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.

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.

Impact of the COVID-19 Pandemic on the Short-Term Course of Obsessive-Compulsive Disorder.

ABSTRACT: There is an understandable concern that obsessive-compulsive disorder (OCD) may worsen during the COVID-19 pandemic, but there are little empirical data. We report the impact of COVID-19 pandemic on the short-term course of OCD. A cohort of patients with a primary diagnosis of OCD (n = 240) who were on regular follow-up at a tertiary care specialty OCD clinic in India were assessed telephonically, about 2 months after the declaration of the pandemic ("pandemic" cohort). Data from the medical records of an independent set of patients with OCD (n = 207) who were followed up during the same period, 1 year prior, was used for comparison (historical controls). The pandemic group and historical controls did not differ in the trajectories of the Yale-Brown Obsessive-Compulsive Scale scores (chi-square likelihood ratio test of the group × time interaction = 2.73, p = 0.255) and relapse rate (21% vs. 20%; adjusted odds ratio, 0.81; 95% confidence interval, 0.41-1.59; p = 0.535). Preexisting contamination symptoms and COVID-19-related health anxiety measured by the COVID-Threat Scale did not predict relapse. Only a small proportion of patients (6%) reported COVID-19-themed obsessive-compulsive symptoms. The COVID-19 pandemic, at least in the short run, did not influence the course of illness.

Plasma IL-6 levels in unmedicated, comorbidity free obsessive-compulsive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) is increasingly being evaluated for a neuro-immune basis. Interleukin-6 (IL-6) is the most widely studied cytokine with a potential role in altering neurotransmission. The evidence for plasma IL-6 alterations in OCD has yielded mixed results. Psychotropic medications are known to modulate inflammatory processes and cytokine levels. METHODS: In this study, we recruited unmedicated, co-morbidity-free adult OCD patients (n = 49) and sex-matched healthy controls HC (n = 47) and compared their plasma IL-6 levels and their correlation with age at onset, duration of illness, and severity. RESULTS: IL-6 plasma level (ng/ml) in unmedicated OCD patients (1.31 ± 0.67) was significantly greater compared to HC (1.03 ± 0.47) [t = 2.33 (p = 0.02)]. The group differences persisted even after controlling for age and sex [F(1, 91) = 4.57, p = 0.035, η2 = 0.05]. Plasma IL-6 did not correlate significantly with any clinical variables. CONCLUSIONS: This study adds to the existing literature on immune alterations in OCD. Alterations in plasma IL-6 might have implications in the neurotransmitter alterations and stress-response in OCD. The current study results in unmedicated and comorbidity-free OCD patients give us a better understanding of the immune alterations in OCD. Future studies in such a population will probably help in reducing the heterogeneity of findings.

Long-term Outcomes of Intensive Inpatient Care for Severe, Resistant Obsessive-Compulsive Disorder: Résultats à long terme de soins intensifs à des patients hospitalisés pour un trouble obsessionnel-compulsif grave et résistant.

OBJECTIVE: A substantial proportion of severely ill patients with obsessive-compulsive disorder (OCD) do not respond to serotonin reuptake inhibitors (SRIs) and are unable to practice cognitive behavioral therapy (CBT) on an out-patient basis. We report the short-term (at discharge) and long-term (up to 2 years) outcome of a multimodal inpatient treatment program that included therapist-assisted intensive CBT with adjunctive pharmacotherapy for severely ill OCD patients who are often resistant to SRIs and are either unresponsive or unable to practice outpatient CBT. METHODS: A total of 420 patients, admitted between January 2012 and December 2017 were eligible for the analysis. They were evaluated using the Mini International Neuropsychiatric Interview, the Yale-Brown Obsessive Compulsive Scale (YBOCS), and the Clinical Global Impression (CGI) scale. All patients received 4 to 5 therapist-assisted CBT sessions per week along with standard pharmacotherapy. Naturalistic follow-up information at 3, 6, 12, and 24 months were recorded. RESULTS: At baseline, patients were mostly severely ill (YBOCS = 29.9 ± 4.5) and nonresponsive to ≥2 SRIs (83%). Mean duration of inpatient stay was 42.7 ± 25.3 days. At discharge, there was a significant decline in the mean YBOCS score (29.9 ± 4.5 vs. 18.1 ± 7.7, P < .001, Cohen's d = 1.64); 211/420 (50%) were responders (≥35% YBOCS reduction and CGI-I≤2) and an additional 86/420 (21%) were partial responders (25% to 35% YBOCS reduction and CGI-I≤3). Using latent class growth modeling of the follow-up data, 4 distinct classes were identified, which include "remitters" (14.5%), "responders" (36.5%), "minimal responders" (34.7%), and "nonresponders" (14.6%). Shorter duration of illness, better insight, and lesser contamination/washing symptoms predicted better response in both short- and long-term follow-up. CONCLUSION: Intensive, inpatient-based care for OCD may be an effective option for patients with severe OCD and should be considered routinely in those who do not respond with outpatient treatment.

