The identification of novel schizophrenia-related metabolites using untargeted lipidomics.

Human lipidome still remains largely unexplored among Chinese schizophrenia patients. We aimed to identify novel lipid molecules associated with schizophrenia and cognition among schizophrenia patients. The current study included 96 male schizophrenia patients and 96 gender-matched healthy controls. Untargeted lipidomics profiling was conducted among all participants. Logistic regression models were used to assess metabolite associations with schizophrenia. We further assessed the incremental predictive value of identified metabolites beyond conventional risk factors on schizophrenia status. In addition, identified metabolites were tested for association with cognitive function among schizophrenia patients using linear regression models. A total of 34 metabolites were associated with schizophrenia. Addition of these identified metabolites to age, body mass index, smoking, and education significantly increased the risk reclassification of schizophrenia. Among the schizophrenia-related metabolites, 10 were further associated with cognition in schizophrenia patients, including four metabolites associated with immediate memory, two metabolites associated with delayed memory, three metabolites associated with visuospatial, four metabolites associated with language, one metabolite associated with attention, and two metabolites associated with the total score. Our findings provide novel insights into the biological mechanisms of schizophrenia, suggesting that lipid metabolites may serve as potential diagnostic or therapeutic targets of schizophrenia.

The causal effect of schizophrenia on fractures and bone mineral density: a comprehensive two-sample Mendelian randomization study of European ancestry.

BACKGROUND: Schizophrenia was clinically documented to co-occur with fractures and aberrant bone mineral density (BMD), but the potential causal relationship remained unclear. This study aimed to test the causal effects between schizophrenia and fractures as well as aberrant BMD by conducting Mendelian randomization (MR) analyses. METHODS: Two-sample MR was utilized, based on instrumental variables from large genome-wide association studies (GWAS) of schizophrenia as exposure, to identify the causal association of schizophrenia with mixed fractures, fractures at different body sites (including skull and facial bones, shoulder and upper arm, wrist and hand, and femur) and BMDs of forearm (FA), femoral neck (FN), lumbar spine (LS) and estimated BMD (eBMD). Multivariable Mendelian randomization (MVMR) analysis was performed to minimize the confounding effect of body mass index (BMI). RESULTS: Result from inverse variance weighting (IVW) method provided evidence schizophrenia increased the risk of fractures of skull and facial bones [odds ratio (OR) = 1.0006, 95% confidence interval (CI): 1.0003 to 1.0010] and femur [OR =1.0007, 95% CI: 1.0003 to 1.0011], whereas, decreased the level of eBMD [ß (95%CI): -0.013 (-0.021, -0.004)]. These causal effects still existed after adjusting for BMI. Sensitivity analyses showed similar results. However, no causal effect of schizophrenia on fracture or BMD in other parts was detected. CONCLUSION: The current finding confirmed that schizophrenia was causally associated with the fractures of skull, face and femur as well as eBMD, which might remind psychiatrists to pay close attention to the fracture risk in schizophrenic patients when formulating their treatment strategies.

Brain-derived neurotrophic factor, sex hormones and cognitive decline in male patients with schizophrenia receiving continuous antipsychotic therapy.

BACKGROUND: There are systematic differences in clinical features between women and men with schizophrenia (SCZ). The regulation of sex hormones may play a potential role in abnormal neurodevelopment in SCZ. Brain-derived neurotrophic factor (BDNF) and sex hormones have complex interacting actions that contribute to the etiology of SCZ. AIM: To investigate the influence of BDNF and sex hormones on cognition and clinical symptomatology in chronic antipsychotic-treated male SCZ patients. METHODS: The serum levels of follicle-stimulating hormone, luteinizing hormone (LH), estradiol (E2), progesterone, testosterone (T), prolactin (PRL) and BDNF were compared between chronic antipsychotic-treated male (CATM) patients with SCZ (n = 120) and healthy controls (n = 120). The Positive and Negative Syndrome Scale was used to quantify SCZ symptoms, while neuropsychological tests were used to assess cognition. Neuropsychological tests, such as the Digit Cancellation Test (DCT), Semantic Verbal Fluency (SVF), Spatial Span Test (SS), Paced Auditory Serial Addition Test (PASAT), Trail Making Task (TMT-A), and Block Design Test (BDT), were used to assess executive functions (BDT), attention (DCT, TMT-A), memory (SS, PASAT), and verbal proficiency (SVF). RESULTS: Although E2 levels were significantly lower in the patient group compared to the healthy controls, T, PRL, and LH levels were all significantly higher. Additionally, the analysis revealed that across the entire sample, there were positive correlations between E2 Levels and BDNF levels as well as BDNF levels and the digital cancellation time. In CATM patients with SCZ, a significant correlation between the negative symptoms score and PRL levels was observed. CONCLUSION: Sex hormones and BDNF levels may also be linked to cognitive function in patients with chronic SCZ.

