Obsessive Compulsive Disorder: Systematic Review with ☸️SAIMSARA.

DOI: 10.62487/saimsara99e2ed0c

• Generated: 2026-02-18 01:31:30 CET
• Plan: Pro (expanded craft tokens; source: Europe PMC)
• Source: Europe PMC
• Scope: Titles/Abstracts (tiab)
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• Total Abstracts/Papers: 21820
• Downloaded Abstracts/Papers: 21820
• Included original Abstracts/Papers: 13404
• Total study participants (naïve ΣN): 13033702

• Bias: Qualitatively inferred from study design fields. The included studies predominantly comprise cohort studies (many without specified directionality), mixed-design studies, and randomized controlled trials (RCTs), with fewer cross-sectional or case-control designs. The lack of explicit directionality in many cohort studies and the reliance on cross-sectional designs in some prevalence studies limit causal inference. Small sample sizes in several intervention studies and case reports also introduce potential for bias and limit generalizability.

• Comorbidity with Autism Spectrum Disorder (ASD): Onychophagia (nail-biting) in OCD patients is highly associated with ASD (96.2% vs. 18.0% in OCD-only) [6]. ASD is frequently comorbid with OCD, with 9% prevalence in autistic populations [9442] and shared repetitive behaviors [2056, 6719, 7830].
• OCPD Traits and OCD Severity: Pathological obsessive-compulsive personality disorder (OCPD) traits positively correlate with OCD symptom severity (r = 0.42, p < .001) and the number of obsessive-compulsive related disorder (OCRD) symptom domains (r = 0.39, p < .001) [11]. OCPD diagnosis can be unstable over time [35].
• Neurobiological Abnormalities: OCD is characterized by widespread functional connectivity density abnormalities within and beyond the cortico-striatal-thalamic loop [13, 653], abnormal spontaneous white matter neural activity [14], and distinct EEG microstate patterns [19, 27]. Structural alterations in the orbitofrontal cortex (OFC) and insula are associated with illness severity [199, 1043, 11285, 799].
• Neurological Comorbidities: OCD has an increased prevalence in people with multiple sclerosis (10.7%, OR = 3.25) [32, 2940], Huntington's disease [5038], and is associated with delayed walking acquisition in chronic tic disorders (OR: 1.01-1.27) [1528]. Focal epilepsy shows a significant genetic causality with OCD (OR, 1.44) [3152].
• Psychotic Symptoms and Health Impact: Psychotic symptoms fully mediate the relationship between compulsions and health in individuals with OCD, with high prevalence of positive (53.9%), negative (74.7%), and depressive (83.5%) psychotic symptoms [33]. Comorbid OCD is found in 13.5% of clinical high-risk for psychosis samples [2098], and OCD-like symptoms can be early warning signs for psychosis [9953].
• Relationship Obsessive-Compulsive Disorder (ROCD): Married women with ROCD experience marital difficulties due to chronic doubt, emotional dysregulation, and maladaptive coping [15]. Dyadic interaction patterns can exacerbate ROCD symptoms [243].
• Technology as Trigger and Coping Tool: Adults with OCD describe technology as both a trigger and a coping tool, with features like notifications and complex user interfaces reinforcing compulsive behaviors [10]. Smartphone apps are top choices for self-management [165].
• Perinatal OCD: A significant proportion of pregnant women (8.4%) experience OCD onset during pregnancy and postpartum, with socioeconomic and psychological vulnerabilities increasing risk [21, 1404, 8091]. Birth trauma was not significantly associated with OCD risk in postpartum women [986].
• Genetic and Epigenetic Factors: Genome-wide analyses identified 30 independent loci associated with OCD, with genetic risk shared with many other psychiatric disorders [206, 3883]. Rare variants in KNCN/MKNK1-AS1 overlap region are associated with OCD [314]. Differentially methylated regions (DMRs) are associated with OCD diagnosis [909]. Polygenic scores for AN and OCD are linked to lower adverse perinatal events [1432].
