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Recently, graph theoretical approaches applied to neuroimaging data have advanced understanding of the human brain connectome and its abnormalities in psychiatric disorders. However, little is known about the topological organization of brain white matter networks in posttraumatic stress disorder (PTSD). Seventy‐six patients with PTSD and 76 age, gender, and years of education‐matched trauma‐exposed controls were studied after the 2008 Sichuan earthquake using diffusion tensor imaging and graph theoretical approaches. Topological properties of brain networks including global and nodal measurements and modularity were analyzed. At the global level, patients showed lower clustering coefficient (p = .016) and normalized characteristic path length (p = .035) compared with controls. At the nodal level, increased nodal centralities in left middle frontal gyrus, superior and inferior temporal gyrus and right inferior occipital gyrus were observed (p

Gang Wang,1 Tian-Mei Si,2 Lingjiang Li3,4Yiru Fang,5 Chun-Xue Wang,6 Li-Na Wang,7 Kristin Hui Xian Tan,8 Anders Ettrup,9 Hanne-Lise Falgreen Eriksen,9 Si Luo,10 Lan Ge101Beijing An Ding Hospital, Capital Medical University, China National Clinical Research Center for Mental Disorders, Beijing, People’s Republic of China; 2Peking University Sixth Hospital & Peking University Institute of Mental Health, Beijing, 100191, People’s Republic of China; 3Key Laboratory of Mental Health, Ministry of Health (Peking University) &National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, 100191, People’s Republic of China; 4The Second Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 5Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 6Beijing Tian Tan Hospital, Department of Neuropsychiatry and Behavioral Neurology, Capital Medical University, National Clinical Research Center for Neurological Disease, Beijing, People’s Republic of China; 7Tianjin Anding Hospital, Tianjin, People’s Republic of China; 8Lundbeck Singapore Pte Ltd, Singapore; 9H. Lundbeck A/S, Valby, Denmark; 10Lundbeck China, Beijing, People’s Republic of ChinaObjective: Cognitive symptoms in major depressive disorder (MDD) are common and may negatively impact clinical and functional outcomes. The Prospective Research Observation to Assess Cognition in Treated patients with MDD (PROACT) study aimed to assess the prevalence and course of cognitive symptoms, and their associations with clinical and functional outcomes during 6 months of antidepressant treatment, in a real-world setting among Chinese patients with MDD.Patients and methods: Outpatients (n=598) aged 18–65 years with MDD and a total score ≥17 on the Hamilton Depression Rating Scale – 17 Items (HAM-D17) were observed over 6 months after initiating new antidepressant monotherapy, with follow-up visits at months 1, 2, and 6. Cognitive symptoms were assessed using the Perceived Deficits Questionnaire – Depression (PDQ-D) and cognitive performance using the Digit Symbol Substitution Test (DSST).Results: At baseline, 76.9% of patients had indications of cognitive symptoms (PDQ-D total score ≥21); at month 6, this was reduced, but still present in 32.4%. Across the 6-month study period, patients improved across cognitive, clinical and functional assessments. High levels of cognitive symptoms (PDQ-D) consistently predicted worse clinical outcomes, ie, lower odds for remission and increased odds for relapse, as well as worse patient-reported functional outcomes and lower quality of life. In contrast, cognitive performance (DSST) predicted performance-based functioning but only a few patient-reported functional outcomes (absenteeism and quality of life), and no clinical outcomes. PDQ-D and DSST scores were uncorrelated at baseline.Conclusion: The study highlights the importance of assessing and targeting cognitive symptoms for increasing patients’ chances of recovery and restoring functioning in the treatment of MDD. The results further highlight the relevance of complementary assessment methods to fully capture aspects of cognitive symptoms in patients with depression.Keywords: MDD, antidepressants, cognitive performance, real-world evidence, PDQ-D, DSST

Antipsychotic-induced metabolic disturbance (AIMD) is a common adverse effect of antipsychotics with genetics partly underpinning variation in susceptibility among schizophrenia patients. Melanocortin4 receptor (MC4R) gene, one of the candidate genes for AIMD, has been under-studied in the Chinese patients. We conducted a pharmacogenetic study in a large cohort of Chinese patients with schizophrenia. In this study, we investigated the genetic variation of MC4R in Chinese population by genotyping two SNPs (rs489693 and rs17782313) in 1,991 Chinese patients and examined association of these variants with the metabolic effects that were often observed to be related to AIMD. Metabolic measures, including body mass index (BMI), waist circumference (WC), glucose, triglyceride, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) levels were assessed at baseline and after 6-week antipsychotic treatment. We found that interaction of SNP×medication status (drug-naïve/medicated) was significantly associated with BMI, WC, and HDL change %, respectively. Both SNPs were significantly associated with baseline BMI and WC in the medicated group. Moderate association of rs489693 with WC, Triglyceride, and HDL change % were observed in the whole sample. In the drug-naïve group, we found recessive effects of rs489693 on BMI gain more than 7%, WC and Triglyceride change %, with AA incurring more metabolic adverse effects. In conclusion, the association between rs489693 and the metabolic measures is ubiquitous but moderate. Rs17782313 is less involved in AIMD. Two SNPs confer risk of AIMD to patients treated with different antipsychotics in a similar way.

BackgroundThe prevention of COVID-19 pandemic is highly complicated by the prevalence of asymptomatic and recurrent infection. Many previous immunological studies have focused on symptomatic and convalescent patients, while the immune responses in asymptomatic patients and re-detectable positive cases remain unclear.MethodsHere we comprehensively analyzed the peripheral T-cell receptor (TCR) repertoire of 54 COVID-19 patients in different phases, including asymptomatic, symptomatic, convalescent and re-detectable positive cases.ResultsWe found progressed immune responses from asymptomatic to symptomatic phase. Furthermore, the TCR profiles of re-detectable positive cases were highly similar to those of asymptomatic patients, which could predict the risk of recurrent infection.ConclusionTherefore, TCR repertoire surveillance has the potential to strengthen the clinical management and the immunotherapy development for COVID-19.FundingThe Science and Technology Innovation Project of Foshan Municipality (2020001000431) and the National Key Research and Development Project (2020YFA0708001).

Malaria is a fatal disease that presents clinically as a continuum of symptoms and severity, which are determined by complex host-parasite interactions. Clearance of infection is believed to be accomplished by the spleen and mononuclear phagocytic system (MPS), both in the presence and absence of artemisinin treatment. The spleen filters infected RBCs from circulation through immune-mediated recognition of the infected RBCs followed by phagocytosis. Using different strains of mice infected with P. berghei K173 (PbK173), the mechanisms leading to splenomegaly, histopathology, splenocyte activation and proliferation, and their relationship to control of parasitemia and host mortality were examined. Survival time of mice infected with PbK173 varied, although the infection was uniformly lethal. Mice of the C57BL/6 strain were the most resistant, while mice of the strain ICR were the most susceptible. BALB/c and KM mice were intermediate. In the course of PbK173 infection, both strains of mice experienced significant splenomegaly. Parasites were observed in the red pulp at 3 days post infection in all animals. All spleens retained late trophozoite stages as well as a fraction of earlier ring-stage parasites. The percentages of macrophages in infected C57BL/6 and KM mice were higher than uninfected mice on 8 dpi. Spleens of infected ICR and KM mice exhibited structural disorganization and remodeling. Furthermore, parasitemia was significantly higher in KM versus C57BL/6 mice at 8 dpi. The percentages of macrophages in ICR infected mice were lower than uninfected mice, and the parasitemia was higher than other strains. The results presented here demonstrate the rate of splenic mechanical filtration and the splenic macrophages likely contribute to an individual’s total parasite burden. This in turn can influence the pathogenesis of malaria. Finally, different genetic backgrounds of mice have different splenic mechanisms for controlling malaria infection.

