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Previous diffusion MRI studies have reported mixed findings on white matter microstructure alterations in obsessive-compulsive disorder (OCD), likely due to variation in demographic and clinical characteristics, scanning methods, and underpowered samples. The OCD global study was created across five international sites to overcome these challenges by harmonizing data collection to identify consistent brain signatures of OCD that are reproducible and generalizable. Single-shell diffusion measures (e.g., fractional anisotropy), multi-shell Neurite Orientation Dispersion and Density Imaging (NODDI) and fixel-based measures, were extracted from skeletonized white matter tracts in 260 medication-free adults with OCD and 252 healthy controls. We additionally performed structural connectome analysis. We compared cases with controls and cases with early (<18) versus late (18+) OCD onset using mixed-model and Bayesian multilevel analysis. Compared with healthy controls, adult OCD individuals showed higher fiber density in the sagittal stratum (B[SE] = 0.10[0.05], P = 0.04) and credible evidence for higher fiber density in several other tracts. When comparing early (n = 145) and late-onset (n = 114) cases, converging evidence showed lower integrity of the posterior thalamic radiation -particularly radial diffusivity (B[SE] = 0.28[0.12], P = 0.03)-and lower global efficiency of the structural connectome (B[SE] = 15.3[6.6], P = 0.03) in late-onset cases. Post-hoc analyses indicated divergent direction of effects of the two OCD groups compared to healthy controls. Age of OCD onset differentially affects the integrity of thalamo-parietal/occipital tracts and the efficiency of the structural brain network. These results lend further support for the role of the thalamus and its afferent fibers and visual attentional processes in the pathophysiology of OCD.
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Edad de Inicio , Encéfalo , Conectoma , Imagen de Difusión Tensora , Trastorno Obsesivo Compulsivo , Sustancia Blanca , Humanos , Trastorno Obsesivo Compulsivo/patología , Sustancia Blanca/patología , Adulto , Masculino , Femenino , Conectoma/métodos , Imagen de Difusión Tensora/métodos , Encéfalo/patología , Persona de Mediana Edad , Imagen de Difusión por Resonancia Magnética/métodos , Adulto Joven , Anisotropía , Teorema de Bayes , Estudios de Casos y Controles , AdolescenteRESUMEN
BACKGROUND: Specific pathways of intergenerational transmission of behavioral traits remain unclear. Here, we aim to investigate how parental genetics influence offspring cognition, educational attainment, and psychopathology in youth. METHODS: Participants for the discovery sample were 2,189 offspring (aged 6-14 years), 1898 mothers and 1,017 fathers who underwent genotyping, psychiatric, and cognitive assessments. We calculated polygenic scores (PGS) for cognition, educational attainment, attention-deficit hyperactivity disorder (ADHD), and schizophrenia for the trios. Phenotypes studied included educational and cognitive measures, ADHD and psychotic symptoms. We used a stepwise approach and multiple mediation models to analyze the effect of parental PGS on offspring traits via offspring PGS and parental phenotype. Significant results were replicated in a sample of 1,029 adolescents, 363 mothers, and 307 fathers. RESULTS: Maternal and paternal PGS for cognition influenced offspring general intelligence and executive function via offspring PGS (genetic pathway) and parental education (phenotypic pathway). Similar results were found for parental PGS for educational attainment and offspring reading and writing skills. These pathways fully explained associations between parental PGS and offspring phenotypes, without residual direct association. Associations with maternal, but not paternal, PGS were replicated. No associations were found between parental PGS for psychopathology and offspring specific symptoms. CONCLUSIONS: Our findings indicate that parental genetics influences offspring cognition and educational attainment by genetic and phenotypic pathways, suggesting the expression of parental phenotypes partially explain the association between parental genetic risk and offspring outcomes. Multiple mediations might represent an effective approach to disentangle distinct pathways for intergenerational transmission of behavioral traits.
