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Feasibility and effectiveness of the Bergen 4-Day Treatment for obsessive-compulsive disorder in Australia: A pilot comparison with 3-week inpatient obsessive-compulsive disorder treatment.

OBJECTIVES: Obsessive-compulsive disorder is a debilitating and chronic condition that, when untreated or unresponsive to treatment, imposes a significant health and economic burden on individuals and families. This prospective non-randomised inpatient study compared the acceptability and clinical outcomes of the Bergen 4-Day Treatment programme with those of a standard 3-week specialised treatment programme for obsessive-compulsive disorder in Australia. METHOD: Twenty-five participants diagnosed with obsessive-compulsive disorder were non-randomly assigned to Bergen 4-Day Treatment (n = 12) or a 3-week standard (n = 13) inpatient programme. Independent assessments were completed at pre-treatment, 10 days post treatment and at 3-month follow-up. The Yale-Brown Obsessive-Compulsive Scale was rated to assess obsessive-compulsive disorder severity, while secondary measures of depression, anxiety, obsessive beliefs and wellbeing were self-rated by participants. RESULTS: Baseline characteristics of both groups were comparable, with obsessive-compulsive disorder symptom severity within the moderate to severe range. After treatment, obsessive-compulsive disorder symptoms as well as secondary depression and anxiety symptoms were reduced in both treatment groups. Participants receiving Bergen 4-Day Treatment had significantly lower Yale-Brown Obsessive-Compulsive Scale scores at 10 days (M = 13.46) and 3 months (M = 11.84), compared to standard treatment (M = 19.04 and M = 19.15, respectively). Response (91.9%) and remission (45.8%) rates for the Bergen 4-Day Treatment group were significantly higher at both post-treatment timepoints, compared to the standard treatment group. No dropouts occurred in the Bergen 4-Day Treatment group, and participant satisfaction was high. CONCLUSION: The findings of this pilot open-label study suggest that Bergen 4-Day Treatment shows promise as an acceptable, efficient and effective treatment for obsessive-compulsive disorder, warranting further investigation as a scalable alternative for improving access to specialised obsessive-compulsive disorder treatment in Australia.

Humans

Clinical impact of obsessive-compulsive disorder comorbidity in bipolar disorder: a systematic review and meta-analysis.

BACKGROUND: Bipolar disorder (BD) is commonly comorbid with other psychiatric conditions, such as obsessive-compulsive disorder (OCD). Despite increasing interest in this comorbidity, quantitative data on its clinical characteristics remain limited. This systematic review and meta-analysis aimed to evaluate the clinical impact of OCD comorbidity in BD by comparing individuals with BD and OCD (BD-OCD) to those with BD without OCD. METHODS: We systematically searched the PubMed/MEDLINE, Scopus, PsycINFO, and Web of Science databases up to April 15, 2024. Meta-analyses were conducted to compare BD-OCD and BD without OCD groups across multiple clinical domains. RESULTS: From 11,959 initial records screened, 26 studies were included in the qualitative synthesis, with 22 eligible for meta-analysis. Individuals with BD-OCD showed higher odds of experiencing chronic mood episodes (OR = 9.42; 95%CI = 2.23, 39.9), rapid cycling (OR = 1.92; 95%CI = 1.04, 3.53), comorbid eating disorders (OR = 3.37; 95%CI = 1.99, 5.7), panic disorder (OR = 3.3; 95%CI = 2.11, 5.2), substance use disorders (OR = 1.39; 95%CI = 1.02, 1.89), and lifetime suicide attempts (OR = 1.85; 95%CI = 1.21, 2.84). Additionally, they presented earlier onset of BD (SMD = -0.27; 95%CI = -0.52, -0.01) and reduced functioning (SMD = -0.42; 95%CI = -0.59, -0.24). Most data were derived from adult populations, limiting the evidence available for children and adolescents. CONCLUSIONS: BD-OCD presents a more severe and complex clinical profile, requiring specialized assessment and integrated treatment approaches. Identifying these features may support earlier recognition and inform personalized interventions for this population.

