Michael E Benros

Copenhagen University Hospital · Department of Psychiatry

Depression is a frequent mental disorder with a substantial contribution to years lived with disability worldwide. In the search for new treatment targets, the immune system’s contribution to the pathogenesis of depression has received increased attention as immune activation has been associated with depression in various epidemiological and case-c...

IntroductionCOVID-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 ot...

Background: Poor school performance is linked to higher risks of self-harm. The association might be explained through genetic liabilities for depression or educational attainment. We investigated the association between school performance and self-harm in a population-based sample while assessing the potential influence of polygenic risk scores (...

Animal models are useful preclinical tools for studying the pathogenesis of mental disorders and the effectiveness of their treatment. While it is not possible to mimic all symptoms occurring in humans, it is however possible to investigate the behavioral, physiological and neuroanatomical alterations relevant for these complex disorders in control...

Background: Social deprivation, psychiatric and medical disorders have been associated with increased risk of infection and severe COVID-19-related health problems. We aimed to study the rates of SARS-CoV-2 vaccination in these high-risk groups. Methods: Using health, vaccination, and administrative registers, we performed a population-based cohort...

Background: Mood stabilisers are the main treatment for bipolar disorder. However, it is uncertain which drugs have the best outcomes. Aims: To investigate whether rates of suicide, self-harm and psychiatric hospital admission in individuals with bipolar disorder differ between mood stabilisers. Method: A cohort design was applied to people ag...

Importance: Depression has been associated with alterations in neurotransmitters, hormones, and inflammatory and neurodegenerative biomarkers, and biomarkers quantified in the cerebrospinal fluid (CSF) are more likely to reflect ongoing biochemical changes within the brain. However, a comprehensive overview of CSF biomarkers is lacking and could c...

Background Traumatic brain injury (TBI) can cause long-lasting sequelae that may increase the risk of suicidal or criminal behaviour, but large-scale longitudinal studies are lacking on the link between TBI and events of suicide attempt and violent crime. This study examined the incidence of suicide attempt and violent crime following hospital cont...

Background Neuroinflammation has been linked to depression; however, neuroinflammatory biomarkers in the cerebrospinal fluid (CSF) have not previously been thoroughly investigated in a large group of patients with recent onset depression compared to healthy controls. Methods Individually matched case-control study comparing patients with recent on...

Context Persons with severe mental illness (SMI) are at increased risk to develop type 2 diabetes. Objective It is unclear whether persons with diabetes and SMI are also at increased risk of diabetes complications and the potential age-specific differences in development of these. Design, setting, and participants Utilizing nationwide register da...

Importance: Prolonged neuropsychiatric and cognitive symptoms are increasingly reported in patients after COVID-19, but studies with well-matched controls are lacking. Objective: To investigate cognitive impairment, neuropsychiatric diagnoses, and symptoms in survivors of COVID-19 compared with patients hospitalized for non-COVID-19 illness. De...

Study objectives Sleep disorders are related to mental disorders. Yet few studies have examined their association with suicide. We examined whether males and females diagnosed with sleep disorders had higher rates of suicide than individuals not diagnosed with sleep disorders. Methods In a cohort study, nationwide data on all males and females age...

Digital health technology is promising for improving mental healthcare by enabling continuous monitoring of behaviour by smartphones and wearables, new paradigms for testing in virtual reality, and analysis of big data through machine learning for prediction models. This might advance prevention efforts, and contribute to diagnostics and treatment;...

Background Schizophrenia (SCZ) is a heterogeneous neuropsychiatric disorder, for which current treatment has insufficient efficacy and severe adverse effects. The modifiable gut microbiome might be a potential target for intervention to improve neurobiological functions through the gut-microbiome-brain axis. Methods In this case-control study, gut...

BACKGROUND Several recent studies have suggested a role for infections in the development of mental disorders; however, the genetic contribution to this association is understudied. METHODS We use the iPSYCH case-cohort genotyped sample (N = 65,534) and Danish healthcare registry data to study the genetic association between infections and mental...

