Unmedicated Obsessive-compulsive Disorder Patients Research Articles

Hyperconnecitivity between dorsal attention and frontoparietal networks predicts treatment response in obsessive-compulsive disorder

Obsessive-compulsive disorder (OCD) presented with repetitive obsessions and/or compulsions were associated with disrupted resting-state functional connectivity (rs-FC). To investigate the pharmacological treatment effect on rs-FC changes in OCD patients we conducted the seed-to-voxel FC analyses using dorsal attention network (DAN), default mode network (DMN), salience network (SN) and frontoparietal network (FPN) and basal ganglia seeds. Twenty-two healthy subjects and twenty-four unmedicated OCD patients underwent resting-state functional magnetic resonance imaging. Patients were rescanned after 12 weeks of escitalopram treatment. We found increased FC both within the DAN and between the DAN and the FPN which was ameliorated after medication and correlated significantly with the clinical improvement in obsession scores. We also observed an anticorrelation between the left caudate and the supplementary motor area in unmedicated OCD patients which also normalized with treatment. Results further showed treatment related normalization of orbitofrontal cortex hyperconnectivity with DMN and hypoconnectivity with DAN whereas aberrant FC between the SN and visual areas appears to be a medication effect. We suggest that DAN to FPN hyperconnectivity which is positively correlated with clinical improvement in obsession scores at pre-treatment stage in present study has a potential for being a neuroimaging marker to predict the treatment response in OCD.

Associations of medication with subcortical morphology across the lifespan in OCD: Results from the international ENIGMA Consortium

BackgroundWidely used psychotropic medications for obsessive-compulsive disorder (OCD) may change the volumes of subcortical brain structures, and differently in children vs. adults. We measured subcortical volumes cross-sectionally in patients finely stratified for age taking various common classes of OCD drugs. MethodsThe ENIGMA-OCD consortium sample (1081 medicated/1159 unmedicated OCD patients and 2057 healthy controls aged 6–65) was divided into six successive 6–10-year age-groups. Individual structural MRIs were parcellated automatically using FreeSurfer into 8 regions-of-interest (ROIs). ROI volumes were compared between unmedicated and medicated patients and controls, and between patients taking serotonin reuptake inhibitors (SRIs), tricyclics (TCs), antipsychotics (APs), or benzodiazepines (BZs) and unmedicated patients. ResultsCompared to unmedicated patients, volumes of accumbens, caudate, and/or putamen were lower in children aged 6–13 and adults aged 50–65 with OCD taking SRIs (Cohen's d = −0.24 to −0.74). Volumes of putamen, pallidum (d = 0.18–0.40), and ventricles (d = 0.31–0.66) were greater in patients aged 20–29 receiving APs. Hippocampal volumes were smaller in patients aged 20 and older taking TCs and/or BZs (d = −0.27 to −1.31). ConclusionsResults suggest that TCs and BZs could potentially aggravate hippocampal atrophy of normal aging in older adults with OCD, whereas SRIs may reduce striatal volumes in young children and older adults. Similar to patients with psychotic disorders, OCD patients aged 20–29 may experience subcortical nuclear and ventricular hypertrophy in relation to APs. Although cross-sectional, present results suggest that commonly prescribed agents exert macroscopic effects on subcortical nuclei of unknown relation to therapeutic response.

Abnormal white-matter rich-club organization in obsessive-compulsive disorder.

Rich‐club organization is key to efficient global neuronal signaling and integration of information. Alterations interfere with higher‐order cognitive processes, and are common to several psychiatric and neurological conditions. A few studies examining the structural connectome in obsessive–compulsive disorder (OCD) suggest lower efficiency of information transfer across the brain. However, it remains unclear whether this is due to alterations in rich‐club organization. In the current study, the structural connectome of 28 unmedicated OCD patients, 8 of their unaffected siblings and 28 healthy controls was reconstructed by means of diffusion‐weighted imaging and probabilistic tractography. Topological and weighted measures of rich‐club organization and connectivity were computed, alongside global and nodal measures of network integration and segregation. The relationship between clinical scores and network properties was explored. Compared to healthy controls, OCD patients displayed significantly lower topological and weighted rich‐club organization, allocating a smaller fraction of all connection weights to the rich‐club core. Global clustering coefficient, local efficiency, and clustering of nonrich club nodes were significantly higher in OCD patients. Significant three‐group differences emerged, with siblings displaying highest and lowest values in different measures. No significant correlation with any clinical score was found. Our results suggest weaker structural connectivity between rich‐club nodes in OCD patients, possibly resulting in lower network integration in favor of higher network segregation. We highlight the need of looking at network‐based alterations in brain organization and function when investigating the neurobiological basis of this disorder, and stimulate further research into potential familial protective factors against the development of OCD.

