Deep brain stimulation in obsessive-compulsive disorder

Deep brain stimulation (DBS) is under investigation for severe obsessive-compulsive disorder (OCD) resistant to other therapies. As a crucial part of the anxiety circuit in the brain, the bed nucleus of stria terminalis (BNST) has been proposed as a target for DBS in OCD. However, the mechanism of action of BNST DBS in OCD is not yet fully understood. In our studies, the aim was to evaluate the effect and side effects of DBS in the BNST in severe OCD, to investigate which anatomical areas are being affected by the stimulation and what could be the potential mechanism of action of DBS in this target. We also explored the knowledge and concerns regarding DBS in OCD among psychiatrists, psychotherapists and patients suffering from the disorder. We investigate clinical outcomes and safety of DBS in the BNST in a series of 11 participants with severe therapy-refractory OCD. The primary outcome was a change in the Yale-Brown Obsessive-Compulsive Scale (YBOCS) scores one year after surgery. Using image and stimulation parameter data from the study above, we investigate through participant-specific simulation of the electric field, which anatomical areas are affected by the electric field, and if this can be related to the clinical results. Six of the participants were evaluated with symptom provocation fMRI pre-operatively and in DBS ON and OFF conditions. A web-based study surveyed psychiatrists, patients, and cognitive-behavioural therapists regarding previous knowledge of DBS, source of knowledge, attitudes, and concerns towards the therapy. At baseline, the mean±SD YBOCS score was 33±3.0. One year after DBS, mean±SD YBOCS score was 20±4.8 (38% improvement (range 10- 60%) p &lt;0.01). Of the 11 participants, six were considered responders (decrease in YBOCS ≥35%) and four partial responders (decrease in YBOCS 25-34%). Surgical adverse events included one case of skin infection leading to reimplantation. The most common transient stimulation-related side-effects were anxiety and insomnia. The individual electric stimulation fields by stimulation in the BNST were similar at the 12 and 24-months follow up, involving mainly the anterior limb of the internal capsule (ALIC), genu of the internal capsule, BNST, fornix, anteromedial globus pallidus externa (GPe) and the anterior commissure. A statistically significant correlation (p &lt; 0.05) between clinical effect measured by the YBOCS and simulation was found at the 12-month follow-up in the ventral ALIC and anteromedial GPe. A significant decrease in anxiety-related brain activity in the pre-supplementary motor area (pre-SMA) and the anterior insula was seen in 3/6 participants, with a comparable reduction (below significance level) in the other three participants. Results from the survey found that the primary source of information was from scientific sources among psychiatrists and psychotherapists. The patients' primary source of information was the media. Common concerns among the groups included complications from surgery, anaesthesia, stimulation side effects, and the novelty of the treatment. Specific concerns for the groups included; personality changes mentioned by patients and psychotherapists and ethical concerns among psychiatrists. BNST DBS is a promising therapy in severe therapy-refractory OCD. Our results are in line with previous publications regarding effect and safety profiles. We hypothesise that possible mechanisms of BNST DBS in OCD could be modulation of anxiety-related activity in the pre-SMA and anterior insula, two regions that play an important role in the pathophysiology of OCD. Many of the targets under investigation for OCD are in anatomical proximity, and as seen in our study, offtarget effects overlap. Therefore, DBS in the region of ALIC, NA, and BNST may perhaps be considered to be stimulation of the same target. DBS challenges in obsessive-compulsive disorder consist of source and quality of information, potential long-term adverse effects and eligibility. A broad research agenda is needed for studies as we advance in this field.Serietillhörighet saknas i publikationen.</p

Deep brain stimulation for obsessive-compulsive disorder : knowledge and concerns among psychiatrists, psychotherapists and patients

Background: Deep brain stimulation (DBS) is under investigation for severe obsessive-compulsive disorder (OCD) resistant to other therapies. The number of implants worldwide is slowly increasing. Therefore, it is of importance to explore knowledge and concerns of this novel treatment among patients and their psychiatric healthcare contacts. This information is relevant for scientific professionals working with clinical studies for DBS for this indication. Especially, for future study designs and the creation of information targeting healthcare professionals and patients. The aim of this study was to explore the knowledge and concerns toward DBS among patients with OCD, psychiatrists, and cognitive behavioral therapists. Methods: The study was conducted through web-based surveys for the aimed target groups -psychiatrist, patients, and cognitive behavioral therapists. The surveys contained questions regarding previous knowledge of DBS, source of knowledge, attitudes, and concerns towards the therapy. Results: The main source of information was from scientific sources among psychiatrists and psychotherapists. The patient's main source of information was the media. Common concerns among the groups included complications from surgery, anesthesia, stimulation side effects, and the novelty of the treatment. Specific concerns for the groups included; personality changes mentioned by patients and psychotherapists, and ethical concerns among psychiatrists. Conclusion: There are challenges for DBS in OCD as identified by the participants of this study; source and quality of information, efficacy, potential adverse effects, and eligibility. In all of which the current evidence base still is limited. A broad research agenda is needed for studies going forward

Deep Brain Stimulation in the Bed Nucleus of Stria Terminalis in Obsessive-Compulsive Disorder : 1-Year Follow-up

