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1.
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
2.
Hum Brain Mapp ; 43(1): 167-181, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-32420672

RESUMO

Left-right asymmetry of the human brain is one of its cardinal features, and also a complex, multivariate trait. Decades of research have suggested that brain asymmetry may be altered in psychiatric disorders. However, findings have been inconsistent and often based on small sample sizes. There are also open questions surrounding which structures are asymmetrical on average in the healthy population, and how variability in brain asymmetry relates to basic biological variables such as age and sex. Over the last 4 years, the ENIGMA-Laterality Working Group has published six studies of gray matter morphological asymmetry based on total sample sizes from roughly 3,500 to 17,000 individuals, which were between one and two orders of magnitude larger than those published in previous decades. A population-level mapping of average asymmetry was achieved, including an intriguing fronto-occipital gradient of cortical thickness asymmetry in healthy brains. ENIGMA's multi-dataset approach also supported an empirical illustration of reproducibility of hemispheric differences across datasets. Effect sizes were estimated for gray matter asymmetry based on large, international, samples in relation to age, sex, handedness, and brain volume, as well as for three psychiatric disorders: autism spectrum disorder was associated with subtly reduced asymmetry of cortical thickness at regions spread widely over the cortex; pediatric obsessive-compulsive disorder was associated with altered subcortical asymmetry; major depressive disorder was not significantly associated with changes of asymmetry. Ongoing studies are examining brain asymmetry in other disorders. Moreover, a groundwork has been laid for possibly identifying shared genetic contributions to brain asymmetry and disorders.


Assuntos
Transtorno do Espectro Autista/patologia , Córtex Cerebral/anatomia & histologia , Transtorno Depressivo Maior/patologia , Substância Cinzenta/anatomia & histologia , Imageamento por Ressonância Magnética , Neuroimagem , Transtorno Obsessivo-Compulsivo/patologia , Transtorno do Espectro Autista/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Transtorno Depressivo Maior/diagnóstico por imagem , Substância Cinzenta/diagnóstico por imagem , Humanos , Estudos Multicêntricos como Assunto , Transtorno Obsessivo-Compulsivo/diagnóstico por imagem
3.
J Am Acad Child Adolesc Psychiatry ; 61(2): 321-330, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34217835

RESUMO

OBJECTIVE: Pediatric obsessive-compulsive disorder (OCD) and clinically relevant obsessive-compulsive symptoms in the general population are associated with increased thalamic volume. It is unknown whether this enlargement is explained by specific thalamic subregions. The relation between obsessive-compulsive symptoms and volume of thalamic subregions was investigated in a population-based sample of children. METHOD: Obsessive-compulsive symptoms were measured in children (9-12 years of age) from the Generation R Study using the Short Obsessive-Compulsive Disorder Screener (SOCS). Thalamic nuclei volumes were extracted from structural 3T magnetic resonance imaging scans using the ThalamicNuclei pipeline and regrouped into anterior, ventral, intralaminar/medial, lateral, and pulvinar subregions. Volumes were compared between children with symptoms above clinical cutoff (probable OCD cases, SOCS ≥ 6, n = 156) and matched children without symptoms (n = 156). Linear regression models were fitted to investigate the association between continuous SOCS score and subregional volume in the whole sample (N = 2500). RESULTS: Children with probable OCD had larger ventral nuclei compared with children without symptoms (d = 0.25, p = .025, false discovery rate adjusted p = .126). SOCS score showed a negative association with pulvinar volume when accounting for overall thalamic volume (ß = -0.057, p = .009, false discovery rate adjusted p = .09). However, these associations did not survive multiple testing correction. CONCLUSION: The results suggest that individual nuclei groups contribute in varying degrees to overall thalamic volume in children with probable OCD, although this did not survive multiple comparisons correction. Understanding the role of thalamic nuclei and their associated circuits in pediatric OCD could lead toward treatment strategies targeting these circuits.


