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Background The symptoms that patients with major depressive disorder (MDD) experience are the dominant contributing factors to its heavy disease burden. This study sought to identify key symptoms leading to disability in patients with MDD. Methods Subjects consisted of patients who had a 12-month MDD diagnosis based on the China Mental Health Survey (CMHS). World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) was used to assess the degree of disability. The associations between depressive symptoms and disability were analyzed using a linear regression and logistic regression with a complex sampling design. Results Of the 32,552 community residents, 655 patients were diagnosed with 12-month MDD. The disability rate due to MDD was 1.06% (95% CI: 0.85%–1.28%) among adults in Chinese community and 50.7% (95% CI: 44.3%–57.1%) among MDD patients. Depression was associated with all functional losses measured by the WHODAS. Feelings of worthlessness in life or inappropriate guilt, and psychomotor agitation or retardation were the key symptoms related to disability. Economic status, co-morbidity of physical diseases or anxiety disorders were correlates of disability scores. Limitations The disability rate might be underestimated due to the exclusion of MDD patients living in hospitals. The effect of treatments on disability was excluded. Conclusions Psychological symptoms, not somatic symptoms, contribute to disability in MDD patients. Disability worsens when physical diseases or anxiety disorders are present. More attention could be paid to psychological symptoms, physical diseases, and anxiety disorders in MDD patients with disabilities.

Summary Background In China, depressive disorders have been estimated to be the second leading cause of years lived with disability. However, nationally representative epidemiological data for depressive disorders, in particular use of mental health services by adults with these disorders, are unavailable in China. The present study, part of the China Mental Health Survey, 2012–15, aims to describe the socioeconomic characteristics and the use of mental health services in people with depressive disorders in China. Methods The China Mental Health Survey was a cross-sectional epidemiological survey of mental disorders in a multistage clustered-area probability sample of adults of Chinese nationality (≥18 years) from 157 nationwide representative population-based disease surveillance points in 31 provinces across China. Trained investigators interviewed the 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, dysthymic disorder, and depressive disorder not otherwise specified. Participants with 12-month depressive disorders were asked whether they received any treatment for their emotional problems during the past 12 months and, if so, the specific types of treatment providers. The Sheehan Disability Scale (SDS) was used to assess impairments associated with 12-month depressive symptoms. Data-quality control procedures included logic check by computers, sequential recording check, and phone-call check by the quality controllers, and reinterview check by the psychiatrists. Data were weighted according to the age–sex–residence distribution data from China's 2010 census population survey to adjust for differential probabilities of selection and differential response, as well as to post-stratify the sample to match the population distribution. Findings 28 140 respondents (12 537 [44·6%] men and 15 603 [55·4%] women) completed the survey between July 22, 2013, and March 5, 2015. Ethnicity data (Han or non-Han) were collected for only a subsample. Prevalence of any depressive disorders was higher in women than men (lifetime prevalence odds ratio [OR] 1·44 [95% CI 1·20–1·72] and 12-month prevalence OR 1·41 [1·12–1·78]), in unemployed people than employed people (lifetime OR 2·38 [95% CI 1·68–3·38] and 12-month OR 2·80 [95% CI 1·88–4·18]), and in people who were separated, widowed, or divorced compared with those who were married or cohabiting (lifetime OR 1·87 [95% CI 1·39–2·51] and 12-month OR 1·85 [95% CI 1·40–2·46]). Overall, 574 (weighted % 75·9%) of 744 people with 12-month depressive disorders had role impairment of any SDS domain: 439 (83·6%) of 534 respondents with major depressive disorder, 207 (79·8%) of 254 respondents with dysthymic disorder, and 122 (59·9%) of 189 respondents with depressive disorder not otherwise specified. Only an estimated 84 (weighted % 9·5%) of 1007 participants with 12-month depressive disorders were treated in any treatment sector: 38 (3·6%) in speciality mental health, 20 (1·5%) in general medical, two (0·3%) in human services, and 21 (2·7%) in complementary and alternative medicine. Only 12 (0·5%) of 1007 participants with depressive disorders were treated adequately. Interpretation Depressive disorders in China were more prevalent in women than men, unemployed people than employed, and those who were separated, widowed, or divorced than people who were married or cohabiting. Most people with depressive disorders reported social impairment. Treatment rates were very low, and few people received adequate treatment. National programmes are needed to remove barriers to availability, accessibility, and acceptability of care for depression in China. Funding National Health Commission and Ministry of Science and Technology of People's Republic of China. Translation For the Chinese translation of the abstract see Supplementary Materials section.

Aberrations in intracortical myelination are increasingly being considered as a cardinal feature in the pathophysiology of schizophrenia. We investigated the network-level distribution of intracortical myelination across various cortex depths. We enrolled 126 healthy subjects and 106 first-episode drug-naïve schizophrenia patients. We used T1w/T2w ratio as a proxy of intracortical myelination, parcellated cortex into several equivolumetric surfaces based on cortical depths and mapped T1w/T2w ratios to each surface. Non-negative matrix factorization was used to generate depth-dependent structural covariance networks (dSCNs) of intracortical myelination from 2 healthy controls datasets—one from our study and another from 100-unrelated dataset of the Human Connectome Project. For patient versus control comparisons, partial least squares approach was used; we also related myelination to clinical features of schizophrenia. We found that dSCNs were highly reproducible in 2 independent samples. Network-level myelination was reduced in prefrontal and cingulate cortex and increased in perisylvian cortex in schizophrenia. The abnormal network-level myelination had a canonical correlation with symptom burden in schizophrenia. Moreover, myelination of prefrontal cortex correlated with duration of untreated psychosis. In conclusion, we offer a feasible and sensitive framework to study depth-dependent myelination and its relationship with clinical features.

Objective The findings of olfaction are inconsistent in anxiety disorders, and few studies have reported on the olfactory performance in generalized anxiety disorder (GAD). Therefore, we aim to investigate the olfactory function of patients with GAD and the association between olfactory function and anxiety symptoms. Methods We conducted a case–control study by selecting 107 patients with GAD and 107 healthy controls matched for sex and age, to investigate olfaction deficits in GAD and the association between anxiety severity and olfaction. All patients were treatment-naive prior to the inclusion. Anxiety severity and olfaction were assessed by the Hamilton anxiety rating scale (HAM-A) and the Sniffin’ Sticks test (SST), respectively. Partial correlations were used to analyze the relationship between olfaction and anxiety severity. False discovery rate (FDR) correction was used in multi-correlation analyses. Results Compared with healthy controls, patients in the GAD group demonstrated odor threshold, discrimination and identification deficits. In the moderate/severe anxiety subgroup, discrimination score was significantly and inversely correlated with the somatic anxiety score (γ=−0.44, q = 0.03), and identification score was significantly and inversely correlated with the HAM-A total score (γ=−0.42, q= 0.04). The TDI score (the sum of threshold, discrimination and identification scores) was significantly and inversely correlated with the somatic (γ=−0.44, q = 0.04) and psychic (γ=−0.45, q = 0.04) anxiety scores in the moderate/severe anxiety subgroup. Conclusion This study demonstrated the olfactory impairment in patients with GAD and that poorer odor discrimination was correlated with greater severity of somatic anxiety.

