Yanchun Yang

Abnormal small-world architecture of top–down control networks in obsessive–compulsive disorder

BACKGROUND Obsessive-compulsive disorder (OCD) is a common neuropsychiatric disorder that is characterized by recurrent intrusive thoughts, ideas or images and repetitive ritualistic behaviours. Although focal structural and functional abnormalities in specific brain regions have been widely studied in populations with OCD, changes in the functional relations among them remain poorly understood. This study examined OCD-related alterations in functional connectivity patterns in the brains top-down control network. METHODS We applied resting-state functional magnetic resonance imaging to investigate the correlation patterns of intrinsic or spontaneous blood oxygen level-dependent signal fluctuations in 18 patients with OCD and 16 healthy controls. The brain control networks were first constructed by thresholding temporal correlation matrices of 39 brain regions associated with top-down control and then analyzed using graph theory-based approaches. RESULTS Compared with healthy controls, the patients with OCD showed decreased functional connectivity in the posterior temporal regions and increased connectivity in various control regions such as the cingulate, precuneus, thalamus and cerebellum. Furthermore, the brains control networks in the healthy controls showed small-world architecture (high clustering coefficients and short path lengths), suggesting an optimal balance between modularized and distributed information processing. In contrast, the patients with OCD showed significantly higher local clustering, implying abnormal functional organization in the control network. Further analysis revealed that the changes in network properties occurred in regions of increased functional connectivity strength in patients with OCD. LIMITATIONS The patient group in the present study was heterogeneous in terms of symptom clusters, and most of the patients with OCD were medicated. CONCLUSION Our preliminary results suggest that the organizational patterns of intrinsic brain activity in the control networks are altered in patients with OCD and thus provide empirical evidence for aberrant functional connectivity in the large-scale brain systems in people with this disorder.

Microstructural Brain Abnormalities in Patients with Obsessive-Compulsive Disorder: Diffusion-Tensor MR Imaging Study at 3.0 T

PURPOSE To use diffusion-tensor (DT) magnetic resonance (MR) imaging to explore the integrity and connectivity of brain white matter in patients with obsessive-compulsive disorder (OCD) and to correlate DT parameters with clinical measures. MATERIALS AND METHODS This study was approved by the local ethical committee, and written informed consent was obtained from all participants. DT imaging was performed by using a 3.0-T MR imager in 23 patients with OCD and 23 healthy control subjects matched for age, sex, education level, and handedness. By using voxel-based analysis, fractional anisotropy (FA) and axial and radial diffusivities were compared between patients and control subjects with a two-sample t test and were tested for correlation with symptom severity, as measured by using the Yale-Brown Obsessive-Compulsive Scale and obsessive-compulsive subscale scores, and with illness duration, as measured by using simple regression in statistical parametric mapping program. RESULTS Compared with control subjects, OCD patients demonstrated significantly increased FA in the genu and body of corpus callosum and white matter of right superior frontal gyrus and corpus callosum; no areas of significantly decreased FA were found. For areas of increased FA, axial diffusivity was higher than that in control subjects, while radial diffusivity was not significantly different. The FA values in the white matter of left middle temporal gyrus in OCD patients correlated positively with clinical measures (r = 0.542, P < .001). CONCLUSION OCD is associated with axonal microstructural abnormalities within the white matter, which may indicate impaired axonal integrity and increased connectivity. The positive correlation between DT abnormalities and symptom severity suggests that DT imaging may be of clinical value in measuring and following disability in OCD patients.

Multivariate pattern analysis of DTI reveals differential white matter in individuals with obsessive-compulsive disorder.

