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.

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.

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.

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 multiple domains.

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.

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.

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.

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.

TMS-induced plasticity improving cognitive control in OCD I: Clinical and neuroimaging outcomes from a randomised trial.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is an emerging treatment for obsessive-compulsive disorder (OCD). The neurobiological mechanisms of rTMS in OCD have been incompletely characterized. We compared clinical outcomes and changes in task-based brain activation following three different rTMS stimulation protocols, all combined with exposure and response prevention (ERP). METHODS: In this three-arm proof-of-concept randomized trial, 61 treatment-refractory adult OCD patients received 16 sessions of rTMS immediately prior to ERP over 8 weeks, with task-based functional MRI (tb-fMRI) scans and clinical assessments pre- and post-treatment. Patients received either: high frequency (HF) rTMS to the left dorsolateral prefrontal cortex (DLPFC)(n=19(6M/13F)); HF rTMS to the left pre-supplementary motor area (preSMA)(n=23(10M/13F)); or control rTMS to the vertex(n=19(6M/13F)). Changes in tb-fMRI activation pre-post treatment were compared using both a Bayesian region-of-interest and a general linear model whole-brain approach. RESULTS: Mean OCD symptom severity decreased significantly in all treatment groups (delta=-10.836, p<0.001, 95% CI[-12.504,-9.168]), with no differences between groups. Response rate in the entire sample was 57.4%. The DLPFC rTMS group showed decreased planning-related activation post-treatment that was associated with greater symptom improvement. No group-level activation changes were observed for the preSMA or vertex rTMS groups. Participants with greater symptom improvement in the preSMA group showed decreased error-related activation, and symptom improvement in the vertex group was associated with increased inhibition-related activation. CONCLUSIONS: PreSMA and DLPFC rTMS combined with ERP led to activation decreases in targeted task networks in individuals showing greater symptom improvement, although we observed no differences in symptom reduction between groups.

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.

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.

Outcomes and return to sport after osteochondral autograft transplantation for osteochondritis dissecans of the capitellum: a systematic review.

Background: Capitellar osteochondritis dissecans (OCD) lesions are common in athletes. Osteochondral autograft transfer (OAT) is one possible treatment option, though outcomes including return to sport (RTS) data are limited to small series. The purpose of this study was to systematically review RTS following OAT for capitellar OCD lesions. Our secondary objectives were to evaluate patient-reported outcomes (PROs), range of motion (ROM), and complications after OAT. Methods: PubMed, Embase, and Cumulative Index to Nursing and Allied Health Literature were searched for peer-reviewed articles on "osteochondral autograft transfer" and related terms for capitellar OCD lesions. Articles were included if they reported an RTS rate and had a follow-up time point of at least 12 months. Data on RTS rates, PRO measures, complications, and ROM were extracted. Articles were assessed for methodological quality using the Methodological Index for Non-randomized Studies criteria. Results: Six hundred sixty-six articles were retrieved, and 24 articles (470 patients) met the inclusion criteria. In total, 454/470 patients (97%) returned to sports following OAT for OCD. The RTS rate ranged from 79% to 100%. Return to previous level of performance ranged from 10% to 100%. Timmerman-Andrews postoperative scores (range = 169-193) were most often reported, with 87% of patients showing scores within the excellent range. Disabilities of the Arm, Shoulder, and Hand and Japanese Orthopedic Association scores were also excellent postoperatively for all studies reporting, with higher scores among centralized lesions vs. lateral. Conclusions: Following OAT for capitellar OCD lesions, RTS rates are high; however, athletes should be counseled on the potential of a return to lower performance or the need to change positions. Lateral lesion location may negatively impact outcomes. PRO scores are typically excellent and postoperative ROM consistently improves. This information helps counsel patients regarding expectations and outcomes of OAT for OCD of the capitellum.

Online CBT Versus Standard CBT for Pediatric Obsessive-Compulsive Disorder.

