Publications by authors named "Yuqi Cheng"

48 Publications

Roles of 5,10-Methylenetetrahydrofolate Reductase C677T Polymorphisms in First-Episode, Drug-Naive Adult Patients With Depression.

Front Psychiatry 2020 7;11:531959. Epub 2020 Dec 7.

Department of Psychiatry, First Affiliated Hospital of Kunming Medical University, Kunming, China.

5,10-Methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism is considered as a predisposition and promising genetic candidate to major depressive disorder (MDD), as it is associated with impaired one-carbon cycles, which may be involved in the pathogenesis of depression. Cortical thickness (CT) and subcortical structure volumes have been extensively studied in MDD and have been proposed as one of the phenotypes for MDD. We intend to discuss the association between CT, subcortical structure volume, and C677T polymorphism in first-episode, treatment-naive patients with MDD. In this study, 127 adult patients with MDD and 101 age- and gender-matched healthy controls (HCs) were included. All subjects underwent T1-weighted MRI, C677T genotyping, and FreeSurfer software-based morphological analysis. MDD patients have been detected to have significantly decreased volumes in the left nucleus accumbens ( < 0.001). The 677 T allele carriers manifested with thinner CT in the left caudal anterior cingulate cortex (cACC, = 0.009) compared with CC genotype. There were significant genotype-by-diagnosis interactions for the CT in the left cACC ( = 0.009), isthmus cingulate ( = 0.002), medial orbitofrontal lobe ( = 0.012), posterior cingulate ( = 0.030), and the right lateral orbitofrontal lobe ( = 0.012). We also found a trend in the interaction effect on the volume of the left putamen ( = 0.050). Our results revealed that C677T polymorphism may be involved in the dysfunction of limbic-cortical-striatal-pallidal-thalamic (LCSPT) circuits mediating emotion processing, which may contribute to pathogenesis of MDD.
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http://dx.doi.org/10.3389/fpsyt.2020.531959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7751613PMC
December 2020

Cropland heterogeneity changes on the Northeast China Plain in the last three decades (1980s-2010s).

PeerJ 2020 8;8:e9835. Epub 2020 Sep 8.

Department of Earth System Science, Ministry of Education Key Laboratory for Earth System Modeling, Tsinghua University, Beijing, China.

The Northeast China Plain is one of the major grain-producing areas of China because of its fertile black soil and large fields adapted for agricultural machinery. It has experienced some land-use changes, such as urbanization, deforestation, and wetland reclamation in recent decades. A comprehensive understanding of these changes in terms of the total cropping land and its heterogeneity during this period is important for policymakers. In this study, we used a series of cropland products at the 30-m resolution for the period 1980-2015. The heterogeneity for dominant cropland decreased slowly over the three decades, especially for the large pieces of cropland, showing a general trend of increased cropland homogeneity. The spatial patterns of the averaged heterogeneity index were nearly the same, varying from 0.5 to 0.6, and the most heterogeneous areas were mainly located in some separate counties. Cropland expansion occurred across most of Northeast China, while cropland shrinking occurred only in the northern and eastern sections of Northeast China and around the capital cities, in the flat areas. Also, changes in land use away from cropland mainly occurred in areas with low elevation (50-200 m) and a gentle slope (less than 1 degree). The predominant changes in cropland were gross gain and homogeneity, occurring across most of the area except capital cities and boundary areas. Possible reasons for the total cropland heterogeneity changes were urbanization, restoration of cropland to forest, and some government land-use policies. Moreover, this study evaluates the effectiveness of cropland policies influencing in Northeast China.
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http://dx.doi.org/10.7717/peerj.9835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485484PMC
September 2020

Structural neuroimaging biomarkers for obsessive-compulsive disorder in the ENIGMA-OCD consortium: medication matters.

Transl Psychiatry 2020 10 8;10(1):342. Epub 2020 Oct 8.

Department of Psychiatry, Yale University School of Medicine, New Haven, CT, 06510, USA.

No diagnostic biomarkers are available for obsessive-compulsive disorder (OCD). Here, we aimed to identify magnetic resonance imaging (MRI) biomarkers for OCD, using 46 data sets with 2304 OCD patients and 2068 healthy controls from the ENIGMA consortium. We performed machine learning analysis of regional measures of cortical thickness, surface area and subcortical volume and tested classification performance using cross-validation. Classification performance for OCD vs. controls using the complete sample with different classifiers and cross-validation strategies was poor. When models were validated on data from other sites, model performance did not exceed chance-level. In contrast, fair classification performance was achieved when patients were grouped according to their medication status. These results indicate that medication use is associated with substantial differences in brain anatomy that are widely distributed, and indicate that clinical heterogeneity contributes to the poor performance of structural MRI as a disease marker.
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http://dx.doi.org/10.1038/s41398-020-01013-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598942PMC
October 2020

Brain-derived neurotrophic factor Val66Met polymorphism affects cortical thickness of rostral anterior cingulate in patients with major depressive disorder.

Neuroreport 2020 11;31(16):1146-1153

Departments of Psychiatry.

Objective: The neuro-anatomical substrates of major depressive disorder (MDD) remain poorly understood. Brain-derived neurotrophic factor (BDNF) gene polymorphism (Val66Met/rs6265) is associated with neuro-plasticity and development. In the present study, we explore the influence of BDNF gene polymorphism on cortical thickness in nonelderly, first episode, drug-naive patients with MDD.

Methods: Two hundred and sixteen participants (105 MDD patients and 111 healthy controls) were divided into subgroups based on the BDNF genotype. High-resolution MRI was obtained in all participants. A relationship of BDNF Val66Met gene polymorphism and cortical thickness was investigated.

Results: The significant main effect of diagnosis was identified in the left rostal anterior cingulate (rACC), right inferior temporal and right lateral orbitofrontal (lOFC). The main effect of the genotype was observed in the left posterior cingulate cortex. The diagnosis-by-genotype interaction effect was found located in the left rACC. MDD patients who were Met-carriers exhibited thinner cortical thickness in the left rACC than healthy controls Met-carriers. Neither the symptom severity nor the illness duration was correlated significantly with cortical thickness.

Conclusion: Our findings suggested that the BDNF gene polymorphism was associated with cortical thickness alterations of the left rACC in MDD patients, and genotype that carries Met may serve as a vulnerability factor in MDD regarding the cortical thickness loss in the left rACC. This finding can be considered as a supportive evidence for the neurotrophic factor hypothesis of depression.
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http://dx.doi.org/10.1097/WNR.0000000000001528DOI Listing
November 2020

Age-related atrophy of cortical thickness and genetic effect of ANK3 gene in first episode MDD patients.

