Age of onset of obsessive-compulsive disorder differentially affects white matter microstructure.

Previous diffusion MRI studies have reported mixed findings on white matter microstructure alterations in obsessive-compulsive disorder (OCD), likely due to variation in demographic and clinical characteristics, scanning methods, and underpowered samples. The OCD global study was created across five international sites to overcome these challenges by harmonizing data collection to identify consistent brain signatures of OCD that are reproducible and generalizable. Single-shell diffusion measures (e.g., fractional anisotropy), multi-shell Neurite Orientation Dispersion and Density Imaging (NODDI) and fixel-based measures, were extracted from skeletonized white matter tracts in 260 medication-free adults with OCD and 252 healthy controls. We additionally performed structural connectome analysis. We compared cases with controls and cases with early (<18) versus late (18+) OCD onset using mixed-model and Bayesian multilevel analysis. Compared with healthy controls, adult OCD individuals showed higher fiber density in the sagittal stratum (B[SE] = 0.10[0.05], P = 0.04) and credible evidence for higher fiber density in several other tracts. When comparing early (n = 145) and late-onset (n = 114) cases, converging evidence showed lower integrity of the posterior thalamic radiation -particularly radial diffusivity (B[SE] = 0.28[0.12], P = 0.03)-and lower global efficiency of the structural connectome (B[SE] = 15.3[6.6], P = 0.03) in late-onset cases. Post-hoc analyses indicated divergent direction of effects of the two OCD groups compared to healthy controls. Age of OCD onset differentially affects the integrity of thalamo-parietal/occipital tracts and the efficiency of the structural brain network. These results lend further support for the role of the thalamus and its afferent fibers and visual attentional processes in the pathophysiology of OCD.

The functional connectome in obsessive-compulsive disorder: resting-state mega-analysis and machine learning classification for the ENIGMA-OCD consortium.

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.

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

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.

Toward a neurocircuit-based taxonomy to guide treatment of obsessive-compulsive disorder.

An important challenge in mental health research is to translate findings from cognitive neuroscience and neuroimaging research into effective treatments that target the neurobiological alterations involved in psychiatric symptoms. To address this challenge, in this review we propose a heuristic neurocircuit-based taxonomy to guide the treatment of obsessive-compulsive disorder (OCD). We do this by integrating information from several sources. First, we provide case vignettes in which patients with OCD describe their symptoms and discuss different clinical profiles in the phenotypic expression of the condition. Second, we link variations in these clinical profiles to underlying neurocircuit dysfunctions, drawing on findings from neuropsychological and neuroimaging studies in OCD. Third, we consider behavioral, pharmacological, and neuromodulatory treatments that could target those specific neurocircuit dysfunctions. Finally, we suggest methods of testing this neurocircuit-based taxonomy as well as important limitations to this approach that should be considered in future research.

Screening for Dementia and Cognitive Decline in Adults With Down Syndrome: A Novel Approach Using the Informant Questionnaire on Cognitive Decline in the Elderly.

OBJECTIVE: The aim was to examine the psychometric properties of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) as a diagnostic tool to screen for dementia in aging individuals with Down syndrome (DS). METHODS: This was a cross-sectional study of 92 individuals with DS 30 y or above of age) evaluated with the IQCODE. Using the informant questionnaire of the Cambridge Examination for Mental Disorders of Older People with Down's Syndrome and Others with Intellectual Disabilities, we divided the subjects into 3 diagnostic groups: stable cognition; prodromal dementia; and dementia. The ability of the IQCODE to discriminate between diagnostic groups was analyzed by calculating the areas under the receiver operator characteristic curves (AUCs). RESULTS: The optimal IQCODE cutoffs were 3.14 for dementia versus stable cognition (AUC=0.993; P<0.001) and 3.11 for prodromal dementia+dementia versus stable cognition (AUC=0.975; P<0.001), with sensitivity/specificity/accuracy of 100%/96.8%/97.3%, and 93.3%/91.9%/92.4%, respectively. The IQCODE showed a weak-to-moderate correlation with cognitive performance (P<0.05). CONCLUSION: The IQCODE is a useful tool to screen for cognitive decline in individuals with DS and is suitable for use in a primary care setting.

Brain structural covariance networks in obsessive-compulsive disorder: a graph analysis from the ENIGMA Consortium.

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.

Using supervised machine learning on neuropsychological data to distinguish OCD patients with and without sensory phenomena from healthy controls.