Peiyan Ni,1– 3 Manli Liu,1– 3 Dequan Wang,1– 3 Yang Tian,1– 3 Liansheng Zhao,1– 3 Jinxue Wei,1– 3 Xueli Yu,1– 3 Xueyu Qi,1– 3 Xiaojing Li,1– 3 Hua Yu,1– 3 Rongjun Ni,1– 3 Xiaohong Ma,1– 3 Wei Deng,1– 3 Wanjun Guo,1– 3 Qiang Wang,1– 3 Tao Li1– 4 1The Psychiatric Laboratory, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Mental Health Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 3Huaxi Brain Research Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 4Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangzhou, People’s Republic of ChinaCorrespondence: Tao LiThe Psychiatric Laboratory, West China Hospital, Sichuan University, 28 Dian Xin Nan Road, Chengdu, Sichuan, 610041, People’s Republic of ChinaTel/Fax +86-28-85423561Email litaohx@scu.edu.cnIntroduction: Schizophrenia, bipolar disorder (BD), and major depressive disorder are three common mental disorders. Although their diagnosis and treatment differ, they partially overlap.Methods: To explore the similarities and characteristics of these three psychiatric diseases, an intelligence quotient (IQ) assessment was performed to evaluate cognitive deficits. Relative catechol-O-methyltransferase (COMT) expression in peripheral blood mononuclear cells was examined in all three groups compared with healthy controls (HCs).Results: The results indicated that patients with any of the three psychiatric diseases presented IQ deficits, and that the first-episode schizophrenia (FES) group had even lower cognitive function than the other two groups. The relative COMT expression decreased in the FES group and increased in the BD group compared with the HC group. The correlation analysis of COMT expression level and IQ scores showed a positive correlation between relative COMT expression and full-scale IQ in the HC group. However, this correlation disappeared in all three psychiatric diseases studied.Conclusion: In conclusion, this cross-disease strategy provided important clues to explain lower IQ scores and dysregulated COMT expression among three common mental illnesses.Keywords: first-episode schizophrenia, FES, bipolar disorder, BD, first-episode major depressive disorder, MDD, catechol-O-methyltransferase, COMT, intelligence quotient, IQ

Background Dimensions are recommended as replacements for diagnostic categories of depression, but clinicians continue to use categories. Categories are appropriate if major, underlying changes in symptom structure occur above a clinical cut-off on a depression continuum. Methods Cross-sectional surveys of Chinese undergraduates (n = 39,446) 2014–2018 measured self-reported depressive symptoms, associated psychopathology and etiological risk factors using standardised instruments. We created a continuum using PHQ-9 scores and tested linear and extra-linear contrasts in associated psychopathology, and etiology. We carried out latent class analyses (LCA). Results Most symptoms showed linear increase, but depressed mood, anhedonia, and suicidal ideation showed marked increase at the severe end of the continuum. There was extra-linear increase in associated psychotic symptoms, other psychopathology, age, low family income, chronic pain and physical illness, childhood physical and sexual abuse, and neglect. Four LCs corresponding to Melancholic, Severe melancholic, Non-melancholic, and Mild depression were confirmed, but only above a clinical cut-off along the continuum. Etiological risk factors did not differentiate between classes but showed overall dramatic increase in impact above threshold of clinical severity. Limitations Only one self-report instrument was used (PHQ-9) to measure depression and diagnoses were not validated by clinical interviews. Conclusions Categories are necessary to describe the dramatic changes in underlying structure and symptom associations above a clinical threshold of severity. These result from extra-linear impact of etiological risk factors at the severe end of the depression continuum. Although the study confirmed melancholic and non-melancholic subtypes, further investigation should investigate etiological factors that determine this subdivision.

OBJECTIVES Low recognition and intervention rates of emotional disorders among nonpsychiatric clinical patients are primarily attributable to poor mental health awareness of patients and a paucity of mental health care resources. This study aims to investigate the association of a resource-saving brief web-based emotional-disorder self-screening plus a health self-education program (BWBED-SS + HSE) with improved mental health awareness and service-seeking attitudes among nonpsychiatric clinical patients. METHOD A sample of 2065 patients seeking health services in nonpsychiatric clinical settings underwent BWBED-SS + HSE using mobile terminals. Participants were defined as being at high risk of anxiety and/or depression according to the optimal cut-off point of ≥11 on the Huaxi emotional-distress index (HEI). RESULTS The rate of participants at high risk of anxiety and/or depression was 6.63%. Following participation in the BWBED-SS + HSE, after controlling for demographics, type of hospital, and test time, the rates of participants considering themselves as having an emotional disorder and willing to seek mental health services among those at high risk of anxiety and/or depression increased from 29.93% to 47.45% (adjusted odds ratio [aOR] = 2.28, p = .002) and from 11.68% to 29.93% (aOR = 3.65, p

Overexpression of RAD51 is found in many cancers including breast cancer and is associated with poor survival. Compared with normal cells, RAD51 promoter is hyperactive in cancer cells indicating that RAD51 is transcriptionally activated. However, little is known about the mechanisms and factors involved in RAD51 transcription regulation. Transcription corepressor, C-terminal binding protein 1 (CtBP1), is an oncogene repressing a panel of tumor suppressors transcription, which contributes to cancer progression. In this study, immunohistochemistry (IHC) revealed that RAD51 expression was positively correlated with CtBP1 expression in breast cancer patient tissues; short hairpin RNA-mediated CtBP1 depletion, chromatin immunoprecipitation, and dual-luciferase reporter assays showed that CtBP1 activated RAD51 transcription in breast cancer cells. Depletion of CtBP1 increased breast cancer cells' sensitivity to cisplatin and, in turn, expression of exogenous RAD51 in the CtBP1-depleted breast cancer cells increased resistance to cisplatin. The results demonstrated that CtBP1 conferred breast cancer cells resistance to cisplatin through transcriptional activation of RAD51.

Objective: To identify the potential biomarkers for predicting depression in diabetes mellitus using support vector machine to analyze routine biochemical tests and vital signs between two groups: subjects with both diabetes mellitus and depression, and subjects with diabetes mellitus alone.Methods: Electronic medical records upon admission and biochemical tests and vital signs of 135 patients with both diabetes mellitus and depression and 187 patients with diabetes mellitus alone were identified for this retrospective study. After matching on factors of age and sex, the two groups (n = 72 for each group) were classified by the recursive feature elimination-based support vector machine, of which, the training data, validation data, and testing data were split for ranking the parameters, determine the optimal parameters, and assess classification performance. The biomarkers were identified by 10-fold cross validation.Results: The experimental results identified 8 predictive biomarkers with classification accuracy of 78%. The 8 biomarkers are magnesium, cholesterol, AST/ALT, percentage of monocytes, bilirubin indirect, triglyceride, lactic dehydrogenase, and diastolic blood pressure. Receiver operating characteristic curve analysis was also adopted with area under the curve being 0.72.Conclusions: Some biochemical parameters may be potential biomarkers to predict depression among the subjects with diabetes mellitus.

Objective Inflammation plays a crucial role in the pathogenesis of major depressive disorder (MDD) and bipolar disorder (BD). However, the underlying neurobiological mechanisms are poorly understood. This study aimed to examine whether the dysregulation of complement components contributes to brain structure deficits in BD and MDD patients. Methods A total of 52 BD patients, 35 MDD patients, and 53 mentally healthy controls were recruited from the inpatient and outpatient departments of West China Hospital of Sichuan University. The human complement panel 2-immunology multiplex assay was used to measure the levels of complement C1q, C3, C3b, C4, factor B, factor H, and properdin. Whole brain-based comparison was performed to investigate differences in gray matter volume and cortical thickness among the BD, MDD, and control groups, and relationships were explored between neuroanatomical differences and levels of complement components.Results The gray matter volume in the medial orbital frontal cortex (mOFC) and middle cingulum decreased in both patient groups, while the cortical thickness of the left precentral and left superior frontal gyrus was affected differently. Log10-transformed concentrations of C1q, C4, factor B, factor H, and properdin were higher in both patient groups than in controls, while levels of C1q, factor H, and properdin showed a significant negative correlation with gray matter volume in the mOFC at the voxel-wise level.Conclusion Greater inflammation in mOFC was observed in BD and MDD patients than in controls. Structural deficits in both patient groups were associated with elevated levels of certain complement factors, providing insight into the neuro-inflammatory pathogenesis of mood disorders.

