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1.
medRxiv ; 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38712091

RESUMO

Obsessive-compulsive disorder (OCD) affects ~1% of the population and exhibits a high SNP-heritability, yet previous genome-wide association studies (GWAS) have provided limited information on the genetic etiology and underlying biological mechanisms of the disorder. We conducted a GWAS meta-analysis combining 53,660 OCD cases and 2,044,417 controls from 28 European-ancestry cohorts revealing 30 independent genome-wide significant SNPs and a SNP-based heritability of 6.7%. Separate GWAS for clinical, biobank, comorbid, and self-report sub-groups found no evidence of sample ascertainment impacting our results. Functional and positional QTL gene-based approaches identified 249 significant candidate risk genes for OCD, of which 25 were identified as putatively causal, highlighting WDR6, DALRD3, CTNND1 and genes in the MHC region. Tissue and single-cell enrichment analyses highlighted hippocampal and cortical excitatory neurons, along with D1- and D2-type dopamine receptor-containing medium spiny neurons, as playing a role in OCD risk. OCD displayed significant genetic correlations with 65 out of 112 examined phenotypes. Notably, it showed positive genetic correlations with all included psychiatric phenotypes, in particular anxiety, depression, anorexia nervosa, and Tourette syndrome, and negative correlations with a subset of the included autoimmune disorders, educational attainment, and body mass index.. This study marks a significant step toward unraveling its genetic landscape and advances understanding of OCD genetics, providing a foundation for future interventions to address this debilitating disorder.

3.
Mol Psychiatry ; 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38326559

RESUMO

White matter pathways, typically studied with diffusion tensor imaging (DTI), have been implicated in the neurobiology of obsessive-compulsive disorder (OCD). However, due to limited sample sizes and the predominance of single-site studies, the generalizability of OCD classification based on diffusion white matter estimates remains unclear. Here, we tested classification accuracy using the largest OCD DTI dataset to date, involving 1336 adult participants (690 OCD patients and 646 healthy controls) and 317 pediatric participants (175 OCD patients and 142 healthy controls) from 18 international sites within the ENIGMA OCD Working Group. We used an automatic machine learning pipeline (with feature engineering and selection, and model optimization) and examined the cross-site generalizability of the OCD classification models using leave-one-site-out cross-validation. Our models showed low-to-moderate accuracy in classifying (1) "OCD vs. healthy controls" (Adults, receiver operator characteristic-area under the curve = 57.19 ± 3.47 in the replication set; Children, 59.8 ± 7.39), (2) "unmedicated OCD vs. healthy controls" (Adults, 62.67 ± 3.84; Children, 48.51 ± 10.14), and (3) "medicated OCD vs. unmedicated OCD" (Adults, 76.72 ± 3.97; Children, 72.45 ± 8.87). There was significant site variability in model performance (cross-validated ROC AUC ranges 51.6-79.1 in adults; 35.9-63.2 in children). Machine learning interpretation showed that diffusivity measures of the corpus callosum, internal capsule, and posterior thalamic radiation contributed to the classification of OCD from HC. The classification performance appeared greater than the model trained on grey matter morphometry in the prior ENIGMA OCD study (our study includes subsamples from the morphometry study). Taken together, this study points to the meaningful multivariate patterns of white matter features relevant to the neurobiology of OCD, but with low-to-moderate classification accuracy. The OCD classification performance may be constrained by site variability and medication effects on the white matter integrity, indicating room for improvement for future research.