Aberrant cortico-striatal white matter connectivity and associated subregional microstructure of the striatum in obsessive-compulsive disorder.

The striatum and its cortical circuits play central roles in the pathophysiology of obsessive-compulsive disorder (OCD). The striatum is subdivided by cortical connections and functions; however, the anatomical aberrations in different cortico-striatal connections and coexisting microstructural anomalies in striatal subregions of OCD patients are poorly understood. Thus, we aimed to elucidate the aberrations in cortico-striatal white matter (WM) connectivity and the associated subregional microstructure of the striatum in patients with OCD. From diffusion tensor/kurtosis imaging of 107 unmedicated OCD patients and 110 matched healthy controls (HCs), we calculated the cortico-striatal WM connectivity and segmented the striatum using probabilistic tractography. For the segmented striatal subregions, we measured average diffusion kurtosis values, which represent microstructural complexity. Connectivity and mean kurtosis values in each cortical target and associated striatal subregions were compared between groups. We identified significantly reduced orbitofrontal WM connectivity with its associated striatal subregion in patients with OCD compared to that in HCs. However, OCD patients exhibited significantly increased caudal-motor and parietal connectivity with the associated striatal subregions. The mean kurtosis values of the striatal subregions connected to the caudal-motor and parietal cortex were significantly decreased in OCD patients. Our results highlighted contrasting patterns of striatal WM connections with the orbitofrontal and caudal-motor/parietal cortices, thus supporting the cortico-striatal circuitry imbalance model of OCD. We suggest that aberrations in WM connections and the microstructure of their downstream regions in the caudal-motor-/parietal-striatal circuits may underlie OCD pathophysiology and further provide potential neuromodulation targets for the treatment of OCD.

Reduced T cell immunity in unmedicated, comorbidity-free obsessive-compulsive disorder: An immunophenotyping study

BackgroundImmune system aberrations have been postulated to play a role in the pathophysiology of Obsessive-compulsive disorder (OCD). This study was aimed to examine the profile of immune cell subsets in peripheral blood of un-medicated OCD patients. MethodThirteen drug-naïve/free OCD patients and twenty-six age & sex matched healthy controls were recruited. Immunophenotyping was carried out by staining the whole blood specimens with fluorescent monoclonal antibodies against the cell surface markers such as CD45, CD3, CD16, CD56, CD8, CD4, CD28, CD25 and CD127, followed by data acquisition on BD FACSVerse™ flow cytometer. The proportions of CD4 and CD8 T cells; T regulatory (Tregs), Natural Killer (NK) cells and NK-T cells were compared between patients with OCD and healthy control subjects. ResultsSignificantly reduced percentage of T regulatory (Treg) cells was observed in individuals with OCD compared to healthy control subjects [1.0 ± 0.7 vs. 1.9 ± 1.4; p = 0.03, r = 0.33]. ConclusionTreg cells play a crucial role in regulating the immune response, especially by suppressing the functional activities of T cells. In this study, decreased population of Treg cells essentially indicates a dysregulated T cell and/or T cell mediated immune activation in drug-naïve OCD patients. This preliminary observation might form the basis of further studies examining the immuno-inflammatory/autoimmune origin of OCD.