Background: Neurobiological mechanisms underlying the development of major depressive disorder (MDD) may differ depending on onset ages. Our aim was to determine whether regional homogeneity (ReHo) changes in early-onset depression (EOD) and late-onset depression (LOD) are different, which could also delineate EOD and LOD.Methods: Ninety-one MDD patients and 115 healthy controls (HCs) were recruited, and resting-state functional magnetic resonance imaging data were collected. The ReHo comparison was conducted using analysis of variance.Results: Compared with HCs, MDD patients showed decreased ReHo in the left precentral gyrus and the left middle cingulum area, and increased ReHo in the left middle orbital frontal gyrus and superior temporal gyrus. Compared with LOD patients, young HC separately, EOD patients had significantly increased ReHo in the right inferior frontal triangular gyrus and the left postcentral gyrus. However, compared with young HC, EOD patients showed decreased ReHo in the right superior frontal gyrus/supplementary motor area and the right medial frontal gyrus. ReHo in the right inferior frontal triangular gyrus was negatively correlated with the severity of cognitive disturbance in LOD patients (r = −0.47, p = 0.002), but not in EOD patients (r = 0.21, p = 0.178).Conclusion: MDD patients with different onset ages may have different pathophysiological mechanisms; the EOD patients had more abnormal ReHo than LOD patients in the prefrontal lobe, especially the right inferior frontal triangular gyrus.

Background: Major depressive disorder (MDD) is a common disease which is complicated by metabolic disorder. Although MDD has been studied relatively intensively, its metabolism is yet to be elucidated.Methods: To profile the global pathophysiological processes of MDD patients, we used metabolomics to identify differential metabolites and applied a new database Metabolite set enrichment analysis (MSEA) to discover dysfunctions of metabolic pathways of this disease. Hydrophilic metabolomics were applied to identify metabolites by profiling the plasma from 55 MDD patients and 100 sex-, gender-, BMI-matched healthy controls. The metabolites were then analyzed in MSEA in an attempt to discover different metabolic pathways. To investigate dysregulated pathways, we further divided MDD patients into two cohorts: (1) MDD patients with anxiety symptoms and (2) MDD patients without anxiety symptoms.Results: Metabolites which were hit in those pathways correlated with depressive and anxiety symptoms. Altogether, 17 metabolic pathways were enriched in MDD patients, and 23 metabolites were hit in those pathways. Three metabolic pathways were enriched in MDD patients without anxiety, including glycine and serine metabolism, arginine and proline metabolism, and phenylalanine and tyrosine metabolism. In addition, L-glutamic acid was positively correlated with the severity of depression and retardation if hit in MDD patients without anxiety symptoms.Conclusions: Different kinds of metabolic pathophysiological processes were found in MDD patients. Disorder of glycine and serine metabolism was observed in both MDD patients with anxiety and those without.

Background Relatively few studies have compared posttraumatic stress disorder (PTSD) symptoms following a disaster among children of different ethnicities. We sought to investigate the differences in PTSD symptoms between the ethnic Hui and Han child survivors of the 2008 Wenchuan earthquake in China. Methods This study collected data from 1,951 Han and 247 Hui child survivors of the 2008 Wenchuan earthquake in China. The children ranged from 7 to 15 years of age. Earthquake-related exposures were measured using a modified version of the PsySTART Rapid Triage System. PTSD symptoms were evaluated using the University of California, Los Angeles PTSD-Reaction Index (UCLA PTSD-RI). Personality characteristics were assessed using the Junior Eysenck Personality Questionnaire (JEPQ). Multiple linear regression was used to investigate the association between the ethnicity and the severity of PTSD symptoms. Multiple logistic regression was used to investigate the association between the ethnicity and the percentage of screening positive for PTSD symptoms. Results The average UCLA PTSD-RI total score of the ethnic Hui group (27.01 ± 9.24) was significantly higher than that of the ethnic Han group (25.12 ± 9.17) (t = −3.05, p = 0.002), as were the avoidance/numbness (Hui: 10.02 ± 4.82; Han: 9.04 ± 4.60, t = −3.12, p = 0.002) and arousal scores (Hui: 9.36 ± 3.64; Han: 8.79 ± 3.42, t = −2.44, p = 0.015). The percentage of screening positive for D criteria (arousal symptoms) also differed significantly between the ethnic Han (41.9%, 95% CI [39.7–44.1%]) and Hui (48.6%, 95% CI [42.3–54.9%]) groups (χ2 = 3.97, p = 0.046). Ethnicity was associated with the avoidance/numbness symptom score following adjustments for sex, age, personality traits and earthquake exposure experiences by multiple linear regression (B: 0.61, 95% CI [0.04–1.17], p = 0.035). The initial significant associations between the ethnicity and the arousal symptoms score and the PTSD total score disappeared while adjusting for the subjective earthquake exposure experiences (Model 5: arousal symptoms, B = 0.41, 95% CI [−0.01 to 0.83], p = 0.056; PTSD, B = 1.00, 95% CI [−0.07 to 2.07], p = 0.066). The initial significant association between the ethnicity and the percentage of screening positive for D criteria disappeared while adjusting for the objective earthquake exposure experiences (Model 4: OR = 1.32, 95% CI [1.00–1.75], p = 0.052). Conclusion This study is the first to report the relationship between the ethnicity and PTSD symptoms among child survivors following a disaster. The findings of this study suggest that the trauma-focused cognitive behavior therapy could also be an effective treatment for Chinese ethnic Hui and Han children who are suffering from PTSD. Future research could be designed to examine whether cultural differences in perceptions and interpretations may account for the variations in subjective experiences. More attention should be paid to the ethnic minority children with PTSD in the future.

Background It is widely acknowledged that childhood adversities (CAs) and recent stress are potential risk factors for adult depression. However, the mechanism(s) by which interactions of CAs with recent stress affect adult depression remain unclear. Aims To investigate the predictive association of the interaction among CAs and recent stress with early-adult depression. Method We conducted an annual survey of all freshmen for the period of 2016-2018 in a Chinese comprehensive university, with a sample size of 23,206. An online questionnaire including standardized self-report instruments was used to assess sociodemographic factors, childhood experiences of left-behind (CELB), and maltreatments (CEMTs) including beating (CEB), neglect (CEN), sexual abuse (CESA), recent stress, and current depression (measured by the 9-item Patient Health Questionnaire). Results The correlation of Individual CAs and recent stress was significant. In addition to their significant independent/direct incremental effects, all surveyed CAs were associated with increased severity of early-adult depression, and increased frequency of clinically significant depression (CSD), through significant associations with recent stress (mediation effect). History of CEMTs including CEB, CEN, and CESA significantly increased the effects of recent stress on depression (moderation effect). Conclusions Chinese undergraduate students reported frequent history of exposure to CAs, which increased the likelihood of depression in early adulthood, not only directly but also through the increasing the likelihood (mediation effect) and impact (moderation effect) of recent stress on depression. These novel findings may help to extend our understanding of environmental determinants of depression, and to guide further research, clinical practice, and policy in this context.

Background Previous research using whole-brain neuroimaging techniques has revealed structural differences of grey matter (GM) in alcohol use disorder (AUD) patients. However, some of the findings diverge from other neuroimaging studies and require further replication. The quantity of relevant research has, thus far, been limited and the association between GM and abstinence duration of AUD patients has not yet been systematically reviewed. Methods The present research conducted a meta-analysis of voxel-based GM studies in AUD patients published before Jan 2021. The study utilised a whole brain-based d-mapping approach to explore GM changes in AUD patients, and further analysed the relationship between GM deficits, abstinence duration and individual differences. Results The current research included 23 studies with a sample size of 846 AUD patients and 878 controls. The d-mapping approach identified lower GM in brain regions including the right cingulate gyrus, right insula and left middle frontal gyrus in AUD patients compared to controls. Meta-regression analyses found increasing GM atrophy in the right insula associated with the longer mean abstinence duration of the samples in the studies in our analysis. GM atrophy was also found positively correlated with the mean age of the samples in the right insula, and positively correlated with male ratio in the left middle frontal gyrus. Conclusions GM atrophy was found in the cingulate gyrus and insula in AUD patients. These findings align with published meta-analyses, suggesting they are potential deficits for AUD patients. Abstinence duration, age and gender also affect GM atrophy in AUD patients. This research provides some evidence of the underlying neuroanatomical nature of AUD.