4.
J Am Acad Child Adolesc Psychiatry ; 62(4): 403-414, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36526161

RESUMO

OBJECTIVE: Cognitive-behavioral therapy (CBT) is considered a first-line treatment for obsessive-compulsive disorder (OCD) in pediatric and adult populations. Nevertheless, some patients show partial or null response. The identification of predictors of CBT response may improve clinical management of patients with OCD. Here, we aimed to identify structural magnetic resonance imaging (MRI) predictors of CBT response in 2 large series of children and adults with OCD from the worldwide ENIGMA-OCD consortium. METHOD: Data from 16 datasets from 13 international sites were included in the study. We assessed which variations in baseline cortical thickness, cortical surface area, and subcortical volume predicted response to CBT (percentage of baseline to post-treatment symptom reduction) in 2 samples totaling 168 children and adolescents (age range 5-17.5 years) and 318 adult patients (age range 18-63 years) with OCD. Mixed linear models with random intercept were used to account for potential cross-site differences in imaging values. RESULTS: Significant results were observed exclusively in the pediatric sample. Right prefrontal cortex thickness was positively associated with the percentage of CBT response. In a post hoc analysis, we observed that the specific changes accounting for this relationship were a higher thickness of the frontal pole and the rostral middle frontal gyrus. We observed no significant effects of age, sex, or medication on our findings. CONCLUSION: Higher cortical thickness in specific right prefrontal cortex regions may be important for CBT response in children with OCD. Our findings suggest that the right prefrontal cortex plays a relevant role in the mechanisms of action of CBT in children.


Assuntos
Terapia Cognitivo-Comportamental , Transtorno Obsessivo-Compulsivo , Adulto , Adolescente , Humanos , Criança , Pré-Escolar , Córtex Pré-Frontal/diagnóstico por imagem , Transtorno Obsessivo-Compulsivo/diagnóstico por imagem , Transtorno Obsessivo-Compulsivo/terapia , Imageamento por Ressonância Magnética , Lobo Frontal , Terapia Cognitivo-Comportamental/métodos
5.
Front Psychiatry ; 13: 951065, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36186877

RESUMO

Initial controlled trials of the serotonergic antidepressant fluvoxamine showed promise for treatment of mild to moderate COVID-19 in outpatients, although more recent outpatient data have been less encouraging. Turning to studies of hospitalized patients, a retrospective cohort study by Hoertel and associates in 2021 found a markedly reduced risk of intubation or death among patients hospitalized with COVID-19 who were receiving serotonergic antidepressants at the time of admission vs. those not receiving antidepressants. In an attempt to replicate these latter findings, we performed a similarly designed study of 500 individuals hospitalized with COVID-19 in a large academic hospital system who were taking a serotonergic antidepressant at the time of admission compared with two groups (N = 573 and N = 593) not receiving an antidepressant. In analyses controlling for demographic and clinical variables, we found no significant difference in effect between the antidepressant group and either of the two comparison groups [hazard ratios (95% CI) for intubation or death 1.1 (0.83-1.5) and 1.1 (0.86-1.5); and for death alone 1.3 (0.93-1.8) and 1.1 (0.85-1.7)]. Examining the results of our study, along with those of Hoertel et al. and three additional retrospective cohort studies in inpatients published in the interim, the data permit only very limited conclusions, with the findings on the effect of serotonergic antidepressants ranging from a strongly protective effect to no effect. Although there are numerous threats to validity that might account for this wide range of findings, we could not identify any principal factor or set of factors that could clearly explain the differences.

6.
J Affect Disord ; 318: 204-216, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36041582

RESUMO

BACKGROUND: Widely used psychotropic medications for obsessive-compulsive disorder (OCD) may change the volumes of subcortical brain structures, and differently in children vs. adults. We measured subcortical volumes cross-sectionally in patients finely stratified for age taking various common classes of OCD drugs. METHODS: The ENIGMA-OCD consortium sample (1081 medicated/1159 unmedicated OCD patients and 2057 healthy controls aged 6-65) was divided into six successive 6-10-year age-groups. Individual structural MRIs were parcellated automatically using FreeSurfer into 8 regions-of-interest (ROIs). ROI volumes were compared between unmedicated and medicated patients and controls, and between patients taking serotonin reuptake inhibitors (SRIs), tricyclics (TCs), antipsychotics (APs), or benzodiazepines (BZs) and unmedicated patients. RESULTS: Compared to unmedicated patients, volumes of accumbens, caudate, and/or putamen were lower in children aged 6-13 and adults aged 50-65 with OCD taking SRIs (Cohen's d = -0.24 to -0.74). Volumes of putamen, pallidum (d = 0.18-0.40), and ventricles (d = 0.31-0.66) were greater in patients aged 20-29 receiving APs. Hippocampal volumes were smaller in patients aged 20 and older taking TCs and/or BZs (d = -0.27 to -1.31). CONCLUSIONS: Results suggest that TCs and BZs could potentially aggravate hippocampal atrophy of normal aging in older adults with OCD, whereas SRIs may reduce striatal volumes in young children and older adults. Similar to patients with psychotic disorders, OCD patients aged 20-29 may experience subcortical nuclear and ventricular hypertrophy in relation to APs. Although cross-sectional, present results suggest that commonly prescribed agents exert macroscopic effects on subcortical nuclei of unknown relation to therapeutic response.