Network-based functional connectivity predicts response to exposure therapy in unmedicated adults with obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is associated with alterations in cortico-striato-thalamo-cortical brain networks, but some resting-state functional magnetic resonance imaging studies report more diffuse alterations in brain connectivity. Few studies have assessed functional connectivity within or between networks across the whole brain in unmedicated OCD patients or how patterns of connectivity predict response to exposure and ritual prevention (EX/RP) therapy, a first-line treatment for OCD. Herein, multiband resting-state functional MRI scans were collected from unmedicated, adult patients with OCD (n = 41) and healthy participants (n = 36); OCD patients were then offered twice weekly EX/RP (17 sessions). A whole-brain-network-based statistic approach was used to identify group differences in resting-state connectivity. We detected altered pre-treatment functional connectivity between task-positive regions in the temporal gyri (middle and superior) and regions of the cingulo-opercular and default networks in individuals with OCD. Signal extraction was performed using a reconstruction independent components analysis and isolated two independent subcomponents (IC1 and IC2) within this altered connectivity. In the OCD group, linear mixed-effects models tested whether IC1 or IC2 values predicted the slope of change in Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores across EX/RP treatment. Lower (more different from controls) IC2 score significantly predicted greater symptom reduction with EX/RP (Bonferroni-corrected p = 0.002). Collectively, these findings suggest that an altered balance between task-positive and task-negative regions centered around temporal gyri may contribute to difficulty controlling intrusive thoughts or urges to perform ritualistic behaviors.

Disrupted functional connectivity of precuneus subregions in obsessive-compulsive disorder

Obsessive-compulsive disorder (OCD) is a chronic and disablingpsychiatric disorder with high lifetime prevalence, yet the underlying pathogenesis remains not fully understood. Increasing neuroimaging evidence has shown that the disrupted activity of brain functional hubs might contribute to the pathophysiology of OCD. Precuneus is an important brain hub which showed structural and functional abnormalities in OCD patients. However, the functional heterogeneity of the precuneus subregion has not been considered and its relation to OCD symptomatology remains to be elucidated. In this paper, a total of 73 unmedicated OCD patients and 79 matched healthy subjects were recruited and the heterogeneous functional connectivities (FCs) of the precuneus subregions were investigated using resting-state functional magnetic resonance imaging. The FC-based subdivision of the precuneus was performed using the K-means clustering algorithm, which led to a tripartite functional parcellation of precuneus. For each subregion, the distinct connectivity pattern with the whole brain was shown, using both voxel-wise and module-wise analysis, respectively. Decreased FC between dorsal posterior precuneus and vermis (corrected p<0.01) was shown in the patient group, which was negatively correlated with patient compulsions score (ρ = − 0.393, p = 0.001), indicating its contribution to the compulsive behavior inhibition of OCD. Our work might provide new insights into the understanding of precuneus subregion function and the importance of dorsal precuneus-cerebellum functional connectivity in OCD pathophysiology.

Disrupted pathways from the frontal-parietal cortices to basal nuclei and the cerebellum are a feature of the obsessive-compulsive disorder spectrum and can be used to aid in early differential diagnosis

A marker for distinguishing patients with obsessive-compulsive disorder (OCD) spectrum has not yet been identified. Whole-brain resting-state effective and functional connectivity (rsEC and rsFC, respectively) networks were constructed for 50 unmedicated OCD (U-OCD) patients, 45 OCD patients in clinical remission (COCD), 47 treatment-resistant OCD (T-OCD) patients, 42 chronic schizophrenia patients who exhibit OCD symptoms (SCHOCD), and 50 healthy controls (HCs). Multivariate pattern analysis (MVPA) was performed to investigate the accuracy of using connectivity alterations to distinguished among the aforementioned groups. Compared to HCs, rsEC connections were significantly disrupted in the U-OCD (n = 15), COCD (n = 8), and T-OCD (n = 19) groups. Additionally, 21 rsEC connections were significantly disrupted in the T-OCD group compared to the SCHOCD group. The disrupted rsEC networks were associated mainly with the frontal-parietal cortex, basal ganglia, limbic regions, and the cerebellum. Classification accuracies for distinguishing OCD patients from HCs and SCHOCD patients ranged from 66.6% to 98.0%. In conclusion, disrupted communication from the frontal-parietal cortices to subcortical basal nuclei and the cerebellum may represent a functional pathological feature of the OCD spectrum. MVPA based on both abnormal rsEC and rsFC patterns may aid in early differential diagnosis of OCD.

