A large population-based investigation into the genetics of susceptibility to gastrointestinal infections and the link between gastrointestinal infections and mental illness.

Gastrointestinal infections can be life threatening, but not much is known about the host's genetic contribution to susceptibility to gastrointestinal infections or the latter's association with psychiatric disorders. We utilized iPSYCH, a genotyped population-based sample of individuals born between 1981 and 2005 comprising 65,534 unrelated Danish individuals (45,889 diagnosed with mental disorders and 19,645 controls from a random population sample) in which all individuals were linked utilizing nationwide population-based registers to estimate the genetic contribution to susceptibility to gastrointestinal infections, identify genetic variants associated with gastrointestinal infections, and examine the link between gastrointestinal infections and psychiatric and neurodevelopmental disorders. The SNP heritability of susceptibility to gastrointestinal infections ranged from 3.7% to 6.4% on the liability scale. Significant correlations were found between gastrointestinal infections and the combined group of mental disorders (OR = 2.09; 95% CI: 1.82-2.4, P = 1.87 × 10-25). Correlations with autism spectrum disorder, attention deficit hyperactivity disorder, and depression were also significant. We identified a genome-wide significant locus associated with susceptibility to gastrointestinal infections (OR = 1.13; 95% CI: 1.08-1.18, P = 2.9 × 10-8), where the top SNP was an eQTL for the ABO gene. The risk allele was associated with reduced ABO expression, providing, for the first time, genetic evidence to support previous studies linking the O blood group to gastrointestinal infections. This study also highlights the importance of integrative work in genetics, psychiatry, infection, and epidemiology on the road to translational medicine

Trends in incidence of hospitalization for hypoglycemia and diabetic ketoacidosis in individuals with type 1 or type 2 diabetes with and without severe mental illness, in Denmark from 1996-2020:A nationwide study

OBJECTIVETo examine trends in incidence of acute diabetes complications in individuals with type 1 or type 2 diabetes with and without severe mental illness (SMI) in Denmark by age and calendar year.RESEARCH DESIGN AND METHODSWe conducted a cohort study using nationwide registers from 1996-2020 to identify individuals with diabetes, ascertain SMI status (schizophrenia, bipolar disorder, or major depression) and identify the outcomes, hospitalization for hypoglycemia and diabetic ketoacidosis (DKA). We used Poisson regression to estimate incidence rates (IRs) and incidence rate ratios (IRRs) of recurrent hypoglycemia and DKA events by SMI, age, calendar year, accounting for sex, diabetes duration, education, and country of origin.RESULTSAmongst 433,609 individuals with diabetes, 9% had SMI. Risk of (first and subsequent) hypoglycemia events was higher in individuals with SMI versus without SMI (IRR for first hypoglycemia event: type 1 diabetes: 1.77 [95% CI, 1.56-2.00], type 2 diabetes: 1.64 [95% CI, 1.56-1.74]). Individuals with schizophrenia were particularly at risk of recurrent hypoglycemia events. Risk of first DKA event was higher in individuals with SMI (IRR of first DKA event: type 1 diabetes: 1.78 [95% CI. 1.50-2.11], type 2 diabetes: 1.85 [95% CI. 1.64-2.09]). Except for DKA in the type 2 diabetes group, incidence rate differences between individuals with and without SMI were highest in younger individuals (&lt;50 years) but stable across calendar year. CONCLUSIONSSMI is an important risk factor for acute diabetes complication and effective prevention is needed in this population, especially among the younger population and those with schizophrenia.<br/

Polygenic risk scores, school achievement, and risk for schizophrenia: a Danish population-based study

Background: Studies have suggested that poor school achievement is associated with increased risk of schizophrenia; however, the possible genetic contribution to this association is unknown. We investigated the possible effect of the polygenic risk score (PRS) for schizophrenia (PRS) and for educational attainment (PRS) on the association between school performance and later schizophrenia. Methods: We conducted a case-cohort study on a Danish population-based sample born from 1987 to 1995 comprising 1470 individuals with schizophrenia and 7318 subcohort noncases. Genome-wide data, school performance, and family psychiatric and socioeconomic background information were obtained from national registers and neonatal biobanks. PRS and PRS were calculated using discovery effect size estimates from a meta-analysis of 34,600 cases and 45,968 controls and 293,723 individuals. Results: Higher PRS increased the risk (incidence rate ratio [IRR]: 1.28; 95% confidence interval [CI], 1.19–1.36), whereas higher PRS decreased the risk of schizophrenia (IRR, 0.87; 95% CI, 0.82–0.92) per standard deviation. Not completing primary school and receiving low school marks were associated with increased risk of schizophrenia (IRR, 2.92; 95% CI, 2.37–3.60; and IRR, 1.58; 95% CI, 1.27–1.97, respectively), which was not confounded by PRS or PRS. Adjusting for social factors and parental psychiatric history, effects of not completing primary school and receiving low school marks were attenuated by up to 25% (IRR, 2.19; 95% CI, 1.75–2.73; and IRR, 1.39; 95% CI, 1.11–1.75, respectively). Increasing PRS correlated with better school performance (p < .01; R = 7.6%). PRS and PRS was significantly negatively correlated (r = −.31, p < .01). Conclusions: The current PRS did not account for the observed association between primary school performance and risk of schizophrenia