Assuntos
Antipsicóticos , Transtorno Obsessivo-Compulsivo , Idoso , Antipsicóticos/efeitos adversos , Benzodiazepinas/uso terapêutico , Criança , Pré-Escolar , Estudos Transversais , Humanos , Longevidade , Imageamento por Ressonância Magnética , Transtorno Obsessivo-Compulsivo/diagnóstico por imagem , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos
8.
Hum Brain Mapp ; 43(1): 23-36, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-32154629

RESUMO

Neuroimaging has played an important part in advancing our understanding of the neurobiology of obsessive-compulsive disorder (OCD). At the same time, neuroimaging studies of OCD have had notable limitations, including reliance on relatively small samples. International collaborative efforts to increase statistical power by combining samples from across sites have been bolstered by the ENIGMA consortium; this provides specific technical expertise for conducting multi-site analyses, as well as access to a collaborative community of neuroimaging scientists. In this article, we outline the background to, development of, and initial findings from ENIGMA's OCD working group, which currently consists of 47 samples from 34 institutes in 15 countries on 5 continents, with a total sample of 2,323 OCD patients and 2,325 healthy controls. Initial work has focused on studies of cortical thickness and subcortical volumes, structural connectivity, and brain lateralization in children, adolescents and adults with OCD, also including the study on the commonalities and distinctions across different neurodevelopment disorders. Additional work is ongoing, employing machine learning techniques. Findings to date have contributed to the development of neurobiological models of OCD, have provided an important model of global scientific collaboration, and have had a number of clinical implications. Importantly, our work has shed new light on questions about whether structural and functional alterations found in OCD reflect neurodevelopmental changes, effects of the disease process, or medication impacts. We conclude with a summary of ongoing work by ENIGMA-OCD, and a consideration of future directions for neuroimaging research on OCD within and beyond ENIGMA.


Assuntos
Neuroimagem , Transtorno Obsessivo-Compulsivo , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/patologia , Humanos , Aprendizado de Máquina , Estudos Multicêntricos como Assunto , Transtorno Obsessivo-Compulsivo/diagnóstico por imagem , Transtorno Obsessivo-Compulsivo/patologia
9.
Psychiatry Res ; 300: 113853, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33975093

RESUMO

Obsessive-compulsive disorder (OCD) affects approximately one person in 40 and causes substantial suffering. Evidence-based treatments can benefit many; however, optimal treatment can be difficult to access. Diagnosis is frequently delayed, and pharmacological and psychotherapeutic interventions often fail to follow evidence-based guidelines. To ameliorate this distressing situation, the International OCD Accreditation Task Force of the Canadian Institute for Obsessive-Compulsive Disorders has developed knowledge and competency standards for specialized treatments for OCD through the lifespan. These are foundational to evidence-based practice and will form the basis for upcoming ATF development of certification/accreditation programs. Here, we present specialty standards for the pharmacological treatment of adult OCD. We emphasize the importance of integrating pharmacotherapy with clear diagnosis, appreciation of complicating factors, and evidence-based cognitive behavioral therapy. Clear evidence exists to inform first- and second-line pharmacological treatments. In disease refractory to these initial efforts, multiple strategies have been investigated, but the evidence is more equivocal. These standards summarize this limited evidence to give the specialist practitioner a solid basis on which to make difficult decisions in complex cases. It is hoped that further research will lead to development of a clear, multi-step treatment algorithm to support each step in clinical decision-making.


