Distinct cognitive and functional connectivity features from healthy cohorts can identify clinical obsessive-compulsive disorder.

Improving diagnostic accuracy of obsessive-compulsive disorder (OCD) using models of brain imaging data is a key goal of the field, but this objective is challenging due to the limited size and phenotypic depth of clinical datasets. Leveraging the phenotypic diversity in large non-clinical datasets such as the UK Biobank (UKBB), offers a potential solution to this problem. Nevertheless, it remains unclear whether classification models trained on non-clinical populations will generalise to individuals with clinical OCD. This question is also relevant for the conceptualisation of OCD; specifically, whether the symptomology of OCD exists on a continuum from normal to pathological. Here, we examined a recently published "meta-matching" model trained on functional connectivity data from five large normative datasets (N=45,507) to predict cognitive, health and demographic variables. Specifically, we tested whether this model could classify OCD status in three independent clinical datasets (N=345). We found that the model could identify out-of-sample OCD individuals. Notably, the most predictive functional connectivity features mapped onto known cortico-striatal abnormalities in OCD and correlated with genetic brain expression maps previously implicated in the disorder. Further, the meta-matching model relied upon estimates of cognitive functions, such as cognitive flexibility and inhibition, to successfully predict OCD. These findings suggest that variability in non-clinical brain and behavioural features can discriminate clinical OCD status. These results support a dimensional and transdiagnostic conceptualisation of the brain and behavioural basis of OCD, with implications for research approaches and treatment targets.

A prospective longitudinal investigation of the trajectory of obsessive-compulsive symptoms during adolescence.

Obsessive-compulsive symptoms (OCS) increase with age during childhood and adolescence, and subthreshold OCS in childhood associate with a higher probability of obsessive-compulsive disorder (OCD) diagnosis in adulthood. Additionally, average age of onset for OCD is in adolescence, with the majority of OCD cases emerging by early adulthood. Despite these trends, the specific course of OCS development in adolescence is relatively unknown. To this end, the present prospective longitudinal study used latent growth mixture modeling and a diverse community sample of 3,335 high schoolers to identify and characterize growth trajectories of OCS across middle to late adolescence. Results identified three trajectories: High-but-Remitting, Moderate-but-Escalating, and Low-and-Stable. Results also indicated age, gender, anxiety sensitivity, and distress tolerance as significant predictors of trajectory group membership, such that younger age and being female predicted classification in the High-but Remitting group, greater anxiety sensitivity predicted classification in both the High-but-Remitting and Moderate-but Escalating groups, and greater distress tolerance predicted a lower likelihood of classification in the High-but-Remitting and Moderate-but-Escalating groups. Taken together, these trajectories have illustrated the temporal course and development of OCS across key developmental years. Moreover, the trajectories and their corresponding predictors may help identify adolescents who are particularly vulnerable to developing OCD.

The psychosocial and educational burden of obsessive-compulsive disorder in youth.

BACKGROUND: Pediatric OCD is associated with functional impairment in multiple environments. However, relatively little is known about the impact of comorbid conditions, as well as OCD severity on psychosocial functioning in this population. Furthermore, most studies did not include a control sample, nor examined differences between children and adolescents. The goal of this investigation was to assess psychosocial functioning and its associations with age, symptom severity, and comorbid conditions in a large well characterized sample of pediatric OCD probands, and controls. METHODS: Participants included 117 pediatric OCD probands and 147 controls, that underwent a careful diagnostic process, and completed several questionnaires and interviews. RESULTS: Results revealed significant psychosocial impairments across multiple domains/settings, some of which were affected by symptom severity as well as by conduct related comorbidities and to a lesser extent affective disorders. In addition, different aspects of psychosocial impairments were found between children and adolescents. CONCLUSION: This study provides high resolution information regarding the types and extent of psychosocial dysfunction in youth with OCD, as well as its relationship with clinical and diagnostic correlates. It is recommended that evaluation and management of OCD in youth in research and clinical settings regularly include qualitative and semi-quantitative assessment of function across these domains.

Juvenile Osteochondritis Dissecans: A Case Report.