Immune Cell Alterations in Patients with Psychosis: A Comprehensive Systematic Review and Meta-analysis

Background: Psychotic disorders have consistently been associated with inflammatory changes, including alterations in the number of immune cells in the peripheral blood. However, there have been no comprehensive meta-analysis, which have evaluated the amount of circulating immune cells from both the myeloid and lymphoid line including specialized subsets in blood and cerebrospinal fluid (CSF) of patients with psychotic disorders compared to healthy controls. The aim of this study was therefore to systematically evaluate the circulating immune cells including subsets in blood and CSF from patients with psychotic disorders compared to healthy controls. Methods: Multiple databases (PubMed, EMBASE, Cochrane Library, Web of Science, ClinicalTrials.gov and PsycINFO) were searched for eligible studies up until the 18th of October 2022. All studies investigating circulating immune cells in blood and CSF from patients with psychotic disorders (ICD-10: F20 and F22-29) compared to healthy controls were included. One author screened titles and abstracts, and 2 independent reviewers examined full-text reports. Studies that did not include healthy control individuals or included control individuals with recent hospital contacts or admissions that might affect immune cell functioning were excluded. Results: A total of 16,585 articles were identified, after the removal of duplicates and screening by title and abstract, 465 studies were included for full text inspection. Data-extraction is still ongoing and thus the final results of the meta-analysis are not yet available, but preliminary results will be presented from the number of articles where data-extraction have been completed. Conclusion: The preliminary review of the articles has pointed towards a lack of articles that examines potential differences in the number of immune cells including subsets in the CSF of patients with psychotic disorders compared to healthy controls. The CSF is a medium of particular interest because of its closer proximity to the brain compared to peripheral blood. Furthermore, there is a need for more studies with results that are controlled for obesity and smoking, which are both seen more frequently in psychotic patients, and both influence inflammatory parameters

Frequency of Neurological Diseases After COVID-19, Influenza A/B and Bacterial Pneumonia

INTRODUCTION: COVID-19 might affect the incidence of specific neurological diseases, but it is unknown if this differs from the risk following other infections. Here, we characterized the frequency of neurodegenerative, cerebrovascular, and immune-mediated neurological diseases after COVID-19 compared to individuals without COVID-19 and those with other respiratory tract infections. METHODS: This population-based cohort study utilized electronic health records covering ~50% of Denmark's population (n = 2,972,192). Between 02/2020 and 11/2021, we included individuals tested for COVID-19 or diagnosed with community-acquired bacterial pneumonia in hospital-based facilities. Additionally, we included individuals tested for influenza in the corresponding pre-pandemic period between 02/ 2018 and 11/2019. We stratified cohorts for in- and outpatient status, age, sex, and comorbidities. RESULTS: In total, 919,731 individuals were tested for COVID-19, of whom 43,375 tested positive (35,362 outpatients, 8,013 inpatients). Compared to COVID-negative outpatients, COVID-19 positive outpatients had an increased RR of Alzheimer's disease (RR = 3.5; 95%CI: 2.2–5.5) and Parkinson's disease (RR = 2.6; 95%CI: 1.7–4.0), ischemic stroke (RR = 2.7; 95%CI: 2.3–3.2) and intracerebral hemorrhage (RR = 4.8; 95%CI: 1.8–12.9). However, when comparing to other respiratory tract infections, only the RR for ischemic stroke was increased among inpatients with COVID-19 when comparing to inpatients with influenza (RR = 1.7; 95%CI: 1.2–2.4) and only for those >80 years of age when comparing to inpatients with bacterial pneumonia (RR = 2.7; 95%CI: 1.2–6.2). Frequencies of multiple sclerosis, myasthenia gravis, Guillain-Barré syndrome and narcolepsy did not differ after COVID-19, influenza and bacterial pneumonia. CONCLUSION: The risk of neurodegenerative and cerebrovascular, but not neuroimmune, disorders was increased among COVID-19 positive outpatients compared to COVID-negative outpatients. However, except for ischemic stroke, most neurological disorders were not more frequent after COVID-19 than after other respiratory infections