Obsessive-compulsive Research Articles

Introduction: Resistant hypertension, defined as blood pressure uncontrolled despite optimal use of three or more antihypertensives, is often attributed to physiological causes. However, nonadherence—frequently driven by psychological factors—remains under-recognized. Emerging evidence suggests that untreated psychiatric comorbidities, including obsessive-compulsive disorder (OCD), can drive medication nonadherence through ritualistic behaviors or irrational fears. Cognitive-behavioral therapy (CBT), particularly Exposure and Response Prevention (ERP), is a first-line intervention for OCD and has shown benefit in improving adherence. This case illustrates how targeted ERP for undiagnosed OCD in a patient with presumed treatment-resistant hypertension led to dramatic improvements in both adherence and blood pressure control. Case Description: A 52-year-old male with long-standing hypertension (BP 170/100 mmHg) presented repeatedly to the ED despite being on triple antihypertensive therapy. The patient reported anxiety surrounding medication side effects, and disclosed compulsive pill-counting, hoarding, and dose-skipping behaviors, especially if routines were disrupted. Psychiatric evaluation revealed previously undiagnosed OCD (Y-BOCS score 28), primarily centered on contamination fears. He underwent 12 weeks of structured ERP therapy focusing on medication-related rituals. Following treatment, his BP decreased to 128/82 mmHg, and medication adherence improved to 100%, confirmed through pill counts and electronic monitors. Emergency room visits dropped from six per year to zero. Discussion: This case underscores how OCD can present as “compulsive non-adherence,” where rituals—rather than deliberate refusal—drive treatment failure. Traditional adherence strategies (education, reminders) would likely have failed in this case. Instead, ERP successfully disrupted the OCD cycle, resolving the core behavioral barrier to adherence. This case reframes nonadherence not as defiance but as a psychiatric symptom, demanding psychiatric solutions. It advocates for routine mental health screening in patients with apparent treatment-resistant conditions and highlights the critical role of behavioral cardiology in managing chronic disease. Recognizing psychological drivers of nonadherence can lead to transformative improvements in both physiological outcomes and quality of life.

ABSTRACT While well characterized in Western populations, obsessive compulsive disorder (OCD) and its symptoms have received limited investigation among Eastern populations in comparison. This study examined symptom prevalence and clinical correlates of OCD symptoms across 400 Japanese college students using the obsessive-compulsive inventory revised (OCI-R)–an evidence-based self-report OCD assessment. A randomly selected subset of participants with elevated (n = 73) and non-elevated (n = 67) obsessive-compulsive symptoms completed follow-up assessments characterizing OCD symptom severity, anxiety, depression, stress, emotion regulation, and quality of life. Nearly half of 400 surveyed participants (46.5%) had clinically elevated OCD symptoms on the OCI-R. Elevated OCD symptom participants were found to have OCD symptoms that were mild to moderate in severity with around 4.3% of the total participants with moderate OCD symptoms. Greater OCD symptom severity corresponded with higher depression, stress, and anxiety–as well as lower emotion regulation and quality of life. Findings highlight the common prevalence of obsessive-compulsive symptoms and identify the significant effect that obsessive-compulsive symptoms have upon individuals who experience them. While future research is needed to ascertain the specific contributions of cultural factors in OCD, findings further emphasize the importance of early OCD symptom identification that can result in timely evidence-based treatment of OCD in Japanese college students.

Abnormal intrinsic brain activity of the sensory-motor area as a predictor of the response to selective serotonin reuptake inhibitors in treatment-naïve obsessive-compulsive disorder.

Exploring the interrelations of obsessions, compulsions, and health: the mediating role of psychotic symptoms in individuals with obsessive-compulsive disorder.

Pavlovian fear reversal learning predicts outcome of exposure-based cognitive behavioral therapy for adult obsessive-compulsive disorder.

Development and validation of a machine learning model to predict cognitive behavioral therapy outcome in obsessive-compulsive disorder using clinical and neuroimaging data.