(1) Background: This report aims to illustrate the development, progression, diagnosis, and treatment of chronically present articular surface lesions. (2) Methods: In this report, two patients are described from the point of the initial presentation of symptoms to surgical consultation based on radiologic findings. These patients underwent corrective surgery in the form of mosaicplasty to repair lesions present on the articular surface and the underlying subchondral bone. (3) Discussion: Diagnosing juvenile OCD remains challenging due to its variable clinical presentation and minute radiologic discoveries. X-rays are useful; however, the gold standard remains arthroscopy, which can be both diagnostic and therapeutic. Future prospects include the use of novel sonographic methods and the use of artificial intelligence within the given modalities. (4) Conclusions: The detailed imaging provided by MRI, combined with the insights from X-rays and potentially other modalities, allows for a nuanced understanding of this disease. This comprehensive approach ensures that treatment decisions are well-informed, optimising outcomes for young patients with this condition.

Disgust as a primary emotional system and its clinical relevance.

This paper advocates for considering disgust as a primary emotional system within Panksepp's Affective Neuroscience framework, which has the potential to improve the efficacy of psychotherapy with obsessive-compulsive disorder, hypochondriasis, and emetophobia. In 2007, Toronchuk and Ellis provided comprehensive evidence that DISGUST system, as they defined it, matched all Panksepp's criteria for a primary emotional system. A debate ensued and was not unambiguously resolved. This paper is an attempt to resume this discussion and supplement it with the data that accumulated since then on DISGUST's relationship with the immune system and the role of DISGUST dysregulation in psychopathology. We hope that renewed research interest in DISGUST has the potential to improve clinical efficacy with hard-to-treat conditions.

A systematic scoping review of the literature on sexual orientation obsessive compulsive disorder (SOOCD): Important clinical considerations and recommendations.

Obsessive Compulsive Disorder (OCD) is characterised by the occurrence of persistent thoughts, urges, or images that are experienced as intrusive and unwanted (obsessions), and compulsive actions that the individual feels driven to act on in response to an obsession. These actions are carried out by an individual in order to try and prevent or reduce anxiety or distress, or to prevent something terrible from happening (American Psychiatric Association, APA, 2013). The aim of this review was to identify studies which have explored SOOCD. Because this is a relatively under-researched field, the decision was made for the present systematic review to take an inclusive approach. A systematic PRISMA review was conducted. A total of eleven studies were identified in this review. Two were cases and nine were empirical studies. Overall, the studies in this review highlight that although relatively common in individuals with OCD, SOOCD is frequently misunderstood by both clinicians and patients. This emphasises the need for education and training (or they are not even aware of the condition).

Neuropsychological Functioning Among Patients with OCD in Asian Countries: A Systematic Review.

Objective: This systematic review aimed to identify the effect of obsessive compulsive disorder (OCD) on cognitive processes, such as memory, executive functioning, and cognitive flexibility, among the adult populations of Asian countries. Methods: The systematic review progressed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. It is comprised of articles sourced from Asian countries published from 2018 to 2022, and literature about deficits in memory, executive functioning, and cognitive flexibility in the OCD population was gathered from five electronic databases, including Google Scholar, PubMed, Research Gate, Science Direct, and Wiley Online Library. Full-text impact factor articles in the English language were considered in this study. Results: This study screened 44 articles; five were included based on the eligibility criteria for the present systematic review. Four articles found cognitive deficits in the domains of executive functioning, memory, and cognitive flexibility among patients with OCD, whereas results of one article showed normal cognitive performance of the patients. Demographic variables showed no significant differences between patients with OCD and healthy controls. Conclusion: This systematic review indicated deficits specifically in the cognitive functioning and flexibility of patients with OCD. Despite a noticeable prevalence of OCD in Asian countries, the literature on correlates and neurological functioning is scarce. Further studies are required to examine the effects on the larger population and provide knowledge in those countries and areas where people are suffering because of minimal knowledge regarding OCD.

Isolated in-situ mosaicplasty fixation of unstable knee osteochondritis dissecans in skeletally mature patients; A combined mechanical and biological solution with excellent outcomes and a low re-operation rate.