Background A proinflammatory response has been suggested to be involved in the pathophysiology of depression in a subgroup of patients. However, comprehensive largescale studies on neuroimmunological investigations of the cerebrospinal fluid (CSF) are lacking and no largescale longitudinal CSF studies comparing patients with depression to healthy c...

Introduction People with psychiatric disorders have increased risk of premature death partly due to diabetes. This study aims to explore the quality of diabetes care, diabetes management, diabetes support and well-being of people with psychiatric disorders and diabetes. Research design and methods A total of 107 participants aged ≥18 years with di...

Multiple lines of evidence indicate that immunological and inflammatory alterations contribute at least in a subgroup to the pathophysiology of schizophrenia. In this retrospective chart review, we investigated whether clinical factors contribute to altered cerebrospinal fluid (CSF) findings in schizophrenia-spectrum disorders. Clinical data from e...

Schizophrenia is a heterogeneous disorder, exhibiting variability in presentation and outcomes that complicate treatment and recovery. To explore this heterogeneity, we leverage the comprehensive Danish health registries to conduct a prospective, longitudinal study from birth of 5432 individuals who would ultimately be diagnosed with schizophrenia,...

Background Researchers have long investigated a hypothesized interaction between genetic risk and stressful life events in the etiology of depression, but studies on the topic have yielded inconsistent results. Methods We conducted a genome-wide environment interaction study in 18,532 patients with depression from hospital-based settings and 20,18...

Purpose of ReviewWe present biological and psychological factors implicated in psychiatric manifestations of SARS-CoV-2, as well as its neuroinvasive capability and immune pathophysiology.Recent FindingsPreexisting mental illness leads to worse clinical outcomes in COVID-19. The presence of the virus was reported in the cerebrospinal fluid (CSF) an...

To assess whether patient-controlled admissions (PCA) to psychiatric hospital wards have an effect on total health care costs in the short term and longer term compared with patients receiving treatment as usual (TAU). Based on Danish register data and using coarsened exact matching, patients who signed a contract for PCA during 2013–2016 were matc...

Background Though many previous studies have indicated immunological alterations in psychotic disorders, the role and prevalence of neuroinflammation is still unknown. Studies previously investigating immune related biomarkers in the cerebrospinal fluid (CSF) of these patients are mainly small studies on few markers, and many have not compared pati...

Researchers have long investigated a hypothesized interaction between genetic risk and stressful life events in the etiology of depression, but studies on the topic have yielded inconsistent results. We conducted a genome-wide environment interaction study in 18,532 depression cases from hospital-based settings and 20,184 population-representative...

Objective To systematically describe central (CNS) and peripheral (PNS) nervous system complications in hospitalized COVID-19 patients. Methods We conducted a prospective, consecutive, observational study of adult patients from a tertiary referral center with confirmed COVID-19. All patients were screened daily for neurological and neuropsychiatri...

Objective To assess the patterns in psychiatric admissions, referrals and suicidal behavior before and during the COVID-19 pandemic. Methods This study utilized health records from hospitals and Emergency Medical Services (EMS) covering 46 % of the Danish population (n=2,693,924). In an time-trend study, we compared the number of psychiatric in-pa...

Abstract Background Anorexia nervosa (AN), a serious eating disorder, and inflammatory bowel diseases (IBD) share a number of key symptoms, for example, discomfort during eating and early satiety. Despite the symptom overlap, studies on comorbidity are limited and mostly conducted in relatively small samples. This study investigates the comorbidity...

Schizophrenia (SCZ) is a severe brain disorder, characterized by psychotic, negative and cognitive symptoms, affecting 1% of the population worldwide. The precise aetiology of SCZ is still unknown; however, SCZ has a high heritability, and is associated with genetic, environmental and social risk factors. Even though the genetic contribution is ind...

Both epidemiological and clinical studies support an association between infections and autoimmune diseases with mental disorders. It has been suggested that infections and autoimmune diseases can increase the risk of mental disorders by inducing neuroinflammation potentially through immunopathological mechanisms. These mechanisms might increase th...