• Inflammation and Gut Microbiota: Evidence supports gut microbiota as a modifiable co-factor in OCD, with reduced short-chain fatty acid capacity and pro-inflammatory pathways [195, 5897, 3258]. TH22 immunity is related to OCD [714]. Neuroinflammation is implicated in OCD [1232, 2741, 6093].
• Cognitive and Emotional Dysregulation: OCD patients exhibit higher impulsivity and maladaptive cognitive emotion regulation strategies [41], impaired planning and problem-solving [570], and biased attention towards stimuli associated with compulsive acts [832]. Alexithymia is significantly higher in OCD patients and associated with impaired sexual functioning and dyadic adjustment [45, 224]. Intolerance of uncertainty is a transdiagnostic vulnerability [1178, 5591, 2094].
• Treatment Modalities – Psychotherapy:
• Exposure and Response Prevention (ERP): VC ERP shows significant, persistent reductions in YBOCS scores, comparable to in-person ERP [36]. Parent training in ERP is an innovative approach for pediatric OCD [91]. Leaning into anxiety during ERP tasks predicts symptom improvement [460, 2901]. ERP combined with SSRIs is more effective than SSRI-only in adolescents [53]. Pavlovian fear reversal learning predicts ERP response [230]. Psychological interventions have large average effects (g = 1.18) [1839].
• Cognitive Behavioral Therapy (CBT): Digital sensor-assisted CBT reduces symptoms with high satisfaction [42]. ICBT is sought due to lack of access or previous unhelpful face-to-face treatment [450, 3294]. VERP is safe with fewer side effects than usual care [454]. CBT improves task control deficits [462]. Family-based CBT is effective for pediatric OCD [279]. Transdiagnostic CBT is effective [6173].
• Acceptance and Commitment Therapy (ACT): Group-delivered ACT is non-inferior to CBT+ERP in reducing OCD symptoms [376]. ACT combined with ERP is effective, with adaptation protocols for cultural contexts [394, 6908].
• Other Psychotherapies: Chairwork-based interventions show efficacy [1011]. Mindfulness- and acceptance-based programs (MABPs) show large reductions in OCD severity, comparable to CBT/ERP [363]. Farm-based therapy may improve OCD symptoms [924].
• Treatment Modalities – Pharmacotherapy:
• SSRIs: SSRIs are cornerstone treatments [835]. Lower zfALFF in the sensory-motor area (SMA) predicts SSRI response [249]. Fluoxetine is effective in child and adolescent OCD [11841]. Antidepressants are prescribed to 55% of pediatric OCD patients [353]. Antidepressants are associated with an increased risk of OCD [1555].
• Augmentation Strategies: Brexpiprazole augmentation to SRIs shows significant symptom reduction in treatment-resistant OCD [273]. Lurasidone and fluvoxamine combination shows rehabilitation effects in AN-r with comorbid OCD [96]. Quetiapine monotherapy is beneficial for bipolar depression with comorbid OCD [2050]. Cariprazine add-on therapy rapidly resolves OCD symptoms in schizophrenia patients [2055, 5559]. Ondansetron augmentation to SRIs reduced overall OCD severity [2131]. Vortioxetine monotherapy shows preliminary efficacy in SSRI-resistant OCD [1655].
• Novel Pharmacotherapies: Psilocybin produces rapid, clinically meaningful, and sustained reductions in treatment-resistant OCD [779, 326, 5576, 7546, 10831]. Ketamine shows potential for treatment-resistant OCD [1877, 4516]. Saffron is as effective as fluvoxamine for mild-to-moderate OCD [3210]. Medicinal cannabinoid-rich cannabis (NTI164) improved OCD in children with PANS [951]. Evidence for medicinal cannabis in treating OCD is inconclusive [1380, 6502].