Humans

Functional neuroimaging subtypes of obsessive-compulsive disorder: A systematic review and meta-analysis.

Obsessive-compulsive disorder (OCD) exhibits substantial clinical heterogeneity that may reflect underlying neurobiological diversity. Neuroimaging-based subtyping may advance precision psychiatry by identifying biologically distinct subgroups with differential treatment responses. This study systematically synthesized evidence from functional neuroimaging subtyping studies in OCD to identify reproducible neurobiological subtypes, characterize their clinical profiles, and establish a consensus-based classification framework. We reviewed 40 original studies employing machine learning, clustering, normative modeling, or classification approaches, encompassing approximately 8,150 patients. Consensus clustering identified three reproducible neurobiological subtypes. The Limbic-Hyperactive subtype, comprising approximately 40% of patients, exhibited amygdala and insula hyperconnectivity, elevated anxiety levels, predominant contamination and washing symptoms, and favorable response to cognitive-behavioral therapy. The Fronto-Striatal-Hypoconnected subtype, comprising approximately 35% of patients, demonstrated reduced orbitofrontal-striatal connectivity, cognitive inflexibility, predominant checking and ordering symptoms, and a favorable response to selective serotonin reuptake inhibitors. The Global-Disrupted subtype, comprising approximately 25% of patients, exhibited widespread connectivity disruption, greater symptom severity, and poor treatment response. Support vector machine classification achieved 81.5% accuracy for subtype assignment, though classification of OCD versus healthy controls showed limited generalizability in multisite settings (AUC 0.567-0.673). These findings support a neuroimaging-based framework for personalized treatment selection but require prospective validation.

Humans

Phenotypic Impact of Rare Potentially Damaging Copy Number Variation in Obsessive-Compulsive Disorder and Chronic Tic Disorders.

BACKGROUND: Recent studies report an important-and previously underestimated-role of rare variation in risk of obsessive-compulsive disorder (OCD) and chronic tic disorders (CTD). Using data from a large epidemiological study, we evaluate the distribution of potentially damaging copy number variation (pdCNV) in OCD and CTD, examining associations between pdCNV and the phenotypes of probands, including a consideration of early- vs. late-diagnoses. METHOD: The Obsessive-Compulsive Inventory-Revised (OCI-R) questionnaire was used to ascertain psychometric profiles of OCD probands. CNV were identified genome-wide using chromosomal microarray data. RESULTS: For 993 OCD cases, 86 (9%) were identified as pdCNV carriers. The most frequent pdCNV found was at the 16p13.11 region. There was no significant association between pdCNV and the OCI-R total score. However, pdCNV was associated with Obsessing and Checking subscores. There was no significant difference in pdCNV frequency between early- vs. late-diagnosed OCD probands. Of the 217 CTD cases, 18 (8%) were identified as pdCNV carriers. CTD probands with pdCNV were significantly more likely to have co-occurring autism spectrum disorder (ASD). CONCLUSIONS: pdCNV represents part of the risk architecture for OCD and CTD. If replicated, our findings suggest pdCNV impact some OCD symptoms. Genes within the 16p13.11 region are potential OCD risk genes.

