Comparative genetic architectures of schizophrenia in East Asian and European populations

Schizophrenia is a debilitating psychiatric disorder with approximately 1% lifetime risk globally. Large-scale schizophrenia genetic studies have reported primarily on European ancestry samples, potentially missing important biological insights. Here, we report the largest study to date of East Asian participants (22,778 schizophrenia cases and 35,362 controls), identifying 21 genome-wide-significant associations in 19 genetic loci. Common genetic variants that confer risk for schizophrenia have highly similar effects between East Asian and European ancestries (genetic correlation = 0.98 ± 0.03), indicating that the genetic basis of schizophrenia and its biology are broadly shared across populations. A fixed-effect meta-analysis including individuals from East Asian and European ancestries identified 208 significant associations in 176 genetic loci (53 novel). Trans-ancestry fine-mapping reduced the sets of candidate causal variants in 44 loci. Polygenic risk scores had reduced performance when transferred across ancestries, highlighting the importance of including sufficient samples of major ancestral groups to ensure their generalizability across populations

Pollution assessment and source analysis of heavy metals in agricultural soil around Zijiang River estuary

Zijiang River is the second largest tributary of Dongting Lake. The developed antimony (Sb) mine mining and smelting industry in the upper and middle reaches of Zijiang River bring serious heavy metal pollution risks to the lower reaches of Zijiang River and the Dongting Lake. Taking Zijiang river Estuary as the study area, 132 agriculture soil samples and 7 water samples of Zijiang River were collected, and then multi-methods of contamination assessment, spatial analysis and multivariate statistical analysis methods were comprehensively used to evaluate pollution status and sources of the heavy metal this site. The results showed that the average concentration of heavy metals in farmland soil in the study area was Zn>Cr>Ni>Pb>Cu>As>Sb>Cd, and the average concentration of heavy metals in upland fields was higher than that in paddy fields except for Pb. Sb, As and Cd were the main pollution elements. Besides, Sb reached the level of medium pollution and medium ecological risk, and the site was generally at a slight-medium ecological risk level. The Sb concentration of Zijiang river was relatively high, with an average of 10.51μg/L. Sb mainly came from the antimony mining industry in the upper and middle reaches, and was controlled by human activities such as high antimony concentration surface water irrigation, landfills and coal burning; Cd mainly came from human activities such as pesticides, fertilizers, household garbage and urban wastewater; Cr was mainly derived from soil parent material, while Cu, Zn, As, Ni, Pb were controlled by soil parent material and human activities

HINT1 in Neuropsychiatric Diseases: A Potential Neuroplastic Mediator

Although many studies have investigated the functions of histidine triad nucleotide-binding protein 1 (HINT1), its roles in neurobiological processes remain to be fully elucidated. As a member of the histidine triad (HIT) enzyme superfamily, HINT1 is distributed in almost every organ and has both enzymatic and nonenzymatic activity. Accumulating clinical and preclinical evidence suggests that HINT1 may play an important role as a neuroplastic mediator in neuropsychiatric diseases, such as schizophrenia, inherited peripheral neuropathies, mood disorders, and drug addiction. Though our knowledge of HINT1 is limited, it is believed that further research on the neuropathological functions of HINT1 would eventually benefit patients with neuropsychiatric and even psychosomatic diseases

Association of Objective and Self‐Reported Sleep Duration With All‐Cause and Cardiovascular Disease Mortality: A Community‐Based Study

Background Previous studies found an association between self‐reported sleep duration and mortality. This study aimed to compare the effects of objective and self‐reported sleep duration on all‐cause and cardiovascular disease (CVD) mortality. Methods and Results A total of 2341 men and 2686 women (aged 63.9±11.1 years) were selected from the SHHS (Sleep Heart Health Study). Objective sleep duration was acquired using in‐home polysomnography records, and self‐reported sleep duration on weekdays and weekends was based on a sleep habits questionnaire. The sleep duration was categorized as ≤4 hours, 4 to 5 hours, 5 to 6 hours, 6 to 7 hours, 7 to 8 hours, and >8 hours. Multivariable Cox regression analysis was used to investigate the association of objective and self‐reported sleep duration with all‐cause and CVD mortality. During a mean follow‐up period of 11 years, 1172 (23.3%) participants died, including 359 (7.1%) deaths from CVD. All‐cause and CVD mortality rates decreased gradually with increasing objective sleep duration. In multivariable Cox regression analysis, the greatest association for all‐cause and CVD mortality was with an objective sleep duration of 5 hours or shorter. In addition, we found a J‐shaped association of self‐reported sleep duration on both weekdays and weekends with all‐cause and CVD mortality. Self‐reported short (≤4 hours) and long (>8 hours) sleep duration on weekdays and weekends were associated with an increased risk of all‐cause and CVD mortality compared with 7 to 8 hours sleep duration. Furthermore, a weak correlation was observed between objective and self‐reported sleep duration. Conclusions This study showed that both objective and self‐reported sleep duration were associated with all‐cause and CVD mortality, but with different characteristics. Registration URL: https://clinicaltrials.gov/ct2/show/NCT00005275; Unique identifier: NCT00005275