OBJECTIVES: While theoretical models link obsessive-compulsive disorder (OCD) with executive function deficits, empirical findings from the neuropsychological literature remain mixed. These inconsistencies are likely exacerbated by the challenge of high-dimensional data (i.e., many variables per subject), which is common across neuropsychological paradigms and necessitates analytical advances. More unique to OCD is the heterogeneity of symptom presentations, each of which may relate to distinct neuropsychological features. While researchers have traditionally attempted to account for this heterogeneity using a symptom-based approach, an alternative involves focusing on underlying symptom motivations. Although the most studied symptom motivation involves fear of harmful events, 60-70% of patients also experience sensory phenomena, consisting of uncomfortable sensations or perceptions that drive compulsions. Sensory phenomena have received limited attention in the neuropsychological literature, despite evidence that symptoms motivated by these experiences may relate to distinct cognitive processes. METHODS: Here, we used a supervised machine learning approach to characterize neuropsychological processes in OCD, accounting for sensory phenomena. RESULTS: Compared to logistic regression and other algorithms, random forest best differentiated healthy controls (n = 59; balanced accuracy = .70), patients with sensory phenomena (n = 29; balanced accuracy = .59), and patients without sensory phenomena (n = 46; balanced accuracy = .62). Decision-making best distinguished between groups based on sensory phenomena, and among the patient subsample, those without sensory phenomena uniquely displayed greater risk sensitivity compared to healthy controls (d = .07, p = .008). CONCLUSIONS: Results suggest that different cognitive profiles may characterize patients motivated by distinct drives. The superior performance and generalizability of the newer algorithms highlights the utility of considering multiple analytic approaches when faced with complex data. PRACTITIONER POINTS: Practitioners should be aware that sensory phenomena are common experiences among patients with OCD. OCD patients with sensory phenomena may be distinguished from those without based on neuropsychological processes.

Evolution of gamma knife capsulotomy for intractable obsessive-compulsive disorder.

For more than half a century, stereotactic neurosurgical procedures have been available to treat patients with severe, debilitating symptoms of obsessive-compulsive disorder (OCD) that have proven refractory to extensive, appropriate pharmacological, and psychological treatment. Although reliable predictors of outcome remain elusive, the establishment of narrower selection criteria for neurosurgical candidacy, together with a better understanding of the functional neuroanatomy implicated in OCD, has resulted in improved clinical efficacy for an array of ablative and non-ablative intervention techniques targeting the cingulum, internal capsule, and other limbic regions. It was against this backdrop that gamma knife capsulotomy (GKC) for OCD was developed. In this paper, we review the history of this stereotactic radiosurgical procedure, from its inception to recent advances. We perform a systematic review of the existing literature and also provide a narrative account of the evolution of the procedure, detailing how the procedure has changed over time, and has been shaped by forces of evidence and innovation. As the procedure has evolved and adverse events have decreased considerably, favorable response rates have remained attainable for approximately one-half to two-thirds of individuals treated at experienced centers. A reduction in obsessive-compulsive symptom severity may result not only from direct modulation of OCD neural pathways but also from enhanced efficacy of pharmacological and psychological therapies working in a synergistic fashion with GKC. Possible complications include frontal lobe edema and even the rare formation of delayed radionecrotic cysts. These adverse events have become much less common with new radiation dose and targeting strategies. Detailed neuropsychological assessments from recent studies suggest that cognitive function is not impaired, and in some domains may even improve following treatment. We conclude this review with discussions covering topics essential for further progress of this therapy, including suggestions for future trial design given the unique features of GKC therapy, considerations for optimizing stereotactic targeting and dose planning using biophysical models, and the use of advanced imaging techniques to understand circuitry and predict response. GKC, and in particular its modern variant, gamma ventral capsulotomy, continues to be a reliable treatment option for selected cases of otherwise highly refractory OCD.

Amnestic and non-amnestic symptoms of dementia: An international study of Alzheimer's disease in people with Down's syndrome.