In less than 30 years, Deep Brain Stimulation (DBS) has evolved from an antiparkinsonian rescue intervention into a flexible neuromodulatory therapy with the potential for personalized, adaptive, and enhancement-focused interventions. In this review we collected evidence from seven areas: (i) modern eligibility criteria, and ways to practically improve on these, outside of ‘Core Assessment Program of Surgical Interventional Therapies in Parkinson’s Disease’ (CAPSIT-PD); (ii) cost-effectiveness, where long-horizon models now show positive incremental net monetary benefit for Parkinson’s disease, and rechargeable-devices lead the way in treatment-resistant depression and obsessive–compulsive disorder; (iii) anatomical targets, from canonical subthalamic nucleus (STN) / globus pallidus internus (GPi) sites, to new dual-node and cortical targets; (iv) mechanistic theories from informational lesions, antidromic cortical drive, and state-dependent network modulation made possible by optogenetics and computational modeling; (v) psychiatric and metabolic indications, and early successes in subcallosal and nucleus-accumbens stimulation for depression, obsessive–compulsive disorder (OCD), anorexia nervosa, and schizophrenia; (vi) procedure- and hardware-related safety, summarized through five reviews, showing that the risks were around 4% for infection, 4–5% for revision surgery, 3% for lead malposition or fracture, and 2% for intracranial hemorrhage; and (vii) future directions in connectomics, closed-loop sensing, and explainable machine learning pipelines, which may change patient selection, programming, and long-term stewardship. Overall, the DBS is entering a “third wave” focused on a better understanding of neural circuits, the integration of AI-based adaptive technologies, and an emphasis on cost-effectiveness, in order to extend the benefits of DBS beyond the treatment of movement disorders, while remaining sustainable for healthcare systems.

Adverse events associated with four atypical antipsychotics used as augmentation treatment for major depressive disorder: A pharmacovigilance study based on the FAERS database.

The orbitofrontal cortex (OFC) plays a pivotal role in integrating sensory, emotional, and cognitive signals to support flexible, goal-directed behavior. This review synthesizes converging evidence from lesion studies, neuroimaging, intracranial recordings and stimulations to elucidate the OFC's contribution to emotional regulation, social behavior, and value-based decision making. Lesions in the OFC are associated with affective disturbances, social disinhibition, and impaired behavioral adaptation to feedback. The OFC evaluates the hedonic valence of stimuli across sensory modalities-visual, gustatory, olfactory, somatosensory, and auditory-thereby contributing to subjective affective experience. Intracranial and neuroimaging data further underscore the OFC's involvement in processing emotional facial expressions, tactile pleasure, and social cues such as attractiveness and vocal identity. Stimulation studies provide causal evidence for the OFC's role in modulating emotional perception and mood. Structural and functional alterations of the OFC are consistently observed across multiple neuropsychiatric conditions, including major depressive disorder, obsessive-compulsive disorder, borderline personality disorder, and addiction. These abnormalities manifest as impaired reward processing, increased impulsivity, and affective dysregulation, and may be ameliorated by targeted neuromodulatory interventions such as deep brain stimulation and repetitive transcranial magnetic stimulation. Collectively, findings highlight the OFC as a central hub for affective-cognitive integration and as a promising target for therapeutic modulation in psychiatric disorders.

Neighborhood experience and hoarding disorder.

Early-life social isolation stress worsens compulsive- and anxiety-like behaviour and alters gene expression in the prefrontal cortex of SAPAP3 knockout mice.

Previous studies have highlighted alterations of white matter (WM) integrity underlying mechanisms of obsessive-compulsive disorder (OCD). However, whole-brain WM abnormalities in OCD at the tract-level still remain largely unknown. In current study, we evaluated the integrity of 42 WM tracts in individuals with OCD using the novel tractography toolbox, TRActs Constrained by UnderLying Anatomy (TRACULA), and investigated the grey matter changes linked to the white matter alterations. Furthermore, we investigated the association of diffusion measures with clinical symptom severity. DTI and T1-weighted image data were collected from 54 medication-free OCD patients and 39 age- and sex-matched healthy controls (HCs). TRACULA was used to reconstruct 42 WM tracts and produce tract volume, fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) of each tract, and grey matter measures were extracted from T1-weighted images. Group comparisons of these measures were evaluated with analysis of covariance. Comparing to HCs, OCD patients showed widespread decreased FA, including rostrum of the corpus callosum, uncinate fasciculus, frontal aslant tract, inferior longitudinal fasciculus, acoustic radiation and optic radiation. Additionally, we found grey matter changes linking to the detected white matter changes, including abnormalities in the medial orbital frontal cortex, superior frontal gyrus, pars opercularis, precentral gyrus, postcentral gyrus, lingual gyrus, and Heschl’s Gyrus. Our results demonstrated that OCD had structural disconnection not only within the traditional frontal-limbic networks but also extended to the visual and auditory systems.

Deep brain stimulation has been used to treat severe, refractory obsessive-compulsive disorder (OCD) with variable outcomes across multiple anatomical targets. To overcome these limitations, we developed an invasive brain mapping paradigm in which electrodes were implanted across the OCD cortico-striato-thalamo-cortical circuit. We then performed extensive stimulation mapping during a multi-day inpatient stay to identify personalized therapeutic targets and characterize their downstream circuit effects. We found two targets within the right ventral capsule (VC) that acutely reduced OCD symptoms. Prolonged VC stimulation suppressed high frequency activity within the structurally and functionally connected orbitofrontal and cingulate cortex, which were identified to be cortical nodes encoding the severity of OCD symptoms. These VC sites were implanted for DBS and combined stimulation of these targets led to a rapid therapeutic response. This case provides the first proof-of-concept that invasive brain mapping can be used to guide a novel personalized, multi-site neuromodulation approach to treat refractory OCD.