Morinda officinalis oligosaccharides mitigate chronic mild stress-induced inflammation and depression-like behaviour by deactivating the MyD88/PI3K pathway via E2F2.

Morinda officinalis oligosaccharides (MOs) are natural herbal extracts that have been shown to exert antidepressant effects. However, the mechanism of this effect remains unclear. Here, we explored the mechanism by which MOs improved experimental depression. Using a chronic mild stress (CMS) murine model, we examined whether MOs could protect against depressive-like behaviour. Lipopolysaccharide (LPS)- and ATP-treated BV2 cells were used to examine the potential mechanism by which MOs mediate the inflammatory response. We found that MOs prevented the CMS-induced reduction in the sucrose preference ratio in the sucrose preference test (SPT) and shortened the immobility durations in both the tail suspension test (TST) and forced swim test (FST). We also noticed that MOs suppressed inflammatory effects by deactivating the MyD88/PI3K pathway via E2F2 in CMS mice or LPS- and ATP-stimulated BV2 cells. Furthermore, overexpression of E2F2 blunted the beneficial effects of MOs in vitro. Collectively, these data showed that MOs exerted antidepressant effects in CMS mice by targeting E2F2-mediated MyD88/PI3K signalling pathway.

LAMC1 is a Novel Prognostic Factor and a Potential Therapeutic Target in Gastric Cancer.

Purpose: To investigate the role of LAMC1 in gastric cancer (GC), if it is of great importance to identify tumour driver genes with prognostic value. Patients and Methods: GC-related gene expression profile data were downloaded from TCGA. R-limma package and univariate Cox regression were used to identify the differentially expressed genes (DEGs) and survival-genes, respectively. Then, the ClusterProfiler package was used to analyse the Gene Ontology and pathway enrichment of DEGs. Cytoscape was used to build a protein interaction network (PPI) and identify key genes. The GEPIA2 and TIMER databases were used to validate the differential expression of LAMC1. The relationship between LAMC1 and the prognosis of GC was analysed by the KM. GSEA and GSVA were used to analyse the major activated and mutated pathways, respectively. Real-time fluorescence quantitative PCR (RT-qPCR) was used to reidentify the expression of LAMC1 in GES-1 and 5 GC cell lines. Finally, we explored the relationship between LAMC1 and FGFR1. Results: A total of 266 DEGs were be selected, which were mainly enriched in extracellular structure organization. LAMC1 was identified as one of the hub genes. The expression of LAMC1 was significantly higher in GC tissue than in paracancerous tissues, and the prognosis of the GC patient with high expression of LAMC1 was relatively poor. Univariate and multivariate Cox analysis indicated that LAMC1 could be used as an independent prognostic indicator. The results of GSEA and GSVA showed that LAMC1 was mainly enriched in pathways such as MYOGENESIS and UV_RESPONSE_DN. The RT-qPCR results showed that the expression level in AGS cells was significantly higher than that in gastric epithelial cells. LAMC1 may play a role in the development of gastric cancer by influencing FGFR1. Conclusion: LAMC1 may mediate the occurrence and development of GC and has potential as a biomarker for the prognosis and treatment of GC.

Erratum: Mental health needs of the COVID-19 patients and staff in the Fangcang shelter hospital: a qualitative research in Wuhan, China - ERRATUM.

[This corrects the article DOI: 10.1017/gmh.2021.23.].

Structural family factors and bullying at school: a large scale investigation based on a Chinese adolescent sample.

