Search Results (456)

Using the Hierarchical Taxonomy of Psychopathology (HiTOP) as our framework, the current study examines how 13 common psychological disorders can be grouped into different spectra in two groups of adolescents: a community sample (N = 951), and a clinic-referred sample (N = 173). Scores for the disorders were obtained using the parent version of the Child and Adolescent PsychProfiler. Taken together, the findings across the two samples for factor structure, reliability, and discriminant and concurrent validity indicate the most support for a three-factor CFA oblique model with primary factors for neurodevelopment disorders (that include Specific Learning Disorder, Autism Spectrum Disorder, Language Disorder, and Speech Sound Disorder), internalizing disorder problems (that include Generalized Anxiety Disorder, Persistent Depressive Disorder, Separation Anxiety Disorder, Obsessive–Compulsive Disorder, Posttraumatic Stress Disorder, Anorexia Nervosa, and Bulimia Nervosa), and externalizing disorder problems [(that include Attention Deficit/Hyperactivity Disorder (ADHD), and Oppositional Defiant Disorder/Conduct Disorder (ODD/CD)], with a covariance for the error variance for Anorexia Nervosa and Bulimia Nervosa. Additionally, the analysis for Sample 2 supports the concurrent validity of the factors in this model. A modification of this model, with ADHD cross-loading on the neurodevelopment disorders factor, did not produce an admissible solution. The findings indicate support for a neurodevelopmental spectrum in the HiTOP model, with ADHD and ODD/CD showing stronger statistical association with the externalizing factor than with the neurodevelopmental factor in the models tested. This finding pertains to dimensional structure and does not invalidate the neurodevelopmental classification of ADHD in DSM-5-TR. Full article

The rapid integration of artificial intelligence (AI) into mental healthcare presents opportunities and ethical challenges, particularly for complex conditions like obsessive–compulsive disorder (OCD). In this perspective, we argue for a Dual Imperative: establishing safety architectures for AI-powered therapeutic tools to prevent algorithmic sycophancy (symptom accommodation), while mandating explainable AI (XAI) in prognostic models to ensure clinical auditability. In therapeutics, we propose a Guardian Angel architecture that utilizes patient-specific fear hierarchies and linguistic stance detection to distinguish compulsive reassurance-seeking from legitimate patient questions. This approach transforms potential therapeutic ruptures into opportunities for distress tolerance via the Digital Ulysses Pact, a patient-authorized, algorithmically enforced response prevention protocol. In diagnostics, we address the black box problem in precision psychiatry. We argue that as AI evolves from detection to high-stakes treatment selection, safety and accountability become a prerequisite for clinical application. Although distinct in implementation, these architectures form an integrated framework for aligning therapeutic and diagnostic AI. These architectures are not parallel tracks but a unified ecosystem: A patient’s XAI-audited profile can inform the Guardian Angel’s configuration, while the longitudinal data gathered during therapy enriches diagnostic precision. Grounded in ethical principles and best practices in OCD, this suggests a path toward AI that is auditable in its diagnostic logic, firm in its therapeutic boundaries, and enforceable through emerging regulatory frameworks. Full article

