Obsessive-compulsive Disorder Subjects Research Articles

Potential biomarkers and therapeutic targets for obsessive compulsive disorder: Evidences from clinical studies.

Obsessive compulsive disorder (OCD) is a prevalent behavioral disorder with a complex etiology. However, the underlying pathogenic molecular pathways and the associated risk factors are largely obscure. This has hindered both the identification of relevant prognostic biomarkers and the development of effective treatment strategies. Because of the diverse range of clinical manifestations, not all patients benefit from therapies currently practiced in the clinical setting. Nevertheless, several lines of evidence indicate that neurotrophic, neurotransmitter, and oxidative signaling are involved in the pathophysiology of OCD. Based upon evidences from clinical (and pre-clinical studies), the present review paper sets out to decipher the utilities of three parameters (i.e. brain-derived neurotrophic factor; BDNF, noradrenalin-synthesizing enzyme dopamine beta-hydroxylase; DBH; and oxidative damage marker malondialdehyde; MDA) as diagnostic peripheral biomarkers as well as bio-targets for therapeutic strategies. While the data indicates promising results, there is necessitation for future studies to further confirm and establish these. Further, based again on the available clinical data, we investigated the possibilities of exploiting the etiological links between disruptions in the sleep-wake cycle and insulin signaling, and OCD for the identification of potential anti-OCD ameliorative agents with the ability to elicit multimodal effects, including attenuation of the alterations in BDNF, noradrenergic and redox pathways. In this respect, agomelatine and metformin may represent particularly interesting candidates; however, further clinical studies are warranted to establish these as singular or complementary medications in OCD subjects.

Mechanisms underlying capsulotomy for refractory obsessive-compulsive disorder: neural correlates of negative affect processing overlap with deep brain stimulation targets

Ablative procedures such as anterior capsulotomy are potentially effective in refractory obsessive-compulsive disorder (OCD). Converging evidence suggests the ventral internal capsule white matter tracts traversing the rostral cingulate and ventrolateral prefrontal cortex and thalamus is the optimal target for clinical efficacy across multiple deep brain stimulation targets for OCD. Here we ask which prefrontal regions and underlying cognitive processes might be implicated in the effects of capsulotomy by using both task fMRI and neuropsychological tests assessing OCD-relevant cognitive mechanisms known to map across prefrontal regions connected to the tracts targeted in capsulotomy. We tested OCD patients at least 6 months post-capsulotomy (n = 27), OCD controls (n = 33) and healthy controls (n = 34). We used a modified aversive monetary incentive delay paradigm with negative imagery and a within session extinction trial. Post-capsulotomy OCD subjects showed improved OCD symptoms, disability and quality of life with no differences in mood or anxiety or cognitive task performance on executive, inhibition, memory and learning tasks. Task fMRI revealed post-capsulotomy decreases in the nucleus accumbens during negative anticipation, and in the left rostral cingulate and left inferior frontal cortex during negative feedback. Post-capsulotomy patients showed attenuated accumbens-rostral cingulate functional connectivity. Rostral cingulate activity mediated capsulotomy improvement on obsessions. These regions overlap with optimal white matter tracts observed across multiple stimulation targets for OCD and might provide insights into further optimizing neuromodulation approaches. Our findings also suggest that aversive processing theoretical mechanisms may link ablative, stimulation and psychological interventions.

Behavioural addictions in obsessive compulsive disorder – Prevalence and clinical correlates

