Vacuum-Vapor-Deposited 0D/3D All-Inorganic Perovskite Composite Films toward Low-Threshold Amplified Spontaneous Emission and Lasing.

Vacuum vapor deposition (VVD) is a promising way to advancing the commercialization of perovskite light sources owing to its convenience for wafer-scale mass production and compatibility with silicon photonics manufacturing infrastructure. However, the light emission performance of VVD-grown perovskites still lags far behind that of the conventional solution-processed counterparts due to their inferior luminescence properties. Here, a 0D/3D cesium-lead-bromide perovskite composite film is prepared on Si/SiO2 substrates through composition modulation with the VVD method, which exhibits an ultralow amplified spontaneous emission (ASE) threshold down to 14.3 µJ cm-2 in the optimal films, which is on par with that of the solution-processed counterparts. Meanwhile, they also display intriguing operational stability with negligible emission intensity decay under continuous excitation above ASE threshold for 4 h in the air. The outstanding ASE performance mainly originates from the reduced trap density and weakened electron-phonon coupling in the 3D CsPbBr3 phase enabled by the incorporation of the 0D Cs4 PbBr6 phase. Finally, by integrating the composite film with the distributed feedback (DFB) cavity, DFB lasing is achieved with a low threshold of 18.2 µJ cm-2 under nanosecond-pulsed laser pumping, which highlights the potential of VVD-processed perovskites for developing high-performance lasers.

Childhood adversity, adulthood adversity and suicidal ideation in Chinese patients with major depressive disorder: in line with stress sensitization.

The stress sensitization model indicates that early adversity (e.g., childhood stress) sensitizes individuals to subsequent proximal stress (e.g., stressful life events in adult life), thereby increasing their vulnerability to psychiatric disorders. However, the effect of stress sensitization on suicidality in patients with major depressive disorder (MDD) has not been previously investigated. Data for the present study were derived from the Objective Diagnostic Markers and Personalized Intervention in MDD Patients (ODMPIM) study. The psychiatric diagnosis and suicidal ideation were evaluated by the Mini-International Neuropsychiatric Interview (M.I.N.I.). We used a multiple logistic analysis to examine the association among childhood adversity (CA), adulthood adversity (AA) and suicidal ideation. Among 1084 MDD patients, 48.6% had suicidal ideation and 65.6% experienced life adversity during their childhood or adulthood. Patients who reported suicidal ideation were more likely to report CA (46.7% vs. 38.7%, P = 0.008) or AA (49.5% vs. 40.9%, P = 0.004) than patients without suicidal ideation. Patients who experienced two waves of adversity (both CA and AA) were associated with higher rates of suicidal ideation (odds ratio = 1.68, 95% CI = 1.19-2.37, P = 0.003); however, neither CA nor AA alone was associated with suicidal ideation. This study first verifies the hypothesis of stress sensitization on suicidal ideation in patients with MDD. Focusing on stress sensitization may enhance the early identification of MDD patients at suicidal risk and the ability to provide timely and appropriate intervention. Clinicaltrials.gov identifier: NCT02023567.

Common and distinct brain functional alterations in pharmacotherapy treatment-naïve female borderline personality disorder patients with and without auditory verbal hallucinations: a pilot study.