Assuntos
Transtorno Obsessivo-Compulsivo , Tálamo , Criança , Humanos , Imageamento por Ressonância Magnética , Transtorno Obsessivo-Compulsivo/diagnóstico por imagem , Transtorno Obsessivo-Compulsivo/patologia , Tálamo/diagnóstico por imagem , Tálamo/patologia
4.
Ocul Immunol Inflamm ; 30(2): 428-432, 2022 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32946294

RESUMO

BACKGROUND: To evaluate choroidal vascularity index (CVI) and to investigate the association of CVI with neutrophil-to-lymphocyte ratio (NLR) as an indicator of inflammation in obsessive-compulsive disorder (OCD). MATERIAL AND METHODS: This prospective study included newly diagnosed OCD patients and healthy controls. All patients underwent EDI-OCT imaging to assess the subfoveal choroidal thickness (sCT) and peripapillary CT (pCT). CVI was defined as the ratio of luminal area to stromal area after binarization on EDI-OCT images. RESULTS: A total of 39 patients with OCD and 25 controls were included. The sCT, pCT, and CVI values were significantly higher in the OCD vs. control group (p˂0.05 for all). The NLR values were significantly higher in the OCD vs. control group (p = .007). A significant positive correlation was noted between CVI and NLR (p = .039). CONCLUSION: Our findings suggest that systemic inflammation may play a role in the pathogenesis of OCD.


Assuntos
Transtorno Obsessivo-Compulsivo , Tomografia de Coerência Óptica , Biomarcadores , Corioide/patologia , Humanos , Inflamação/diagnóstico , Inflamação/patologia , Transtorno Obsessivo-Compulsivo/diagnóstico , Transtorno Obsessivo-Compulsivo/patologia , Estudos Prospectivos , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos
5.
Hum Brain Mapp ; 42(12): 3871-3886, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34105832

RESUMO

The objective of the current study is to determine robust transdiagnostic brain structural markers for compulsivity by capitalizing on the increasing number of case-control studies examining gray matter volume (GMV) alterations in substance use disorders (SUD) and obsessive-compulsive disorder (OCD). Voxel-based meta-analysis within the individual disorders and conjunction analysis were employed to reveal common GMV alterations between SUDs and OCD. Meta-analytic coordinates and signed brain volumetric maps determining directed (reduced/increased) GMV alterations between the disorder groups and controls served as the primary outcome. The separate meta-analysis demonstrated that SUD and OCD patients exhibited widespread GMV reductions in frontocortical regions including prefrontal, cingulate, and insular. Conjunction analysis revealed that the left inferior frontal gyrus (IFG) consistently exhibited decreased GMV across all disorders. Functional characterization suggests that the IFG represents a core hub in the cognitive control network and exhibits bidirectional (Granger) causal interactions with the striatum. Only OCD showed increased GMV in the dorsal striatum with higher changes being associated with more severe OCD symptomatology. Together the findings demonstrate robustly decreased GMV across the disorders in the left IFG, suggesting a transdiagnostic brain structural marker. The functional characterization as a key hub in the cognitive control network and casual interactions with the striatum suggest that deficits in inhibitory control mechanisms may promote compulsivity and loss of control that characterize both disorders.


Assuntos
Córtex Cerebral , Corpo Estriado , Função Executiva , Substância Cinzenta , Rede Nervosa , Transtorno Obsessivo-Compulsivo , Transtornos Relacionados ao Uso de Substâncias , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/patologia , Córtex Cerebral/fisiopatologia , Corpo Estriado/diagnóstico por imagem , Corpo Estriado/patologia , Corpo Estriado/fisiopatologia , Função Executiva/fisiologia , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Substância Cinzenta/fisiopatologia , Humanos , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/patologia , Rede Nervosa/fisiopatologia , Transtorno Obsessivo-Compulsivo/diagnóstico por imagem , Transtorno Obsessivo-Compulsivo/patologia , Transtorno Obsessivo-Compulsivo/fisiopatologia , Transtornos Relacionados ao Uso de Substâncias/diagnóstico por imagem , Transtornos Relacionados ao Uso de Substâncias/patologia , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia
6.
Genes Genomics ; 43(9): 1049-1057, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34146253

RESUMO

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is one of the most common primary forms of glomerulonephritis, while IgA vasculitis (IgAV) is the most common systemic vasculitis in children. OBJECTIVE: Herein we aimed to uncover single nucleotide polymorphism (SNP) markers associated with these two related diseases by applying association tests and Sanger sequencing. METHODS: Within the discovery stage, genomic DNA in blood samples from 101 enrolled patients were genotyped by the Korean Biobank Array. Association tests were performed with 397 Korean reference genomes. In the validation stage, 26 independent samples were genotyped by Sanger sequencing. RESULTS: Four SNPs were identified (P < 5 × 10-8) in the discovery stage. To determine whether the genotypes determined by SNP array were accurate, additional genotyping via Sanger sequencing was performed. As a result, only one SNP, rs9428555, was properly genotyped. In the validation stage, the minor allele (A > G) was found in as many as 15 out of 26 samples (minor allele frequency = 0.288), even though this minor allele is rare in East Asians (< 3%). CONCLUSIONS: We found rs9428555 as a novel susceptible locus associated with the development of both IgAN and IgAV in Koreans. Though we cannot conclude rs9428555 is the unique susceptible locus of IgAN and IgAV, it is likely a good marker as the minor allele of this SNP occurred much more often in the patient group here versus within East Asians as a whole.