Background Cerebrospinal fluid (CSF) immune alterations have been associated with mental disorders, neurological disease, and CNS infections; however, comprehensive large-scale longitudinal CSF studies are lacking. Methods By using the Clinical Laboratory Information System (LABKA) Research Database in the Central Denmark Region (1994-2012), we in...

Objective: Lyme borreliosis is a tick-borne infectious disease that may confer an increased risk of mental disorders, but previous studies have been hampered by methodological limitations, including small sample sizes. The authors used a nationwide retrospective cohort study design to examine rates of mental disorders following Lyme borreliosis....

Background In the continuation of the first wave of the Covid-19 outbreak in Denmark, unprecedented restrictions with great impact on the citizen’s everyday life were implemented. The objectives of this study were to investigate the influence of the Covid-19 pandemic on mental and physical health in the Danish population during the spring 2020 firs...

Background: Mental disorders might be a risk factor for severe COVID-19. We aimed to assess the specific risks of COVID-19-related mortality, hospitalisation, and intensive care unit (ICU) admission associated with any pre-existing mental disorder, and specific diagnostic categories of mental disorders, and exposure to psychopharmacological drug c...

Objective: To investigate vagotomy, the severance of the vagus nerve, and its association with mental disorders, as gut-brain communication partly mediated by the vagus nerve have been suggested as a risk factor. Methods: Nationwide population-based Danish register study of all individuals alive and living in Denmark during the study period 1977...

Objective To explore the association of the number of TBIs and temporal associations with the subsequent risk of depression in the population. Methods National register-based cohort study on all individuals registered with TBI (ICD-10: S06, ICD-8: 85.0-85.5) from 1977 to 2015 in Denmark (n=494,216) and a sex- and age-matched reference population (...

Disrupted pain regulation has been proposed as a component in functional somatic disorders (FSD). The objective of this study was to examine a general population sample, encompassing three delimitations of FSD while assessing pain sensitivity and conditioning pain modulation (CPM). Pressure pain thresholds (PPTs) at the tibialis and trapezius muscl...

Background Infections are a major disease burden worldwide. While they are caused by external pathogens, host genetics also plays a part in susceptibility to infections. Past studies have reported diverse associations between human leukocyte antigen (HLA) alleles and infections, but many were limited by small sample sizes and/or focused on only one...

Background: In this study, we examined the relationship between polygenic liability for depression and number of stressful life events (SLEs) as risk factors for early-onset depression treated in inpatient, outpatient or emergency room settings at psychiatric hospitals in Denmark. Methods: Data were drawn from the iPSYCH2012 case-cohort sample,...

Background Infectious mononucleosis is a clinical diagnosis characterized by fever, sore throat, lymph node enlargement and often prolonged fatigue, most commonly caused by Epstein-Barr virus infection. Previous studies have indicated that infectious mononucleosis can be followed by depression; however, large-scale studies are lacking. We used nati...

To the Editor The Tetens et al nationwide matched cohort study¹ of cases with positive Borrelia intrathecal antibody index¹ reported increased use of psychiatric medications during the first year after diagnosis, but no significant association was shown with hospital-based psychiatric diagnosis or psychiatric in-patient or outpatient hospital conta...

A Correction to this paper has been published: https://doi.org/10.1038/s41431-020-00772-y

Background: As of October 2020, COVID-19 has caused 1,000,000 deaths worldwide. However, large-scale studies of COVID-19 mortality and new-onset comorbidity compared to individuals tested negative for COVID-19 and individuals tested for influenza A/B are lacking. We investigated COVID-19 30-day mortality and new-onset comorbidity compared to indivi...

Circulating inflammatory markers are essential to human health and disease, and they are often dysregulated or malfunctioning in cancers as well as in cardiovascular, metabolic, immunologic and neuropsychiatric disorders. However, the genetic contribution to the physiological variation of levels of circulating inflammatory markers is largely unknow...

Objective To systematically describe CNS and PNS complications in hospitalized COVID-19 patients. Methods We conducted a prospective, consecutive, observational study of adult patients from a tertiary referral center with confirmed COVID-19. All patients were screened daily for neurological and neuropsychiatric symptoms during admission, at discha...

