Search for schizophrenia susceptibility variants at the HLA-DRB1 locus among a British population.

Schizophrenia is a complex mental disorder with unknown aetiology. Both candidate gene and genome-wide association (GWA) studies suggest that the human leukocyte antigen (HLA) system may play a part in development of the illness, but the causal HLA variant(s) remain(s) unclear. Previous studies showed that the DRB1*0101 and DRB1*13 alleles might be associated with a high risk of schizophrenia. Therefore, the present study was undertaken to test their association with the disease by genotyping seven DRB1-tagging single nucleotide polymorphisms (SNPs) in a British population. The results showed that, of the previously reported variants that were associated with schizophrenia, the DRB1*1303 allele was the only one marginally associated with a protective effect on the illness in our sample set (χ² = 4.138, P = 0.042, odds ratio (OR) = 0.42, 95 % confidence interval (CI) 0.27-0.66). Interestingly, a significant association was found for rs424232 (χ² = 9.404, P = 0.002, OR = 0.69, 95 % CI 0.54-0.88), which is a tag SNP for the DRB1*1303 allele and located near to the NOTCH4 gene that is a schizophrenia susceptibility locus confirmed by GWA studies. Analysis with the Haploview program demonstrated that rs424232 was in complete linkage disequilibrium with rs3130297 and rs3131296 present in the NOTCH4 locus. While we have failed to confirm association of the candidate alleles in the DRB1 gene with a high risk of schizophrenia, the present work suggests that the association signal detected in the HLA class II locus may extend a relatively long distance, and more work is needed in order to identify the true causal variants within this region or nearby.

The mental health of NHS staff during the COVID-19 pandemic: two-wave Scottish cohort study.

BACKGROUND: Health and social care workers (HSCWs) are at risk of experiencing adverse mental health outcomes (e.g. higher levels of anxiety and depression) because of the COVID-19 pandemic. This can have a detrimental effect on quality of care, the national response to the pandemic and its aftermath. AIMS: A longitudinal design provided follow-up evidence on the mental health (changes in prevalence of disease over time) of NHS staff working at a remote health board in Scotland during the COVID-19 pandemic, and investigated the determinants of mental health outcomes over time. METHOD: A two-wave longitudinal study was conducted from July to September 2020. Participants self-reported levels of depression (Patient Health Questionnaire-9), anxiety (Generalised Anxiety Disorder-7) and mental well-being (Warwick-Edinburgh Mental Well-being Scale) at baseline and 1.5 months later. RESULTS: The analytic sample of 169 participants, working in community (43%) and hospital (44%) settings, reported substantial levels of depression and anxiety, and low mental well-being at baseline (depression, 30.8%; anxiety, 20.1%; well-being, 31.9%). Although mental health remained mostly constant over time, the proportion of participants meeting the threshold for anxiety increased to 27.2% at follow-up. Multivariable modelling indicated that working with, and disruption because of, COVID-19 were associated with adverse mental health changes over time. CONCLUSIONS: HSCWs working in a remote area with low COVID-19 prevalence reported substantial levels of anxiety and depression, similar to those working in areas with high COVID-19 prevalence. Efforts to support HSCW mental health must remain a priority, and should minimise the adverse effects of working with, and disruption caused by, the COVID-19 pandemic.

No association observed between schizophrenia and non-HLA coeliac disease genes: integration with the initial MYO9B association with coeliac disease.

Schizophrenia is a severe psychotic illness with a heterogeneous presentation and a devastating impact on social and occupational function. Worldwide variations in schizophrenia incidence rates suggest that local conditions may modify disease risk. The human leukocyte antigen (HLA) region has been confirmed to be associated with schizophrenia by genome-wide association studies in populations across the world. While the presence of autoimmune processes in a subgroup of schizophrenia cases is contentious, the immune system could allow environmental exposures to lead to schizophrenia by generating improper immune response. To investigate this topic, we reviewed the current evidence of the relationship between schizophrenia and coeliac disease. Based on this review, we performed genetic analysis of the MYO9B gene and the IL-2/IL-21 locus by genotyping SNPs that have been previously associated with coeliac disease or schizophrenia in 223 families, 108 unrelated individuals with schizophrenia and 120 controls. Finding no evidence for association with these two loci in our study samples, we applied meta-analytic techniques to combine our findings with previous reports. This synthesis, in light of our review of previous reports, suggests a differing developmental trajectory for schizophrenia and coeliac disease. It is possible that these two conditions do not share any functional overlap.

Early renal failure detection by cystatin C in Type 2 diabetes mellitus: varying patterns of renal analyte expression.

AIM: The early stages of renal failure are poorly diagnosed by current routine tests. We studied cystatin C and routine renal analyte patterns in Type 2 diabetes mellitus. METHODS: Type 2 diabetes mellitus patients (n = 48) were tested for serum cystatin C, urine albumin, haemoglobin A1c, serum creatinine, serum urea, urine creatinine, glucose, triglycerides and low density lipoproteins (LDL). Glomerular filtration rate (GFR) estimates were made using Cockroft-Gault and Modification of Diet in Renal Disease formulae. RESULTS: The cystatin C (95%CI) reference range was 0.78-0.86 mg/L. While serum cystatin C showed general correlation with routine renal tests, a plateau was observed in analytes measured against cystatin C. Cystatin C improved sensitivity led to detection of renal abnormality in 19% of patients not diagnosed by routine tests. CONCLUSIONS: Cystatin C is a more sensitive marker of renal disease in Type 2 diabetes mellitus where estimated GFR is unreported at >60 mL/min and where antihypertensive medications render microalbuminuria detection unreliable. Its incorporation into a panel of renal function tests is highly recommended.