A trans-diagnostic perspective on obsessive-compulsive disorder

© Cambridge University Press 2017. This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.Progress in understanding the underlying neurobiology of obsessive-compulsive disorder (OCD) has stalled in part because of the considerable problem of heterogeneity within this diagnostic category, and homogeneity across other putatively discrete, diagnostic categories. As psychiatry begins to recognize the shortcomings of a purely symptom-based psychiatric nosology, new data-driven approaches have begun to be utilized with the goal of solving these problems: specifically, identifying trans-diagnostic aspects of clinical phenomenology based on their association with neurobiological processes. In this review, we describe key methodological approaches to understanding OCD from this perspective and highlight the candidate traits that have already been identified as a result of these early endeavours. We discuss how important inferences can be made from pre-existing case-control studies as well as showcasing newer methods that rely on large general population datasets to refine and validate psychiatric phenotypes. As exemplars, we take 'compulsivity' and 'anxiety', putatively trans-diagnostic symptom dimensions that are linked to well-defined neurobiological mechanisms, goal-directed learning and error-related negativity, respectively. We argue that the identification of biologically valid, more homogeneous, dimensions such as these provides renewed optimism for identifying reliable genetic contributions to OCD and other disorders, improving animal models and critically, provides a path towards a future of more targeted psychiatric treatments.Peer reviewedFinal Published versio

An overview of the first 5 years of the ENIGMA obsessive–compulsive disorder working group: The power of worldwide collaboration

Abstract Neuroimaging has played an important part in advancing our understanding of the neurobiology of obsessive?compulsive disorder (OCD). At the same time, neuroimaging studies of OCD have had notable limitations, including reliance on relatively small samples. International collaborative efforts to increase statistical power by combining samples from across sites have been bolstered by the ENIGMA consortium; this provides specific technical expertise for conducting multi-site analyses, as well as access to a collaborative community of neuroimaging scientists. In this article, we outline the background to, development of, and initial findings from ENIGMA's OCD working group, which currently consists of 47 samples from 34 institutes in 15 countries on 5 continents, with a total sample of 2,323 OCD patients and 2,325 healthy controls. Initial work has focused on studies of cortical thickness and subcortical volumes, structural connectivity, and brain lateralization in children, adolescents and adults with OCD, also including the study on the commonalities and distinctions across different neurodevelopment disorders. Additional work is ongoing, employing machine learning techniques. Findings to date have contributed to the development of neurobiological models of OCD, have provided an important model of global scientific collaboration, and have had a number of clinical implications. Importantly, our work has shed new light on questions about whether structural and functional alterations found in OCD reflect neurodevelopmental changes, effects of the disease process, or medication impacts. We conclude with a summary of ongoing work by ENIGMA-OCD, and a consideration of future directions for neuroimaging research on OCD within and beyond ENIGMA

Therapist-Supported Online Remote Behavioural Intervention for Tics (ORBIT) in Children and Adolescents: A Single-Blind Randomised Controlled Trial

Background: Behaviour therapy is an effective treatment in children and adolescents with tic disorders but is rarely available. Online delivery could widen access to therapy. We evaluated the efficacy of internet-delivered, therapist-supported and parent-assisted Exposure and Response Prevention (ERP) for tics. / Methods: Multi-centre, parallel group, single-blind, randomised controlled trial. Eligible participants were aged 9-17 years with Tourette syndrome/chronic tic disorder, who had not received behaviour therapy for tics within 12 months, and had a Yale Global Tic Severity Scale (YGTSS) Total Tic Severity Score (TTSS) of >15, or >10 if motor or vocal tics only. Participants were recruited via 16 patient identification centres, two study sites, or online self-referral, and were randomised (1:1) by blinded outcome-assessors to receive either 10 weeks of ERP or psychoeducation (active control). The primary outcome was YGTSS-TTSS at 3 months’ post-randomisation, analysis was by intention-to-treat. The mean cost per patient for the intervention and health care costs were calculated. Registrations are ISRCTN (ISRCTN70758207) and ClinicalTrials.gov (NCT03483493). / Findings: Between 8 th May 2018 and 30 th September 2019, 224 participants were enrolled; 112 to ERP and 112 to psychoeducation. The ERP intervention reduced YGTSS-TTSS by 2 . 29 points (95% CI: ‑3 . 86 to -0 . 71) compared to the psychoeducation group at 3 months, an effect that increased by 6 months post-randomisation (-2 . 64, 95% CI: -4 . 56 to -0 . 73). The average therapist time spent supporting the intervention was 2 . 5 hours. The additional cost per participant of the ERP intervention compared to psychoeducation was £159 (95% CI -£53 to £370). There were two unrelated serious adverse events, both in the psychoeducation group. / Interpretation: Online-delivered, therapist-supported ERP therapy is clinically effective at reducing tics, with minimal therapist contact time. Online delivery could improve access to evidence-based treatment for tics in children and adolescents