Behavioural addictions (BAs) share phenomenological overlap and neuropsychological similarities with obsessive-compulsive disorder (OCD); however, the relationship remains understudied. This study reports the prevalence of BAs in patients with OCD and healthyxcontrols (HCs). It compares the clinical characteristics including impulsivity traits among OCD subjects with and without BAs. A total of 150 OCD patients and 131 ​HCs were assessed using structured instruments for the following BAs (Internet/Sex/Pornography/Mobile phone/Kleptomania/Compulsive buying/Pyromania/Gambling/Food/Exercise). Impulsivity was assessed using Barratt Impulsiveness Scale (BIS-11). with OCD reported significantly higher prevalence of atleast one co-occurring BA compared to HC [OCD (70%); HC (58%), p ​< ​0.036]. They also reported a significantly higher prevalence of Internet Addiction (29.3% vs 3.1%), pornographic addiction (12.7% vs 0%), and sex addiction (10% vs 1.5%). Though use of mobile phone use and food addiction were not significantly different when compared using the diagnostic criteria, subjects with OCD reported significantly higher intensity of symptoms when comparison was made using severity scores. When OCD patients with and without BAs were compared, those with BAs were significantly male, with a lower age at onset and assessment. They had significantly higher total impulsivity scores, motor and attentional sub-scale scores on BIS. The two groups did not differ in symptom profile and comorbidities of OCD. To conclude, the co-occurrence of BAs among subjects with OCD is common. Additionally, OCD subjects with co-occurring BAs have certain specific demographic characteristics and higher impulsivity. • Behavioural addictions (BAs) in OCD subjects and healthyxcontrols were examined. • OCD subjects had higher prevalence of internet, pornographic and sex addiction. • OCD subjects with BAs when compared to those without were more likely to be male. • They also had lower age of onset, assessment and significantly higher impulsivity.

GDNF rs2910702, rs3096140, and rs3812047 polymorphisms in obsessive compulsive disorder: Preliminary study

The neurobiology of obsessive-compulsive disorder (OCD) is evidenced by a strong demonstration of malfunctions in the serotonergic and dopaminergic system. Recently, glial cell line-derived neurotrophic factor (GDNF) gene polymorphisms have been emphasized in psychiatric diseases and treatment strategies that have been tried to be developed in this regard. In the literature, there are several studies investigating the relationship between GDNF gene polymorphisms and psychiatric diseases excluding OCD. Therefore, this study aimed to compare the symptomatology and GDNF gene polymorphisms in early and late-onset OCD patients. For this purpose, patients diagnosed with OCD according to DSM-V diagnostic criteria in structured clinical interviews were grouped as early and late-onset based on the age of initiation. DNA was isolated from blood samples collected from 140 subjects (70 OCD and 70 healthy controls) in EDTA tubes, and rs2910702, rs3096140, and rs3812047 polymorphisms in GDNF gene were examined by Real-Time PCR. No significant correlation was detected between GDNF and the rs2910702, rs3096140, and rs3812047 polymorphisms in early and late-onset OCD subjects (P&gt;0.05). Failure to detect correlations between OCD and GDNF gene polymorphisms might be due to the variable expression pattern of the GDNF gene in different tissues and pathologies. Therefore, future studies might be improved by including a larger group of patients and examining a wider range of tissues for the expression pattern of GDNF.

Validation of Symptom Dimensions and Sub-Type Responses in Cognitive Behavioral Therapy in Obsessive Compulsive Disorder: A Systemic Review and Meta-Analysis

Background: Obsessive-compulsive disorder (OCD) is a clinically heterogeneous condition without a conclusive subtype dimension. This study will focus on the meta-analysis of the clinical responses of OCD subtypes to cognitive behavioral therapy (CBT), which might clarify this issue. Methods: We performed a systematic search and a meta-analysis for the studies of OCD subtypes and the response to CBT in PubMed, ScienceDirect, Embase, Web of Science, and Scopus databases. The selective criteria were the OCD without significant medical or psychiatric co-morbidities and pre-and post-treatment changes in scores of OCD dimension. In addition, different subtypes of OCD in symptom dimensions, such as symmetry, contamination, unacceptable thoughts, and hoarding, were compared to find the most significant subtype using the treatment response parameters by CBT. After limited selection, four studies and 479 OCD subjects were enrolled. The meta-analysis was performed by Review Manager 5.4, and only significant results were reported. Results: Among the OCD subtypes, the meta-analysis favors the hoarding subtype with poorer responses to CBT than symmetry, contamination, and unacceptable thoughts. The meta-analysis results were negative mean differences, significant tests for overall effect, and limited heterogeneities in the random effects model. In addition, the results were more significant when the hoarding subtype was compared with non-hoarding subtypes. Conclusion: The hoarding subtype might be the most significant representative subtype of OCD symptom dimension under the impression of unfavorable clinical response to CBT. However, future studies with more treatment parameters will be warranted to confirm this finding.