Background: Treatment-resistant obsessive–compulsive disorder (TR-OCD) remains a major therapeutic challenge. Although current guidelines recommend optimized serotonin reuptake inhibitor (SRI) therapy, clomipramine switching, exposure and response prevention, and antipsychotic augmentation, a substantial proportion of patients continue to experience severe and disabling symptoms. In such cases, clinicians may consider pharmacological intensification strategies beyond guideline-endorsed algorithms. Methods: This study combines a structured narrative synthesis of pharmacological strategies for TR-OCD with a retrospective observational case series from a tertiary OCD referral clinic. Treatment resistance was defined as failure to achieve at least a 35% reduction in Yale–Brown Obsessive Compulsive Scale (Y-BOCS) score after at least two adequate SRI trials, including clomipramine, and optimized exposure and response prevention when available. Five patients treated with pharmacological intensification strategies were included. The primary outcome was percentage change in Y-BOCS score at 12 weeks. Results: The case series illustrates five strategies used in highly refractory OCD: supratherapeutic SSRI dosing, SSRI plus mirtazapine augmentation, dual SSRI therapy, serotonergic intensification in a clozapine-treated patient, and glutamatergic/GABAergic augmentation with topiramate. Baseline Y-BOCS scores ranged from 28 to 32. At 12 weeks, symptom reduction ranged from 23% to 36%. One patient met criteria for response, three showed near-response, and one demonstrated partial improvement. No cases of serotonin toxicity or clinically significant cardiac complications occurred. Conclusions: These cases suggest that carefully monitored pharmacological intensification may be feasible in selected specialist settings, but efficacy and safety require confirmation in prospective controlled studies. Recommendations: Pharmacological intensification should be reserved for highly refractory patients managed in specialist services, implemented with gradual titration, structured serotonin toxicity and electrocardiographic monitoring, and explicit individualized risk–benefit discussion; dual SSRI therapy should be regarded as the most experimental and highest-risk serotonergic option; and prospective controlled studies incorporating standardized functional outcomes are needed to refine patient-selection criteria and clarify which patients may benefit. Full article

Obsessive–compulsive disorder (OCD) is a chronic and disabling psychiatric condition whose neurobiological underpinnings remain incompletely characterized. A growing body of evidence suggests that vitamin D, through its modulatory actions on neuroinflammation, serotonin synthesis, and cortico-striato-thalamo-cortical circuitry, may be implicated in its clinical expression. The present cross-sectional study examined the association between serum 25-hydroxyvitamin D levels and OCD severity in 306 adult outpatients with a diagnosis of OCD, of whom 173 had vitamin D measurements available. Symptom severity was assessed through the Yale–Brown Obsessive–Compulsive Scale (Y-BOCS), and associations were examined using non-parametric tests, partial correlations and multivariable linear regression adjusted for age, gender, age at onset, and bipolar comorbidity. Mean vitamin D was 20.0 ± 13.1 ng/mL, with 60.1% of patients meeting criteria for deficiency. Lower vitamin D levels correlated inversely with Y-BOCS total score (ρ = −0.26, p = 0.001) and with both subscales, and deficient patients showed a mean Y-BOCS total approximately 5.5 points higher than non-deficient ones. In multivariable models, lower vitamin D (β = −0.253, p = 0.001) and earlier age at onset (β = −0.278, p = 0.001) independently predicted greater severity (R² = 0.133), while a history of suicide attempts neither predicted severity nor moderated the vitamin D association. These findings support vitamin D status as a biological correlate of OCD severity and warrant longitudinal and interventional investigation. Full article

Perinatal mental illness affects up to 20% of new mothers worldwide, yet despite a growing research interest over the past decade, the etiology is still not fully understood, and clinical treatment guidelines remain inconsistent across countries and services. In this review, recent findings on neurobiological processes and evolutionary mechanisms, as they occur during the menstrual cycle, pregnancy, birth, postpartum and breastfeeding, are discussed. The intention is to raise awareness of physiological changes in pregnancy that might be relevant to the differential diagnosis and clinical treatment of perinatal psychiatric disorders such as depression, anxiety, PTSD after childbirth, bipolar relapse, postpartum psychosis, obsessive-compulsive symptoms, substance-use disorders, and suicidality. Areas addressed include the activities of the immune system, thyroid gland, cortisol, sleep and individual sensitivity to ovarian hormone fluctuations. Evolutionary biological mechanisms intended to sustain pregnancy and to ensure the survival of the newborn are assumed to have potent effects on the maternal brain. These non-pathological adaptations could provide grounds for a better understanding of risk factors and the etiology of perinatal mental illness. Full article