Background: To assess the subjective concordance on mental health service needs in hospitalized patients between patients and doctors in China. Methods: A cross-sectional study was performed in one day. All hospitalized inpatients from selected departments of West China Hospital were recruited as potential participants. A questionnaire set including demographic variables and the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder 7-item scale (GAD-7) questionnaires were completed by the included patients. They and their doctors in-charge were asked if they perceived that the patients needed mental health services. Results: The overall response rate in patients was 84.25% and the final sample consisted of 1,273 patients. Among those, 605 patients (47.53%) themselves believed that they needed mental health services, whereas only 345 patients (27.10%) were deemed to be in need of mental health services only by their doctors. Kappa statistics showed that the concordance rate between patients and doctors was low in the total patient group (kappa =0.055) and in the group of patients with significant depression or anxiety (kappa =0.080). A logistic regression analysis showed that the ward where the patients were treated was related to a consistent recognition of mental health needs (OR =1.667). Conclusions: The concordance between Chinese inpatient perception and doctor evaluation of mental health service needs for these patients was low. Therefore, it seems necessary to develop effective strategies to improve the detection rate, such as the use of screening-instruments and the training of health professionals in the detection of psycho-social distress.

We conducted a 24-week, randomized, double-blind parallel-controlled trial to test whether buspirone is beneficial to improve cognitive deficits of schizophrenia because it remains unclear. Two hundred patients received in random order either co-treatment buspirone with AAPDs or monotherapy with AAPDs. All patients had been treated with a stable dosage of AAPDs for at least three months. The positive and negative syndrome scale (PANSS), Hamilton Depression Scale-24 (HAMD-24), and 14-item Hamilton Rating Scale for Anxiety (HAMA-14) were used to evaluate clinical symptoms. The short version of Wechsler Adult Intelligence Scale-Revised in China (WAIS-RC) was used to assess neurocognitive function. Social function and family burden were evaluated by Social Disability Screening Schedule (SDSS) and Family Burden Interview Schedule (FBIS). All patients were enrolled at baseline and followed up after 12 and 24 weeks. A total of 196 patients completed the trial, with 99 in the combined treatment group and 97 in the control group. During the intervention, the score of PANSS, HAMD-24, and HAMA-14 decreased slightly without group differences. Repeated measures ANOVA showed significant differences between the two groups in the score of arithmetic, similarities, picture completion, block design, SDSS, and FBIS (P 0.05), but no difference was found with regard to the score of information, digital span test, or digital symbols (P 0.05). In conclusion, co-treatment with buspirone and APPDs outperformed APPDs alone in improving cognitive deficit and reducing family burden of schizophrenia. Buspirone may be a promising candidate for co-treatment of schizophrenia-associated cognitive deficits.

Background: Research on antipsychotics and early mortality in schizophrenia has arisen from Western countries and results show that mortality from natural causes is obviously increased in schizophrenia. China, differs largely from Western countries in health and social welfare systems, and Asian patients are more susceptible to side-effects and might require less antipsychotics than their Western counterparts. We, therefore, investigated the association between antipsychotic use and increased mortality from natural causes among patients with schizophrenia in China. Methods: We conducted a population-based nested case-control study using patients' hardcopy archives obtained from the Severe Mental Health Disorder Systems of Chengdu between January 1, 2006 and December 31, 2013. We identified all schizophrenic patients aged 18-65 years who died of natural causes in 2013 (N=157), and their age- and gender-matched controls (N=444). Results: Antipsychotic use was more frequent in controls than in cases (59.9% vs 32.5%). Risk of death decreased significantly in those receiving antipsychotic monotherapy (adjusted odds ratio=0.27, 95% CI=0.16-0.46) and antipsychotic polypharmacy (adjusted odds ratio=0.29, 95% CI=0.12-0.70) than antipsychotic-free patients. Compared with monotherapy, antipsychotic-free treatment was associated with prominently increased mortality (adjusted odds ratio=3.64, 95% CI=2.18-6.08). When stratified by age and gender, the results remained unchanged. Conclusion: Antipsychotic monotherapy significantly decreased mortality from natural causes in schizophrenic patients while antipsychotic polypharmacy did not contribute to the excess mortality and deserves further clarification. We need to improve the physical health of schizophrenic patients and promote health education among community mental health staff and primary caregivers.

This study compared the topological organization of brain function in never-treated and treated long-term schizophrenia patients. In a cross-sectional study, 21 never-treated schizophrenia patients with illness duration over 5 years, 26 illness duration-matched antipsychotic-treated patients and 24 demographically-matched healthy controls underwent a resting-state functional magnetic resonance imaging (MRI) scan. The topological properties of brain functional networks were compared across groups, and then we tested for differential age-related effects in regions with significant group differences. Both never-treated and antipsychotic-treated schizophrenia patient groups showed altered nodal centralities in left pre-/postcentral gyri relative to controls. Never-treated patients demonstrated reduced global efficacy, decreased nodal centralities in right amygdala/hippocampus and bilateral putamen/caudate relative to antipsychotic-treated patients and controls. No significant relationships of age and altered functional metrics were seen in either patient group, and no alterations were greater in the treated group. These findings provide insight into brain function deficits over the longer-term course of schizophrenia independent from potential effects of antipsychotic medication. The presence of greater alterations in never-treated than treated patients suggests that long-term antipsychotic treatment may partially protect or enhance brain global and nodal topological function over the course of schizophrenia, notably involving the amygdala, hippocampus, and striatum that have long been associated with the disorder.

Purpose: Major depression disorder (MDD) was associated with inflammatory processes, but association results of inflammatory syndrome and MDD were inconsistent. To provide more evidence, we measured the plasma levels of IL-1β, IL-6, interferon (INT)-α2, INT-γ, and tumor necrosis factor (TNF)-α in patients having MDD and explored correlations between the five proinflammatory cytokines and specific depressive symptoms. Patients and methods: Plasma concentrations of IL-1β, IL-6, INT-α2, INT-γ, and TNF-α were measured using ELISA for 44 MDD patients and 54 healthy controls. Patients with MDD were assessed on the 17-item Hamilton Depression Rating Scale (HAMD-17), and a total score and five syndrome scores were acquired. Results: IL-6 levels in depressed patients were significantly elevated than in healthy controls, but no significant differences were observed in the levels of INF-α2, INF-γ, IL-1β, or TNF-α. In addition, correlation analysis revealed that sleep disturbances positively correlated with IL-6. Although there was no significant difference between the two groups in the levels of INF-α2, a significant positive correlation between IFN-α2 and retardation was observed. Conclusion: Elevated IL-6 levels were observed in MDD patients and IL-6 may correlate with sleep disturbances.

Progressive brain volume atrophy has been reported in patients with schizophrenia. However, whether this progress differs between patients with primary negative symptoms (deficit schizophrenia; DS) and those without such symptoms (nondeficit schizophrenia; NDS) is unknown. Here, we examined grey matter volume (GMV) and white matter volume (WMV) changes over 12 months in 34 first-episode treatment-naive patients with schizophrenia (14 DS and 20 NDS) and 32 healthy controls (HCs) using structural magnetic resonance imaging and voxel-based morphometry. At baseline, compared to HCs, patients with DS but not NDS had less WMV in bilateral posterior limb of the internal capsule (PLIC) and cerebellar tonsil (P 0.05, FDR corrected) and smaller GMV in the cerebellar culmen (P 0.05, FWE corrected). At follow-up, NDS group showed WMV reduction in bilateral PLIC (P 0.05, FDR corrected), while DS group showed no progressive WMV changes. While both patient groups exhibited GMV reduction in the hippocampus and insular cortex, patients with NDS showed additional GMV loss in the frontal and cingulate cortex and a selective increase in GMV in the left thalamus (P 0.05 FWE corrected). Our study revealed double dissociations in developmental brain volume changes in the first year after clinical contact for psychosis in DS versus NDS patients.