Dysfunctional Metacognitive Beliefs in Patients With Obsessive-Compulsive Disorder and Pattern of Their Changes Following a 3-Month Treatment.

Introduction: Metacognitions are considered to be crucial factors for the development and maintenance of pathologic anxiety. The present case–control study aimed to examine how metacognitive beliefs are associated with the diagnostic status and subtypes of obsessive–compulsive disorder (OCD). In addition, we examined the pattern of changes in metacognitive beliefs after a 3-month pharmacological treatment in patients with OCD.Methods: A total of 562 cases with OCD and 236 healthy controls were assessed with the Metacognitions Questionnaire (MCQ) and various measures of OC symptom severity. Multivariate analyses of variance (MANOVAs) with covariates were conducted to explore the relationship between subdimensions of metacognitive beliefs and OCD disease status. In addition, for the OCD patients, Pearson's correlation was performed between baseline MCQ subdimensions and Obsessive–Compulsive Inventory-Revised-Korean subscales (OCI-R-K). Finally, in a subset of drug-free OCD patients (n = 144), the MCQ was reassessed after 3 months of treatment and patterns of changes in subdimensions of the MCQ were examined.Results: Patients with OCD scored significantly higher on the four dimensions of the MCQ. There were significant associations between all MCQ subdimensions and OCI-R-K subscales. In the repeated-measure MANOVA, a significant group (non-responders vs. responders)-by-time interaction effect was found only for the negative beliefs about the uncontrollability and danger of worry (NB) subdimension (F = 10.75; η2 = 0.072; p = 0.001).Conclusion: The presence of dysfunctional metacognitive beliefs in OCD subjects and their association with OCD characteristics suggest that dysfunctional metacognitions may play a crucial role in the pathophysiology of OCD. Improvement of metacognitive beliefs in the NB dimension may be a clinically meaningful correlate of good treatment response in the pharmacological treatment of OCD.

Epigenetic modulation in obsessive-compulsive disorder: Methylation and hydroxymethylation of the bdnf gene exon I promoter

IntroductionSeveral evidence recognizes Brain Derived Neurotrophic Factor (BDNF) as a promising biomarker in the pathophysiology of psychiatric disorders, including Obsessive-Compulsive Disorder (OCD), considering the involvement of epigenetic regulation in BDNF altered expression.ObjectivesThis study aims to investigate, in a sample of OCD patients, the epigenetic modulation in terms of levels of methylation and hydroxymethylation on the BDNF gene exon I promoter.MethodsFifty OCD patients, recruited from Psychiatry Unit 2, Sacco University Hospital in Milan and fifty healthy controls, comparable by age and gender. Saliva samples were collected by oral swab and epigenetic analysis were performed at the University of Teramo. Statistical analyses were performed with t test with Bonferroni correction.ResultsData analysis showed a significant decrease in 5-methyl cytosine levels (5mC) (mean OCD: 1.221%; mean CTRL: 1.784%; p &lt; 0.001) and a significant increase in 5-Hydroxy-methyl cytosine levels (5hmC) (mean OCD: 1.018%; mean CTRL: 0.527% p&lt; 0.0001) in BDNF gene exon I promoter of OCD patients compared to controls. Regarding 5mC of site 3 and 5hmC of site 1 and 2 of the exon I promoter CpG islands, no statistical significance was found.ConclusionsPresent results showed significant differences in epigenetic modulation of BDNF gene, which might not be univocally interpreted. They could represent an intrinsic OCD characteristic or the effect of antidepressant drugs, assumed by all recruited patients. Further studies, comparing OCD subjects in treatment vs drug-free, are necessary to define BDNF epigenetic modulation role and its possible use as biomarker in the characterization of OCD.DisclosureNo significant relationships.

