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1.
Article in English | MEDLINE | ID: mdl-38705507

ABSTRACT

BACKGROUND: Skin-picking disorder (SPD) is conceptualized as an obsessive-compulsive and related disorder (OCRD). Patients with SPD excessively manipulate their skin, which leads to skin lesions, psychological distress, and functional impairment. The neuroanatomical facets of this disorder are still poorly understood. METHODS: A total of 220 participants (123 patients with a primary diagnosis of SPD and 97 healthy controls; mean age = 30 years, 80% female) were recruited for a voxel-based morphometry (VBM) study. VBM data were compared between patients and controls, and between three SPD subgroups, each characterized by a distinct age of symptom onset (before puberty, during puberty, adulthood). RESULTS: Relative to the healthy comparison group, patients with SPD had significantly less grey matter volume (GMV) in regions of interest (ROIs: insula, orbitofrontal cortex, pallidum, cerebellum, supramarginal gyrus) and in the frontal pole and occipital regions (whole-brain findings). Early onset of symptoms (before puberty) was associated with elevated levels of focused skin-picking, in addition to less GMV in specific ROIs (insula, orbitofrontal cortex) as well as in paracingulate/ superior temporal regions (whole-brain findings). CONCLUSIONS: SPD-related reductions in GMV were identified in brain regions involved in interoception, emotion regulation, and motor control. This partially aligns with findings for OCD. The detection of different age-of-onset groups based on clinical as well as morphometric data points to the heterogeneity of the disorder and warrants further investigation.


Subject(s)
Brain , Gray Matter , Magnetic Resonance Imaging , Neuroimaging , Obsessive-Compulsive Disorder , Humans , Female , Male , Adult , Magnetic Resonance Imaging/methods , Obsessive-Compulsive Disorder/diagnostic imaging , Obsessive-Compulsive Disorder/pathology , Neuroimaging/methods , Gray Matter/diagnostic imaging , Gray Matter/pathology , Brain/diagnostic imaging , Brain/pathology , Skin/diagnostic imaging , Skin/pathology , Young Adult
2.
J Affect Disord ; 350: 887-894, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38272366

ABSTRACT

BACKGROUND: Ablative surgery using bilateral anterior capsulotomy (BAC) is an option for treatment resistant depression (TRD) and obsessive-compulsive disorder (TROCD). The location and extent of the lesion within anterior limb of the internal capsule (ALIC) remains uncertain. Accumulating evidence has suggested that the lesion should be located ventrally while limiting the dorsal extent. Our center is now targeting specific fiber tracts within the lower half of the ALIC. METHOD: Presurgical diffusion tensor Magnetic Resonance Imaging (MRI) was used to identify individual fibre tracts within the ventral aspect of the ALIC in the last two patients who underwent BAC at our center. One patient had TRD and the other had both TROCD and TRD. Radiofrequency-induced thermal lesions were created in the identified targets with lesion volumes between 20 and 229 mm3 (average 95 mm3). FINDINGS: Both patients were responders with neither experiencing significant side effects including compromised executive functions. LIMITATIONS: The generalizability of our findings is limited because the outcome is based on two subjects. CONCLUSION: This work suggests that BAC can be individually tailored and more limited to the ventral aspect of the ALIC and is effective and safe for TRD and TROCD. Accumulating data also suggests that to be clinically effective the length of the capsulotomy should be about 10mm. BAC's use may increase with the growing utilization and mastery of magnetic resonance guided focused ultrasound.


