We conducted a cross-trait meta-analysis of genome-wide association study on schizophrenia (SCZ) (n = 65,967), bipolar disorder (BD) (n = 41,653), autism spectrum disorder (ASD) (n = 46,350), attention deficit hyperactivity disorder (ADHD) (n = 55,374), and depression (DEP) (n = 688,809). After the meta-analysis, the number of genomic loci increased from 14 to 19 in ADHD, from 3 to 10 in ASD, from 45 to 57 in DEP, from 8 to 54 in BD, and from 64 to 87 in SCZ. We observed significant enrichment of overlapping genes among different disorders and identified a panel of cross-disorder genes. A total of seven genes were found being commonly associated with four out of five psychiatric conditions, namely GABBR1, GLT8D1, HIST1H1B, HIST1H2BN, HIST1H4L, KCNB1, and DCC. The SORCS3 gene was highlighted due to the fact that it was involved in all the five conditions of study. Analysis of correlations unveiled the existence of two clusters of related psychiatric conditions, SCZ and BD that were separate from the other three traits, and formed another group. Our results may provide a new insight for genetic basis of the five psychiatric disorders.

Objective: The purpose of this meta-analysis was to summarize the prevalence and risk factors of mental health problems among healthcare workers during the COVID-19 pandemic.Methods: We applied an optimized search strategy across the PubMed, EMBASE, Scopus, PsycINFO, and four Chinese databases, with hand searching supplemented to identify relevant surveys. Studies were eligible for inclusion if they were published in peer-reviewed literature and used a validated method to assess the prevalence and risk factors of mental health problems among healthcare workers during the COVID-19 pandemic. Heterogeneity was quantified using Q statistics and the I² statistics. The potential causes of heterogeneity were investigated using subgroup analysis and meta-regression analysis. Sensitivity analysis was performed to examine the robustness of the results.Results: We pooled and analyzed data from 20 studies comprising 10,886 healthcare workers. The prevalence of depression, anxiety, insomnia, post-traumatic stress symptoms, phobia, obsessive–compulsive symptoms, and somatization symptoms was 24.1, 28.6, 44.1, 25.6, 35.0, 16.2, and 10.7%, respectively. Female and nurses had a high prevalence of depression and anxiety. Frontline healthcare workers had a higher prevalence of anxiety and a lower prevalence of depression than the those in the second-line. Furthermore, the proportion of moderate–severe depression and anxiety is higher in the frontline. Additionally, four studies reported on risk factors of mental health problems.Conclusions: In this systematic review, healthcare workers have a relatively high prevalence of depression, anxiety, insomnia, post-traumatic stress symptoms, phobia, obsessive–compulsive symptoms, and somatization symptoms during the COVID-19 pandemic, and focus should be on the healthcare workers at high risk of mental problems. Mental health problems in healthcare workers should be taken seriously, and timely screening and appropriate intervention for the high-risk group are highly recommended.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020179189.

BACKGROUND. Major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) are highly comorbid and exhibit strong correlations with one another. We aimed to investigate mechanisms of underlying relationships between PTSD and 3 kinds of depressive phenotypes, namely, MDD, depressed affect (DAF), and depression (DEP, including both MDD and the broad definition of depression). METHODS. Genetic correlations between PTSD and the depressive phenotypes were tested using linkage disequilibrium score regression. Polygenic overlap analysis was used to estimate shared and trait-specific causal variants across a pair of traits. Causal relationships between PTSD and the depressive phenotypes were investigated using Mendelian randomization. Shared genomic loci between PTSD and MDD were identified using cross-trait meta-analysis. RESULTS. Genetic correlations of PTSD with the depressive phenotypes were in the range of 0.71–0.80. The estimated numbers of causal variants were 14,565, 12,965, 10,565, and 4,986 for MDD, DEP, DAF, and PTSD, respectively. In each case, causal variants contributing to PTSD were completely or largely covered by causal variants defining each of the depressive phenotypes. Mendelian randomization analysis indicated that the genetically determined depressive phenotypes confer a causal effect on PTSD (b = 0.21–0.31). Notably, genetically determined PTSD confers a causal effect on DEP (b = 0.14) and DAF (b = 0.15), but not MDD. Cross-trait meta-analysis of MDD and PTSD identified 47 genomic loci, including 29 loci shared between PTSD and MDD. CONCLUSION. Evidence from shared genetics suggests that PTSD is a subtype of MDD. This study provides support to the efforts in reducing diagnostic heterogeneity in psychiatric nosology. FUNDING. The National Key Research and Development Program of China and the National Natural Science Foundation of China.