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.

Transcriptome alterations are enriched for synapse-associated genes in the striatum of subjects with obsessive-compulsive disorder

Obsessive-compulsive disorder (OCD) is a chronic and severe psychiatric disorder for which effective treatment options are limited. Structural and functional neuroimaging studies have consistently implicated the orbitofrontal cortex (OFC) and striatum in the pathophysiology of the disorder. Recent genetic evidence points to involvement of components of the excitatory synapse in the etiology of OCD. However, the transcriptional alterations that could link genetic risk to known structural and functional abnormalities remain mostly unknown. To assess potential transcriptional changes in the OFC and two striatal regions (caudate nucleus and nucleus accumbens) of OCD subjects relative to unaffected comparison subjects, we sequenced messenger RNA transcripts from these brain regions. In a joint analysis of all three regions, 904 transcripts were differentially expressed between 7 OCD versus 8 unaffected comparison subjects. Region-specific analyses highlighted a smaller number of differences, which concentrated in caudate and nucleus accumbens. Pathway analyses of the 904 differentially expressed transcripts showed enrichment for genes involved in synaptic signaling, with these synapse-associated genes displaying lower expression in OCD subjects relative to unaffected comparison subjects. Finally, we estimated that cell type fractions of medium spiny neurons were lower whereas vascular cells and astrocyte fractions were higher in tissue of OCD subjects. Together, these data provide the first unbiased examination of differentially expressed transcripts in both OFC and striatum of OCD subjects. These transcripts encoded synaptic proteins more often than expected by chance, and thus implicate the synapse as a vulnerable molecular compartment for OCD.

Efficacy of intensive orbitofrontal continuous Theta Burst Stimulation (iOFcTBS) in Obsessive Compulsive Disorder: A Randomized Placebo Controlled Study

Transcranial magnetic stimulation (TMS) can non-invasively modulate specific brain regions in Obsessive-compulsive disorder (OCD). Citing orbito-frontal cortex (OFC) hyper-connectivity with striatum as the most consistent finding implicated in patho-physiologically of OCD, we aimed to study the effect of novel continuous Theta Burst Stimulation (cTBS) targeting OFC in OCD subjects on a randomized placebo control design. Thirty-three patients were randomly allocated to active cTBS (n= 18) and sham (n= 15) groups. They received 10 TBS sessions, 2 per day (total of 1200 pulses; intensive protocol) for 5 days in a week. The Yale Brown Obsessive Compulsive Scale (Y-BOCS), Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), and Clinical Global Impression-Severity (CGI-S) scores were assessed at baseline, after last session and at 2 weeks post-rTMS. On repeated measures-ANOVA, a significant group*time effect (from pretreatment to 2 weeks post TBS) for obsessions, compulsions, HAM-A, HAM-D, and CGI scores was found. But when controlled for confounding variables, only HAM-A scores and CGI effect retained statistical significance. We conclude that intensive OFC cTBS (iOFcTBS) in OCD is well tolerated with clinically significant improvements in anxiety symptoms and global severity. This improvement in anxiety symptoms could be due to modulations of state dependent dysregulation in OCD.

Identifying CBT non-response among OCD outpatients: A machine-learning approach

Objectives: Machine learning models predicting treatment outcomes for individual patients may yield high clinical utility. However, few studies tested the utility of easy to acquire and low-cost sociodemographic and clinical data. In previous work, we reported significant predictions still insufficient for immediate clinical use in a sample with broad diagnostic spectrum. We here examined whether predictions will improve in a diagnostically more homogeneous yet large and naturalistic obsessive-compulsive disorder (OCD) sample. Methods: We used sociodemographic and clinical data routinely acquired during CBT treatment of n = 533 OCD subjects in a specialized outpatient clinic. Results: Remission was predicted with 65% (p = 0.001) balanced accuracy on unseen data for the best model. Higher OCD symptom severity predicted non-remission, while higher age of onset of first OCD symptoms and higher socioeconomic status predicted remission. For dimensional change, prediction achieved r = 0.31 (p = 0.001) between predicted and actual values. Conclusions: The comparison with our previous work suggests that predictions within a diagnostically homogeneous sample, here OCD, are not per se superior to a more diverse sample including several diagnostic groups. Using refined psychological predictors associated with disorder etiology and maintenance or adding further data modalities as neuroimaging or ecological momentary assessments are promising in order to further increase prediction accuracy.