The presence of age-related neuropathology characteristic of Alzheimer's disease (AD) in people with Down syndrome (DS) is well-established. However, the early symptoms of dementia may be atypical and appear related to dysfunction of prefrontal circuitry. OBJECTIVE: To characterize the initial informant reported age-related neuropsychiatric symptoms of dementia in people with DS, and their relationship to AD and frontal lobe function. METHODS: Non-amnestic informant reported symptoms (disinhibition, apathy, and executive dysfunction) and amnestic symptoms from the CAMDEX-DS informant interview were analyzed in a cross-sectional cohort of 162 participants with DS over 30 years of age, divided into three groups: stable cognition, prodromal dementia, and AD. To investigate age-related symptoms prior to evidence of prodromal dementia we stratified the stable cognition group by age. RESULTS: Amnestic and non-amnestic symptoms were present before evidence of informant-reported cognitive decline. In those who received the diagnosis of AD, symptoms tended to be more marked. Memory impairments were more marked in the prodromal dementia than the stable cognition group (OR = 35.07; P < .001), as was executive dysfunction (OR = 7.16; P < .001). Disinhibition was greater in the AD than in the prodromal dementia group (OR = 3.54; P = .04). Apathy was more pronounced in the AD than in the stable cognition group (OR = 34.18; P < .001). CONCLUSION: Premorbid amnestic and non-amnestic symptoms as reported by informants increase with the progression to AD. For the formal diagnosis of AD in DS this progression of symptoms needs to be taken into account. An understanding of the unique clinical presentation of DS in AD should inform treatment options.

Toward identifying reproducible brain signatures of obsessive-compulsive profiles: rationale and methods for a new global initiative.

BACKGROUND: Obsessive-compulsive disorder (OCD) has a lifetime prevalence of 2-3% and is a leading cause of global disability. Brain circuit abnormalities in individuals with OCD have been identified, but important knowledge gaps remain. The goal of the new global initiative described in this paper is to identify robust and reproducible brain signatures of measurable behaviors and clinical symptoms that are common in individuals with OCD. A global approach was chosen to accelerate discovery, to increase rigor and transparency, and to ensure generalizability of results. METHODS: We will study 250 medication-free adults with OCD, 100 unaffected adult siblings of individuals with OCD, and 250 healthy control subjects at five expert research sites across five countries (Brazil, India, Netherlands, South Africa, and the U.S.). All participants will receive clinical evaluation, neurocognitive assessment, and magnetic resonance imaging (MRI). The imaging will examine multiple brain circuits hypothesized to underlie OCD behaviors, focusing on morphometry (T1-weighted MRI), structural connectivity (Diffusion Tensor Imaging), and functional connectivity (resting-state fMRI). In addition to analyzing each imaging modality separately, we will also use multi-modal fusion with machine learning statistical methods in an attempt to derive imaging signatures that distinguish individuals with OCD from unaffected siblings and healthy controls (Aim #1). Then we will examine how these imaging signatures link to behavioral performance on neurocognitive tasks that probe these same circuits as well as to clinical profiles (Aim #2). Finally, we will explore how specific environmental features (childhood trauma, socioeconomic status, and religiosity) moderate these brain-behavior associations. DISCUSSION: Using harmonized methods for data collection and analysis, we will conduct the largest neurocognitive and multimodal-imaging study in medication-free subjects with OCD to date. By recruiting a large, ethno-culturally diverse sample, we will test whether there are robust biosignatures of core OCD features that transcend countries and cultures. If so, future studies can use these brain signatures to reveal trans-diagnostic disease dimensions, chart when these signatures arise during development, and identify treatments that target these circuit abnormalities directly. The long-term goal of this research is to change not only how we conceptualize OCD but also how we diagnose and treat it.

Caudate volume differences among treatment responders, non-responders and controls in children with obsessive-compulsive disorder.

Treatment response in obsessive-compulsive disorder (OCD) is heterogeneous and the neurobiological underpinnings of such variability are unknown. To investigate this issue, we looked for differences in brain structures possibly associated with treatment response in children with OCD. 29 children with OCD (7-17 years) and 28 age-matched controls underwent structural magnetic resonance imaging. Patients then received treatment with fluoxetine or group cognitive-behavioral therapy during 14 weeks, and were classified as treatment responders or non-responders. The caudate nucleus, thalamus and orbitofrontal cortex were selected a priori, according to previous evidence of their association with OCD and its treatment. Gray matter (GM) volume comparisons between responders, non-responders and controls were performed, controlling for total GM volume. 17 patients were classified as responders. Differences among responders, non-responders and controls were found in both caudate nuclei (both p-values = 0.041), but after Bonferroni correction for multiple comparisons, these findings were non-significant. However, after excluding the effect of an outlier, findings were significant for the right caudate (p = 0.004). Pairwise comparisons showed larger caudate GM volume in responders versus non-responders and controls, bilaterally. The right caudate accounted for 20.2% of the variance in Y-BOCS changes after treatment in a linear regression model, with a positive correlation (p = 0.016). We present a possible neural substrate for treatment response in pediatric OCD, which is in line with previous evidence regarding the caudate nucleus. Considering the limitations, further research is needed to replicate this finding and elucidate the heterogeneity of treatment response in children with OCD (National Clinical Trials Registration Number: NCT01148316).