The effects of cognitive behavioral therapy on the whole brain structural connectome in unmedicated patients with obsessive-compulsive disorder

Cognitive behavioral therapy (CBT) is considered a first-line treatment for patients with obsessive-compulsive disorder (OCD), and it possesses advantages over pharmacological treatments in stronger tolerance to distress, lower rates of drop out and relapse, and no physical “side-effects”. Previous studies have reported CBT-related alterations in focal brain regions and connections. However, the effects of CBT on whole-brain structural networks have not yet been elucidated. Here, we collected diffusion MRI data from 34 unmedicated OCD patients before and after 12 weeks of CBT. Fifty healthy controls (HCs) were also scanned twice at matched intervals. We constructed individual brain white matter connectome and performed a graph-theoretical network analysis to investigate the effects of CBT on whole-brain structural topology. We observed significant group-by-time interactions on the global network clustering coefficient and the nodal clustering of the left lingual gyrus, the left middle temporal gyrus, the left precuneus, and the left fusiform gyrus of 26 CBT responders in OCD patients. Further analysis revealed that these CBT responders showed prominently higher global and nodal clustering compared to HCs at baseline and reduced to normal levels after CBT. Such significant changes in the nodal clustering of the left lingual gyrus were also found in 8 CBT non-responders. The pre-to-post decreases in nodal clustering of the left lingual gyrus and the left fusiform gyrus positively correlated with the improvements in obsessive-compulsive symptoms in the CBT-responding patients. These findings indicated that the network segregation of the whole-brain white matter network in OCD patients was abnormally higher and might recover to normal after CBT, which provides mechanistic insights into the CBT response in OCD and potential imaging biomarkers for clinical practice.

Evidence for trial-by-trial dynamic adjustment of task control in unmedicated adults with OCD

According to the conflict monitoring theory, executive control requires two separable processes: conflict-monitoring and conflict-resolution. Deficits in executive control have been observed in adults with obsessive-compulsive disorder (OCD). However, it is not yet clear whether these deficits can be attributed to deficits in conflict-monitoring, in conflict-resolution, or in both. We examined this question by administrating the Simon task to 67 unmedicated adults with OCD and 67 matched controls. The interference effect (incongruent minus congruent) was used to measure conflict-resolution. Trial-by-trial dynamic adaptation (i.e., the Gratton effect), which is indicated by smaller interference effect after conflict-laden trials compared to after non-conflict-laden trials, was used to measure conflict-monitoring. A similar interference effect was found in both the OCD and HC groups with no significant between group differences. Following incongruent trials, the interference effect became smaller for the control group as expected, but was completely eliminated for the OCD group. These data add to the accumulating evidence indicating that conflict-resolution is not globally deficient in unmedicated OCD patients and provide direct evidence that conflict-monitoring is heightened in OCD patients. Our results challenge the assumption of cognitive inflexibility in OCD and highlight the importance of studying unmedicated subjects when investigating executive control.

Static and dynamic network properties of the repetitive transcranial magnetic stimulation target predict changes in emotion regulation in obsessive-compulsive disorder

BackgroundRepetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation technique to treat psychiatric disorders, such as obsessive-compulsive disorder (OCD). However, the rTMS response varies across subjects. Objective/hypothesisWe hypothesize that baseline network properties of the rTMS target may help understand this variation and predict response. MethodsExcitatory rTMS to the dorsolateral prefrontal cortex (dlPFC) was applied in 19 unmedicated OCD patients, while inhibitory dlPFC-rTMS was applied in 17 healthy controls. The vertex was used as an active control target (19 patients, 18 controls). The rTMS response was operationalized as the individual change in state distress rating during an emotion regulation task. At baseline, subjects underwent resting-state functional MRI. The brain network was constructed by calculating wavelet coherence between regional activity of regions in the Brainnetome atlas. Local and integrative static connectivity and the dynamic network role of the target were calculated. Baseline target region network features were non-parametrically correlated to rTMS response. ResultsIn the dlPFC-stimulated patients, greater local connectivity (Kendall’s Tau = −0.415, p = 0.013) and less promiscuous role of the target (Kendall’s Tau = 0.389, p = 0.025) at baseline were related to greater distress reduction after excitatory rTMS. There were no significant associations in healthy subjects nor in the active control stimulated patients. ConclusionsPre-treatment network topological indices predict rTMS-induced emotional response changes in OCD, such that greater baseline resting-state local connectivity and less temporal integration of the target region imply greater stimulation effects. These results may lead the way towards personalized neuromodulation in OCD.