Assuntos
Terapia Cognitivo-Comportamental , Transtorno Obsessivo-Compulsivo , Adulto , Canadá , Transtorno da Personalidade Compulsiva , Humanos , Conhecimento , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Inibidores Seletivos de Recaptação de Serotonina
10.
JAMA Psychiatry ; 78(1): 47-63, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32857118

RESUMO

IMPORTANCE: Large-scale neuroimaging studies have revealed group differences in cortical thickness across many psychiatric disorders. The underlying neurobiology behind these differences is not well understood. OBJECTIVE: To determine neurobiologic correlates of group differences in cortical thickness between cases and controls in 6 disorders: attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and schizophrenia. DESIGN, SETTING, AND PARTICIPANTS: Profiles of group differences in cortical thickness between cases and controls were generated using T1-weighted magnetic resonance images. Similarity between interregional profiles of cell-specific gene expression and those in the group differences in cortical thickness were investigated in each disorder. Next, principal component analysis was used to reveal a shared profile of group difference in thickness across the disorders. Analysis for gene coexpression, clustering, and enrichment for genes associated with these disorders were conducted. Data analysis was conducted between June and December 2019. The analysis included 145 cohorts across 6 psychiatric disorders drawn from the ENIGMA consortium. The numbers of cases and controls in each of the 6 disorders were as follows: ADHD: 1814 and 1602; ASD: 1748 and 1770; BD: 1547 and 3405; MDD: 2658 and 3572; OCD: 2266 and 2007; and schizophrenia: 2688 and 3244. MAIN OUTCOMES AND MEASURES: Interregional profiles of group difference in cortical thickness between cases and controls. RESULTS: A total of 12 721 cases and 15 600 controls, ranging from ages 2 to 89 years, were included in this study. Interregional profiles of group differences in cortical thickness for each of the 6 psychiatric disorders were associated with profiles of gene expression specific to pyramidal (CA1) cells, astrocytes (except for BD), and microglia (except for OCD); collectively, gene-expression profiles of the 3 cell types explain between 25% and 54% of variance in interregional profiles of group differences in cortical thickness. Principal component analysis revealed a shared profile of difference in cortical thickness across the 6 disorders (48% variance explained); interregional profile of this principal component 1 was associated with that of the pyramidal-cell gene expression (explaining 56% of interregional variation). Coexpression analyses of these genes revealed 2 clusters: (1) a prenatal cluster enriched with genes involved in neurodevelopmental (axon guidance) processes and (2) a postnatal cluster enriched with genes involved in synaptic activity and plasticity-related processes. These clusters were enriched with genes associated with all 6 psychiatric disorders. CONCLUSIONS AND RELEVANCE: In this study, shared neurobiologic processes were associated with differences in cortical thickness across multiple psychiatric disorders. These processes implicate a common role of prenatal development and postnatal functioning of the cerebral cortex in these disorders.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/patologia , Transtorno do Espectro Autista/patologia , Transtorno Bipolar/patologia , Córtex Cerebral/patologia , Transtorno Depressivo Maior/patologia , Desenvolvimento Fetal/fisiologia , Expressão Gênica/fisiologia , Desenvolvimento Humano/fisiologia , Transtorno Obsessivo-Compulsivo/patologia , Esquizofrenia/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico por imagem , Transtorno do Espectro Autista/diagnóstico por imagem , Transtorno Bipolar/diagnóstico por imagem , Estudos de Casos e Controles , Córtex Cerebral/citologia , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/crescimento & desenvolvimento , Criança , Pré-Escolar , Estudos de Coortes , Biologia Computacional , Transtorno Depressivo Maior/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Transtorno Obsessivo-Compulsivo/diagnóstico por imagem , Análise de Componente Principal , Esquizofrenia/diagnóstico por imagem , Adulto Jovem
11.
Transl Psychiatry ; 10(1): 342, 2020 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-33033241