Background: Deep brain stimulation (DBS) is under investigation as a treatment for therapy-refractory obsessive-compulsive disorder (OCD). As a crucial part of the anxiety circuit, the bed nucleus of stria terminalis (BNST) has been proposed as a target for DBS in OCD. Here, we investigate clinical outcomes and safety of DBS in the BNST in a series of 11 participants with severe therapy-refractory OCD. Methods: Eleven consecutive participants diagnosed with refractory OCD were treated with BNST DBS and completed follow-up. The primary outcome was a change in scores of the Yale Brown Obsessive Compulsive Scale (YBOCS) at 1 year after surgery. Secondary outcomes included changes in scores of the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Global Assessment of Functioning. Results: At baseline, the mean ± SD YBOCS score was 33 ± 3.0, MADRS score was 29 ± 4.5, and GAF score was 49 ± 5.4. One year after DBS, mean ± SD YBOCS score was 20 ± 4.8 (38% improvement (range 10%−60%) P &lt; 0.01), MADRS score was 21 ± 5.8 (27% improvement, range 4%−74%, P &lt; 0.01), and Global Assessment of Functioning score was 55 ± 6.5 (12% improvement, range 4%−29%, P &lt; 0.05). Of the 11 participants, 6 were considered responders (decrease in YBOCS ≥35%) and 4 partial responders (decrease in YBOCS 25%−34%). Surgical adverse events included 1 case of skin infection leading to reimplantation. The most common transient stimulation-related side effects were anxiety and insomnia. Conclusions: BNST DBS is a promising therapy in severe therapy-refractory OCD. Our results are in line with previous publications regarding effect and safety profile. Nevertheless, DBS for OCD remains an investigational therapy and should therefore be performed in multidisciplinary clinical studies

Translation and linguistic validation of the Swedish Recovering Quality of Life (ReQoL) : A brief research report

In research and among clinicians, the focus has shifted from mainly symptom reduction and increasing functionality to a more recovery-oriented focus. Although there are instruments measuring recovery, there has been a lack of instruments sensitive enough to measure the quality of life for people with severe mental health disorders. Therefore, this study aimed to obtain a Swedish version of the Recovering Quality of Life (ReQoL) questionnaire adhering to best practice guidelines using various steps of translation, linguistic validation, and cognitive debriefing. The cognitive debriefing was conducted with seven participants, and all felt the items in the questionnaire were relevant to their health, apprehensible, and easy to complete. However, some issues were raised regarding wording and the concepts behind certain items. All feedback was considered, and some items were revised in response to criticism after continuous discussions. A Swedish version of ReQoL now exists, and although there is a need for ReQoL in different clinical research settings in Sweden, further research is required to psychometrically test the construct validity as well as reliability of the Swedish version in Sweden

Distribution of electric field in patients with obsessive compulsive disorder treated with deep brain stimulation of the bed nucleus of stria terminalis

Background: Deep brain stimulation (DBS) is being investigated as a treatment for therapy-refractory obsessive-compulsive disorder (OCD). Many different brain targets are being trialled. Several of these targets such as the ventral striatum (including the nucleus accumbens (NAc)), the ventral capsule, the inferior thalamic peduncle and the bed nucleus of stria terminalis (BNST)) belong to the same network, are anatomically very close to one another, or even overlap. Data is still missing on how various stimulation parameters in a given target will affect surrounding anatomical areas and impact the clinical outcome of DBS. Methods: In a pilot study of eleven participants with DBS of the BNST, we investigate through patient-specific simulation of electric field, which anatomical areas are affected by the electric field, and if this can be related to the clinical results. Our study, combined individual patient’s stimulation parameters at 12 and 24-months follow-up with image data from the preoperative MRI and postoperative CT. These data were used to calculate the distribution of electric field and create individual anatomical models of the field of stimulation. Results: The individual electric stimulation fields by stimulation in the BNST were similar at both the 12 and 24-months follow up, involving mainly anterior limb of the internal capsule (ALIC), genu of the internal capsule (IC), BNST, fornix, anteromedial globus pallidus externa (GPe) and the anterior commissure. A statistical significant correlation (p &lt; 0.05) between clinical effect measured by the Yale-Brown Obsessive Compulsive Scale and stimulation was found at the 12-month follow up in the ventral ALIC and anteromedial GPe. Conclusions: Many of the targets under investigation for OCD are in anatomical proximity. As seen in our study, off-target effects are overlapping. Therefore, DBS in the region of ALIC, NAc and BNST may perhaps be considered to be stimulation of the same target.Originally included in thesis in manuscript form with title: "Distribution of electric field in patients with obsessive-compulsive disorder treated with deep brain stimulation of the bed nucleus of stria terminalis".This article is part of the Topical Collection on Functional Neurosurgery - Other</p

Genomics of severe and treatment-resistant obsessive–compulsive disorder treated with deep brain stimulation : a preliminary investigation