Assuntos
Doenças Autoimunes/genética , Predisposição Genética para Doença , Glomerulonefrite por IGA/genética , Imunoglobulina A/genética , Transtorno Obsessivo-Compulsivo/genética , Adolescente , Alelos , Doenças Autoimunes/patologia , Criança , Feminino , Frequência do Gene , Estudo de Associação Genômica Ampla , Glomerulonefrite por IGA/epidemiologia , Humanos , Masculino , Transtorno Obsessivo-Compulsivo/patologia , Polimorfismo de Nucleotídeo Único/genética , República da Coreia/epidemiologia
7.
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
8.
Neuroimage ; 223: 117318, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32882386

RESUMO

Diffusion functional magnetic resonance imaging (DfMRI) has been proposed as an alternative functional imaging method to detect brain activity without confounding hemodynamic effects. Here, taking advantage of this DfMRI feature, we investigated abnormalities of dynamic brain function in a neuropsychiatric disease mouse model (glial glutamate transporter-knockdown mice with obsessive-compulsive disorder [OCD]-related behavior). Our DfMRI approaches consisted of three analyses: resting state brain activity, functional connectivity, and propagation of neural information. We detected hyperactivation and biased connectivity across the cortico-striatal-thalamic circuitry, which is consistent with known blood oxygen-level dependent (BOLD)-fMRI patterns in OCD patients. In addition, we performed ignition-driven mean integration (IDMI) analysis, which combined activity and connectivity analyses, to evaluate neural propagation initiated from brain activation. This analysis revealed an unbalanced distribution of neural propagation initiated from intrinsic local activation to the global network, while these were not detected by the conventional method with BOLD-fMRI. This abnormal function detected by DfMRI was associated with OCD-related behavior. Together, our comprehensive DfMRI approaches can successfully provide information on dynamic brain function in normal and diseased brains.


Assuntos
Encéfalo/patologia , Encéfalo/fisiopatologia , Imagem de Difusão por Ressonância Magnética , Transtorno Obsessivo-Compulsivo/patologia , Transtorno Obsessivo-Compulsivo/fisiopatologia , Animais , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico/métodos , Modelos Animais de Doenças , Transportador 2 de Aminoácido Excitatório/genética , Técnicas de Silenciamento de Genes , Camundongos , Vias Neurais/diagnóstico por imagem , Vias Neurais/patologia , Vias Neurais/fisiopatologia , Transtorno Obsessivo-Compulsivo/diagnóstico por imagem
9.
J Psychiatry Neurosci ; 45(5): 334-343, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32293840

RESUMO

Background: The amygdala has been implicated in obsessive-compulsive disorder (OCD), a common, disabling illness. However, the regional distribution of anatomic alterations in this structure and their association with the symptoms of OCD remains to be established. Methods: We collected high-resolution 3D T1-weighted images from 81 untreated patients with OCD and no lifetime history of comorbid psychotic, affective or anxiety disorders, and from 95 age- and sex-matched healthy controls. We extracted the volume of the central nucleus of the amygdala (CeA) and the basolateral complex of the amygdala (BLA) and compared them across groups using FreeSurfer 6.0. In exploratory analyses, we evaluated other subnuclei, including the cortical medial nuclei, the anterior amygdaloid area, and the corticoamygdaloid transition area. Results: Patients with OCD had reduced amygdala volume bilaterally compared with healthy controls (left, p = 0.034; right, p = 0.002). Volume reductions were greater in the CeA (left: -11.9%, p = 0.002; right: -13.3%, p < 0.001) than in the BLA (left lateral nucleus: -3.3%, p = 0.029; right lateral nucleus: -3.9%, p = 0.018; right basal nucleus: -4.1%, p = 0.017; left accessory basal nucleus: -6.5%, p = 0.001; right accessory basal nucleus: -9.3%, p < 0.001). Volume reductions in the CeA were associated with illness duration. Exploratory analysis revealed smaller medial (left: -15.4%, p < 0.001, η2 = 0.101) and cortical (left: -9.1%, p = 0.001, η2 = 0.058; right: -15.4%, p < 0.001, η2 = 0.175) nuclei in patients with OCD compared with healthy controls. Limitations: Although the strict exclusion criteria used in the study helped us to identify OCD-specific alterations, they may have limited generalizability to the broader OCD population. Conclusion: Our results provide a comprehensive anatomic profile of alterations in the amygdala subnuclei in untreated patients with OCD and highlight a distinctive pattern of volume reductions across subnuclei in OCD. Based on the functional properties of the amygdala subnuclei established from preclinical research, CeA impairment may contribute to behavioural inflexibility, and BLA disruption may be responsible for altered fear conditioning and the affective components of OCD.


