Structural neuroimaging biomarkers for obsessive-compulsive disorder in the ENIGMA-OCD consortium: medication matters.
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SUBMITTER: Bruin WB
PROVIDER: S-EPMC7598942 | biostudies-literature | 2020 Oct
REPOSITORIES: biostudies-literature
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Structural neuroimaging biomarkers for obsessive-compulsive disorder in the ENIGMA-OCD consortium: medication matters.
Bruin Willem B WB Taylor Luke L Thomas Rajat M RM Shock Jonathan P JP Zhutovsky Paul P Abe Yoshinari Y Alonso Pino P Ameis Stephanie H SH Anticevic Alan A Arnold Paul D PD Assogna Francesca F Benedetti Francesco F Beucke Jan C JC Boedhoe Premika S W PSW Bollettini Irene I Bose Anushree A Brem Silvia S Brennan Brian P BP Buitelaar Jan K JK Calvo Rosa R Cheng Yuqi Y Cho Kang Ik K KIK Dallaspezia Sara S Denys Damiaan D Ely Benjamin A BA Feusner Jamie D JD Fitzgerald Kate D KD Fouche Jean-Paul JP Fridgeirsson Egill A EA Gruner Patricia P Gürsel Deniz A DA Hauser Tobias U TU Hirano Yoshiyuki Y Hoexter Marcelo Q MQ Hu Hao H Huyser Chaim C Ivanov Iliyan I James Anthony A Jaspers-Fayer Fern F Kathmann Norbert N Kaufmann Christian C Koch Kathrin K Kuno Masaru M Kvale Gerd G Kwon Jun Soo JS Liu Yanni Y Lochner Christine C Lázaro Luisa L Marques Paulo P Marsh Rachel R Martínez-Zalacaín Ignacio I Mataix-Cols David D Menchón José M JM Minuzzi Luciano L Moreira Pedro S PS Morer Astrid A Morgado Pedro P Nakagawa Akiko A Nakamae Takashi T Nakao Tomohiro T Narayanaswamy Janardhanan C JC Nurmi Erika L EL O'Neill Joseph J Pariente Jose C JC Perriello Chris C Piacentini John J Piras Fabrizio F Piras Federica F Reddy Y C Janardhan YCJ Rus-Oswald Oana G OG Sakai Yuki Y Sato João R JR Schmaal Lianne L Shimizu Eiji E Simpson H Blair HB Soreni Noam N Soriano-Mas Carles C Spalletta Gianfranco G Stern Emily R ER Stevens Michael C MC Stewart S Evelyn SE Szeszko Philip R PR Tolin David F DF Venkatasubramanian Ganesan G Wang Zhen Z Yun Je-Yeon JY van Rooij Daan D Thompson Paul M PM van den Heuvel Odile A OA Stein Dan J DJ van Wingen Guido A GA
Translational psychiatry 20201008 1
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 compl ...[more]
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Project description:Current knowledge about functional connectivity in obsessive-compulsive disorder (OCD) is based on small-scale studies, limiting the generalizability of results. Moreover, the majority of studies have focused only on predefined regions or functional networks rather than connectivity throughout the entire brain. Here, we investigated differences in resting-state functional connectivity between OCD patients and healthy controls (HC) using mega-analysis of data from 1024 OCD patients and 1028 HC from 28 independent samples of the ENIGMA-OCD consortium. We assessed group differences in whole-brain functional connectivity at both the regional and network level, and investigated whether functional connectivity could serve as biomarker to identify patient status at the individual level using machine learning analysis. The mega-analyses revealed widespread abnormalities in functional connectivity in OCD, with global hypo-connectivity (Cohen's d: -0.27 to -0.13) and few hyper-connections, mainly with the thalamus (Cohen's d: 0.19 to 0.22). Most hypo-connections were located within the sensorimotor network and no fronto-striatal abnormalities were found. Overall, classification performances were poor, with area-under-the-receiver-operating-characteristic curve (AUC) scores ranging between 0.567 and 0.673, with better classification for medicated (AUC = 0.702) than unmedicated (AUC = 0.608) patients versus healthy controls. These findings provide partial support for existing pathophysiological models of OCD and highlight the important role of the sensorimotor network in OCD. However, resting-state connectivity does not so far provide an accurate biomarker for identifying patients at the individual level.