Many medical treatments, from oncology to psychiatry, can lower white blood cell counts and thus access to these treatments can be restricted to individuals with normal levels of white blood cells, principally in order to minimise risk of serious infection. This adversely affects individuals of African or Middle Eastern ancestries who have on avera...

Objective: The Whiteley Index (WI) is the most widely used screening tool for health anxiety/illness worry. Diverse versions (different number of items and factors) have been used. We aimed to examine psychometric properties of 7 items of the WI besides adding a new item on obsessive illness rumination for better future detection of health anxiety...

An amendment to this paper has been published and can be accessed via the original article.

Objective: Antipsychotic effects of immunomodulating drugs have been suggested; however, a thorough, comprehensive meta-analysis on the effect and safety of anti-inflammatory add-on treatment on psychotic disorders is lacking. Method: Multiple databases were searched up until February 2020. Only double-blinded, randomized, placebo-controlled cli...

Background: Bullous pemphigoid (BP) is an autoimmune blistering skin disease that takes a profound physical and mental toll on those affected. The aim of the study was to investigate the bidirectional association between BP and all bullous disorders (ABD) with a broad array of psychiatric disorders, exploring the influence of prescribed medication...

Background As of July 2020, COVID-19 has caused 500,000 deaths worldwide. However, large-scale studies of COVID-19 mortality and new-onset comorbidity compared to influenza and individuals tested negative for COVID-19 are lacking. We aimed to investigate COVID-19 30-day mortality and newonset comorbidity compared to individuals with negative COVID-...

Antibody indices to MRZ are of diagnostic value in multiple sclerosis (MS). Here, we have investigated, if this panel could be extended to increase diagnostic value. Samples from relapsing-remitting (RR) MS and optic neuritis (ON) patients were tested for reactivity to antigens from Epstein-Barr, Varicella Zoster, Measles, Mumps and Rubella (EMMRZ)...

Background Previous studies have indicated the bidirectionality between autoimmune and mental disorders. However, genetic studies underpinning the co-occurrence of the two disorders have been lacking. In this study, we examined the potential genetic contribution to the association between autoimmune and mental disorders and investigated the genetic...

Background Blood-brain barrier (BBB) pathology may be associated with mental disorders. The aim of this systematic review and meta-analysis is to identify, evaluate and summarize available evidence on whether potential biomarkers of BBB pathology are altered in patients with schizophrenia spectrum disorders, major depression and bipolar disorder co...

Background Substance-induced psychosis is an under-researched phenomenon, and little is known about its etiology (other than exposure to substances) and long-term prognosis. In this presentation, we aim to present results from two recent studies, one of which was recently published and the other is currently in the process of being analyzed. The fi...

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...

Background During the COVID-19 pandemic general medical complications have received the most attention, whereas only few studies address the potential direct effect on mental health of SARS-CoV-2 and the neurotropic potential. Furthermore, the indirect effects of the pandemic on general mental health are of increasing concern, particularly since th...

Background Persons with mental disorders are at a higher risk than the general population for the subsequent development of certain medical conditions. Methods We used a population-based cohort from Danish national registries that included data on more than 5.9 million persons born in Denmark from 1900 through 2015 and followed them from 2000 thro...

Background CNS infections have been suggested as risk factors for cognitive decline and mental disorders; however, large-scale studies have been lacking regarding types and agents of CNS infections. Methods We utilized the unique personal registration number to create a cohort of 1,709,867 individuals born 1977-2010. CNS infection was exposure and...

There is an increasing evidence that inflammation contributes to clinical and functional outcomes in traumatic brain injury (TBI). Many successful target-engaging, lesion-reducing, symptom-alleviating, and function-improving interventions in animal models of TBI have failed to show efficacy in clinical trials. Timing and immunological context are p...

Prevalence of functional somatic syndromes (FSS) in the general population varies with observed overlap between syndromes. However, studies including a range of FSS are sparse. We investigated prevalence and characteristics of various FSS and the unifying diagnostic construct bodily distress syndrome (BDS), and identified mutual overlap of the FSS...