Assuntos
Complexo Nuclear Basolateral da Amígdala/patologia , Núcleo Central da Amígdala/patologia , Transtorno Obsessivo-Compulsivo/patologia , Adulto , Complexo Nuclear Basolateral da Amígdala/diagnóstico por imagem , Núcleo Central da Amígdala/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Transtorno Obsessivo-Compulsivo/diagnóstico por imagem , Adulto Jovem
10.
PLoS One ; 15(4): e0231390, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32294104

RESUMO

OBJECTIVE: Analyze a large sample with detailed clinical data of misophonia subjects in order to determine the psychiatric, somatic and psychological nature of the condition. METHODS: This observational study of 779 subjects with suspected misophonia was conducted from January 2013 to May 2017 at the outpatient-clinic of the Amsterdam University Medical Centers, location AMC, the Netherlands. We examined DSM-IV diagnoses, results of somatic examination (general screening and hearing tests), and 17 psychological questionnaires (e.g., SCL-90-R, WHOQoL). RESULTS: The diagnosis of misophonia was confirmed in 575 of 779 referred subjects (74%). In the sample of misophonia subjects (mean age, 34.17 [SD = 12.22] years; 399 women [69%]), 148 (26%) subjects had comorbid traits of obsessive-compulsive personality disorder, 58 (10%) mood disorders, 31 (5%) attention-deficit (hyperactivity) disorder, and 14 (3%) autism spectrum conditions. Two percent reported tinnitus and 1% hyperacusis. In a random subgroup of 109 subjects we performed audiometry, and found unilateral hearing loss in 3 of them (3%). Clinical neurological examination and additional blood test showed no abnormalities. Psychological tests revealed perfectionism (97% CPQ>25) and neuroticism (stanine 7 NEO-PI-R). Quality of life was heavily impaired and associated with misophonia severity (rs (184) = -.34 p = < .001, p = < .001). LIMITATIONS: This was a single site study, leading to possible selection-and confirmation bias, since AMC-criteria were used. CONCLUSIONS: This study with 575 subjects is the largest misophonia sample ever described. Based on these results we propose a set of revised criteria useful to diagnose misophonia as a psychiatric disorder.


Assuntos
Comportamento Impulsivo , Transtornos Mentais/diagnóstico , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/complicações , Transtorno do Deficit de Atenção com Hiperatividade/patologia , Transtorno Autístico/complicações , Transtorno Autístico/patologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Masculino , Transtornos Mentais/complicações , Transtornos Mentais/patologia , Pessoa de Meia-Idade , Transtornos do Humor/complicações , Transtornos do Humor/patologia , Países Baixos , Transtorno Obsessivo-Compulsivo/complicações , Transtorno Obsessivo-Compulsivo/patologia , Índice de Gravidade de Doença , Adulto Jovem
11.
Psychiatry Res Neuroimaging ; 298: 111046, 2020 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-32106018

RESUMO

Recent neuroimaging studies in OCD have reported structural alterations in the brain, not limited to frontostriatal regions. While Diffusion Tensor Imaging (DTI) is typically used to interrogate WM microstructure in OCD, additional imaging metric, such as Magnetization Transfer Imaging (MTI), allows for further identification of subtle but important structural changes across both GM and WM. In this study, both MTI and DTI were utilised to investigate the structural integrity of the brain, in OCD in relation to healthy controls. 38 adult OCD patients were recruited, along with 41 age- and gender-matched controls. Structural T1, MTI and DTI data were collected. Case-control differences in Magnetization Transfer Ratio (MTR) and DTI metrics (FA, MD) were examined, along with MTR/DTI-related associations with symptom severity in patients. No significant group differences were found across MTR, FA, and MD. However, OCD symptom severity was positively correlated with MTR in a distributed network of brain regions, including the striatum, cingulate, orbitofrontal area and insula. Within the same regions, OCD symptoms were also positively correlated with FA in WM, and negatively correlated with MD in GM. These results indicate a greater degree of myelination in certain cortical and subcortical regions in the more severe cases of OCD.