OBJECTIVES: Unstable Osteochondritis dissecans (OCD) of the knee can result in substantial morbidity; the aims of surgical management are to provide stability to the lesion and to stimulate biological healing. The aims of this paper were to review the outcomes of a previously described, but uncommonly used, technique involving isolated mosaicplasty fixation of unstable knee OCD. METHODS: A retrospective review of skeletally mature patients treated with in-situ mosaicplasty fixation of unstable OCD of the knee was performed. Two out of thirteen knees also underwent concomitant realignment osteotomy. Post-operative Magnetic Resonance Imaging (MRI) and patient reported outcome measures were reviewed. RESULTS: Twelve patients (13 knees) were included; there were 5 females and 7 males. The mean age at time of surgery was 22 years (range 16-32). The lesion location was lateral femoral condyle in 7 cases and medial femoral condyle in 6 cases. Follow-up MRI scans confirmed fragment healing in 12 knees (92%). One patient required further surgical intervention for ongoing symptoms and radiological non-union: the patient underwent an off-loading distal femoral osteotomy to correct valgus mal-alignment. CONCLUSION: This series describes the outcomes following an uncommonly performed, yet reproducible and effective method of fixation of unstable knee OCDs. We believe in-situ mosaicplasty fixation represents an opportunity to provide both mechanical stability and biological augmentation of OCD healing and the series confirms that excellent results can be achieved, with a low re-operation rate. LEVEL OF EVIDENCE: Level IV.

Deep Brain Stimulation for Childhood Treatment-Resistant Obsessive-Compulsive Disorder: Mental Health Clinician Views on Candidacy Factors.

INTRODUCTION: Deep brain stimulation (DBS) is approved under a humanitarian device exemption to manage treatment-resistant obsessive-compulsive disorder (TR-OCD) in adults. It is possible that DBS may be trialed or used clinically off-label in children and adolescents with TR-OCD in the future. DBS is already used to manage treatment-resistant childhood dystonia. Evidence suggests it is a safe and effective intervention for certain types of dystonia. Important questions remain unanswered about the use of DBS in children and adolescents with TR-OCD, including whether mental health clinicians would refer pediatric patients for DBS, and who would be a good candidate for DBS. OBJECTIVES: To explore mental health clinicians' views on what clinical and psychosocial factors they would consider when determining which children with OCD would be good DBS candidates. MATERIALS AND METHODS: In depth, semi-structured interviews were conducted with n = 25 mental health clinicians who treat pediatric patients with OCD. The interviews were transcribed, coded, and analyzed using thematic content analysis. Three questions focused on key, clinical, and psychosocial factors for assessing candidacy were analyzed to explore respondent views on candidacy factors. Our analysis details nine overarching themes expressed by clinicians, namely the patient's previous OCD treatment, OCD severity, motivation to commit to treatment, presence of comorbid conditions, family environment, education on DBS, quality of life, accessibility to treatment, and patient age and maturity. CONCLUSIONS: Clinicians generally saw considering DBS treatment in youth as a last resort and only for very specific cases. DBS referral was predominantly viewed as acceptable for children with severe TR-OCD who have undertaken intensive, appropriate treatment without success, whose OCD has significantly reduced their quality of life, and who exhibit strong motivation to continue treatment given the right environment. Appropriate safeguards, eligibility criteria, and procedures should be discussed and identified before DBS for childhood TR-OCD becomes practice.

A concentrated approach for treating OCD: a pilot study examining the feasibility and potential effectiveness of the Bergen Four Day Treatment in the U.S.

The Bergen Four Day Treatment (B4DT) is a concentrated treatment for OCD that has demonstrated promising effectiveness in Nordic country samples. The B4DT is delivered over four days and provides individual treatment in a group context. The effectiveness of the B4DT for OCD has not been tested outside Nordic countries. The current pilot study evaluated the feasibility and the potential effectiveness of B4DT in a different culture and health-care system in the United States. Findings from 48 adults with OCD who completed the B4DT indicated that OCD, anxiety, and depression symptom severity significantly decreased from pre- to post-treatment, and gains were maintained at six month follow-up. The Yale-Brown Obsessive Compulsive Scale scores were reduced from moderate to subclinical; specifically, the average scores of 27.0 (pre-treatment) fell to 11.7 (post-treatment), 12.7 (3-month follow-up), and 13.7 (6-month follow-up). The B4DT was rated as highly acceptable by the US patients. Over 95% of the patients stated that they would recommend the treatment to a friend. These findings provide the first preliminary evidence for the generalizability of the B4DT to patients outside Nordic countries. Cultural and context-dependent issues that affected this dissemination pilot study are discussed in addition to future clinical and research directions.

Advances in Pediatric Obsessive-Compulsive Disorder (OCD) Treatment: A Comprehensive Narrative Review.

