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- Naesström, Matilda, 1987-
(författare)
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Deep brain stimulation in obsessive-compulsive disorder
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 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 <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 < 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.
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| 2. |
- Naesström, Matilda, et al.
(författare)
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Deep Brain Stimulation in the Bed Nucleus of Stria Terminalis in Obsessive-Compulsive Disorder : 1-Year Follow-up
- 2021
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Ingår i: World Neurosurgery. - : Elsevier. - 1878-8750 .- 1878-8769. ; 149, s. e794-e802
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Tidskriftsartikel (refereegranskat)abstract
- 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 < 0.01), MADRS score was 21 ± 5.8 (27% improvement, range 4%−74%, P < 0.01), and Global Assessment of Functioning score was 55 ± 6.5 (12% improvement, range 4%−29%, P < 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.
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| 3. |
- Naesström, Matilda, et al.
(författare)
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Distribution of electric field in patients with obsessive compulsive disorder treated with deep brain stimulation of the bed nucleus of stria terminalis
- 2022
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Ingår i: Acta Neurochirurgica. - : Springer. - 0001-6268 .- 0942-0940. ; 164, s. 193-202
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Tidskriftsartikel (refereegranskat)abstract
- 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 < 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.
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| 4. |
- Özel, Faith, et al.
(författare)
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Exploring gender dysphoria and related outcomes in a prospective cohort study: protocol for the Swedish Gender Dysphoria Study (SKDS)
- 2023
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Ingår i: Bmj Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 13:4
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Tidskriftsartikel (refereegranskat)abstract
- Introduction There has been a drastic increase in the reported number of people seeking help for gender dysphoria in many countries over the last two decades. Yet, our knowledge of gender dysphoria and related outcomes is restricted due to the lack of high-quality studies employing comprehensive approaches. This longitudinal study aims to enhance our knowledge of gender dysphoria; different aspects will be scrutinised, focusing primarily on the psychosocial and mental health outcomes, prognostic markers and, secondarily, on the underlying mechanisms for its origin. Methods and analysis The Swedish Gender Dysphoria Study is an ongoing multicentre longitudinal cohort study with 501 registered participants with gender dysphoria who are 15 years old or older. Participants at different phases of their clinical evaluation process can enter the study, and the expected follow-up duration is three years. The study also includes a comparison group of 458 age- and county-matched individuals without gender dysphoria. Data on the core outcomes of the study, which are gender incongruence and experienced gender dysphoria, body satisfaction and satisfaction with gender-affirming treatments, as well as other relevant outcomes, including mental health, social functioning and life satisfaction, are collected via web surveys. Two different research visits, before and after starting on gender-affirming hormonal treatment (if applicable), are planned to collect respective biological and cognitive measures. Data analysis will be performed using appropriate biostatistical methods. A power analysis showed that the current sample size is big enough to analyse continuous and categorical outcomes, and participant recruitment will continue until December 2022. Ethics and dissemination The ethical permission for this study was obtained from the Local Ethical Review Board in Uppsala, Sweden. Results of the study will be presented at national and international conferences and published in peer-reviewed journals. Dissemination will also be implemented through the Swedish Gender Dysphoria Study network in Sweden.
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