Leveraging haplotype information in heritability estimation and polygenic prediction.

Polygenic prediction has yet to make a major clinical breakthrough in precision medicine and psychiatry, where the application of polygenic risk scores is expected to improve clinical decision-making. Most widely used approaches for estimating polygenic risk scores are based on summary statistics from external large-scale genome-wide association studies, which rely on assumptions of matching data distributions. This may hinder the impact of polygenic risk scores in modern diverse populations due to small differences in genetic architectures.

Risk factors of long-term brain health outcomes after hospitalization for critical illness.

Background: Brain health may be impaired years after hospitalization for critical illness, and similar impairments occur after hospitalization for COVID-19. However, it remains unclear which patients are most likely to experience long-term brain health consequences and whether these adverse events differ between non-COVID critical illness and COVID-19.

Methods: In a prospective observational study, we enrolled patients hospitalized for (1) non-COVID critical illness (pneumonia, myocardial infarction, or ICU-requiring conditions) or for (2) COVID-19, from March 2020 to June 2021.

Antibodies against SARS-CoV-2 spike protein in the cerebrospinal fluid of COVID-19 patients and vaccinated controls: a multicentre study.

Introduction: SARS-CoV-2 antibodies in the cerebrospinal fluid (CSF) of COVID-19 patients possibly reflect blood-cerebrospinal fluid barrier (BCB) disruption due to systemic inflammation. However, some studies indicate that CSF antibodies signal a neurotropic infection. Currently, larger studies are needed to clarify this, and it is unknown if CSF antibodies appear solely after infection or also after COVID-19 vaccination.

Associations Between Mental Disorders in Donors and Matched Recipients of Hematopoietic Stem Cell Transplants: A Population-Based Cohort Study.

Background: Immunological mechanisms have been implicated in the development of mental disorders, and interestingly, case reports have suggested that hematopoietic stem cell transplantation (HSCT) can both transmit and cure psychotic disorders by replacing immune progenitor cells.

Methods: Using Danish registers, we followed patients who received HSCT from donors with a psychiatric diagnosis or psychotropic medication use. We assessed risk of incident mental disorders or psychotropic medication use compared with recipients with unaffected donors.

Fluctuation of functional somatic disorders in a population-based cohort. The DanFunD study.

Background: Evidence of incidence of functional somatic disorders (FSD) is hampered by unclear delimitations of the conditions and little is known about the possible interchangeability between syndromes. Further, knowledge on remission and persistence of FSD in the general population is limited. We aimed to assess the natural course of various FSD over 5 years in the general population.

Antipsychotic exposure and infection risk in people with schizophrenia spectrum disorders during the COVID-19 pandemic: a Danish nationwide registry study.

Background: Infection risk and mortality are increased in schizophrenia spectrum disorders, which was corroborated during the COVID-19 pandemic. However, evidence is lacking regarding the additional impact of antipsychotic drugs, and the highly debated safety of clozapine treatment during large-scale infection outbreaks. Therefore, we aimed to investigate risk of COVID-19 and non-COVID respiratory infections during exposure to antipsychotics.

White blood cell counts, ratios, and C-reactive protein among individuals with schizophrenia spectrum disorder and associations with long-term outcomes: a population-based study.

Background: Immune mechanisms are associated with adverse outcomes in schizophrenia; however, the predictive value of various peripheral immune biomarkers has not been collectively investigated in a large cohort before.

Objective: To investigate how white blood cell (WBC) counts, ratios, and C-Reactive Protein (CRP) levels influence the long-term outcomes of individuals with schizophrenia spectrum disorder (SSD).

Methods: We identified all adults in the Central Denmark Region during 1994-2013 with a measurement of WBC counts and/or CRP at first diagnosis of SSD.

Brain network changes and cognitive function after cardiac arrest.

Survival rates after out-of-hospital cardiac arrest have improved over the past two decades. Despite this progress, long-term cognitive impairment remains prevalent even in those with early recovery of consciousness after out-of-hospital cardiac arrest; however, little is known about the determinants and underlying mechanisms. We utilized the REcovery after cardiac arrest surVIVAL cohort of out-of-hospital cardiac arrest survivors who fully regained consciousness to correlate cognition measurements with brain network changes using resting-state functional MRI and the Montreal Cognitive Assessment at hospital discharge and a comprehensive neuropsychological assessment at three-month follow-up.

Traumatic brain injury and long-term associations with work, divorce and academic achievement.

Objective: Traumatic brain injuries (TBI), irrespective of severity, may have long-term social implications. This study explores the relationships between TBI severity and outcomes related to work stability, divorce, and academic achievement.

Methods: Using a Danish nationwide sample of persons with and without TBI, we employed case-control and longitudinal cohort designs.

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 to 2020: A Nationwide Study.

Objective: To 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 Methods: We conducted a cohort study using nationwide registers from 1996 to 2020 to identify individuals with diabetes, ascertain SMI status (namely, 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, and calendar year, accounting for sex, diabetes duration, education, and country of origin.

Genetic evidence for the causal effects of C-reactive protein on self-reported habitual sleep duration.