Neuroimage Clin 2020 26;28:102384. Epub 2020 Aug 26.

Department of Psychiatry, First Affiliated Hospital of Kunming Medical University, Kunming 650032, China.

Brain ageing is thought to be related to geriatric depression, but the relationship between ageing and depression among middle aged individuals is unknown. The present study aimed to evaluate whether the age-related reduction of brain cortical thickness (CT) can be found in adult first-episode MDD patients, as well as to identify the possible genetic effect of the ANK3 gene polymorphism age-relates CT reduction. This study recruited 153 first-episode MDD patients with a disease duration < 2 years and 276 healthy controls (HC), and the CT of 68 whole brain regions and two ANK3 SNPs (rs1994336 and rs10994359) were analyzed. The results showed that although the CT of both groups was negative correlated with age, the MDD group had significant greater age-related decrease in CT than the HC group (-9.35 × 10 mm/year for MDD vs. -1.23 × 10 mm/year for HC in the left lateral orbitofrontal lobe). The multivariate analysis of covariance (MANCOVA) results yielded significant interactions of diagnosis × age, genotype × age and diagnosis × genotype interaction for rs10994359. In HC, the C allele showed a protective effect on age-related CT reduction. The reduction in CT with age was several times as greater in non-C carriers as in C carriers (-3.54 × 10 vs.-0.15 × 10 mm/year in left supramarginal gyrus) for HC. However, this protective effect disappeared in patients with MDD. We did not find a clear effect of rs1994336 on the age-related CT reduction. The findings indicate that the widespread accelerated brain ageing occurs early in adult-onset depression and this ageing may be a pathological mechanisms of depression rather than an outcome of the disease. The ANK3 rs10994359 polymorphism may partially affect regional cortical ageing in MDD.
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http://dx.doi.org/10.1016/j.nicl.2020.102384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490581PMC
August 2020

Virtual Histology of Cortical Thickness and Shared Neurobiology in 6 Psychiatric Disorders.

JAMA Psychiatry 2021 Jan;78(1):47-63

Department of Psychiatry and Neuropsychology, School of Mental Health and Neuroscience, Maastricht University, the Netherlands.

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.
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http://dx.doi.org/10.1001/jamapsychiatry.2020.2694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7450410PMC
January 2021

Hippocampal Atrophy in Systemic Lupus Erythematosus Patients without Major Neuropsychiatric Manifestations.

J Immunol Res 2020 12;2020:2943848. Epub 2020 Jun 12.

Department of Rheumatology and Immunology, First Affiliated Hospital of Kunming Medical University, Kunming 650032, China.

This study was conducted to explore hippocampal structural changes and their possible associations with clinical characteristics, emotional status, and treatment regimens in patients with systemic lupus erythematosus (SLE) without major neuropsychiatric manifestations (non-NPSLE). Eighty-five non-NPSLE patients with normal conventional magnetic resonance imaging (MRI) and seventy-seven matched healthy control (HC) subjects were recruited. All participants underwent the standard high-resolution volumetric MRI. The bilateral hippocampal volume (HIPV) and hippocampal density (HIPD) were calculated, respectively, for each participant. We found that the bilateral HIPV and HIPD of the SLE patient group were significantly less than those of the HC group. The bilateral HIPV of female patients were significantly less than those of male patients. The SLE disease activity index (SLEDAI) was negatively correlated with the bilateral HIPV and the right HIPD. Urine protein quantity was negatively correlated with the bilateral HIPV and HIPD. Hydroxychloroquine (HCQ) showed a protective effect on right HIPV. In conclusion, we found that the early hippocampal atrophy could occur before obvious neuropsychiatric manifestations and might be associated with SLE disease activity and organ damages. Early detection and intervention of hippocampal damage might prevent the progression to NPSLE. More studies are needed to fully understand the underlying mechanisms of hippocampal atrophy in SLE.
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http://dx.doi.org/10.1155/2020/2943848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7306071PMC
May 2021

Subcortical Brain Volume, Regional Cortical Thickness, and Cortical Surface Area Across Disorders: Findings From the ENIGMA ADHD, ASD, and OCD Working Groups.

Am J Psychiatry 2020 09 16;177(9):834-843. Epub 2020 Jun 16.

The full list of authors in the ENIGMA working groups, author affiliations, author disclosures, and acknowledgments are provided in online supplements.

Objective: Attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) are common neurodevelopmental disorders that frequently co-occur. The authors sought to directly compare these disorders using structural brain imaging data from ENIGMA consortium data.

Methods: Structural T-weighted whole-brain MRI data from healthy control subjects (N=5,827) and from patients with ADHD (N=2,271), ASD (N=1,777), and OCD (N=2,323) from 151 cohorts worldwide were analyzed using standardized processing protocols. The authors examined subcortical volume, cortical thickness, and cortical surface area differences within a mega-analytical framework, pooling measures extracted from each cohort. Analyses were performed separately for children, adolescents, and adults, using linear mixed-effects models adjusting for age, sex, and site (and intracranial volume for subcortical and surface area measures).

Results: No shared differences were found among all three disorders, and shared differences between any two disorders did not survive correction for multiple comparisons. Children with ADHD compared with those with OCD had smaller hippocampal volumes, possibly influenced by IQ. Children and adolescents with ADHD also had smaller intracranial volume than control subjects and those with OCD or ASD. Adults with ASD showed thicker frontal cortices compared with adult control subjects and other clinical groups. No OCD-specific differences were observed across different age groups and surface area differences among all disorders in childhood and adulthood.

Conclusions: The study findings suggest robust but subtle differences across different age groups among ADHD, ASD, and OCD. ADHD-specific intracranial volume and hippocampal differences in children and adolescents, and ASD-specific cortical thickness differences in the frontal cortex in adults, support previous work emphasizing structural brain differences in these disorders.
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http://dx.doi.org/10.1176/appi.ajp.2020.19030331DOI Listing
September 2020

Low microalgae availability increases the ingestion rates and potential effects of microplastics on marine copepod Pseudodiaptomus annandalei.

Mar Pollut Bull 2020 Mar 17;152:110919. Epub 2020 Feb 17.