Abnormal Regional Homogeneity in Patients With Obsessive-Compulsive Disorder and Their Unaffected Siblings: A Resting-State fMRI Study.

Objective: Previous studies suggest that abnormal brain structure and function may be neuroimaging endophenotypes of obsessive-compulsive disorder (OCD). Comparing the intrinsic brain activity of OCD patients and their unaffected siblings will help to further understand the susceptibility to, and pathological mechanisms of, OCD. We used a case–control study design aiming to establish whether the abnormal regional homogeneity (ReHo) found in OCD patients also exists in their unaffected siblings. Method: Fifteen unmedicated OCD patients, 15 of their unaffected siblings, and 30 healthy controls (HCs) received resting-state functional magnetic resonance imaging (r-s fMRI) scanning and clinical evaluation. We used the ReHo method to analyze the inter-regional synchronized activity of all participants. One-way analysis of covariance with post hoc tests was used to compare the ReHo maps across groups. A Pearson correlation analysis was conducted to assess the correlations between clinical characteristics and abnormal ReHo in OCD patients. Results: Relative to HCs, OCD patients and their unaffected siblings showed overlapping higher ReHo values in the right dorsolateral prefrontal cortex (DLPFC). Patients with OCD showed increased ReHo in left middle frontal gyrus (MFG) relative to both their unaffected siblings and HCs. In addition to the right DLPFC and left MFG, OCD patients, compared with HCs, also showed abnormal ReHo in other regions, including higher ReHo in the right superior parietal cortex and lower ReHo in the left inferior parietal cortex, right parahippocampal region, left thalamus, and right inferior temporal cortex. Compared with HCs, the unaffected siblings of patients with OCD had significantly higher ReHo in the right inferior parietal cortex, right MFG, and right supplementary motor area. There was no association between clinical symptoms and abnormal ReHo values in OCD patients. Conclusions: This study found overlapping higher ReHo values in the right DLPFC of OCD patients and their unaffected siblings. Our results suggest that the higher ReHo in the right DLPFC may be a potential neuroimaging endophenotype, which may reflect an increased genetic risk of OCD.

Brain neurochemistry in unmedicated obsessive-compulsive disorder patients and effects of 12-week escitalopram treatment: 1 H-magnetic resonance spectroscopy study.

The purpose of this study was to examine treatment-related neurochemical changes in 28 unmedicated obsessive-compulsive disorder (OCD) patients using 1 H-magnetic resonance spectroscopy (1 H-MRS). We included subjects diagnosed with OCD (n = 28), each with a total duration of illness of less than 5 years, as a study group and age- and sex-matched healthy controls (n = 26). The inclusion criteria for the OCD group were right-handed individuals aged 18 years or older who had not been on any specific treatment for OCD for the last at least 8 weeks and who had no other psychiatric comorbidity. A pre-post and case-control design was employed in which OCD patients underwent 1 H-MRS at baseline and 12 weeks after treatment with escitalopram (n = 21). Clinical assessment was carried out using a semi-structured pro forma Yale-Brown Obsessive Compulsive Scale and the World Health Organization Disability Assessment Scale 2.0 before and after treatment. Volume-localized 1 H-MRS was carried out with a 3-Tesla Philips MR scanner. Our data suggested higher levels of myoinositol (mI), total choline (tCho), and glutamate+glutamine (Glx) in the medial thalamus at pre-assessment in OCD subjects as compared to healthy controls and a significant reduction in tCho and Glx after treatment in OCD subjects. The mI levels in the caudate nucleus and Glx levels in the anterior cingulate cortex were significantly correlated with disease severity on the Yale-Brown Obsessive Compulsive Scale. Our study supports the hypothesis of a hyper-glutaminergic state (as suggested by increased Glx levels) and neurodegeneration (as suggested by increased tCho and mI in the thalamus) in cortico-striato-thalamocortical circuitry in OCD patients as suggested by previous studies using MRS as well as other functional imaging studies.