Humans

Transcranial Magnetic Stimulation for Patients with Exposure Therapy Resistant Obsessive-Compulsive Disorder (TETRO): Study Protocol for a Multicenter Randomized Controlled Trial.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a disabling mental disorder, characterized by obsessions, compulsions, and substantial morbidity. Approximately 50% of adults with OCD fail to achieve satisfactory outcomes from first-line treatments, such as exposure therapy with response prevention (ERP), with or without medication. This leads to chronic social, educational, and occupational impairment. While invasive procedures such as deep brain stimulation are available for severe, treatment-refractory cases, a need remains for less invasive alternatives. Repetitive transcranial magnetic stimulation (rTMS), a noninvasive intervention, shows promise in reducing OCD symptoms. Unlike in depression, rTMS is not yet reimbursed for OCD in the Dutch healthcare system. OBJECTIVE: This study examines the efficacy and cost-effectiveness of low-frequency (1Hz) rTMS targeting the presupplementary motor area (pre-SMA) compared to sham rTMS as an adjuvant treatment to ERP in adults with OCD with inadequate response to first-line treatment. METHODS: A total of 250 adults with OCD will be enrolled in this multicenter randomized controlled trial. Participants will be randomly assigned to ERP combined with either active or sham 1Hz rTMS over the pre-SMA. Treatment is administered 4 times weekly for at least 5 weeks (20 rTMS-ERP sessions), with optional extension of 1 to 2 weeks, up to 28 rTMS-ERP sessions. Clinical assessments occur at baseline, weekly during treatment, posttreatment, and at 3, 6, and 12 months follow-up. Participants undergo pre- and posttreatment (functional) (MRI) scans, including a symptom provocation task. Blood sampling takes place pre- and posttreatment and at 3-month follow-up. The primary outcome is OCD severity at posttreatment, as measured by the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Secondary outcomes include functional improvement, quality of life, and societal costs. Pretreatment symptom profiles, genotype, and brain network topology will be analyzed as predictors of response and relapse risk. Pre-to-post treatment change in blood-based and magnetic resonance (MR)-based neuroplasticity markers will help explore differential mechanisms between ERP alone and combined rTMS-ERP. We expect that the verum rTMS protocol will be cost-effective compared to sham-rTMS. RESULTS: Recruitment started in April 2022, and as of February 2026, 201 participants have been enrolled. Posttreatment assessments are projected to be completed in December 2026, with final one-year follow-up evaluations anticipated by the end of 2027. CONCLUSIONS: To our knowledge, this study is the first adequately powered randomized controlled trial examining efficacy, cost-effectiveness, and mechanism of action of rTMS for OCD as adjuvant therapy to ERP. In case of efficacy and/or cost-effectiveness, it will pave the way for rTMS as insured health care for adults with OCD in the Netherlands, and possibly other European countries. Furthermore, this trial will provide insight into the mechanisms of treatment response to intensive ERP, with and without adjunctive rTMS, as well as potential side effects, individual variability, and long-term outcomes in adults with OCD.

Humans

Advancements in the Understanding of the Genetics of Obsessive-Compulsive Disorder (OCD).

PURPOSE OF REVIEW: This review summarizes recent advances in the genetics of Obsessive-Compulsive Disorder (OCD), their contribution to understanding disorder biology, and implication for clinical translation. RECENT FINDINGS: Recent GWAS identified 30 genome-wide significant loci and prioritized 25 putatively causal genes. Rare variant studies implicated specific genes, including CHD8, CELSR3, SLITRK5, and QRICH1. Evidence from common and rare variants support brain- and immune-related pathways. Genetic overlap with obsessive compulsive symptoms and other psychiatric disorders indicate shared underlying biology. Current evidence is largely based on individuals of European ancestry, although global efforts are underway to improve ancestral diversity in OCD genetics. Given the urgent need for improved treatment, genetically informed clinical translation approaches hold promise, including pharmacogenetics and drug repurposing. Recent advances in OCD genetics support a highly polygenic architecture, implicate specific neuro-biological and immune pathways, and provide new opportunities for clinical translation.

Humans

Obsessive-compulsive disorder with hoarding behavior: unravelling key differences.