Diffusion tensor imaging (DTI) studies have revealed group differences in white matter between patients with obsessive‐compulsive disorder (OCD) and healthy controls. However, the results of these studies were based on average differences between the two groups, and therefore had limited clinical applicability. The objective of this study was to investigate whether fractional anisotropy (FA) of white matter can be used to discriminate between patients with OCD and healthy controls at the level of the individual. DTI data were acquired from 28 OCD patients and 28 demographically matched healthy controls, scanned using a 3T MRI system. Differences in FA values of white matter between OCD and healthy controls were examined using a multivariate pattern classification technique known as support vector machine (SVM). SVM applied to FA images correctly identified OCD patients with a sensitivity of 86% and a specificity of 82% resulting in a statistically significant accuracy of 84% (P ≤ 0.001). This discrimination was based on a distributed network including bilateral prefrontal and temporal regions, inferior fronto‐occipital fasciculus, superior fronto‐parietal fasciculus, splenium of corpus callosum and left middle cingulum bundle. The present study demonstrates subtle and spatially distributed white matter abnormalities in individuals with OCD, and provides preliminary support for the suggestion that that these could be used to aid the identification of individuals with OCD in clinical practice. Hum Brain Mapp 35:2643–2651, 2014.

Multivariate pattern analysis of obsessive–compulsive disorder using structural neuroanatomy

Magnetic resonance imaging (MRI) studies have revealed brain structural abnormalities in obsessive-compulsive disorder (OCD) patients, involving both gray matter (GM) and white matter (WM). However, the results of previous publications were based on average differences between groups, which limited their usages in clinical practice. Therefore, the aim of this study was to examine whether the application of multivariate pattern analysis (MVPA) to high-dimensional structural images would allow accurate discrimination between OCD patients and healthy control subjects (HCS). High-resolution T1-weighted images were acquired from 33 OCD patients and 33 demographically matched HCS in a 3.0 T scanner. Differences in GM and WM volume between OCD and HCS were examined using two types of well-established MVPA techniques: support vector machine (SVM) and Gaussian process classifier (GPC). We also drew a receiver operating characteristic (ROC) curve to evaluate the performance of each classifier. The classification accuracies for both classifiers using GM and WM anatomy were all above 75%. The highest classification accuracy (81.82%, P<0.001) was achieved with the SVM classifier using WM information. Regional brain anomalies with high discriminative power were based on three distributed networks including the fronto-striatal circuit, the temporo-parieto-occipital junction and the cerebellum. Our study illustrated that both GM and WM anatomical features may be useful in differentiating OCD patients from HCS. WM volume using the SVM approach showed the highest accuracy in our population for revealing group differences, which suggested its potential diagnostic role in detecting highly enriched OCD patients at the level of the individual.

Morphometric brain characterization of refractory obsessive-compulsive disorder: diffeomorphic anatomic registration using exponentiated Lie algebra.

BACKGROUND Few studies have used neuroimaging to characterize treatment-refractory obsessive-compulsive disorder (OCD). This study sought to explore gray matter structure in patients with treatment-refractory OCD and compare it with that of healthy controls. METHODS A total of 18 subjects with treatment-refractory OCD and 26 healthy volunteers were analyzed by MRI using a 3.0-T scanner and voxel-based morphometry (VBM). Diffeomorphic anatomical registration using exponentiated Lie algebra (DARTEL) was used to identify structural changes in gray matter associated with treatment-refractory OCD. A partial correlation model was used to analyze whether morphometric changes were associated with Yale-Brown Obsessive-Compulsive Scale scores and illness duration. RESULTS Gray matter volume did not differ significantly between the two groups. Treatment-refractory OCD patients showed significantly lower gray matter density than healthy subjects in the left posterior cingulate cortex (PCC) and mediodorsal thalamus (MD) and significantly higher gray matter density in the left dorsal striatum (putamen). These changes did not correlate with symptom severity or illness duration. CONCLUSIONS Our findings provide new evidence of deficits in gray matter density in treatment-refractory OCD patients. These patients may show characteristic density abnormalities in the left PCC, MD and dorsal striatum (putamen), which should be verified in longitudinal studies.