RESUMO

No diagnostic biomarkers are available for obsessive-compulsive disorder (OCD). Here, we aimed to identify magnetic resonance imaging (MRI) biomarkers for OCD, using 46 data sets with 2304 OCD patients and 2068 healthy controls from the ENIGMA consortium. We performed machine learning analysis of regional measures of cortical thickness, surface area and subcortical volume and tested classification performance using cross-validation. Classification performance for OCD vs. controls using the complete sample with different classifiers and cross-validation strategies was poor. When models were validated on data from other sites, model performance did not exceed chance-level. In contrast, fair classification performance was achieved when patients were grouped according to their medication status. These results indicate that medication use is associated with substantial differences in brain anatomy that are widely distributed, and indicate that clinical heterogeneity contributes to the poor performance of structural MRI as a disease marker.


Assuntos
Transtorno Obsessivo-Compulsivo , Biomarcadores , Encéfalo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Neuroimagem , Transtorno Obsessivo-Compulsivo/diagnóstico por imagem , Transtorno Obsessivo-Compulsivo/tratamento farmacológico
12.
Am J Psychiatry ; 177(9): 834-843, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32539527

RESUMO

OBJECTIVE: Attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) are common neurodevelopmental disorders that frequently co-occur. The authors sought to directly compare these disorders using structural brain imaging data from ENIGMA consortium data. METHODS: Structural T1-weighted whole-brain MRI data from healthy control subjects (N=5,827) and from patients with ADHD (N=2,271), ASD (N=1,777), and OCD (N=2,323) from 151 cohorts worldwide were analyzed using standardized processing protocols. The authors examined subcortical volume, cortical thickness, and cortical surface area differences within a mega-analytical framework, pooling measures extracted from each cohort. Analyses were performed separately for children, adolescents, and adults, using linear mixed-effects models adjusting for age, sex, and site (and intracranial volume for subcortical and surface area measures). RESULTS: No shared differences were found among all three disorders, and shared differences between any two disorders did not survive correction for multiple comparisons. Children with ADHD compared with those with OCD had smaller hippocampal volumes, possibly influenced by IQ. Children and adolescents with ADHD also had smaller intracranial volume than control subjects and those with OCD or ASD. Adults with ASD showed thicker frontal cortices compared with adult control subjects and other clinical groups. No OCD-specific differences were observed across different age groups and surface area differences among all disorders in childhood and adulthood. CONCLUSIONS: The study findings suggest robust but subtle differences across different age groups among ADHD, ASD, and OCD. ADHD-specific intracranial volume and hippocampal differences in children and adolescents, and ASD-specific cortical thickness differences in the frontal cortex in adults, support previous work emphasizing structural brain differences in these disorders.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Transtorno do Espectro Autista , Cérebro , Neuroimagem/métodos , Transtorno Obsessivo-Compulsivo , Adolescente , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/fisiopatologia , Transtorno do Espectro Autista/psicologia , Cérebro/diagnóstico por imagem , Cérebro/patologia , Cérebro/fisiopatologia , Criança , Feminino , Desenvolvimento Humano/fisiologia , Humanos , Masculino , Transtorno Obsessivo-Compulsivo/diagnóstico , Transtorno Obsessivo-Compulsivo/fisiopatologia , Transtorno Obsessivo-Compulsivo/psicologia , Tamanho do Órgão , Psicopatologia , Relatório de Pesquisa , Análise de Sistemas
13.
Biol Psychiatry ; 87(12): 1022-1034, 2020 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-31178097