College of Marine Life Sciences, Ocean University of China, Qingdao 266003, China. Electronic address:

Microplastics have aroused great concern for their potential threats to marine organisms. This study investigated the interaction between three sizes of microplastics (0.5, 2, and 10 μm) and the marine copepod Pseudodiaptomus annandalei under two different microalgae concentrations (1 × 10 and 1 × 10 cells/mL). The results revealed that low microalgae supply increased microplastic ingestion through enhancing the encounter rates, and moreover increased the retention time of 0.5 μm microplastics. When the microalgae concentration was 1 × 10 cells/mL, 0.5 μm microplastics could be observed in the copepods after depuration in clear seawater for 24 h, but almost totally excreted at 1 × 10 cells/mL of microalgae. In addition, 0.5 μm microplastics induced significant effects on the ingestion of microalgae by P. annandalei both after 24 h of exposure and depuration. These results suggest that low microalgae availability may increase the ingestion and retention of microplastics in marine copepods, which might increase the ecological risk of microplastics.
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http://dx.doi.org/10.1016/j.marpolbul.2020.110919DOI Listing
March 2020

Association of a SIRT1 polymorphism with changes of gray matter volume in patients with first-episode medication-naïve major depression.

Psychiatry Res Neuroimaging 2020 07 15;301:111101. Epub 2020 May 15.

Department of Psychiatry, First Affiliated Hospital of Kunming Medical University, No. 295 Xichang RD, Kunming 650032, Kunming, Yunnan, China. Electronic address:

A single nucleotide polymorphism (SNP) rs12415800 of the silent mating type information regulation 2 homolog 1 gene (SIRT1) has shown a genome-wide significant association with major depression disorder (MDD) in a recent GWAS using a large sample. Subsequent studies of SIRT1's biological functions were supportive of a possible role in the pathophysiology of MDD. However, SIRT1-mediated physiopathology of MDD may be brain region specific. In the present study, we investigated the impact of SIRT1 rs12415800 genotypes on gray matter volumes (GMV) among different brain regions in both MDD patients and healthy controls. The rs12415800 was genotyped in 170 patients with first-episode medication-naïve MDD (cases) and 170 healthy controls. Magnetic resonance imaging was conducted and the voxel-based morphometry (VBM) approach was employed to analyze obtained images. When compared with the cases carrying GG genotype, the cases carrying GA or AA genotypes (A for risk allele) showed decreased GMV in right precuneus, left cuneus/precuneus, and right frontal superior. In contrast, the rs12415800-associated GMV abnormalities were not observed in controls. The SIRT1-rs12415800 polymorphism may be associated with the changes of GMV in MDD patients.
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http://dx.doi.org/10.1016/j.pscychresns.2020.111101DOI Listing
July 2020

Altered white matter structural networks in drug-naïve patients with obsessive-compulsive disorder.

Brain Imaging Behav 2021 Apr;15(2):700-710

Department of Psychiatry, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, China.

White matter (WM) alteration is considered to be a vital neurological mechanism of obsessive-compulsive disorder (OCD). However, little is known regarding the changes in topological organization of WM structural network in OCD. We acquired diffusion tensor imaging (DTI) datasets from 28 drug-naïve OCD patients and 28 well-matched healthy controls (HC). A deterministic fiber tracking approach was used to construct the whole-brain structural connectome. Group differences in global and nodal topological properties as well as rich-club organizations were compared by using graph theory analysis. The relationship between the altered network metrics and the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) was calculated. Compared with controls, OCD patients exhibited a significantly decreased small-worldness (σ), normalized clustering coefficient (γ) and shortest path length (L), as well as an increased global efficiency (E). The nodal efficiency (E) was found to be reduced in the left middle frontal gyrus, and increased in the right parahippocampal gyrus and bilateral putamen in OCD patients. Besides, OCD patients showed increased rich-club, feeder and local connection strength, and the connection strength of the rich-club was positively correlated with the total Y-BOCS score. Our findings emphasized a central role for the complicatedly changed topological architecture of brain structural networks in the pathological mechanism underlying OCD.
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http://dx.doi.org/10.1007/s11682-020-00278-7DOI Listing
April 2021

A neuroimaging biomarker for striatal dysfunction in schizophrenia.

Nat Med 2020 04 23;26(4):558-565. Epub 2020 Mar 23.

Department of Psychiatry, Henan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.

Mounting evidence suggests that function and connectivity of the striatum is disrupted in schizophrenia. We have developed a new hypothesis-driven neuroimaging biomarker for schizophrenia identification, prognosis and subtyping based on functional striatal abnormalities (FSA). FSA scores provide a personalized index of striatal dysfunction, ranging from normal to highly pathological. Using inter-site cross-validation on functional magnetic resonance images acquired from seven independent scanners (n = 1,100), FSA distinguished individuals with schizophrenia from healthy controls with an accuracy exceeding 80% (sensitivity, 79.3%; specificity, 81.5%). In two longitudinal cohorts, inter-individual variation in baseline FSA scores was significantly associated with antipsychotic treatment response. FSA revealed a spectrum of severity in striatal dysfunction across neuropsychiatric disorders, where dysfunction was most severe in schizophrenia, milder in bipolar disorder, and indistinguishable from healthy individuals in depression, obsessive-compulsive disorder and attention-deficit hyperactivity disorder. Loci of striatal hyperactivity recapitulated the spatial distribution of dopaminergic function and the expression profiles of polygenic risk for schizophrenia. In conclusion, we have developed a new biomarker to index striatal dysfunction and established its utility in predicting antipsychotic treatment response, clinical stratification and elucidating striatal dysfunction in neuropsychiatric disorders.
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http://dx.doi.org/10.1038/s41591-020-0793-8DOI Listing
April 2020

Brain structural covariance networks in obsessive-compulsive disorder: a graph analysis from the ENIGMA Consortium.

Brain 2020 02;143(2):684-700

Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany.

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.
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http://dx.doi.org/10.1093/brain/awaa001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7009583PMC
February 2020

Altered resting-state dynamic functional brain networks in major depressive disorder: Findings from the REST-meta-MDD consortium.

Neuroimage Clin 2020 7;26:102163. Epub 2020 Jan 7.

Faculty of Psychology, Southwest University, Chongqing 400716, China.

Background: Major depressive disorder (MDD) is known to be characterized by altered brain functional connectivity (FC) patterns. However, whether and how the features of dynamic FC would change in patients with MDD are unclear. In this study, we aimed to characterize dynamic FC in MDD using a large multi-site sample and a novel dynamic network-based approach.

Methods: Resting-state functional magnetic resonance imaging (fMRI) data were acquired from a total of 460 MDD patients and 473 healthy controls, as a part of the REST-meta-MDD consortium. Resting-state dynamic functional brain networks were constructed for each subject by a sliding-window approach. Multiple spatio-temporal features of dynamic brain networks, including temporal variability, temporal clustering and temporal efficiency, were then compared between patients and healthy subjects at both global and local levels.