Obsessive-compulsive disorder (OCD), characterized by recurring obsessions and compulsions, affects 1-3% of the childhood population, often leading to severe impairment and reduced quality of life. Cognitive behavioral therapy (CBT) is well-documented as first choice treatment for pediatric OCD. Traditionally delivered face-to-face CBT has limitations in terms of accessibility, availability, and quality of delivery. Online CBT using video conferencing (online-CBT) at home aims to address some of these barriers. In this pilot study, we aimed to compare acceptability, feasibility and effectiveness of online CBT against face-to-face CBT. Online CBT outcomes of 29 children with OCD were analyzed benchmarked against outcomes of face-to-face CBT (n = 269) from the Nordic Long-term OCD Treatment Study, the largest CBT follow up study in pediatric OCD to date. Acceptability rated by online CBT participants and their parents was very high (Client Satisfaction Questionnaire total scores about 30, range 8-32). Feasibility assessed as dropout rate was comparable to NordLOTS (10.3% versus 9.7%). The online CBT group compared to NordLOTS showed a higher response rate (90% versus 60%; p = .002) and remission rate (81% versus 53%; p = .231). Our results suggest that the trusting therapeutic relationship necessary for demanding exposure-based treatment can be established by online CBT. Online CBT seems to be at least as effective in reducing OCD symptoms than standard CBT. Trial ID: ISRCTN37530113.

Therapeutic DBS for OCD Suppresses the Default Mode Network.

Background: Deep brain stimulation (DBS) of the anterior limb of the internal capsule (ALIC) is an emerging treatment for severe, refractory obsessive-compulsive disorder (OCD). The therapeutic effects of DBS are hypothesized to be mediated by direct modulation of a distributed cortico-striato-thalmo-cortical network underlying OCD symptoms. However, the exact underlying mechanism by which DBS exerts its therapeutic effects still remains unclear. Method: In five participants receiving DBS for severe, refractory OCD (3 responders, 2 non-responders), we conducted a DBS On/Off cycling paradigm during the acquisition of functional MRI to determine the network effects of stimulation across a variety of bipolar configurations. We also performed tractography using diffusion-weighted imaging (DWI) to relate the functional impact of DBS to the underlying structural connectivity between active stimulation contacts and functional brain networks. Results: We found that therapeutic DBS had a distributed effect, suppressing BOLD activity within regions such as the orbitofrontal cortex, dorsomedial prefrontal cortex, and subthalamic nuclei compared to non-therapeutic configurations. Many of the regions suppressed by therapeutic DBS were components of the default mode network (DMN). Moreover, the estimated stimulation field from the therapeutic configurations exhibited significant structural connectivity to core nodes of the DMN. Conclusions: Therapeutic DBS for OCD suppresses BOLD activity within a distributed set of regions within the DMN relative to non-therapeutic configurations. We propose that these effects may be mediated by interruption of communication through structural white matter connections surrounding the DBS active contacts.

An Observational Longitudinal Study on Seasonal Variations in Tourette Syndrome: Evidence for a Role of Ambient Temperature in Tic Exacerbation.

Tourette syndrome (TS) is a high-incidence neurobehavioral disorder that generally begins in childhood. Several factors play a role in its etiology, including genetic influence and auto-immune activation by streptococcal infections. In general, symptoms subside after the end of adolescence, but, in a significant number of patients, they remain in adulthood. In this study, we evaluated temporal variations in the two core clinical features of TS including tics and obsessive-compulsive disorder (OCD) symptoms. An observational longitudinal study lasting 15 months (2017-2019) was conducted on a cohort of 24 people recruited in Milan (Italy) who were diagnosed with a subtype of TS known as obsessive-compulsive tic disorder. Inclusion criteria included a global score of the Yale global tic severity scale (Y-GTSS) > 50, a Yale-Brown obsessive-compulsive scale (Y-BOCS) global score > 15, and TS onset at least one year prior. Y-GTSS and Y-BOCS data were acquired at six time points, together with local environmental data. Tics, but not OCD symptoms, were found to be more severe in spring and summer compared with winter and autumn (p < 0.001). Changes in tics displayed an appreciable oscillation pattern in the same subject and also a clear synchrony among different subjects, indicating an external orchestrating factor. Ambient temperature showed a significant correlation with Y-GTSS measurements (p < 0.001). We argue that the increase in tics observed during hot seasons can be related to increasing ambient temperature. We believe that our results can shed light on the seasonal dynamics of TS symptomatology and provide clues for preventing their worsening over the year.

Ceftriaxone Inhibits Conditioned Fear and Compulsive-like Repetitive Marble Digging without Central Nervous System Side Effects Typical of Diazepam-A Study on DBA2/J Mice and a High-5HT Subline of Wistar-Zagreb 5HT Rats.