RESUMO

BACKGROUND: Lateralized dysfunction has been suggested in obsessive-compulsive disorder (OCD). However, it is currently unclear whether OCD is characterized by abnormal patterns of brain structural asymmetry. Here we carried out what is by far the largest study of brain structural asymmetry in OCD. METHODS: We studied a collection of 16 pediatric datasets (501 patients with OCD and 439 healthy control subjects), as well as 30 adult datasets (1777 patients and 1654 control subjects) from the OCD Working Group within the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Consortium. Asymmetries of the volumes of subcortical structures, and of measures of regional cortical thickness and surface areas, were assessed based on T1-weighted magnetic resonance imaging scans, using harmonized image analysis and quality control protocols. We investigated possible alterations of brain asymmetry in patients with OCD. We also explored potential associations of asymmetry with specific aspects of the disorder and medication status. RESULTS: In the pediatric datasets, the largest case-control differences were observed for volume asymmetry of the thalamus (more leftward; Cohen's d = 0.19) and the pallidum (less leftward; d = -0.21). Additional analyses suggested putative links between these asymmetry patterns and medication status, OCD severity, or anxiety and depression comorbidities. No significant case-control differences were found in the adult datasets. CONCLUSIONS: The results suggest subtle changes of the average asymmetry of subcortical structures in pediatric OCD, which are not detectable in adults with the disorder. These findings may reflect altered neurodevelopmental processes in OCD.


Assuntos
Transtorno Obsessivo-Compulsivo , Adulto , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Criança , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Transtorno Obsessivo-Compulsivo/diagnóstico por imagem , Tálamo/diagnóstico por imagem
14.
PLoS Biol ; 17(3): e2007032, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30908490

RESUMO

Functional MRI (fMRI) studies have traditionally relied on intersubject normalization based on global brain morphology, which cannot establish proper functional correspondence between subjects due to substantial intersubject variability in functional organization. Here, we reliably identified a set of discrete, homologous functional regions in individuals to improve intersubject alignment of fMRI data. These functional regions demonstrated marked intersubject variability in size, position, and connectivity. We found that previously reported intersubject variability in functional connectivity maps could be partially explained by variability in size and position of the functional regions. Importantly, individual differences in network topography are associated with individual differences in task-evoked activations, suggesting that these individually specified regions may serve as the "localizer" to improve the alignment of task-fMRI data. We demonstrated that aligning task-fMRI data using the regions derived from resting state fMRI may lead to increased statistical power of task-fMRI analyses. In addition, resting state functional connectivity among these homologous regions is able to capture the idiosyncrasies of subjects and better predict fluid intelligence (gF) than connectivity measures derived from group-level brain atlases. Critically, we showed that not only the connectivity but also the size and position of functional regions are related to human behavior. Collectively, these findings suggest that identifying homologous functional regions across individuals can benefit a wide range of studies in the investigation of connectivity, task activation, and brain-behavior associations.


Assuntos
Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Adulto , Algoritmos , Encéfalo/metabolismo , Encéfalo/fisiologia , Feminino , Humanos , Masculino , Vias Neurais/fisiologia , Adulto Jovem
15.
J Affect Disord ; 245: 827-833, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30699866

RESUMO

BACKGROUND: This study investigated distinct trajectories of treatment response in a naturalistic intensive/residential treatment (IRT) program for adults with severe obsessive-compulsive disorder (OCD). We hypothesized that: (1) distinct trajectories would emerge and (2) demographic variables, psychiatric comorbidity, OCD symptom subtype, level of insight, previous exposure and response prevention (ERP) treatment, and quality of life, would differentially predict assignment to these trajectories. METHODS: Participants included 305 individuals with primary OCD admitted for IRT. RESULTS: Two trajectories emerged over the course of the first eight weeks of treatment, with the vast majority of participants demonstrating treatment response. The first trajectory (96%, n = 292) showed a negative, linear treatment response (a.k.a. "linear responders") and more severe OCD symptoms at admission. The second trajectory (4%, n = 13) had less severe OCD symptoms at admission and did not exhibit a significant overall change in symptoms over the course of treatment. More specifically, this second trajectory or "u-shaped responders" show a non-significant linear response through week four of treatment, followed by slightly increased symptoms in week five. Assignment to these classes was not differentially predicted by hypothesized predictor variables. LIMITATIONS: Our final model had inconsistent fit indices and small class prevalance of the u-shaped responder group; therefore, model selection was based on both fit indices and substantive meaning. CONCLUSIONS: This study emprically derived two distinct trajectories of OCD symptom severity over the course of IRT. These findings have the potential to refine IRT for patients with severe OCD, and to potentially guide future investigation into the optimal delivery of ERP treatment for OCD generally.