Background: In China, depressive disorders have been estimated to be the second leading cause of years lived with disability (YLDs). However, nationally representative epidemiological data for depressive disorders, in particular depressed adults’ mental health services use, are still unavailable in China. The present study is a part of the Chinese National Mental Health Survey (CMHS), 2012–15, which reported the prevalence, treatment, and associated disability of depressive disorders in the Chinese general population. Methods: The CMHS recruited a representative sample of 28140 Chinese residents (≥ 18 years) by using multistage proportional-to-population-size sampling method. Trained investigators interviewed participants with the Composite International Diagnostic Interview 3.0 to ascertain the presence of lifetime and 12-month depressive disorders according to DSM-IV criteria, including major depressive disorder (MDD), dysthymic disorder (DD), and depressive disorder not otherwise specified (DD-NOS). Participants with 12-month depressive disorders were asked whether they ever received any 12-month treatment for their emotional problems and the specific types of treatment providers. The Quick Inventory of Depressive Symptomatology and Sheehan Disability Scale (SDS) were used to evaluate the severity of and role impairments associated with 12-month depressive symptoms. Findings: The weighted lifetime and 12-month prevalence rates of any depressive disorder were 6.8% (95%CI: 5.8-7.8%) and 3.6% (95%CI: 3.0-4.2%), respectively; the corresponding figures were 3.4% (95%CI: 2.0-3.9%) and 2.1% (95%CI: 1.8-2.4%) for MDD, 1.4% (95%CI: 1.1-1.7%) and 1.0% (95%CI: 0.8-1.3%) for DD, and 3.2% (95%CI: 2.6-3.9%) and 1.4% (95%CI: 1.1-1.7%) for DD-NOS. Overall, 77.2% of persons with 12-month depressive disorders had role impairment of any SDS domain: 82.2% for MDD, 81.5% for DD, and 64.6% for DD-NOS. Depressed participants reported an average of 41.0 days out of role in the past year due to depression; the corresponding figures were 49.7 days for MDD, 54.9 days for DD, and 12.2 days for DD-NOS. In total, 88.9% of individuals with 12-month depressive disorders had clinically significant depressive symptoms: 93.7% for MDD, 91.7% for DD, and 77.5% for DD-NOS. MDD and DD had similar proportions of “severe” or “very severe” depressive symptoms (43.0% and 42.1%), which were higher than DD-NOS (13.9%). 9.5% of participants with 12-month depressive disorders were treated in any treatment sector: 3.6% in the specialty mental health (SMH), 1.5% in the general medical (GM), 0.3% in the human services (HS), and 3.3% in the complementary-alternative medical (CAM) sector. Respondents with MDD and DYS had the highest proportion of seeking treatment in SMH sector (4.7% and 3.0%) while those with DD-NOS had the highest proportion of seeking treatment in CAM sector (most treatments were Traditional Chinese Medicine) (3.3%). Only 0.5% of participants with depressive disorders were treated adequately. Rates of treatment adequacy of MDD and DYS in SMH sector were 9.2% and 2.4%, respectively. Both rates in GM sector were 0%. Interpretation: Compared to western countries, our data show a relatively low prevalence of depressive disorders in China. Nevertheless, their associated role impairments, symptom severities, and disabilities are severe. Importantly, the treatment rates are rather low, let alone adequate treatment. Nationwide programs aiming at removing barriers in availability, accessibility, and acceptability to mental healthcare are needed in China. Funding: The study was funded by the Special Research Project for Non-profit Public Service of the Chinese Ministry of Health (grant number 201202022), the National Twelfth Five-Year Plan for Science and Technology Support of the Chinese Ministry of Science and Technology (grant numbers 2012BAI01B01 & 2015BAI13B00) and the National Key R&D Program of China (grant numbers 2017YFC0907800, 2017YFC0907801). Declaration of Interests: The authors have no conflicts of interest to declare Ethical Approval: The study protocol of CMHS was approved by the Ethics Committee of the Sixth Hospital of Peking University (No.: IMH-IRB-2013-13-1).

This study sought to assess the differences in mental health conditions among the general population, quarantined population and healthcare workers during the COVID-19 outbreak in China. An online rapid assessment captured depressive and anxiety symptoms, and sleep quality data. A total of 2689 participants (n=374 general population, n=403 healthcare workers, n=1912 quarantined population) were included in the final statistical analysis. The proportion of individuals with mild and/or serious depression and anxiety were higher in the general population when compared to the quarantined population and healthcare workers (58.6% vs. 25.1%vs. 48.6%, P

Background: Cognitive deficits have shown progressive feature in major depressive disorder (MDD). However, it remains unknown which component of cognitive function is progressively impaired across episodes of MDD. Here we aim to identify the progressively impaired cognitive components in patients with MDD.Methods: A comprehensive neurocognitive test battery was used to assess the cognitive components (executive function, attention, processing speed, memory, working memory, inhibition, shifting, and verbal fluency) in 35 patients with first-episode MDD (FED), 60 patients with recurrent MDD (RD) and 111 matched healthy controls (HCs). After 6 months of treatment with antidepressant, 20 FED and 36 RD patients achieved clinical remission and completed their second-time neurocognitive tests. Statistical analyses were conducted to identify the impaired cognitive components in the FED and RD groups before and after treatment, and to assess the relationship between the cognitive components and the number of episodes and total illness duration in the MDD patient group.Results: At baseline, both the FED and RD groups showed impairments in all of the cognitive components; the FED and RD groups showed no significant difference in all of the components except for shifting. After remission, only shifting in the RD group showed no significant improvement and remained in an impaired status. Furthermore, shifting was the only component negatively correlated with the number of episodes as well as the total illness duration.Conclusions: Shifting may serve as the progressive cognitive deficit across episodes of MDD.Clinical Trials Registration: Registry name: HPA function and MRI study of trauma-related depression; Registration number: ChiCTR1800014591; URL: http://www.chictr.org.cn/edit.aspx?pid=24669&htm=4.

BackgroundPatients with major depressive disorder (MDD) exhibit concurrent deficits in sensory processing and high-order cognitive functions such as self-awareness and rumination. Connectome mapping studies have suggested a principal primary-to-transmodal gradient in functional brain networks, supporting the spectrum from sensation to cognition. However, whether this principal connectome gradient is disrupted in patients with MDD and how this disruption is associated with gene expression profiles remain unclear.MethodsUsing a large cohort of resting-state functional magnetic resonance imaging data from 2,234 participants (1,150 patients with MDD and 1,084 healthy controls) recruited at 10 sites, we investigated MDD-related alterations in the principal connectome gradient. We further used Neurosynth and postmortem gene expression data to assess the cognitive functions and transcriptional profiles related to the gradient alterations in MDD, respectively.ResultsRelative to controls, patients with MDD exhibited abnormal global topography of the principal primary-to-transmodal gradient, as indicated by reduced explanation ratio, gradient range, and gradient variation (Cohen’sd= −0.16∼-0.21). Focal alterations of gradient scores were mostly in the primary systems involved in sensory processing and in the transmodal systems implicated in high-order cognition. The transcriptional profiles explained 53.9% of the spatial variance in the altered gradient patterns, with the most correlated genes enriched in transsynaptic signaling and calcium ion binding.ConclusionsThese results highlight the dysfunction of the core connectome hierarchy in MDD and its linkage with gene expression profiles, providing insights into the neurobiological and molecular genetic underpinnings of sensory-cognitive deficits in this disorder.

Background Understanding the patterns of treatment response is critical for the treatment of patients with schizophrenia; one way to achieve this is through using a longitudinal dynamic process study design. Aims This study aims to explore the response trajectory of antipsychotics and compare the treatment responses of seven different antipsychotics over 6 weeks in patients with schizoprenia (trial registration: Chinese Clinical Trials Registry Identifier: ChiCTR-TRC-10000934). Method Data were collected from a multicentre, randomised open-label clinical trial. Patients were evaluated with the Positive and Negative Syndrome Scale (PANSS) at baseline and follow-up at weeks 2, 4 and 6. Trajectory groups were classified by the method of k-means cluster modelling for longitudinal data. Trajectory analyses were also employed for the seven antipsychotic groups. Results The early treatment response trajectories were classified into a high-trajectory group of better responders and a low-trajectory group of worse responders. The results of trajectory analysis showed differences compared with the classification method characterised by a 50% reduction in PANSS scores at week 6. A total of 349 patients were inconsistently grouped by the two methods, with a significant difference in the composition ratio of treatment response groups using these two methods (χ2 = 43.37, P < 0.001). There was no differential contribution of high- and low trajectories to different drugs (χ2 = 12.52, P = 0.051); olanzapine and risperidone, which had a larger proportion in the >50% reduction at week 6, performed better than aripiprazole, quetiapine, ziprasidone and perphenazine. Conclusions The trajectory analysis of treatment response to schizophrenia revealed two distinct trajectories. Comparing the treatment responses to different antipsychotics through longitudinal analysis may offer a new perspective for evaluating antipsychotics.