OBJECTIVE: Hoarding disorder remains underexplored and poorly understood despite its significant impact on individuals and communities. While historically linked to obsessive-compulsive disorder (OCD), emerging evidence suggests they may be distinct conditions. This study aims to investigate these differences. METHODS: Adults aged 18-88 years old (M = 39.86, SD = 14.86) were part of the Genomic Psychiatry Cohort study, including 1247 individuals with OCD without presumed hoarding disorder (OCD-pHD) and 663 individuals with OCD and presumed hoarding disorder (OCD+pHD). Sociodemographic data were collected, and participants were screened for other psychiatric conditions. All met DSM-5 criteria for OCD, with severity assessed using the Florida Obsessive-Compulsive Inventory and Y-BOCS. Statistical significance was set at p ≤ 0.0007, adjusted for multiple comparisons. RESULTS: The OCD+pHD group had significantly lower educational attainment, was more likely to live alone or in supervised living, and less likely to be married. This group also had more severe OCD and poorer insight. All types of obsessions and compulsions were more frequent in the OCD+pHD group, except for obsessions related to harming others. Additionally, the OCD+pHD group had higher rates of major depressive disorder, post-traumatic stress disorder, bipolar disorder, schizophrenia, body dysmorphic disorder, trichotillomania and previous diagnosis and/or symptoms of attention deficit and hyperactivity disorder. No significant difference was found for substance use and Tic/Tourette disorders. CONCLUSIONS: Significant clinical differences were observed between the groups, highlighting the need for further research to improve diagnosis, conceptualization, awareness, and support for individuals with hoarding disorder in the context of OCD.

Humans

Prader-Willi syndrome as a neurogenetic model for psychosis and obsessive-compulsive disorder: A review of clinical, behavioral, and biological insights.

Prader-Willi syndrome (PWS) is a complex neurodevelopmental disorder classically defined by hyperphagia and obesity. However, its profound psychiatric phenotype offers a unique genetic framework for understanding major mental illnesses. This review positions PWS as a potentially informative biological model for psychosis and obsessive-compulsive disorder (OCD), bridging the gap between 15q11-q13 imprinting defects and neural circuit dysfunction. We synthesize evidence demonstrating that psychosis in PWS is not a uniform trait but is disproportionately linked to the maternal uniparental disomy (mUPD) subtype. This genotype-phenotype correlation suggests that overexpression of maternally imprinted genes and loss of paternal expression disrupt cortical excitatory-inhibitory balance, resembling the "schizophrenia-bipolar" genomic architecture. Furthermore, synthesized evidence characterizes the repetitive, ritualistic behaviors in PWS not merely as behavioral challenges, but as a developmentally arrested OCD-spectrum phenotype driven by distinct serotonergic-oxytocinergic imbalances and hypothalamic-limbic dysconnectivity. Mechanistic insights from preclinical models of MAGEL2, SNORD116, and NDN deficiency are integrated with clinical findings to highlight shared neurobiological substrates. Finally, we outline a roadmap for precision psychiatry in PWS, emphasizing the necessity of pharmacogenomics in antipsychotic management and the potential of targeted circuit-based therapeutics. By deconstructing the psychiatric comorbidities of PWS, we provide a framework for translating genomic architecture into mechanistic understanding and targeted treatment for complex neuropsychiatric disorders.

15q11-q13

The efficacy of non-invasive brain stimulation interventions in obsessive-compulsive disorder management: A network meta-analysis of randomized controlled trials.

Non-invasive brain stimulation (NIBS) has been widely used as an alternative treatment for obsessive compulsive disorder (OCD). However, the most effective NIBS parameters are unclear. To compare the efficacy of NIBS in OCD. We conducted a systematic review and network meta-analyses (NMA) to combine direct and indirect comparisons of NIBS.Systematic searches were conducted in Cochrane CENTRAL, EMBASE, PubMed, and Web of Science from inception to June 20, 2025. Forty-two randomized sham-controlled trials (n = 1456) were included. All statistical analyses were conducted with R statistical software. Bayesian NMAs mainly using the BUGSnet package and gemtc package. Five NIBS protocols produced statistically significant reductions in Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores compared with sham stimulation: high-frequency rTMS over the FzFCz (Hf-rTMS-FzFCz; MD -11.77, 95% CrI -20.62 to -3.09), low-frequency rTMS over F3F4 (Lf-rTMS-F3F4; MD -9.93, 95% CrI -18.07 to -1.65), low-frequency rTMS over FCz (Lf-rTMS-FCz; MD -3.25, 95% CrI -6.06 to -0.40), high-frequency deep TMS over FzFC (Hf-dTMS-FzFC; MD -6.48, 95% CrI -12.32 to -0.50), and 2 mA anodal tDCS over F3 with cathodal over Fp2 (MD -9.34, 95% CrI -16.01 to -3.03).For secondary outcomes, high-frequency deep rTMS over FzFCz produced the largest reduction both in depressive symptoms (SMD -1.24, 95% CrI -1.92 to -0.55) and anxiety scores (SMD -1.88, 95% CrI -2.62 to -1.11), but had no effect on Clinical Global Impression-Severity (CGI-S) scores.Specific NIBS protocols are safe and effective adjunctive treatments for OCD, with promising yet inconclusive improvements in comorbid depressive symptoms. Further high-quality, head-to-head trials are needed.