Assuntos
Transtornos Mentais/epidemiologia , Transtorno Obsessivo-Compulsivo/terapia , Tratamento Domiciliar/métodos , Adulto , Comorbidade , Feminino , Humanos , Masculino , Massachusetts/epidemiologia , Modelos Psicológicos , Transtorno Obsessivo-Compulsivo/epidemiologia , Qualidade de Vida , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
16.
Artigo em Inglês | MEDLINE | ID: mdl-30262337

RESUMO

BACKGROUND: Existing functional connectivity studies of obsessive-compulsive disorder (OCD) support a model of circuit dysfunction. However, these group-level observations have failed to yield neuroimaging biomarkers sufficient to serve as a test for the OCD diagnosis, predict current or future symptoms, or predict treatment response, perhaps because these studies failed to account for the substantial intersubject variability in structural and functional brain organization. METHODS: We used functional regions, localized in each of 41 individual OCD patients, to identify cortical connectivity biomarkers of both global and dimension-specific symptom severity and to detect functional connections that track changes in symptom severity following intensive residential treatment. RESULTS: Global OCD symptom severity was directly linked to dysconnectivity between large-scale intrinsic brain networks-particularly among the dorsal attention, default, and frontoparietal networks. Changes within a subset of connections among these networks were associated with symptom resolution. Additionally, distinct and nonoverlapping cortical connectivity biomarkers were identified that were significantly associated with the severity of contamination/washing and responsibility for harm/checking symptoms, highlighting the contribution of dissociable neural networks to specific OCD symptom dimensions. By contrast, when we defined functional regions conventionally, using a population-level brain atlas, we could no longer identify connectivity biomarkers of severity or improvement for any of the symptom dimensions. CONCLUSIONS: Our findings would seem to encourage the use of individual-level approaches to connectivity analyses to better delineate the cortical and subcortical networks underlying symptom severity and improvement at the dimensional level in OCD patients.


Assuntos
Córtex Cerebral/fisiopatologia , Transtorno Obsessivo-Compulsivo/diagnóstico , Transtorno Obsessivo-Compulsivo/fisiopatologia , Adolescente , Adulto , Biomarcadores , Mapeamento Encefálico , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Vias Neurais/fisiopatologia , Índice de Gravidade de Doença , Adulto Jovem
18.
JAMA Psychiatry ; 75(10): 1081-1087, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30140845

RESUMO

Importance: Obsessive-compulsive disorder (OCD) is a common and often debilitating psychiatric illness. Recent advances in the understanding of the neuroscience of OCD have provided valuable insights that have begun to transform the way we think about the management of this disorder. This educational review provides an integrated neuroscience perspective on formulation and treatment planning for patients with OCD. The article is organized around key neuroscience themes most relevant for OCD. Observations: An integrated neuroscience formulation of OCD is predicated on a fundamental understanding of phenomenology and symptom dimensions, fear conditioning and extinction, neurochemistry, genetics and animal models, as well as neurocircuitry and neurotherapeutics. Symptom dimensions provide a means to better understand the phenotypic heterogeneity within OCD with an eye toward more personalized treatments. The concept of abnormal fear extinction is central to OCD and to the underlying therapeutic mechanism of exposure and response prevention. A framework for understanding the neurochemistry of OCD focuses on both traditional monoaminergic systems and more recent evidence of glutamatergic and γ-aminobutyric acid-ergic dysfunction. Obsessive-compulsive disorder is highly heritable, and future work is needed to understand the contribution of genes to underlying pathophysiology. A circuit dysregulation framework focuses on cortico-striato-thalamo-cortical circuit dysfunction and the development of neurotherapeutic approaches targeting this circuit. The impact of these concepts on how we think about OCD diagnosis and treatment is discussed. Suggestions for future investigations that have the potential to further enhance the clinical management of OCD are presented. Conclusions and Relevance: These key neuroscience themes collectively inform formulation and treatment planning for patients with OCD. The ultimate goal is to increase crosstalk between clinicians and researchers in an effort to facilitate translation of advances in neuroscience research to improved care for patients with OCD.