Subject(s)
Depressive Disorder, Treatment-Resistant , Obsessive-Compulsive Disorder , Humans , Depression , Depressive Disorder, Treatment-Resistant/diagnostic imaging , Depressive Disorder, Treatment-Resistant/surgery , Depressive Disorder, Treatment-Resistant/pathology , Obsessive-Compulsive Disorder/diagnostic imaging , Obsessive-Compulsive Disorder/surgery , Obsessive-Compulsive Disorder/pathology , Executive Function , Magnetic Resonance Imaging , Internal Capsule/diagnostic imaging , Internal Capsule/surgery , Internal Capsule/pathology , Treatment Outcome
3.
J Hand Surg Am ; 49(2): 150-159, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37865912

ABSTRACT

Osteochondritis dissecans (OCD) of the capitellum occurs relatively infrequently but can be found in young overhead-throwing athletes, most commonly in baseball players and gymnasts. Although non-operative management can effectively treat stable lesions, unstable lesions can lead to debilitating symptoms of the elbow and diminished quality of life without surgical intervention. This article reviews methods of treating OCD of the capitellum categorized by stability, size, and patient characteristics, and seeks to familiarize the reader with the appropriate selection of osteochondral allograft versus autograft in treating large, unstable lesions. We complement this review with 3 case examples, each using either an osteochondral autograft or allograft, and discuss the decision-making methodology used in each case.


Subject(s)
Elbow Joint , Obsessive-Compulsive Disorder , Osteochondritis Dissecans , Humans , Osteochondritis Dissecans/surgery , Autografts/pathology , Quality of Life , Treatment Outcome , Elbow Joint/surgery , Elbow Joint/pathology , Allografts/pathology , Obsessive-Compulsive Disorder/pathology
4.
Psychiatry Res Neuroimaging ; 332: 111644, 2023 07.
Article in English | MEDLINE | ID: mdl-37087810

ABSTRACT

Many studies have shown that limbic system abnormalities are seen in obsessive-compulsive disorder (OCD), but the neurobiological changes in OCD are still unclear. Moreover, olfactory bulb volume (OBV) and its association with symptom severity have not been yet investigated in patients with OCD. This is the first study on OBV and olfactory sulcus depth (OSD) values in OCD patients, to the best of our knowledge. Between January 2018 and March 2022, 25 patients with OCD and 26 healthy controls with brain magnetic resonance imaging (MRI) were included. Detailed disease history of OCD patients was taken, and Yale-Brown obsessive-compulsive scale (YBOCS) was applied. The mean age of the patient group was 33.40±9.58, the mean age of the control group was 32.84±8.01. LOBV, ROBV, TOBV, and LOSD in the patient group were significantly lower than in the control group (p=.013, p=.005, p=.001, p=.015, respectively). ROBV and TOBV were negatively correlated with YBOCS total and subscale scores. A negative correlation was found between ROBV and TOBV and disease duration (r=-0.749 and r=-0.640, respectively). The negative correlation of ROBV and TOBV values with disease duration and disease severity can be used to monitor the neurodegenerative process of OCD disease.


Subject(s)
Obsessive-Compulsive Disorder , Olfactory Bulb , Humans , Olfactory Bulb/diagnostic imaging , Olfactory Bulb/pathology , Brain/pathology , Obsessive-Compulsive Disorder/diagnostic imaging , Obsessive-Compulsive Disorder/pathology , Limbic System/pathology , Prefrontal Cortex/pathology
5.
BMC Psychiatry ; 23(1): 289, 2023 04 25.
Article in English | MEDLINE | ID: mdl-37098479

ABSTRACT

BACKGROUND: Previous studies discovered the presence of abnormal structures and functions in the brain regions of patients with obsessive-compulsive disorder (OCD). Nevertheless, whether structural changes in brain regions are coupled with alterations in dynamic functional connectivity (dFC) at rest in medicine-free patients with OCD remains vague. METHODS: Three-dimensional T1-weighed magnetic resonance imaging (MRI) and resting-state functional MRI were performed on 50 medicine-free OCD and 50 healthy controls (HCs). Firstly, the differences in gray matter volume (GMV) between OCD and HCs were compared. Then, brain regions with aberrant GMV were used as seeds for dFC analysis. The relationship of altered GMV and dFC with clinical parameters in OCD was explored using partial correlation analysis. Finally, support vector machine was applied to examine whether altered multimodal imaging data might be adopted to distinguish OCD from HCs. RESULTS: Our findings indicated that GMV in the left superior temporal gyrus (STG) and right supplementary motor area (SMA) was reduced in OCD, and the dFC between the left STG and the left cerebellum Crus I and left thalamus, and between the right SMA and right dorsolateral prefrontal cortex (DLPFC) and left precuneus was decreased at rest in OCD. The brain regions both with altered GMV and dFC values could discriminate OCD from HCs with the accuracy of 0.85, sensitivity of 0.90 and specificity of 0.80. CONCLUSION: The decreased gray matter structure coupling with dynamic function in the left STG and right SMA at rest may be crucial in the pathophysiology of OCD. TRIAL REGISTRATION: Study on the mechanism of brain network in obsessive-compulsive disorder with multi-model magnetic resonance imaging (registration date: 08/11/2017; registration number: ChiCTR-COC-17,013,301).