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.

Recent studies have associated immune abnormalities with dementia. IL-6 is a crucial cytokine in inflammatory responses, and recent evidence has linked elevated IL-6 levels to changes in brain structure and cognitive decline. However, the connection between IL and 6 levels, cognition, brain volumes, and dementia risk requires exploration in large prospective cohorts. This study utilized a longitudinal cohort from the UK Biobank to analyze the correlation between IL and 6 expression levels, cognitive performance, and cortical and subcortical brain volumes through linear regression. Additionally, we assessed the association between IL and 6 levels and long-term dementia risk using Cox regression analysis. We also used one-sample Mendelian randomization to analyze the impact of genetic predisposition of dementia on elevated IL-6 levels. A total of 50,864 participants were included in this study, with 1,391 new cases of all-cause dementia identified. Higher plasma IL-6 levels are associated with cortical and subcortical atrophy in regions such as the fusiform, thalamus proper, hippocampus, and larger ventricle volumes. IL-6 levels are negatively associated with cognitive performance in pair matching, numeric memory, prospective memory, and reaction time tests. Furthermore, elevated IL-6 levels are linked to a 23-35 % increased risk of all-cause dementia over an average follow-up period of 13.2 years. The one-sample Mendelian randomization analysis did not show associations between the genetic predisposition of dementia and elevated IL-6 levels. Increased IL-6 levels are associated with worse cognition, brain atrophy, and a heightened risk of all-cause dementia. Our study highlights the need to focus on the role of peripheral IL-6 levels in managing brain health and dementia risk.

The correlation between human gut microbiota and psychiatric diseases has long been recognized. Based on the heritability of the microbiome, genome-wide association studies on human genome and gut microbiome (mbGWAS) have revealed important host-microbiome interactions. However, establishing causal relationships between specific gut microbiome features and psychological conditions remains challenging due to insufficient sample sizes of previous studies of mbGWAS. Cross-cohort meta-analysis (via METAL) and multi-trait analysis (via MTAG) were used to enhance the statistical power of mbGWAS for identifying genetic variants and genes. Using two large mbGWAS studies (7,738 and 5,959 participants respectively) and12 disease-specific studies from the Psychiatric Genomics Consortium (PGC), we performed bidirectional two-sample mendelian randomization (MR) analyses between microbial features and psychiatric diseases (up to 500,199 individuals). Additionally, we conducted downstream gene- and gene-set-based analyses to investigate the shared biology linking gut microbiota and psychiatric diseases. METAL and MTAG conducted in mbGWAS could boost power for gene prioritization and MR analysis. Increases in the number of lead SNPs and mapped genes were witnessed in 13/15 species and 5/10 genera after using METAL, and MTAG analysis gained an increase in sample size equivalent to expanding the original samples from 7% to 63%. Following METAL use, we identified a positive association between Bacteroides faecis and ADHD (OR, 1.09; 95 %CI, 1.02-1.16; P = 0.008). Bacteroides eggerthii and Bacteroides thetaiotaomicron were observed to be positively associated with PTSD (OR, 1.11; 95 %CI, 1.03-1.20; P = 0.007; OR, 1.11; 95 %CI, 1.01-1.23; P = 0.03). These findings remained stable across statistical models and sensitivity analyses. No genetic liabilities to psychiatric diseases may alter the abundance of gut microorganisms.Using biological annotation, we identified that those genes contributing to microbiomes (e.g., GRIN2A and RBFOX1) are expressed and enriched in human brain tissues. Our statistical genetics strategy helps to enhance the power of mbGWAS, and our genetic findings offer new insights into biological pleiotropy and causal relationship between microbiota and psychiatric diseases.