Cortical thickness in obsessive-compulsive disorder: multisite mega-analysis of 780 brain scans from six centres.

BACKGROUND: There is accumulating evidence for the role of fronto-striatal and associated circuits in obsessive-compulsive disorder (OCD) but limited and conflicting data on alterations in cortical thickness. AIMS: To investigate alterations in cortical thickness and subcortical volume in OCD. METHOD: In total, 412 patients with OCD and 368 healthy adults underwent magnetic resonance imaging scans. Between-group analysis of covariance of cortical thickness and subcortical volumes was performed and regression analyses undertaken. RESULTS: Significantly decreased cortical thickness was found in the OCD group compared with controls in the superior and inferior frontal, precentral, posterior cingulate, middle temporal, inferior parietal and precuneus gyri. There was also a group × age interaction in the parietal cortex, with increased thinning with age in the OCD group relative to controls. CONCLUSIONS: Our findings are partially consistent with earlier work, suggesting that group differences in grey matter volume and cortical thickness could relate to the same underlying pathology of OCD. They partially support a frontostriatal model of OCD, but also suggest that limbic, temporal and parietal regions play a role in the pathophysiology of the disorder. The group × age interaction effects may be the result of altered neuroplasticity.

Epigenetic evidence for involvement of the oxytocin receptor gene in obsessive-compulsive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a chronic neurodevelopmental disorder that affects up to 3% of the general population. Although epigenetic mechanisms play a role in neurodevelopment disorders, epigenetic pathways associated with OCD have rarely been investigated. Oxytocin is a neuropeptide involved in neurobehavioral functions. Oxytocin has been shown to be associated with the regulation of complex socio-cognitive processes such as attachment, social exploration, and social recognition, as well as anxiety and other stress-related behaviors. Oxytocin has also been linked to the pathophysiology of OCD, albeit inconsistently. The aim of this study was to investigate methylation in two targets sequences located in the exon III of the oxytocin receptor gene (OXTR), in OCD patients and healthy controls. We used bisulfite sequencing to quantify DNA methylation in peripheral blood samples collected from 42 OCD patients and 31 healthy controls. RESULTS: We found that the level of methylation of the cytosine-phosphate-guanine sites in two targets sequences analyzed was greater in the OCD patients than in the controls. The higher methylation in the OCD patients correlated with OCD severity. We measured DNA methylation in the peripheral blood, which prevented us from drawing any conclusions about processes in the central nervous system. CONCLUSION: To our knowledge, this is the first study investigating DNA methylation of the OXTR in OCD. Further studies are needed to evaluate the roles that DNA methylation and oxytocin play in OCD.

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.

Obsessive-compulsive symptoms are associated with psychiatric comorbidities, behavioral and clinical problems: a population-based study of Brazilian school children.

Pediatric-onset obsessive-compulsive disorder (OCD) is underdiagnosed, and many affected children are untreated. The present study seeks to evaluate the presence and the clinical impact of OCD and obsessive-compulsive symptoms (OCS) in a large sample of school-age children. In Phase I, we performed an initial screening using the Family History Screen (FHS). In Phase II, we identified an "at-risk" sample, as well as a randomly selected group of children. A total of 2,512 children (6-12 years old) were assessed using the FHS, the Development and Well-Being Assessment (DAWBA), the Strengths and Difficulties Questionnaire (SDQ), and the Child Behavior Checklist (CBCL). Data analyses included descriptive and multivariate analytical techniques. 2,512 children (mean age: 8.86 ± 1.84 years; 55.0% male) were categorized into one of the three diagnostic groups: OCD (n = 77), OCS (n = 488), and unaffected controls (n = 1,947). There were no significant socio-demographic differences (age, gender, socioeconomic status) across groups. The OCS group resembled the OCD on overall impairment, including school problems and delinquent behaviors. However, the OCD group did have significantly higher rates of several comorbid psychiatric disorders, including separation anxiety, generalized anxiety, and major depressive disorder, than OCS or unaffected controls. Moreover, the OCD group also scored higher than the SDQ, as well as on each of CBCL items rated by the parent. Our findings suggest that there is a psychopathological continuum between OCS and OCD in school-aged children. The presence of OCS is associated with functional impairment, which needs further investigation in longitudinal studies.

Brain structural correlates of sensory phenomena in patients with obsessive-compulsive disorder.