Subject(s)
Gray Matter , Obsessive-Compulsive Disorder , Humans , Gray Matter/diagnostic imaging , Gray Matter/pathology , Cerebral Cortex/pathology , Brain , Parietal Lobe , Magnetic Resonance Imaging , Obsessive-Compulsive Disorder/pathology
6.
Transl Psychiatry ; 12(1): 328, 2022 08 10.
Article in English | MEDLINE | ID: mdl-35948535

ABSTRACT

Obsessive-compulsive symptoms (OCS) are common in school-aged children and predict the development of obsessive compulsive disorder (OCD). White-matter abnormalities have been described in OCD, but the white matter correlates of OCS in the developing brain are unclear. Some correlates of OCS (or a diagnosis of OCD) may reflect correlates of a transdiagnostic or even general psychopathology factor. We examined these questions in a large sample of typically developing youth (N = 1208), using a hierarchical analysis of fixel-based white matter measures in relation to OCS and general psychopathology. General psychopathology was associated with abnormalities in the posterior corpus callosum and forceps major in an age-dependent manner, suggesting altered maturation (specifically, hypermaturation in younger subjects). A unidimensional measure of OCS did not associate with any white-matter abnormalities, but analysis of separate OCS dimensions (derived from factor analysis within this sample) revealed the 'Bad Thoughts' dimension to associate with white-matter abnormalities in dorsal parietal white-matter and descending corticospinal tracts, and the 'Symmetry' dimension to associate with abnormalities in the anterior corpus callosum. Repetition/checking and Symmetry OCS were additionally associated with posterior abnormalities overlapping with the correlates of general psychopathology. Contamination symptoms had no white-matter correlates. Secondary analysis of fractional anisotropy (FA) revealed distinct white-matter abnormalities, suggesting that fixel-based and FA analyses identify distinct features of white matter relevant to psychopathology. These findings suggest that OCS dimensions correlate with dissociable abnormalities in white matter, implicating separable networks. Future studies should examine these white-matter signatures in a longitudinal framework.


Subject(s)
Obsessive-Compulsive Disorder , White Matter , Adolescent , Anisotropy , Child , Humans , Obsessive-Compulsive Disorder/diagnostic imaging , Obsessive-Compulsive Disorder/pathology , White Matter/diagnostic imaging , White Matter/pathology
7.
Brain Imaging Behav ; 16(5): 1946-1953, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35867324

ABSTRACT

Little is known about the underlying neurobiological mechanisms in patients with obsessive-compulsive disorder (OCD). We aimed to examine cortical thickness and surface area in individuals with OCD and their unaffected siblings, comparing them to healthy controls. 30 patients with OCD, 21 unaffected siblings (SIB) and 30 controls underwent structural magnetic resonance imaging. Structural images were analyzed using the FreeSurfer software package (version 6.0). Compared to healthy controls, both OCD and SIB groups showed significantly lower cortical thickness in the right anterior insula. Surface areas of the superior frontal gyrus, paracentral gyrus and precuneus of the right hemisphere were also reduced in OCD patients compared to controls. There were no significant differences in cortical thickness and surface area between the OCD and SIB groups. We did not detect any significant differences in subcortical volumes between groups. Lower cortical thickness in the right anterior insula in both OCD patients and unaffected siblings may represent a potential structural endophenotype for OCD.