• Neuromodulation:
• Deep Brain Stimulation (DBS): DBS of the VC/VS region leads to rapid symptom improvement in OCD [50, 285]. Pre-treatment connectome characteristics predict treatment response [1302]. DBS is effective for severe, treatment-refractory OCD, with a decrease of 5.1 YBOCS points compared to sham [285, 2871, 7178, 10763, 10267, 9600, 9836, 11291, 3277]. Robot-assisted stereotaxy shows high accuracy for DBS lead placement [5455]. DBS increases BMI in patients with AN and OCD [3225]. Personalized stimulation sites can be identified using sEEG [2287].
• Transcranial Magnetic Stimulation (TMS): Pretreatment parietal beta power bands predict dTMS response in treatment-resistant OCD [202]. Low-frequency rTMS to the right dlPFC is being assessed [270, 4002]. Single-session inhibitory TMS reduces compulsions [2096]. rTMS leads to reorganization of brain functional networks [3189, 3403].
• Transcranial Direct Current Stimulation (tDCS): Early augmentation with tDCS rapidly reduces symptom severity [225]. Dual-site cathodal tDCS over OFC and pre-SMA shows promise [471]. tDCS may reduce Y-BOCS scores, especially with ≤20 days treatment [346]. Intensified tDCS over the right inferior frontal cortex showed limited efficacy [2701]. Online tDCS to pre-SMA reduces disgust sensitivity [2085].
• Other Neurosurgical Interventions: Gamma knife capsulotomy is effective for refractory OCD [4712]. Limbic leukotomy provides substantial benefit for severe OCD [12604]. High-intensity focused ultrasound (FUS) lesioning shows promise [1533]. Endoscopic interhemispheric bilateral anterior cingulotomy is used for OCD [8417].
• Impact on Family and Social Life: Family accommodation (FA) is pervasive in OCD, occurring in over 90% of cases [196]. OCD indirectly impacts family members, often leading them to seek medical attention [239]. OCD is the most trivialized mental health condition on social media [8780].
• Diagnostic Challenges and Misdiagnosis: Over one-third of psychologists incorrectly diagnose OCD vignettes, impacting treatment recommendations [198]. Bipolar disorder is commonly misdiagnosed as OCD [9814]. Scepticism regarding online presentations of psychiatric disorders is common for OCD [1033].
• Cognitive Inflexibility and Reward/Punishment Sensitivity: OCD patients show impaired performance on reversal learning tasks [9506, 462], and poor behavioral adaptation to changing reinforcement-punishment contingencies, with greater sensitivity to punishment under uncertainty [1401]. Deletion of 5-HT3A receptor enhances cognitive flexibility in mice [1191].
• Suicidality: OCD symptoms are strongly correlated with suicidal ideation [2132, 2970, 7826]. Psychotic symptoms fully mediate the relationship between compulsions and health, including suicidality [33]. Pre-existing mental health disorders, including OCD, increase the speed of transition from suicidal ideation to plans/attempts [5649].
• Childhood and Adolescent OCD: Children with OCD demonstrate marked domain-specific functional impairments, particularly during school, after school, and nighttime routines [37]. Early-onset OCD may be a distinct subtype with glutamatergic imbalance [1616]. Early intervention protocols aim to reduce chronicity [223, 4263]. Pediatric OCD patients tolerate lower doses of antidepressants/antipsychotics due to side effects [7091].
• Co-occurring Behaviors and Conditions:
• Body-Focused Repetitive Behaviors (BFRBs): Onychophagia is present in 8.6% of OCD patients [6]. Bruxism is more frequent in OCD patients [558, 235]. Trichotillomania (TTM) patients have a significantly higher risk of subsequent OCD diagnoses [1710] and shares features with OCD [1417, 3949, 7544, 13042].
• Eating Disorders (EDs): OCD is a common comorbidity in young people with Anorexia Nervosa (AN) and Atypical Anorexia Nervosa (AAN) [1270, 1389, 3002, 3388, 6256, 12301, 12481]. Lack of identity predicts OCPD traits in female ED patients [1124]. Orthorexia nervosa shares traits with OCD [1878, 4973, 8064]. OCD symptoms related to symmetry, checking, and aversion to dirt/germs predict ED symptoms [8542].