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Project description:BACKGROUND:Obsessive-compulsive disorder (OCD) is associated with affective and cognitive symptoms causing personal distress and reduced global functioning. These have considerable societal costs due to healthcare service utilization. OBJECTIVE:Our aim was to assess the efficacy of pharmacological interventions in OCD and clinical guidelines, providing a comprehensive overview of this field. METHODS:We searched the PubMed database for papers dealing with drug treatment of OCD, with a specific focus on clinical guidelines, treatments with antidepressants, antipsychotics, mood stabilizers, off-label medications, and pharmacogenomics. RESULTS:Prolonged administration of selective serotonin reuptake inhibitors (SSRIs) is most effective. Better results can be obtained with a SSRI combined with cognitive behavioral therapy (CBT) or the similarly oriented exposure and response prevention (ERP). Refractory OCD could be treated with different strategies, including a switch to another SSRI or clomipramine, or augmentation with an atypical antipsychotic. The addition of medications other than antipsychotics or intravenous antidepressant administration needs further investigation, as the evidence is inconsistent. Pharmacogenomics and personalization of therapy could reduce treatment resistance. CONCLUSIONS:SSRI/clomipramine in combination with CBT/ERP is associated with the optimal response compared to each treatment alone or to other treatments. New strategies for refractory OCD are needed. The role of pharmacogenomics could become preponderant in the coming years.
| S-EPMC7059159 | biostudies-literature
Project description:BackgroundLateralized dysfunction has been suggested in obsessive-compulsive disorder (OCD). However, it is currently unclear whether OCD is characterized by abnormal patterns of brain structural asymmetry. Here we carried out what is by far the largest study of brain structural asymmetry in OCD.MethodsWe studied a collection of 16 pediatric datasets (501 patients with OCD and 439 healthy control subjects), as well as 30 adult datasets (1777 patients and 1654 control subjects) from the OCD Working Group within the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Consortium. Asymmetries of the volumes of subcortical structures, and of measures of regional cortical thickness and surface areas, were assessed based on T1-weighted magnetic resonance imaging scans, using harmonized image analysis and quality control protocols. We investigated possible alterations of brain asymmetry in patients with OCD. We also explored potential associations of asymmetry with specific aspects of the disorder and medication status.ResultsIn the pediatric datasets, the largest case-control differences were observed for volume asymmetry of the thalamus (more leftward; Cohen's d = 0.19) and the pallidum (less leftward; d = -0.21). Additional analyses suggested putative links between these asymmetry patterns and medication status, OCD severity, or anxiety and depression comorbidities. No significant case-control differences were found in the adult datasets.ConclusionsThe results suggest subtle changes of the average asymmetry of subcortical structures in pediatric OCD, which are not detectable in adults with the disorder. These findings may reflect altered neurodevelopmental processes in OCD.
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Project description:Brain structural covariance networks reflect covariation in morphology of different brain areas and are thought to reflect common trajectories in brain development and maturation. Large-scale investigation of structural covariance networks in obsessive-compulsive disorder (OCD) may provide clues to the pathophysiology of this neurodevelopmental disorder. Using T1-weighted MRI scans acquired from 1616 individuals with OCD and 1463 healthy controls across 37 datasets participating in the ENIGMA-OCD Working Group, we calculated intra-individual brain structural covariance networks (using the bilaterally-averaged values of 33 cortical surface areas, 33 cortical thickness values, and six subcortical volumes), in which edge weights were proportional to the similarity between two brain morphological features in terms of deviation from healthy controls (i.e. z-score transformed). Global networks were characterized using measures of network segregation (clustering and modularity), network integration (global efficiency), and their balance (small-worldness), and their community membership was assessed. Hub profiling of regional networks was undertaken using measures of betweenness, closeness, and eigenvector centrality. Individually calculated network measures were integrated across the 37 datasets using a meta-analytical approach. These network measures were summated across the network density range of K?=?0.10-0.25 per participant, and were integrated across the 37 datasets using a meta-analytical approach. Compared with healthy controls, at a global level, the structural covariance networks of OCD showed lower clustering (P?<?0.0001), lower modularity (P?<?0.0001), and lower small-worldness (P?=?0.017). Detection of community membership emphasized lower network segregation in OCD compared to healthy controls. At the regional level, there were lower (rank-transformed) centrality values in OCD for volume of caudate nucleus and thalamus, and surface area of paracentral cortex, indicative of altered distribution of brain hubs. Centrality of cingulate and orbito-frontal as well as other brain areas was associated with OCD illness duration, suggesting greater involvement of these brain areas with illness chronicity. In summary, the findings of this study, the largest brain structural covariance study of OCD to date, point to a less segregated organization of structural covariance networks in OCD, and reorganization of brain hubs. The segregation findings suggest a possible signature of altered brain morphometry in OCD, while the hub findings point to OCD-related alterations in trajectories of brain development and maturation, particularly in cingulate and orbitofrontal regions.