The comparison of risky and ambiguity decision making and cool executive functions between patients with obsessive compulsive disorder and healthy controls

Background: Executive functioning has been evaluated in obsessive compulsive disorder (OCD). Cool and hot executive functioning discrimination provided a different way of conceptualising executive functions. Objectives: The aim of this study was to compare ambiguity and risky decision-making and cool executive functions in an OCD and a healthy control group. The relationship between decision-making and cool executive functioning was investigated. Methods: Sixty-two OCD patients and 48 healthy control participants were compared. Decision-making was measured using the Iowa Gambling Task. The cool executive functioning was assessed using the Stroop Test and the Wisconsin Card Sorting Task (WCST). Results: The OCD group completed the WCST and the Stroop Test statistically significantly with a lower score than that of the control group. The OCD group had impaired response inhibition and set-shifting that indicate impaired cool executive functioning. In contrast to a lack of a statistically significant difference, the risky decision-making performance was worse in the OCD group than in the healthy control group and in the unmedicated OCD patients than in the medicated OCD patients. Discussion: The OCD patients had a poorer performance in risky decision-making and cool executive functioning. There was a link between risky decision-making performance and impaired cool executive functions.

Altered Fractional Amplitude of Low Frequency Fluctuations in Unmedicated Female Patients with Obsessive-Compulsive Disorder.

A number of resting-state functional magnetic resonance imaging (rs-fMRI) studies indicate dysfunction of large-scale brain networks underlying the pathophysiology of obsessive-compulsive disorder (OCD). Recent epidemiology studies show that the prevalence of female OCD patients is higher than that of males. However, the underlying neurobiology mechanism for female OCD patients remains not fully understood. In this study, we are aimed to explore the spontaneous brain neuronal activity in unmedicated female OCD patients using rs-fMRI methodology and fractional amplitude of low frequency fluctuations (fALFF) analysis. Additionally, we examine the relationship between fALFF changes and female OCD symptomatology. Increased fALFF values in right brainstem, right rectus, left middle temporal gyrus and right angular were found in OCD females. And decreased fALFF values in right cerebellum, left middle occipital gyrus, left insula, postcentral gyrus and left precentral gyrus were shown in female OCD patients. Moreover, the fALFF values in left precentral gyrus and left middle temporal gyrus were positively associated with patients YBOCS-Obsessions scores and HAMD scores, respectively. Our findings bring additional insights in understanding the pathophysiology of female OCD patients.