Deep brain stimulation (DBS) in the anterior limb of the internal capsule (ALIC) for obsessive-compulsive disorder (OCD) can result in large improvements in symptoms and quality of life. However, without a consistent stimulation target within the anatomically variable ALIC region, the therapy has required long and unpredictable trial-and-error periods of parameter optimization to achieve these clinically meaningful benefits. To facilitate scalability and clinical implementation of ALIC DBS for OCD, this study aimed to demonstrate the evolution of prospective DBS targeting using patient-specific tractography. Initially, the authors targeted a white matter map of ALIC bundles and cortical regions previously implied in DBS for OCD. They then generated a map of the ALIC connection shared by 6 participants with OCD who responded to DBS. This common responder map implicated white matter connections to the ventromedial prefrontal/orbitofrontal cortex (vmPFC/OFC), ventrolateral prefrontal cortex (vlPFC), and midbrain. Next, we prospectively targeted a new series of 7 patients guided by this common map. Finally, we generated a tractography-based predictive model based on individual stimulation-response outcomes to estimate the relative importance of each targeted ALIC pathway. Targeting a sweet spot in the common responder ALIC map that optimally connected the patient-specific vmPFC/OFC, vlPFC, and midbrain led to a consistent and predictable reduction of OCD symptoms, with 8 of 10 patients attaining a clinically meaningful Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score reduction in symptom severity of at least 35%. Individualized tractography-based targeting improved the primary OCD symptoms independent of hypomania or other changes in mood or anxiety and required minimal parameter changes away from the empirical tractography-based target spot. The tractography-based stimulation model generated a connectivity profile of left and right ALIC pathways that selectively predicted Y-BOCS score reduction and could be used to optimize future targeting further. The authors' results show how patient-specific tractography can facilitate clinically effective precision targeting in ALIC DBS for OCD.

Childhood-onset obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder with a strong genetic component. De novo variants (DNVs) have been shown to have a role in childhood-onset OCD, but to date, no DNV analysis has been performed in patients from a genetically isolated population. Here, we aimed to investigate the impact of rare de novo single nucleotide variants (dnSNVs) on childhood-onset OCD risk in the French-Canadian population. In a cohort of 36 French-Canadian trios comprised of 36 probands with childhood-onset OCD and 72 unaffected parents, we identified 34 dnSNVs harboured in 34 different genes. We found that four of these genes were previously associated with OCD, replicating their contribution to its risk. We also observed complete overlap between our 34 candidate genes and genes associated with 11 related neuropsychiatric disorders, supporting a shared underlying genetic susceptibility across psychopathologies. Among genes harbouring DNVs across three childhood-onset OCD cohorts, we observed an overrepresentation of genes involved in clathrin-dependent endocytosis (GO:0072583; p-adj = 0.0498) and phosphatidylinositol binding (GO:0035091; p-adj = 0.0431), offering potential biological mechanisms underlying childhood-onset OCD. No association was found between the number of dnSNVs in childhood-onset OCD probands and OCD symptom severity. Altogether, this study offers a framework for performing DNV analyses of complex disorders in genetically isolated populations. Additionally, we have provided the first list of candidate childhood-onset OCD genes in the French-Canadian population.

Background This study aimed to assess the risk of major psychiatric and neurodevelopmental disorders in first degree relatives (FDRs) of individuals with panic disorder (PD), including PD, bipolar Disorder (BD), major depressive disorder (MDD), schizophrenia, obsessive-compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD), and autism spectrum disorder (ASD). Material and methods Between 2001 to 2010, we included 153,091 FDRs of individuals with PD and 1:4 matched controls based on age and sex from the Taiwan National Health Insurance Research Database. Poisson regression model with a robust error variance to estimate the relative. Results After adjusting for demographics and psychiatric disorders, FDRs of individuals with PD had a higher risk of PD (reported as adjusted relative risk with 95% confidence interval: (ARR:2.74, 95%CI: 2.56 to 2.93), BD (ARR:1.24, 95%CI: 1.15 to 1.34), MDD (ARR: 1.46, 95%CI: 1.40 to 1.53), ADHD (ARR: 1.25, 95%CI: 1.18 to 1.32), and OCD (ARR:1.54, 95%CI:1.40 to 1.69) compared to their matched controls. Conclusion Our findings may aid in counselling and early awareness of major psychiatric and neurodevelopmental disorders. Future genetic and population studies are needed to investigate the underlying mechanisms and confirm our findings.