Background Persistent neurocognitive deficits are often associated with poor outcomes of major depressive disorder (MDD). Executive dysfunction is the most common cognitive deficit in MDD. However, it remains unclear which subcomponent of executive dysfunction is state-independent with distinct neural substrates. Methods A comprehensive neurocognitive test battery was used to assess four subcomponents of executive function (working memory, inhibition, shifting, and verbal fluency) in 95 MDD patients and 111 matched healthy controls (HCs). After 6 months of paroxetine treatment, 56 patients achieved clinical remission (rMDD) and completed the second-time neurocognitive test. Network-based statistics analysis was utilized to explore the changes in functional connectivity (FC). Results Compared with the HCs, all the four subcomponents of MDD patients were significantly impaired. After treatment, there was a significant improvement in working memory, inhibition, and verbal fluency in the rMDD group. And shifting and verbal fluency of the rMDD group remained impaired compared with the HCs. Fifteen functional connections were interrupted in the MDD group, and 11 connections remained in a disrupted state after treatment. Importantly, verbal fluency was negatively correlated with the disrupted FC between the right dorsal prefrontal cortex and the left inferior parietal lobule in patients with MDD and remitted MDD. Limitations The correlation analysis of the association between cognitive impairment and connectivity alterations precluded us from making causal inferences. Conclusions Verbal fluency is the potential state-independent cognitive deficit with distinct neural basis in patients with MDD.

The continued spread of the coronavirus disease 2019 (COVID-19) has a serious impact on everyone across the globe, both physically and psychologically. In addition to proactive measures addressing physical survival needs and health protection, China has launched a mental health support system to cope with the widespread psychological stress during the pandemic and its aftermath. In this debate, the authors attempted to depict and reflect upon the overall framework of China’s mental health support, with particular reference to the psychological intervention in response to COVID-19 over the last few months. Although a lot of effort has been made to meet the mental health needs, the accessibility, acceptability and effectiveness of the support system still have much room for improvement. Therefore, it is very important to re-think the predicament and challenge on ways of enhancing public mental health emergency responses in China. The concepts of universality, timeliness and scientific rigour were proposed as a possible reform in preparation for large-scale natural or man-made disasters in the coming future.

Major depressive disorder (MDD) is a main type of mood disorder, characterized by significant and lasting depressed mood. Until now, the pathogenesis of MDD is not clear, but it is certain that biological, psychological, and social factors are involved. Childhood trauma is considered to be an important factor in the development of this disease. Previous studies have found that nearly half of the patients with MDD have experienced childhood trauma, and different types of childhood trauma, gender, and age show different effects on this disease. In addition, the clinical characteristics of MDD patients with childhood trauma are also different, which often have more severe depressive symptoms, higher risk of suicide, and more severe cognitive impairment. The response to antidepressants is also worse. In terms of biological mechanisms and marker characteristics, the serotonin transporter gene and the FKBP prolyl isomerase 5 have been shown to play an important role in MDD and childhood trauma. Moreover, some brain imaging and biomarkers showed specific features, such as changes in gray matter in the dorsal lateral prefrontal cortex, and abnormal changes in hypothalamic-pituitary-adrenal axis function.抑郁症又称抑郁障碍，以显著而持久的心境低落为主要临床特征，是心境障碍的主要类型。目前，抑郁症的病因并不非常清楚，但可以肯定的是，生物、心理与社会环境诸多因素参与了抑郁症的发病过程。其中童年创伤被认为是影响抑郁症发生和发展的一个重要因素。既往研究发现近一半的抑郁症患者曾经历过童年创伤，不同类型的童年创伤、性别、年龄对抑郁症的影响也不同。此外，伴童年创伤的抑郁症患者的临床特点也不同，抑郁症状往往更严重，自杀风险更高，认知受损程度更严重，对抗抑郁药物的治疗应答也更差。在生物学机制和标志物方面，5-羟色胺转运体基因和FKBP前体异构酶5已被证实在抑郁症与童年创伤相互作用中发挥了重要作用。此外，在伴童年创伤抑郁症患者的脑影像学和生物特征上亦有一些特异性的改变，如背外侧前额叶皮层的灰质改变，异常亢进的下丘脑-垂体-肾上腺轴功能改变。.

Major depressive disorder (MDD) is a prevailing chronic mental disorder with lifetime recurring episodes. Recurrent depression (RD) has been reported to be associated with greater severity of depression, higher relapse rate and prominent functioning impairments than first-episode depression (FED), suggesting the progressive nature of depression. However, there is still little evidence regarding brain functional connectome. In this study, 95 medication-free MDD patients (35 with FED and 60 with RD) and 111 matched healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (fMRI) scanning. After six months of treatment with paroxetine, 56 patients achieved clinical remission and finished their second scan. Network-based statistics analysis was used to explore the changes in functional connectivity. The results revealed that, compared with HCs, patients with FED exhibited hypoconnectivity in the somatomotor, default mode and dorsal attention networks, and RD exhibited hyperconnectivity in the somatomotor, salience, executive control, default mode and dorsal attention networks, as well as within and between salience and executive control networks. Moreover, the disrupted components in patients with current MDD did not change significantly when the patients achieved remission after treatment, and sub-hyperconnectivity and sub-hypoconnectivity were still found in those with remitted RD. Additionally, the hypoconnectivity in FED and hyperconnectivity in RD were associated with the number of episodes and total illness duration. This study provides initial evidence supporting that impairment of intrinsic functional connectivity across the course of depression is a progressive process.

The hippocampus, a key structure with distinct subfield functions, is strongly implicated in the pathophysiology of post-traumatic stress disorder (PTSD); however, few studies of hippocampus subfields in PTSD have focused on pediatric patients. We therefore investigated the hippocampal subfield volume using an automated segmentation method and explored the subfield-centered functional connectivity aberrations related to the anatomical changes, in a homogenous population of traumatized children with and without PTSD. To investigate the potential diagnostic value in individual patients, we used a machine learning approach to identify features with significant discriminative power for diagnosis of PTSD using random forest classifiers. Compared to controls, we found significant mean volume reductions of 8.4% and 9.7% in the right presubiculum and hippocampal tail in patients, respectively. These two subfields’ volumes were the most significant contributors to group discrimination, with a mean classification accuracy of 69% and a specificity of 81%. These anatomical alterations, along with the altered functional connectivity between (pre)subiculum and inferior frontal gyrus, may underlie deficits in fear circuitry leading to dysfunction of fear extinction and episodic memory, causally important in post-traumatic symptoms such as hypervigilance and re-experience. For the first time, we suggest that hippocampal subfield volumes might be useful in discriminating traumatized children with and without PTSD.

Convergent studies have highlighted the amygdala-based and dorsal anterior cingulate cortex (dACC)-based circuit or network dysfunction in post-traumatic stress disorder (PTSD). However, previous studies are often complicated by various traumatic types, psychiatric comorbidities, chronic illness duration, and medication effect on brain function. Besides, little is known whether the functional integration with amygdala-dACC interaction disrupted or not in PTSD. Here, we investigated effective connectivity (EC) between the amygdala-dACC and rest of the cortex by applying psycho-physiological interaction (PPI) approach to resting-state functional magnetic resonance imaging data of 63 drug-naive PTSD patients and 74 matched trauma-exposed non-PTSD controls. Pearson correlation analysis was performed between EC values extracted from regions with between-group difference and clinical profiles in PTSD patients. We observed distinct amygdala-dACC interaction pattern between PTSD group and the control group, which is composed primarily by positive EC in the former and negative in the latter. In addition, compared with non-PTSD controls, PTSD patients showed increased EC between amygdala-dACC and the prefrontal cortex, left inferior parietal lobule, and bilateral ventral occipital cortex, and decreased EC between amygdala-dACC and the left fusiform gyrus. The EC increase between amygdala-dACC and the right middle frontal gyrus was negatively correlated with the clinician-administered PTSD scale scores in PTSD patients. Aberrent communication between amgydala-dACC and brain regions involved in central executive network and visual systems might be associated with the pathophysiology of PTSD. Further, these findings suggested that dysconnectivity of the amygdala and dACC could be adapted as a relatively early course diagnostic biomarker of PTSD.