Auditory verbal hallucinations (AVHs) are experienced by approximately 25% of patients with borderline personality disorder (BPD). Despite the high incidence, the pathological features of AVH in BPD remain unclear. This study aimed to investigate whole-brain functional connectivity (FC), as measured by functional connectivity density (FCD), and its relationship with AVH in BPD. 65 pharmacotherapy treatment-naïve female BPD patients (30 with AVH and 35 without AVH), and 35 female healthy controls were investigated. Functional magnetic resonance imaging (fMRI) data were collected to assess whole-brain FC and functional connectivity density mapping (FCDM) was applied to the fMRI data to compute FCD features. Compared to the healthy controls, both BPD groups (BPD-AVH and BPD without AVH) exhibited significantly higher gFCD values in the bilateral prefrontal lobe, bilateral orbital lobule, and bilateral insula, and significantly lower gFCD values in the SMA, right anterior temporal lobule, and the ACC. These altered regions were significantly associated with AVH in the BPD subjects. Moreover, higher gFCD values were observed in the left posterior temporal lobule and posterior frontal lobule. Aberrant alterations also emerged in the left posterior temporal lobule and posterior frontal lobule, mainly in Broca and Wernicke regions. Nevertheless, there was no significant correlation between gFCD values and the severity of AVH as measured by the AVH scores. In summary, we have identified aberrations in the FC and brain metabolism of the aforementioned neural circuits/networks, which may provide new insights into BPD-AVH and facilitate the development of therapeutic approaches for treating AVH in BPD patients.

Severe sleep disturbance is associated with executive function impairment in patients with first-episode, treatment-naïve major depressive disorders.

BACKGROUND: Sleep disturbance and executive function impairment are common in patients with major depressive disorder (MDD), though the relationship between the two remains unclear. We investigated this association in first-episode, treatment-naïve patients with MDD. METHODS: We analyzed data from 242 patients with MDD. We divided the patients into 2 groups based on sleep disturbance severity and compared the executive function odds ratios between the groups. RESULTS: A total of 121 pairs of patients were matched (age 39.4 ± 10.1, 70.2% female). After propensity score matching, the odds ratios for cognitive impairment in patients with MDD and severe sleep disturbance were 1.922 (1.068-3.459, P = 0.029, q = 0.044) in executive functioning; 2.023 (1.211-3.379, P = 0.007, q = 0.021) in executive shifting. CONCLUSIONS: Sleep disturbance is associated with executive functioning impairment in first-episode, treatment-naïve patients with MDD. Severe sleep disturbance can be a marker and aid in recognizing executive function impairment in patients with first-episode treatment-naïve MDD. Severe sleep disturbance can be a potential modifiable factor to improve executive function in MDD, as well as an effective measurement to improve cognition for sleep symptom management that should be enforced at initial treatment of first-episode MDD. Further study is required to confirm our results. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02023567 ; registration date: December 2013.

Mental health stigma and mental health knowledge in Chinese population: a cross-sectional study.

BACKGROUND: Little is known about the public stigma on mental illness and mental health knowledge (MHK) in China, public stigma and low MHK can negatively affect patients' health and increase the burden of mental disorders on society. This study aimed at investigating the rates of stigma and MHK, the correlates of stigma and MHK, and the association between MHK and stigma among a Chinese population. METHODS: The data is from the Tianjin Mental Health Survey (TJMHS), which involved a large and a representative sample of adult community residents in the Chinese municipality of Tianjin (n = 11,748). In a 12% random subsample (n = 1775) the Perceived Discrimination and Devaluation scale (PDD) and a Mental Health Knowledge Questionnaire (MHKQ) were administered. First, percentages of the responses to the individual items of the PDD and MHKQ were investigated. Second, sociodemographic correlates of PDD and MHK, and the association between stigma and MHK were investigated. RESULTS: We found that a sizable proportion of participants responded that others would hold a negative attitude towards (former) mental patients, especially with regard to engaging in closer personal relationships. Most people were not familiar about the causes, treatments and prevention of mental illness. Resident area, age, education level, Per capita family income and employment status were related to devaluation score and MHKQ score. MHK was negatively associated with public stigma. CONCLUSIONS: There is room for improvement with regard to levels of public stigma and MHK in China. Providing psychoeducation to improve public MHK could also contribute to reduction of public stigma.

Help-seeking behaviors among Chinese people with mental disorders: a cross-sectional study.