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Project description:BACKGROUND:Obsessive-compulsive disorder (OCD) is a highly prevalent, severe, and chronic disease. There is a need for alternative strategies for treatment-resistant OCD. OBJECTIVE:This review aims to assess the effect of brain stimulation techniques in OCD. METHODS:We included papers published in peer-reviewed journals dealing with brain stimulation techniques in OCD. We conducted treatment-specific searches for OCD (Technique AND ((randomized OR randomised) AND control* AND trial) AND (magnetic AND stimulation OR (rTMS OR dTMS)) AND (obsess* OR compuls* OR OCD)) on six databases, i.e., PubMed, Cochrane, Scopus, CINAHL, PsycINFO, and Web of Science to identify randomised controlled trials and ClinicalTrials.gov for possible additional results. RESULTS:Different add-on stimulation techniques could be effective for severely ill OCD patients unresponsive to drugs and/or behavioural therapy. Most evidence regarded deep brain stimulation (DBS) and transcranial magnetic stimulation (TMS), while there is less evidence regarding transcranial direct current stimulation (tDCS), electroconvulsive therapy, and vagus nerve stimulation (for these last two there are no sham-controlled studies). Low-frequency TMS may be more effective over the supplementary motor area or the orbitofrontal cortex. DBS showed best results when targeting the crossroad between the nucleus accumbens and the ventral capsule or the subthalamic nucleus. Cathodal tDCS may be better than anodal in treating OCD. Limitations. We had to include methodologically inconsistent underpowered studies. CONCLUSION:Different brain stimulation techniques are promising as an add-on treatment of refractory OCD, although studies frequently reported inconsistent results. TMS, DBS, and tDCS could possibly find some use with adequate testing, but their standard methodology still needs to be established.
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Project description:Microstructural alterations in cortico-subcortical connections are thought to be present in obsessive-compulsive disorder (OCD). However, prior studies have yielded inconsistent findings, perhaps because small sample sizes provided insufficient power to detect subtle abnormalities. Here we investigated microstructural white matter alterations and their relation to clinical features in the largest dataset of adult and pediatric OCD to date. We analyzed diffusion tensor imaging metrics from 700 adult patients and 645 adult controls, as well as 174 pediatric patients and 144 pediatric controls across 19 sites participating in the ENIGMA OCD Working Group, in a cross-sectional case-control magnetic resonance study. We extracted measures of fractional anisotropy (FA) as main outcome, and mean diffusivity, radial diffusivity, and axial diffusivity as secondary outcomes for 25 white matter regions. We meta-analyzed patient-control group differences (Cohen's d) across sites, after adjusting for age and sex, and investigated associations with clinical characteristics. Adult OCD patients showed significant FA reduction in the sagittal stratum (d = -0.21, z = -3.21, p = 0.001) and posterior thalamic radiation (d = -0.26, z = -4.57, p < 0.0001). In the sagittal stratum, lower FA was associated with a younger age of onset (z = 2.71, p = 0.006), longer duration of illness (z = -2.086, p = 0.036), and a higher percentage of medicated patients in the cohorts studied (z = -1.98, p = 0.047). No significant association with symptom severity was found. Pediatric OCD patients did not show any detectable microstructural abnormalities compared to controls. Our findings of microstructural alterations in projection and association fibers to posterior brain regions in OCD are consistent with models emphasizing deficits in connectivity as an important feature of this disorder.