ObjectiveThe coronavirus disease 2019 (COVID-19) – a novel and highly infectious pneumonia – has now spread across China and beyond for over four months. However, its psychological impact on patients is unclear. We aim to examine the prevalence and associated risk factors for psychological morbidities and fatigue in patients with confirmed COVID-19 infection.MethodsAmidst the disease outbreak, 41 out of 105 COVID-19 patients in a local designated hospital in China were successfully assessed using a constellation of psychometric questionnaires to determine their psychological morbidities and fatigue. Several potential biopsychosocial risk factors (including pre-existing disabilities, CT severity score of pneumonia, social support, coping strategies) were assessed through multivariable logistic regression analyses to clarify their association with mental health in patients.Results43.9% of 41 patients presented with impaired general mental health, 12.2% had post-traumatic stress disorder (PTSD) symptoms, 26.8% had anxiety and/or depression symptoms, and 53.6% had fatigue. We did not find any association between pneumonia severity and psychological morbidities or fatigue in COVID-19 patients. However, high perceived stigmatization was associated with an increased risk of impaired general mental health and high perceived social support was associated with decreased risk. Besides, negative coping inclination was associated with an increased risk of PTSD symptoms; high perceived social support was associated with a decreased risk of anxiety and/or depression symptoms.ConclusionsPsychological morbidities and chronic fatigue are common among COVID-19 patients. Negative coping inclination and being stigmatized are primary risk factors while perceived social support is the main protective factor.

BackgroundThis study proposed a computational method to detect the cancer areas and calculate the tumor proportion score (TPS) of PD-L1 immunohistochemistry (IHC) expression for lung adenocarcinoma based on deep learning and transfer learning.Patients and methodsPD-L1 22C3 and SP142 IHC slides of lung adenocarcinoma samples on digitized whole-slide images (WSI) database were employed. We build a deep convolutional neural network (DCNN) to automatically segment cancer regions. TPS was calculated based on segmented areas and then compared with the interpretations of pathologists.ResultsWe trained a DCNN model based on 22C3 dataset and fine-tuned it with SP142 dataset. We obtain a robust performance on cancer region detection on both datasets, with a sensitivity of 93.36% (22C3) and 92.80% (SP142) and a specificity of 93.97% (22C3) and 89.25% (SP142). With all the coefficient of determinations larger than 0.9 and Fleiss’ and Cohen’s Kappa larger than 0.8 (between mean or median of pathologists and TPS calculated by our method), we also found out the strong correlation between the TPS estimated by our computational method and estimation from multiple pathologists’ interpretations of 22C3 and SP142 respectively.ConclusionWe provide an AI method to efficiently predict cancer region and calculate TPS in PD-L1 IHC slide of lung adenocarcinoma on two different antibodies. It demonstrates the potential of using deep learning methods to conveniently access PD-L1 IHC status. In the future, we will further validate the AI tool for automated scoring PD-L1 in large volume samples.

Background Previous studies have suggested that individuals with generalized anxiety disorder (GAD) would show inefficient whole-brain communication and dysconnectivity in the fronto-parietal-subcortical sub-networks in the white matter (WM) structural network. However, these hypotheses have yet to be tested. Methods Individual WM structural networks were constructed based on diffusion MRI data and deterministic tractography in 34 first-episode, medication-naive adolescents with GAD and 27 healthy controls (HCs). Graph theory was applied to investigate the topological organization alterations of the structural network. Results GAD patients showed disrupted small-world configurations (i.e., increased path length and decreased clustering coefficient) and hub organization (i.e., less connection strength in the feeder and local connections). A decreased connection strength was found in a GAD-related sub-network (mainly involving the frontal-subcortical circuits), which was able to distinguish GAD patients from HCs with higher accuracy (area under the curve of 0.96, sensitivity of 94%, specificity of 89%) than clinical scores and other topological alternations. Limitations The current study just compared GAD patients with HCs based on a small sample, leaving whether the alternations found here are specific to GAD still an open question. Future studies are recommended to recruit patients with other anxiety disorders (e.g., social anxiety disorder) and/or comorbid mood disorders to identify the GAD-specific WM alterations using a larger sample. Conclusions Our findings highlight the disruption of the topological organization of the whole-brain WM structural network (especially the frontal-subcortical circuits) in GAD, and suggest the potential of using structural connectivity of the GAD-related sub-network as a biomarker for GAD patients.

To compare longitudinal metabolic effects of 7 antipsychotics, including body mass index (BMI), waist circumference (WC), blood pressure (BP), glucose, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C); to investigate risk factors for metabolic syndrome (MetS); and to make recommendations on frequency and timing of monitoring metabolic measurements.This randomized, open-label, pharmacologic trial was conducted among patients with schizophrenia (DSM-IV) in 32 hospitals across China. Patients were randomly assigned to 7 groups and assessed at baseline, 2, 4, and 6 weeks. Linear mixed-effect models were used to assess changes of metabolic measures over time. Multivariable logistic regression analysis was performed to investigate the risk factors for MetS.In total, 2,550 (718 drug-naïve) of 2,774 patients finished the study between July 6, 2010, and November 30, 2011. We found significant (P.05) changes for BMI, WC, TG, and LDL-C, with TG and LDL-C reaching a plateau. Interactions between baseline metabolic condition and changes over time were observed for BMI (χ² = 43.11, P.001), WC (χ² = 36.34, P.001), systolic BP (χ² = 11.92, P = .002), glucose (χ² = 6.09, P = .01), and TG (χ² = 6.01, P = .01). Antipsychotics generally had greater adverse effects on patients who were initially screened as metabolically normal. After controlling for other associated factors, we found that antipsychotics resulted in differing risk for incident MetS, with a similar pattern to findings in other populations: olanzapine (odds ratio [OR] = 3.36, P.001)quetiapine (OR = 3.29, P.001)perphenazine (OR = 2.73, P = .007)risperidone (OR = 2.21, P = .02)aripiprazole (OR = 1.74, P = .15) ≈ haloperidol (OR = 1.75, P = .22) ≈ ziprasidone (OR = 1, reference).Metabolic traits should be monitored frequently in early stages of antipsychotic treatment due to rapid and substantial changes. Clinicians should not assume low risk for patients with normal metabolic parameters at baseline.Chinese Clinical Trial Registry identifier: ChiCTR-TRC-10000934.

The stress-related gene FKBP5 has been related to dysregulated glucocorticoid receptor (GR) signaling, showing increased GR sensitivity in trauma-exposed subjects with post-traumatic stress disorder (PTSD) but not in those without PTSD. However, the neural mechanism underlying the effects of FKBP5 remains poorly understood. Two hundred and thirty-seven Han Chinese adults who had lost their only child were included. Four FKBP5 single nucleotide polymorphisms (rs3800373, rs9296158, rs1360780, and rs9470080) were genotyped. All 179 participants were successfully divided into three FKBP5 diplotype subgroups according to two major FKBP5 H1 and H2 yin yang haplotypes. Brain average spectral power was compared using a two-way (PTSD diagnosis and FKBP5 diplotypes) analysis of covariance within four separate frequency bands (slow-5, slow-4, slow-3, and slow-2). Adults with PTSD showed lower spectral power in bilateral parietal lobules in slow-4 and in left inferior frontal gyrus (IFG) in slow-5. There was significant FKBP5 diplotype main effect in anterior cingulate cortex (ACC) in slow-4 (H1/H1 higher than other two subgroups), and in precentral/postcentral gyri and middle cingulate cortex (MCC) in slow-3 (H2/H2 higher than other two subgroups). Also, there was a significant diagnosis × FKBP5 diplotype interaction effect in right parietal lobule in slow-3. These findings suggest that adults with PTSD have lower low-frequency power in executive control network regions. Lower power in ACC and greater power in the motor/sensory areas in FKBP5 high-risk diplotype group suggest a disturbance of emotional processing and hypervigilance/sensitization to threatening stimuli. The interaction effect of diagnosis × FKBP5 in parietal lobule may contribute to PTSD development.