BACKGROUND: Failure to seek treatment for mental health disorders is a serious public health concern. Unfortunately, there is little insight into help-seeking and its associated factors in China which has undergone rapid economic development in the past 30 years and has an increasing prevalence of mental disorder. Therefore, this study aimed to (1) investigate help-seeking rates in healthcare and non-healthcare settings and (2) investigate the correlates of help-seeking behavior in a large Chinese survey. METHODS: Data came from the Tianjin Mental Health Survey (TJMHS), a representative sample of adult community residents in the Chinese municipality of Tianjin (n = 11,748). Of these, 1759 individuals had ≥1 axis-I diagnosis according to the Diagnostic and Statistical manual- fourth edition (DSM-IV) and were administered a Help-Seeking Questionnaire. RESULTS: 15.7% of patients reported that they had ever sought help during their entire lifetime before the interview, with 4.5% seeking help in mental healthcare, 3.2% in other healthcare and 8.1% in non-healthcare settings (e.g., family, friends, and spiritual advisor). Among help-seekers, the first help was mostly sought in non-healthcare settings (58.4%), followed by healthcare (27.5%) and mental healthcare settings (24.5%). Female gender, younger age, having 7-9 years vs 0-6 years of education, a low income, a psychotic disorder and having ≥2 disorders were associated with increased help-seeking. Older age, being married and having a psychotic or organic disorder were associated with increased help-seeking in healthcare vs. non-healthcare settings. CONCLUSION: A small percentage of persons with mental disorders in the Tianjin region seek help and among those who do, variations in the types of help-seeking may be partially explained by demographic and clinical characteristics.

Does Depressive-Type Schizophrenia Exist? How Do We Prove It?: An Updated Review and Overview.

Depressive symptoms can occur at any point in the duration of schizophrenia. However, we are unable to predict if or when depression will occur in schizophrenic patients. Simultaneously, the standard treatment of depression in schizophrenic patients is the combination of antidepressants and antipsychotics, which has been minimally effective for most patients. Based on several studies, we hypothesized the existence of depressive-type schizophrenia and reviewed the substantial evidence supporting the hypothesis of depressive-type schizophrenia. Simultaneously, we propose technical methods to explore the neuropathology of depressive-type schizophrenia in order to identify the disease during its early stages and to predict how patients will respond to the standard treatment strategies. We believe that the new classification of depressive-type schizophrenia will differentiate it from other forms of depression. In return, this will aid in the discovery of new therapeutic strategies for combatting this disease.

Brain structural and functional dissociated patterns in schizophrenia.

BACKGROUND: Although previous studies found that aberrations in gray matter volume (GMV) and global functional connectivity density (gFCD) are important characteristics of schizophrenia, to the best of our knowledge no study to date has investigated the associations between the spatial distribution patterns of GMV and gFCD alterations. We investigated pattern changes in gFCD and GMV among patients with schizophrenia and their associated spatial distributions. METHODS: Ninety-five patients with schizophrenia and 93 matched healthy controls underwent structural and resting-state functional MRI scanning to assess gFCD and GMV. RESULTS: We found that gFCD increased in the subcortical regions (caudate, pallidum, putamen, and thalami) and limbic system (left hippocampus and parahippocampus), and decreased in the posterior parieto-occipito-temporal cortices (postcentral gyri, occipital cortex, temporo-occipital conjunction, and inferior parietal lobule), in patients with schizophrenia. By contrast, we found decreased GMV in brain regions including the frontal, parietal, temporal, occipital, cingulate cortices, and the insular, striatum, thalamus in these patients. Increased gFCD primarily occurred in subcortical regions including the basal ganglia and some regions of the limbic system. Decreased gFCD appeared primarily in the cortical regions. There were no statistically significant correlations between changes in gFCD and GMV, and their spatial distribution patterns, in different regions. CONCLUSIONS: Our findings indicate that gFCD and GMV are both perturbed in multiple brain regions in schizophrenia. gFCD and GMV consistently decreased in the cortical regions, with the exception of the Supplementary Motor Area (SMA). However, in the sub-cortical regions, the alterations of gFCD and GMV showed the opposite pattern, with increased gFCD and decreased GMV simultaneously observed in these regions. Overall, our findings suggest that structural and functional alterations appear to contribute independently to the neurobiology of schizophrenia.