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Trastorno por Déficit de Atención con Hiperactividad , Padres , Femenino , Humanos , Cognición , Escolaridad , Madres , Trastorno por Déficit de Atención con Hiperactividad/genética , FenotipoRESUMEN
BACKGROUND: The obsession of turning into another person (transformation obsessions [TO]), and its related compulsions have been initially conceptualised as a form of mental contamination. Nevertheless, it has remained understudied in the current obsessive-compulsive disorder (OCD) literature. In parallel, disturbances of the self have been identified as markers of prodromal psychosis in patients with schizophrenia. Based on the later association, this study aimed to investigate the sociodemographic and clinical correlates of TO. METHODS: In all, 1001 OCD outpatients from the Brazilian OCD Research Consortium were included in this study. Several semi-structured and structured instruments were used to compare 48 OCD patients with TO with 953 OCD patients without TO. A repression model investigated the relationships between the presence of current TO and statistically significant univariate test outcomes. RESULTS: Participants with TO presented an overall younger age, a longer period of time between the onset of the OCD symptoms and an OCD diagnosis, greater severity of the sexual/religious dimension and increased suicidality symptoms. CONCLUSIONS: These results indicate that TO may be better conceptualised as a form of forbidden/taboo thoughts rather than contamination. While no significant associations with psychotic features (e.g. decreased insight) were observed, TO patients displayed increased suicidality, overall younger age and a significantly larger disparity between seeking treatment and OCD diagnosis. This demonstrates that further clinical awareness and research into TO as an OCD symptom is most needed.
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Trastorno Obsesivo Compulsivo , Humanos , Trastorno Obsesivo Compulsivo/diagnóstico , Conducta Compulsiva , Conducta Obsesiva , Psicopatología , Ideación SuicidaRESUMEN
BACKGROUND: Obsessional slowness (OS) is characterised by debilitating motor slowness during initiation and completion of daily tasks such as washing, dressing, eating or walking. Yet, the clinical features of OS are still poorly understood. METHODS: This study aimed to delineate demographics, comorbid disorders and obsessive-compulsive symptoms (OCS) associated with OS. Cross sectional data from 667 OCD outpatients aged 9-82 years (M = 37.86, SD = 12.78) who underwent comprehensive standardised assessments administered by trained clinicians were analysed. Participants with (n = 189) and without (n = 478) OS were compared and contrasted. RESULTS: Logistic regression revealed that being single, having tics and displaying higher severity of aggression, contamination, symmetry and hoarding symptoms significantly predicted participants having OS. CONCLUSIONS: This is the largest-scale descriptive study of OS, which also provides preliminary evidence that OS may be a more severe form of OCD. Further empirical validation of these findings is required, and future research should focus on developing OS assessment.Key PointsThis was the first large-scale descriptive study of obsessional slowness (OS), that provided preliminary evidence for an OS phenotype within obsessive-compulsive disorderOS is associated with increased severity of aggression, contamination, symmetry and hoarding obsessive-compulsive symptomsIndividuals with OS are more likely to have comorbid tics, suggesting that there may be underlying motor factors contributing to this conditionFuture research would benefit from collecting both qualitative and quantitative data when assessing OS.
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Trastorno Obsesivo Compulsivo , Trastornos de Tic , Tics , Humanos , Tics/complicaciones , Estudios Transversales , Trastorno Obsesivo Compulsivo/epidemiología , Trastorno Obsesivo Compulsivo/diagnóstico , ComorbilidadRESUMEN
BACKGROUND: The symptoms of obsessive-compulsive disorder (OCD) are highly heterogeneous and it is unclear what is the optimal way to conceptualize this heterogeneity. This study aimed to establish a comprehensive symptom structure model of OCD across the lifespan using factor and network analytic techniques. METHODS: A large multinational cohort of well-characterized children, adolescents, and adults diagnosed with OCD (N = 1366) participated in the study. All completed the Dimensional Yale-Brown Obsessive-Compulsive Scale, which contains an expanded checklist of 87 distinct OCD symptoms. Exploratory and confirmatory factor analysis were used to outline empirically supported symptom dimensions, and interconnections among the resulting dimensions were established using network analysis. Associations between dimensions and sociodemographic and clinical variables were explored using structural equation modeling (SEM). RESULTS: Thirteen first-order symptom dimensions emerged that could be parsimoniously reduced to eight broad dimensions, which were valid across the lifespan: Disturbing Thoughts, Incompleteness, Contamination, Hoarding, Transformation, Body Focus, Superstition, and Loss/Separation. A general OCD factor could be included in the final factor model without a significant decline in model fit according to most fit indices. Network analysis showed that Incompleteness and Disturbing Thoughts were most central (i.e. had most unique interconnections with other dimensions). SEM showed that the eight broad dimensions were differentially related to sociodemographic and clinical variables. CONCLUSIONS: Future research will need to establish if this expanded hierarchical and multidimensional model can help improve our understanding of the etiology, neurobiology and treatment of OCD.