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.

BackgroundWhether borderline personality disorder (BPD) and bipolar disorder are the same or different disorders lacks consistency.AimsTo detect whether grey matter volume (GMV) and grey matter density (GMD) alterations show any similarities or differences between BPD and bipolar disorder.MethodWeb-based publication databases were searched to conduct a meta-analysis of all voxel-based studies that compared BPD or bipolar disorder with healthy controls. We included 13 BPD studies (395 patients with BPD and 415 healthy controls) and 47 bipolar disorder studies (2111 patients with bipolar disorder and 3261 healthy controls). Peak coordinates from clusters with significant group differences were extracted. Effect-size signed differential mapping meta-analysis was performed to analyse peak coordinates of clusters and thresholds (P< 0.005, uncorrected). Conjunction analyses identified regions in which disorders showed common patterns of volumetric alteration. Correlation analyses were also performed.ResultsPatients with BPD showed decreased GMV and GMD in the bilateral medial prefrontal cortex network (mPFC), bilateral amygdala and right parahippocampal gyrus; patients with bipolar disorder showed decreased GMV and GMD in the bilateral medial orbital frontal cortex (mOFC), right insula and right thalamus, and increased GMV and GMD in the right putamen. Multi-modal analysis indicated smaller volumes in both disorders in clusters in the right medial orbital frontal cortex. Decreased bilateral mPFC in BPD was partly mediated by patient age. Increased GMV and GMD of the right putamen was positively correlated with Young Mania Rating Scale scores in bipolar disorder.ConclusionsOur results show different patterns of GMV and GMD alteration and do not support the hypothesis that bipolar disorder and BPD are on the same affective spectrum.Declaration of interestNone.

Substantial evidence supports the neurodevelopmental hypothesis of schizophrenia. Meanwhile, progressive neurodegenerative processes have also been reported, leading to the hypothesis that neurodegeneration is a characteristic component in the neuropathology of schizophrenia. However, a major challenge for the neurodegenerative hypothesis is that antipsychotic drugs used by patients have profound impact on brain structures. To clarify this potential confounding factor, we measured the cortical thickness across the whole brain using high-resolution T1-weighted magnetic resonance imaging in 145 first-episode and treatment-naïve patients with schizophrenia and 147 healthy controls. The results showed that, in the patient group, the frontal, temporal, parietal, and cingulate gyri displayed a significant age-related reduction of cortical thickness. In the control group, age-related cortical thickness reduction was mostly located in the frontal, temporal, and cingulate gyri, albeit to a lesser extent. Importantly, relative to healthy controls, patients exhibited a significantly smaller age-related cortical thickness in the anterior cingulate, inferior temporal, and insular gyri in the right hemisphere. These results provide evidence supporting the existence of neurodegenerative processes in schizophrenia and suggest that these processes already occur in the early stage of the illness.

Objective: To investigate the prevalence rates of depression anxiety and suicidal ideation among Chinese general hospital inpatients and to identify the potential associations with sociodemographic...

BackgroundPrevious studies have inferred a strong genetic component in schizophrenia. However, the genetic variants involved in the susceptibility to schizophrenia remain unclear.AimsTo detect potential gene pathways and networks associated with schizophrenia, and to explore the relationship between common and rare variants in these pathways and abnormal white matter integrity in schizophrenia.MethodThe analysis included 100 first-episode treatment-naïve patients with schizophrenia and 140 healthy controls. A network-based analysis was carried out on the data collected from the Psychiatric Genomics Consortium Phase I (PGC-I). Based on our genome-wide association study and whole-exome sequencing data-sets, we performed a gene-set analysis to detect associations between the combining effects of common and rare genetic variants and abnormal white matter integrity in schizophrenia.ResultsPatients had significantly reduced functional anisotropy in the left and right anterior cingulate cortex, left and right precuneus and extra-nuclear (t = 4.61–5.10, PFDR < 0.01), compared with controls. Generated from co-expression network analysis of the PGC-1 summary statistics of schizophrenia, a subnetwork of 207 genes associated with schizophrenia was identified (P < 0.01), and 176 genes were co-expressed in four gene modules. Functional enrichment analysis for genes in each module revealed that the yellow module was enriched with highly co-expressed, innate immune response genes. Furthermore, rare variants of enriched genes in the yellow module were associated with reduced functional anisotropy in the left anterior cingulate cortex (P = 0.006; Padjusted = 0.024) in patients only.ConclusionsThe pathogenesis of schizophrenia may be substantially influenced by genes involved in the immune system, via both pathway and network.Declaration of interestsNone.

Background Coronavirus disease 2019 (COVID-19) is leading to numerous psychological outcomes, especially emotional distress. Individuals with early life adversity (ELA) may be more susceptible to those psychological stresses during this epidemic. Aims To measure the effect of the ELA on acute stress reactions, anxiety and depression during the COVID-19 epidemic, and to examine whether specific trauma types and frequencies of exposure are associated with a more severe acute stress reaction and increased risk of anxiety and depressive symptoms. Method This investigation was performed at college students in a comprehensive University of China. The online self-report questionnaire included ELA experiences, exposure to epidemic-related events, acute stress reactions, and anxiety and depression symptoms during the COVID-19 epidemic. Logistic regression and stepwise regression were used to assess the associations and interactions among these variables. Results Participants with ELA reported more exposure to epidemic-related events and more severe stress reactions during the epidemics than did those with no ELA. The experience of ELA is associated with acute stress reactions, anxiety and depression in early adulthood. Furthermore, experiencing more ELA during childhood may not only increase the risk of anxiety and depression episode in early adulthood but also lead to more severe acute stress reactions during the epidemic. Conclusion Regardless of specific ELA types, ELAs have longer time effects on individual's susceptibility to stress. Under this epidemic, the mental health in young adults with ELA needs more attention.

Background It is unclear whether psychotic experiences (PEs) gradually merge into states of clinical psychosis along a continuum which correspond to a dimensional classification or whether latent classes appear above a certain severity threshold which correspond better to diagnostic categories of psychosis. Methods Annual cross-sectional surveys, 2014–19, among Chinese undergraduates (N = 47,004) measured PEs, depression and etiological risk factors using standardized self-report instruments. We created a psychosis continuum with five levels and tested linear and extra-linear contrasts in associated etiological risk factors, before and after adjustment for depression. We carried out latent class analysis. Results Categorical expression of psychosis, including hallucinations and delusions, nuclear symptoms, and nuclear symptoms and depression were found at severe level 5. Etiological risk factors which impacted linearly across the continuum were more common for depression. Child maltreatment impacted extra-linearly on both psychosis and depression. Family history of psychosis impacted linearly on psychosis; male sex and urban birth impacted extra-linearly and were specific for psychosis. Four latent classes were found, but only at level 5. These corresponded to nuclear schizophrenia symptoms, nuclear schizophrenia and depressive symptoms, severe depression, and an unclassified category with moderate prevalence of PEs. Conclusion Quantitative and qualitative changes in the underlying structure of psychosis were observed at the most severe level along a psychosis continuum, where four latent classes emerged. These corresponded to existing categorical classifications but require confirmation with clinical interview. PEs are non-specific and our findings suggest some are on a continuum with depression, whilst others are on a continuum with non-affective psychosis. Differing patterns of impact from etiological risk factors across the spectrum of psychopathology determine outcome at the most severe level of these continua.