Chemotherapy Effectiveness and Prognosis of Gastric Cancer Influenced by PTPN11 Polymorphisms.

OBJECTIVE: Since gastric cancer (GC) cells exhibited higher grades of SHP-2 encoded by PTPN11 than normal cells, it would be intriguing to explore whether PTPN11 single nucleotide polymorphisms (SNPs) would influence chemotherapy effectiveness and GC prognosis among a Chinese population. METHODS: Altogether 430 late-stage GC patients and 960 healthy controls matched with age and sex were incorporated. Three PTPN11 SNPs (i.e. rs7958372, rs12229892 and rs2301756) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Chemotherapies of cisplatin and 5-fluorouracil were performed for 4 cycles. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using the logistic regression. Survival curves were plotted with Kaplan-Meier method and the COX proportional hazard model was used to analyze independent factors for GC prognosis. RESULTS: For rs12229892, AA and GA genotypes would cause 1.60-fold increase of GC risk in comparison to homozygote GG (OR = 1.60; 95% CI = 1.23-2.07; P < 0.001). The A allele of rs2301756 was significantly associated with a decrease in the risk of GC when compared with G allele (OR = 0.81; 95% CI = 0.65-0.99; P = 0.043). Results from both 2-cycle and 4-cycle chemotherapy suggested that chemotherapy was significantly more effective for GA and AA genotypes of rs2301756 compared with homozygote GG (P < 0.001). Besides, the joint impact of rs12229892 (AA) and environmental factors (i.e. smoking, family history, intake of processed food and H .pylori infection) on GC risk was considered as positive interaction, while that of rs2301756 (AA) and the above parameters was deemed as negative interaction. Finally, differentiation degree, axillary lymph node metastasis, rs12229892 and rs2301756 appeared as independent risk factors for GC development (all P < 0.05). CONCLUSION: Since rs2301756 polymorphism of PTPN11 was associated with reduced risk of GC and better effects of chemotherapy on GC, it can be considered as a predictor of GC prognosis and the treatment target for GC.

The China Mental Health Survey (CMHS): I. background, aims and measures.

The China Mental Health Survey (CMHS) is the first nationally representative community survey on mental disorders and mental health services in China. One-step diagnoses for mood disorders, anxiety disorders and substance use disorders were obtained using the Composite International Diagnostic Interview-3.0 (CIDI-3.0), according to the criteria and definition of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). A two-step procedure was applied for schizophrenia and other psychotic disorders, using psychosis screening section in CIDI-3.0 as a screening instrument and the Structured Clinical Interview for DSM-IV Axis I disorders (SCID) as a diagnostic tool. Dementia was diagnosed by the 10/66 dementia diagnosis package in a two-step design. The main aims of the CMHS were: (1) to investigate the prevalence of mood disorders, anxiety disorders, substance use disorders, schizophrenia and other psychotic disorders, and dementia; (2) to obtain data of service use of individuals with mental disorders in China; and (3) to analyse the social and psychological risk factors or correlates of mental disorders and mental health services. This paper presents a brief review of the background of the CMHS, its aims and measures.

The China Mental Health Survey: II. Design and field procedures.

China Mental Health Survey (CMHS), which was carried out from July 2013 to March 2015, was the first national representative community survey of mental disorders and mental health services in China using computer-assisted personal interview (CAPI). Face-to-face interviews were finished in the homes of respondents who were selected from a nationally representative multi-stage disproportionate stratified sampling procedure. Sample selection was integrated with the National Chronic Disease and Risk Factor Surveillance Survey administered by the National Centre for Chronic and Non-communicable Disease Control and Prevention in 2013, which made it possible to obtain both physical and mental health information of Chinese community population. One-stage design of data collection was used in the CMHS to obtain the information of mental disorders, including mood disorders, anxiety disorders, and substance use disorders, while two-stage design was applied for schizophrenia and other psychotic disorders, and dementia. A total of 28,140 respondents finished the survey with 72.9% of the overall response rate. This paper describes the survey mode, fieldwork organization, procedures, and the sample design and weighting of the CMHS. Detailed information is presented on the establishment of a new payment scheme for interviewers, results of the quality control in both stages, and evaluations to the weighting.