Do Individuals With Obsessive-Compulsive Disorder and Obsessive-Compulsive Personality Disorder Share Similar Neural Mechanisms of Decision-Making Under Ambiguous Circumstances?

Impaired decision-making is well documented in obsessive-compulsive disorder (OCD) and a range of electrophysiological and functional neuroimaging measures have begun to reveal the pathological mechanisms that underlie the decision-making process. Obsessive-compulsive personality disorder (OCPD) has core symptoms that often overlap with OCD, but similarities between these disorders at the behavioral and neurological levels are often unclear, including whether OCPD exhibits similar decision-making deficits and shared neurological dysfunction. To address these issues, we examined 24 cases of OCD, 19 cases of OCPD, and 26 matched normal control (NC) subjects during the revised Iowa Gambling Task (IGT) using event-related potentials (ERPs). The net IGT scores were lower for OCD subjects than for OCPD or NC subjects, thus indicating that OCD subjects chose more disadvantageous options and were “short-sighted” with regards to information. The feedback-related negativity (FRN) waveform (lose-win) was larger in both OCD and OCPD subjects, which suggested that obstacles exist in the feedback process. Consequently, these subjects might share similar neural mechanisms under ambiguous decision-making circumstances. Furthermore, IGT net scores were significantly and negatively correlated with Hamilton Anxiety Rating Scale (HAMA) and Hamilton Depression Rating Scale (HAMD) scales. This implies that more severe obsessive-compulsive symptoms inspired more negative emotions that led to worse decision-making ability. Therefore, although similar neural mechanisms might exist, this led to different behaviors in which OCPD is associated with better behavioral performance compared to OCD patients.

Conditioned Fear Extinction, Neuropsychological, and Psychological Aspects of OCD in Latinos

Background: Although culture can affect emotional and behavioral reactions, there is little research on the manifestations of obsessive-compulsive disorder (OCD) among Latinos. Previous studies using a fear extinction model with a non-Latino population showed that individuals with OCD have difficulty maintaining safety memories. Their neuropsychological performance has shown inconsistent findings. We compared Puerto Ricans with OCD and healthy controls on fear extinction retention, neuropsychological performance, and psychological self-reports. Methods: 17 healthy and 11 Puerto Rican adults with OCD underwent a fear conditioning and extinction paradigm using neutral visual cues that were paired or unpaired with an electric stimulus to elicit skin conductance responses. Neuropsychological tests (WCST,EST,MSIT) and psychological self-reports (BAI,BDI,STAI,PANAS,EDS)were administered. Results: OCD subjects did not show impaired extinction recall. However, they showed higher reaction times towards neutral than threat-related words on the EST, compared to healthy controls. No differences on neuropsychological tests that lacked emotional content were observed. OCD subjects showed increased symptoms of anxiety, trait anxiety, depression, negative affect, and emotional dysregulation. Conclusions: Puerto Ricans with OCD may have physiological and neuropsychological characteristics that are similar to healthy subjects, but a different psychological profile, which can be used to tailor cultural adaptations of evidence-based treatments for OCD.