Background: Procrastination is a voluntary and irrational delay in taking action despite negative consequences. We aimed to conceive/suggest a definition of procrastination, assess the behavior, and determine its psychopathological features (within the contexts of attention-deficit/hyperactivity disorder and obsessive–compulsive disorder. Method: In this scoping study, we systematically reviewed original research studies with conceptual and clinical data related to procrastination. Data were extracted regarding definitions, populations, instruments used, and psychopathology. Results: A total of 387 studies were included. Only 13% utilized clinical/subclinical populations. Definitions of procrastination showed no single consensus. The most cited elements involved irrational delay, awareness of consequences, task aversiveness, and self-regulation failure. The most frequently used assessment tool was Lay’s General Procrastination Scale. A considerable number of studies identified associations between procrastination and clinical constructs such as impulsivity, perfectionism, executive dysfunction, low self-esteem, and mood instability. Few studies directly assessed procrastination in formal diagnostic categories, suggesting that procrastination shares neurocognitive and emotional regulation deficits with these disorders, especially in domains involving task initiation, inhibitory control, and intolerance of discomfort. Conclusions: Procrastination is a transdiagnostic construct rather than a unitary behavioral trait. Its multifactorial nature calls for further clinical investigation, particularly in structured diagnostic settings. A unified definition is needed to distinguish between normative delay and clinically relevant procrastination. Full article

Gambling disorder (GD) constitutes a worldwide social and economic burden and is associated with impaired functioning and reduced quality of life. GD shares important mechanistic substrates with obsessive–compulsive disorder (OCD), including dysfunction of cortico-striato-thalamo-cortical circuitry and dysregulation of serotonergic pathways involved in impulsivity, compulsivity, and impaired inhibitory control. On this basis, selective serotonin reuptake inhibitors (SSRIs), widely used in several psychiatric disorders, have been investigated as potential pharmacological treatments for GD. Evidence concerning fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, and escitalopram is heterogeneous and overall limited. Some early single-blind, randomized, and open-label studies have reported reductions in gambling urges, severity, and compulsive symptoms. However, larger and more rigorous placebo-controlled trials have frequently failed to demonstrate consistent superiority over placebo. Interpretation of these findings is further limited by small sample sizes, short observation periods, high dropout rates, heterogeneous outcome measures, and substantial placebo response. While SSRIs remain biologically plausible candidates for modulating the compulsive and impulsive dimensions of GD, current evidence does not support their routine use as first-line pharmacological treatment. Their role appears most justified in the presence of psychiatric comorbidity or within individualized, phenotype-oriented treatment strategies. Full article

The hypothesis that Group A beta-haemolytic Streptococcus (GAS) triggers an autoimmune cascade targeting basal ganglia dopaminergic circuits—producing obsessive–compulsive disorder (OCD), tic disorders, or chorea depending on the receptor subtype involved—is biologically compelling and supported by emerging molecular evidence. Yet PANDAS has remained a diagnostic conundrum since its original description in 1998, with ongoing uncertainty surrounding diagnostic criteria, the interpretation of streptococcal serology, and the distinction from primary neurodevelopmental disorders. This study aimed to review the diagnostic challenges of PANDAS, with focus on streptococcal serology interpretation, advances in dopamine receptor autoantibody biology, the genetic epidemiology of primary tic disorders, and the differential diagnosis of acute neuropsychiatric presentations in children. A structured narrative review was conducted using PubMed, MEDLINE, EMBASE, and the Cochrane Library for publications from 1998 to early 2025 addressing PANDAS, PANS, streptococcal antibodies, childhood movement disorders, autoimmune encephalitis, and the genetics of tic disorders. No currently available biomarker—including ASO, anti-DNase B, anti-basal-ganglia antibodies, or the Cunningham Panel—has demonstrated adequate individual-level diagnostic accuracy for PANDAS. Emerging molecular evidence identifies anti-D1R autoantibodies, acting via G protein-and beta-arrestin-mediated signalling, as candidate biomarkers for PANDAS/PANS neuropsychiatric phenotypes, and anti-D2R autoantibodies for Sydenham chorea movement phenotypes; independent replication in unselected populations is required. Primary tic disorders carry heritability estimates of 50–80% and first-degree familial risk ratios of approximately 18-fold in large population-based cohorts. Prospective blinded studies have not demonstrated a consistent population-level association between GAS infections and tic or OCD exacerbations: PANDAS and PANS remain diagnoses of exclusion. The high background prevalence of both GAS exposure and primary neurodevelopmental disorders in overlapping paediatric age ranges creates conditions for incidental temporal co-occurrence. In the absence of validated molecular biomarkers, diagnostic imprecision carries direct clinical consequences: children may be exposed to treatments with significant risk profiles—including IVIG, plasma exchange, and prolonged antibiotic prophylaxis—while evidence-based therapies are delayed. A stepwise diagnostic approach incorporating the full differential diagnosis is both an epistemological and a patient safety imperative. Full article