Reproducibility of diffusion tensor imaging in normal subjects: an evaluation of different gradient sampling schemes and registration algorithm.

INTRODUCTION: Diffusion tensor imaging (DTI) is very useful for investigating white matter integrity in ageing and neurological disorders; thus, evaluating its reproducibility under different acquisition protocols and analysis methods may assist in the design of clinical studies. METHODS: To measure the reproducibility of DTI in normal subjects, this study include (1) depicting the reproducibility of DTI measurements in commonly used regions-of-interest analysis by intraclass correlation coefficient (ICC) and coefficient of variation (CV), (2) evaluating and comparing inter and intrasession test-retest reproducibility, and (3) illustrating the effect of the number of diffusion-encoding directions (NDED) and registration algorithms on measurement reproducibility. RESULTS: DTI measurements exhibit high reproducibility, with overall (430/480) ICC ≥ 0.70, (478/480) within-subject CV (CVws) ≤10.00 % and between-subject CV (CVbs) ranging from 1.32 to 13.63 %. Repeated measures ANOVAs and paired t tests were conducted to compare inter and intrasession reproducibility with different diffusion sampling schemes and registration algorithms. Our results also confirmed that increasing the NDED could improve the accuracy and reproducibility of DTI measurements. In addition, we compared reproducibility indices that were derived using different registration algorithms, and a tensor-based deformable registration yielded the most reproducible results. Finally, we found that increasing the NDED could reduce the difference between the reproducibility of measurement derived using different registration algorithms and between the reproducibility of intersession and intrasession. CONCLUSION: Our results suggest that the choice of DTI acquisition protocol and post-processing methods can influence the accurate estimation and reproducibility of DTI measurements and should be considered carefully for clinical applications.

Insulin Resistance/Diabetes and Schizophrenia: Potential Shared Genetic Factors and Implications for Better Management of Patients with Schizophrenia.

Schizophrenia is a complex psychotic disorder with co-occurring conditions, including insulin resistance and type 2 diabetes (T2D). It is well established that T2D and its precursors (i.e., insulin resistance) are more prevalent in patients with schizophrenia who are treated with antipsychotics, as well as in antipsychotic-naïve patients experiencing their first episode of psychosis, compared with the general population. However, the mechanism(s) underlying the increased susceptibility, shared genetics, and possible cause-effect relationship between schizophrenia and T2D remain largely unknown. The objective of this narrative review was to synthesize important studies, including Mendelian randomization (MR) analyses that have integrated genome-wide association studies (GWAS), as well as results from in vitro models, in vivo models, and observational studies of patients with schizophrenia. Both GWAS and MR studies have found that schizophrenia and T2D/insulin resistance share genetic risk factors, and this may mediate a connection between peripheral or brain insulin resistance and T2D with cognition impairment and an increased risk of developing prediabetes and T2D in schizophrenia. Moreover, accumulating evidence supports a causal role for insulin resistance in schizophrenia and emphasizes the importance of a genetic basis for susceptibility to T2D in patients with schizophrenia before they receive psychotic treatment. The present findings and observations may have clinical implications for the development of better strategies to treat patients with schizophrenia, with both pharmacological (i.e., samidorphan, empagliflozin) and/or nonpharmacological (i.e., lifestyle changes) approaches. Additionally, this review may benefit the design of future studies by physicians and clinical investigators.

Molecular mechanisms of quetiapine bidirectional regulation of bipolar depression and mania based on network pharmacology and molecular docking: Evidence from computational biology.