BACKGROUNDS: Various family factors have been identified in association with school bullying and the involvement of children and adolescents in bullying behaviors. METHODS: A total of 11,919 participants (female = 6671, mean age = 15) from 22 middle schools in Suzhou City, China completed the questionnaire. The associations between structural family factors (family socio-economic status, living arrangement, number of siblings, whether they were local residents/migrants, had an urban/rural hukou [a household registration system in China], parental and maternal education levels, and other various bullying-related constructs (i.e. bullying witnessing, bullying involvement, bystander intervention, and fear of being bullied) were all examined. Odds ratios (ORs) adjusted for covariates were calculated for the four bullying-related constructs (bullying witness, bullying involvement, bystander intervention, and reactions to being bullied) using structural family factors. RESULTS: The result showed that all demographic household characteristics were associated with bullying at school except for being from a single-child family. Adolescents from rural families witnessed more bullying incidents than those from local families (OR = 1.35, 95% CI: [1.09, 1.68]). Adolescents who come from migrant families (OR = 1.12, 95% CI: [1.07, 1.43]) with a rural hukou (OR = 1.31, 95% CI: [1.00, 1.74]) and low parental education levels (OR = 1.42, 95% CI: [1.01, 2.57]) were more likely to be bullies. Adolescents who came from migrant families (OR = 1.37, 95% CI: [1.03, 1.82]), with low maternal education levels (OR = 1.42, 95% CI: [1.06, 1.91]) engaged in more negative bystander intervention behaviors. Furthermore, adolescents with less educated mothers experienced a higher fear of being bullied (never versus sometimes: OR = 1.33, 95% CI: [1.00, 1.85]; never versus usually OR = 1.39, 95% CI: [1.01, 1.20]). CONCLUSIONS: A systematic examination of the relationship between school bullying and demographic household characteristics may be used to inform school policies on bullying, such as training management on the importance of paying attention to adolescents from disadvantage household backgrounds. Identifying demographic factors that may predict bullying can also be used to prevent individuals from becoming involved in bullying and reduce the related negative consequences from being bullied.

Mental health needs of the COVID-19 patients and staff in the Fangcang shelter hospital: a qualitative research in Wuhan, China.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, Fangcang shelter hospitals were opened in Wuhan, China, to isolate and care for patients with mild or moderate symptoms. The patients and staff in the hospitals faced mental health challenges. This paper reports the experiences and mental health needs from them. METHOD: Following the qualitative design, semi-structured interviews were conducted in the EastWest Lake Fangcang Shelter Hospital, Wuhan on March 2020. Data collection and analysis was based on grounded theory. Open coding was adapted and a structured codebook was developed through coding seminars. The themes and subthemes were then confirmed through thematic analysis. The findings were further explained and integrated in a theoretical framework. RESULTS: A total of 10 COVID-19 patients and 13 staff, including doctors, nurses, psychiatrists, and policemen participated in the interviews. They have common needs, as well as their own needs. The perspectives from the staff also did complement for needs of the patients. The mental health needs were generalized into four themes, that is, basic needs, information and communication, emotional needs, and social support, each with several subthemes. In addition, there were some external factors that regulated the internal needs, which were summarized in a theoretical framework. CONCLUSIONS: The study indicates the directions on hospital management, mental health services, policy making, and social work to meet the mental health needs of the inpatients and staff from temporary shelter hospitals like Fangcang in Wuhan during the COVID-19 pandemic.

The Role of Mitophagy in Regulating Cell Death.

Mitochondria are multifaceted organelles that serve to power critical cellular functions, including act as power generators of the cell, buffer cytosolic calcium overload, production of reactive oxygen species, and modulating cell survival. The structure and the cellular location of mitochondria are critical for their function and depend on highly regulated activities such as mitochondrial quality control (MQC) mechanisms. The MQC is regulated by several sets of processes: mitochondrial biogenesis, mitochondrial fusion and fission, mitophagy, and other mitochondrial proteostasis mechanisms such as mitochondrial unfolded protein response (mtUPR) or mitochondrial-derived vesicles (MDVs). These processes are important for the maintenance of mitochondrial homeostasis, and alterations in the mitochondrial function and signaling are known to contribute to the dysregulation of cell death pathways. Recent studies have uncovered regulatory mechanisms that control the activity of the key components for mitophagy. In this review, we discuss how mitophagy is controlled and how mitophagy impinges on health and disease through regulating cell death.

Association between stereopsis deficits and attention decline in patients with major depressive disorder.