Structural brain abnormalities correlate with clinical features in patients with drug-naïve OCD: A DARTEL-enhanced voxel-based morphometry study

BACKGROUND Abnormal brain structure has been reported in obsessive-compulsive disorder (OCD), but findings from these reports have been inconsistent. This study aimed to gain more detailed insights into gray matter structure and correlate this structure with clinical features in patients with drug-naïve OCD using voxel-based morphometry (VBM). METHODS Voxel-based morphometry and tools of Diffeomorphic Anatomical Registration through Exponentiated Lie Algebra (DARTEL) were used to investigate structural differences in gray matter volume between 26 drug-naïve OCD patients and 32 healthy controls. Partial correlation analysis was used to analyze associations of gray matter abnormalities with Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores and illness duration. RESULTS Compared to healthy controls, drug-naïve OCD patients showed significantly smaller gray matter volume in the right dorsolateral prefrontal cortex (DLPFC), left superior temporal gyrus, left precuneus and right precentral gyrus, as well as significantly greater gray matter volume in the left anterior insula and right parahippocampal gyrus (p<0.05, corrected using the familywise error rate). Y-BOCS scores correlated positively with gray matter volume in the left anterior insula, while they correlated negatively with gray matter volume in the right DLPFC. CONCLUSIONS OCD pathophysiology may involve structural changes in the DLPFC-parietal regions, including the dorsolateral prefrontal cortex, precuneus, superior temporal gyrus and connected limbic structures such as the parahippocampal gyrus and anterior insula. Longitudinal studies are needed that integrate anatomical, functional and diffusion MRI data.

Gray Matter Alterations in Post-Traumatic Stress Disorder, Obsessive–Compulsive Disorder, and Social Anxiety Disorder

Post-traumatic stress disorder (PTSD), obsessive–compulsive disorder (OCD), and social anxiety disorder (SAD) all bear the core symptom of anxiety and are separately classified in the new DSM-5 system. The aim of the present study is to obtain evidence for neuroanatomical difference for these disorders. We applied voxel-based morphometry (VBM) with Diffeomorphic Anatomical Registration Through Exponentiated Lie to compare gray matter volume (GMV) in magnetic resonance images obtained for 30 patients with PTSD, 29 patients with OCD, 20 patients with SAD, and 30 healthy controls. GMV across all four groups differed in left hypothalamus and left inferior parietal lobule and post hoc analyses revealed that this difference is primarily due to reduced GMV in the PTSD group relative to the other groups. Further analysis revealed that the PTSD group also showed reduced GMV in frontal lobe, temporal lobe, and cerebellum compared to the OCD group, and reduced GMV in frontal lobes bilaterally compared to SAD group. A significant negative correlation with anxiety symptoms is observed for GMV in left hypothalamus in three disorder groups. We have thus found evidence for brain structure differences that in future could provide biomarkers to potentially support classification of these disorders using MRI.

Mental health and psychosocial problems among Chinese left-behind children: A cross-sectional comparative study

BACKGROUND Separation from migrant parents threatens the mental health of approximately 61 million left-behind children (LBC) in China. This study compared the prevalence of mental health and psychosocial problems between LBC and controls in Sichuan province, China. METHODS We randomly recruited LBC and adolescents aged 12-16 years old from 16 rural high schools in 8 counties in Sichuan province. We compared frequency of school bullying, self-esteem, panic symptoms, depression and severe psychological distress(SPD) between LBC and controls from the same schools. These variables were assessed through face-to-face interviews and self-report questionnaires. RESULTS The prevalence of mental health problems was 43.4% among LBC(n = 1663) but 30.8% among controls(n = 1683), and the prevalence of specific psychological symptoms was also higher among LBC: SPD, 12.1% vs. 4.8%; panic, 32.4% vs. 22.1%; and depressive symptoms, 26.5% vs. 16.3%. Low self-esteem was more prevalent among LBC(26.6% vs. 18.2%) as was severe school bullying(18.5% vs. 11.3%). Among LBC, low self-esteem was associated with an increased risk of depression or SPD, and school bullying was a significant predictor of depression, panic symptoms and SPD. Low self-esteem and depression increased with longer separation from parents, and this risk was higher when the primary caregivers were LBC themselves or relatives compared to single parents or grandparents. LIMITATION LBC misbehavior, such as internet addiction, smoking and drinking, may also explain our findings; these factors need to be explored in future studies. CONCLUSION Our results highlight the urgent need for school-based and targeted interventions for LBC to prevent negative mental health outcomes.