The effects of acute serotonin challenge on executive planning in patients with obsessive-compulsive disorder (OCD), their first-degree relatives, and healthy controls

© 2020 Springer-Verlag. The final publication is available at Springer via https://doi.org/10.1007/s00213-020-05597-7.Rationale: OCD is characterized by executive function impairment and by clinical responsivity to selective serotonin reuptake inhibitors (SSRIs). Executive planning deficits constitute a candidate endophenotype for OCD. It is not known whether this endophenotype is responsive to acute serotonin manipulation. Objective: To investigate the effects of acute SSRI administration on executive function in patients with OCD, first-degree relatives of patients with OCD and healthy controls. Methods: A randomized double-blind crossover study assessed the effects of single dose escitalopram (20mg) and placebo on executive planning in 24 patients with OCD, 13 clinically unaffected first-degree relatives of patients with OCD and 28 healthy controls. Performance on a Tower of London task measuring executive planning was assessed 4 hours after oral administration of the pharmacological challenge / placebo, and compared across and within groups using a mixed model ANOVA. Results: On the outcome measure of interest, i.e. the mean number of choices to obtain the correct solution, there was a marginally significant effect of group (F(2, 59)=3.1; p=0.052), with patients (Least square [LS] mean: 1.43; Standard Error [SE]: 0.06; 95% confidence interval [CI], 1.31-1.55) and their relatives (LS mean: 1.46; SE: 0.08; 95% CI, 1.30-1.62) performing worse than matched healthy controls (LS mean: 1.26; SE: 0.05; 95% CI, 1.15-1.37) on placebo. There was a trend towards a significant group x treatment interaction (F(2, 58)=2.8, p=0.069), with post hoc tests showing (i) patients (p=0.009; LS mean difference: 0.23; SE: 0.08) and relatives (p=0.03; LS mean difference: 0.22; SE: 0.10) were more impaired compared to controls and (ii) escitalopram was associated with improved executive planning in patients with OCD (p=0.013; LS mean difference: 0.1; SE: 0.04), but not other groups (both p>0.1; controls: LS mean difference: -0.03; SE: 0.04; relatives: LS mean difference: 0.02; SE: 0.05). Conclusion: Our findings are consistent with a view that there is impaired executive planning in OCD, and that this constitutes a behavioral endophenotype. In patients with OCD, but not in relatives, acute SSRI administration ameliorated this deficit. Further investigation is needed to understand common and differential involvement of neurochemical systems in patients with OCD and their relatives.Peer reviewe

Structural covariance of neostriatal and limbic regions in patients with obsessive-compulsive disorder

Background: Frontostriatal and frontoamygdalar connectivity alterations in patients with obsessive-compulsive disorder (OCD) have been typically described in functional neuroimaging studies. However, structural covariance, or volumetric correlations across distant brain regions, also provides network-level information. Altered structural covariance has been described in patients with different psychiatric disorders, including OCD, but to our knowledge, alterations within frontostriatal and frontoamygdalar circuits have not been explored. Methods: We performed a mega-analysis pooling structural MRI scans from the Obsessive-compulsive Brain Imaging Consortium and assessed whole-brain voxel-wise structural covariance of 4 striatal regions (dorsal and ventral caudate nucleus, and dorsal-caudal and ventral-rostral putamen) and 2 amygdalar nuclei (basolateral and centromedial-superficial). Images were preprocessed with the standard pipeline of voxel-based morphometry studies using Statistical Parametric Mapping software. Results: Our analyses involved 329 patients with OCD and 316 healthy controls. Patients showed increased structural covariance between the left ventral-rostral putamen and the left inferior frontal gyrus/frontal operculum region. This finding had a significant interaction with age; the association held only in the subgroup of older participants. Patients with OCD also showed increased structural covariance between the right centromedial-superficial amygdala and the ventromedial prefrontal cortex. Limitations: This was a cross-sectional study. Because this is a multisite data set analysis, participant recruitment and image acquisition were performed in different centres. Most patients were taking medication, and treatment protocols differed across centres. Conclusion: Our results provide evidence for structural network-level alterations in patients with OCD involving 2 frontosubcortical circuits of relevance for the disorder and indicate that structural covariance contributes to fully characterizing brain alterations in patients with psychiatric disorders