Assuntos
Córtex Cerebral , Corpo Estriado , Imageamento por Ressonância Magnética , Neuroimagem , Transtorno Obsessivo-Compulsivo , Índice de Gravidade de Doença , Adolescente , Adulto , Estudos de Casos e Controles , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/patologia , Córtex Cerebral/fisiopatologia , Corpo Estriado/diagnóstico por imagem , Corpo Estriado/patologia , Corpo Estriado/fisiopatologia , Imagem de Tensor de Difusão/métodos , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Transtorno Obsessivo-Compulsivo/diagnóstico por imagem , Transtorno Obsessivo-Compulsivo/patologia , Transtorno Obsessivo-Compulsivo/fisiopatologia , Adulto Jovem
12.
BMC Psychiatry ; 20(1): 68, 2020 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-32059696

RESUMO

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.


Assuntos
Mapeamento Encefálico , Encéfalo/diagnóstico por imagem , Imagem de Tensor de Difusão , Internacionalidade , Imageamento por Ressonância Magnética , Estudos Multicêntricos como Assunto/métodos , Transtorno Obsessivo-Compulsivo/diagnóstico por imagem , Adolescente , Adulto , Encéfalo/patologia , Encéfalo/fisiopatologia , Brasil , Estudos de Casos e Controles , Feminino , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Países Baixos , Transtorno Obsessivo-Compulsivo/patologia , Transtorno Obsessivo-Compulsivo/fisiopatologia , Projetos de Pesquisa , Irmãos/psicologia , África do Sul , Estados Unidos , Adulto Jovem
13.
Neurosci Biobehav Rev ; 112: 83-94, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32006553

RESUMO

Neuroimaging research has shown that patients with obsessive-compulsive disorder (OCD) may present brain structural and functional alterations, but the results across imaging modalities and task paradigms are difficult to reconcile. Are the same brain systems that are structurally different in OCD patients also involved in executive function and emotional processing? To answer this, we conducted separate meta-analyses of voxel-based morphometry studies, executive function functional magnetic resonance imaging (fMRI) studies, and emotional processing fMRI studies. Next, with a multimodal approach (conjunction analysis), we identified the common alterations across meta-analyses. Patients presented increased gray matter volume and hyperactivation in the putamen, but the putamen subregions affected differed depending on the psychological process. Left posterior/dorsal putamen showed hyperactivation during executive processing tasks, while predominantly right anterior/ventral putamen showed hyperactivation during emotional processing tasks. Interestingly, age was significantly associated with increased right putamen volume. Finally, the left dorsolateral prefrontal cortex was hyperactive in both functional domains. Our findings highlight task-specific correlates of brain structure and function in OCD and help integrate a growing literature.


Assuntos
Emoções , Função Executiva , Transtorno Obsessivo-Compulsivo , Córtex Pré-Frontal , Putamen , Estudos de Casos e Controles , Emoções/fisiologia , Função Executiva/fisiologia , Humanos , Imageamento por Ressonância Magnética , Transtorno Obsessivo-Compulsivo/diagnóstico por imagem , Transtorno Obsessivo-Compulsivo/patologia , Transtorno Obsessivo-Compulsivo/fisiopatologia , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/patologia , Córtex Pré-Frontal/fisiopatologia , Putamen/diagnóstico por imagem , Putamen/patologia , Putamen/fisiopatologia
14.
Brain ; 143(2): 684-700, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-32040561