Results: The group of MDD patients showed significantly higher temporal variability, lower temporal correlation coefficient (indicating decreased temporal clustering) and shorter characteristic temporal path length (indicating increased temporal efficiency) compared with healthy controls (corrected p < 3.14×10). Corresponding local changes in MDD were mainly found in the default-mode, sensorimotor and subcortical areas. Measures of temporal variability and characteristic temporal path length were significantly correlated with depression severity in patients (corrected p < 0.05). Moreover, the observed between-group differences were robustly present in both first-episode, drug-naïve (FEDN) and non-FEDN patients.

Conclusions: Our findings suggest that excessive temporal variations of brain FC, reflecting abnormal communications between large-scale bran networks over time, may underlie the neuropathology of MDD.
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http://dx.doi.org/10.1016/j.nicl.2020.102163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229351PMC
February 2021

Genotoxic biomarkers and histological changes in marine medaka (Oryzias melastigma) exposed to 17α-ethynylestradiol and 17β-trenbolone.

Mar Pollut Bull 2020 Jan 6;150:110601. Epub 2019 Nov 6.

College of Marine Life Sciences, Ocean University of China, Qingdao, 266003, China. Electronic address:

Endocrine-disrupting pollutants in marine environments have aroused great concern for their adverse effects on the reproduction of marine organisms. This study aimed to seek promising biomarkers for estrogenic/androgenic chemicals. First, two possible male-specific genes, SRY-box containing gene 9a2 (sox9a2) and gonadal soma-derived factor (gsdf), were cloned from marine medaka (Oryzias melastigma). Then the responses of sox9a2, gsdf, choriogenin (chgH and chgL), vitellogenin (vtg1 and vtg2), and cytochrome P450 aromatase (cyp19a and cyp19b) were investigated after exposure to 17α-ethynylestradiol (EE) and 17β-trenbolone (TB) at 2, 10, and 50 ng/L. The results showed that gsdf was specifically expressed in the testes and easily induced in the ovaries after TB exposure, indicating that gsdf was a potential biomarker of environmental androgens. ChgL was a useful biomarker of weak estrogen pollution for its high sensitivity to low levels of EE. In addition, both EE and TB exposure damaged gonadal structures and inhibited gonadal development.
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http://dx.doi.org/10.1016/j.marpolbul.2019.110601DOI Listing
January 2020

Effects of hypertension on cerebral cortical thickness alterations in patients with type 2 diabetes.

Diabetes Res Clin Pract 2019 Nov 5;157:107872. Epub 2019 Oct 5.

Department of Psychiatry, The First Affiliated Hospital of Kunming Medical University, Kunming, China. Electronic address:

Aims: Although hypertension (HTN) is the high comorbidity of Type 2 diabetes mellitus (T2DM) and known to be a vascular risk factor for brain damage, the effects of HTN on brain function in T2DM patients are not well understood. Present study was performed to investigate whether HTN might accelerate the Cerebral cortical thickness (CT) alterations in patients with T2DM.

Methods: We enrolled 35 participants with only T2DM, 25 T2DM patients with HTN (HT2DM) and 28 healthy controls (HCs). The cognitive function was assessed and brain image data was collected then the CT was calculated for each participant. Partial correlations between the CT of each brain region and standard laboratory testing data and neuropsychological scale scores were also analyzed. Multivariable regression analysis was performed to evaluated the vascular risk factors and brain regions with different CT in HT2DM patients.

Results: Cognitive impairment is associated with thinning of the cerebral cortical thickness reduction in T2DM patients. CT thinning in the left inferior parietal lobe, left posterior cingulate and right precuneus were observed in HT2DM group relative to only T2DM group. Furthermore, the CT decreasing in the right precuneus was negatively correlated with duration of HTN.

Conclusion: The current study revealed that coexistent HTN may accelerate the CT reduction in T2DM patients.
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http://dx.doi.org/10.1016/j.diabres.2019.107872DOI Listing
November 2019

Association of cortical thickness with age of onset in first-episode, drug-naïve major depression.

Neuroreport 2019 11;30(16):1074-1080

Departments of Psychiatry.

Objective: We previously showed differences in brain grey matter volume changes between patients with early-onset adult depression (EOD) and late-onset adult depression (LOD). Here, we aim to identify whether cortical thickness (CT) is affected by the age of onset in patients with depression.

Methods: High-resolution MRI images were obtained for 54 major depressive disorder (MDD) patients with EOD, 58 patients with LOD, 57 young healthy controls (HCs), and 58 aged HCs. Depression severity was assessed using the Hamilton Depression Rating Scale 17-item (HDRS17). Associations between CT of patients and clinical scores were analyzed.

Results: There was a significant main effect of diagnosis for the left rostal anterior cingulate (rACC), right inferior temporal, right lateral orbitofrontal cortex (lOFC), and bilateral pericalcarine. A remarkable onset age-group effect on CT was observed in the rACC and bilateral caudal anterior cingulate (cACC). The diagnosis-by-onset age interaction effect was found in bilateral rACC and right lOFC. Thinning CT in bilateral rACC was observed in EOD patients compared to young HCs. Compared to older HCs, thicker CT in lOFC was seen in the LOD patient group. Compared with the LOD group, the EOD group showed cortical thinning of the right cACC and posterior cingulate cortex (PCC). There were no significant associations between CT in right cACC or PCC with symptom severity or illness duration.

Conclusions: MDD patients with different age at onset show distinct CT alterations, suggesting potentially divergent pathological mechanisms of EOD and LOD.
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http://dx.doi.org/10.1097/WNR.0000000000001314DOI Listing
November 2019

Reduced Interhemispheric Functional Connectivity in Obsessive-Compulsive Disorder Patients.

Front Psychiatry 2019 13;10:418. Epub 2019 Jun 13.

Department of Psychiatry, First Affiliated Hospital of Kunming Medical University, Kunming, China.

Neuroimaging studies have shown that the high synchrony of spontaneous neural activity in the homotopic regions between hemispheres is an important functional structural feature of normal human brains, and this feature is abnormal in the patients with various mental disorders. However, little is known about this feature in obsessive-compulsive disorder (OCD). This study aimed to further analyze the underlying neural mechanisms of OCD and to explore whether clinical characteristics are correlated with the alerted homotopic connectivity in patients with OCD. Using voxel-mirrored homotopic connectivity (VMHC) during resting state, we compared 46 OCD patients and 46 healthy controls (HCs) matched for age, gender, and education level. A partial correlation analysis was used to investigate the relationship between altered VMHC and clinical characteristics in patients with OCD. Patients with OCD showed lower VMHC than HCs in fusiform gyrus/inferior occipital gyrus, lingual gyrus, postcentral gyrus/precentral gyrus, putamen, and orbital frontal gyrus. A significant positive correlation was observed between altered VMHC in the angular gyrus/middle occipital gyrus and illness duration in patients. Interhemispheric functional imbalance may be an essential aspect of the pathophysiological mechanism of OCD, which is reflected not only in the cortico-striato-thalamo-cortical (CSTC) loop but also elsewhere in the brain.
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http://dx.doi.org/10.3389/fpsyt.2019.00418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6584782PMC
June 2019

Mapping Cortical and Subcortical Asymmetry in Obsessive-Compulsive Disorder: Findings From the ENIGMA Consortium.