Impact of antipsychotic medication on IL-6/STAT3 signaling axis in peripheral blood mononuclear cells of drug-naive schizophrenia patients.

AIM: Immunopathogenesis remains a widely appreciated etiopathological model of schizophrenia. Persistent efforts have aimed to identify schizophrenia biomarkers indexing immune system abnormalities and also immuno-dampening effects of antipsychotic medications. Although data arising from published reports are encouraging, such studies are limited to a few immune parameters and not focused on a specific pathway. Th17 cells-mediated immuno-inflammatory responses have emerged as a potential mechanism in various neuropsychiatric conditions, including schizophrenia. The Th17 pathway is distinctly regulated through a coordinated action of multiple cytokines and transcription factors. In this study, we explored whether antipsychotic medication has any effect on the cytokines and transcription factors of the Th17 pathway. METHODS: A total of 27 drug-naive schizophrenia patients were recruited and followed up for 3 months after initiation of antipsychotic medication. Lymphocyte gene expression levels of two transcription factors (STAT3 and RORC) and one of their upstream regulators, IL6, were quantified before and after treatment. Plasma levels of cytokines, such as interleukin (IL)-1ß, IL-6, IL-17A, IL-23, and IL-33, were also analyzed before and after treatment. RESULTS: Treatment with antipsychotic medication for 3 months resulted in significant downregulation of STAT3 gene expression as well as reduction in plasma levels of IL-1ß, IL-6, and IL-17A. Significant reduction in total scores for the Scale for Assessment of Positive Symptoms and the Scale for Assessment of Negative Symptoms was also observed in schizophrenia patients after 3 months of antipsychotic treatment. CONCLUSION: Our findings suggest possible immuno-modulatory effects of antipsychotic medication on the critical regulators, such as IL-6 and STAT3, of the Th17 pathway in schizophrenia patients. The IL-6/STAT3 signaling axis involved in the transcriptional regulation of Th17 cells might appear as an important target of antipsychotic treatment in schizophrenia patients. Alternatively, irrespective of the effect of antipsychotic drugs, the IL-6/STAT3 signaling axis might be crucially involved in ameliorating psychotic symptoms.

Effectiveness of Venlafaxine in Selective Serotonin Reuptake Inhibitor-Resistant Obsessive-Compulsive Disorder: Experience From a Specialty Clinic in India.

BACKGROUND: Despite its favorable pharmacological profile and efficacy in major depression and anxiety disorders, evidence for the use of venlafaxine in obsessive-compulsive disorder (OCD) is limited. We sought to examine the real-world effectiveness of venlafaxine from a large database of an OCD clinic in India. METHODS: A total of 1704 consecutive patients who registered at the OCD clinic between June 2014 and December 2016 were evaluated with structured interviews and scales. Patients with symptomatic OCD (Yale-Brown Obsessive-Compulsive Severity ≥16) despite treatment with selective serotonin reuptake inhibitors and initiated on venlafaxine were included for analysis. The main outcome measures were response as defined by 35% or more reduction in the Yale-Brown Obsessive-Compulsive Severity total score and "all-cause discontinuation." RESULTS: Of a total of 65 patients who were eligible for analysis, 29(45%) were responders at the end of 16 weeks and 27 (42%) continued to remain on venlafaxine. Repeated measures analysis of variance yielded significant reduction in the Yale-Brown Obsessive-Compulsive Severity total score (F(1.29, 82.4) = 56.54, P < 0.001, partial η = 0.469). On regression analysis, only lower insight (P = 0.048) predicted poor response. CONCLUSIONS: The study suggests that venlafaxine may be useful in a proportion of patients with poor response to selective serotonin reuptake inhibitors and therefore requires to be studied in controlled trials.

Online Theta Frequency Transcranial Alternating Current Stimulation for Cognitive Remediation in Schizophrenia: A Case Report and Review of Literature.