CAN EXPOSURE-BASED CBT EXTEND IV KETAMINE’S EFFECTS IN OCD? AN OPEN-LABEL TRIAL

Abtract Introduction A single subanesthetic intravenous (IV) dose of ketamine leads to rapid anti-obsessional effects in obsessive-compulsive disorder (OCD) patients with near-constant intrusive obsessions, but these effects usually do not persist. We tested whether a brief course of exposure-based cognitive behavioral therapy (CBT) could extend ketamine’s effects in a two week pilot open trial and if this effect was maintained (without additional treatment) two weeks later. Our rationale was: 1) ketamine is reported to enhance plasticity and extinction learning in rodents, and 2) enhanced extinction learning may facilitate CBT gains, as reported in trials that combined CBT with agents thought to facilitate extinction learning (e.g. D-cycloserine). Mimicking those trials, CBT was abbreviated (i.e. 10 one-hour exposure sessions) but delivered during the putative time interval when ketamine facilitates extinction learning (within 14 days). Methods Ten unmedicated OCD outpatients (aged 18-55) with near-constant intrusive obsessions (>8 hours/day) and at least moderate symptoms (Y-BOCS score ≥16) were recruited. Exclusion criteria included severe depression (HDRS >25), current CBT, and comorbid psychiatric or medical conditions that made participation unsafe. In an open-label design, participants received a single 40-minute IV infusion of ketamine (dose=0.5 mg/kg), followed by 10 one-hour exposure sessions delivered over two weeks. The CBT treatment was planned in a 90-minute session the day before the ketamine infusion. At baseline, during the infusion, at 20, 90, 110, 230 minutes post-infusion, patients rated their obsessional severity using the OCD-VAS. At baseline and weekly for four weeks post-ketamine, an independent evaluator, blind to study design, evaluated patients using the Y-BOCS, which appraises obsessive and compulsive symptoms over the prior week. Treatment response was defined a priori as ≥35% Y-BOCS reduction at week 2. Y-BOCS outcomes were analyzed using mixed-effects regression to model symptoms as a function of time. Results Of the 10 patients who started ketamine, nine completed the infusion. Eight reported a rapid reduction in obsessive severity as measured by the OCD-VAS, which persisted up to 230 minutes post-infusion in seven patients. Eight completed the 10 hours of exposure and the two week follow-up and were included in the Y-BOCS analyses. From baseline to four weeks post-infusion, OCD severity, as measured by the YBOCS, was significantly decreased over time (F=14.36, df=4,28, p Conclusions These results corroborate prior findings that IV ketamine can rapidly reduce obsessions in unmedicated OCD patients. The data suggest that a brief course of CBT may help some individuals maintain the improvement they experienced from ketamine; however, this needs to be formally tested in a randomized controlled trial to determine whether the improvement seen after two weeks of CBT is due to the addition of CBT, or whether the effects of ketamine persist longer in some than previously described.

Anterior thalamic radiation structural and metabolic changes in obsessive-compulsive disorder: A combined DTI-MRS study

Numerous studies indicate the cortico-striato-thalamo-cortical (CSTC) circuit plays an important role in the pathophysiology of obsessive-compulsive disorder (OCD). The anterior thalamic radiation (ATR), as a major fiber in the fronto-thalamic circuitry, contributes to symptomology of OCD. However, the underlying biochemical mechanism in relation with its structural alteration remains not understood. This study investigated the structural abnormality of ATR and its correlation with thalamic metabolic alteration in OCD, using diffusion tensor image (DTI) and proton magnetic resonance spectroscopy (1H-MRS). Twenty-six unmedicated adult OCD patients and twenty-six matched healthy controls participated in DTI study. Thirteen OCD patients and thirteen healthy controls, a subset of DTI participants, took part in MRS study. The results showed that mean fiber length of right ATR negatively correlated with ipsilateral thalamic choline (Cho) level in OCD patients. Additionally, significantly higher Cho concentration was detected in right thalamus of OCD patients compared to healthy controls. Moreover, the mean fractional anisotropy (FA) value of right ATR positively correlated with patients Yale–Brown Obsessive Compulsive Scale (YBOCS) total score, as well as YBOCS compulsion score. These results suggested the coupling of structural and metabolic changes in right ATR, which might serve as a multi-modal biomarker contributing to the pathogenesis of OCD.

Schizotypy and smooth pursuit eye movements as potential endophenotypes of obsessive-compulsive disorder.

Patients with obsessive-compulsive disorder (OCD) show dysfunctions of the fronto-striatal circuitry, which imply corresponding oculomotor deficits including smooth pursuit eye movements (SPEM). However, evidence for a deficit in SPEM is inconclusive, with some studies reporting reduced velocity gain while others did not find any SPEM dysfunctions in OCD patients. Interestingly, psychosis-like traits have repeatedly been linked to both OCD and impaired SPEM. Here, we examined a large sample of n = 168 patients with OCD, n = 93 unaffected first-degree relatives and n = 171 healthy control subjects to investigate whether elevated levels of schizotypy and SPEM deficits represent potential endophenotypes of OCD. We applied a SPEM task with high demands on predictive pursuit that is more sensitive to assess executive dysfunctions than a standard task with continuous visual feedback, as episodes of target blanking put increased demands on basal ganglia and prefrontal involvement. Additionally, we examined the relation between schizotypy and SPEM performance in OCD patients and their relatives. Results indicate that OCD patients and unaffected relatives do not show deficient performance in either standard or predictive SPEM. Yet, both patients and relatives exhibited elevated levels of schizotypy, and schizotypy was significantly correlated with velocity gain during standard trials in unmedicated and depression-free OCD patients. These findings highlight the role of schizotypy as a candidate endophenotype of OCD and add to the growing evidence for predisposing personality traits in OCD. Furthermore, intact gain may represent a key characteristic that distinguishes the OCD and schizophrenia patient populations.