Biol Psychiatry 2020 06 30;87(12):1022-1034. Epub 2019 Apr 30.

Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric Hospital, University of Zürich, Zürich, Switzerland; Max Planck UCL Centre for Computational Psychiatry and Ageing Research, University College London, London, United Kingdom; Wellcome Centre for Human Neuroimaging, University College London, London, United Kingdom.

Background: Lateralized dysfunction has been suggested in obsessive-compulsive disorder (OCD). However, it is currently unclear whether OCD is characterized by abnormal patterns of brain structural asymmetry. Here we carried out what is by far the largest study of brain structural asymmetry in OCD.

Methods: We studied a collection of 16 pediatric datasets (501 patients with OCD and 439 healthy control subjects), as well as 30 adult datasets (1777 patients and 1654 control subjects) from the OCD Working Group within the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Consortium. Asymmetries of the volumes of subcortical structures, and of measures of regional cortical thickness and surface areas, were assessed based on T1-weighted magnetic resonance imaging scans, using harmonized image analysis and quality control protocols. We investigated possible alterations of brain asymmetry in patients with OCD. We also explored potential associations of asymmetry with specific aspects of the disorder and medication status.

Results: In the pediatric datasets, the largest case-control differences were observed for volume asymmetry of the thalamus (more leftward; Cohen's d = 0.19) and the pallidum (less leftward; d = -0.21). Additional analyses suggested putative links between these asymmetry patterns and medication status, OCD severity, or anxiety and depression comorbidities. No significant case-control differences were found in the adult datasets.

Conclusions: The results suggest subtle changes of the average asymmetry of subcortical structures in pediatric OCD, which are not detectable in adults with the disorder. These findings may reflect altered neurodevelopmental processes in OCD.
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http://dx.doi.org/10.1016/j.biopsych.2019.04.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7094802PMC
June 2020

New methods for purification of Paralichthys olivaceus lipovitellin and immunoassay-based detection of vitellogenin.

Ecotoxicol Environ Saf 2019 Sep 24;180:624-631. Epub 2019 May 24.

College of Marine Life Sciences, Ocean University of China, Qingdao, 266003, China. Electronic address:

Increasing levels of estrogenic pollution in marine environments has made the development of reliable biological detection techniques urgently needed. In this study, Japanese flounder (Paralichthys olivaceus) lipovitellin (Lv) was purified and used to establish three immunological methods for the detection of vitellogenin (Vtg), a biomarker for environmental estrogens. Firstly, five different methods were employed to purify Lv, among which water-precipitation was the fastest and easiest way to purify Lv. Japanese flounder Lv was characterized as a phospholipoglycoprotein with a molecular weight of ∼369 kDa. Using purified Lv and its specific polyclonal antibody, a sandwich enzyme-linked immunosorbent assay (ELISA) was developed. This assay had a working range from 7.8 to 250 ng/mL and a detection limit of 3.1 ng/mL. Furthermore, we developed an immunohistochemistry (IHC) and an immunofluorescence (IF) assay, both of which allowed visual detection of liver Vtg. Finally, Vtg induction in plasma and liver of juvenile Japanese flounders exposed to 17β-ethinylestradiol (EE) was measured using these three methods. Exposure to 10 and 50 ng/L EE significantly increased plasma Vtg levels, and obvious positive fluorescence signals were observed near the liver sinusoidal vessels. These results confirmed that the methods developed effectively detected estrogenic activity of exogenous chemicals. Therefore, this study provides reliable methodologies for biomonitoring of estrogenic pollution in marine environments.
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http://dx.doi.org/10.1016/j.ecoenv.2019.04.087DOI Listing
September 2019

Tryptophan hydroxylase-2 polymorphism is associated with white matter integrity in first-episode, medication-naïve major depressive disorder patients.

Psychiatry Res Neuroimaging 2019 04 19;286:4-10. Epub 2019 Feb 19.

Department of Psychiatry, First Affiliated Hospital of Kunming Medical University, No. 295 Xichang RD, Kunming 650032, Kunming, Yunnan, China. Electronic address:

Considerable evidence suggests that the tryptophan hydroxylase-2 (TPH2) gene is associated with the pathophysiology of major depressive disorder (MDD). In the present study, we investigated alterations of white matter (WM) integrity and the impact of TPH2 polymorphism on WM in a sample of 118 first-episode, medication-naïve, MDD patients and 118 well-matched healthy controls. Whole brain analyses of fractional anisotropy (FA) were performed using tract-based spatial statistics (TBSS). The results showed that the MDD group had significantly reduced FA values for the genu and body of the corpus callosum (CC) and the bilateral anterior corona radiate (ACR). In the MDD patient group, the GG homozygote subgroup exhibited a widespread reduction of FA (uncorrected) and significantly reduced FA in the left retrolenticular portion of the internal capsule and left superior longitudinal fasciculus (SLF) compared with those of the T carriers (GT/TT) (FWE corrected). No significant correlation was found between the FA values in any brain region and the patients' clinical variables. Our findings demonstrate the presence of abnormal white matter integrity in untreated patients with first-episode depression. TPH2-rs4570625 polymorphisms may be involved in the pathological mechanism of WM microarchitecture in patients.
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http://dx.doi.org/10.1016/j.pscychresns.2019.02.002DOI Listing
April 2019

An Empirical Comparison of Meta- and Mega-Analysis With Data From the ENIGMA Obsessive-Compulsive Disorder Working Group.

Front Neuroinform 2018 8;12:102. Epub 2019 Jan 8.

