| 1. |
- Andersson, Erik, et al.
(författare)
-
d-Cycloserine vs Placebo as Adjunct to Cognitive Behavioral Therapy for Obsessive-Compulsive Disorder and Interaction With Antidepressants A Randomized Clinical Trial
- 2015
-
Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 72:7, s. 659-667
-
Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE It is unclear whether D-cycloserine (DCS), a partial N-methyl-D-aspartate agonist that enhances fear extinction, can augment the effects of exposure-based cognitive behavioral therapy (CBT) for obsessive-compulsive disorder (OCD). OBJECTIVES To examine whether DCS augments the effects of CBT for OCD and to explore (post hoc) whether concomitant antidepressant medication moderates the effects of DCS. DESIGN, SETTING, AND PARTICIPANTS A 12-week, double-blind randomized clinical trial with 3-month follow-up conducted at an academic medical center between September 4, 2012, and September 26, 2013. Participants included 128 adult outpatients with a primary diagnosis of OCD and a Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score of 16 or higher. Concurrent antidepressant medication was permitted if the dose had been stable for at least 2 months prior to enrollment and remained unchanged during the trial. The main analysis was by intention-to-treat population. INTERVENTIONS All participants received a previously validated Internet-based CBT protocol over 12 weeks and were randomized to receive either 50 mg of DCS or placebo, administered 1 hour before each of 5 exposure and response prevention tasks. MAIN OUTCOMES AND MEASURES Clinician-administered Y-BOCS score at week 12 and at 3-month follow-up. Remission was defined as a score of 12 or lower on the Y-BOCS. RESULTS In the primary intention-to-treat analyses, DCS did not augment the effects of CBT compared with placebo (mean [SD] clinician-rated Y-BOCS score, DCS: 13.86 [6.50] at week 12 and 12.35 [7.75] at 3-month follow-up; placebo: 11.77 [5.95] at week 12 and 12.37 [6.68] at 3-month follow-up) but showed a significant interaction with antidepressants (clinician-rated Y-BOCS, B = -1.08; Z = -2.79; P = .005). Post hoc analyses revealed that antidepressants significantly impaired treatment response in the DCS group but not the placebo group, at both posttreatment and follow-up (clinician-rated Y-BOCS: t(62) = -3.00; P = .004; and t(61) = -3.49; P < .001, respectively). In the DCS group, a significantly greater proportion of antidepressant-free patients achieved remission status at follow-up (60% [95% CI, 45%-74%]) than antidepressant-medicated patients (24% [95% CI, 9%-48%]) (P = .008). Antidepressants had no effect in the placebo group (50% [95% CI, 36%-64%] remission rate in both groups). CONCLUSIONS AND RELEVANCE The findings suggest that antidepressants may interact with DCS to block its facilitating effect on fear extinction. Use of DCS may be a promising CBT augmentation strategy but only in antidepressant-free patients with OCD.
|
|
| 2. |
- Linde, Johanna, et al.
(författare)
-
Acceptance-Based Exposure Therapy for Body Dysmorphic Disorder : a Pilot Study
- 2015
-
Ingår i: Behavior Therapy. - : Elsevier BV. - 0005-7894 .- 1878-1888. ; 46:4, s. 423-431
-
Tidskriftsartikel (refereegranskat)abstract
- Body dysmorphic disorder (BDD) is an often severe, chronic, and disabling disorder, and although some controlled trials of cognitive behavior therapy (CBT) have shown efficacy, the body of evidence is still limited. The condition is generally considered difficult to treat, and further research to determine the effectiveness of psychological treatments for BDD is needed. The present study is the first to evaluate an acceptance-based therapy for BDD. In total, 21 patients received a 12-week group treatment consisting of weekly sessions of psychoeducation, acceptance and defusion practice, and exposure exercises to foster acceptance of internal discomfort and to strengthen the patients’ committed purposeful actions. The primary outcome was BDD symptomatology (measured on the BDD-YBOCS) assessed by a psychiatrist before and after treatment and at 6 months follow-up. The secondary outcomes were self-rated BDD symptoms, psychological flexibility, depressive symptoms, quality of life, and disability. Reductions in BDD symptomatology from pre- to posttreatment were significant and showed a large effect size, d = 1.93 (95% CI 0.82–3.04). At posttreatment, 68% of the participants showed clinically significant improvement in the primary outcome variable. Treatment gains were maintained at 6 months follow-up. The treatment also resulted in significant improvements in all secondary outcomes. The dropout rate was low; 90.5% of the participants completed treatment. This study suggests that acceptance-based exposure therapy may be an efficacious and acceptable treatment for BDD that warrants further investigation in larger controlled trials.
|
|
| 3. |
- Mataix-Cols, David, et al.