Existing evidence suggests a close association between antidepressants (ATDs) and the increased incidence of psychiatric disorders. However, causality has yet to be confirmed. We aim to evaluate the causal relationship between ATDs and five psychiatric disorders using the Two-sample Mendelian Randomization (TSMR) method. This study utilized TSMR analysis to explore the causal impact of ATDs on convulsion (CONV), schizophrenia (SCZ), obsessive-compulsive disorder (OCD), substance abuse (SA), and suicide or self-harm (SOSH). The primary evaluation of causality was conducted using the Inverse Variance Weighted (IVW) method; supplementary validations were performed using the Weighted median, Weighted mode, and MR Egger methods. Sensitivity analyses, including MR-Egger intercept test, Cochran's Q test, and leave-one-out analysis, were conducted to assess potential heterogeneity and pleiotropy. The IVW method results revealed a significant positive causal relationship between genetically predicted ATDs and CONV (OR = 1.174; 95% CI 1.038, 1.328; P = 0.011), SCZ (OR = 1.177; 95% CI 1.038, 1.335; P = 0.011), OCD (OR = 1.755; 95% CI 1.355, 2.273; P = 2.06E-05), SA (OR = 1.326; 95% CI 1.222, 1.440; P = 1.61E-11), and SOSH (OR = 1.461; 95% CI 1.394, 1.532; P = 1.71E-50). The supplementary and sensitivity analyses indicated robust and reliable findings. Our study suggests that ATDs are potential risk factors for CONV, SCZ, OCD, SA, and SOSH. It is necessary to comprehensively evaluate both the therapeutic effects and potential risks of ATDs in clinical practice. Individualized treatment plans should be formulated for patients with CONV, SCZ, OCD, SA, and SOSH, with increased attention during the clinical use of ATDs.

Event-related potential correlates of visual processing across obsessive-compulsive and anxiety spectrum disorders: a scoping review.

The standard assessment of mental health typically involves clinical interviews conducted by highly trained clinicians. While effective, this approach faces substantial limitations, including high costs, high clinician workload, variability in expertise, and a lack of standardization. Recent progress in large language models (LLMs) offer a promising avenue to address these limitations by simulating clinician-administered interviews through AI-powered systems. However, few studies have rigorously validated such tools. In this study, we used TalkToAlba to develop and evaluat an AI assistant designed to conduct clinical interviews aligned with DSM-5 criteria. Participants (N = 303) included individuals with self-reported clinician-diagnosed mental health disorders, namely, major depressive disorder (MDD), generalized anxiety disorder (GAD), obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), attention-deficit/hyperactivity disorder (ADD/ADHD), autism spectrum disorder (ASD), eating disorders (ED), substance use disorder (SUD), and bipolar disorder (BD)—alongside healthy controls. The AI assistant conducted diagnostic interviews and assessed the likelihood of each disorder, while another AI system analyzed interview transcripts to verify diagnostic criteria and generate comprehensive justifications for its conclusions. The results showed that the AI-powered clinical interview achieved higher agreement (i.e., Cohen’s Kappa), sensitivity, and specificity in identifying self-reported, clinician-diagnosed disorders compared to established rating scales. It also exhibited significantly lower co-dependencies between diagnostic categories. Additionally, most participants rated the AI-powered interview as highly empathic, relevant, understanding, and supportive. These findings suggest that AI-powered clinical interviews can serve as accurate, standardized, and person-centered tools for assessing common mental disorders. Their scalability, low cost, and positive user experience position them as a valuable complement to traditional diagnostic methods, with potential for widespread application in mental health care delivery.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-13429-x.

Obsessive-compulsive disorder (OCD) is a chronic neuropsychiatric condition often resistant to conventional treatments such as cognitive behavioral therapy and pharmacotherapy. For treatment-refractory cases, neuromodulation techniques offer promising alternatives. This review provides an overview of recent advances in three major neuromodulation strategies: transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), and deep brain stimulation (DBS). DBS has demonstrated robust efficacy across several brain targets, though clinical outcomes are influenced by interindividual variability in fiber anatomy, lead positioning, correct parameter adjustments, and symptomatology. Recent efforts focus on connectivity-based targeting, patient-specific imaging, and the development of closed-loop systems guided by electrophysiological and neuroimaging biomarkers. rTMS, a noninvasive neuromodulation technique, shows therapeutic potential but lacks consensus on optimal parameters and cortical targets, despite FDA approval of certain stimulation protocols. tDCS, while the most accessible modality, presents inconclusive evidence due to small sample sizes and heterogeneity in electrode montages. Overall, these neuromodulation techniques are rapidly evolving and hold considerable promise, but further high-quality studies are needed to standardize stimulation protocols, validate reliable biomarkers and tailor interventions to individual patient profiles. Personalized neuromodulation may represent the future of therapeutic strategies in OCD.