Humans

Does Toxoplasma gondii infection have a causal impact on human psychopathology? A Mendelian randomization analysis.

Toxoplasma gondii (T. gondii) is a prevalent zoonotic parasite that has been implicated in influencing human psychiatric disorders and risk-taking behaviors. Using genome-wide association study (GWAS) data, we selected 25 and 76 single-nucleotide polymorphisms as instrumental variables for anti-T. gondii IgG seropositivity and anti-T. gondii IgG levels, respectively, and conducted two-sample Mendelian randomization (MR) analyses across 18 GWAS datasets to investigate potential causal effects on addiction, bipolar disorder, obsessive-compulsive disorder, schizophrenia, and risk-taking behavior in European populations. Contrary to previous epidemiological evidence, our MR analyses do not support a significant causal association between T. gondii infection and any of the studied psychiatric disorders or risk-taking behavior. Collectively, these results establish that any true causal effect of genetic liability to T. gondii infection is likely to be small (OR < 1.18 for schizophrenia,&#x2009;<&#x2009;1.29 for bipolar disorder) and below the effect sizes typically reported in observational seroepidemiological studies, although small or infection-phase-specific effects cannot be excluded.

Humans

Mendel randomization confirmed gastroesophageal reflux disease may increase the risk of mental disorders.

BACKGROUND: The potential causal relationship between gastroesophageal reflux disease (GERD) and mental disorder was analyzed using the mendelian randomization (MR) method. METHODS: Data are derived from genome-wide association study (GWAS) summary data, using gastroesophageal reflux disease (GERD) as the exposure factor. Single nucleotide polymorphisms (SNPs) significantly associated with GERD were selected as instrumental variables (IVs), and mental disorders (bipolar disorder, major depression, Alzheimer's disease, anorexia nervosa, anxiety, and obsessive-compulsive disorder) were used as outcome variables. The inverse variance weighted (IVW) method is used as the main analysis method, and MR-Egger regression, weighted median (WM) method, simple mode and weighted mode are used as supplementary methods for Mendelian randomization (MR) analysis. Cochran's Q&#xa0;test and P&#xa0;value are used to quantify heterogeneity, MR-Egger regression was used to evaluate the multilevel effect test of SNPs, and leave-one-out method to determine whether there are potential SNPs, and to evaluate the stability of the results. Odds ratio (OR) and 95% confidence interval (CI) were used as effect indicators to evaluate whether there is a&#xa0;causal relationship between GERD and mental disorders. RESULTS: IVW demonstrated a&#xa0;causal relationship between GERD and bipolar disorder (OR&#x202f;=&#x2009;1.70, 95%CI&#x202f;=&#x2009;1.39-2.09, P&#x202f;<&#x2009;0.05) and anorexia nervosa (OR&#x202f;=&#x2009;0.71, 95%CI&#x202f;=&#x2009;0.52-0.99, P&#x202f;<&#x2009;0.05). Furthermore, there is a&#xa0;weak causal relationship between GERD and major depression (OR&#x202f;=&#x2009;1.01, 95%CI&#x202f;=&#x2009;1.01-1.02, P&#x202f;<&#x2009;0.05) and anxiety (OR&#x202f;=&#x2009;1.01, 95%CI&#x202f;=&#x2009;1.01-1.01, P&#x202f;<&#x2009;0.05). Similarly, there is no evidence of a&#xa0;causal relationship between GERD and Alzheimer's disease (OR&#x202f;=&#x2009;0.95, 95%CI&#x202f;=&#x2009;0.87-1.03, P&#x202f;>&#x2009;0.05) or obsessive-compulsive disorder (OR&#x202f;=&#x2009;0.95, 95%CI&#x202f;=&#x2009;0.67-1.36, P&#x202f;>&#x2009;0.05). Cochran's Q&#xa0;test for heterogeneity shows that there is no significant heterogeneity (P&#x202f;>&#x2009;0.05) for bipolar disorder, anxiety, and obsessive-compulsive disorder. However, major depression, Alzheimer's disease, and anorexia nervosa have some degree of heterogeneity (P&#x202f;<&#x2009;0.05). Horizontal pleiotropic analysis showed that the P&#xa0;values for six mental disorders (0.750, 0.296, 0.154, 0.798, 0.893, 0.451) were all greater than 0.05. Leave-one-out analysis and funnel plot showed that MR analysis results can be considered relatively stable. All F are >&#x2009;10, indicating no weak IVs bias. CONCLUSION: GERD can obviously increase the risk of bipolar disorder; the increased risk of anxiety disorder is very slight. There is no clear evidence to support the causal relationship between GERD and four other mental disorders, including major depression, Alzheimer's disease, anorexia nervosa, and obsessive-compulsive disorder.