Subject(s)
Magnetic Resonance Imaging , Obsessive-Compulsive Disorder , Humans , Magnetic Resonance Imaging/methods , Siblings , Cerebral Cortex/diagnostic imaging , Cerebral Cortex/pathology , Obsessive-Compulsive Disorder/diagnostic imaging , Obsessive-Compulsive Disorder/pathology , Parietal Lobe/pathology
8.
Int J Radiat Oncol Biol Phys ; 113(5): 960-966, 2022 08 01.
Article in English | MEDLINE | ID: mdl-35595157

ABSTRACT

PURPOSE: Effective treatment options for refractory depression are needed. Recent advancements permit both precise ablative radiation and functional neurologic connectome analysis using standard magnetic resonance imaging. We combined these innovations to perform stereotactic radiosurgical capsulotomy for the treatment of medically refractory major depressive disorder and study connectome response using a novel tractography-based approach. METHODS AND MATERIALS: Patients with medically refractory depression were enrolled on a prospective pilot single-arm observational trial from 2020 to 2021 at a single academic tertiary referral center. Bilateral ablation of the anterior limb of the internal capsule was accomplished by mask-based linear accelerator stereotactic radiosurgery. Beck's Depression Inventory measured efficacy. Montreal Cognitive Assessment evaluated cognition. RESULTS: Three patients were enrolled. Depression burden was improved by 88% at 12-month follow-up and by 55% at 18-month follow-up for patient 1 and 2, respectively. Patient 1 discontinued ketamine therapy, and patient 2 discontinued electroconvulsive therapy. Patient 3 reported global improvement in symptoms and function at 3 months. All 3 patients had reduction or resolution of suicidal ideation. No patient experienced cognitive decline or neurologic toxicity, and Montreal Cognitive Assessment score, as well as subjective patient-reported evaluations of concentration and attention, were superior after treatment. Tractography confirmed intended disruption of the cortico-striatal-thalamo-cortical loop with structural reorganization in the connectome. Connectome change was consistent between patients. Observed increases in caudate and putamen connectivity and decreases in thalamic connectivity may explain improved concentration, attention, and depression. The diversity and magnitude of connectome change may correlate with degree of clinical response. CONCLUSIONS: In 3 patients with refractory depression, radiosurgical capsulotomy significantly reduced the burden of depression. Functional connectome reorganization offers neurobiological evidence to support further investigations of the role of radiosurgery in depression.


Subject(s)
Depressive Disorder, Major , Depressive Disorder, Treatment-Resistant , Obsessive-Compulsive Disorder , Radiosurgery , Depressive Disorder, Major/diagnostic imaging , Depressive Disorder, Major/surgery , Depressive Disorder, Treatment-Resistant/diagnostic imaging , Depressive Disorder, Treatment-Resistant/surgery , Diffusion Tensor Imaging , Humans , Magnetic Resonance Imaging , Obsessive-Compulsive Disorder/pathology , Obsessive-Compulsive Disorder/psychology , Obsessive-Compulsive Disorder/surgery , Prospective Studies , Radiosurgery/methods
9.
Ocul Immunol Inflamm ; 30(2): 428-432, 2022 Feb 17.
Article in English | MEDLINE | ID: mdl-32946294

ABSTRACT

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.


Subject(s)
Obsessive-Compulsive Disorder , Tomography, Optical Coherence , Biomarkers , Choroid/pathology , Humans , Inflammation/diagnosis , Inflammation/pathology , Obsessive-Compulsive Disorder/diagnosis , Obsessive-Compulsive Disorder/pathology , Prospective Studies , Retrospective Studies , Tomography, Optical Coherence/methods
10.
Hum Brain Mapp ; 43(1): 23-36, 2022 01.
Article in English | MEDLINE | ID: mdl-32154629

ABSTRACT

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.


Subject(s)
Neuroimaging , Obsessive-Compulsive Disorder , Cerebral Cortex/diagnostic imaging , Cerebral Cortex/pathology , Humans , Machine Learning , Multicenter Studies as Topic , Obsessive-Compulsive Disorder/diagnostic imaging , Obsessive-Compulsive Disorder/pathology
11.
Hum Brain Mapp ; 43(1): 167-181, 2022 01.
Article in English | MEDLINE | ID: mdl-32420672

ABSTRACT

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.