BACKGROUND: Sensory phenomena (SP) are uncomfortable feelings, including bodily sensations, sense of inner tension, "just-right" perceptions, feelings of incompleteness, or "urge-only" phenomena, which have been described to precede, trigger or accompany repetitive behaviours in individuals with obsessive-compulsive disorder (OCD). Sensory phenomena are also observed in individuals with tic disorders, and previous research suggests that sensorimotor cortex abnormalities underpin the presence of SP in such patients. However, to our knowledge, no studies have assessed the neural correlates of SP in patients with OCD. METHODS: We assessed the presence of SP using the University of São Paulo Sensory Phenomena Scale in patients with OCD and healthy controls from specialized units in São Paulo, Brazil, and Barcelona, Spain. All participants underwent a structural magnetic resonance examination, and brain images were examined using DARTEL voxel-based morphometry. We evaluated grey matter volume differences between patients with and without SP and healthy controls within the sensorimotor and premotor cortices. RESULTS: We included 106 patients with OCD and 87 controls in our study. Patients with SP (67% of the sample) showed grey matter volume increases in the left sensorimotor cortex in comparison to patients without SP and bilateral sensorimotor cortex grey matter volume increases in comparison to controls. No differences were observed between patients without SP and controls. LIMITATIONS: Most patients were medicated. Participant recruitment and image acquisition were performed in 2 different centres. CONCLUSION: We have identified a structural correlate of SP in patients with OCD involving grey matter volume increases within the sensorimotor cortex; this finding is in agreement with those of tic disorder studies showing that abnormal activity and volume increases within this region are associated with the urges preceding tic onset.

ORBITOFRONTAL THICKNESS AS A MEASURE FOR TREATMENT RESPONSE PREDICTION IN OBSESSIVE-COMPULSIVE DISORDER.

BACKGROUND: Early prediction of treatment response could reduce exposure to ineffective treatments and optimize the use of medical resources. Neuroimaging techniques have been used to identify biomarkers that are predictive of outcomes. The aims of this study were to investigate orbitofrontal cortex (OFC) thickness as a potential morphometric biomarker to discriminate outcomes in obsessive-compulsive disorder (OCD) and then to reexamine this biomarker in an independent cohort METHODS: Using a logistic regression model based on the mean baseline thickness of subregions of the OFC, we estimated the probability of treatment response in 29 treatment-naïve OCD patients who participated in a clinical trial. That algorithm was then tested in an independent cohort of 12 patients with a confirmed diagnosis of refractory OCD RESULTS: Among the treatment-naïve OCD patients, measures of OFC thickness statistically significantly differentiated responders (n = 13) and nonresponders (n = 16), with an overall classification accuracy of ≈80%, a sensitivity of 77% (10/13), and a specificity of 81% (13/16). Of the refractory OCD patients in the second independent cohort, 67% were correctly classified as nonresponders. The most discriminative measures in the initial cohort of treatment-naïve patients were the thicknesses of the left and right medial OFC (P = .009 and P = .028, respectively) CONCLUSIONS: We found OFC thickness to be a strong predictor of treatment response in treatment-naïve OCD patients. Although there are not yet any brain imaging biomarkers with clinical utility, our results highlight the potential of these measures as tools for predicting treatment outcomes in OCD.

Social skills in patients with obsessive-compulsive disorder before and after treatment.

OBJECTIVE: We aim to investigate whether: 1) social skills (SS) are impaired in obsessive-compulsive disorder (OCD); 2) SS would change over the course of treatment; and 3) severity of OCD, age of onset of OCD symptoms and illness duration would be associated with SS impairments. METHODS: 41 treatment-naive patients with OCD and 34 control participants (CP) were assessed using a SS inventory. Patients were reevaluated 12-weeks after standardized treatment. Group differences, as well as the treatment effect on OCD symptomatology over time, were analyzed with independent and paired tests, respectively. OCD severity, age at illness onset and illness duration were tested as predictors of SS. RESULTS: Patients had lower total SS scores compared to controls (p-value < 0.001). After treatment, although OCD symptomatology (p-value < 0.001) improved, there was no statistical difference in SS performance (p-value = 0.673). Earlier age of onset of OCD symptoms predicted worse SS total score (p-value = 0.016). CONCLUSION: This study suggests that, despite the amelioration of OCD symptomatology, there was no alteration in Social Skills (SS) performance. Subsequent treatment investigations incorporating larger sample sizes and extended follow-up periods could elucidate whether enhancements in social skills are likely to manifest over time.