Background: Neither the abundance of the exo/endoglucanase GH modules nor the taxonomy affiliation is informative enough in inferring whether a genome is of a potential cellulolytic microbe or not. By interpreting the complete genomes of 2642 microbe strains whose phenotypes have been well documented, we are trying to reveal a more reliable genotype and phenotype correlation on the specific function niche of cellulose hydrolysis.Results: By incorporating into the annotation approach an automatic recognition of the potential synergy machineries, a more reliable prediction on the corresponding microbes’ cellulolytic competency could be achieved. The potential cellulose hydrolyzing microbes could be categorized into 5 groups according to the varying synergy machineries among the carbohydrate active modules/genes annotated. Results of the analysis on the 2642 genomes revealed that some cellulosome gene clusters were in lack of the surface layer homology module (SLH) and microbe strains annotated with such cellulosome gene clusters were not certainly cellulolytic. Hypothesized in this study was that cellulosome-independent genes harboring both the SLH module (mediate the attachment of the enzymes to the host microbe’s cell surface) and the cellulose-binding carbohydrate binding module (mediate the attachment of the enzymes to the cellulose substrate) were likely an alternative gene apparatus initiating the formation of the cellulose-enzyme-microbe (CEM) complexes; and their role is important especially for the cellulolytic anaerobes without cellulosome gene clusters. Conclusions: In the genome-centric prediction on the corresponding microbes’ cellulolytic activity, recognition of the synergy machineries that include but are not limited to the cellulosome gene clusters is equally important as the annotation of the individual carbohydrate active modules or genes. This is the first time that a pipeline was developed for an automatic recognition of the synergy among the carbohydrate active units annotated. With promising resolution and reliability, this pipeline should be a good add to the bioinformatic tools for the genome-centric interpretations on the specific function niche of cellulose hydrolysis.

The aim of the study was to explore the tendency of modified electroconvulsive therapy (MECT)-related working memory and subjective memory deficits in depressed patients.Sixty patients with unipolar/bipolar depression were prepared and enrolled for MECT and 56 subjects were enrolled as healthy controls (HCs). Their demographics (sex, age, body mass index, years of schooling, etc) and clinical characteristics (dosage and number of MECT, etc) were compared. Depression severity, working memory, and subjective memory were measured using the Hamilton Depression Rating Scale 17 (HAMD17), a Digit Span Backwards (DSB), and self-reported assessments, respectively. Measurements were taken at baseline, within 24 hours after each MECT session, and in every month for a 6-month follow-up period.(a) The patients had poorer performance than the HCs on DSB and HAMD17 at baseline, and the DSB score and HAMD17 total scores were negatively correlated. However, after the second MECT session, the patients' HAMD17 score was significantly improved compared with that at the baseline (P0.05), whereas the DSB score showed no significant difference compared with the HCs (P0.05). (b) After the first MECT session, 62% of the patients reported subjective memory deficits, which were exacerbated over the subsequent sessions and relieved with antidepressant treatment during the follow-up period. (c) The risk factors for prolonged subjective memory deficits were overweight and the maximum MECT dosage/age (dosage/age = the percentage of output part of total dosage × 100/age, unit: 1/year) ≥ 1.5/year (odds ratio [OR] = 15.36 and 7.98).Depressed patients showed poorer working memory than the HCs. Such memory deficit may be aggravated by MECT, although it may improve with the relief of depression. Although subjective memory deficits can occur after the first MECT session and gradually recover after the treatment, they may last for 6 months or longer. Persistent deficits may be related to being overweight and having a high MECT dosage.

Background Major depressive disorder (MDD) is a debilitating mental illness with more than 50% of patients not achieving an adequate response using first-line treatments. Reliable models that predict antidepressant treatment outcome are needed to guide clinical decision making. We aimed to build predictive models of treatment improvement for MDD patients using machine learning approaches based on fMRI resting-state functional connectivity patterns. Methods Resting-state fMRI data were acquired from 192 untreated MDD patients at recruitment, and their severity of depression was assessed by Hamilton Rating Scale for Depression (HAMD) at baseline. Patients were given medication after the initial MR scan and their symptoms were monitored through HAMD for a period of six months. Connectome-based predictive modeling (CPM) algorithms were implemented to predict the improvement in HAMD score at one month from resting-state connectivity at baseline. Additionally, by selectively combining the features from all leave-one-out iterations in the model building stage, we created a consensus model that could be generalized to predict improvement in HAMD score in samples of non-overlapping subjects at different time points. Results Using baseline functional connectivity, CPM successfully predicted symptom improvement of depression at one month. In addition, a consensus ‘MDD improvement model’ could predict symptom improvement for novel individuals at the two-week, one-month, two-month and three-month time points after antidepressant treatment. Conclusions Individual pre-treatment functional brain networks contain meaningful information that can be gleaned to build predictors of treatment outcome. The identified MDD improvement networks could be an appropriate biomarker for predicting individual therapeutic response of antidepressant treatment. Replication and validation using other large datasets will be a key next step before these models can be used in clinical practice.

Background: Childhood trauma is an important early social risk factor for the development of the major depressive disorder (MDD). Both childhood trauma and depression are associated with dysfunctional attitudes and dysregulation in stress hormones. We aimed to clarify the path from childhood trauma to depression and identify potential predictors of antidepressant treatment outcomes. Objectives: One hundred and thirty-nine MDD patients and 112 healthy controls were included at baseline. Depressive symptoms were assessed with both self-reported and expert-rated scales. Childhood trauma and dysfunctional attitudes were evaluated and blood cortisol levels were assayed. Patients received an open-label antidepressant trial with paroxetine and their depressive symptoms were monitored by the Hamilton Depression Rating Scale (HAMD) during 6 months of treatment. After 6 months, 94 patients received the same assessments as the baseline. Results: At baseline, the influence of childhood trauma on depression diagnosis was mediated by dysfunctional attitudes. In patients with MDD, the influence of childhood trauma on depression severity was mediated by both dysfunctional attitudes and cortisol levels. Baseline childhood trauma predicted the antidepressant treatment outcome during early treatment phase and baseline cortisol levels predicted the antidepressant treatment outcome at later treatment phase. After 6-month antidepressant treatment, a significant remission by time effect was found on dysfunctional attitudes and depression severity but not on cortisol levels. Conclusion: Effect of childhood trauma on depression onset was mediated by dysfunctional attitudes. The relationship between childhood trauma and depressive symptoms was mediated by dysfunctional attitudes and cortisol levels in MDD patients. Baseline childhood trauma and cortisol levels may be moderators for antidepressant treatment response at different treatment phase.

Objective The aim of this study includes: (1) using resting-state functional magnetic resonance imaging (rsfMRI) to explore the aberrant brain regional spontaneous brain activities in acute major depressive disorder (MDD) patients; (2) to determine whether the abnormalities could be restored after 6 months of antidepressant treatment; (3) to investigate whether the differences in regional spontaneous brain activities are associated with clinical variables in MDD. Method RsfMRI scanning was performed in 149 MDD patients and 122 healthy control (HC) subjects at baseline. After 6 months of antidepressant treatment, rsfMRI scanning was reperformed in remitted MDD patients (MDD-R) (n=63). The characteristics of the amplitude of low-frequency fluctuations (ALFF), and the relationship between the fMRI representatives and clinical variables in the MDD group were analyzed. Results (1) Compared to healthy controls, significantly decreased ALFF in the right precuneus/posterior cingulate cortex (PCUN/PCC) was detected in MDD. (2) The ALFF value of precuneus in MDD-R group did not change significantly after a 6-month antidepressant treatment and was still lower than the HC group when remission was achieved (P = 0.002). (3) No correlations were found between ALFF in the right PCUN/PCC and Hamilton Depression Rating Scale(HAMD) total score, illness duration, age of onset, and the number of episodes in the baseline MDD group. The ALFF change was not correlated with depressive symptom improvement in MDD-R group. Conclusions The reduction of ALFF in the precuneus persisted in MDD who achieved clinical remission, suggesting that the decreased ALFF in PCUN/PCC may be a trait marker of MDD.