Review of source-monitoring processes in obsessive-compulsive disorder

Obsessive-compulsive disorder (OCD) is a severe mental illness characterized by persistent, intrusive and distressing obsessions and/or compulsions. Such symptoms have been conceptualized as resulting from a failure in source-monitoring processes, suggesting that patients with OCD fail to distinguish actions they perform from those they just imagine doing. In this study, we aimed to provide an updated and exhaustive review of the literature examining the relationship between source-monitoring and OCD. A systematic search in the literature through January 2019 allowed us to identify 13 relevant publications investigating source-monitoring abilities in patients with OCD or participants with subclinical compulsive symptoms. Most of the retrieved studies did not report any source-monitoring deficits in clinical and subclinical subjects compared with healthy volunteers. However, most of the studies reported that patients with OCD and subclinical subjects displayed reduced confidence in source-monitoring judgments or global cognitive confidence compared to controls. The present review highlighted some methodological and statistical limitations. Consequently, further studies are needed to explore source monitoring with regard to the subcategories of OCD symptoms (i.e., symmetry-ordering, contamination-washing, hoarding, aggressive obsession-checking, sexual-religious thoughts) and to clarify the relationship between source-monitoring subtypes (i.e., reality or internal source-monitoring) and confidence in these populations.

Obsessive-Compulsive Disorder in Singapore: Prevalence, Comorbidity, Quality of Life and Social Support

Using data from Singapore Mental Health Study 2016 (SMHS 2016), we examined the prevalence of lifetime and 12-month obsessive-compulsive disorder (OCD), its sociodemographic correlates and association with comorbid psychiatric disorders and physical conditions, perceived social support and quality of life. The World Mental Health Composite International Diagnostic Interview (version 3.0) was administered by trained interviewers to 6126 residents aged ≥18 years old to assess OCD prevalence and that of other select psychiatric disorders. Details on sociodemographics, perceived social support and health-related quality of life were obtained. Lifetime and 12-month prevalence of OCD was 3.6% and 2.9%, respectively. Adjusted regression analysis showed that those with OCD had significantly higher odds of major depressive disorder (odds ratio [OR], 5.4), bipolar disorder (OR, 8.9), generalised anxiety disorder (OR, 7.3) and alcohol abuse (OR, 2.7). OCD was significantly associated with suicidal ideation and suicidality (OR, 5.1). OCD subjects also had higher odds of chronic pain (OR, 2.4) and diabetes (OR, 3.1). Finally, OCD subjects had lower mean mental composite summary scores than controls (respondents without any of the psychiatric disorders and physical conditions included in SMHS 2016) and those with other lifetime psychiatric disorders and physical conditions. OCD prevalence in Singapore is high. Most people with OCD do not seek treatment despite experiencing significant comorbidity and loss of quality of life.

Optical Coherence Tomography Findings in Obsessive Compulsive Disorder: A preliminary Receiver Operating Characteristic Analysis On Ganglion Cell Layer Volume for Neurodegeneration

Objective: Many theories have been proposed to explain the etiology of obsessive compulsive disorder (OCD), but neuroimaging studies suggest neurodegeneration as a possible cause. Neurodegenerative diseases may cause a reduction in the retinal nerve fiber layer (RNFL) and the ganglion cell complex (GCC), and these changes can be detected by optical coherence tomography (OCT). The aim of this study was to examine the potential relationship between OCT findings and the clinical features of patients with OCD versus the findings for a healthy control (HC) group. Methods: Patients with OCD (n=42) and HC subjects (n=50) completed sociodemographic, Beck Anxiety Inventory, and Beck Depression Inventory forms and underwent OCT. Patients undertook clinical interviews for Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) (SCID-I) and Yale-Brown Obsessive Compulsive Scale scores, whereas the HC group interviews used the SCID non-patient version. Results: The RNFL and GCC values were significantly lower in the OCD than in the HC group (p

Sub-graph entropy based network approaches for classifying adolescent obsessive-compulsive disorder from resting-state functional MRI.