Inflammatory responses to acute stimuli are proposed to regulate sleep, but the relationship between chronic inflammation and habitual sleep duration is elusive. Here, we study this relation using genetically predicted level of chronic inflammation, indexed by CRP and IL6 signaling, and self-reported sleep duration. By Mendelian randomization analysis, we show that elevated CRP level within <10 mg/L has a homeostatic effect that facilitates maintaining 7-8 h sleep duration per day - making short-sleepers sleep longer (p = 2.

Possible temporal relationship between SARS-CoV-2 infection and anti-NMDA receptor encephalitis: a meta-analysis.

The global impact of SARS-CoV-2 infection has raised concerns about secondary diseases beyond acute illness. This review explores the significance and potential underlying mechanisms of how SARS-CoV-2 infection might elicit an immune response targeting N-methyl-D-aspartate (NMDA) receptors, and its implications for autoimmune-driven neuropsychiatric manifestations. We identified 19 published case reports of NMDA receptor encephalitis associated with SARS-CoV-2 infection or vaccination by a systematic literature search.

Is reduced heart rate variability associated with functional somatic disorders? A cross-sectional population-based study; DanFunD.

Objectives: It has been hypothesised that functional somatic disorders (FSD) could be initiated by sympathetic predominance in the autonomic nervous system as measured by low heart rate variability (HRV). Earlier studies on the association between HRV and FSD are small case-control studies hampered by selection bias and do not consider the great overlap between the various FSDs. The aim of the present study is to assess any associations between HRV and various FSDs and whether chronic stress confounds such an association.

Lipid metabolism and functional somatic disorders in the general population. The DanFunD study.

Objectives: Earlier studies on the association between plasma lipid profiles and functional somatic disorders (FSD) are mainly small case control studies hampered by selection bias and do not consider the great overlap between the various FSDs. The aim of the present study was to investigate the associations between various FSDs and plasma lipid profiles (total cholesterol, HDL cholesterol, non-HDL cholesterol and triglycerides) in a large, unselected population.

Design: A cross-sectional general population-based study.

Immune Cell Alterations in Psychotic Disorders: A Comprehensive Systematic Review and Meta-Analysis.

Background: A comprehensive meta-analysis on the composition of circulating immune cells from both the myeloid and the lymphoid lines including specialized subsets in blood and cerebrospinal fluid (CSF) of patients with psychotic disorders compared with healthy control participants has been lacking.

Methods: Multiple databases (PubMed, EMBASE, Cochrane Library, Web of Science, ClinicalTrials.gov, and PsycINFO) were searched for eligible studies up until October 18, 2022.

Levels of cytokines in the cerebrospinal fluid of patients with psychotic disorders compared to individually matched healthy controls.

Background: Increased peripheral cytokine levels have been observed in patients with psychotic disorders; however, large high-quality studies with individually matched healthy controls have been lacking regarding cytokines in cerebrospinal fluid (CSF) of individuals with psychotic disorders.

Methods: Patients diagnosed with a non-organic, non-affective psychotic disorder (ICD-10: F20/22-29) within a year prior to inclusion and individually age- and sex-matched healthy controls were included by identical in- and exclusion criteria's except for the psychiatric diagnoses. All participants were aged 18-50 years and individuals with neurological or immunological disorders were excluded.

Brain Health After COVID-19, Pneumonia, Myocardial Infarction, or Critical Illness.

Importance: Brain health is most likely compromised after hospitalization for COVID-19; however, long-term prospective investigations with matched control cohorts and face-to-face assessments are lacking.

Objective: To assess whether long-term cognitive, psychiatric, or neurological complications among patients hospitalized for COVID-19 differ from those among patients hospitalized for other medical conditions of similar severity and from healthy controls.

Design, Setting, And Participants: This prospective cohort study with matched controls was conducted at 2 academic hospitals in Copenhagen, Denmark.

SARS-CoV-2 and autoantibodies in the cerebrospinal fluid of COVID-19 patients: prospective multicentre cohort study.

Disease mechanisms underlying neurological and neuropsychiatric symptoms after coronavirus disease 2019 (COVID-19), termed neuro-COVID, are poorly understood. Investigations of the cerebrospinal fluid (CSF) for the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA and antibodies, as well as autoantibodies against neuronal surface antigens, could improve our understanding in that regard. We prospectively collected CSF and blood from patients investigated by lumbar puncture for neurological or neuropsychiatric symptoms during or after COVID-19.

Antineuronal Autoantibodies in the Cerebrospinal Fluid and Serum From 106 Patients With Recent-Onset Depression Compared With 106 Individually Matched Healthy Control Subjects.

No large studies have investigated the prevalence of cerebrospinal fluid antineuronal autoantibodies in isolated depression. In this case-control study comparing 106 patients with isolated depression (ICD-10 code F32) with 106 healthy control subjects, cerebrospinal fluid and serum samples were tested for 7 immunoglobulin G autoantibodies using commercial fixed cell-based assays. To explore validity of methods, positive samples were retested twice by cell-based assays and once by tissue-based assays (monkey cerebellum).