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Trastorno Obsesivo Compulsivo , Adulto , Adolescente , Niño , Humanos , Trastorno Obsesivo Compulsivo/diagnóstico , Análisis Factorial , Determinación de la PersonalidadRESUMEN
BACKGROUND: Despite the multitude of clinical manifestations of post-acute sequelae of SARS-CoV-2 infection (PASC), studies applying statistical methods to directly investigate patterns of symptom co-occurrence and their biological correlates are scarce. METHODS: We assessed 30 symptoms pertaining to different organ systems in 749 adults (age = 55 ± 14 years; 47% female) during in-person visits conducted at 6-11 months after hospitalization due to coronavirus disease 2019 (COVID-19), including six psychiatric and cognitive manifestations. Symptom co-occurrence was initially investigated using exploratory factor analysis (EFA), and latent variable modeling was then conducted using Item Response Theory (IRT). We investigated associations of latent variable severity with objective indices of persistent physical disability, pulmonary and kidney dysfunction, and C-reactive protein and D-dimer blood levels, measured at the same follow-up assessment. RESULTS: The EFA extracted one factor, explaining 64.8% of variance; loadings were positive for all symptoms, and above 0.35 for 16 of them. The latent trait generated using IRT placed fatigue, psychiatric, and cognitive manifestations as the most discriminative symptoms (coefficients > 1.5, p < 0.001). Latent trait severity was associated with decreased body weight and poorer physical performance (coefficients > 0.240; p ⩽ 0.003), and elevated blood levels of C-reactive protein (coefficient = 0.378; 95% CI 0.215-0.541; p < 0.001) and D-dimer (coefficient = 0.412; 95% CI 0.123-0.702; p = 0.005). Results were similar after excluding subjects with pro-inflammatory comorbidities. CONCLUSIONS: Different symptoms that persist for several months after moderate or severe COVID-19 may unite within one latent trait of PASC. This trait is dominated by fatigue and psychiatric symptoms, and is associated with objective signs of physical disability and persistent systemic inflammation.
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COVID-19 , Adulto , Anciano , Proteína C-Reactiva , COVID-19/complicaciones , Sistema Nervioso Central , Progresión de la Enfermedad , Fatiga/etiología , Femenino , Humanos , Inflamación , Masculino , Persona de Mediana Edad , SARS-CoV-2 , Síndrome Post Agudo de COVID-19RESUMEN
An important challenge in mental health research is to translate findings from cognitive neuroscience and neuroimaging research into effective treatments that target the neurobiological alterations involved in psychiatric symptoms. To address this challenge, in this review we propose a heuristic neurocircuit-based taxonomy to guide the treatment of obsessive-compulsive disorder (OCD). We do this by integrating information from several sources. First, we provide case vignettes in which patients with OCD describe their symptoms and discuss different clinical profiles in the phenotypic expression of the condition. Second, we link variations in these clinical profiles to underlying neurocircuit dysfunctions, drawing on findings from neuropsychological and neuroimaging studies in OCD. Third, we consider behavioral, pharmacological, and neuromodulatory treatments that could target those specific neurocircuit dysfunctions. Finally, we suggest methods of testing this neurocircuit-based taxonomy as well as important limitations to this approach that should be considered in future research.
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Trastorno Obsesivo Compulsivo , Humanos , Neuroimagen , Trastorno Obsesivo Compulsivo/terapiaRESUMEN
BACKGROUND: The present study explored the influence of romantic love on the expression of several obsessive-compulsive disorder (OCD) characteristics, including symptom severity, symptom dimensions, age at onset, sensory phenomena (SP), and developmental course, as well as other related comorbid disorders. It was hypothesized that love-precipitated OCD would be associated with a set of distinct characteristics and exhibit greater rates of comorbid disorders. METHODS: The analyses were performed using a large sample (n = 981) of clinical patients with a primary diagnosis of OCD (Females = 67.3%, M age = 35.31). RESULTS: Love-precipitated OCD was associated with greater severity of SP and later age at onset of obsessions. However, symptom severity, symptom dimension, developmental course, and psychiatric comorbidities were not associated with love-precipitated OCD. CONCLUSION: It was concluded that romantic love does shape the expression of OCD, especially with regard to SP and onset age. These findings encourage further exploration to determine its clinical significance as a phenotype.