Background: Treatment-resistant obsessive–compulsive disorder (OCD) is a heterogeneous and clinically challenging condition. Growing evidence suggests alterations in glutamatergic signaling within cortico–striatal–thalamo–cortical circuits, including those involving medium spiny neurons (MSNs), as well as genetic factors affecting synaptic organization, although the biological mechanisms underlying differential treatment response remain incompletely understood. Methods: This multicenter study presents a translational research framework aimed at investigating potential molecular and cellular correlates of treatment response in a cohort of patients with OCD, stratified according to their response to pharmacological treatments and transcranial magnetic stimulation (TMS). Peripheral blood mononuclear cells from clinically defined subgroups are reprogrammed into human induced pluripotent stem cells and differentiated into MSN-enriched neuronal cultures, enabling in vitro investigation of morphological, biochemical, and transcriptomic features associated with different clinical profiles. Optogenetic and pharmacological stimulation paradigms are applied to probe selected aspects of neuronal activation in vitro, providing a controlled and simplified experimental framework to explore cellular responses under different treatment conditions. By integrating clinical phenotyping with patient-derived cellular models, this study establishes a translational platform for hypothesis generation in the investigation of treatment response in OCD. Results and Conclusions: Preliminary clinical observations from an initial cohort undergoing neuromodulation are also reported to document feasibility and early clinical implementation of the study, providing an initial characterization of the cohort. Full article

Background: Obsessive–compulsive disorder (OCD) frequently co-occurs with autism spectrum disorder (ASD), but the prevalence and clinical correlates of this comorbidity remain incompletely understood. Methods: We examined a clinical sample of 603 patients with a primary diagnosis of OCD, of whom 149 (24.7%) presented with comorbid ASD. Sociodemographic variables, clinical characteristics, comorbidities, and obsessive–compulsive symptom dimensions were compared between patients with and without ASD. Results: Patients with OCD + ASD reported an earlier onset of both obsessive–compulsive symptoms and full-blown disorder. While overall symptom severity (Y-BOCS, HAM-D, and HAM-A) was comparable, OCD + ASD patients were characterized by a higher exposure to stressful and traumatic life events, including severe trauma (e.g., death of a close family member, sexual abuse, physical violence, serious illness, and bullying). Severe traumatic events, in particular, were independently associated with ASD comorbidity in our OCD cohort (exploratory model). Comorbidities were also distinct: onychophagia (66.4% vs. 0.4%) and trichotillomania (8.7% vs. 0%) were markedly more prevalent in the OCD + ASD group. Phenomenologically, OCD + ASD patients more often exhibited religious and somatic obsessions, as well as repetition compulsions. Specifically, somatic obsessions were independently associated with ASD in our regression analysis. Conclusions: OCD with comorbid ASD represents a clinically distinct subgroup, characterized by greater vulnerability to trauma, earlier onset, unique symptom profiles, and specific comorbidities. Recognition of these features, and in particular a history of severe traumatic experiences and the presence of somatic obsessions, may support earlier consideration of ASD comorbidity during OCD assessment and may inform personalized treatment planning. Full article