BACKGROUND. Losing one’s only child is a major traumatic life event that may lead to post-traumatic stress disorder (PTSD); however, the underlying mechanisms of its psychological consequences remain poorly understood. Here, we investigated subregional hippocampal functional connectivity (FC) networks based on resting-state functional magnetic resonance imaging and the deoxyribonucleic acid methylation of the human glucocorticoid receptor gene (NR3C1) in adults who had lost their only child. METHODS. A total of 144 Han Chinese adults who had lost their only child (51 adults with PTSD and 93 non-PTSD adults [trauma-exposed controls]) and 50 controls without trauma exposure were included in this fMRI study (age: 40–67 years). FCs between hippocampal subdivisions (four regions in each hemisphere: cornu ammonis1 [CA1], CA2, CA3, and dentate gyrus [DG]) and methylation levels of the NR3C1 gene were compared among the three groups. RESULTS. Trauma-exposed adults, regardless of PTSD diagnosis, had weaker positive FC between the left hippocampal CA1, left DG, and the posterior cingulate cortex, and weaker negative FC between the right CA1, right DG, and several frontal gyri, relative to healthy controls. Compared to non-PTSD adults, PTSD adults showed decreased negative FC between the right CA1 region and the right middle/inferior frontal gyri (MFG/IFG), and decreased negative FC between the right DG and the right superior frontal gyrus and left MFG. Both trauma-exposed groups showed lower methylation levels of the NR3C1 gene. CONCLUSIONS. Adults who had lost their only child may experience disrupted hippocampal network connectivity and NR3C1 methylation status, regardless of whether they have developed PTSD.

Objective Efficacy and safety of long-term use of antidepressants (AD) in bipolar disorder (BD) patients remains highly controversial. Here we performed a meta-analysis of randomized controlled trials (RCTs) exploring the efficacy and safety of long-term AD use in BD patients. Methods English-written literature published in peer-reviewed journal was systematically searched from Pubmed, EMBASE, CENTRAL, PsycINFO and Clinicaltrials.gov. Each database was searched from its first available time to August 31, 2016. Additional papers were searched from recent guidelines, expert consensus and systematic reviews by hand. RCTs exploring the efficacy and safety of long-term (≥4 m) antidepressant treatment for patients with bipolar disorder were eligible. Two authors (HF, JL) independently extracted the data. Risk ratio (RR), number needed to treat (NNT) and/or number needed to harm (NNH) for new depressive episodes and new manic/hypomanic episodes were calculated. Subgroup analyses were performed based on treatment regimen (AD monotherapy or combined with MS), types of antidepressants, funding source, bipolar subtypes and treatment duration. Results Eleven trials with 692 bipolar disorder patients were included in the meta-analysis. The risk of bias assessment demonstrated moderate bias risk. Antidepressants were superior to placebo in reducing new depressive episodes in bipolar disorders without increasing risk of new manic/hypomanic episodes either used as monotherapy or in combination with MS. Subgroup analyses revealed that greater benefit and lower risk may be achieved in BD II than in BD I. However, compared with MS monotherapy, AD monotherapy significantly increased the risk of affective switch with no improvement in prophylaxis of new depressive episodes. Conclusions Reduced new depressive episodes may be achieved by long-term AD treatment with no significantly increased risk of new manic/hypomanic episodes in BD, particularly in BD II. The elevated risk of affective switch of AD monotherapy compared with MS monotherapy may be contributed to the protective effect of MS in diminishing manic/hypomanic episodes. Further studies are needed to verify our findings.

Encoding specificity theory predicts most effective recall by the original conditions at encoding, while generalization endows recall flexibly under circumstances which deviate from the originals. The CA1 regions have been implicated in memory and generalization but whether and which locally separated mechanisms are involved is not clear. We report here that fear memory is quickly formed, but generalization develops gradually over 24 h. Generalization but not fear memory is impaired by inhibiting ipsilateral (ips) or contralateral (con) CA1, and by optogenetic silencing of the ipsCA1 projections onto conCA1. By contrast, in vivo fEPSP recordings reveal that ipsCA1–conCA1 synaptic efficacy is increased with delay over 24 h when generalization is formed but it is unchanged if generalization is disrupted. Direct excitation of ipsCA1–conCA1 synapses using chemogenetic hM3Dq facilitates generalization formation. Thus, rapid generalization is an active process dependent on bilateral CA1 regions, and encoded by gradual synaptic learning in ipsCA1–conCA1 circuit., Previous work has documented a slow form of memory generalization although a rapid one is demanded. Here the authors elucidate the role of the interhemispheric CA1-CA1 projection in a form of rapid generalization of contextual fear memory via gradual potentiation of these synapses over 24 h.

Introduction: Objective to summarize the work flow list during epidemic period, and to discuss and summarize the process management and prevention and control methods of each link in Tumor area during epidemic period of novel coronavirus pneumonia (NCP), in order to achieve the orderly completion of radiotherapy and chemotherapy for tumor patients, and prevent a tumor patient from contracting novel coronavirus pneumonia Methods: According to the characteristics of the transmission of NCP and the relevant documents of the National Health Commission, the list of management work was carded out, to establish various prevention and control processes in tumor wards, control key population, establish correct infection control measures, scientifically protect key personnel and effectively manage protective materials Results: During the epidemic period of NCP, the tumor inpatients could complete the radiotherapy and chemotherapy in time and effectively, and the infection of NCP was avoided The ability and knowledge of prevention and control of hospital infection of new pneumonia were improved [Formula presented] Conclusion: The nursing managers adopt and implement correct measures to prevent and control NCP infection through the management work list system, which can effectively ensure the safety of tumor patients and the occupational safety of medical workers The purpose of this study is to provide practical experience for the establishment of infectious emergency nursing management system in common disease areas Keywords: List of management, Oncology ward, coronavirus pneumonia

Previous studies using resting-state functional MRI (rs-fMRI) have revealed alterations in graphical metrics in groups of individuals with posttraumatic stress disorder (PTSD). To explore the ability of graph measures to diagnose PTSD and capture its essential features in individual patients, we used a deep learning (DL) model based on a graph-theoretic approach to discriminate PTSD from trauma-exposed non-PTSD at the individual level and to identify its most discriminant features. Our study was performed on rs-fMRI data from 91 individuals with PTSD and 126 trauma-exposed non-PTSD patients. To evaluate our DL method, we used the traditional support vector machine (SVM) classifier as a reference. Our results showed that the proposed DL model allowed single-subject discrimination of PTSD and trauma-exposed non-PTSD individuals with higher accuracy (average: 80%) than the traditional SVM (average: 57.7%). The top 10 DL features were identified within the default mode, central executive, and salience networks, the first two of these networks were also identified in the SVM classification. We also found that nodal efficiency in the left fusiform gyrus was negatively correlated with the Clinician Administered PTSD Scale score. These findings demonstrate that DL based on graphical features is a promising method for assisting in the diagnosis of PTSD.

Background Whether there are distinct subtypes of schizophrenia is an important issue to advance understanding and treatment of schizophrenia. Aims To understand and treat individuals with schizophrenia, the aim was to advance understanding of differences between individuals, whether there are discrete subtypes, and how first-episode patients (FEP) may differ from multiple episode patients (MEP). Method These issues were analysed in 687 FEP and 1880 MEP with schizophrenia using the Positive and Negative Syndrome Scale for (PANSS) schizophrenia before and after antipsychotic medication for 6 weeks. Results The seven Negative Symptoms were correlated with each other and with P2 (conceptual disorganisation), G13 (disturbance of volition), and G7 (motor retardation). The main difference between individuals was in the cluster of seven negative symptoms, which had a continuous unimodal distribution. Medication decreased the PANSS scores for all the symptoms, which were similar in the FEP and MEP groups. Conclusions The negative symptoms are a major source of individual differences, and there are potential implications for treatment. Declaration of interests L.P. received speaker fees from Otsuka Canada and educational grant from Janssen Canada in 2017. Copyright and usage © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