BACKGROUND: Quetiapine monotherapy is recommended as the first-line option for acute mania and acute bipolar depression. However, the mechanism of action of quetiapine is unclear. Network pharmacology and molecular docking were employed to determine the molecular mechanisms of quetiapine bidirectional regulation of bipolar depression and mania. METHODS: Putative target genes for quetiapine were collected from the GeneCard, SwissTargetPrediction, and DrugBank databases. Targets for bipolar depression and bipolar mania were identified from the DisGeNET and GeneCards databases. A protein-protein interaction (PPI) network was generated using the String database and imported into Cytoscape. DAVID and the Bioinformatics platform were employed to perform the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of the top 15 core targets. The drug-pathway-target-disease network was constructed using Cytoscape. Finally, molecular docking was performed to evaluate the interactions between quetiapine and potential targets. RESULTS: Targets for quetiapine actions against bipolar depression (126 targets) and bipolar mania (81 targets) were identified. Based on PPI and KEGG pathway analyses, quetiapine may affect bipolar depression by targeting the MAPK and PI3K/AKT insulin signaling pathways via BDNF, INS, EGFR, IGF1, and NGF, and it may affect bipolar mania by targeting the neuroactive ligand-receptor interaction signaling pathway via HTR1A, HTR1B, HTR2A, DRD2, and GRIN2B. Molecular docking revealed good binding affinity between quetiapine and potential targets. LIMITATIONS: Pharmacological experiments should be conducted to verify and further explore these results. CONCLUSIONS: Our findings suggest that quetiapine affects bipolar depression and bipolar mania through distinct biological core targets, and thus through different mechanisms. Furthermore, our results provide a theoretical basis for the clinical use of quetiapine and possible directions for new drug development.

Gender differences in the association between childhood maltreatment and the onset of major depressive disorder.

BACKGROUND: Childhood maltreatment is widely acknowledged as a risk factor for developing major depressive disorders (MDDs) in adulthood. However, the influence of gender on age at MDD onset and the relationships between various forms of maltreatment remain unclear. AIMS: This study aimed to evaluate the effect of gender on the relationship between childhood maltreatment and depressive disorder onset with regard to maltreatment severity, age at onset, and the correlation between different forms of maltreatment. METHODS: Data for this study were derived from the Objective Diagnostic Marker and Personalized Intervention in MDD Patients (ODMPIM) study, a multi-center collaborative research project. The data used here include 1001 patients diagnosed with depressive disorder and 494 healthy participants. Childhood maltreatment levels were assessed using the Childhood Trauma Questionnaire-Short Form (CTQ-SF). RESULTS: Emotional abuse was correlated with physical abuse, and emotional neglect was correlated with physical neglect in the MDD patient population. Emotional abuse significantly contributed to early onset of MDD in both genders. Regarding gender differences, male patients with MDD experienced more severe physical abuse during childhood. The correlation between childhood sexual abuse and physical abuse was stronger among males than among females. Levels of physical abuse and neglect tended to be positively associated with the age of MDD onset. Gender is a moderator in the relationship between MDD onset age and childhood physical abuse or neglect. CONCLUSIONS: Gender plays a role in certain aspects of the relationship between MDD and childhood maltreatment.

Selective disrupted gray matter volume covariance of amygdala subregions in schizophrenia.