Transcranial alternating current stimulation (tACS), a noninvasive brain stimulation technique that uses low-intensity alternating current, has been postulated to be a potential therapeutic option in treating the cognitive deficits in schizophrenia. Transcranial alternating current stimulation synchronizes the neural oscillations to the applied stimulation frequency in the stimulated cortical regions. In this report, we have reviewed the literature pertinent to the clinical application of tACS in psychiatric disorders; in addition, we have described the clinical use of online theta tACS in a schizophrenia patient with cognitive deficits. Online theta tACS led to improvement in working memory, attention, processing speed, and emotional processing. The beneficial effect of tACS persisted during reassessment of the patient after 50 days. Transcranial alternating current stimulation, given its noninvasiveness, safety, and ease of administration, has the potential to ameliorate cognitive deficits in neuropsychiatric disorders like schizophrenia.

Role of IL-6/RORC/IL-22 axis in driving Th17 pathway mediated immunopathogenesis of schizophrenia.

The immuno-inflammatory origin of schizophrenia in a subset of patients is viewed as a key element of an overarching etiological construct. Despite substantial research, the immune components exerting major effect are yet to be fully clarified. Disrupted T cell networks have consistently been linked to the pathogenesis of schizophrenia. Amongst the Th cell subsets, the Th17 cells have emerged as a paradigmatic lineage with significant functional implications in a vast number of immune mediated diseases including brain disorders such as schizophrenia. The present study was aimed at examining the functional role of the Th17 pathway in schizophrenia. To address this, genotyping of IL17A (rs2275913; G197A) Single Nucleotide Polymorphism was carried out by the PCR-RFLP method in 221 schizophrenia patients and 223 healthy control subjects. Gene expression of two transcription factors STAT3 and RORC was quantified in a subset of drug naïve schizophrenia patients (n = 56) and healthy controls (n = 52) by TaqMan assay. The plasma levels of fifteen cytokines belonging to Th17 pathway were estimated in a subset of drug naïve schizophrenia patients (n = 61) and healthy controls (n = 50) by using Bio-Plex Pro Human Th17 cytokine assays. The AA genotype was associated with higher total score of bizarre behaviour and apathy in female schizophrenia patients. A high gene expression level of RORC was observed in drug naïve schizophrenia patients. In addition, significantly elevated plasma levels of IL-6 and IL-22, and reduced levels of IL-1ß and IL-17F were noted in schizophrenia patients. Taken together, these findings indicate a dysregulated Th17 pathway in schizophrenia patients.

Influence of correlation between HLA-G polymorphism and Interleukin-6 (IL6) gene expression on the risk of schizophrenia.

Converging evidence suggests important implications of immuno-inflammatory pathway in the risk and progression of schizophrenia. Prenatal infection resulting in maternal immune activation and developmental neuroinflammation reportedly increases the risk of schizophrenia in the offspring by generating pro-inflammatory cytokines including IL-6. However, it is not known how prenatal infection can induce immuno-inflammatory responses despite the presence of immuno-inhibitory Human Leukocyte Antigen-G (HLA-G) molecules. To address this, the present study was aimed at examining the correlation between 14 bp Insertion/Deletion (INDEL) polymorphism of HLA-G and IL-6 gene expression in schizophrenia patients. The 14 bp INDEL polymorphism was studied by PCR amplification/direct sequencing and IL-6 gene expression was quantified by using real-time RT-PCR in 56 schizophrenia patients and 99 healthy controls. We observed significantly low IL6 gene expression in the peripheral mononuclear cells (PBMCs) of schizophrenia patients (t = 3.8, p = .004) compared to the controls. In addition, schizophrenia patients carrying Del/Del genotype of HLA-G 14 bp INDEL exhibited significantly lower IL6 gene expression (t = 3.1; p = .004) than the Del/Ins as well as Ins/Ins carriers. Our findings suggest that presence of "high-expressor" HLA-G 14 bp Del/Del genotype in schizophrenia patients could attenuate IL-6 mediated inflammation in schizophrenia. Based on these findings it can be assumed that HLA-G and cytokine interactions might play an important role in the immunological underpinnings of schizophrenia.

CHRFAM7A gene expression in schizophrenia: clinical correlates and the effect of antipsychotic treatment.

