Exploring gender dysphoria and related outcomes in a prospective cohort study: protocol for the Swedish Gender Dysphoria Study (SKDS).

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.

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-month 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-month 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.

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 < 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.

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 the stria terminalis and medial forebrain bundle in a patient with major depressive disorder and anorexia nervosa.

Deep brain stimulation (DBS) may be considered in severe cases of therapy-refractory major depressive disorder (MDD). However, DBS for MDD is still an experimental therapy. Therefore, it should only be administered in clinical studies driven by multidisciplinary teams, including surgeons with substantial experience of DBS in the treatment of other conditions.

[Deep brain stimulation for psychiatric disorders]. / Djup hjärnstimulering vid psykiska sjukdomar visar lovande resultat - Men behandlingen är fortfarande experimentell.

Deep brain stimulation for psychiatric disorders Deep brain stimulation is an established treatment for movement disorders. It has been proven to be a safe method; only minor complications have been reported in larger studies. New indications for deep brain stimulation are under investigation; among them major depressive disorder and obsessive-compulsive disorder. Deep brain stimulation for severe and therapy-resistant major depressive disorder and obsessive compulsive-disorder shows promising results. However, the experience of deep brain stimulation in psychiatric disorders is limited. Several potential target areas for stimulation have been presented; which are the most effective is still an open question. Deep brain stimulation in psychiatric disorders is a highly experimental treatment and should only be performed by a multidisciplinary team with extensive experience with deep brain stimulation in other conditions.

A systematic review of psychiatric indications for deep brain stimulation, with focus on major depressive and obsessive-compulsive disorder.

BACKGROUND: Deep brain stimulation is a treatment under investigation for a range of psychiatric disorders. It has shown promising results for therapy-refractory obsessive-compulsive disorder (OCD) and major depressive disorder (MDD). Other indications under investigation include Tourette's syndrome, anorexia nervosa and substance use disorders. AIMS: To review current studies on psychiatric indications for deep brain stimulation (DBS), with focus on OCD and MDD. METHOD: A systematic search was carried out in MEDLINE, and the literature was searched to identify studies with DBS for psychiatric disorders. The identified studies were analysed based on patient characteristics, treatment results and adverse effects of DBS. RESULTS: A total of 52 papers met the inclusion criteria and described a total of 286 unique patients treated with DBS for psychiatric indications; 18 studies described 112 patients treated with DBS for OCD in six different anatomical targets, while nine studies presented 100 patients with DBS for MDD in five different targets. CONCLUSION: DBS may show promise for treatment-resistant OCD and MDD but the results are limited by small sample size and insufficient randomized controlled data. Deep brain stimulation for OCD has received United States Food and Drug Administration approval. Other psychiatric indications are currently of a purely experimental nature.

Moderation and mediation of the effect of attention training in social anxiety disorder.

UNLABELLED: While attention modification programs (AMP) have shown promise as laboratory-based treatments for social anxiety disorder, trials of internet-delivered AMP have not yielded significant differences between active and control conditions. To address these inconsistencies, we examined the moderational and mediational role of attention bias in the efficacy of attention training. We compared data reported by Carlbring et al. (2012) to an identical AMP condition, with the exception that participants were instructed to activate social anxiety fears prior to each attention training session (AMP + FACT; n = 39). We also compared all attention training groups to an internet-delivered cognitive-behavioral therapy (iCBT) condition (n = 40). Participants in the AMP + FACT group experienced greater reductions in social anxiety symptoms than both active (n = 40) and control (n = 39) groups reported by Carlbring et al., and did not differ in symptom reductions from the iCBT group. Higher attention bias predicted greater symptom reductions for participants who completed AMP, but not for the control group. Moreover, change in attention bias mediated the relationship between AMP group (active condition reported by Carlbring et al. versus AMP + FACT) and change in social anxiety symptoms. These results suggest the importance of interpreting findings related to symptom change in attention training studies in the context of bias effects. TRIAL REGISTRATION: ISRCTN01715124.

Altered neural correlates of affective processing after internet-delivered cognitive behavior therapy for social anxiety disorder.

Randomized controlled trials have yielded promising results for internet-delivered cognitive behavior therapy (iCBT) for patients with social anxiety disorder (SAD). The present study investigated anxiety-related neural changes after iCBT for SAD. The amygdala is a critical hub in the neural fear network, receptive to change using emotion regulation strategies and a putative target for iCBT. Twenty-two subjects were included in pre- and post-treatment functional magnetic resonance imaging at 3T assessing neural changes during an affective face processing task. Treatment outcome was assessed using social anxiety self-reports and the Clinical Global Impression-Improvement (CGI-I) scale. ICBT yielded better outcome than ABM (66% vs. 25% CGI-I responders). A significant differential activation of the left amygdala was found with relatively decreased reactivity after iCBT. Changes in the amygdala were related to a behavioral measure of social anxiety. Functional connectivity analysis in the iCBT group showed that the amygdala attenuation was associated with increased activity in the medial orbitofrontal cortex and decreased activity in the right ventrolateral and dorsolateral (dlPFC) cortices. Treatment-induced neural changes with iCBT were consistent with previously reported studies on regular CBT and emotion regulation in general.

Deep brain stimulation in the treatment of obsessive-compulsive disorder.

BACKGROUND: Deep brain stimulation (DBS) has emerged as a treatment for severe cases of therapy-refractory obsessive-compulsive disorder (OCD), and promising results have been reported. The literature might, however, be somewhat unclear, considering the different targets used, and due to repeated inclusion of individual patients in multiple publications. The aim of this report was to review the literature on DBS for OCD. METHODS: The modern literature concerning studies conducted on DBS in the treatment of OCD was reviewed. RESULTS: The results of DBS in OCD have been presented in 25 reports with 130 patients, of which, however, only 90 contained individual patients. Five of these reports included at least 5 individual patients not presented elsewhere. Sixty-eight of these patients underwent implantation in the region of the internal capsule/ventral striatum, including the nucleus accumbens. The target in this region has varied between groups and over time, but the latest results from bilateral procedures in this area have shown a 50% reduction of OCD scores, depression, and anxiety. The subthalamic nucleus has been suggested as an alternative target. Although beneficial effects have been demonstrated, the efficacy of this procedure cannot be decided, because only results after 3 months of active stimulation have been presented so far. CONCLUSIONS: DBS is a promising treatment for therapy-refractory OCD, but the published experience is limited and the method is at present an experimental therapy.