Obsessive-compulsive disorder (OCD), characterized by persistent, intrusive thoughts (obsessions) and repetitive behaviors or mental acts (compulsions), can significantly impact a child's daily functioning, academic performance, and overall quality of life. As the prevalence of pediatric OCD continues to rise, there is a critical demand for evidence-based treatments that not only alleviate symptoms but also enhance the quality of life for affected children and adolescents. By identifying gaps in knowledge and suggesting directions for future research, this narrative review contributes to the ongoing discourse on pediatric OCD treatments. Ultimately, the synthesis of evidence aims to enhance our understanding and inform best practices in the compassionate and effective management of OCD in children and adolescents. The aim of this study is to provide a comprehensive overview of current trends and emerging strategies in the treatment of pediatric obsessive-compulsive disorder (OCD) and highlights the significance of tailoring treatment approaches to individual patient needs, considering factors such as symptom severity and treatment response. Concentrating on interventions supported by empirical evidence, the review delves into cognitive-behavioral therapy (CBT), pharmacotherapy, the synergistic effects of these modalities, and inventive therapeutic approaches, all while considering the distinctive developmental aspects pertinent to pediatric populations. We conducted this review by searching for titles in the PubMed database from 2013 to present. Our comprehensive literature review focused on advancements in treating pediatric OCD, using keywords like "Obsessive-compulsive disorder," "Pediatric," "treatment," "CBT," "SSRI," "Pharmacotherapy," and "combination therapy." While both pharmacotherapy and CBT show individual efficacy, the combination of these approaches appears to be more effective, especially for medication non-responders with no prior exposure to CBT, despite some mixed findings. These findings contribute significantly to the ongoing discussion on optimizing combined therapy strategies tailored to the complexities of pediatric OCD.

The Effect of Brainwave Synchronization Using Binaural Beats on Improving Working Memory and Reducing the Severity of Symptoms in Women With Obsessive-compulsive Disorder.

Introduction: Binaural beats are one of the new methods of brainwave synchronization. However, there is little knowledge about its clinical applications. The positive effect of this method on executive functions, such as attention and working memory, in the γ band has been mainly confirmed in healthy individuals. Still, its effectiveness on disorders such as obsessive-compulsive disorder (OCD), with a prominent cognitive profile, has not been established. Therefore, the present study was conducted to examine the effect of binaural beats on working memory and the severity of OCD symptoms in the γ band in the affected women. Methods: Twenty-nine OCD women aged 25-40 years referring to psychological clinics in Tehran City, Iran, were selected by convenience sampling. After completing the symptom checklist 90 (SCL90) and the Yale-Brown severity scale (SS), the participants were given the Wechsler memory scale (WMS) digit repetition subtests. Then, they were randomly assigned to the experimental (n=15) and control (n=14) groups. The audio file of the binaural beats in the γ band was provided to the experimental group. The participants in the control group listened to the normal (no-wave) audio file. Both groups listened to the audio files for two weeks, three times a week, for 30 minutes each time. The Yale-Brown SS and digit repetition in post-test and one-month follow-up periods were obtained from both groups. Results: According to the results, the severity of OCD symptoms was significantly reduced in the post-test and follow-up stages by the γ binaural beats (P<0.05). Also, the working memory function was improved, although it was not statistically significant (P>0.05). Conclusion: The results of this study show that binaural beats can be used as a complementary treatment to reduce the severity of OCD symptoms. Also, it seems that the patients' working memory is strengthened with this method.

TMS-induced plasticity improving cognitive control in OCD II: Task-based neural predictors of treatment response.

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) has the potential to increase the clinical effect of exposure with response prevention (ERP) psychotherapy for obsessive-compulsive disorder (OCD). We investigated the use of task-based functional MRI (tb-fMRI) for predicting clinical outcomes to different rTMS protocols combined with ERP in OCD. METHOD: 61 adults with OCD underwent rTMS and ERP and were randomized to different high frequency rTMS conditions: left dorsolateral prefrontal cortex (DLPFC; n=19), left pre-supplementary motor area (preSMA; n=23), and control stimulation at the vertex at low intensity (n=19). The Tower of London task and Stop-Signal Task were used to assess pretreatment activation during planning and inhibitory control, respectively. We adopted a Bayesian region-based approach to test whether clinical improvement can be predicted by tb-fMRI-derived measures of task-related brain activation or functional connectivity between task-relevant regions and the bilateral amygdala. RESULTS: For the vertex group, but not the DLPFC/preSMA rTMS conditions, higher activation in several task-relevant regions during planning and response inhibition, and lower error-related activation, corresponded with better short-term clinical improvement. Lower precuneus activation with increased planning taskload correlated with symptom reduction in the DLPFC group. In the preSMA group, higher error-related activation and lower inhibition-related insular-amygdalar connectivity was associated with symptom reduction. CONCLUSIONS: Pretreatment tb-fMRI-derived measures of activation and connectivity during planning and inhibition-related processes are associated with clinical response for specific rTMS conditions in OCD. Future placebo-controlled trials with larger sample sizes should combine clinical information and neural correlates to improve prediction of clinical outcome.