Background/Objectives: Although obsessive–compulsive disorder (OCD) is clinically heterogeneous, it is unclear whether specific metacognitive belief domains are differentially associated with particular symptom dimensions in adults with confirmed OCD. This systematic review synthesised the available clinical evidence and explored its implications for dimension-informed case formulation and treatment planning. Methods: In March 2026, PubMed/MEDLINE, Scopus, Cochrane CENTRAL and Google Scholar were searched without date or language restrictions. Eligible studies enrolled adults with a confirmed diagnosis of OCD, administered at least one validated metacognitive instrument (MCQ-30/65, TFI, TAF, BARI, SSQ or OBQ-based subscales) and reported associations with validated dimensional OCD measures. The review was preregistered on PROSPERO (CRD420261338178). Due to methodological heterogeneity, the findings were synthesised narratively in accordance with SWiM guidance. Results: Ten studies, including 1320 adults with OCD, were included. These studies were conducted across five countries between 2010 and 2025. Negative beliefs about thought uncontrollability and danger (MCQ-30 NB) showed the broadest associations across the synthesis, particularly with the checking/harm avoidance and the unacceptable thought dimensions. Thought-fusion constructs (TAF/TFI) were most consistently associated with checking/harm avoidance and unacceptable thought presentations. Beliefs about rituals and stop-signal criteria (BARI/SSQ) were most relevant to symmetry/ordering. In contrast, contamination/washing and hoarding exhibited weaker and less consistent metacognitive profiles. Conclusions: The available evidence suggests that metacognitive belief profiles in OCD are not dimensionally uniform. Harm-relevant metacognitions appear to be the most salient factor in the checking and unacceptable thought dimensions, whereas ritual-regulation metacognitions appear to be more relevant to the symmetry/ordering dimension. While these findings may inform dimension-sensitive case formulation and generate testable hypotheses for future metacognitive and exposure-based treatment research, they do not yet justify prescriptive, dimension-specific treatment algorithms. The evidence base remains predominantly cross-sectional and methodologically diverse. Full article

Background: Distinguishing functional dystonia (FD) from idiopathic dystonia (ID) remains a major clinical challenge because both conditions are diagnosed primarily on clinical grounds and may be accompanied by non-motor psychiatric symptoms. Although personality abnormalities have been described in functional neurological disorders, their relevance in the differential diagnosis of dystonia remains insufficiently studied, and comparative data on FD and ID are lacking, particularly in the Russian population. Patients and Methods: A total of 178 patients with idiopathic dystonia (focal and segmental dystonia, ID) and 32 patients with functional dystonia (FD) were observed. A clinical interview by a psychiatrist was conducted; the SCID-II-PD questionnaire and the Five-Factor Personality Questionnaire (5-PFQ) were used to assess PD. Results: Patients with FD more often than patients with ID had such PD as dependent, paranoid, passive–aggressive, borderline, schizoid and schizotypal (p < 0.001), as well as obsessive–compulsive (p < 0.013) and avoidant (p < 0.049) according to SCID-II-PD. In FD, personalities of the eccentric cluster A predominate; patients with FD are characterized in personality terms by significantly greater introversion, detachment, naturalness (irresponsibility, impulsivity, carelessness), emotional restraint and practicality (conservatism, low sensitivity, rigidity) according to 5-PFQ. Conclusions: Patients with FD differ from patients with ID in both categorical and dimensional personality characteristics. The predominance of cluster A personality pathology and the identified pattern of personality-related variables may have potential value as adjunctive markers in the clinical differentiation of FD from ID. Further external validation is required before these findings can be incorporated into diagnostic algorithms. Full article

The concept of the overvalued idea (OVI) has been debated since German psychiatrist Karl Wernicke coined the term in the late nineteenth century, describing it as an emotionally exaggerated yet psychologically comprehensible belief arising from normal cognitive processes that becomes central to an individual’s mental life. Since that time, the construct has been variably reinterpreted through competing theoretical lenses, ranging from Kraepelin’s biological nosology to contemporary cognitive-behavioral and multidimensional models. Despite its clinical relevance across disorders (e.g., anorexia nervosa, body dysmorphic disorder, obsessive–compulsive disorder), overvalued ideas remain inconsistently and insufficiently defined, having been alternately treated as attenuated delusions, markers of poor insight, or disorder-specific severity indicators—interpretations that have limited theoretical coherence, measurement precision, and clinical utility. This review traces the historical evolution of the overvalued idea, clarifies enduring theoretical misinterpretations, and proposes a comprehensive, practical definition. Integrating historical and contemporary perspectives, we define an overvalued idea as a psychologically intelligible, ego-syntonic belief held with disproportionate emotional significance that dominates cognition and behavior without meeting criteria for an obsession or a delusion. We further propose that overvalued ideation is best conceptualized as a transdiagnostic mechanism through which emotionally reinforced beliefs acquire pathological dominance across disorders, a formulation that both honors Wernicke’s original insight and can be operationalized for future research, measurement, diagnosis, and treatment. Full article