Cognitive and sensory deficits were considered a core feature of major depressive disorder (MDD). However, few studies investigated stereopsis integrity in patients with MDD. Thus, the objectives of this study investigated stereopsis integrity and its correlations with cognitive function and depressive symptom in patients with MDD. 90 patients with MDD and 116 healthy controls (HCs) were enrolled in this study. Their stereoacuity was evaluated using the Titmus Stereopsis Test as well as assessing their cognitive function and depressive symptom by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and Hamilton Depression Scale (HAMD). Log seconds of arc was significantly higher in patients than HCs (1.92 ± 0.41 versus 1.67 ± 0.16, t = 5.35, p < 0.0001). The percentage of patients with correct stereopsis detection was markedly declined in 400 (z = 3.06, p = 0.002), 200 (z = 3.84, p < 0.001), 140 (z = 4.73, p < 0.001), 100 (z = 4.58, p < 0.001), 80 (z = 5.06, p < 0.001), 60 (z = 4.72, p < 0.001), 50 (z = 4.24, p < 0.001), and 40 (z = 4.85, p < 0.001) seconds of arc compared with HCs. Log seconds of arc was significantly correlated with the RBANS total score (r = -0.38, p < 0.0001), subscores of attention (r = -0.49, p < 0.0001) and language (r = -0.33, p = 0.001) rather than HAMD score (r = 0.03, p = 0.78) in MDD patients. In addition, log seconds of arc was significantly related to the RBANS total score (r = -0.58, p < 0.0001) and language score (r = -0.45, p = 0.006) rather than attention score (r = -0.30, p = 0.07) in HCs. Further stepwise multivariate regression analyses showed the negative correlation of log seconds of arc with attention score (ß = -0.80, t = -3.95, p < 0.0001) rather than HAMD score (ß = -0.008, t = -0.09, p = 0.93) in MDD patients. However, there was no relationship between log seconds of arc and attention score in HCs (ß = 1.52, t = 1.19, p = 0.24). Our results identified the marked deficits of stereopsis in MDD patients that were tightly correlated with their attention functioning rather than depressive symptom.

Efficacy of Artificial Intelligence-Assisted Psychotherapy in Patients With Anxiety Disorders: A Prospective, National Multicenter Randomized Controlled Trial Protocol.

BACKGROUND: Anxiety disorders have the highest prevalence of all psychiatric disorders in China. Medication and psychotherapy are two main treatment approaches for this group of disorders, and when used in combinations are significantly more beneficial than medication alone. The resources are insufficient. The availability of psychotherapy is low due to the limited resources. Artificial intelligence (AI)-assisted psychotherapy offers an opportunity to develop an efficient and standardized psychotherapy model and improve the availability of psychotherapy, which is key to improve the clinical efficacy of anxiety disorder treatments. OBJECTIVES: The present protocol aims to determine whether medication plus AI-assisted psychotherapy has greater efficacy than medication alone in the treatment of anxiety disorders. METHODS: We will recruit patients in eight hospitals in China. Seven hundred and eight patients with anxiety disorders will be randomly allocated on a 1:1 basis to either medication plus AI-assisted psychotherapy group, or medication alone group. We have built an AI psychotherapy robot named XIAO AN. In this study we will deliver psychotherapy to patients in the medication plus AI-assisted psychotherapy group. Patients will be assessed at baseline and at the end of week 2, 4, 8, and 12. Follow-up assessments will be conducted at 3 and 6 months posttreatment. The primary outcome is change of Hamilton Anxiety Rating Scale (HAMA) score from baseline the end of 12-week treatment. A secondary efficacy outcome will be improvement in treatment at an early stage (score reduction in HAMA ≥25% after 2 weeks of treatment). Other measurements include Hamilton Depression Scale, Clinical Global Impression, Treatment Emergent Symptom Scale, Social Disability Screening Schedule, Insomnia Severity Index and so on. Scales will be assessed by independent raters who are blind to treatment allocation and analyses will be conducted by a statistician who is also blind to treatment allocation. DISCUSSION: This will be the first multicentered randomized controlled single-blind trial in China to assess the efficacy of medication plus AI-assisted psychotherapy compared with medication alone for anxiety disorders. The study has the potential to address the limitations of the limited availability of psychotherapy, and to augment the efficacy of the treatment of anxiety disorders in China.