Macrocytic anemia is associated with the severity of liver impairment in patients with hepatitis B virus-related decompensated cirrhosis: a retrospective cross-sectional study

Abstract Background Macrocytic anemia is common in liver disease. However, its role in hepatitis B virus (HBV)-related decompensated cirrhosis remains unknown. The aim of the present study was to determine the association between macrocytic anemia and the severity of liver impairment in patients with HBV-related decompensated cirrhosis according to the Model for End Stage Liver Disease (MELD) score. Methods A total of 463 participants who fulfilled our criteria were enrolled in this cross-sectional study. Patients were classified into three groups according to anemia types, diagnosed based on their mean corpuscular volume level. Multivariate linear regression analyses were used to determine the association between macrocytic anemia and the MELD score for patients with HBV-related decompensated cirrhosis. Results Patients with macrocytic anemia had evidently higher MELD scores (10.8 ± 6.6) than those with normocytic anemia (8.0 ± 5.5) or microcytic anemia (6.3 ± 5.1). The association remained robust after adjusting for age, gender, smoking, drinking, and total cholesterol (β = 1.94, CI: 0.81–3.07, P < 0.001). Conclusions Macrocytic anemia was found to be associated with the severity of liver impairment and might be a predictor for short-term mortality in patients with HBV-related decompensated cirrhosis

Mendelian randomization suggests that head circumference, but not birth weight and length, associates with intelligence

Abstract Introduction Birth parameters have long been reported to have a role in human intelligence. However, the causalities reported in previous observational studies were controversial. Our study aims to provide an unbiased investigation of the causal associations between birth parameters and human intelligence using the Mendelian randomization (MR) approach. Methods Genetic instrumental variables for MR analyses were extracted from large genome‐wide association studies of infant head circumference (N = 10,768), birth length (N = 28,489), and birth weight (N = 321,223). Data for intelligence were obtained from a meta‐analysis of genome‐wide association studies of 269,867 individuals of the European ancestry. Primary MR analysis was performed using the standard inverse‐variance weighted method, and sensitivity analyses were performed using the weighted median, MR‐Egger, and MR‐PRESSO methods. Results Using 10 single nucleotide polymorphisms as instrumental variables, we found that 1 standard deviation increase in infant head circumference was associated with 0.14‐fold higher scores in intelligence tests (β = 0.14, 95% confidence interval: 0.09 to 0.18, PIVW=2.05 × 10–9). The causal relationship was robust when sensitivity analyses were performed. However, birth length and birth weight had no significant associations with intelligence. Conclusion Our findings suggested infant head circumference, but not birth weight and length were associated with intelligence, which might indicate that brain development rather than general fetal growth was responsible for the development of intelligence

The relationship between maternal anxiety and cortisol during pregnancy and birth weight of chinese neonates

Abstract Background To determine the relationship between maternal anxiety and cortisol values and birth weight at various stages of pregnancy. Methods Two hundred sixteen pregnant Chinese women were assessed for anxiety and depression and had measurement of morning fasting serum cortisol. Women were assessed either in the first (71), second (72) or third (73) trimester. Birth weights of all children were recorded. Results There were significant negative correlations between anxiety level and birth weight of − 0.507 (p  0.5 for all). Maternal cortisol was significantly inversely related to birth weight in trimester 1 (r = − 0.322) and with borderline significance in trimester 2 (r = − 0.229). Anxiety score and maternal cortisol were significantly correlated in each trimester (r = 0.551, 0.650, 0.537). When both anxiety score and maternal cortisol were simultaneously included in multiple regression analyses only anxiety score remained significant. Conclusion Whilst both maternal anxiety score and maternal cortisol are inversely related to birth weight the associations with anxiety score were more robust perhaps indicating the importance of mechanisms other than, or in addition to, maternal cortisol in mediating the effects of anxiety. The findings indicate the importance of measures to reduce maternal anxiety, particularly of a severe degree, at all stages of pregnancy. Trial registration The study was approved by the Ethics Committee of the 1st Affiliated Hospital of Xi’an Jiaotong University

Reliability and validity of the CogState battery Chinese language version in schizophrenia.