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Amor , Trastorno Obsesivo Compulsivo , Femenino , Humanos , Trastorno Obsesivo Compulsivo/psicología , Comorbilidad , Edad de Inicio , FenotipoRESUMEN
Obsessive-compulsive disorder (OCD) commonly co-occurs with other psychiatric conditions. Though research is limited, there is preliminary evidence that OCD also co-occurs with compulsive sexual behavior (CSB). Yet, few studies have investigated the demographic, clinical, and psychiatric comorbidities associated with co-occurring OCD and CSB. To address this gap, the current study aimed to evaluate rates of co-occurring OCD and CSB, identify demographic and clinical factors associated with comorbid OCD and CSB, and assess associated psychiatric comorbidity. Participants (N = 950) were patients of a large multisite treatment for OCD. Standardized self-report measures were used to assess demographic and clinical characteristics such as anxiety, depression, and severity and dimensions of OCD. Semi-structured interviews including the SCID were used to assess psychiatric comorbidities. A total of 36 (3.8%) of participants met the criteria for CSB. Binary logistic regression analysis revealed that males were significantly more likely to present with CSB than females and CSB was associated with greater psychiatric comorbidity, particularly impulse control disorders. These findings suggest that individuals with co-occurring OCD and CSB may have more complex treatment needs, and more tailored interventions may be necessary.
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Trastorno Obsesivo Compulsivo , Disfunciones Sexuales Psicológicas , Masculino , Femenino , Humanos , Trastorno Obsesivo Compulsivo/complicaciones , Trastorno Obsesivo Compulsivo/epidemiología , Trastorno Obsesivo Compulsivo/psicología , Conducta Compulsiva/complicaciones , Conducta Compulsiva/epidemiología , Conducta Compulsiva/psicología , Comorbilidad , Disfunciones Sexuales Psicológicas/complicaciones , Disfunciones Sexuales Psicológicas/epidemiología , Conducta SexualRESUMEN
OBJECTIVE: The aim of this study was to assess mental health in Latin American pediatric rheumatologists (LAPRs) during the COVID-19 pandemic. METHODS: A cross-sectional study was performed with 318 LAPRs based on an online, self-rated survey about clinical practice/mental health impacts during the COVID-19 pandemic. Validated self-reported scales for anxiety (Generalized Anxiety Disorder [GAD-7]) and depression (Patient Health Questionnaire [PHQ-9]) were evaluated. RESULTS: The response rate was 126 of 318 (40%), including 13 of 20 (65%) Latin American countries. Working on the COVID-19 frontline was reported by 27% of LAPRs. Anxiety and moderate/severe depression were observed in 49% and 25%, respectively. No LAPRs reported previous mental health disorders. Deaths of childhood-onset systemic lupus erythematosus and juvenile idiopathic arthritis patients with confirmed/suspected COVID-19 were reported by 8% and 2% of LAPRs, respectively. Further analysis of LAPRs revealed that the median current age was significantly lower in LAPRs with anxiety than in those without anxiety (39 [29-43] vs 45 [30-70] years, p = 0.029). Working on the frontline of COVID-19 (37% vs 17%, p = 0.015), feeling helpless (39% vs 17%, p = 0.009), and experiencing burnout (39% vs 11%, p = 0.0001) were factors significantly higher in LAPRs with anxiety. Median nighttime sleep abnormalities measured by the visual analog scale (VAS) (8 [0-10] vs 4 [0-10], p = 0.009) were significantly higher in the anxiety group, whereas the physical activity VAS was lower (0.5 [0-10] vs 3 [0-10], p = 0.005). A positive Spearman correlation was shown between the GAD-7 score and nighttime sleep abnormality VAS score (r = +0.348, p < 0.001), and a negative correlation was shown between the GAD-7score and physical activity VAS score (r = -0.192, p = 0.031). CONCLUSIONS: Anxiety and depression were relevant to the experience of LAPRs during the COVID-19 pandemic, impacting their mental health. Reporting information about mental health is essential to planning future preventive and health promotion strategies.
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COVID-19 , Adulto , Anciano , Ansiedad/diagnóstico , Ansiedad/epidemiología , Niño , Estudios Transversales , Depresión/diagnóstico , Depresión/epidemiología , Personal de Salud/psicología , Humanos , América Latina/epidemiología , Salud Mental , Persona de Mediana Edad , Pandemias , Reumatólogos , SARS-CoV-2RESUMEN
Single (N = 472, 51.7%), married or living in stable cohabitation (N = 375, 41.1%) and divorced or separated (N = 66, 7.2%) patients with obsessive-compulsive disorder (OCD) were compared in terms of their sociodemographic features, OCD phenotypes, and comorbidity profile. Using single status as a reference group, a multinominal regression analysis found increased age, lower severity of hoarding, increased rates of panic disorder without agoraphobia, and lower rates of dysthymic disorder to be associated with married or stable cohabitation status. Concomitantly, increased age, higher severity of symmetry symptoms, and increased rates of skin picking disorder were found to be associated with divorced status. These findings suggest that there is a relationship between marital status and different OCD phenotypes.