Novel Risk Loci Associated With Genetic Risk for Bipolar Disorder Among Han Chinese Individuals: A Genome-Wide Association Study and Meta-analysis.

Importance: The genetic basis of bipolar disorder (BD) in Han Chinese individuals is not fully understood. Objective: To explore the genetic basis of BD in the Han Chinese population. Design, Setting, and Participants: A genome-wide association study (GWAS), followed by independent replication, was conducted to identify BD risk loci in Han Chinese individuals. Individuals with BD were diagnosed based on DSM-IV criteria and had no history of schizophrenia, mental retardation, or substance dependence; individuals without any personal or family history of mental illnesses, including BD, were included as control participants. In total, discovery samples from 1822 patients and 4650 control participants passed quality control for the GWAS analysis. Replication analyses of samples from 958 patients and 2050 control participants were conducted. Summary statistics from the European Psychiatric Genomics Consortium 2 (PGC2) BD GWAS (20 352 cases and 31 358 controls) were used for the trans-ancestry genetic correlation analysis, polygenetic risk score analysis, and meta-analysis to compare BD genetic risk between Han Chinese and European individuals. The study was performed in February 2020. Main Outcomes and Measures: Single-nucleotide variations with P < 5.00 × 10-8 were considered to show genome-wide significance of statistical association. Results: The Han Chinese discovery GWAS sample included 1822 cases (mean [SD] age, 35.43 [14.12] years; 838 [46%] male) and 4650 controls (mean [SD] age, 27.48 [5.97] years; 2465 [53%] male), and the replication sample included 958 cases (mean [SD] age, 37.82 [15.54] years; 412 [43%] male) and 2050 controls (mean [SD] age, 27.50 [6.00] years; 1189 [58%] male). A novel BD risk locus in Han Chinese individuals was found near the gene encoding transmembrane protein 108 (TMEM108, rs9863544; P = 2.49 × 10-8; odds ratio [OR], 0.650; 95% CI, 0.559-0.756), which is required for dendritic spine development and glutamatergic transmission in the dentate gyrus. Trans-ancestry genetic correlation estimation (ρge = 0.652, SE = 0.106; P = 7.30 × 10-10) and polygenetic risk score analyses (maximum liability-scaled Nagelkerke pseudo R2 = 1.27%; P = 1.30 × 10-19) showed evidence of shared BD genetic risk between Han Chinese and European populations, and meta-analysis identified 2 new GWAS risk loci near VRK2 (rs41335055; P = 4.98 × 10-9; OR, 0.849; 95% CI, 0.804-0.897) and RHEBL1 (rs7969091; P = 3.12 × 10-8; OR, 0.932; 95% CI, 0.909-0.956). Conclusions and Relevance: This GWAS study identified several loci and genes involved in the heritable risk of BD, providing insights into its genetic architecture and biological basis.

Independent replications and integrative analyses confirm TRANK1 as a susceptibility gene for bipolar disorder.

Genetic analyses for bipolar disorder (BD) have achieved prominent success in Europeans in recent years, whereas its genetic basis in other populations remains relatively less understood. We herein report that the leading risk locus for BD in European genome-wide association studies (GWAS), the single-nucleotide polymorphism (SNP) rs9834970 near TRANK1 at 3p22 region, is also genome-wide significantly associated with BD in a meta-analysis of four independent East Asian samples including 5748 cases and 65,361 controls (p = 2.27 × 10-8, odds ratio = 1.136). Expression quantitative trait loci (eQTL) analyses and summary data-based Mendelian randomization (SMR) analyses in multiple human brain samples suggest that lower TRANK1 mRNA expression is a principal BD risk factor explaining its genetic risk signals at 3p22. We also identified another SNP rs4789 in the 3' untranslated region (3'UTR) of TRANK1 showing stronger eQTL associations as well as genome-wide significant association with BD. Despite the relatively unclear neuronal function of TRANK1, our mRNA expression analyses in the human brains and in rat primary cortical neurons reveal that genes highly correlated with TRANK1 are significantly enriched in the biological processes related to dendritic spine, synaptic plasticity, axon guidance and circadian entrainment, and are also more likely to exhibit strong associations in psychiatric GWAS (e.g., the CACNA1C gene). Overall, our results support that TRANK1 is a potential BD risk gene. Further studies elucidating its roles in this illness are needed.