BACKGROUND: Cognitive impairment in patients with schizophrenia is a core symptom of this disease. The computerized CogState Battery (CSB) has been used to detect seven of the most common cognitive domains in schizophrenia. The aim of this study was to examine the reliability and validity of the Chinese version of the CSB (CSB-C), in Chinese patients with schizophrenia. METHODOLOGY/PRINCIPAL FINDINGS: Sixty Chinese patients with schizophrenia and 58 age, sex, and education matched healthy controls were enrolled. All subjects completed the CSB-C and the Repeated Battery for the Assessment of Neuropsychological Status (RBANS). To examine the test-retest reliability of CSB-C, we tested 33 healthy controls twice, at a one month interval. The Cronbach α value of CSB-C in patients was 0.81. The test-retest correlation coefficients of the Two Back Task, Gronton Maze Learning Task, Social Emotional Cognition Task, and Continuous Paired Association Learning Task were between 0.39 and 0.62 (p<0.01) in healthy controls. The composite scores and all subscores for the CSB-C in patients were significantly (p<0.01) lower than those of healthy controls. Furthermore, composite scores for patients on the RBANS were also significantly lower than those of healthy controls. Interestingly, there was a positive correlation (r = 0.544, p<0.001) between the composite scores on CSB-C and RBANS for patients. Additionally, in the attention and memory cognitive domains, corresponding subsets from the two batteries correlated significantly (p<0.05). Moreover, factor analysis showed a two-factor model, consisting of speed, memory and reasoning. CONCLUSIONS/SIGNIFICANCE: The CSB-C shows good reliability and validity in measuring the broad cognitive domains of schizophrenia in affected Chinese patients. Therefore, the CSB-C can be used as a cognitive battery, to assess the therapeutic effects of potential cognitive-enhancing agents in this cohort

TNF-α, IL-6 and hsCRP in patients with melancholic, atypical and anxious depression: an antibody array analysis related to somatic symptoms

Background The association between inflammation and major depressive disorder (MDD) remains poorly understood, given the heterogeneity of patients with MDD.Aims We investigated inflammatory markers, such as interleukin (IL)-6, high-sensitivity C reactive protein (hsCRP) and tumour necrosis factor-α (TNF-α) in melancholic, atypical and anxious depression and explored whether baseline inflammatory protein levels could indicate prognosis.Methods The sample consisted of participants (aged 18–55 years) from a previously reported multicentre randomised controlled trial with a parallel-group design registered with ClinicalTrials.gov, including melancholic (n=44), atypical (n=37) and anxious (n=44) patients with depression and healthy controls (HCs) (n=33). Subtypes of MDD were classified according to the 30-item Inventory of Depressive Symptomatology, Self-Rated Version and the 17-item Hamilton Depression Rating Scale. Blood levels of TNF-α, IL-6 and hsCRP were assessed using antibody array analysis.Results Patients with MDD, classified according to melancholic, atypical and anxious depression subtypes, and HCs did not differ significantly in baseline TNF-α, IL-6 and hsCRP levels after adjustment. In patients with anxious depression, hsCRP levels increased significantly if they experienced no pain (adjusted (adj.) p=0.010) or mild to moderate pain (adj. p=0.038) compared with those with severe pain. However, the patients with anxious depression and severe pain showed a lower trend in hsCRP levels than patients with atypical depression who experienced severe pain (p=0.022; adj. p=0.155). Baseline TNF-α (adj. p=0.038) and IL-6 (adj. p=0.006) levels in patients in remission were significantly lower than those in patients with no remission among the participants with the atypical depression subtype at the eighth-week follow-up.Conclusions This study provides evidence of differences in inflammatory proteins in patients with varied symptoms among melancholic, atypical and anxious depression subtypes. Further studies on the immunoinflammatory mechanism underlying different subtypes of depression are expected for improved individualised therapy.Trial registration number NCT03219008