Individuals with severe and treatment-resistant obsessive-compulsive disorder (trOCD) represent a small but severely disabled group of patients. Since trOCD cases eligible for deep brain stimulation (DBS) probably comprise the most severe end of the OCD spectrum, we hypothesize that they may be more likely to have a strong genetic contribution to their disorder. Therefore, while the worldwide population of DBS-treated cases may be small (~300), screening these individuals with modern genomic methods may accelerate gene discovery in OCD. As such, we have begun to collect DNA from trOCD cases who qualify for DBS, and here we report results from whole exome sequencing and microarray genotyping of our first five cases. All participants had previously received DBS in the bed nucleus of stria terminalis (BNST), with two patients responding to the surgery and one showing a partial response. Our analyses focused on gene-disruptive rare variants (GDRVs; rare, predicted-deleterious single-nucleotide variants or copy number variants overlapping protein-coding genes). Three of the five cases carried a GDRV, including a missense variant in the ion transporter domain of KCNB1, a deletion at 15q11.2, and a duplication at 15q26.1. The KCNB1 variant (hg19 chr20-47991077-C-T, NM_004975.3:c.1020G&gt;A, p.Met340Ile) causes substitution of methionine for isoleucine in the trans-membrane region of neuronal potassium voltage-gated ion channel KV2.1. This KCNB1 substitution (Met340Ile) is located in a highly constrained region of the protein where other rare missense variants have previously been associated with neurodevelopmental disorders. The patient carrying the Met340Ile variant responded to DBS, which suggests that genetic factors could potentially be predictors of treatment response in DBS for OCD. In sum, we have established a protocol for recruiting and genomically characterizing trOCD cases. Preliminary results suggest that this will be an informative strategy for finding risk genes in OCD

Genomics of severe and treatment-resistant obsessive–compulsive disorder treated with deep brain stimulation : a preliminary investigation

Individuals with severe and treatment-resistant obsessive-compulsive disorder (trOCD) represent a small but severely disabled group of patients. Since trOCD cases eligible for deep brain stimulation (DBS) probably comprise the most severe end of the OCD spectrum, we hypothesize that they may be more likely to have a strong genetic contribution to their disorder. Therefore, while the worldwide population of DBS-treated cases may be small (~300), screening these individuals with modern genomic methods may accelerate gene discovery in OCD. As such, we have begun to collect DNA from trOCD cases who qualify for DBS, and here we report results from whole exome sequencing and microarray genotyping of our first five cases. All participants had previously received DBS in the bed nucleus of stria terminalis (BNST), with two patients responding to the surgery and one showing a partial response. Our analyses focused on gene-disruptive rare variants (GDRVs; rare, predicted-deleterious single-nucleotide variants or copy number variants overlapping protein-coding genes). Three of the five cases carried a GDRV, including a missense variant in the ion transporter domain of KCNB1, a deletion at 15q11.2, and a duplication at 15q26.1. The KCNB1 variant (hg19 chr20-47991077-C-T, NM_004975.3:c.1020G&gt;A, p.Met340Ile) causes substitution of methionine for isoleucine in the trans-membrane region of neuronal potassium voltage-gated ion channel KV2.1. This KCNB1 substitution (Met340Ile) is located in a highly constrained region of the protein where other rare missense variants have previously been associated with neurodevelopmental disorders. The patient carrying the Met340Ile variant responded to DBS, which suggests that genetic factors could potentially be predictors of treatment response in DBS for OCD. In sum, we have established a protocol for recruiting and genomically characterizing trOCD cases. Preliminary results suggest that this will be an informative strategy for finding risk genes in OCD

Deep brain stimulation for obsessive-compulsive disorder:a crisis of access

Deep brain stimulation is an effective treatment for obsessive–compulsive disorder but is rarely used. Action is needed by psychologists, psychiatrists and insurers so that patients with otherwise intractable cases can receive this therapy to improve their mental health

Deep brain stimulation for refractory obsessive-compulsive disorder (OCD): emerging or established therapy?

A consensus has yet to emerge whether deep brain stimulation (DBS) for treatment-refractory obsessive-compulsive disorder (OCD) can be considered an established therapy. In 2014, the World Society for Stereotactic and Functional Neurosurgery (WSSFN) published consensus guidelines stating that a therapy becomes established when “at least two blinded randomized controlled clinical trials from two different groups of researchers are published, both reporting an acceptable risk-benefit ratio, at least comparable with other existing therapies. The clinical trials should be on the same brain area for the same psychiatric indication.” The authors have now compiled the available evidence to make a clear statement on whether DBS for OCD is established therapy. Two blinded randomized controlled trials have been published, one with level I evidence (Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score improved 37% during stimulation on), the other with level II evidence (25% improvement). A clinical cohort study (N = 70) showed 40% Y-BOCS score improvement during DBS, and a prospective international multi-center study 42% improvement (N = 30). The WSSFN states that electrical stimulation for otherwise treatment refractory OCD using a multipolar electrode implanted in the ventral anterior capsule region (including bed nucleus of stria terminalis and nucleus accumbens) remains investigational. It represents an emerging, but not yet established therapy. A multidisciplinary team involving psychiatrists and neurosurgeons is a prerequisite for such therapy, and the future of surgical treatment of psychiatric patients remains in the realm of the psychiatrist