The role of lipoprotein profile in depression and cognitive performance: a network analysis.

Lipid profile (total cholesterol and lipoprotein fractions) has been found to correlate with depression and cognitive impairment across the lifespan. However, the role of lipid levels in self-rated depressive state and cognitive impairment remains unclear. In this study, we examined the relationship between lipid profile (total cholesterol, triglycerides, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol) and cognition in adults with and without self-rated depression. Four hundred and thirty-eight healthy participants completed the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), the Self-Rating Depression Scale (SDS), and a serum lipoprotein test. Using multivariate ANOVA, partial correlation and network analysis, a network linking lipoprotein profile, depressive state and cognition was constructed. A significant difference in serum lipid profile between the high and low depressive groups was detected. Depressive state had a strong negative correlation with cognitive performance. Of the lipid profile, only high-density lipoprotein was positively correlated with depressive symptom severity, whereas the other three indices showed negative correlation with both depressive state and cognitive performance. Our results suggest that serum lipid profile may be directly linked to self-rated depression and cognitive performance. Further studies recruiting larger clinical samples are needed to elucidate the specific effect of lipoprotein on cognitive impairment in mood disorder.

Mental Health Status of Cisgender and Gender-Diverse Secondary School Students in China.

Importance: Transgender or gender nonconforming (TGNC) adolescents face a wide range of physical and mental health concerns. However, there has been no school-based study to explore the prevalence and mental health status of these adolescents in mainland China. Objectives: To assess the mental well-being of TGNC adolescents in China by comparing them with their cisgender peers. Design, Setting, and Participants: This was a cross-sectional survey study. Of the 12 354 adolescents who completed the questionnaire, 246 did not specify to which sex they identified and were therefore excluded from further analysis. Therefore, a total of 12 108 adolescents were included from 18 secondary schools in Suzhou city, China, from June 2019 to July 2019. Participants provided consent and answered questions on sex assigned at birth and gender identity. Main Outcomes and Measures: All participants completed questionnaires, including the Patient Health Questionnaire for the measurement of depressive symptoms, a generalized anxiety disorder screening, the Pittsburgh Sleep Quality Index, and a self-harm and suicide risk checklist. The frequency of being bullied at school was also measured. Participants who reported their perceived gender as the opposite of their assigned sex at birth were classified as transgender, those who identified as neither male nor female were classified as nonbinary, and those who were not sure about their perceived gender were classified as questioning. All of these participants were categorized as TGNC adolescents. Results: A total of 12 108 adolescents (mean [SD] age, 15.8 [1.0] years; 6518 [53.8%] assigned male at birth [AMAB]) participated in the study. Of the 6518 