// Shaojia Lu 1 , Fen Pan 1 , Weijia Gao 2 , Zhaoguo Wei 3, 4 , Dandan Wang 1 , Shaohua Hu 1 , Manli Huang 1 , Yi Xu 1 and Lingjiang Li 3 1 Department of Psychiatry, The First Affiliated Hospital, Zhejiang University School of Medicine, Key Laboratory of Mental Disorder’s Management of Zhejiang Province, Hangzhou, Zhejiang, China 2 Department of Child Psychology, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China 3 Mental Health Institute of The Second Xiangya Hospital, Key Laboratory of Psychiatry and Mental Health of Hunan Province, Central South University, Changsha, Hunan, China 4 Department of Psychiatry, Shenzhen Kangning Hospital, Shenzhen, Guangdong, China Correspondence to: Shaojia Lu, email: 1314004@zju.edu.cn Lingjiang Li, email: llj2920@163.com Keywords: childhood trauma, default mode network, fractional amplitude of low frequency fluctuation, functional connectivity, executive function Received: June 24, 2017 Accepted: July 26, 2017 Published: August 07, 2017 ABSTRACT The aim of this study was to investigate the relationship among childhood trauma, executive impairments, and altered resting-state brain function in young healthy adults. Twenty four subjects with childhood trauma and 24 age- and gender-matched subjects without childhood trauma were recruited. Executive function was assessed by a series of validated test procedures. Localized brain activity was evaluated by fractional amplitude of low frequency fluctuation (fALFF) method and compared between two groups. Areas with altered fALFF were further selected as seeds in subsequent functional connectivity analysis. Correlations of fALFF and connectivity values with severity of childhood trauma and executive dysfunction were analyzed as well. Subjects with childhood trauma exhibited impaired executive function as assessed by Wisconsin Card Sorting Test and Stroop Color Word Test. Traumatic individuals also showed increased fALFF in the right precuneus and decreased fALFF in the right superior temporal gyrus. Significant correlations of specific childhood trauma severity with executive dysfunction and fALFF value in the right precuneus were found in the whole sample. In addition, individuals with childhood trauma also exhibited diminished precuneus-based connectivity in default mode network with left ventromedial prefrontal cortex, left orbitofrontal cortex, and right cerebellum. Decreased default mode network connectivity was also associated with childhood trauma severity and executive dysfunction. The present findings suggest that childhood trauma is associated with executive deficits and aberrant default mode network functions even in healthy adults. Moreover, this study demonstrates that executive dysfunction is related to disrupted default mode network connectivity.

Using resting-state functional magnetic resonance imaging, we test the hypothesis that subjects with post-traumatic stress disorder (PTSD) are characterized by reduced temporal variability of brain connectivity compared to matched healthy controls. Specifically, we test whether PTSD is characterized by elevated static connectivity, coupled with decreased temporal variability of those connections, with the latter providing greater sensitivity toward the pathology than the former. Static functional connectivity (FC; nondirectional zero-lag correlation) and static effective connectivity (EC; directional time-lagged relationships) were obtained over the entire brain using conventional models. Dynamic FC and dynamic EC were estimated by letting the conventional models to vary as a function of time. Statistical separation and discriminability of these metrics between the groups and their ability to accurately predict the diagnostic label of a novel subject were ascertained using separate support vector machine classifiers. Our findings support our hypothesis that PTSD subjects have stronger static connectivity, but reduced temporal variability of connectivity. Further, machine learning classification accuracy obtained with dynamic FC and dynamic EC was significantly higher than that obtained with static FC and static EC, respectively. Furthermore, results also indicate that the ease with which brain regions engage or disengage with other regions may be more sensitive to underlying pathology than the strength with which they are engaged. Future studies must examine whether this is true only in the case of PTSD or is a general organizing principle in the human brain. Hum Brain Mapp 38:4479-4496, 2017. © 2017 Wiley Periodicals, Inc.

MicroRNAs (miRs) play critical roles in the development and malignant progression of human cancers. miR-148a has previously been found to inhibit the migration and invasion of breast cancer cells. However, the underlying mechanism of miR-148a in regulating the viability and migration of estrogen receptor (ER) α-positive breast cancer cells is still unknown. In this study, ERα-positive breast cancer MCF7 cells were treated with estradiol (E2). Data from MTT and wound healing assays showed that E2 treatment promoted the viability and migration of MCF7 cells. A bioinformatics analysis and luciferase reporter assay identified ERα as a direct target of miR-148a. Ectopic expression of miR-148a significantly decreased the protein expression of ERα (P

Kaida Jiang,1 Lingjiang Li,2 Xueyi Wang,3 Maosheng Fang,4 Jianfei Shi,5 Qiuyun Cao,6 Jincai He,7 Jinan Wang,8 Weihao Tan,8 Cuili Hu8 1Psychiatry Department, Shanghai Mental Health Center, Shanghai, 2Psychiatry Department,The Second Xiangya Hospital, Central South University, Changsha, 3Psychiatry Department, First affiliated Hospital of Hebei Medical University, Shijiazhuang, 4Psychiatry Department, Wuhan Mental Health Center, Wuhan, 5Psychiatry Department, Hangzhou the 7th Hospital, Hangzhou, 6Psychology Department, Nanjing Drum Tower Hospital, Nanjing, 7Neurology Department, First affiliated Hospital of Wenzhou Medical University, Wenzhou, 8Medical Affairs Department, Xi’an Janssen Pharmaceutical Ltd., Beijing, People’s Republic of China Background: Significant anxiety symptoms are associated with poor clinical course and outcome in major depressive disorder (MDD). This single-arm, open-label study aimed to evaluate the efficacy and tolerability of escitalopram treatment in patients with MDD and anxiety symptoms. Methods: Adult patients with MDD and anxiety symptoms (Montgomery–Asberg Depression Rating Scale [MADRS] ≥22 and Hamilton Anxiety Rating Scale [HAM-A] ≥14) were enrolled and received escitalopram (10–20 mg/day) treatment for 24 weeks. Symptom status was assessed by MADRS, 17-item-Hamilton Depression Rating Scale, HAM-A, and Clinical Global Impression Scale at baseline and the following visits. Quality of life was assessed by Short Form-12, and safety was evaluated by adverse events, laboratory investigations, vital signs, and physical findings. Results: Overall, 200 of 318 (66.2%) enrolled patients completed the 24-week treatment. The remission (MADRS ≤10 and HAM-A ≤7) rate in the full analysis set (N=285) was 73.3% (95% confidence interval: 67.80, 78.38) at week 24. Mean (± standard deviation) MADRS total score was 33.4 (±7.13) and HAM-A score was 27.6 (±7.26) at baseline, which reduced to 6.6 (±10.18) and 6.0 (±8.39), respectively, at week 24. Patients with higher baseline depression and anxiety level took longer to achieve similar remission rates. Overall, 80 of the 302 (26.5%) patients included in the safety set reported at least 1 treatment-emergent adverse event (TEAE). Most frequently reported TEAEs (>2%) were headache (4.0%), nasopharyngitis (3.6%), nausea (3.0%), and dizziness (2.6%). Serious TEAEs were reported by 1.3% patients; no deaths were reported. Conclusion: Escitalopram 10–20 mg/day was effective and well-tolerated in the long-term treatment of MDD with anxiety symptoms in adult Chinese population. Keywords: anxiety, Chinese, escitalopram, long term, major depressive disorder

[Image: see text] COVER ILLUSTRATION Illustrations of disrupted information processing of brain white matter network involving fronto‐temporo‐occipital regions (illustrated as yellow lines in the picture) in post‐traumatic stress disorder patients following an earthquake (illustrated as black circles in the picture).

Major depressive disorder (MDD) patients with comorbid anxiety symptoms showed obvious cognitive deficits. However, it remains unclear whether comorbid anxiety symptoms will make a specific contribution to cognitive deficits in MDD.Executive function, processing speed, attention and memory were assessed in 162 MDD patients, and 142 healthy controls (HCs) by a comprehensive neuropsychological battery. 14-item Hamilton Anxiety Rating Scale (HAM-A) was used for anxiety symptoms and MDD patients with HAM-A total score14 were classified into MDD with comorbid anxiety (MDDA) group. A multivariate analysis of covariance and regression models was conducted to evaluate the effects of anxiety symptoms on cognitive deficits.There were no significantly differences in all 4 cognitive domains between MDD alone and MDDA patients (all p 0.05). In MDDA subgroup, HAM-A total score contributed to executive function and memory (both p 0.05), while HAM-A psychic symptoms contributed to all 4 domains (all p 0.05). Moreover, after controlling for the severity of depression, either anxiety symptoms shown as HAMA total score or psychic anxiety symptoms only contributed significantly to the executive function performance.The cross-sectional design made it hard to acquire a cognitive performance trajectory accompanied by the fluctuations in anxiety symptoms.Our findings suggest that there is no significant difference in cognitive performance between MDD alone and MDDA patients. However, comorbid anxiety, especially psychic anxiety may contribute to extensive cognitive deficits in MDDA patients. Notably, anxiety symptoms only independently triggered executive dysfunction when eliminating effect of the severity of depression.