RESUMO

Brain structural covariance networks reflect covariation in morphology of different brain areas and are thought to reflect common trajectories in brain development and maturation. Large-scale investigation of structural covariance networks in obsessive-compulsive disorder (OCD) may provide clues to the pathophysiology of this neurodevelopmental disorder. Using T1-weighted MRI scans acquired from 1616 individuals with OCD and 1463 healthy controls across 37 datasets participating in the ENIGMA-OCD Working Group, we calculated intra-individual brain structural covariance networks (using the bilaterally-averaged values of 33 cortical surface areas, 33 cortical thickness values, and six subcortical volumes), in which edge weights were proportional to the similarity between two brain morphological features in terms of deviation from healthy controls (i.e. z-score transformed). Global networks were characterized using measures of network segregation (clustering and modularity), network integration (global efficiency), and their balance (small-worldness), and their community membership was assessed. Hub profiling of regional networks was undertaken using measures of betweenness, closeness, and eigenvector centrality. Individually calculated network measures were integrated across the 37 datasets using a meta-analytical approach. These network measures were summated across the network density range of K = 0.10-0.25 per participant, and were integrated across the 37 datasets using a meta-analytical approach. Compared with healthy controls, at a global level, the structural covariance networks of OCD showed lower clustering (P < 0.0001), lower modularity (P < 0.0001), and lower small-worldness (P = 0.017). Detection of community membership emphasized lower network segregation in OCD compared to healthy controls. At the regional level, there were lower (rank-transformed) centrality values in OCD for volume of caudate nucleus and thalamus, and surface area of paracentral cortex, indicative of altered distribution of brain hubs. Centrality of cingulate and orbito-frontal as well as other brain areas was associated with OCD illness duration, suggesting greater involvement of these brain areas with illness chronicity. In summary, the findings of this study, the largest brain structural covariance study of OCD to date, point to a less segregated organization of structural covariance networks in OCD, and reorganization of brain hubs. The segregation findings suggest a possible signature of altered brain morphometry in OCD, while the hub findings point to OCD-related alterations in trajectories of brain development and maturation, particularly in cingulate and orbitofrontal regions.


Assuntos
Encéfalo/fisiopatologia , Córtex Cerebral/fisiopatologia , Vias Neurais/fisiopatologia , Transtorno Obsessivo-Compulsivo/fisiopatologia , Adulto , Encéfalo/patologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Masculino , Transtorno Obsessivo-Compulsivo/patologia
15.
Neuroimage Clin ; 25: 102165, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31954987

RESUMO

BACKGROUND: Major depression (MD) and obsessive-compulsive disorder (OCD) are psychiatric diseases with a huge impact on individual well-being. Despite optimal treatment regiments a subgroup of patients remains treatment resistant and stereotactic surgery (stereotactic lesion surgery, SLS or Deep Brain Stimulation, DBS) might be an option. Recent research has described four networks related to MD and OCD (affect, reward, cognitive control, default network) but only on a cortical and the adjacent sub-cortical level. Despite the enormous impact of comparative neuroanatomy, animal science and stereotactic approaches a holistic theory of subcortical and cortical network interactions is elusive. Because of the dominant hierarchical rank of the neocortex, corticofugal approaches have been used to identify connections in subcortical anatomy without anatomical priors and in part confusing results. We here propose a different corticopetal approach by identifying subcortical networks and search for neocortical convergences thereby following the principle of phylogenetic and ontogenetic network development. MATERIAL AND METHODS: This work used a diffusion tensor imaging data from a normative cohort (Human Connectome Project, HCP; n = 200) to describe eight subcortical fiber projection pathways (PPs) from subthalamic nucleus (STN), substantia nigra (SNR), red nucleus (RN), ventral tegmental area (VTA), ventrolateral thalamus (VLT) and mediodorsal thalamus (MDT) in a normative space (MNI). Subcortical and cortical convergences were described including an assignment of the specific pathways to MD/OCD-related networks. Volumes of activated tissue for different stereotactic stimulation sites and procedures were simulated to understand the role of the distinct networks, with respect to symptoms and treatment of OCD and MD. RESULTS: The detailed course of eight subcortical PPs (stnPP, snrPP, rnPP, vlATR, vlATRc, mdATR, mdATRc, vtaPP/slMFB) were described together with their subcortical and cortical convergences. The anterior limb of the internal capsule can be subdivided with respect to network occurrences in ventral-dorsal and medio-lateral gradients. Simulation of stereotactic procedures for OCD and MD showed dominant involvement of mdATR/mdATRc (affect network) and vtaPP/slMFB (reward network). DISCUSSION: Corticofugal search strategies for the evaluation of stereotactic approaches without anatomical priors often lead to confusing results which do not allow for a clear assignment of a procedure to an involved network. According to our simulation of stereotactic procedures in the treatment of OCD and MD, most of the target regions directly involve the reward (and affect) networks, while side-effects can in part be explained with a co-modulation of the control network. CONCLUSION: The here proposed corticopetal approach of a hierarchical description of 8 subcortical PPs with subcortical and cortical convergences represents a new systematics of networks found in all different evolutionary and distinct parts of the human brain.