Earlier studies have implicated CHRNA7, coding α-7 nicotinic acetylcholine receptor (α7 nAChR), and its partially duplicated chimeric gene CHRFAM7A in schizophrenia. However, the relationship between the alterations in peripheral gene expression of CHRFAM7A and severity of clinical symptoms has not been examined. Furthermore, potential influence of the antipsychotic medication on CHRFAM7A expression in drug-naive or drug-free schizophrenia is an unexplored area. CHRFAM7A gene expression in lymphocytes was analyzed in 90 antipsychotic-naïve or free schizophrenia patients using TaqMan-based quantitative RT-PCR. Psychotic symptoms were assessed using Scale for Assessment of Positive Symptoms and Scale for Assessment of Negative Symptoms (SANS). The relationship between psychopathology and CHRFAM7A expression was examined. In addition, measurement of CHRFAM7A gene expression was repeated during follow-up after short-term antipsychotic treatment in 38 patients. There was significant inverse correlation between CHRFAM7A expression and total negative psychopathology score-SANS, and this relationship persisted after accounting for possible confounders such as age, sex and smoking. On exploration of the factor structure of psychopathology using principal component analysis, all the negative symptoms-affective flattening, alogia, apathy, anhedonia and inattention were found to be inversely associated with CHRFAM7A expression. Furthermore, analysis of repeated measures revealed a significant increase in CHRFAM7A expression in patients after short-term administration of antipsychotic medication. Our study observations support the role for CHRFAM7A gene in schizophrenia pathogenesis and suggest a potential novel link between deficient CHRFAM7A expression and negative psychopathology. Furthermore, up-regulation of CHRFAM7A gene expression by antipsychotics suggests that it could be a potential state marker for clinical severity.

Discovery biology of neuropsychiatric syndromes (DBNS): a center for integrating clinical medicine and basic science.

BACKGROUND: There is emerging evidence that there are shared genetic, environmental and developmental risk factors in psychiatry, that cut across traditional diagnostic boundaries. With this background, the Discovery biology of neuropsychiatric syndromes (DBNS) proposes to recruit patients from five different syndromes (schizophrenia, bipolar disorder, obsessive compulsive disorder, Alzheimer's dementia and substance use disorders), identify those with multiple affected relatives, and invite these families to participate in this study. The families will be assessed: 1) To compare neuro-endophenotype measures between patients, first degree relatives (FDR) and healthy controls., 2) To identify cellular phenotypes which differentiate the groups., 3) To examine the longitudinal course of neuro-endophenotype measures., 4) To identify measures which correlate with outcome, and 5) To create a unified digital database and biorepository. METHODS: The identification of the index participants will occur at well-established specialty clinics. The selected individuals will have a strong family history (with at least another affected FDR) of mental illness. We will also recruit healthy controls without family history of such illness. All recruited individuals (N = 4500) will undergo brief clinical assessments and a blood sample will be drawn for isolation of DNA and peripheral blood mononuclear cells (PBMCs). From among this set, a subset of 1500 individuals (300 families and 300 controls) will be assessed on several additional assessments [detailed clinical assessments, endophenotype measures (neuroimaging- structural and functional, neuropsychology, psychophysics-electroencephalography, functional near infrared spectroscopy, eye movement tracking)], with the intention of conducting repeated measurements every alternate year. PBMCs from this set will be used to generate lymphoblastoid cell lines, and a subset of these would be converted to induced pluripotent stem cell lines and also undergo whole exome sequencing. DISCUSSION: We hope to identify unique and overlapping brain endophenotypes for major psychiatric syndromes. In a proportion of subjects, we expect these neuro-endophenotypes to progress over time and to predict treatment outcome. Similarly, cellular assays could differentiate cell lines derived from such groups. The repository of biomaterials as well as digital datasets of clinical parameters, will serve as a valuable resource for the broader scientific community who wish to address research questions in the area.

Gene polymorphisms and response to transcranial direct current stimulation for auditory verbal hallucinations in schizophrenia.

OBJECTIVE: Recent observations demonstrate a significant ameliorative effect of add-on transcranial direct current stimulation (tDCS) on auditory verbal hallucinations (AVHs) in schizophrenia. Of the many SNPs, NRG1 rs35753505 and catechol-o-methyl transferase (COMT) rs4680 polymorphisms have shown to have a strong association with neuroplasticity effect in schizophrenia. METHODS: Schizophrenia patients (n=32) with treatment resistant auditory hallucinations were administered with an add-on tDCS. The COMT (rs4680) and NRG1 (rs35753505) genotypes were determined. The COMT genotypes were categorised into Val group (GG; n=15) and Met group (GG/AG; n=17) and NRG1 genotypes were categorised into AA group (n=12) and AG/GG group (n=20). RESULTS: The reduction in auditory hallucination sub-scale score was significantly affected by COMT-GG genotype [Time×COMT interaction: F(1,28)=10.55, p=0.003, ɳ2=0.27]. Further, COMT-GG effect was epistatically influenced by the co-occurrence of NRG1-AA genotype [Time×COMT×NRG1 interaction: F(1,28)=8.09, p=0.008, ɳ2=0.22]. Irrespective of genotype, females showed better tDCS response than males [Time×Sex interaction: F(1,21)=4.67, p=0.04, ɳ2=0.18]. CONCLUSION: COMT-GG and NRG1-AA genotypes aid the tDCS-induced improvement in AVHs in schizophrenia patients. Our preliminary observations need replication and further systematic research to understand the neuroplastic gene determinants that modulate the effect of tDCS.