Background: Severe, treatment-resistant Obsessive–Compulsive Disorder (OCD) remains a major clinical challenge. When conventional pharmacological and psychotherapeutic strategies fail, neuromodulatory interventions such as repetitive transcranial magnetic stimulation (rTMS) and psychosurgical approaches are increasingly considered. Although both modalities target nodes within the cortico-striato-thalamo-cortical (CSTC) circuit, their relative effectiveness has not been examined within a unified analytical framework. Objective: We aimed to compare responder rates between rTMS and psychosurgical interventions in adults with treatment-resistant OCD through a systematic review and meta-analysis. Methods: A PRISMA-guided search of PubMed and Scopus (2015–2025) identified clinical studies reporting treatment response. Pooled responder rates were estimated separately for each modality using random-effects models. Between-study heterogeneity and publication bias were systematically assessed. Results: Fourteen studies met inclusion criteria, including 10 rTMS studies (416 participants) and four lesion-based psychosurgical studies (142 participants). Both modalities demonstrated clinically meaningful responder rates. Pooled analyses suggested higher responder proportions in psychosurgical cohorts (RR = 3.06, 95% CI 1.43–6.54); however, this finding was accompanied by substantial heterogeneity (I² = 63%) and signals of publication bias. Follow-up duration differed markedly between modalities (mean 2.4 months for rTMS vs. 33.0 months for psychosurgery), reflecting fundamentally different study designs and outcome assessment timepoints. Conclusions: Differences in pooled responder rates should be interpreted as exploratory rather than as evidence of comparative efficacy. The lack of a shared comparator, differences in patient selection, and large discrepancies in follow-up limit direct comparisons between modalities. These findings support a stepped-care framework for neuromodulation in treatment-resistant OCD and highlight the need for methodologically harmonized studies to better define the role of each intervention across distinct clinical profiles of treatment resistance. Full article

Background: Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) shares numerous clinical features with Tourette syndrome (TS), notably the presence of tics and frequent comorbidities such as obsessive-compulsive disorder, irritability, and ADHD-like behaviors, often indistinguishable, particularly in the early stages of the two syndromes. Also, pathogenic similarities between PANS and TS constitute a diagnostic challenge, highlighting the need for biomarkers elucidating the underpinnings of the two disorders. In this context, metabolomics has emerged as a powerful tool for identifying distinct biochemical patterns in various diseases. We previously compared PANS, autism patients, and controls, identifying specific metabolic patterns. However, no studies have directly compared the metabolomic profiles of Tourette syndrome and PANS patients. The present study aims to compare the serum metabolomic profiles of TS patients with those of PANS and healthy controls to advance the molecular understanding and clinical differentiation of these two pediatric neuropsychiatric disorders. Methods: Thirty-four PANS patients and twenty-three Tourette patients were matched with twenty-five healthy subjects (C), and their blood samples were analyzed with ¹H NMR spectroscopy. Subsequently, data were analysed with multivariate and univariate statistical approaches. Results: Supervised models indicated that the metabolomic profile of TS patients was significantly different from that of controls (p = 0.02), with altered concentrations of glutamate, glycerol, glycine, lactate, and proline. No significant differences were found in the comparison between PANS and TS patients. Conclusions: These preliminary data suggest that Tourette and Pans also seem to share the metabolic profiles, while differences were found in TS patients compared to controls. On the other hand, the PANS phenotype comprises symptoms that largely overlap with those of all other NDDs, including TS, outlining a spectrum of disorders that share common pathogenetic pathways. Larger studies are needed to confirm these findings. Full article