• Tourette Syndrome (TS): OCD is a significant predictor of increased tic severity [1254, 4162, 4065, 8219]. Comorbid ADHD and OCD influence long-term adaptive outcomes in TS [11992].
• Sleep Disorders: Poor sleep quality is associated with probable OCD [542]. REM sleep deprivation in rats leads to OCD-like behaviors [2159]. Phase angle between dim light melatonin onset and sleep midpoint is associated with OCD symptom severity [3724]. Burn survivors with new sleep disorders have increased OCD risk [1339].
• Addictive Behaviors: Problematic gaming is associated with OCD [7029]. Smartphone addiction is linked to higher OCD scores [3808, 4455, 1560]. Obsessive-compulsive personality traits show a heterogeneous relationship with gambling severity [1781, 8094, 9498, 11164, 5397].
• Public Perception and Stigma: OCD received higher "true self" ratings compared to other severe mental disorders [1392, 1393]. It is among the least stigmatized diagnoses [4032] but also among the most trivialized on social media [8780]. Belief in a symptom continuum reduces desire for social distance [9954].
• Biomarkers and Predictive Factors: Resting-state EEG-derived sensorimotor network alterations in theta and high alpha bands are candidate biomarkers [27]. Alterations in miR-132 and miR-125b-5p expression, and higher serotonin levels, are promising biomarkers [226]. Pretreatment parietal beta power bands predict dTMS response [202]. Structural-functional multilayer network properties predict rTMS outcome [233]. Regional vulnerability index (RVI) differentiates OCD patients from controls and correlates with symptoms [425].
• COVID-19 Impact: Remote mental healthcare maintained treatment efficacy for OCD during the pandemic [1583, 6294, 8235]. OCD symptoms increased in young subjects during the pandemic [2089]. COVID-19 infection was associated with a higher prevalence of OCD symptoms [2996, 5555]. Primary care contacts for OCD dropped during restrictions [6871]. Anxiety, depressive disorders, and OCD increased in psychiatric emergency department admissions during the pandemic [3229, 8803].
• Transdiagnostic Features: Amygdala functional connectivity alterations converge across major psychiatric disorders, including OCD [792]. Intolerance of uncertainty and negative problem orientation are transdiagnostic vulnerabilities [1178]. Cognitive biases are transdiagnostic, with OCD showing the highest severity for interpretation biases [4039, 3668]. Increased frequency of involuntary memories is a transdiagnostic phenomenon [1838]. Midfrontal theta activity is a neural index of cognitive control differing in psychiatric conditions with cognitive control deficiencies, including OCD [5496].
• Specific OCD Presentations: Religious content obsessions in young men can be typified into three forms [325, 10952]. Scrupulosity is a pediatric OCD symptom dimension [1686]. Suicidal obsessions in OCD differ from suicidal ideation [1703]. Contamination-based OCD involves higher contamination ratings and looming vulnerability [2715, 3164].
• Early Onset and Risk Factors: Lower socioeconomic status, lower IQ, younger age, maternal stress during pregnancy, absence of breastfeeding, and parental/youth baseline OCS predict higher follow-up OCS [7374]. Failing early educational transitions increases OCD risk [4001]. Prenatal exposure to maternal autoimmune diseases increases offspring OCD risk [6735]. Cesarean delivery is associated with increased odds of OCD [8385].
• Other Comorbidities: OCD is comorbid with myofascial pain dysfunction syndrome (MPDS) [235], Sjögren's syndrome (HR 3.31) [2088], and higher rates in patients with severe acne treated with systemic therapies [1817]. Women with bipolar disorder have a higher prevalence of comorbid OCD [874]. First-degree relatives of TRD patients have increased OCD risk (aRR 3.14) [3366]. Genetic predisposition to fatty liver disease is associated with increased OCD risk [2881].
• AI and Digital Health: AI technologies offer transformative potential for early detection and treatment enhancement in OCD [216]. Automated classification systems can accurately label exposure and encourage events in pediatric OCD therapy sessions [1642]. Large language models (LLMs) show potential in providing accurate responses to OCD queries [4508].