Subject(s)
Autism Spectrum Disorder/pathology , Cerebral Cortex/anatomy & histology , Depressive Disorder, Major/pathology , Gray Matter/anatomy & histology , Magnetic Resonance Imaging , Neuroimaging , Obsessive-Compulsive Disorder/pathology , Autism Spectrum Disorder/diagnostic imaging , Cerebral Cortex/diagnostic imaging , Depressive Disorder, Major/diagnostic imaging , Gray Matter/diagnostic imaging , Humans , Multicenter Studies as Topic , Obsessive-Compulsive Disorder/diagnostic imaging
12.
J Am Acad Child Adolesc Psychiatry ; 61(2): 321-330, 2022 02.
Article in English | MEDLINE | ID: mdl-34217835

ABSTRACT

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.


Subject(s)
Obsessive-Compulsive Disorder , Thalamus , Child , Humans , Magnetic Resonance Imaging , Obsessive-Compulsive Disorder/diagnostic imaging , Obsessive-Compulsive Disorder/pathology , Thalamus/diagnostic imaging , Thalamus/pathology
13.
Genes Genomics ; 43(9): 1049-1057, 2021 09.
Article in English | MEDLINE | ID: mdl-34146253

ABSTRACT

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.


Subject(s)
Autoimmune Diseases/genetics , Genetic Predisposition to Disease , Glomerulonephritis, IGA/genetics , IgA Vasculitis/genetics , Immunoglobulin A/genetics , Obsessive-Compulsive Disorder/genetics , Adolescent , Alleles , Autoimmune Diseases/pathology , Child , Female , Gene Frequency , Genome-Wide Association Study , Glomerulonephritis, IGA/epidemiology , Humans , IgA Vasculitis/epidemiology , Male , Obsessive-Compulsive Disorder/pathology , Polymorphism, Single Nucleotide/genetics , Republic of Korea/epidemiology
14.
Hum Brain Mapp ; 42(12): 3871-3886, 2021 08 15.
Article in English | MEDLINE | ID: mdl-34105832

ABSTRACT

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.


Subject(s)
Cerebral Cortex , Corpus Striatum , Executive Function , Gray Matter , Nerve Net , Obsessive-Compulsive Disorder , Substance-Related Disorders , Cerebral Cortex/diagnostic imaging , Cerebral Cortex/pathology , Cerebral Cortex/physiopathology , Corpus Striatum/diagnostic imaging , Corpus Striatum/pathology , Corpus Striatum/physiopathology , Executive Function/physiology , Gray Matter/diagnostic imaging , Gray Matter/pathology , Gray Matter/physiopathology , Humans , Nerve Net/diagnostic imaging , Nerve Net/pathology , Nerve Net/physiopathology , Obsessive-Compulsive Disorder/diagnostic imaging , Obsessive-Compulsive Disorder/pathology , Obsessive-Compulsive Disorder/physiopathology , Substance-Related Disorders/diagnostic imaging , Substance-Related Disorders/pathology , Substance-Related Disorders/physiopathology
15.
JAMA Psychiatry ; 78(1): 47-63, 2021 Jan 01.
Article in English | MEDLINE | ID: mdl-32857118

ABSTRACT

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.


Subject(s)
Attention Deficit Disorder with Hyperactivity/pathology , Autism Spectrum Disorder/pathology , Bipolar Disorder/pathology , Cerebral Cortex/pathology , Depressive Disorder, Major/pathology , Fetal Development/physiology , Gene Expression/physiology , Human Development/physiology , Obsessive-Compulsive Disorder/pathology , Schizophrenia/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Attention Deficit Disorder with Hyperactivity/diagnostic imaging , Autism Spectrum Disorder/diagnostic imaging , Bipolar Disorder/diagnostic imaging , Case-Control Studies , Cerebral Cortex/cytology , Cerebral Cortex/diagnostic imaging , Cerebral Cortex/growth & development , Child , Child, Preschool , Cohort Studies , Computational Biology , Depressive Disorder, Major/diagnostic imaging , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Obsessive-Compulsive Disorder/diagnostic imaging , Principal Component Analysis , Schizophrenia/diagnostic imaging , Young Adult
16.
Neuroimage ; 223: 117318, 2020 12.
Article in English | MEDLINE | ID: mdl-32882386

ABSTRACT

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.