Aripiprazole augmentation in highly treatment-resistant obsessive-compulsive disorder - experience from a specialty clinic in India.

OBJECTIVE: To study the effectiveness and tolerability of aripiprazole augmentation in patients with highly treatment-resistant obsessive-compulsive disorder (OCD) in a real-world scenario. METHODS: We conducted a chart review of patients who were initiated on aripiprazole augmentation at a specialty OCD clinic in India between 2004 and 2014. Primary outcome measure was all-cause discontinuation. RESULTS: 23 patients were eligible for analysis. Patients had not achieved symptom remission despite a mean of over 3 prior SRI trials. Aripiprazole was continued to be used in seven patients (30%) at the time of last follow-up. Thirteen patients (57%) discontinued the drug due to side effects, and three patients (13%) discontinued aripiprazole citing no improvement. Six patients (26%) were noted to have ≥25% reduction on the Yale-Brown Obsessive-Compulsive Scale. CONCLUSIONS: The study demonstrated, in a real-world setting, that aripiprazole may be a useful augmenting agent in a proportion of patients with highly treatment-resistant OCD. However, side effects may lead to premature discontinuation in many of them.

Bipolar disorder comorbidity in patients with a primary diagnosis of OCD.

OBJECTIVE: Bipolar disorder (BD) is considered to be a common comorbid condition in subjects with obsessive-compulsive disorder (OCD), but there is limited literature on the prevalence of BD and its clinical correlates in those with a primary diagnosis of OCD. METHODS: We studied the prevalence of BD in a sample of consecutively registered outpatients attending a specialty OCD clinic in India over a period of 13 months. One hundred and seventy-one patients with a primary diagnosis of OCD were assessed systematically using structured and semi-structured instruments. RESULTS: The prevalence of lifetime BD in OCD was 4%. The OCD + BD group had an episodic course of OCD and higher rate of lifetime suicide attempts. CONCLUSIONS: BD may not be as highly prevalent in OCD as reported in literature. Those with OCD seem to have only a marginally higher risk for developing BD than the general population. A diagnosis of BD seems to have a pathoplastic effect on the course of OCD. Patients with OCD-BD comorbidity have to be specifically assessed for suicide risk.

Effectiveness of Risperidone Augmentation in Obsessive-Compulsive Disorder: Experience From a Specialty Clinic in India.

Risperidone is the most widely used augmenting agent in the treatment of obsessive-compulsive disorder (OCD). However, a recent controlled study found risperidone to be no different from placebo, raising doubts about its effectiveness. In this context, we sought to examine the real-world effectiveness of risperidone from the large database of an OCD clinic in India. A total of 1314 consecutive patients who registered at the OCD clinic between 2004 and 2014 were evaluated with structured interviews and scales. Patients with OCD initiated on risperidone augmentation without concurrent cognitive behavior therapy and who were on stable and adequate doses of serotonin reuptake inhibitors for at least 12 preceding weeks were included for analysis. The primary outcome measure was all-cause discontinuation. Logistic regression was performed to identify the factors predicting improvement with risperidone augmentation. A total of 92 patients were eligible for analysis. Risperidone continued to be used in 23 patients (25%) at the time of last follow-up, and the remaining discontinued either because of ineffectiveness or intolerability. The fall in the Yale-Brown Obsessive-Compulsive Scale scores was significantly greater in patients who continued to take risperidone when compared with those who did not (41.6% vs 3.7%, t = 6.95, P < 0.001). A total of 22 patients (24%) were noted to have at least a 25% reduction on the Yale-Brown Obsessive-Compulsive Scale scores. On regression analysis, no predictors of improvement with risperidone augmentation could be identified. The study demonstrated, in a real-world setting, that risperidone may be a useful augmenting agent in a proportion of patients with partial/poor response to serotonin reuptake inhibitors.