Background Posttraumatic stress disorder (PTSD) is a debilitating mental illness that is thought to be associated with brain white matter (WM) alterations. Individual diffusion tensor imaging (DTI) studies to date have reported inconsistent alterations in FA across different brain regions in patients with PTSD. Here, we aimed to investigate FA in PTSD using both region-of-interest (ROI)-based and whole-brain-based meta-analytic approaches. Objectives Individual ROI-based meta-analysis was carried out in each eligible white matter tract and seed-based D mapping (SDM) meta-analysis was conducted in the whole brain to identify the convergence of FA alterations in PTSD relative to controls. Results Seventeen studies were included in ROI-based meta-analysis (≥ 3 studies were included for each ROI, NPTSD ≥ 80 and Ncontrol ≥ 103 per ROI). Fourteen studies with a total of 322 PTSD and 335 controls were included in whole-brain based meta-analysis. Both ROI and whole-brain meta-analyses showed that patients with PTSD have significantly higher FA in the inferior fronto-occipital fasciculus and lower FA in the genu of corpus callosum. Whole-brain meta-analyses also identified higher FA in the left inferior temporal gyrus and lower FA in the anterior cingulum and left corticospinal tract. Limitations A small number of studies were included in some ROI tracts. Thus the results should be interpreted with caution. Conclusions Our results suggest that PTSD patients have increased FA in areas related to visual processing, but decreased FA in anterior brain regions critical to cognition association and fear regulation.

Background To investigate mental and physical health comorbidity with chronic back or neck pain in the Chinese population, and assess the level of disability associated with chronic back or neck pain. Methods Data were derived from a large-scale and nationally representative community survey of adult respondents on mental health disorders in China (n = 28,140). Chronic back or neck pain, other chronic pain conditions and chronic physical conditions were assessed by self-report. Mental disorders were assessed by the Composite International Diagnostic Interview (CIDI). Role disability during the past 30 days was assessed with the World Health Organization Disability Assessment Schedule (WHO-DAS-II). Results The 12-month prevalence of chronic back or neck pain was 10.8%. Most of respondents with chronic back or neck pain (71.2%) reported at least one other comorbid condition, including other chronic pain conditions (53.4%), chronic physical conditions (37.9%), and mental disorders (23.9%). It was found by logistic regression that mood disorders (OR = 3.7, 95%CI:2.8–4.8) showed stronger association with chronic back or neck pain than anxiety disorders and substance disorders. Most common chronic pains and physical conditions were significantly associated with chronic back or neck pain. Chronic back or neck pain was associated with role disability after controlling for demographics and for comorbidities. Physical and mental comorbidities explained 0.7% of the association between chronic back or neck pain and role disability. Conclusions Chronic back or neck pain and physical-mental comorbidity is very common in China and chronic back or neck pain may increase the likelihood of other physical and mental diseases. This presents a great challenge for both clinical treatment and public health education. We believe that further study needs to be conducted to improve the diagnostic and management skills for comorbidity conditions.

Previous studies have shown that posttraumatic stress disorder (PTSD) is associated with dysfunction of the limbic system, in which the amygdala plays an important role. The purpose of this study was to evaluate whether the neurochemical concentrations assessed by proton magnetic resonance spectroscopy (1H-MRS) in the amygdala are abnormal in children and adolescents with PTSD. Twenty-eight pediatric PTSD patients (11 boys, 17 girls) and 24 matched trauma-exposed control subjects (9 boys, 15 girls) underwent magnetic resonance brain imaging and 1H-MRS of the bilateral amygdalae. The concentrations of N-acetylaspartate (NAA), myo-inositol (mI), total creatine (tCr) and total choline (tCho) in the right amygdala were significantly increased in PTSD patients compared with trauma-exposed control subjects. There were significant group-by-age interactions in the left amygdala NAA and right amygdala mI concentrations: older pediatric patients with PTSD had higher left amygdala NAA concentration and younger patients had higher right amygdala mI concentration than trauma-exposed control subjects. There was also a significant correlation between right mI concentration and time since trauma in PTSD patients. Finally, there was significant group-by-age interaction in the left amygdala volume; intragroup analysis revealed that the right amygdala volume was significantly lower than the left in the PTSD group, but not in the control group. These neurochemical abnormalities of the amygdala may indicate that dysfunctions of both neurons and glial cells are involved in the pathology of pediatric PTSD.

BackgroundMany structural and functional magnetic resonance imaging (MRI) studies have reported differences in brain functional anatomy associated with eating disorders (EDs). We aimed to quantitatively synthesize the current literature of anorexia nervosa (AN) and bulimia nervosa (BN) with a goal of deriving a consensus across these studies.MethodsWe performed a hierarchical series of 49 activation likelihood estimation meta-analyses of 101 experiments from 63 studies at the disorder (AN+BN), diagnosis (AN or BN), and task (food-, body-, emotion- or cognitive function-related tasks) levels. We further performed sub-analyses at the diagnosis level to assess the influence of disease stage (current or recovered AN), subtype (restrictive AN, rAN), psychiatric comorbidity, medication, and data processing.ResultsWe did not observe consistent differences in brain activity across all hierarchies. Rather, we observed differences in brain activity in the right fusiform, left inferior parietal lobule and left precuneus that were primarily related to food (representing 19 experiments) and emotion (25 experiments) tasks performed by current AN patients (56 experiments).ConclusionsThe task-based functional MRI literature in AN and BN represents a heterogenous set of tasks and patients. Given this heterogeneity, we found very limited convergence across a rather large literature. Such limited convergence suggests individual task-based studies of EDs should be interpreted cautiously. We recommend that future studies of EDs carefully characterize patients based on nutritional status and that, beyond clinical diagnosis, studies utilize a trait- or cognitive-domain-based approach to define their populations of interest.Meta-ananlysis Registration“Meta-analysis of functional magnetic resonance imaging studies of eating disorders”, https://www.crd.york.ac.uk/prospero (Registration Number: CRD42018086497).

Both major depressive disorder (MDD) and childhood trauma have been linked with brain structural changes. As childhood trauma is more highly prevalent in MDD patients, previous morphometric findings in MDD therefore might have been confounded by childhood trauma. This study aimed to differentiate the impact of childhood trauma from the influence of MDD diagnosis on gray matter volume (GMV). Seventy-eight subjects were recruited into four study groups (n = 16, MDD patients with childhood trauma exposures, CTE/MDD; n = 14, MDD patients without CTE, non-CTE/MDD; n = 24, healthy controls with CTE, CTE/HC; and n = 24, HCs without CTE, non-CTE/HC). All participants underwent high-resolution structural magnetic resonance scans. Voxel-based morphometry was used to investigate GM alterations, and a 2 × 2 analysis of variance was performed to identify the main effects of diagnosis, childhood trauma, and their interactions. The main effects of diagnosis displayed abnormal GMV located in the left superior parietal lobule (MDD HC) and right middle occipital gyrus (MDD HC). While the left dorsolateral prefrontal cortex (DLPFC) volume revealed a significant main effect of childhood trauma, as shown by decreased GMV of the left DLPFC in subjects with CTE, regardless of diagnosis. A negative correlation was also found between the left DLPFC volume and emotional neglect in individuals reporting CTE. The present findings suggest that decreased GMV of the left DLPFC is a function of childhood trauma rather than MDD, which may represent the biological risk for developing MDD.

Resting-state functional MRI (R-fMRI) studies have demonstrated widespread alterations in brain function in patients with major depressive disorder (MDD). However, a clear and consistent conclusion regarding a repeatable pattern of MDD-relevant alterations is still limited due to the scarcity of large-sample, multisite datasets. Here, we address this issue by including a large R-fMRI dataset with 1,434 participants (709 patients with MDD and 725 healthy controls) from five centers in China. Individual functional activity maps that represent very local to long-range connections are computed using the amplitude of low-frequency fluctuations, regional homogeneity and distance-related functional connectivity strength. The reproducibility analyses involve different statistical strategies, global signal regression, across-center consistency, clinical variables, and sample size. We observed significant hypoactivity in the orbitofrontal, sensorimotor, and visual cortices and hyperactivity in the frontoparietal cortices in MDD patients compared to the controls. These alterations are not affected by different statistical analysis strategies, global signal regression and medication status and are generally reproducible across centers. However, these between-group differences are partially influenced by the episode status and the age of disease onset in patients, and the brain-clinical variable relationship exhibits poor cross-center reproducibility. Bootstrap analyses reveal that at least 400 subjects in each group are required to replicate significant alterations (an extent threshold of PP