Assuntos
Transtorno Depressivo Maior/patologia , Imagem de Tensor de Difusão/métodos , Cápsula Interna/patologia , Mesencéfalo/patologia , Neocórtex/patologia , Rede Nervosa/patologia , Transtorno Obsessivo-Compulsivo/patologia , Adulto , Estudos de Coortes , Conectoma , Transtorno Depressivo Maior/diagnóstico por imagem , Humanos , Cápsula Interna/diagnóstico por imagem , Mesencéfalo/diagnóstico por imagem , Neocórtex/diagnóstico por imagem , Rede Nervosa/diagnóstico por imagem , Vias Neurais/diagnóstico por imagem , Vias Neurais/patologia , Transtorno Obsessivo-Compulsivo/diagnóstico por imagem
16.
Schizophr Bull ; 46(2): 442-453, 2020 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-31355879

RESUMO

A phenomenon in schizophrenia patients that deserves attention is the high comorbidity rate with obsessive-compulsive disorder (OCD). Little is known about the neurobiological basis of schizo-obsessive comorbidity (SOC). We aimed to investigate whether specific changes in white matter exist in patients with SOC and the relationship between such abnormalities and clinical parameters. Twenty-eight patients with SOC, 28 schizophrenia patients, 30 OCD patients, and 30 demographically matched healthy controls were recruited. Using Tract-based Spatial Statistics and Probabilistic Tractography, we examined the pattern of white matter abnormalities in these participants. We also used ANOVA and Support Vector Classification of various white matter indices and structural connection probability to further examine white matter changes among the 4 groups. We found that patients with SOC had decreased fractional anisotropy (FA) and increased radial diffusivity in the right sagittal stratum and the left crescent of the fornix/stria terminalis compared with healthy controls. We also found changed connection probability in the Default Mode Network, the Subcortical Network, the Attention Network, the Task Control Network, the Visual Network, the Somatosensory Network, and the cerebellum in the SOC group compared with the other 3 groups. The classification results further revealed that FA features could differentiate the SOC group from the other 3 groups with an accuracy of .78. These findings highlight the specific white matter abnormalities found in patients with SOC.


Assuntos
Imagem de Tensor de Difusão/métodos , Rede Nervosa/patologia , Transtorno Obsessivo-Compulsivo/patologia , Esquizofrenia/patologia , Máquina de Vetores de Suporte , Substância Branca/patologia , Adolescente , Adulto , Comorbidade , Feminino , Humanos , Masculino , Rede Nervosa/diagnóstico por imagem , Transtorno Obsessivo-Compulsivo/diagnóstico por imagem , Transtorno Obsessivo-Compulsivo/epidemiologia , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/epidemiologia , Substância Branca/diagnóstico por imagem , Adulto Jovem
17.
J Nerv Ment Dis ; 208(1): 21-27, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31688495

RESUMO

Tic-related obsessive-compulsive disorder (OCD) may be a unique OCD subtype. This study examined whether neurological soft signs (NSSs) of patients with tic-related and tic-free OCD enable discrimination of these subgroups. We used the Neurological Evaluation Scale to assess 32 patients with tic-related and 94 with tic-free OCD, as well as 84 controls. Most patients with tic-related OCD were male, with earlier illness onset and poorer insight scores than those of patients with tic-free OCD. Patients with tic-related OCD had poorer motor coordination, sensory integration, and motor sequencing than did tic-free patients. Logistic regression using NSS subscale scores predicted tic-related OCD. Patients with tic-related OCD displayed greater neurodevelopmental abnormalities than did tic-free patients. NSSs of the former group suggest the need to separate this subgroup. Our results also support the newly introduced tic-related specifier in the fifth edition of the Diagnostic and statistical manual of mental disorders.


Assuntos
Transtorno Obsessivo-Compulsivo/diagnóstico , Tiques/psicologia , Adulto , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Masculino , Transtorno Obsessivo-Compulsivo/classificação , Transtorno Obsessivo-Compulsivo/patologia , Transtorno Obsessivo-Compulsivo/fisiopatologia , Escalas de Graduação Psiquiátrica , Tiques/diagnóstico , Tiques/patologia , Tiques/fisiopatologia
18.
Biosci Rep ; 39(12)2019 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-31808517

