvement of the BNST in fear, anxiety and reward has been discussed for a longer period of time, the BNST has not been integrated in a model of OCD pathophysiology, however the observations outlined above definitely call for further investigations.

The BNST is located posterior to the NAcc and has three major pathways that connect the small structure with the lateral amygdala (posterior bundle), hypothalamus (ventral bundle), and via the caudate and the NAcc with the prefrontal and orbitofrontal cortices (anterior pathway).1 Moreover, optogenetically induced activation of the anterior pathway could be linked to reduced anxiety in rodents.9 Due to its anatomical connections and functional focus, the anterior pathway could constitute the link between the BNST and the dysfunctional cortico-striato-thalamo-cortical network described in OCD pathophysiology.

Another interesting fact in this context is the use of selective serotonin reuptake inhibitors (SSRI) in OCD. Although Lebow and Chen point out that the BNST has a high level of serotonin receptors and that SSRIs activate the BNST chronically and thereby modulate BNST-dependent behavior (sustained fear), it is important to note that in OCD, SSRI therapy is the first choice of pharmacological treatment with response rates of 60–70%. Further acute injection of SSRI into BNST causes anxiety-like behavior in rodents, whereas chronic administration has anxiolytic effects.10 Similar observations have been reported in SSRI treatment of OCD, where in the beginning of the treatment, patients often report an increased anxiety level that decreases with time.

Taken together, the arguments outlined above, make an involvement of the BNST in the pathophysiology of OCD very likely. However, as OCD is a very heterogeneous disorder it is possible that the BNST is dominantly involved in only some OCD subtypes. For example, OCD subtypes of washing or checking are more likely to be related to fear than subtypes of symmetry and order. Therefore the BNST may not be related to all, but probably only to fear-related forms of OCD. More extensive research is definitely necessary in order to further increase the understanding of OCD pathology and the role of the BNST.

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Correspondence to S Kohl.

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Kohl, S., Baldermann, J. & Kuhn, J. The bed nucleus: a future hot spot in obsessive compulsive disorder research?. Mol Psychiatry 21, 990–991 (2016). https://doi.org/10.1038/mp.2016.54

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