Objective Seed-based resting-state functional connectivity (rs-FC) of inferior frontal gyrus (IFG), as well as sustained attention cognitive deficit are consistently reported to be impaired in bipolar disorders. However, whether these deficits exist across mood states and euthymic state are lacking. We compared rs-FC of IFG and sustained attention of bipolar patients in (hypo) mania, depression and euthymia, with controls. We also explored the interrelationships between clinical, cognitive, and imaging measurements. Methods Participants included 110 bipolar subjects: 46 manic/hypomanic, 35 euthymic, and 29 depressed, matched with 41 healthy controls (HCs) underwent structural magnetic resonance imaging (MRI) and resting-state functional MRI scans. Seed-based functional connectivity analyses were performed focused on bilateral IFG seeds. Clinical symptoms and sustained attention function were measured. Stepwise linear regression analysis was conducted to explore predictors of sustained attention measurements. Results Increased rs-FC between right IFG and bilateral frontal pole/superior frontal gyrus, precuneus, and posterior cingulate gyrus, as well as decreased rs-FC between right IFG and sensorimotor areas, anterior middle cingulate gyrus were found in all three bipolar subgroups compared with HCs. Impaired sustained attention measurement was found in bipolar manic/hypomanic and depressive subgroups compared with HCs. Linear regression analyses revealed a significant impact of the manic symptoms and psychotic symptoms on the performance of sustained attention task. Conclusions Our results revealed that IFG seed-based resting-state functional networks involved in emotion regulation and cognitive function were trait-like deficit in bipolar patients. Higher manic levels and psychotic symptoms were predictors of a worse sustained attention performance.

In early 2020, the COVID-19 outbreak complicated the diagnosis, treatment and rehabilitation of patients with substance use disorders and increased the risks of substance abuse and addictive behaviours, such as online gaming disorders, in the general public. Substance use disorder is a chronic recurrent brain disease characterised by strong cravings, high recurrence rates, and a high proportion of comorbidity of mental and physical disorders.1 Therefore, regular long-term therapeutic interventions are critical to preventing drug relapses while maintaining withdrawal. COVID-19 severely affects normal medical diagnoses, treatments and managements of patients with substance use disorder coupled with addiction-related behaviour. It also adversely impacts the mental state of the general public in several ways and leads to broader symptoms, including anxiety, tension and insomnia, that may increase the risk of alcohol abuse, sedative and hypnotic drug abuse, and other addictive behaviours. The State Council’s Comprehensive Team for Joint Prevention and Control of COVID-19 released a series of documents to address the importance of focusing on the prevention and control of both imported cases and internal transmission in particularly vulnerable places, such as supervision sites, pension facilities, welfare homes and mental health institutions.2 3 It is also of utmost importance to ensure the continuous, regular and effective treatment of existing patients with addiction problems, reduce the risk of drug relapse and prevent new cases of addiction during the pandemic. To this end, the Chinese Association of Drug Abuse Prevention and Treatment, the Academic Group of Drug Dependence of the Chinese Society of Psychiatry, the Academic Group of Addiction of the Chinese Society of Psychosomatic Medicine, and the Specialty Committee of Addiction Medicine of the Chinese Psychiatrist Association jointly published an expert consensus to inform the public with proper guidance to prevent addiction and provide professional diagnoses, treatment and management of these addictions. …

Objective This study aims to better characterize the metabolic effects of antipsychotics in the early stage of treatment in first-episode patients with schizophrenia. Methods We performed a retrospective real-world study in a naturalistic setting that included inpatients with first-episode drug-naive schizophrenia; metabolic profiles were measured at baseline and 2 weeks and 4 weeks after antipsychotic treatment. The metabolic profiles of medicated patients with first-episode schizophrenia were also included. Results Insulin resistance, based on the ratio of triglycerides to high-density lipoprotein cholesterol (TG/HDL-C), increased significantly after 2 weeks of antipsychotic treatment, whereas fasting glucose (FG) decreased significantly. Regarding lipid metabolism, triglycerides (TG), cholesterol (CHOL) and low-density lipoprotein cholesterol (LDL-C) increased significantly after 2 weeks of antipsychotic treatment; however, high-density lipoprotein cholesterol (HDL-C) decreased significantly after 4 weeks of antipsychotic treatment. There were no statistically significant differences between the antipsychotic groups in any of the metabolic parameters evaluated. Conclusion Our study revealed that insulin resistance and lipid metabolic abnormalities occurred as early as two weeks after the initiation of antipsychotic treatment. Our findings suggest that metabolic profiles should been monitored in the early stage of antipsychotics treatment in clinical practice. Further research is needed to explore the underlying mechanisms of the short-term effects of antipsychotics on metabolic parameters.

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.

Background Posterior cingulate cortex (PCC) is a key aspect of the default mode network (DMN). Aberrant PCC functional connectivity (FC) is implicated in schizophrenia, but the potential for PCC related changes as biological classifier of schizophrenia has not yet been evaluated. Methods We conducted a data-driven approach using resting-state functional MRI data to explore differences in PCC-based region- and voxel-wise FC patterns, to distinguish between patients with first-episode schizophrenia (FES) and demographically matched healthy controls (HC). Discriminative PCC FCs were selected via false discovery rate estimation. A gradient boosting classifier was trained and validated based on 100 FES vs. 93 HC. Subsequently, classification models were tested in an independent dataset of 87 FES patients and 80 HC using resting-state data acquired on a different MRI scanner. Results Patients with FES had reduced connectivity between PCC and frontal areas, left parahippocampal regions, left anterior cingulate cortex, and right inferior parietal lobule, but hyperconnectivity with left lateral temporal regions. Predictive voxel-wise clusters were similar to region-wise selected brain areas functionally connected with PCC in relation to discriminating FES from HC subject categories. Region-wise analysis of FCs yielded a relatively high predictive level for schizophrenia, with an average accuracy of 72.28% in the independent samples, while selected voxel-wise connectivity yielded an accuracy of 68.72%. Conclusion FES exhibited a pattern of both increased and decreased PCC-based connectivity, but was related to predominant hypoconnectivity between PCC and brain areas associated with DMN, that may be a useful differential feature revealing underpinnings of neuropathophysiology for schizophrenia.

Schizophrenia is genetic in origin and associated with a fecundity disadvantage. The deficits in schizophrenia have been attributed to variation related to the human capacity for language or brain laterality. How sex influences the relative connectivity of the 2 hemispheres is a route to understanding these 2 functions. Using resting-state functional magnetic resonance imaging (fMRI) we searched for sex- and hemisphere-specific changes in whole-brain functional-connectivity in multi-site datasets (altogether 672 subjects including 286 patients, all right-handed) in the first-episode schizophrenia (illness duration ≤ 1 year, mostly drug naive) and in chronic stages of schizophrenia (illness duration > 1 year), respectively. We used meta-analyses to integrate data from different sources concerning individuals at the same illness stage. We found first-episode male patients are predominantly left-lateralized in aberrant connectivity with a focus on Broca's area. Female patients show a lesser degree of lateralization than males, but to the right particularly in orbital frontal cortex. In the chronic stage, the focus of aberrant connectivity shifted from anterior to posterior structures with prominent involvement of the thalamus and pre- and post-central gyri bilaterally and in both sexes. While the "deviant connectivity" is right-sided in both the first-episode and the chronic stages in females, in males there is a shift between stages from the left to the right hemisphere. We hypothesized that the pathophysiology of schizophrenia may lie in the interaction between sex and lateralization, ie, in genetic mechanisms located on the X and Y chromosomes, intrinsic to the evolution of language.