A narrative review of factors affecting memory confidence in the context of compulsive checking: A search for evidence-based potential therapeutic targets to improve memory confidence.

BACKGROUND AND OBJECTIVES: According to current models of compulsive checking, memory confidence greatly contributes to the development and maintenance of checking behaviours. However, how to intervene in memory confidence in an evidence-based manner has not yet been fully understood. Thus, the purpose of the current paper was to identify the factors influencing memory confidence through the review of experimental evidence. METHODS: PubMed, Google Scholar, OpenGrey and ProQuest databases were searched by combining two sets of keywords related to memory confidence and checking. Our search yielded 24 experiments. Due to the considerable heterogeneity of the studies regarding questionnaires, tasks and paradigms used, data were synthesized using a narrative review approach. RESULTS: Six factors emerged from a thorough review of the literature, including negative memory belief, higher memory standard, inflated sense of responsibility, familiarization with the checked stimuli, number of checks and anxious valence of the checked stimuli. CONCLUSION: The findings have important implications for the treatment of compulsive checking. We suggested general guidelines to translate these factors into a novel intervention to increase memory confidence in compulsive checkers.

Glutamate dynamics and BOLD response during OCD symptom provocation in the lateral occipital cortex: A 7 Tesla fMRI-fMRS study.

Obsessive-compulsive disorder (OCD) is linked with dysfunction in frontal-striatal, fronto-limbic, and visual brain regions. Research using proton magnetic resonance spectroscopy (1H-MRS) suggests that altered neurometabolite levels, like glutamate, may contribute to this dysfunction. However, static neurometabolite levels in OCD patients have shown inconsistent results, likely due to previous studies' limited focus on neurometabolite dynamics. We employ functional MRS (fMRS) and functional magnetic resonance imaging (fMRI) to explore these dynamics and brain activation during OCD symptom provocation. We utilized a combined 7-tesla fMRI-fMRS setup to examine task-related BOLD response and glutamate changes in the lateral occipital cortex (LOC) of 30 OCD participants and 34 matched controls during an OCD-specific symptom provocation task. The study examined main effects and between-group differences in brain activation and glutamate levels during the task. A whole sample task-effects analysis on data meeting predefined quality criteria showed significant glutamate increases (n = 41 (22 OCD, 19 controls), mean change: 3.2 %, z = 3.75, p < .001) and task activation (n = 54 (26 OCD, 28 controls), p < .001) in the LOC during OCD blocks compared to neutral blocks. However, no differences in task-induced glutamate dynamics or activation between groups were found, nor a correlation between glutamate levels and task activation. We were able to measure task-induced increases in glutamate and BOLD levels, emphasizing its feasibility for OCD research. The absence of group differences highlights the need for further exploration to discern to what extent neurometabolite dynamics differ between OCD patients and controls. Once established, future studies can use pre-post intervention fMRS-fMRI to probe the effects of therapies modulating glutamate pathways in OCD.

Deep brain stimulation for obsessive compulsive disorder: the functional neurosurgeon armamentarium.

Deep brain stimulation (DBS) is a neurosurgical procedure that utilizes implanted electrodes and electrical stimulation for the treatment of neurological disorders. In cases where patients present with severe functional impairment while being refractory to less invasive treatment options, DBS is considered "gold standard." Still, DBS-related work is still widely under investigation, with ethical issues arising that may impact a patient's physical and psycho-social status. These include patient selection, informed consent, patient autonomy, pre-operation counseling and professional psycho-social preparation and follow-up support. Bioethicists and philosophers have increasingly worked together with in clinicians and researchers to identify, address and present ethical consideration in both clinical practice and research to balance the risk-benefit ratio in DBS treatment for obsessive-compulsive disorder.

Single-plug osteochondral autograft transplantation for knee osteochondritis dissecans: Clinical improvement and long-term survivorship at a minimum ten year follow-up.