Objective: Although extensive structural and functional abnormalities have been reported in schizophrenia, the gray matter volume (GMV) covariance of the amygdala remain unknown. The amygdala contains several subregions with different connection patterns and functions, but it is unclear whether the GMV covariance of these subregions are selectively affected in schizophrenia. Methods: To address this issue, we compared the GMV covariance of each amygdala subregion between 807 schizophrenia patients and 845 healthy controls from 11 centers. The amygdala was segmented into nine subregions using FreeSurfer (v7.1.1), including the lateral (La), basal (Ba), accessory-basal (AB), anterior-amygdaloid-area (AAA), central (Ce), medial (Me), cortical (Co), corticoamygdaloid-transition (CAT), and paralaminar (PL) nucleus. We developed an operational combat harmonization model for 11 centers, subsequently employing a voxel-wise general linear model to investigate the differences in GMV covariance between schizophrenia patients and healthy controls across these subregions and the entire brain, while adjusting for age, sex and TIV. Results: Our findings revealed that five amygdala subregions of schizophrenia patients, including bilateral AAA, CAT, and right Ba, demonstrated significantly increased GMV covariance with the hippocampus, striatum, orbitofrontal cortex, and so on (permutation test, P< 0.05, corrected). These findings could be replicated in most centers. Rigorous correlation analysis failed to identify relationships between the altered GMV covariance with positive and negative symptom scale, duration of illness, and antipsychotic medication measure. Conclusion: Our research is the first to discover selectively impaired GMV covariance patterns of amygdala subregion in a large multicenter sample size of patients with schizophrenia.

Latent classes of symptom trajectories among major depressive disorder patients in China.

OBJECTIVE: This study aimed to understand the long-term symptom trajectories of Chinese patients with major depressive disorder (MDD) using piecewise latent growth modeling and growth mixture modeling. The investigation also aimed to identify the baseline characteristics indicative of poorer treatment outcomes. METHODS: A total of 558 outpatients with MDD were assessed using a sequence of surveys. The Hamilton Rating Scale for Depression (HRSD), Hamilton Anxiety Rating Scale (HAMA), and Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) were used to evaluate baseline depression, anxiety, and cognitive function. Depression symptom severity was subsequently measured at the 1-month, 2-month, 6-month, 1-year, and 2-year follow-ups. RESULTS: Results indicated three depressive symptomology trajectories, including (a) severe, improving class (12.72 %), (b) partially responding, later deteriorating class (6.09 %), and (c) moderate, improving class (81.18 %). Logistic regression analyses showed that a history of cardiovascular disease (CVD) increased the odds of belonging to the partially responding, later deteriorating class, whereas higher baseline depression increased the odds of belonging to the severe, improving class compared to the moderate, improving class. Patients who experienced less depression relief during the first month of treatment had a lower probability of belonging to the moderate, improving class. LIMITATIONS: Participant attrition in this study may have inflated the estimated rate of treatment-resistant patients. CONCLUSIONS: The burden of CVD and poorer initial treatment response are plausible risk factors for poorer treatment outcomes, highlighting targets for intervention in Chinese MDD patients.

Microglia and cognitive impairment in schizophrenia: translating scientific progress into novel therapeutic interventions.

Cognitive impairment is a core clinical feature of schizophrenia, exerting profound adverse effects on social functioning and quality of life in a large proportion of patients with schizophrenia. However, the mechanisms underlying the pathogenesis of schizophrenia-related cognitive impairment are not well understood. Microglia, the primary resident macrophages in the brain, have been shown to play important roles in psychiatric disorders, including schizophrenia. Increasing evidence has revealed excessive microglial activation in cognitive deficits related to a broad range of diseases and medical conditions. Relative to that about age-related cognitive deficits, current knowledge about the roles of microglia in cognitive impairment in neuropsychiatric disorders, such as schizophrenia, is limited, and such research is in its infancy. Thus, we conducted this review of the scientific literature with a focus on the role of microglia in schizophrenia-associated cognitive impairment, aiming to gain insight into the roles of microglial activation in the onset and progression of such impairment and to consider how scientific advances could be translated to preventive and therapeutic interventions. Research has demonstrated that microglia, especially those in the gray matter of the brain, are activated in schizophrenia. Upon activation, microglia release key proinflammatory cytokines and free radicals, which are well-recognized neurotoxic factors contributing to cognitive decline. Thus, we propose that the inhibition of microglial activation holds potential for the prevention and treatment of cognitive deficits in patients with schizophrenia. This review identifies potential targets for the development of new treatment strategies and eventually the improvement of care for these patients. It might also help psychologists and clinical investigators in planning future research.