Background Depression and anxiety among general hospital patients are common and under-recognized in China. This study aimed toward developing a short questionnaire for screening depression and anxiety in non-psychiatric clinical settings, and to test its reliability and validity. Methods The item pool which included 35 questions about emotional distress was drafted through a comprehensive literature review. An expert panel review and the first clinical test with 288 general hospital patients were conducted for the primary item selection. The second clinical test was performed to select the final item in 637 non-psychiatric patients. The reliability and validity of the final questionnaire were tested in 763 non-psychiatric patients, in which 211 subjects were interviewed by psychiatrists using Mini International Neuropsychiatric Interview (MINI). Multiple data analysis methods including principal components analysis (PCA), item response theory (IRT), and receiver operating characteristic (ROC) curve were used to select items and validate the final questionnaire. Results The series selection of items resulted in a 9-item questionnaire, namely Huaxi Emotional-distress Index (HEI). The Cronbach's α coefficient of HEI was 0.90. The PCA results showed a unidimensional construct. The area under the ROC curve (AUC) was 0.88 when compared with MINI interview. Using the optimal cut-off score of HEI (11/12), the sensitivity and specificity were 0.880 and 0.766, respectively. Conclusions The HEI is considered as a reliable and valid instrument for screening depression and anxiety, which may have substantial clinical value to detect patients' emotional disturbances especially in the busy non-psychiatric clinical settings in China.

The current study was designed to explore how disruption of specific molecular circuits in the cerebral cortex may cause sensorimotor cortico-striatal community structure deficits in both a mouse model and patients with schizophrenia. We used prepulse inhibition (PPI) and brain structural and diffusion MRI scans in 23 mice with conditional ErbB4 knockout in parvalbumin interneurons and 27 matched controls. Quantitative real-time PCR was used to assess the differential levels of GABA-related transcripts in brain regions. Concurrently, we measured structural and diffusion MRI and the cumulative contribution of risk alleles in the GABA pathway genes in first-episode treatment-naïve schizophrenic patients (n = 117) and in age- and sex-matched healthy controls (n = 86). We present the first evidence of gray and white matter impairment of right sensorimotor cortico-striatal networks and reproduced the sensorimotor gating deficit in a mouse model of schizophrenia. Significant correlations between gray matter volumes (GMVs) in the somatosensory cortex and PPI as well as glutamate decarboxylase 1 mRNA expression were found in controls but not in knockout mice. Furthermore, these findings were confirmed in a human sample in which we found significantly decreased gray and white matter in sensorimotor cortico-striatal networks in schizophrenic patients. The psychiatric risk alleles of the GABA pathway also displayed a significant negative correlation with the GMVs of the somatosensory cortex in patients. Our study identified that ErbB4 ablation in parvalbumin interneurons induced GABAergic dysregulation, providing valuable mechanistic insights into the sensorimotor cortico-striatal community structure deficits associated with schizophrenia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12264-019-00416-2) contains supplementary material, which is available to authorized users.

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.

Background Visual deficits have been reported in abundance by recent studies on major depressive disorder. Pattern glare manifests as visual distortions, such as the symptoms of headache, glare, eyestrain, illusions of shapes, colors, and motion when viewing repetitive striped patterns, of which some can be observed in major depressive disorder. Inspired by what mentioned, the present study aims to explore whether there exists association between pattern glare and major depressive disorder and further attempts to explore possible clinical diagnostic value of pattern glare in major depressive disorder. Methods Twenty-four patients diagnosed with major depressive disorder (MDDs group) were compared with 30 age-, gender- and education level-matched healthy control subjects (HCs group) on their visual stress with black-and-white gratings of different spatial frequencies-0.3 (low-SF), 2.3 (mid-SF), and 9.4 (high-SF) cycles per degree (c/deg)-which was named pattern glare test. The MDDs group divided into first episode medication-free group (fMDD) and recurrent medicated group (rMDD), comparisons of pattern glare scores (PGS) were performed within the MDDs group. We used Pearson and Spearman analysis to explore the relationship between some clinical indexes and pattern glare scores. ROC (receiver operating characteristic) curve was used to evaluate whether pattern glare test was able to discriminate patients and healthy controls. Results The mid-SF pattern glare score significantly elevated in patients with major depressive disorder compared to control subjects. No differences of pattern glare scores were found between fMDD and rMDD. A significant negative correlation between mid-high difference and age in HCs group was found. There were no correlations between other variables and pattern glare scores. The mid-SF score has limited value in the diagnosis of major depressive disorder. Conclusions We observed an increased level of pattern glare in patients with major depressive disorder, reflecting the existence of cortical hyper-excitability in major depressive disorder. The mid-SF score may have a value in understanding cortical excitability in major depressive disorder.

Objective The frontal-limbic circuit is hypothesized as sub-serving emotional regulation. We performed whole brain resting-state functional connectivity (rs-FC) analysis by studying the key hubs of frontal-limbic circuit: anterior cingulate cortex (ACC), bilateral insula subregions, bilateral amygdala (Amy) as seeds, separately, to discriminate bipolar depression (BipD) from unipolar depression (UniD). Methods We compared seed-based rs-FC of the frontal-limbic seeds with whole brain among 23 BipD participants; 23 age, gender, and depression severity matched patients with UniD, and 23 healthy controls (HCs). We also used support vector machine learning to study classification based on the rs-FC of ACC, bilateral insula subregions, and bilateral Amy seeds with whole brain. Results BipD showed increased rs-FC between the left ventral anterior insula (vAI) seed and the left anterior supramarginal gyrus (aSMG) and left postcentral gyrus, as well as increased rs-FC between left amygdala seed and the left aSMG when compared to HCs and UniD. Compared to UniD, BipD was associated with increased rs-FC between right dorsal anterior insula seed and right superior frontal gyrus, as well as increased rs-FC between left posterior insula seed and right precentral gyrus and right thalamus. Combined rs-FC of ACC, bilateral insula subregions and bilateral Amy seeds with the whole brain discriminated BipD from UniD with an accuracy of 91.30%. Conclusions Rs-FC of the emotional regulation circuit is more widely disturbed in BipD than UniD. Using rs-FC with this circuit may lead to further developments in diagnostic decision-making.

Supplemental Digital Content is available in the text, Major depressive disorder (MDD) is a common disease with both affective and cognitive disorders. Alterations in metabolic systems of MDD patients have been reported, but the underlying mechanisms still remains unclear. We sought to identify abnormal metabolites in MDD by metabolomics and to explore the association between differential metabolites and neurocognitive dysfunction. Plasma samples from 53 MDD patients and 83 sex-, gender-, BMI-matched healthy controls (HCs) were collected. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) system was then used to detect metabolites in those samples. Two different algorithms were applied to identify differential metabolites in 2 groups. Of the 136 participants, 35 MDD patients and 48 HCs had completed spatial working memory test. Spearman rank correlation coefficient was applied to explore the relationship between differential metabolites and working memory in these 2 groups. The top 5 metabolites which were found in sparse partial least squares-discriminant analysis (sPLS-DA) model and random forest (RF) model were the same, and significant difference was found in 3 metabolites between MDD and HCs, namely, gamma-glutamyl leucine, leucine-enkephalin, and valeric acid. In addition, MDD patients had higher scores in spatial working memory (SWM) between errors and total errors than HCs. Valeric acid was positively correlated with working memory in MDD group. Gamma-glutamyl leucine, leucine-enkephalin, and valeric acid were preliminarily proven to be decreased in MDD patients. In addition, MDD patients performed worse in working memory than HCs. Dysfunction in working memory of MDD individuals was associated with valeric acid.