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Estado Civil , Trastorno Obsesivo Compulsivo/epidemiología , Adulto , Brasil/epidemiología , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVES: While theoretical models link obsessive-compulsive disorder (OCD) with executive function deficits, empirical findings from the neuropsychological literature remain mixed. These inconsistencies are likely exacerbated by the challenge of high-dimensional data (i.e., many variables per subject), which is common across neuropsychological paradigms and necessitates analytical advances. More unique to OCD is the heterogeneity of symptom presentations, each of which may relate to distinct neuropsychological features. While researchers have traditionally attempted to account for this heterogeneity using a symptom-based approach, an alternative involves focusing on underlying symptom motivations. Although the most studied symptom motivation involves fear of harmful events, 60-70% of patients also experience sensory phenomena, consisting of uncomfortable sensations or perceptions that drive compulsions. Sensory phenomena have received limited attention in the neuropsychological literature, despite evidence that symptoms motivated by these experiences may relate to distinct cognitive processes. METHODS: Here, we used a supervised machine learning approach to characterize neuropsychological processes in OCD, accounting for sensory phenomena. RESULTS: Compared to logistic regression and other algorithms, random forest best differentiated healthy controls (n = 59; balanced accuracy = .70), patients with sensory phenomena (n = 29; balanced accuracy = .59), and patients without sensory phenomena (n = 46; balanced accuracy = .62). Decision-making best distinguished between groups based on sensory phenomena, and among the patient subsample, those without sensory phenomena uniquely displayed greater risk sensitivity compared to healthy controls (d = .07, p = .008). CONCLUSIONS: Results suggest that different cognitive profiles may characterize patients motivated by distinct drives. The superior performance and generalizability of the newer algorithms highlights the utility of considering multiple analytic approaches when faced with complex data. PRACTITIONER POINTS: Practitioners should be aware that sensory phenomena are common experiences among patients with OCD. OCD patients with sensory phenomena may be distinguished from those without based on neuropsychological processes.
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Aprendizaje Automático/normas , Pruebas Neuropsicológicas/normas , Trastorno Obsesivo Compulsivo/diagnóstico , Aprendizaje Automático Supervisado/normas , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Trastorno Obsesivo Compulsivo/psicologíaRESUMEN
For more than half a century, stereotactic neurosurgical procedures have been available to treat patients with severe, debilitating symptoms of obsessive-compulsive disorder (OCD) that have proven refractory to extensive, appropriate pharmacological, and psychological treatment. Although reliable predictors of outcome remain elusive, the establishment of narrower selection criteria for neurosurgical candidacy, together with a better understanding of the functional neuroanatomy implicated in OCD, has resulted in improved clinical efficacy for an array of ablative and non-ablative intervention techniques targeting the cingulum, internal capsule, and other limbic regions. It was against this backdrop that gamma knife capsulotomy (GKC) for OCD was developed. In this paper, we review the history of this stereotactic radiosurgical procedure, from its inception to recent advances. We perform a systematic review of the existing literature and also provide a narrative account of the evolution of the procedure, detailing how the procedure has changed over time, and has been shaped by forces of evidence and innovation. As the procedure has evolved and adverse events have decreased considerably, favorable response rates have remained attainable for approximately one-half to two-thirds of individuals treated at experienced centers. A reduction in obsessive-compulsive symptom severity may result not only from direct modulation of OCD neural pathways but also from enhanced efficacy of pharmacological and psychological therapies working in a synergistic fashion with GKC. Possible complications include frontal lobe edema and even the rare formation of delayed radionecrotic cysts. These adverse events have become much less common with new radiation dose and targeting strategies. Detailed neuropsychological assessments from recent studies suggest that cognitive function is not impaired, and in some domains may even improve following treatment. We conclude this review with discussions covering topics essential for further progress of this therapy, including suggestions for future trial design given the unique features of GKC therapy, considerations for optimizing stereotactic targeting and dose planning using biophysical models, and the use of advanced imaging techniques to understand circuitry and predict response. GKC, and in particular its modern variant, gamma ventral capsulotomy, continues to be a reliable treatment option for selected cases of otherwise highly refractory OCD.