The COVID-19 pandemic and its impact on tic symptoms in children and young people: a prospective cohort study

To understand how children and young people with tic disorders were affected by COVID-19, we compared pre and during pandemic scores on the Yale Global Tic Severity Scale (YGTSS). Participants were young people (N = 112; male:78%; 9–17 years) randomised to the control arm of the “ORBIT-Trial” (ISRCTN70758207, ClinicalTrials.gov-NCT03483493). For this analysis, the control arm was split into two groups: one group was followed up to 12-months’ post-randomisation before the pandemic started (pre-COVID group, n = 44); the other group was impacted by the pandemic at the 12-month follow-up (during-COVID group, n = 47). Mixed effects linear regression modelling was conducted to explore differences in YGTSS at 6- and 12-months post-randomisation. There were no significant differences in tic symptom or severity between participants who were assessed before and during COVID-19. This finding was not influenced by age, gender, symptoms of anxiety or autism spectrum disorder. Thus, the COVID-19 pandemic did not significantly impact existing tic symptoms

Self-help interventions for anxiety disorders: An overview.

Anxiety disorders are highly prevalent and are associated with a marked impairment in quality of life and a huge economic cost to society. Unfortunately, a considerable number of people who struggle with anxiety do not seek or receive adequate treatment. Self-help interventions have been proposed to constitute a relatively cheap, effective, efficient, and low-threshold intervention for anxiety disorders. This paper offers a critical discussion of their advantages and disadvantages and the evidence for their effectiveness. We conclude that guided self-help can play a major role in mental health care for patients with anxiety disorders. However, several research questions need to be answered before broad-scale dissemination is possible. The Internet will continue to play a prominent role in the further development of this field of research and clinical practice

Brain activation of the defensive and appetitive survival systems in obsessive compulsive disorder

Several studies have shown that basic emotions are responsible for a significant enhancement of early visual processes and increased activation in visual processing brain regions. It may be possible that the cognitive uncertainty and repeated behavioral checking evident in Obsessive Compulsive Disorder (OCD) is due to the existence of abnormalities in basic survival circuits, particularly those associated with the visual processing of the physical characteristics of emotional-laden stimuli. The objective of the present study was to test if patients with OCD show evidence of altered basic survival circuits, particularly those associated with the visual processing of the physical characteristics of emotional stimuli. Fifteen patients with OCD and 12 healthy controls underwent functional magnetic resonance imaging acquisition while being exposed to emotional pictures, with different levels of arousal, intended to trigger the defensive and appetitive basic survival circuits. Overall, the present results seem to indicate dissociation in the activity of the defense and appetitive survival systems in OCD. Results suggest that the clinical group reacts to basic threat with a strong activation of the defensive system mobilizing widespread brain networks (i.e., frontal, temporal, occipital-parietal, and subcortical nucleus) and blocking the activation of the appetitive system when facing positive emotional triggers from the initial stages of visual processing (i.e., superior occipital gyrus)

Structural neuroimaging biomarkers for obsessive-compulsive disorder in the ENIGMA-OCD consortium: medication matters

No diagnostic biomarkers are available for obsessive-compulsive disorder (OCD). Here, we aimed to identify magnetic resonance imaging (MRI) biomarkers for OCD, using 46 data sets with 2304 OCD patients and 2068 healthy controls from the ENIGMA consortium. We performed machine learning analysis of regional measures of cortical thickness, surface area and subcortical volume and tested classification performance using cross-validation. Classification performance for OCD vs. controls using the complete sample with different classifiers and cross-validation strategies was poor. When models were validated on data from other sites, model performance did not exceed chance-level. In contrast, fair classification performance was achieved when patients were grouped according to their medication status. These results indicate that medication use is associated with substantial differences in brain anatomy that are widely distributed, and indicate that clinical heterogeneity contributes to the poor performance of structural MRI as a disease marker