Humans

[Tics and Tourette Syndrome].

Tics disorders and Tourette syndrome (TS) are neurodevelopmental conditions characterized by motor and/or vocal tics with onset in childhood. Their clinical presentation is heterogeneous and fluctuating over time, with exacerbations related to emotional, environmental, and medical factors. Diagnosis is clinical and based on medical history and neurological examination, following DSM-5-TR criteria, with ancillary testing rarely required. The prevalence of TS is estimated at 0.7%, while transient tic disorders affect up to 10% of children. The natural history is generally favorable, with symptom improvement during adolescence, although a subset of patients continues to experience tics into adulthood. Most individuals with TS present psychiatric comorbidities, particularly attention-deficit/hyperactivity disorder and obsessive-compulsive disorder, which significantly impact quality of life and should be prioritized in management decisions. Treatment is recommended only when tics cause functional impairment and follows a stepwise approach including psychoeducation, behavioral interventions, and individualized pharmacological therapy. Comprehensive behavioral intervention for tics is considered first-line treatment when available. Alpha-2 adrenergic agonists and dopamine antagonists are the most commonly used pharmacological options. Neuromodulation therapies are reserved for severe, refractory cases. These recommendations from the Ibero-American Academy of Pediatric Neurology summarize current evidence and provide a practical, updated framework for the diagnosis and management of tic disorders and Tourette syndrome in pediatric patients.

Humans

Sequential rTMS for MDD and OCD in a patient with left parietal perinatal ischemic infarct: a case report.

Major depressive disorder (MDD) commonly co-occurs with obsessive-compulsive disorder (OCD), resulting in greater symptom severity, functional impairment, and suboptimal response to standard pharmacologic and psychotherapeutic interventions. These challenges underscore the need for neuromodulation strategies to target distinct neural networks implicated in mood regulation and compulsivity. This report describes outcomes of high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC), and low-frequency (LF) rTMS of the right orbitofrontal cortex (OFC), in a patient with comorbid MDD, OCD, and a left parietal perinatal ischemic infarct. Over the course of treatment, serial psychometric assessments demonstrated progressive reductions in frequency and intensity of depressive symptoms, anxiety, and obsessive-compulsive behaviors, measured via Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder 7-Item Scale (GAD-7), and Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). This case adds to the growing body of literature demonstrating efficacy of DLPFC and OFC stimulation for depression and OCD. Further large-scale, blinded, and randomized trials are warranted to examine the efficacy of sequential DLPFC and OFC stimulation for comorbid MDD and OCD compared with single-site DLPFC stimulation.