Assuntos
Encéfalo , Estimulação Encefálica Profunda/métodos , Extinção Psicológica/fisiologia , Medo/fisiologia , Neurociências/métodos , Transtorno Obsessivo-Compulsivo , Estimulação Magnética Transcraniana/métodos , Animais , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Humanos , Transtorno Obsessivo-Compulsivo/genética , Transtorno Obsessivo-Compulsivo/metabolismo , Transtorno Obsessivo-Compulsivo/fisiopatologia , Transtorno Obsessivo-Compulsivo/terapia
19.
J Clin Psychol ; 74(10): 1791-1807, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29696644

RESUMO

OBJECTIVES: A shorter version of the Obsessive Beliefs Questionnaire (OBQ-44) is needed to promote the use of this measure in research and increase our understanding of cognitive phenomena maintaining obsessive-compulsive disorder (OCD). Additionally, an abbreviated version of the OBQ-44 would encourage frequent monitoring of dysfunctional beliefs in intensive care settings. This study aimed to validate a nine-item version of the questionnaire (OBQ-9). METHOD: Participants seeking intensive/residential treatment for OCD (N = 311) completed relevant measures on a weekly basis and at admission and discharge. RESULTS: A confirmatory factor analysis revealed that the OBQ-9's factor structure replicated the three-factor solution of the OBQ-44. The OBQ-9 demonstrated good psychometric properties and convergent validity and was sensitive to treatment effects. Finally, the OBQ-9 subscales predicted specific OCD dimensions over and above depressive symptoms. CONCLUSION: The OBQ-9 appears to be a psychometrically sound tool for routine outcome monitoring of dysfunctional beliefs in hospital-based settings.


Assuntos
Transtorno Obsessivo-Compulsivo/diagnóstico , Escalas de Graduação Psiquiátrica/normas , Psicometria/normas , Pensamento/fisiologia , Adolescente , Adulto , Análise Fatorial , Feminino , Humanos , Masculino , Transtorno Obsessivo-Compulsivo/fisiopatologia , Reprodutibilidade dos Testes , Tratamento Domiciliar , Adulto Jovem
20.
J Clin Psychol ; 74(6): 916-925, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29139125

RESUMO

OBJECTIVE: This study aimed to develop and validate the Distress Tolerance Scale-Short Form (DTS-SF), a modification of the original Distress Tolerance Scale, in a severe/complex sample of individuals with obsessive compulsive disorder (OCD). Currently, there are multiple self-report measurements of distress tolerance (DT), highlighting the need for a more refined measure. METHOD: Participants included 222 individuals with a primary diagnosis of OCD (57% male, average age = 31) seeking intensive/residential treatment. Participants completed surveys at admission, discharge, and each week. RESULTS: An exploratory factor analysis revealed a one-factor solution representing overall DT ability. The DTS-SF was found to be sensitive to treatment effects. Appropriate associations between the DTS-SF and other measures were also found, with lower DT associated with greater OCD and depression severity and lower reported quality of life. CONCLUSION: The DTS-SF was found to be a valid and reliable measure with high clinical utility for quickly and accurately measuring DT.


Assuntos
Transtorno Obsessivo-Compulsivo/diagnóstico , Escalas de Graduação Psiquiátrica/normas , Resiliência Psicológica , Estresse Psicológico/diagnóstico , Adulto , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes
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