Shanghai Mental Health Center Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Brain imaging communities focusing on different diseases have increasingly started to collaborate and to pool data to perform well-powered meta- and mega-analyses. Some methodologists claim that a one-stage individual-participant data (IPD) mega-analysis can be superior to a two-stage aggregated data meta-analysis, since more detailed computations can be performed in a mega-analysis. Before definitive conclusions regarding the performance of either method can be drawn, it is necessary to critically evaluate the methodology of, and results obtained by, meta- and mega-analyses. Here, we compare the inverse variance weighted random-effect meta-analysis model with a multiple linear regression mega-analysis model, as well as with a linear mixed-effects random-intercept mega-analysis model, using data from 38 cohorts including 3,665 participants of the ENIGMA-OCD consortium. We assessed the effect sizes and standard errors, and the fit of the models, to evaluate the performance of the different methods. The mega-analytical models showed lower standard errors and narrower confidence intervals than the meta-analysis. Similar standard errors and confidence intervals were found for the linear regression and linear mixed-effects random-intercept models. Moreover, the linear mixed-effects random-intercept models showed better fit indices compared to linear regression mega-analytical models. Our findings indicate that results obtained by meta- and mega-analysis differ, in favor of the latter. In multi-center studies with a moderate amount of variation between cohorts, a linear mixed-effects random-intercept mega-analytical framework appears to be the better approach to investigate structural neuroimaging data.
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http://dx.doi.org/10.3389/fninf.2018.00102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331928PMC
January 2019

A Conscious Resting State fMRI Study in SLE Patients Without Major Neuropsychiatric Manifestations.

Front Psychiatry 2018 7;9:677. Epub 2018 Dec 7.

Department of Rheumatology and Immunology, First Affiliated Hospital of Kunming Medical University, Kunming, China.

Neuropsychiatric systemic lupus erythematosus (NPSLE) is one of the main causes of death in patients with systemic lupus erythematosus (SLE). Signs and symptoms of NPSLE are heterogeneous, and it is hard to diagnose, and treat NPSLE patients in the early stage. We conducted this study to explore the possible brain activity changes using resting state functional magnetic resonance imaging (rs-fMRI) in SLE patients without major neuropsychiatric manifestations (non-NPSLE patients). We also tried to investigate the possible associations among brain activity, disease activity, depression, and anxiety. In our study, 118 non-NPSLE patients and 81 healthy controls (HC) were recruited. Rs-fMRI data were used to calculate the regional homogeneity (ReHo) in all participants. We found decreased ReHo values in the fusiform gyrus and thalamus and increased ReHo values in the parahippocampal gyrus and uncus. The disease activity was positively correlated with ReHo values of the cerebellum and negatively correlated with values in the frontal gyrus. Several brain areas showed correlations with depressive and anxiety statuses. These results suggested that abnormal brain activities might occur before NPSLE and might be the foundation of anxiety and depression symptoms. Early detection and proper treatment of brain dysfunction might prevent the progression to NPSLE. More studies are needed to understand the complicated underlying mechanisms.
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http://dx.doi.org/10.3389/fpsyt.2018.00677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6292957PMC
December 2018

Support Vector Machine Classification of Obsessive-Compulsive Disorder Based on Whole-Brain Volumetry and Diffusion Tensor Imaging.

Front Psychiatry 2018 23;9:524. Epub 2018 Oct 23.

Department of Psychiatry, First Affiliated Hospital of Kunming Medical University, Kunming, China.

Magnetic resonance imaging (MRI) methods have been used to detect cerebral anatomical distinction between obsessive-compulsive disorder (OCD) patients and healthy controls (HC). Machine learning approach allows for the possibility of discriminating patients on the individual level. However, few studies have used this automatic technique based on multiple modalities to identify potential biomarkers of OCD. High-resolution structural MRI and diffusion tensor imaging (DTI) data were acquired from 48 OCD patients and 45 well-matched HC. Gray matter volume (GMV), white matter volume (WMV), fractional anisotropy (FA), and mean diffusivity (MD) were extracted as four features were examined using support vector machine (SVM). Ten brain regions of each feature contributed most to the classification were also estimated. Using different algorithms, the classifier achieved accuracies of 72.08, 61.29, 80.65, and 77.42% for GMV, WMV, FA, and MD, respectively. The most discriminative gray matter regions that contributed to the classification were mainly distributed in the orbitofronto-striatal "affective" circuit, the dorsolateral, prefronto-striatal "executive" circuit and the cerebellum. For WMV feature and the two feature sets of DTI, the shared regions contributed the most to the discrimination mainly included the uncinate fasciculus, the cingulum in the hippocampus, corticospinal tract, as well as cerebellar peduncle. Based on whole-brain volumetry and DTI images, SVM algorithm revealed high accuracies for distinguishing OCD patients from healthy subjects at the individual level. Computer-aided method is capable of providing accurate diagnostic information and might provide a new perspective for clinical diagnosis of OCD.
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http://dx.doi.org/10.3389/fpsyt.2018.00524DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6206075PMC
October 2018

Cortical thickness and white matter integrity abnormalities in obsessive-compulsive disorder: A combined multimodal surface-based morphometry and tract-based spatial statistics study.

Depress Anxiety 2018 08 7;35(8):742-751. Epub 2018 May 7.

Department of Psychiatry, First Affiliated Hospital of Kunming Medical University, Kunming, China.

Background: Cerebral morphological abnormalities may play a key role in pathogenesis of obsessive-compulsive disorder (OCD). However, few studies have used multimodal imaging strategies to investigate alterations of cortical morphometry and white matter (WM) integrity. This study aimed to evaluate cortical thickness, cortical and subcortical volume, and WM integrity characteristics in OCD patients comprehensively.

Methods: We acquired magnetic resonance imaging (MRI) scans from 52 OCD patients and 46 well-matched healthy controls (HCs). Cortical thickness and cortical and subcortical volume were measured using the surface-based morphometry (SBM) approach. We also evaluated fractional anisotropy (FA) and mean diffusivity (MD) derived from diffusion tensor imaging (DTI) using tract-based spatial statistics (TBSS). The disease severity was evaluated by score of the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). For those brain regions exhibiting altered structure, correlations between alterations and clinical symptoms severity were analyzed in all patients and medication-naïve patients, respectively.

Results: Compared with controls, OCD patients exhibited cortical thinning in right posterior cingulate cortex (PCC), as well as significantly decreased FA values in the genu and body of corpus callosum (CC). In medication-naïve patients group, the total Y-BOCS score and obsession score were significantly negative correlated with right PCC cortical thickness.

Conclusions: OCD patients demonstrated symptom-related reduced cortical thickness structural alteration of the right PCC, and altered WM integrity in the genu and body of CC. Medication seems could alleviate the alteration of cortical thickness but not WM integrity. Combined multimodal neuroimaging methods may provide a more comprehensive perspective to clarify the pathological mechanism of OCD.
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http://dx.doi.org/10.1002/da.22758DOI Listing
August 2018

Association between abnormal serum myelin-specific protein levels and white matter integrity in first-episode and drug-naïve patients with major depressive disorder.