participants AMAB in the sample, 5855 (89.8%) were classified as cisgender boys, 208 (3.2%) as transgender girls (transgender youth who perceive their current gender identity to be female), 138 (2.1%) as nonbinary youth AMAB, and 317 (4.9%) as questioning youth AMAB. Of the 5590 participants assigned female at birth (AFAB), 4142 (74.1%) were classified as cisgender girls, 861 (15.4%) as transgender boys (transgender youth who perceive their current gender identity to be male), 112 (2.0%) as nonbinary youth AFAB, and 475 (8.5%) as questioning youth AFAB. Compared with cisgender adolescents, TGNC adolescents reported significantly higher health concerns including lower overall health (t11 872 = -7.36; P < .001), poorer sleep (t11 683 = 10.49; P < .001), higher depression and anxiety symptoms (t11 830 = 12.43 and t11 847 = 11.47, respectively; P < .001), and higher rate of self-harm and suicide ideation (t11 860 = 12.22; P < .001). The TGNC youth who were AMAB were also more likely to be bullied at school than cisgender boys (transgender girls: odds ratio [OR], 2.34 [95% CI, 1.64-3.33]; nonbinary youth AMAB: OR, 1.97 [95% CI, 1.23-3.16]; and questioning youth AMAB: OR, 1.95 [95% CI, 1.43-2.67]). The TGNC groups also reported significantly greater amounts of thoughts of self-harm (transgender girls: OR, 3.06 [95% CI, 2.24-4.19]; transgender boys: OR, 4.06 [95% CI, 3.47-4.74]; nonbinary youth AMAB: OR, 2.86 [95% CI, 1.93-4.23]; nonbinary youth AFAB: OR, 3.71 [95% CI, 2.46-5.59]; questioning youth AMAB: OR, 2.61 [95% CI, 1.98-3.44]; and questioning youth AFAB: OR, 3.35 [95% CI, 2.70-4.16]), thoughts of suicide (transgender girls: OR, 3.93 [95% CI, 2.88-5.38]; transgender boys: OR, 3.71 [95% CI, 3.10-4.21]; nonbinary youth AMAB: OR, 3.13 [95% CI, 2.11-4.63]; nonbinary youth AFAB: OR, 3.78 [95% CI, 2.50-5.71]; questioning youth AMAB: OR, 2.53 [95% CI, 1.93-3.33]; and questioning youth AFAB: OR, 3.94 [95% CI, 3.17-4.88]), suicide plan formation (transgender girls: OR, 4.44 [95% CI, 2.88-6.83]; transgender boys: OR, 2.66 [95% CI, 2.03-3.50]; nonbinary youth AMAB: OR, 5.36 [95% CI, 3.22-8.93]; nonbinary youth AFAB: OR, 4.06 [95% CI, 2.25-7.30]; and questioning youth AFAB: OR, 2.36 [95% CI, 1.63-3.43]), deliberate self-harm during the last month (cisgender girls: OR, 1.49 [95% CI, 1.33-1.68]; transgender girls: OR, 2.74 [95% CI, 1.93-3.91]; transgender boys: OR, 3.06 [95% CI, 2.57-3.66]; nonbinary youth AMAB: OR, 2.56 [95% CI, 1.66-3.94]; nonbinary youth AFAB: OR, 3.06 [95% CI, 1.95-4.81]; questioning youth AMAB: OR, 2.14 [95% CI, 1.56-2.92]; and questioning youth AFAB: OR, 2.53 [95% CI, 2.00-3.01]), and attempts of suicide (transgender girls: OR, 4.35 [95% CI, 2.88-6.56]; transgender boys: OR, 2.92 [95% CI, 2.26-3.76]; nonbinary youth AMAB: OR, 3.94 [95% CI, 2.36-6.55]; nonbinary youth AFAB: OR, 3.06 [95% CI, 1.67-5.63]; questioning youth AMAB: OR, 2.61 [95% CI, 1.73-3.94]; and questioning youth AFAB: OR, 1.93 [95% CI, 1.33-2.81]) compared with cisgender boys. Conclusions and Relevance: Results of this cross-sectional survey study suggest poor mental health status among TGNC adolescents in China; in addition, findings suggest a compelling need for researchers, practitioners, and policy makers to address these mental health problems. Particular school-based interventions are recommended to support the mental health well-being of TGNC adolescents.