(författare)
-
Nordic OCD & Related Disorders Consortium : Rationale, design, and methods.
- 2020
-
Ingår i: American Journal of Medical Genetics Part B. - : Wiley. - 1552-4841 .- 1552-485X. ; 183:1, s. 38-50
-
Tidskriftsartikel (refereegranskat)abstract
- Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder, yet its etiology is unknown and treatment outcomes could be improved if biological targets could be identified. Unfortunately, genetic findings for OCD are lagging behind other psychiatric disorders. Thus, there is a pressing need to understand the causal mechanisms implicated in OCD in order to improve clinical outcomes and to reduce morbidity and societal costs. Specifically, there is a need for a large-scale, etiologically informative genetic study integrating genetic and environmental factors that presumably interact to cause the condition. The Nordic countries provide fertile ground for such a study, given their detailed population registers, national healthcare systems and active specialist clinics for OCD. We thus formed the Nordic OCD and Related Disorders Consortium (NORDiC, www.crowleylab.org/nordic), and with the support of NIMH and the Swedish Research Council, have begun to collect a large, richly phenotyped and genotyped sample of OCD cases. Our specific aims are geared toward answering a number of key questions regarding the biology, etiology, and treatment of OCD. This article describes and discusses the rationale, design, and methodology of NORDiC, including details on clinical measures and planned genomic analyses.
|
|
| 4. |
- Noh, Hyun Ji, et al.
(författare)
-
Integrating evolutionary and regulatory information with multispecies approach implicates genes and pathways in obsessive-compulsive disorder
- 2017
-
Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Obsessive-compulsive disorder is a severe psychiatric disorder linked to abnormalities in glutamate signaling and the cortico-striatal circuit. We sequenced coding and regulatory elements for 608 genes potentially involved in obsessive-compulsive disorder in human, dog, and mouse. Using a new method that prioritizes likely functional variants, we compared 592 cases to 560 controls and found four strongly associated genes, validated in a larger cohort. NRXN1 and HTR2A are enriched for coding variants altering postsynaptic protein-binding domains. CTTNBP2 (synapse maintenance) and REEP3 (vesicle trafficking) are enriched for regulatory variants, of which at least six (35%) alter transcription factor-DNA binding in neuroblastoma cells. NRXN1 achieves genome-wide significance (p = 6.37 x 10(-11)) when we include 33,370 population-matched controls. Our findings suggest synaptic adhesion as a key component in compulsive behaviors, and show that targeted sequencing plus functional annotation can identify potentially causative variants, even when genomic data are limited.
|
|
| 5. |
- Plaven-Sigray, Pontus, et al.
(författare)
-
Extrastriatal dopamine D2-receptor availability in social anxiety disorder
- 2017
-
Ingår i: European Neuropsychopharmacology. - : Elsevier BV. - 0924-977X .- 1873-7862. ; 27:5, s. 462-469
-
Tidskriftsartikel (refereegranskat)abstract
- Alterations in the dopamine system are hypothesized to influence the expression of social anxiety disorder (SAD) symptoms. However, molecular imaging studies comparing dopamine function between patients and control subjects have yielded conflicting results. Importantly, while all previous investigations focused on the striatum, findings from activation and blood flow studies indicate that prefrontal and limbic brain regions have a central role in the pathophysiology. The objective of this study was to investigate extrastriatal dopamine D2-receptor (D2-R) availability in SAD. We examined 12 SAD patients and 16 healthy controls using positron emission tomography and the high-affinity D2-R radioligand [C-11]FLB457. Parametric images of D2-R binding potential were derived using the Logan graphical method with cerebellum as reference region. Two-tailed one-way independent ANCOVAs, with age as covariate, were used to examine differences in D2-R availability between groups using both region-based and voxel-wise analyses. The region-based analysis showed a medium effect size of higher D2-R levels in the orbitofrontal cortex (OFC) in patients, although this result did not remain significant after correction for multiple comparisons. The voxel-wise comparison revealed elevated D2-R availability in patients within OFC and right dorsolateral prefrontal cortex after correction for multiple comparisons. These preliminary results suggest that an aberrant extrastriatal dopamine system may be part of the disease mechanism in SAD.
|
|
| 6. |
- Wu, Hemmings, et al.
(författare)
-
Deep brain stimulation for refractory obsessive-compulsive disorder (OCD) : emerging or established therapy?
- 2021
-
Ingår i: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 26, s. 60-65
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
|
|