Background: Ceftriaxone upregulates GLT1 glutamate transporter in the brain and may have anti-CFC and anti-OCD effects. Methods: Twenty WZ-5HT rats were used to investigate the effects of ceftriaxone on obsessive-compulsive (OCD)-like behaviour in the marble-burying (MB) test, freezing behaviour in contextual fear conditioning (CFC) and expression of GLT1 protein in the hippocampus or amygdala using immunoblots. Fifteen DBA/2J mice were used in the MB test. We also compared diazepam with ceftriaxone in open-field, beam-walking, and wire-hanging tests on 47 DBA/2J mice. Ceftriaxone (200 mg/kg) and saline were applied intraperitoneally, once daily for 7 (rats) or 5 (mice) consecutive days. A single dose of diazepam (1.5-3.0 mg/kg) or saline was injected 30 min before the behavioural tests. Results: Ceftriaxone significantly diminished OCD-like behaviour (↓ number of marbles buried) and freezing behaviour in CFC context session (↑ latencies, ↓ total duration, ↓ duration over four 2 min periods of the session) but increased GLT1 protein expression in the amygdala and hippocampus of rats. Diazepam induced sedation, ataxia and myorelaxation in mice. Ceftriaxone did not have these side effects. Conclusions: The results of this study confirm the anti-CFC and anti-OCD effects of ceftriaxone, which did not produce the unwanted effects typical of diazepam.

Astrocyte Gi-GPCR signaling corrects compulsive-like grooming and anxiety-related behaviors in Sapap3 knockout mice.

Astrocytes are morphologically complex cells that serve essential roles. They are widely implicated in central nervous system (CNS) disorders, with changes in astrocyte morphology and gene expression accompanying disease. In the Sapap3 knockout (KO) mouse model of compulsive and anxiety-related behaviors related to obsessive-compulsive disorder (OCD), striatal astrocytes display reduced morphology and altered actin cytoskeleton and Gi-G-protein-coupled receptor (Gi-GPCR) signaling proteins. Here, we show that normalizing striatal astrocyte morphology, actin cytoskeleton, and essential homeostatic support functions by targeting the astrocyte Gi-GPCR pathway using chemogenetics corrected phenotypes in Sapap3 KO mice, including anxiety-related and compulsive behaviors. Our data portend an astrocytic pharmacological strategy for rescuing phenotypes in brain disorders that include compromised astrocyte morphology and tissue support.

Individualized functional connectome abnormalities obtained using two normative model unveil neurophysiological subtypes of obsessive compulsive disorder.

The high heterogeneity observed among patients with obsessive-compulsive disorder (OCD) underscores the need to identify neurophysiological OCD subtypes to facilitate personalized diagnosis and treatment. In this study, our aim was to identify potential OCD subtypes based on individualized functional connectome abnormalities. We recruited a total of 99 patients with OCD and 104 healthy controls (HCs) matched for demographic characteristics. Individualized functional connectome abnormalities were obtained using normative models of functional connectivity strength (FCS) and used as features to unveil OCD subtypes. Sensitivity analyses were conducted to assess the reproducibility and robustness of the clustering outcomes. Patients exhibited significant intersubject heterogeneity in individualized functional connectome abnormalities. Two subtypes with distinct patterns of FCS abnormalities relative to HCs were identified. Subtype 1 patients primarily exhibited significantly decreased FCS in regions including the frontal gyrus, insula, hippocampus, and precentral/postcentral gyrus, whereas subtype 2 patients demonstrated increased FCS in widespread brain regions. When all patients were combined, no significant differences were observed. Additionally, the identified subtypes showed significant differences in age of onset. Furthermore, sensitivity analyses confirmed the reproducibility of our subtyping results. In conclusion, the identified OCD subtypes shed new light on the taxonomy and neurophysiological heterogeneity of OCD.

Clarifying the prevalence of OCD: A response to reader comments.

This response to a reader's comment on our paper "The Global Assessment of OCD" addresses the critique regarding the stated prevalence of OCD as the fourth most common mental disorder. We acknowledge an oversight in our initial reference, discuss the variable prevalence rates from various studies, and highlight the significant disability caused by OCD. We have requested a correction to the original citation to reflect more recent findings, aiming to ensure accuracy in the discourse on OCD's public health impact.