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>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.

Cost-effectiveness of internet-delivered cognitive behaviour therapy for body dysmorphic disorder: Results from a randomised controlled trial.

Objectives: To evaluate the cost-effectiveness of internet-delivered cognitive behaviour therapy for body dysmorphic disorder (BDD-NET). Design: Secondary cost-effectiveness analysis from a randomised controlled trial on BDD-NET versus online supportive psychotherapy. Setting: Academic medical center. Participants: Self-referred adult participants with a primary diagnosis of body dysmorphic disorder and a score of 20 or higher on the modified Yale-Brown Obsessive Compulsive Scale for BDD (n = 94). Patients receiving concurrent psychotropic drug treatment were included if the dose had been stable for at least two months. Interventions: Participants received either BDD-NET (n = 47) or online supportive psychotherapy (n = 47) for 12 weeks. Primary and secondary outcome measures: The primary outcome measures were cost-effectiveness and cost-utility from a societal perspective, using remission status from a diagnostic interview and quality-adjusted life years (QALY), respectively. Secondary outcome measures were cost-effectiveness and cost-utility from a health care perspective and the clinic's perspective. Results: Compared to supportive psychotherapy, BDD-NET produced one additional remission for an average societal cost of $4132. The cost-utility analysis showed that BDD-NET generated one QALY to an average cost of $14,319 from a societal perspective. Conclusions: BDD-NET is a cost-effective treatment for body dysmorphic disorder, compared to online supportive psychotherapy. The efficacy and cost-effectiveness of BDD-NET should next be directly compared to in-person cognitive behaviour therapy. Trial registration: NCT02010619.

Longitudinal study of gut microbiome in obsessive-compulsive disorder.

INTRODUCTION: Patients with obsessive-compulsive disorder (OCD) often have limited exposure to a diverse environment and perform repetitive compulsions such as excessive cleaning and washing, which could lead to altered gut microbiome. Therefore, longitudinal studies that investigate changes in gut microbiome before and after cognitive behavioral therapy based on exposure and response prevention (ERP) are warranted. METHODS: All study participants (N = 64) underwent a structured psychiatric diagnostic interview prior to inclusion. Nutritional intake was assessed with a comprehensive food frequency questionnaire. Stool samples were collected from OCD patients before ERP (n = 32) and 1 month after completion of ERP (n = 15), as well as from healthy controls (HCs; n = 32). Taxonomic and functional analyses were performed using data from microbiome whole genome sequencing. RESULTS: Patients with OCD at baseline reported consuming significantly less fiber than HCs (R2  = .12, F(2, 59) = 5.2, p ≤ .01). There were no significant differences in α- and ß-diversity indices, or taxonomic dissimilarities at the species level between patients with OCD and HCs, or within patients before and after ERP. Functional profiling based on gut microbial gene expression was grouped into 56 gut-brain modules with neuroactive potential. None of the gut-brain modules differed significantly in expression between patients with OCD at baseline and HCs or within patients before and after ERP. CONCLUSIONS: The diversity, composition, and functional profile of the gut microbiome in patients with OCD did not differ significantly from HCs and remained stable over time, despite behavioral changes.

Effectiveness of Internet-based cognitive-behavioural therapy for obsessive-compulsive disorder (OCD-NET) and body dysmorphic disorder (BDD-NET) in the Swedish public health system using the RE-AIM implementation framework.