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Project description:ObjectiveBrain imaging studies of structural abnormalities in OCD have yielded inconsistent results, partly because of limited statistical power, clinical heterogeneity, and methodological differences. The authors conducted meta- and mega-analyses comprising the largest study of cortical morphometry in OCD ever undertaken.MethodT1-weighted MRI scans of 1,905 OCD patients and 1,760 healthy controls from 27 sites worldwide were processed locally using FreeSurfer to assess cortical thickness and surface area. Effect sizes for differences between patients and controls, and associations with clinical characteristics, were calculated using linear regression models controlling for age, sex, site, and intracranial volume.ResultsIn adult OCD patients versus controls, we found a significantly lower surface area for the transverse temporal cortex and a thinner inferior parietal cortex. Medicated adult OCD patients also showed thinner cortices throughout the brain. In pediatric OCD patients compared with controls, we found significantly thinner inferior and superior parietal cortices, but none of the regions analyzed showed significant differences in surface area. However, medicated pediatric OCD patients had lower surface area in frontal regions. Cohen's d effect sizes varied from -0.10 to -0.33.ConclusionsThe parietal cortex was consistently implicated in both adults and children with OCD. More widespread cortical thickness abnormalities were found in medicated adult OCD patients, and more pronounced surface area deficits (mainly in frontal regions) were found in medicated pediatric OCD patients. These cortical measures represent distinct morphological features and may be differentially affected during different stages of development and illness, and possibly moderated by disease profile and medication.
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Project description:Patients with obsessive-compulsive disorder (OCD) can be described as cautious and hesitant, manifesting an excessive indecisiveness that hinders efficient decision making. However, excess caution in decision making may also lead to better performance in specific situations where the cost of extended deliberation is small. We compared 16 juvenile OCD patients with 16 matched healthy controls whilst they performed a sequential information gathering task under different external cost conditions. We found that patients with OCD outperformed healthy controls, winning significantly more points. The groups also differed in the number of draws required prior to committing to a decision, but not in decision accuracy. A novel Bayesian computational model revealed that subjective sampling costs arose as a non-linear function of sampling, closely resembling an escalating urgency signal. Group difference in performance was best explained by a later emergence of these subjective costs in the OCD group, also evident in an increased decision threshold. Our findings present a novel computational model and suggest that enhanced information gathering in OCD can be accounted for by a higher decision threshold arising out of an altered perception of costs that, in some specific contexts, may be advantageous.
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Project description:ObjectiveThe purpose of this study was to determine the neural correlates of excessive habit formation in obsessive-compulsive disorder (OCD). The authors aimed to test for neurobiological convergence with the known pathophysiology of OCD and to infer, based on abnormalities in brain activation, whether these habits arise from dysfunction in the goal-directed or habit system.MethodThirty-seven OCD patients and 33 healthy comparison subjects learned to avoid shocks while undergoing a functional MRI scan. Following four blocks of training, the authors tested whether the avoidance response had become a habit by removing the threat of shock and measuring continued avoidance. Task-related differences in brain activity in three regions of interest (the caudate, the putamen, and the medial orbitofrontal cortex) were tested at a statistical threshold set at <0.05 (family-wise-error corrected).ResultsExcessive habit formation in OCD patients, which was associated with hyperactivation in the caudate, was observed. Activation in this region was also associated with subjective ratings of increased urge to perform habits. The OCD group, as a whole, showed hyperactivation in the medial orbitofrontal cortex during the acquisition of avoidance; however, this did not relate directly to habit formation.ConclusionsOCD patients exhibited excessive habits that were associated with hyperactivation in a key region implicated in the pathophysiology of OCD, the caudate nucleus. Previous studies indicate that this region is important for goal-directed behavior, suggesting that habit-forming biases in OCD may be a result of impairments in this system, rather than differences in the buildup of stimulus-response habits themselves.
| S-EPMC4910868 | biostudies-literature
Project description:The notion that some special brain regions may be involved in the pathogenesis of obsessive-compulsive disorder (OCD) dates back to the beginning of the twentieth century. Structural neuroimaging studies in the past 2 decades have revealed important findings that facilitate understanding of OCD pathogenesis. Current knowledge based on functional and structural neuroimaging investigations largely emphasizes abnormalities in fronto-striatal-thalamic-cortical and orbitofronto-striato-thalamic circuits in the pathophysiology of OCD. However, these neuroimaging studies did not focus on refractory OCD. The present review mainly focused on structural neuroimaging performed in OCD, which had been ignored previously, and highlighted current evidence supporting that orbito-frontal cortex and thalamus are key brain regions, and that the hippocampus-amygdala complex is associated with refractoriness to the available treatment strategies. However, to fully reveal the neuroanatomy of refractoriness, longitudinal studies with larger samples are required.
| S-EPMC5560357 | biostudies-other