Differential effects of different antipsychotic drugs on cognitive function in patients with chronic schizophrenia.

BACKGROUND: Cognitive impairment is core feature of schizophrenia. The impact of antipsychotics on cognition remains controversial. This study aimed to examine the effects of long-term use of different types of antipsychotics on cognitive impairment in schizophrenia patients. METHODS: We used the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) to assess the cognition of three groups of schizophrenia patients (318 on clozapine, 125 on risperidone, and 166 on typical antipsychotic drugs) and 399 healthy controls, and used the Positive and Negative Syndrome Scale to assess schizophrenia symptoms of patients. RESULTS: Patients taking typical antipsychotics scored higher on the immediate memory and delayed memory index than those taking clozapine or risperidone (all p < 0.01). Patients taking clozapine scored higher on the language subscale than those taking risperidone (p < 0.05). Multiple regression analysis showed that the drug type was identified as an independent contributor to the immediate memory, language, and delayed memory index of RBANS (all p < 0.05). CONCLUSIONS: Patients taking typical antipsychotics have better memory than those taking clozapine or risperidone. Patients taking clozapine have better language function than those taking risperidone.

Comparative efficacy of add-on rTMS in treating the somatic and psychic anxiety symptoms of depression comorbid with anxiety in adolescents, adults, and elderly patients-A real-world clinical application.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is an effective adjuvant treatment for depression. Many patients with depression have comorbid anxiety symptoms. However, previous rTMS studies have focused on patients with depression, and often excluded comorbid anxiety. This real-world study aimed to investigate the comparative efficacy of add-on rTMS in treating the somatic and psychic anxiety symptoms of depression comorbid with anxiety in adolescents, adults and elderly patients. METHODS: This study included 147 depression patients with anxiety symptoms who were treated with at least 10 sessions of rTMS. The symptoms of anxiety and depression were assessed with the Hamilton Rating Scale for Anxiety (HAMA) and the Hamilton Rating Scale for Depression (HAMD) at baseline and after 2 and 4 weeks of treatment. This was done to compare the improvement degree of add-on rTMS on somatic and psychic anxiety symptoms in adolescents, adults and elderly patients respectively. RESULTS: Both somatic and psychic anxiety symptoms were significantly improved after the add-on rTMS in adolescents, adults and elderly patients. The improvement of somatic anxiety was better than that of psychic anxiety after rTMS treatment in elderly patients (t2w=3.895, P<0.001; t4w=2.823, P = 0.008). LIMITATION: The overall sample was mostly composed of elderly patients, while adolescents and adult patients were fewer. CONCLUSIONS: The add-on rTMS treatment can improve somatic anxiety better than psychic anxiety in depression with anxiety symptoms, especially in elderly patients.

Bullying victimization, bullying witnessing, bullying perpetration and suicide risk among adolescents: A serial mediation analysis.

INTRODUCTION: Prior work suggests that involvement in bullying was associated with a higher suicide risk among adolescents. However, the mechanisms of this association remain unclear. The present study aimed to understand the relationship between direct and indirect involvement in bullying (bullying victimization, bullying perpetration and bullying witnessing) and suicide risk by examining the serial mediation of negative coping styles and depressive symptoms. METHODS: 12,354 Chinese adolescents (mean age = 15.00, 54% male) were recruited from December 2018 to January 2019 in 18 secondary schools. Participants completed questionnaires that measured their direct and indirect involvement in bullying, negative coping styles, depressive symptoms, and suicide risk. RESULTS: The relationship between involvement in bullying and suicide risk was mediated by negative coping styles, depressive symptoms, and also serially mediated by negative coping styles and depressive symptoms. Similar findings were obtained for both direct and indirect involvement in bullying. LIMITATIONS: The present study is limited by a cross-sectional design. Future studies could examine longitudinal changes in the outcome measures CONCLUSIONS: Given the urgent need to reduce the high suicide rate among adolescents in China, our findings suggest that having a less negative coping style is an important protective factor. These results provide direction for the development of prevention strategies and targeted interventions within this population. Additionally, it is essential to develop prevention strategies and interventions not only for those who have been a victim or perpetrator of bullying, but also for those who have witnessed bullying.

Psychotic symptoms in first-episode and drug naïve patients with major depressive disorder: Prevalence and related clinical factors.

BACKGROUND: Many patients with major depressive disorder (MDD) have been found to have psychotic symptoms. However, few studies have reported the prevalence of comorbid psychotic symptoms in first-episode drug naïve (FEDN) MDD patients. This study was to investigate the prevalence of psychotic symptoms and related risk factors in a large sample size of FEDN MDD patients in a Chinese population. METHODS: A total of 573 patients with diagnosis of MDD at their first episode were recruited with their demographic and clinical data. Positive scale of the Positive and Negative Syndrome Scale was utilized for psychotic symptoms, Hamilton Anxiety Rating Scale (HAMA) for anxiety symptoms, and Hamilton Depression Rating Scale (HAMD) for depressive symptoms. RESULTS: The prevalence of psychotic symptoms in these MDD patients was 9.8%. MDD patients with psychotic symptoms had significantly higher HAMD and HAMA total scores than those without psychotic symptoms (both p < .001). A strong association was found between psychotic MDD and anxiety or suicide, with odds ratio of 33.097 for severe anxiety, and 5.012 for suicide. CONCLUSIONS: Our results suggest that psychotic symptoms are common in MDD patients at their first episode. The strong association between psychotic MDD and anxiety or suicide attempts demonstrates the importance of reducing anxiety symptoms in the treatment of psychotic MDD patients as well as the necessity to regularly assess suicide risk in MDD patients with psychotic symptoms to better prevent suicidal behavior.