Subject(s)
Brain/pathology , Brain/physiopathology , Diffusion Magnetic Resonance Imaging , Obsessive-Compulsive Disorder/pathology , Obsessive-Compulsive Disorder/physiopathology , Animals , Brain/diagnostic imaging , Brain Mapping/methods , Disease Models, Animal , Excitatory Amino Acid Transporter 2/genetics , Gene Knockdown Techniques , Mice , Neural Pathways/diagnostic imaging , Neural Pathways/pathology , Neural Pathways/physiopathology , Obsessive-Compulsive Disorder/diagnostic imaging
17.
J Psychiatry Neurosci ; 45(5): 334-343, 2020 09 01.
Article in English | MEDLINE | ID: mdl-32293840

ABSTRACT

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.


Subject(s)
Basolateral Nuclear Complex/pathology , Central Amygdaloid Nucleus/pathology , Obsessive-Compulsive Disorder/pathology , Adult , Basolateral Nuclear Complex/diagnostic imaging , Central Amygdaloid Nucleus/diagnostic imaging , Female , Humans , Magnetic Resonance Imaging , Male , Obsessive-Compulsive Disorder/diagnostic imaging , Young Adult
18.
PLoS One ; 15(4): e0231390, 2020.
Article in English | MEDLINE | ID: mdl-32294104

ABSTRACT

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.


Subject(s)
Impulsive Behavior , Mental Disorders/diagnosis , Adult , Attention Deficit Disorder with Hyperactivity/complications , Attention Deficit Disorder with Hyperactivity/pathology , Autistic Disorder/complications , Autistic Disorder/pathology , Diagnostic and Statistical Manual of Mental Disorders , Female , Humans , Male , Mental Disorders/complications , Mental Disorders/pathology , Middle Aged , Mood Disorders/complications , Mood Disorders/pathology , Netherlands , Obsessive-Compulsive Disorder/complications , Obsessive-Compulsive Disorder/pathology , Severity of Illness Index , Young Adult
19.
Psychiatry Res Neuroimaging ; 298: 111046, 2020 04 30.
Article in English | MEDLINE | ID: mdl-32106018

ABSTRACT

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.


Subject(s)
Cerebral Cortex , Corpus Striatum , Magnetic Resonance Imaging , Neuroimaging , Obsessive-Compulsive Disorder , Severity of Illness Index , Adolescent , Adult , Case-Control Studies , Cerebral Cortex/diagnostic imaging , Cerebral Cortex/pathology , Cerebral Cortex/physiopathology , Corpus Striatum/diagnostic imaging , Corpus Striatum/pathology , Corpus Striatum/physiopathology , Diffusion Tensor Imaging/methods , Female , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Obsessive-Compulsive Disorder/diagnostic imaging , Obsessive-Compulsive Disorder/pathology , Obsessive-Compulsive Disorder/physiopathology , Young Adult
20.
Neurosci Biobehav Rev ; 112: 83-94, 2020 05.
Article in English | MEDLINE | ID: mdl-32006553

ABSTRACT

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.


Subject(s)
Emotions , Executive Function , Obsessive-Compulsive Disorder , Prefrontal Cortex , Putamen , Case-Control Studies , Emotions/physiology , Executive Function/physiology , Humans , Magnetic Resonance Imaging , Obsessive-Compulsive Disorder/diagnostic imaging , Obsessive-Compulsive Disorder/pathology , Obsessive-Compulsive Disorder/physiopathology , Prefrontal Cortex/diagnostic imaging , Prefrontal Cortex/pathology , Prefrontal Cortex/physiopathology , Putamen/diagnostic imaging , Putamen/pathology , Putamen/physiopathology
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