Low-dose lithium adjunct to quetiapine improves cognitive task performance in mice with MK801-induced long-term cognitive impairment: Evidence from a pilot study.

BACKGROUND: Low-dose lithium (LD-Li) has been shown to rescue cognitive impairment in mouse models of short-term mild cognitive impairment, dementia, and schizophrenia. However, few studies have characterized the effects of LD-Li, alone or in conjunction with anti-psychotics, in the mouse model of MK801-induced long term cognitive impairment. METHODS: The present study used in vivo Ca2+ imaging and a battery of cognitive function assessments to investigate the long-term effects of LD-Li on cognition in mice exposed to repeated injections of MK801. Prefrontal Ca2+ activity was visualized to estimate alterations in neural activity in the model mice. Pre-pulse inhibition (PPI), novel object recognition (NOR), Morris water maze (MWM), and fear conditioning (FC) tasks were used to characterize cognitive performance; open field activity (OFA) testing was used to observe psychotic symptoms. Two treatment strategies were tested: LD-Li [250 mg/d human equivalent dose (HED)] adjunct to quetiapine (QTP; 600 mg/d HED); and QTP-monotherapy (mt; 600 mg/d HED). RESULTS: Compared to the QTP-mt group, the LD-Li + QTP group showed greatly improved cognitive performance on all measures between experimental days 29 and 85. QTP-mt improved behavioral measures compared to untreated controls, but the effects persisted only from day 29 to day 43. These data suggest that LD-Li + QTP is superior to QTP-mt for improving long-term cognitive impairments in the MK801 mouse model. LIMITATIONS: There is no medical consensus regarding lithium use in patients with schizophrenia. CONCLUSION: More pre-clinical and clinical studies are needed to further investigate effective treatment strategies for patients with long-term cognitive impairments, such as chronic schizophrenia.

Validation of a modified Chinese-language version of the Davos Assessment of Cognitive Biases Scale (MCL-DACOBS) in a sample of Chinese patients with schizophrenia.

INTRODUCTION: The Davos Assessment of Cognitive Biases Scale (DACOBS) is widely used to assess cognitive biases in patients who have schizophrenia. However, the lack of a modified Chinese-language version of the DACOBS (MCL-DACOBS) precludes Chinese schizophrenic patients from treatment aimed at normalizing cognitive biases, impacting their prognosis. Here, we aimed to produce a DACOBS for China and test the validity and reliability of the resultant MCL-DACOBS. METHODS: Eighteen researchers collaborated to develop the MCL-DACOBS: A total of 15 researchers modified and translated the English version of the DACOBS, 1 native-English-speaking researcher back-translated the scale, and 2 Chinese sinologists localized and optimized the language of the MCL-DACOBS. Forty-two volunteers checked the scale items' comprehensibility, and the two sinologists performed further localization and optimization based on their feedback. The final version of the MCL-DACOBS used in this study was thus derived from the harmonized English-language version of the scale. Confirmatory factor analyses (CFAs) were used to examine the best latent structure of the MCL-DACOBS. Cronbach's α and intraclass correlation coefficients (ICCs) were used to check the reliability. The discriminative ability of the MCL-DACOBS was assessed according to the area under the receiver operating characteristic curve. RESULTS: The CFA showed that all items loaded onto factors with loadings >0.400. A two-factor structure showed a good model fit (root mean square error of approximation = .018, Tucker-Lewis index = .978, comparative fit index = .984). Promax rotation demonstrated that each item had a high factor load (0.432-0.774). Cronbach's α coefficient and ICC for the MCL-DOCABS were .965 and .957, respectively, indicating that the scale has ideal reliability. CONCLUSION: The MCL-DACOBS has good validity and good reliability, and its psychometric properties indicate that it is a valid tool for measuring cognitive biases in Chinese patients with schizophrenia.