J Affect Disord 2018 05 16;232:61-68. Epub 2018 Feb 16.

Department of Psychiatry, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.

Background: Although the structural abnormalities of white matter (WM) have been described in patients with major depressive disorder (MDD), the neuropathological changes remain unclear. The current study aimed to investigate the myelin oligodendrocyte glycoprotein (MOG) and myelin-associated glycoprotein (MAG) levels and their correlations with WM integrity in first-episode, drug-naïve MDD patients.

Methods: We obtained diffusion tensor images of 102 first-episode, drug-naïve MDD patients and 81 age- and sex-matched controls. Serum MOG and MAG levels of all participants were measured and compared between the two groups. The correlations between WM integrity and MOG and MAG levels were examined.

Results: MOG and MAG serum levels were significantly higher in MDD patients than in controls. Patients with MDD also showed decreased fractional anisotropy (FA) and axial diffusivity in the WM of the bilateral thalamus, right hippocampus, right temporal lobe, and left pulvinar. At the whole-brain level, no regions showed any correlations of diffusivity parameters with MOG or MAG levels in healthy subjects. However, we observed two-way correlations between the MOG and MAG levels and the FA and mean diffusivity values in the WM of the left middle frontal lobe, right inferior parietal lobe, and right supplementary motor area in MDD patients.

Limitations: Further investigation with a larger sample size and longitudinal studies are required to better understand the neuropathology of WM integrity in MDD.

Conclusions: Our findings represent the first evidence of a relationship between abnormal serum myelin-specific protein levels and impaired WM integrity, which may help to better understand the neurobiological mechanisms of MDD.
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http://dx.doi.org/10.1016/j.jad.2018.02.044DOI Listing
May 2018

Clinical Factors Associated with Brain Volume Reduction in Systemic Lupus Erythematosus Patients without Major Neuropsychiatric Manifestations.

Front Psychiatry 2018 1;9. Epub 2018 Feb 1.

Department of Rheumatology and Immunology, First Affiliated Hospital of Kunming Medical University, Kunming, China.

The aim of the study was to find structural brain changes in systemic lupus erythematosus patients without major neuropsychiatric manifestations [non-neuropsychiatric systemic lupus erythematosus (non-NPSLE)] using quantitative magnetic resonance imaging (MRI) and possible associations with clinical characteristics. 89 non-NPSLE patients with normal conventional MRI and 84 healthy controls (HCs) were recruited. The whole brain gray matter volume (GMV) and white matter volume (WMV) were calculated for each individual. We found obvious GMV and WMV reduction in the systemic lupus erythematosus (SLE) group compared with HCs. Female patients showed significant reduction of GMV and WMV compared with male patients. Patients treated with immunosuppressive agents (ISA) showed less WMV reduction than those without. Cognitive impairment was the most common subclinical neuropsychiatric manifestation and had a prevalence of 46.1%. Association between WMV reduction with cognitive impairment was found. Thus, we concluded that structural brain atrophy could happen even before occurrence of obvious neuropsychiatric signs and symptoms and was associated with subclinical symptoms such as cognitive impairment. ISA treatment might have a protective effect on the brain atrophy. Early treatment might prevent the progressive damage to the brain. More studies are needed to fully understand the complicated underlying mechanisms of brain atrophy in SLE.
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http://dx.doi.org/10.3389/fpsyt.2018.00008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5799237PMC
February 2018

Cortical Abnormalities Associated With Pediatric and Adult Obsessive-Compulsive Disorder: Findings From the ENIGMA Obsessive-Compulsive Disorder Working Group.

Am J Psychiatry 2018 05 15;175(5):453-462. Epub 2017 Dec 15.

From the Department of Psychiatry and the Department of Anatomy and Neurosciences, VU University Medical Center, Amsterdam; Amsterdam Neuroscience, Amsterdam; Orygen, National Centre of Excellence in Youth Mental Health, Melbourne; the Centre for Youth Mental Health, University of Melbourne, Melbourne; the Department of Psychiatry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; the Department of Psychiatry, Bellvitge University Hospital, Bellvitge Biomedical Research Institute-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain; Centro de Investigación Biomèdica en Red de Salud Mental (CIBERSAM), Barcelona; the Department of Clinical Sciences, University of Barcelona, Barcelona; the Margaret and Wallace McCain Centre for Child, Youth, and Family Mental Health, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto; the Centre for Brain and Mental Health, Hospital for Sick Children, Toronto; the Department of Psychiatry, Yale University School of Medicine, New Haven, Conn.; the Mathison Centre for Mental Health Research and Education, Hotchkiss Brain Institute and Department of Psychiatry, Cumming School of Medicine, University of Calgary, Calgary, Canada; the Department of Psychiatry, Institute of Psychiatry, University of São Paulo School of Medicine, São Paulo, Brazil; Psychiatry and Clinical Psychobiology, Division of Neuroscience, Scientific Institute Ospedale San Raffaele, Milan, Italy; the Department of Psychology, Humboldt-Universität zu Berlin, Berlin; the Obsessive-Compulsive Disorder (OCD) Clinic, Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India; the Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric Hospital, University of Zurich, Zurich; the Magnetic Resonance Image Core Facility, IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona; the Department of Child and Adolescent Psychiatry and Psychology, Institute of Neurosciences, Hospital Clínic Universitari, Barcelona; the Department of Psychiatry, First Affiliated Hospital of Kunming Medical University, Kunming, China; the Institute of Human Behavioral Medicine, SNU-MRC, Seoul, Republic of Korea; the Laboratory of Neuropsychiatry, Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome; the Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam; the Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam; the Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles; the Department of Psychiatry, University of Michigan, Ann Arbor; the Department of Psychiatry, University of Cape Town, Cape Town, South Africa; Yeongeon Student Support Center, Seoul National University College of Medicine, Seoul, Republic of Korea; Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey; Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China; the Bascule, Academic Center for Child and Adolescent Psychiatry, Amsterdam; the Department of Child and Adolescent Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam; the Department of Psychiatry, Oxford University, Oxford, U.K.; the Department of Neuroradiology and the TUM-Neuroimaging Center (TUM-NIC), Klinikum rechts der Isar, Technische Universität München, Munich; the Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea; the Department of Brain and Cognitive Sciences, Seoul National University College of Natural Sciences, Seoul, Republic of Korea; Institut d'Investigacions Biomèdiques, August Pi i Sunyer (IDIBAPS), Barcelona; the Department of Medicine, University of Barcelona, Barcelona; the SU/UCT MRC Unit on Anxiety and Stress Disorders, Department of Psychiatry, University of Stellenbosch, Stellenbosch, South Africa; the Department of Psychiatry, Columbia University Medical College, and New York State Psychiatric Institute, New York; the Department of Clinical Neuroscience, Center for Psychiatry Research, Karolinska Institutet, Stockholm; the Mood Disorders Clinic and the Anxiety Treatment and Research Center, St. Joseph's HealthCare, Hamilton, Ontario; the Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Centro Fermi-Enrico Fermi Historical Museum of Physics and Study and Research Center, Rome; ATR Brain Information Communication Research Laboratory Group, Kyoto, Japan; the Center for Mathematics, Computing, and Cognition, Universidade Federal do ABC, Santo Andre, Brazil; the Center for OCD and Related Disorders, New York State Psychiatric Institute, New York; the Department of Psychobiology and Methodology of Health Sciences, Universitat Autònoma de Barcelona; the Beth K. and Stuart C. Yudofsky Division of Neuropsychiatry, Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston; the Clinical Neuroscience and Development Laboratory, Olin Neuropsychiatry Research Center, Hartford, Conn.; the Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York; the James J. Peters VA Medical Center, Bronx, N.Y.; the Institute of Living, Hartford Hospital, Hartford, Conn.; the Shanghai Key Laboratory of Psychotic Disorders, Shanghai, China; and the Department of Psychiatry, Seoul National University Hospital, Seoul, Republic of Korea.