dorsolateral prefrontal cortex (DLPFC)

Memantine Augmentation for Obsessive-Compulsive Symptoms in Bipolar Disorder: A Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Obsessive-compulsive symptoms are frequently observed in patients with bipolar disorder and present a significant therapeutic challenge. This study evaluated the efficacy and safety of memantine as an adjunctive therapy for obsessive-compulsive disorder in patients with bipolar disorder. METHODS: In this randomized, double-blind, placebo-controlled trial, 46 patients with bipolar disorder and obsessive-compulsive disorder, stabilized on quetiapine and lithium, were randomly assigned to receive either memantine (n = 23) or placebo (n = 23) for 6 weeks. RESULTS: The memantine group showed a significant reduction in Yale-Brown Obsessive-Compulsive Scale scores compared with the placebo group (Cohen d = 1.57 vs 0.42, P < 0.001). Nausea was the most common side effect, but overall adverse effects were minimal. CONCLUSION: Memantine appears to be a safe and effective adjunctive treatment for obsessive-compulsive disorder in patients with bipolar disorder, warranting further investigation.

Humans

Deep brain stimulation for Tourette syndrome: a systematic review and meta-analysis.

Deep brain stimulation (DBS) has emerged as a promising neuromodulatory therapy for patients with refractory Tourette syndrome (TS). Various brain targets-including the globus pallidus internus (GPi) and several thalamic nuclei-have been explored, yet the comparative efficacy of DBS in different targets remain unclear. This meta-analysis aims to evaluate the clinical efficacy of DBS in TS and assess symptom improvements across different stimulation targets. A systematic search of PubMed, Embase, and Web of Science identified studies published between October 2014 and September 2025. Study quality was assessed using the French and Gronseth classification system. Outcomes of interest included pre- and postoperative scores on the Yale Global Tic Severity Scale (YGTSS) and Yale-Brown Obsessive Compulsive Scale (YBOCS). A total of 22 studies involving 358 patients were included in this meta-analysis. Mean YGTSS scores decreased from 69.19&#x2009;&#xb1;&#x2009;18.04 preoperatively to 35.88&#x2009;&#xb1;&#x2009;17.23 postoperatively. There was an average 48% reduction in YGTSS scores. DBS led to a substantial reduction in tic severity (YGTSS: GPi, SMD&#x2009;=&#x2009;2.29, P&#x2009;<&#x2009;0.00001; thalamus, SMD&#x2009;=&#x2009;2.33, P&#x2009;<&#x2009;0.0001). Within the GPi subgroup, stimulation of the anteromedial GPi (amGPi) resulted in significantly better benefits (SMD&#x2009;=&#x2009;3.01, P&#x2009;<&#x2009;0.00001) compared to the posterior-ventrolateral GPi (pvlGPi), which did not reach statistical significance (SMD&#x2009;=&#x2009;1.23, P&#x2009;=&#x2009;0.05). YBOCS scores decreased from a mean of 17.38&#x2009;&#xb1;&#x2009;6.15 preoperatively to 9.16&#x2009;&#xb1;&#x2009;4.12 postoperatively. The average reduction in YBOCS scores was 47%. Obsessive-compulsive disorder (OCD) symptoms also showed significant improvement following DBS (overall YBOCS, SMD&#x2009;=&#x2009;0.94, P&#x2009;<&#x2009;0.00001; amGPi, SMD&#x2009;=&#x2009;1.49, P&#x2009;=&#x2009;0.004; pvlGPi, SMD&#x2009;=&#x2009;0.72; P&#x2009;=&#x2009;0.006). DBS is an effective and target-sensitive intervention for TS, alleviating both motor tics and obsessive-compulsive symptoms. Compared to therapies such as pvlGPi and thalamic-DBS, amGPi-DBS may demonstrate greater therapeutic potential compared with pvlGPi-DBS, suggesting its potential advantage in modulating the associated circuits involved in the pathophysiology of TS.