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Cápsula Interna/cirugía , Trastorno Obsesivo Compulsivo/cirugía , Trastorno Obsesivo Compulsivo/terapia , Lóbulo Frontal/fisiopatología , Humanos , Vías Nerviosas/fisiopatología , Pruebas Neuropsicológicas , Procedimientos Neuroquirúrgicos/métodos , Trastorno Obsesivo Compulsivo/fisiopatología , Radiocirugia/métodos , Resultado del TratamientoRESUMEN
BACKGROUND: Trichotillomania (TTM) is a difficult-to-treat psychiatric condition with no first-line medications approved by the Food and Drug Administration. Individuals with TTM often feel that clinicians know little about this disorder. Here, we present an updated meta-analysis of randomized controlled trials (RCTs) examining treatments for TTM. METHODS: Pubmed, PsychINFO, Embase, and CENTRAL were searched with the terms "Trichotillomania OR Hair Pulling Disorder" to identify randomized controlled clinical trials evaluating treatments for TTM. RESULTS: Twenty-four trials involving 26 comparisons and 857 participants were included in this meta-analysis. Behavioral therapy with habit-reversal training components (BT-HRT) demonstrated a large benefit compared to control conditions (standardized mean difference [SMD] [95% CI] = -1.22 [-1.71, -0.73], p < .0001) for improving TTM symptoms. Clomipramine (SMD [95% CI] = -0.71 [-1.38, -0.05], p = .036), N-acetylcysteine (SMD [95% CI] = -0.75 [-1.36, -0.13], p = .017) and olanzapine (SMD [95% CI] = -0.94 [-1.77, -0.12], p = .025) demonstrated significant benefits compared to placebo in RCTs. CONCLUSIONS: BT-HRT has demonstrated the largest treatment effects and has the strongest evidence base for reducing TTM symptoms. In contrast, several pharmacological agents have demonstrated efficacy in single randomized clinical trials that would benefit from replication. Additional trials are needed to identify other effective medications for TTM and determine the relative efficacy of available agents.
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Tricotilomanía , Acetilcisteína , Terapia Conductista , Clomipramina/uso terapéutico , Humanos , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Tricotilomanía/tratamiento farmacológicoRESUMEN
OBJECTIVE: Mental disorders can have a major impact on brain development. Peripheral blood concentrations of brain-derived neurotrophic factor (BDNF) are lower in adult psychiatric disorders. Serum BDNF concentrations and BDNF genotype have been associated with cortical maturation in children and adolescents. In 2 large independent samples, this study tests associations between serum BDNF concentrations, brain structure, and psychopathology, and the effects of BDNF genotype on BDNF serum concentrations in late childhood and early adolescence. METHODS: Children and adolescents (7-14 years old) from 2 cities (n = 267 in Porto Alegre; n = 273 in São Paulo) were evaluated as part of the Brazilian high-risk cohort (HRC) study. Serum BDNF concentrations were quantified by sandwich ELISA. Genotyping was conducted from blood or saliva samples using the SNParray Infinium HumanCore Array BeadChip. Subcortical volumes and cortical thickness were quantified using FreeSurfer. The Development and Well-Being Behavior Assessment was used to identify the presence of a psychiatric disorder. RESULTS: Serum BDNF concentrations were not associated with subcortical volumes or with cortical thickness. Serum BDNF concentration did not differ between participants with and without mental disorders, or between Val homozygotes and Met carriers. CONCLUSIONS: No evidence was found to support serum BDNF concentrations as a useful marker of developmental differences in brain and behavior in early life. Negative findings were replicated in 2 of the largest independent samples investigated to date.