Amygdala-prefrontal connectivity during appraisal of symptom-related stimuli in obsessive-compulsive disorder.

Cognitive models of obsessive-compulsive disorder (OCD) posit dysfunctional appraisal of disorder-relevant stimuli in patients, suggesting disturbances in the processes relying on amygdala-prefrontal connectivity. Recent neuroanatomical models add to the traditional view of dysfunction in corticostriatal circuits by proposing alterations in an affective circuit including amygdala-prefrontal connections. However, abnormalities in amygdala-prefrontal coupling during symptom provocation, and particularly during conditions that require stimulus appraisal, remain to be demonstrated directly. Amygdala-prefrontal connectivity was examined in unmedicated OCD patients during appraisal (v. distraction) of symptom-provoking stimuli compared with an emotional control condition. Subsequent analyses tested whether hypothesized connectivity alterations could be also identified during passive viewing and the resting state in two independent samples. During symptom provocation, reductions in positive coupling between amygdala and orbitofrontal cortex were observed in OCD patients relative to healthy control participants during appraisal and passive viewing of OCD-relevant stimuli, whereas abnormally high amygdala-ventromedial prefrontal cortex coupling was found when appraisal was distracted by a secondary task. In contrast, there were no group differences in amygdala connectivity at rest. Our finding of abnormal amygdala-prefrontal connectivity during appraisal of symptom-related (relative to generally aversive) stimuli is consistent with the involvement of affective circuits in the functional neuroanatomy of OCD. Aberrant connectivity can be assumed to impact stimulus appraisal and emotion regulation, but might also relate to fear extinction deficits, which have recently been described in OCD. Taken together, we propose to integrate abnormalities in amygdala-prefrontal coupling in affective models of OCD.

Emotion Regulation in Obsessive-Compulsive Disorder, Unaffected Siblings, and Unrelated Healthy Control Participants

BackgroundFunctional neuroimaging endophenotypes of obsessive-compulsive disorder (OCD) have been suggested during executive tasks. The purpose of this study was to investigate whether behavioral and neural responses during emotion processing and regulation also represent an endophenotype of OCD. MethodsForty-three unmedicated adult OCD patients, 19 of their unaffected siblings, and 38 healthy control participants underwent 3T functional magnetic resonance imaging during an emotion regulation task including neutral, fear-inducing, and OCD-related visual stimuli. Stimuli were processed during natural appraisal and during cognitive reappraisal, and distress ratings were collected after each picture. We performed between-group comparisons on task behavior and brain activation in regions of interest during emotion provocation and regulation. ResultsSiblings reported similar distress as healthy control participants during provocation, and significantly less than patients. There was no significant three-group difference in activation during fear provocation or regulation. Three-group comparisons showed that patients had higher amygdala and dorsomedial prefrontal cortex activation during OCD-related emotion provocation and regulation, respectively, while siblings were intermediate between patients and control participants but not significantly different from either. Siblings showed higher left temporo-occipital activation (compared with both healthy control participants and patients) and higher frontolimbic connectivity (compared with patients) during OCD-related regulation. ConclusionsUnaffected siblings do not show the same distress and amygdala activation during emotional provocation as OCD patients. Siblings show distinct activation in a temporo-occipital region, possibly related to compensatory cognitive control. This suggests that emotion regulation is not a strong endophenotype for OCD. When replicated, this contributes to our understanding of familial risk and resilience for OCD.