Objective: Brain imaging studies of structural abnormalities in OCD have yielded inconsistent results, partly because of limited statistical power, clinical heterogeneity, and methodological differences. The authors conducted meta- and mega-analyses comprising the largest study of cortical morphometry in OCD ever undertaken.

Method: T-weighted MRI scans of 1,905 OCD patients and 1,760 healthy controls from 27 sites worldwide were processed locally using FreeSurfer to assess cortical thickness and surface area. Effect sizes for differences between patients and controls, and associations with clinical characteristics, were calculated using linear regression models controlling for age, sex, site, and intracranial volume.

Results: In adult OCD patients versus controls, we found a significantly lower surface area for the transverse temporal cortex and a thinner inferior parietal cortex. Medicated adult OCD patients also showed thinner cortices throughout the brain. In pediatric OCD patients compared with controls, we found significantly thinner inferior and superior parietal cortices, but none of the regions analyzed showed significant differences in surface area. However, medicated pediatric OCD patients had lower surface area in frontal regions. Cohen's d effect sizes varied from -0.10 to -0.33.

Conclusions: The parietal cortex was consistently implicated in both adults and children with OCD. More widespread cortical thickness abnormalities were found in medicated adult OCD patients, and more pronounced surface area deficits (mainly in frontal regions) were found in medicated pediatric OCD patients. These cortical measures represent distinct morphological features and may be differentially affected during different stages of development and illness, and possibly moderated by disease profile and medication.
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http://dx.doi.org/10.1176/appi.ajp.2017.17050485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7106947PMC
May 2018

Alternations of White Matter Structural Networks in First Episode Untreated Major Depressive Disorder with Short Duration.

Front Psychiatry 2017 25;8:205. Epub 2017 Oct 25.

Department of Medical Imaging, The First Affiliated Hospital, Kunming Medical University, Kunming, China.

It is crucial to explore the pathogenesis of major depressive disorder (MDD) at the early stage for the better diagnostic and treatment strategies. It was suggested that MDD might be involving in functional or structural alternations at the brain network level. However, at the onset of MDD, whether the whole brain white matter (WM) alterations at network level are already evident still remains unclear. In the present study, diffusion MRI scanning was adopt to depict the unique WM structural network topology across the entire brain at the early stage of MDD. Twenty-one first episode, short duration (<1 year) and drug-naïve depression patients, and 25 healthy control (HC) subjects were recruited. To construct the WM structural network, atlas-based brain regions were used for nodes, and the value of multiplying fiber number by the mean fractional anisotropy along the fiber bundles connected a pair of brain regions were used for edges. The structural network was analyzed by graph theoretic and network-based statistic methods. Pearson partial correlation analysis was also performed to evaluate their correlation with the clinical variables. Compared with HCs, the MDD patients had a significant decrease in the small-worldness (σ). Meanwhile, the MDD patients presented a significantly decreased subnetwork, which mainly involved in the frontal-subcortical and limbic regions. Our results suggested that the abnormal structural network of the orbitofrontal cortex and thalamus, involving the imbalance with the limbic system, might be a key pathology in early stage drug-naive depression. And the structural network analysis might be potential in early detection and diagnosis of MDD.
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http://dx.doi.org/10.3389/fpsyt.2017.00205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5661170PMC
October 2017

Identify changes of brain regional homogeneity in early and later adult onset patients with first-episode depression using resting-state fMRI.

PLoS One 2017 14;12(9):e0184712. Epub 2017 Sep 14.

Department of Psychiatry, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.

Objective: Previous work exhibited different brain grey matter volume (GMV) changes between patients with early adult onset depression (EOD, age 18-29) and later adult onset depression (LOD, age 30-44) by using 30-year-old as the cut-off age. To identify whether regional homogeneity (ReHo) changes are also different between EOD and LOD by using same cut-off age, we used resting-state functional magnetic resonance imaging (fMRI) to detect the abnormal ReHo between patients with EOD and LOD in the present study.

Methods: Resting-state fMRI scans of 58 patients with EOD, 62 patients with LOD, 60 young healthy controls (HC), and 52 old HC were obtained. The ReHo approach was used to analyze the images.

Results: The ANOVA analysis revealed that the ReHo values in the frontoparietal, occipital, and cerebellar regions were significantly different among the four groups. Relative to patients with LOD, patients with EOD displayed significantly increased ReHo in the left precuneus, and decreased ReHo in the right fusiform. The ReHo values in the left precuneus and the right fusiform had no significant correlation with the score of the depression rating scale or illness duration in both patient subgroups. Compared to young HC, patients with EOD showed significantly increased ReHo in the right frontoparietal regions and the right calcarine. Furthermore, the increased ReHo in the right frontoparietal regions, right insula and left hippocampus, and decreased ReHo in the left inferior occipital gyrus, right middle occipital gyrus, left calcarine, and left supplementary motor area were observed in patients with LOD when compared to old HC.

Conclusions: The ReHo of brain areas that were related to mood regulation was changed in the first-episode, drug-naive adult patients with MDD. Adult patients with EOD and LOD exhibited different ReHo abnormalities relative to each age-matched comparison group, suggesting that depressed adult patients with different age-onset might have different pathological mechanism.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0184712PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5598991PMC
October 2017