• Early Detection and Screening: Given the significant prevalence and impact of OCD, especially in vulnerable populations like pregnant women [21], youth [37], and those with other psychiatric or neurological conditions [32, 542], routine screening for OCD symptoms should be integrated into primary care and specialized medical settings.
• Tailored Treatment Approaches: The heterogeneity of OCD, including specific presentations like ROCD [15], scrupulosity [1686], and contamination fears [2715], necessitates personalized treatment plans. Combined interventions, such as ERP with SSRIs [53] or novel psychotherapies like ACT [376], should be considered, alongside neuromodulation for treatment-resistant cases [779, 285].
• Addressing Comorbidity: The high rates of comorbidity with conditions like ASD [6], OCPD [11], eating disorders [1270], and psychotic symptoms [33] demand a transdiagnostic and multidisciplinary approach to care. Clinicians should be vigilant for co-occurring disorders to optimize treatment outcomes and address overall patient health.
• Leveraging Technology: Technology can be both a trigger and a coping tool for OCD [10]. Integrating digital health solutions, such as smartphone apps for self-management [165] and videoconferencing-delivered therapy [36, 6711], can enhance accessibility and support, particularly for pediatric patients via parent training [91].
• Suicide Risk Mitigation: The strong correlation between OCD symptoms and suicidal ideation [2132, 7826], especially when comorbid with psychotic symptoms [33] or other mental health disorders [5649], emphasizes the critical need for comprehensive suicide risk assessment and intervention strategies within OCD treatment protocols.

• Long-term Efficacy of Novel Therapies: While psilocybin [779] and ketamine [1877] show promise for treatment-resistant OCD, long-term efficacy and safety data are limited, warranting further prospective RCTs with extended follow-up periods.
• Biomarker Validation for Treatment Response: Research on neurophysiological (e.g., EEG microstates [19, 27], ERN [38, 1462]) and genetic/epigenetic biomarkers (e.g., miR-132 [226], DMRs [909]) needs validation in larger, diverse cohorts to predict treatment response and guide personalized interventions.
• Mechanisms of Digital Interventions: The specific mechanisms by which technology-based interventions (e.g., digital CBT [42], AI-enhanced therapy [216]) impact OCD symptoms require further investigation, possibly through process-based studies evaluating cognitive and behavioral changes.
• Impact of Sociocultural Factors: The influence of factors like residential mobility [6847], cultural context [394, 664], and stigma [8780, 9954] on OCD presentation, help-seeking, and treatment outcomes needs more robust, culturally sensitive research, particularly in understudied regions [2968, 6897].
• Neuroinflammation and Gut-Brain Axis: The role of neuroinflammation [1232, 714] and gut microbiota [195, 5897] in OCD pathophysiology requires further elucidation through longitudinal studies and interventional trials targeting these pathways.

• Study Design Heterogeneity — The diverse study designs, including cross-sectional and cohort studies, limit causal inferences.
• Varied Sample Sizes — Small sample sizes in many intervention studies restrict generalizability.
• Inconsistent Outcome Measures — Different scales and metrics for symptom severity hinder direct comparison across studies.
• Lack of Long-Term Follow-up — Many studies lack extended follow-up, limiting understanding of long-term treatment effects.
• Geographic and Demographic Bias — Research may not fully represent global populations or diverse demographic groups.

• Longitudinal Studies on Etiology — Conduct prospective longitudinal studies to clarify causal pathways and risk factors.
• Standardized Biomarker Panels — Develop and validate standardized neurobiological and genetic biomarker panels for diagnosis and treatment prediction.
• AI-Driven Personalized Therapies — Explore AI-driven adaptive interventions for real-time, personalized OCD treatment.
• Culturally Adapted Interventions — Develop and test culturally sensitive and accessible interventions for diverse populations.
• Integrative Neuroimmune Research — Investigate the interplay of neuroinflammation, genetics, and gut microbiota in OCD.