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Factor Neurotrófico Derivado del Encéfalo/genética , Encéfalo/diagnóstico por imagen , Trastornos Mentales/genética , Polimorfismo de Nucleótido Simple , Adolescente , Biomarcadores/sangre , Encéfalo/crecimiento & desarrollo , Factor Neurotrófico Derivado del Encéfalo/sangre , Niño , Femenino , Genotipo , Humanos , Imagen por Resonancia Magnética , Masculino , Trastornos Mentales/sangre , Trastornos Mentales/diagnóstico por imagenRESUMEN
BACKGROUND: Obsessive-compulsive disorder (OCD) has a lifetime prevalence of 2-3% and is a leading cause of global disability. Brain circuit abnormalities in individuals with OCD have been identified, but important knowledge gaps remain. The goal of the new global initiative described in this paper is to identify robust and reproducible brain signatures of measurable behaviors and clinical symptoms that are common in individuals with OCD. A global approach was chosen to accelerate discovery, to increase rigor and transparency, and to ensure generalizability of results. METHODS: We will study 250 medication-free adults with OCD, 100 unaffected adult siblings of individuals with OCD, and 250 healthy control subjects at five expert research sites across five countries (Brazil, India, Netherlands, South Africa, and the U.S.). All participants will receive clinical evaluation, neurocognitive assessment, and magnetic resonance imaging (MRI). The imaging will examine multiple brain circuits hypothesized to underlie OCD behaviors, focusing on morphometry (T1-weighted MRI), structural connectivity (Diffusion Tensor Imaging), and functional connectivity (resting-state fMRI). In addition to analyzing each imaging modality separately, we will also use multi-modal fusion with machine learning statistical methods in an attempt to derive imaging signatures that distinguish individuals with OCD from unaffected siblings and healthy controls (Aim #1). Then we will examine how these imaging signatures link to behavioral performance on neurocognitive tasks that probe these same circuits as well as to clinical profiles (Aim #2). Finally, we will explore how specific environmental features (childhood trauma, socioeconomic status, and religiosity) moderate these brain-behavior associations. DISCUSSION: Using harmonized methods for data collection and analysis, we will conduct the largest neurocognitive and multimodal-imaging study in medication-free subjects with OCD to date. By recruiting a large, ethno-culturally diverse sample, we will test whether there are robust biosignatures of core OCD features that transcend countries and cultures. If so, future studies can use these brain signatures to reveal trans-diagnostic disease dimensions, chart when these signatures arise during development, and identify treatments that target these circuit abnormalities directly. The long-term goal of this research is to change not only how we conceptualize OCD but also how we diagnose and treat it.
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Mapeo Encefálico , Encéfalo/diagnóstico por imagen , Imagen de Difusión Tensora , Internacionalidad , Imagen por Resonancia Magnética , Estudios Multicéntricos como Asunto/métodos , Trastorno Obsesivo Compulsivo/diagnóstico por imagen , Adolescente , Adulto , Encéfalo/patología , Encéfalo/fisiopatología , Brasil , Estudios de Casos y Controles , Femenino , Humanos , India , Masculino , Persona de Mediana Edad , Países Bajos , Trastorno Obsesivo Compulsivo/patología , Trastorno Obsesivo Compulsivo/fisiopatología , Proyectos de Investigación , Hermanos/psicología , Sudáfrica , Estados Unidos , Adulto JovenRESUMEN
OBJECTIVES: The Yale-Brown Obsessive-Compulsive Scale has been considered the gold standard scale to assess obsessive-compulsive disorder severity. Previous studies using exploratory factor analysis and confirmatory factor analysis with this scale showed mixed findings in terms of factor structure and fit of models. Therefore, we used confirmatory factor analysis to compare different Yale-Brown Obsessive-Compulsive Scale models in a large sample aiming to identify the best model fit. METHODS: We assessed adult obsessive-compulsive disorder patients (n = 955) using three measures: Yale-Brown Obsessive-Compulsive Scale severity ratings, the Dimensional Yale-Brown Obsessive-Compulsive Scale and the clinical global impression scale. We tested all factor structures reported by previous studies to investigate which model best fitted the data: one-factor, two-factor, three-factor and their equivalent high-order solutions. We also investigated Yale-Brown Obsessive-Compulsive Scale items correlations with scores from the other measures of obsessive-compulsive disorder severity. RESULTS: Confirmatory factor analysis models presented mediocre to fair goodness-of-fit indexes. Severity items related to resistance to obsessions and compulsions presented low factor loadings. The model with the best fit indexes was a high-order model without obsessive-compulsive disorder resistance items. These items also presented small correlations with other obsessive-compulsive disorder severity measures. CONCLUSION: The obsessive-compulsive disorder field needs to discuss further improvements in the Yale-Brown Obsessive-Compulsive Scale and/or continue to search for better measures of obsessive-compulsive disorder severity.