RESUMO

Many common pathological features have been observed for both autism spectrum disorders (ASDs) and obsessive-compulsive disorder (OCD). However, no systematic analysis of the common gene markers associated with both ASD and OCD has been conducted so far. Here, two batches of large-scale literature-based disease-gene relation data (updated in 2017 and 2019, respectively) and gene expression data were integrated to study the possible association between OCD and ASD at the genetic level. Genes linked to OCD and ASD present significant overlap (P-value <2.64e-39). A genetic network of over 20 genes was constructed, through which OCD and ASD may exert influence on each other. The 2017-based analysis suggested six potential common risk genes for OCD and ASD (CDH2, ADCY8, APOE, TSPO, TOR1A, and OLIG2), and the 2019-based study identified two more genes (DISP1 and SETD1A). Notably, the gene APOE identified by the 2017-based analysis has been implicated to have an association with ASD in a recent study (2018) with DNA methylation analysis. Our results support the possible complex genetic associations between OCD and ASD. Genes linked to one disease are worth further investigation as potential risk factors for the other.


Assuntos
Transtorno do Espectro Autista/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Transtorno Obsessivo-Compulsivo/genética , Adenilil Ciclases/genética , Antígenos CD/genética , Apolipoproteínas E/genética , Transtorno do Espectro Autista/patologia , Caderinas/genética , Feminino , Regulação da Expressão Gênica/genética , Redes Reguladoras de Genes/genética , Histona-Lisina N-Metiltransferase/genética , Humanos , Masculino , Chaperonas Moleculares/genética , Transtorno Obsessivo-Compulsivo/patologia , Fator de Transcrição 2 de Oligodendrócitos/genética , Receptores de GABA/genética
19.
J Vis Exp ; (153)2019 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-31840658

RESUMO

Most methods for conducting meta-analysis of voxel-based neuroimaging studies do not assess whether effects are not null, but whether there is a convergence of peaks of statistical significance, and reduce the assessment of the evidence to a binary classification exclusively based on p-values (i.e., voxels can only be "statistically significant" or "non-statistically significant"). Here, we detail how to conduct a meta-analysis using Seed-based d Mapping with Permutation of Subject Images (SDM-PSI), a novel method that uses a standard permutation test to assess whether effects are not null. We also show how to grade the strength of the evidence according to a set of criteria that considers a range of statistical significance levels (from more liberal to more conservative), the amount of data or the detection of potential biases (e.g., small-study effect and excess of significance). To exemplify the procedure, we detail the conduction of a meta-analysis of voxel-based morphometry studies in obsessive-compulsive disorder, and we provide all the data already extracted from the manuscripts to allow the reader to replicate the meta-analysis easily. SDM-PSI can also be used for meta-analyses of functional magnetic resonance imaging, diffusion tensor imaging, position emission tomography and surface-based morphometry studies.


Assuntos
Mapeamento Encefálico/métodos , Encéfalo/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Neuroimagem/métodos , Transtorno Obsessivo-Compulsivo/diagnóstico por imagem , Encéfalo/patologia , Imagem de Tensor de Difusão/métodos , Humanos , Imageamento por Ressonância Magnética/métodos , Transtorno Obsessivo-Compulsivo/patologia
20.
Rev Colomb Psiquiatr (Engl Ed) ; 48(4): 261-265, 2019.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31779877

RESUMO

INTRODUCTION: Excoriation (skin picking) disorder is included in the DSM-5 in the obsessive compulsive and related disorders category. It is defined as the recurrent urge to touch, scratch, scrape, scrub, rub, squeeze, bite or dig in the skin, leading to skin lesions. It is a rare disorder (1.4-5.4% of the population) and occurs mainly in women. CASE REPORT: this article reports the case of a 31-year-old female patient, initially assessed by dermatology and orthopaedics for the presence of infected ulcerated lesions on her lower limbs, with other superficial lesions from scratching on her chest, arms, forearms, back and head. The patient also reported symptoms of anxiety, so was assessed by consultation-liaison psychiatry. DISCUSSION: skin picking, normal behaviour in mammals, becomes pathological from a psychiatric point of view when it is repetitive and persistent, as in the case of excoriation disorder. In view of the reported relationship with the obsessive-compulsive spectrum, use of selective serotonin reuptake inhibitors and cognitive behavioural therapy are recommended.


Assuntos
Transtorno Obsessivo-Compulsivo/diagnóstico , Poliarterite Nodosa/patologia , Comportamento Autodestrutivo/diagnóstico , Dermatopatias/diagnóstico , Adulto , Ansiedade/psicologia , Feminino , Humanos , Transtorno Obsessivo-Compulsivo/patologia , Transtorno Obsessivo-Compulsivo/terapia , Comportamento Autodestrutivo/patologia , Dermatopatias/patologia , Dermatopatias/terapia
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