PURPOSE: Osteochondritis dissecans (OCD) can lead to detrimental effects in the affected joints. Osteochondral autologous transplantation (OAT) allows to restore the articular surface with an autologous osteochondral unit. While short-term results are documented, there is a lack of long-term data. Aim of this study was to analyze the long-term clinical results of single-plug OAT for the treatment of knee OCD. METHODS: Twenty patients (14 men, 6 women) were treated with single plug-OAT. Mean age was 23.6 ± 9.9 years and BMI was 23.3 ± 3.6 kg/m2. Lesion size was 2.3 ± 1.6 cm2 and defects included 14 medial femoral condyles (MFC) and 6 lateral femoral condyles (LFC). Patients were followed up prospectively at baseline, 24 months, 60 months, and at minimum ten years (12.6 ± 2.0 years) using the IKDC subjective score and through an overall judgment on treatment satisfaction. The activity level was evaluated with the Tegner score and adverse events and failures were also recorded. Factors influencing the clinical outcomes, including age, sex, BMI, lesions size, and lesion location were also investigated. RESULTS: No severe adverse events and no surgical failures were reported and 85.0% of patients were satisfied at a minimum ten year follow-up. Subjective IKDC showed a significant and stable improvement at all follow-ups, passing from 45.3 ± 16.5 at baseline to 73.7 ± 16.6 at 24 months (p < 0.0005), to 72.9 ± 16.6 at 60 months (p < 0.0005), and to 74.1 ± 20.8 at long-term follow-up (p < 0.0005). Patients with OCD lesions localized on the LFC obtained lower results compared to those with MFC lesions at two years and five years (p = 0.034 and p = 0.023). The highest long-term scores were obtained in patients with lesion size lower than 2 cm2 (89.1 ± 8.8) compared to patients with lesion size between 2 and 4 cm2 (69.2 ± 15.7), and patients with lesion size larger than 4 cm2 (63.8 ± 34.6). CONCLUSIONS: OAT is a suitable technique to treat knee OCD in young patients and offers a high patient satisfaction and a significant improvement in terms of clinical subjective scores, with results remaining stable over time, although without reaching the pre-injury activity level. No severe adverse events and no surgical failures have been documented confirming OAT as a valid treatment option, although the best long-term results for lesions smaller than 2 cm2 and for MFC lesions should be considered when choosing this procedure to address knee OCD lesions.

Medial femoral condyle OCD (osteochondritis dissecans): correlation between imaging and arthroscopy.

Osteochondritis dissecans (OCD) describes a pathologic condition centered at the osteochondral junction that may result in an unstable subchondral fragment (progeny), disruption of the overlying cartilage, which may separate from the underlying parent bone. It is one of the causes of chronic knee pain in children and young adults. The current literature on OCD lesions focuses primarily on the medial femoral condyle (MFC), but inconsistent use of terminology, particularly in the distinction of OCD lesions between skeletally immature and mature patients has created uncertainty regarding imaging workup, treatment, and long-term prognosis. This article reviews the pathophysiology of MFC OCD lesions, highlighting the role of endochondral ossification at the secondary growth plate of the immature femoral condyles, the rationale behind the imaging work-up, and key imaging findings that can distinguish between stable lesions, unstable lesions, and physiologic variants. This overview also provides a case-based review to introduce imaging correlates with the ROCK (Research in Osteochondritis of the Knee) arthroscopic classification.

New horizons for obsessive-compulsive disorder drug discovery: is targeting glutamate receptors the answer?

INTRODUCTION: Over the past decade, glutamate has emerged as a prominent focus in the field of obsessive-compulsive disorder (OCD) pathophysiology. A convergence of evidence from genetic, preclinical, and clinical studies points to glutamatergic dysfunction as a key feature of this condition. In light of these findings, there has been a growing interest in exploring the potential of glutamatergic agents in the treatment of OCD. AREAS COVERED: This paper reviews the literature on glutamate transmission in OCD. In addition, the authors examine the results of clinical trials investigating the efficacy of glutamatergic agents in the treatment of OCD patients. EXPERT OPINION: Along with the recognition of neuroinflammation in the brain in OCD, the evidence of glutamate dysfunction represents one of the most promising recent discoveries for understanding the mechanisms involved in OCD. The importance of this discovery lies primarily in its pharmacological implications and has led to intense research activity in the field of glutamatergic agents. While this research has not yet had a substantial clinical impact, targeting glutamate receptors remains a promising horizon for the successful treatment of OCD patients.