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Trastorno Obsesivo Compulsivo/diagnóstico , Escalas de Valoración Psiquiátrica , Adulto , Humanos , Conducta Obsesiva/diagnóstico , Psicometría , Reproducibilidad de los Resultados , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: The Research Domain Criteria seeks to bridge knowledge from neuroscience with clinical practice by promoting research into valid neurocognitive phenotypes and dimensions, irrespective of symptoms and diagnoses as currently conceptualized. While the Research Domain Criteria offers a vision of future research and practice, its 39 functional constructs need refinement to better target new phenotyping efforts. This study aimed to determine which Research Domain Criteria constructs are most relevant to understanding obsessive-compulsive and related disorders, based on a consensus between experts in the field of obsessive-compulsive and related disorders. METHODS: Based on a modified Delphi method, 46 experts were recruited from Australia, Africa, Asia, Europe and the Americas. Over three rounds, experts had the opportunity to review their opinion in light of feedback from the previous round, which included how their response compared to other experts and a summary of comments given. RESULTS: Thirty-four experts completed round one, of whom 28 (82%) completed round two and 24 (71%) completed round three. At the final round, four constructs were endorsed by ⩾75% of experts as 'primary constructs' and therefore central to understanding obsessive-compulsive and related disorders. Of these constructs, one came from the Positive Valence System (Habit), two from the Cognitive Control System (Response Selection/Inhibition and Performance Monitoring) and the final construct was an additional item suggested by experts (Compulsivity). CONCLUSION: This study identified four Research Domain Criteria constructs that, according to experts, cut across different obsessive-compulsive and related disorders. These constructs represent key areas for future investigation, and may have potential implications for clinical practice in terms of diagnostic processes and therapeutic management of obsessive-compulsive and related disorders.
Asunto(s)
Consenso , Técnica Delphi , Internacionalidad , Trastorno Obsesivo Compulsivo/diagnóstico , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Objectives: To assess the rates of co-occurring putative 'behavioural addictions' in patients with obsessive-compulsive disorder (OCD).Methods: Twenty-three international centres specialising in the treatment of OCD were invited to participate in a survey of the rates of behavioural addictions and other relevant comorbidity within their samples.Results: Sixteen of 23 (69.6%) invited centres from 13 countries had sufficient data to participate in the survey. The use of validated diagnostic tools was discrepant, with most centres relying on a 'clinical diagnosis' to diagnose behavioural addictions. The final sample comprised of 6916 patients with a primary diagnosis of OCD. The reported rates of behavioural addictions were as follows: 8.7% for problematic internet use, 6.8% for compulsive sexual behaviour disorder, 6.4% for compulsive buying, 4.1% for gambling disorder and 3.4% for internet gaming disorder.Conclusions: Behavioural addictions should be better assessed for patients with OCD. The absence of diagnostic scales developed specifically for behavioural addictions and overlapping obsessive-compulsive phenomena such as compulsive checking of information on the internet may explain the relatively high rate of problematic internet use in this sample. The study encourages better efforts to assess and to conceptualise the relatedness of behavioural addictions to obsessive-compulsive 'spectrum' disorders.
Asunto(s)
Conducta Adictiva/epidemiología , Juego de Azar/epidemiología , Trastorno Obsesivo Compulsivo/epidemiología , Conducta Sexual/estadística & datos numéricos , Adolescente , Adulto , Comorbilidad , Femenino , Humanos , Trastorno de Adicción a Internet/epidemiología , Masculino , Persona de Mediana Edad , Juegos de Video , Adulto JovenRESUMEN
BACKGROUND: Recent findings suggest an association between attention deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). Thus, we evaluated the clinical associated features of ADHD in a large sample of adult OCD patients. METHODS: A cross-sectional study including 955 adult patients with OCD from the Brazilian Research Consortium of Obsessive-Compulsive Spectrum Disorders (C-TOC). Clinical characteristics in adult OCD patients with and without comorbid ADHD were compared using Fisher's exact test, t-tests or Mann-Whitney tests. Bivariate analyses were followed by logistic regression analysis to identify clinical characteristics independently associated with ADHD comorbidity. RESULTS: The lifetime prevalence of ADHD in adult OCD patients was 13.7%. The current results indicate that OCD + ADHD patients were more severe, had an earlier onset of the obsessive-compulsive symptoms, a higher history of rheumatic fever, with higher frequencies of sensory phenomena and comorbidity with Tourette syndrome. They also had an increased risk for academic impairment and suicide attempts. CONCLUSION: Adult OCD patients with ADHD present some specific clinical features and may represent a special subgroup of adult OCD. Future studies should focus on the development of interventions more tailored to the phenotype of this subgroup of patients.