This paper presents a novel approach for classifying obsessive-compulsive disorder (OCD) in adolescents from resting-state fMRI data. Currently, the state-of-the-art for diagnosing OCD in youth involves interviews with adolescent patients and their parents by an experienced clinician, symptom rating scales based on Diagnostic and Statistical Manual of Mental Disorders (DSM), and behavioral observation. Discovering signal processing and network-based biomarkers from functional magnetic resonance imaging (fMRI) scans of patients has the potential to assist clinicians in their diagnostic assessments of adolescents suffering from OCD. This paper investigates the clinical diagnostic utility of a set of univariate, bivariate and multivariate features extracted from resting-state fMRI using an information-theoretic approach in 15 adolescents with OCD and 13 matched healthy controls. Results indicate that an information-theoretic approach based on sub-graph entropy is capable of classifying OCD vs. healthy subjects with high accuracy. Mean time-series were extracted from 85 brain regions and were used to calculate Shannon wavelet entropy, Pearson correlation matrix, network features and sub-graph entropy. In addition, two special cases of sub-graph entropy, namely node and edge entropy, were investigated to identify important brain regions and edges from OCD patients. A leave-one-out cross-validation method was used for the final predictor performance. The proposed methodology using differential sub-graph (edge) entropy achieved an accuracy of 0.89 with specificity 1 and sensitivity 0.80 using leave-one-out cross-validation with in-fold feature ranking and selection. The high classification accuracy indicates the predictive power of the sub-network as well as edge entropy metric.

Lower excitatory synaptic gene expression in orbitofrontal cortex and striatum in an initial study of subjects with obsessive compulsive disorder.

Obsessive compulsive disorder (OCD) is a severe illness that affects 2-3% of people worldwide. OCD neuroimaging studies have consistently shown abnormal activity in brain regions involved in decision-making (orbitofrontal cortex [OFC]) and action selection (striatum). However, little is known regarding molecular changes that may contribute to abnormal function. We therefore examined expression of synaptic genes in post-mortem human brain samples of these regions from eight pairs of unaffected comparison and OCD subjects. Total grey matter tissue samples were obtained from medial OFC (BA11), lateral OFC (BA47), head of caudate, and nucleus accumbens (NAc). Quantitative polymerase chain reaction (qPCR) was then performed on a panel of transcripts encoding proteins related to excitatory synaptic structure, excitatory synaptic receptors/transporters, and GABA synapses. Relative to unaffected comparison subjects, OCD subjects had significantly lower levels of several transcripts related to excitatory signaling in both cortical and striatal regions. However, a majority of transcripts encoding excitatory synaptic proteins were lower in OFC but not significantly different in striatum of OCD subjects. Composite transcript level measures supported these findings by revealing that reductions in transcripts encoding excitatory synaptic structure proteins and excitatory synaptic receptors/transporters occurred primarily in OFC of OCD subjects. In contrast, transcripts associated with inhibitory synaptic neurotransmission showed minor differences between groups. The observed lower levels of multiple glutamatergic transcripts across both medial and lateral OFC may suggest an upstream causal event. Together, these data provide the first evidence of molecular abnormalities in brain regions consistently implicated in OCD human imaging studies.

Lifetime bipolar disorder comorbidity and related clinical characteristics in patients with primary obsessive compulsive disorder: a report from the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS).

Bipolar disorder (BD) and obsessive compulsive disorder (OCD) are prevalent, comorbid, and disabling conditions, often characterized by early onset and chronic course. When comorbid, OCD and BD can determine a more pernicious course of illness, posing therapeutic challenges for clinicians. Available reports on prevalence and clinical characteristics of comorbidity between BD and OCD showed mixed results, likely depending on the primary diagnosis of analyzed samples. We assessed prevalence and clinical characteristics of BD comorbidity in a large international sample of patients with primary OCD (n = 401), through the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS) snapshot database, by comparing OCD subjects with vs without BD comorbidity. Among primary OCD patients, 6.2% showed comorbidity with BD. OCD patients with vs without BD comorbidity more frequently had a previous hospitalization (p < 0.001) and current augmentation therapies (p < 0.001). They also showed greater severity of OCD (p < 0.001), as measured by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). These findings from a large international sample indicate that approximately 1 out of 16 patients with primary OCD may additionally have BD comorbidity along with other specific clinical characteristics, including more frequent previous hospitalizations, more complex therapeutic regimens, and a greater severity of OCD. Prospective international studies are needed to confirm our findings.

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.