Different patterns of gray matter volume (GMV) abnormalities have been reported between chronic patients with deficit schizophrenia (DS), relative to nondeficit schizophrenia (NDS) patients. However, it is not clear whether these differences are characteristic to the pathophysiology of DS or due to the effects of medications or illness durations. To address this issue, GMV in 88 first-episode, drug-naive patients with schizophrenia (44 DS and 44 NDS), 67 of their first-degree relatives and 84 healthy controls were assessed using voxel- based morphometry (VBM) and compared between groups. Correlations between GMV and clinical symptoms in patients were also assessed. Compared to controls, DS patients displayed more severe GMV reduction in the cerebellar culmen than NDS patients. GMV reduction in culmen was also observed in the first-degree relatives of DS (but not NDS) patients, suggesting possible different genetic risk in DS and NDS. The left insula was significantly smaller in DS patients than both NDS patients and controls, and smaller GMV of this region was associated with more severe negative symptoms in patients. Our results collectively indicate that DS might represent a distinct subtype of schizophrenia from NDS and the GMV change in left insula may be a morphological signature of DS.

Background Internet addiction has become a major global concern and a burden on mental health. However, there is a lack of consensus on its link to mental health outcomes. Objective The aim of this study was to investigate the associations between internet addiction severity and adverse mental health outcomes. Methods First-year undergraduates enrolled at Sichuan University during September 2015, 2016, 2017, and 2018 were invited to participate in the current study survey, 85.13% (31,659/37,187) of whom fully responded. Young’s 20-item Internet Addiction Test, Patient Health Questionnaire-15, Patient Health Questionnaire-9, Symptom Checklist 90, Six-Item Kessler Psychological Distress Scale, and Suicidal Behaviors Questionnaire-Revised were used to evaluate internet addiction, four psychopathologies (high somatic symptom severity, clinically significant depression, psychoticism, and paranoia), serious mental illness, and lifetime suicidality. Results The prevalence of students with mild, moderate, and severe internet addiction was 37.93% (12,009/31,659), 6.33% (2003/31,659), and 0.20% (63/31,659), respectively. The prevalence rates of high somatic symptom severity, clinically significant depression, psychoticism, paranoid ideation, and serious mental illness were 6.54% (2072/31,659), 4.09% (1294/31,659), 0.51% (160/31,659), 0.52% (165/31,659), and 1.88% (594/31,659), respectively, and the lifetime prevalence rates of suicidal ideation, suicidal plan, and suicidal attempt were 36.31% (11,495/31,659), 5.13% (1624/31,659), and 1.00% (315/31,659), respectively. The prevalence rates and odds ratios (ORs) of the four psychopathologies and their comorbidities, screened serious mental illness, and suicidalities in the group without internet addiction were much lower than the average levels of the surveyed population. Most of these metrics in the group with mild internet addiction were similar to or slightly higher than the average rates; however, these rates sharply increased in the moderate and severe internet addiction groups. Among the four psychopathologies, clinically significant depression was most strongly associated with internet addiction after adjusting for the confounding effects of demographics and other psychopathologies, and its prevalence increased from 1.01% (178/17,584) in the students with no addiction to 4.85% (582/12,009), 24.81% (497/2,003), and 58.73% (37/63) in the students with mild, moderate, and severe internet addiction, respectively. The proportions of those with any of the four psychopathologies increased from 4.05% (713/17,584) to 11.72% (1408/12,009), 36.89% (739/2003), and 68.25% (43/63); those with lifetime suicidal ideation increased from 24.92% (4382/17,584) to 47.56% (5711/12,009), 67.70% (1356/2003), and 73.02% (46/63); those with a suicidal plan increased from 2.59% (456/17,584) to 6.77% (813/12,009), 16.72% (335/2003), and 31.75% (20/63); and those with a suicidal attempt increased from 0.50% (88/17,584) to 1.23% (148/12,009), 3.54% (71/2003), and 12.70% (8/63), respectively. Conclusions Moderate and severe internet addiction were strongly associated with a broad group of adverse mental health outcomes, including somatic symptoms that are the core features of many medical illnesses, although clinically significant depression showed the strongest association. This finding supports the illness validity of moderate and severe internet addiction in contrast to mild internet addiction. These results are important for informing health policymakers and service suppliers from the perspective of resolving the overall human health burden in the current era of “Internet Plus” and artificial intelligence.

Purpose C-terminal binding protein 1 (CtBP1) is a transcriptional co-repressor that is overexpressed in many cancers. CtBP1 transcriptionally represses a broad array of tumor suppressors, which promotes cancer cell proliferation, migration, invasion, and resistance to apoptosis. Recent studies have demonstrated that CtBP1 is a potential target for cancer therapy. This study was designed to screen for compounds that potentially target CtBP1. Methods Using a structure-based virtual screening for CtBP1 inhibitors, we found protocatechuic aldehyde (PA), a natural compound found in the root of a traditional Chinese herb, Salvia miltiorrhiza, that directly binds to CtBP1. Microscale thermophoresis assay was performed to determine whether PA and CtBP1 directly bind to each other. Further, clustered regularly interspaced short palindromic repeats associated Cas9 nuclease-mediated CtBP1 knockout in breast cancer cells was used to validate the CtBP1 targeting specificity of PA. Results Functional studies showed that PA repressed the proliferation and migration of breast cancer cells. Furthermore, PA elevated the expression of the downstream targets of CtBP1, p21 and E-cadherin, and decreased CtBP1 binding affinity for the promoter regions of p21 and E-cadherin in breast cancer cells. However, PA did not affect the expression of p21 and E-cadherin in the CtBP1 knockout breast cancer cells. In addition, the CtBP1 knockout breast cancer cells showed resistance to PA-induced repression of proliferation and migration. Conclusion Our findings demonstrated that PA directly bound to CtBP1 and inhibited the growth and migration of breast cancer cells through CtBP1 inhibition. Structural modifications of PA are further required to enhance its binding affinity and selectivity for CtBP1.

Summary Background The China Mental Health Survey was set up in 2012 to do a nationally representative survey with consistent methodology to investigate the prevalence of mental disorders and service use, and to analyse their social and psychological risk factors or correlates in China. This paper reports the prevalence findings. Methods We did a cross-sectional epidemiological survey of the prevalence of mental disorders (mood disorders, anxiety disorders, alcohol-use and drug-use disorders, schizophrenia and other psychotic disorders, eating disorder, impulse-control disorder, and dementia) in a multistage clustered-area probability sample of adults from 157 nationwide representative population-based disease surveillance points in 31 provinces across China. Face-to-face interviews were done with a two-stage design by trained lay interviewers and psychiatrists with the Composite International Diagnostic Interview, the Structured Clinical Interview for DSM-IV Axis I disorders, the Community Screening Instrument for Dementia from the 10/66 dementia diagnostic package, and the Geriatric Mental State Examination. Data-quality control procedures included logic check by computers, sequential recording check, and phone-call check by the quality controllers, and reinterview check by the psychiatrists. Data were weighted to adjust for differential probabilities of selection and differential response as well as to post-stratify the sample to match the population distribution. Findings 32 552 respondents completed the survey between July 22, 2013, and March 5, 2015. The weighted prevalence of any disorder (excluding dementia) was 9·3% (95% CI 5·4–13·3) during the 12 months before the interview and 16·6% (13·0–20·2) during the participants' entire lifetime before the interview. Anxiety disorders were the most common class of disorders both in the 12 months before the interview (weighted prevalence 5·0%, 4·2–5·8) and in lifetime (7·6%, 6·3–8·8). The weighted prevalence of dementia in people aged 65 years or older was 5·6% (3·5–7·6). Interpretation The prevalence of most mental disorders in China in 2013 is higher than in 1982 (point prevalence 1·1% and lifetime prevalence 1·3%), 1993 (point prevalence 1·1% and lifetime prevalence 1·4%), and 2002 (12-month prevalence 7·0% and lifetime prevalence 13·2%), but lower than in 2009 (1-month prevalence 17·5%). The evidence from this survey poses serious challenges related to the high burdens of disease identified, but also offers valuable opportunities for policy makers and health-care professionals to explore and address the factors that affect mental health in China. Funding National Health Commission of Health (Ministry of Health) and Ministry of Science and Technology of China.