Humans

Causal Relationship of Polyunsaturated Fatty Acids With Mental Disorders: A Systematic Review and Meta-analysis.

CONTEXT: Mental disorders (MDs) pose a important global health challenge, with a complex pathogenesis complicating treatment development. Nutritional interventions, particularly polyunsaturated fatty acids (PUFAs), have gained attention as potential therapeutic options. OBJECTIVE: This Mendelian randomization (MR) meta-analysis aimed to evaluate the potential causal relationship between PUFAs and MDs. DATA SOURCES: Genome-wide association study data were utilized to analyze the association between PUFAs (including omega-3, omega-3 percentage [omega-3%], omega-6, omega-6 percentage [omega-6%], and omega-6 to omega-3 ratio) and 12 major MDs. DATA EXTRACTION: Two-sample MR technology was used to assess the role of PUFAs in MDs. DATA ANALYSIS: The MR analysis revealed that genetically predicted omega-3 was causally linked to MDs, such as obsessive-compulsive disorder, bipolar disorder, schizophrenia, and major depressive disorder. Omega-3% exhibited protective effects against emotional personality disorder. Conversely, omega-6 was inversely correlated with attention-deficit/hyperactivity disorder risk, while a high omega-6 to omega-3 ratio was associated with an increased risk of depression and other mood disorders. CONCLUSION: High omega-3 levels and omega-3% may reduce the risk of MDs, whereas a high omega-6:omega-3 ratio may elevate the risk. These findings highlight the potential of PUFAs, particularly omega-3, in MD prevention and treatment, while underscoring the need for further research into the complex interactions between omega-3 and omega-6. The study provides a scientific foundation for future clinical trials and dietary intervention strategies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO no. CRD42024598472.

Humans

Metabolomic ageing across mental and behavioural disorders.

BACKGROUND: Individuals with mental disorders face excess morbidity and premature mortality. Accelerated ageing has been proposed as a contributing mechanism but population-scale evidence across diverse diagnoses is limited. OBJECTIVE: To examine whether metabolomic ageing differs across mental disorders and whether associations vary by sex, age group and genetic liability. METHODS: Using plasma metabolomic profiles from UK Biobank participants, we applied a metabolomic ageing clock (MileAge) to estimate disorder-specific differences between metabolite-predicted and chronological age. Mental disorders were ascertained from health records and self-reported physician diagnoses. We analysed nine diagnostic groups and 45 individual disorders and assessed sex and age group differences and associations with polygenic scores. FINDINGS: Among 225&#x2009;212 participants (54% female; mean age 56.97), 38&#x2009;524 had a diagnosis preceding baseline. Substance use, psychotic, affective and neurotic disorders were associated with a metabolite-predicted age older than chronological age, largest for psychosis (&#x3b2;=0.556, 95% CI 0.250 to 0.861, p<0.001). Obsessive-compulsive and eating disorders were associated with a metabolite-predicted age younger than chronological age. Several associations were stronger in males and in individuals aged <65 years. Higher genetic liability to depression, autism and attention-deficit/hyperactivity disorder predicted an older metabolomic age (&#x3b2; range=0.020&#x2009;to 0.047), whereas polygenic scores for psychosis and tobacco use disorder predicted a younger metabolomic age (&#x3b2; range=-0.023&#x2009;to -0.040). For obsessive-compulsive disorder and anorexia nervosa, clinical and genetic associations indicated younger metabolomic ageing. CONCLUSIONS: Metabolomic ageing in mental disorders is heterogeneous. While many disorders are associated with an older biological age, some are linked to a younger biological age. Divergence between genetic liability and clinical phenotypes suggests that non-genetic factors shape biological ageing differences. CLINICAL IMPLICATIONS: Biological age should not be assumed to uniformly exceed chronological age across mental disorders. Sex and age-specific approaches could improve understanding of biological ageing processes in psychiatry.

Humans