Objectives: Therapist-guided internet-delivered cognitive behaviour therapy (ICBT) is an efficacious treatment for obsessive-compulsive disorder (OCD) and body dysmorphic disorder (BDD), but it is unclear if the results obtained in controlled trials can be reproduced in clinical settings. We evaluated the implementation of ICBT for OCD (OCD-NET) and BDD (BDD-NET) in the Swedish public health system. Methods: Consecutive referrals to an outpatient psychiatric clinic providing ICBT, with a primary diagnosis of OCD or BDD, were included in the study. Four hundred and thirty-four participants started OCD-NET and 163 started BDD-NET. The primary outcome measures were the Yale Brown Obsessive Compulsive Scale (Y-BOCS) and the Y-BOCS for BDD (BDD-YBOCS), respectively. Participants were assessed before treatment, weekly during treatment, and after treatment. The study used the RE-AIM implementation framework, and the elements of reach, effectiveness, adoption, and implementation for the evaluation. Results: Intention to treat analysis of the OCD-NET sample (n = 434) showed a significant decrease in OCD symptoms from pre-treatment to post-treatment (mean reduction = -8.77 [95 % CI -9.48 to -8.05] p < .001, d = 1.94 [95 % CI 1.75 to 2.13]). Forty-nine percent (95 % CI 43 % to 56 %) of the participants in OCD-NET were classified as treatment responders and 21 % (95 % CI 16 % to 27 %) were in remission. Participants in BDD-NET (n = 163) also showed a significant decrease in BDD symptoms from pre-post treatment (mean reduction = -11.37 [95 % CI -12.9 to -9.87] p < .001, d = 2.07 [95 % CI 1.74 to 2.40]) and 69 % (95 % CI 58 % to 79 %) of the participants were classified as treatment responders and 48 % (95 % CI 38 % to 58 %) were in full or partial remission. Eighty-seven percent of the participants in OCD-NET and 78 % in BDD-NET were treatment completers and participants in both treatment groups reported a high treatment satisfaction at post treatment (OCD-NET = 87 %, BDD-NET = 79 %). The most reported negative effects attributed to the treatments were transient experiences of unpleasant feelings (52 %) and anxiety (50 %). The implementation also influenced treatment delivery and dramatically decreased the mean number of patients waiting to receive face-to-face treatment at the clinic. Conclusions: Our results indicate that OCD-NET and BDD-NET are suitable treatments for implementation in a Swedish public health service.

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>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.

Effect of Internet-Based vs Face-to-Face Cognitive Behavioral Therapy for Adults With Obsessive-Compulsive Disorder: A Randomized Clinical Trial.

Importance: Cognitive behavioral therapy (CBT) for obsessive-compulsive disorder (OCD) is a highly specialized treatment that is in short supply worldwide. Objectives: To investigate whether both therapist-guided and unguided internet-based CBT (ICBT) are noninferior to face-to-face CBT for adults with OCD, to conduct a health economic evaluation, and to determine whether treatment effects were moderated by source of participant referral. Design, Setting, and Participants: This study is a single-blinded, noninferiority, randomized clinical trial, with a full health economic evaluation, conducted between September 2015 and January 2020, comparing therapist-guided ICBT, unguided ICBT, and individual face-to-face CBT for adults with OCD. Follow-up data were collected up to 12 months after treatment. The study was conducted at 2 specialist outpatient OCD clinics in Stockholm, Sweden. Participants included a consecutive sample of adults with a primary diagnosis of OCD, either self-referred or referred by a clinician. Data analysis was performed from June 2019 to January 2022. Interventions: Guided ICBT, unguided ICBT, and face-to-face CBT delivered over 14 weeks. Main Outcomes and Measures: The primary end point was the change in OCD symptom severity from baseline to 3-month follow-up. The noninferiority margin was 3 points on the masked assessor-rated Yale-Brown Obsessive Compulsive Scale. Results: A total of 120 participants were enrolled (80 women [67%]; mean [SD] age, 32.24 [9.64] years); 38 were randomized to the face-to-face CBT group, 42 were randomized to the guided ICBT group, and 40 were randomized to the unguided ICBT group. The mean difference between therapist-guided ICBT and face-to-face CBT at the primary end point was 2.10 points on the Yale-Brown Obsessive Compulsive Scale (90% CI, -0.41 to 4.61 points; P = .17), favoring face-to-face CBT, meaning that the primary noninferiority results were inconclusive. The difference between unguided ICBT and face-to-face CBT was 5.35 points (90% CI, 2.76 to 7.94 points; P < .001), favoring face-to-face CBT. The health economic analysis showed that both guided and unguided ICBT were cost-effective compared with face-to-face CBT. Source of referral did not moderate treatment outcome. The most common adverse events were anxiety (30 participants [25%]), depressive symptoms (20 participants [17%]), and stress (11 participants [9%]). Conclusions and Relevance: The findings of this randomized clinical trial of ICBT vs face-to-face CBT for adults with OCD do not conclusively demonstrate noninferiority. Therapist-guided ICBT could be a cost-effective alternative to in-clinic CBT for adults with OCD in scenarios where traditional CBT is not readily available; unguided ICBT is probably less efficacious but could be an alternative when providing remote clinician support is not feasible. Trial Registration: ClinicalTrials.gov Identifier: NCT02541968.