Merete Nordentoft

University of Copenhagen · Psychiatric Center Copenhagen

Aim: This study examines associations between premorbid adjustment and comorbid disorders in individuals at ultra-high risk (UHR) for psychosis. Methods: Premorbid social and academic adjustment data were collected from 146 UHR individuals using the Premorbid Adjustment Scale. Comorbid disorders were determined by the Structural Clinical Intervi...

Autism spectrum disorder (ASD) refers to a group of neurodevelopmental disorders which include deficits in behavior, social interaction and communication. ASD has a complex genetic architecture, and it is also influenced by certain environmental exposures. Both types of predisposing factors may be related to immunological mechanisms, involving, for...

Background Schizophrenia spectrum disorders cause suffering for patients, relatives, and the surrounding society. Paranoid ideations, encompassing ideas of social reference and manifest persecutory delusions, are among the most frequent symptoms in this population and a cause of significant distress. Recent meta-analyses of cognitive behavioral the...

Proportional hazards models have previously been proposed to analyse time-to-event phenotypes in genome-wide association studies(GWAS). While proportional hazards models have many useful applications, their ability to identify genetic associations under different generative models where ascertainment is present in the analysed data is poorly unders...

Background Predicted increases in suicide were not generally observed in the early months of the COVID-19 pandemic. However, the picture may be changing and patterns might vary across demographic groups. We aimed to provide a timely, granular picture of the pandemic's impact on suicides globally. Methods We identified suicide data from official pu...

Background Prior studies have shown high heritability estimates regarding within-function transmission of neurocognition, both in healthy families and in families with schizophrenia but it remains an open question whether transmission from parents to offspring is function specific and whether the pattern is the same in healthy families and families...

Background Infrequent deviants in a rapid sequence of sounds elicit a negative cortical potential over the frontocentral midline (mismatch negativity, MMN) followed by a positive deflection (P3a). Both cortical potentials are consistently attenuated in patients with schizophrenia (SZ), and, to a lesser degree, in patients with bipolar disorder (BP)...

Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder with onset in childhood (childhood ADHD); two-thirds of affected individuals continue to have ADHD in adulthood (persistent ADHD), and sometimes ADHD is diagnosed in adulthood (late-diagnosed ADHD). We evaluated genetic differences among childhood (n = 14,878), persist...

Objective People at ultra-high risk (UHR) for psychosis have a high prevalence of tobacco smoking, and rates are even higher among the subgroup that later develop a psychotic disorder. However, the longitudinal relationship between the course of tobacco smoking and clinical outcomes in UHR subjects is unknown. Methods We investigated associations...

Background The jumping to conclusions (JTC) bias, ie, making decisions based on inadequate evidence, is associated with psychosis in adults and is believed to underlie the formation of delusions. Knowledge on the early manifestations of JTC and its associations with psychotic experiences (PE) in children and adolescents is lacking. Design Preadole...

Background Discontinuation of antipsychotic medication may be linked to high risk of relapse, hospitalization and mortality. This study investigated the use and discontinuation of antipsychotics in individuals with first-episode schizophrenia in relation to cohabitation, living with children, employment, hospital admission and death. Methods Danis...

Background Childbirth may be a traumatic experience and vulnerability to posttraumatic stress disorder (PTSD) may increase the risk of postpartum depression (PPD). We investigated whether genetic vulnerability to PTSD as measured by polygenic score (PGS) increases the risk of PPD and whether a predisposition to PTSD in PPD cases exceeds that of maj...

Treating schizophrenia requires both antipsychotic medication and psychosocial interventions. This review summarises the current knowledge in this area. A mixed treatment meta-analysis has recently concluded that family interventions, psychoeducation and cognitive behavioural therapy show the greatest effect in preventing relapse and reducing sympt...

Study objectives: Melatonin is often prescribed to patients with sleep disorders who are known to have elevated suicide risks. Yet, melatonin's association to suicidal behavior remains to be examined. We investigated whether individuals prescribed melatonin had higher rates of suicide and suicide attempts when compared to individuals who were not...

Currently, psychiatric diagnoses are, in contrast to most other medical fields, based on subjective symptoms and observable signs and call for new and improved diagnostics to provide the most optimal care. On the basis of a deep learning approach, we performed unsupervised patient stratification of 19,636 patients with depression [major depressive...

Polygenic risk scores (PRS) are increasingly used to predict diseases (e.g., schizophrenia). However, the proper application of the PRS in psychological studies is sparse. We aimed to evaluate the methodological aspects of using PRS as a covariate in causal association studies in psychology. We conducted a simulation study using realistic scenarios...

Aim Evidence is insufficient regarding the consequences of discontinuing vs. maintaining antipsychotic medication in patients with first-episode schizophrenia. Our aim was to examine tapered discontinuation vs. maintenance treatment regarding remission of psychotic symptoms and impact on other areas. Methods Patients included had a diagnosis of sc...

Individuals at Clinical High Risk for Psychosis (CHR-P) demonstrate heterogeneity in clinical profiles and outcome features. However, the extent of neuroanatomical heterogeneity in the CHR-P state is largely undetermined. We aimed to quantify the neuroanatomical heterogeneity in structural magnetic resonance imaging measures of cortical surface are...

Background: Knowledge of the adverse problems related to SARS-CoV-2 infection in marginalised and deprived groups may help to prioritise more preventive efforts in these groups. We examined adverse outcomes associated with SARS-CoV-2 infection among vulnerable segments of society. Methods: Using health and administrative registers, a population-...

Sample recruitment for research consortia, hospitals, biobanks, and personal genomics companies span years, necessitating genotyping in batches, using different technologies. As marker content on genotyping arrays varies systematically, integrating such datasets is non-trivial and its impact on haplotype estimation (phasing) and whole genome imputa...

BACKGROUND Shared Decision Making (SDM) is a process aimed at facilitating patient-centered care by ensuring that the patient and the provider are actively involved in treatment decisions. In mental healthcare, SDM has been advocated as a mean for the patient to (re)gain control and responsibility over his/her life and recovery process. To support...

Objective: The aim of this study was to: (1) determine the proportion of callers to a national helpline for suicide prevention who were evaluated to be at risk of suicide; (2) identify characteristics associated with being at risk; (3) determine the level of suicidal ideation among callers, as measured by a clinical scale, and compared to the gene...

The vitamin D binding protein (DBP), encoded by the group-specific component (GC) gene, is a much-studied component of the vitamin D system. In a genome-wide association study of DBP concentration in 65,589 neonates, we identified 26 independent loci, 17 of which were in or close to the GC gene, with fine-mapping identifying 2 loci on chromosomes 1...

Background Schizophrenia Spectrum disorders cause suffering for patients, relatives, and the surrounding society. Paranoid ideations, encompassing ideas of social reference and manifest persecutory delusions, are among the most frequent symptoms in this population and a cause of significant distress. Recent meta-analyses of Cognitive Behavioral The...

This study investigates indicators of disorganized caregiving among caregivers of children who have a familial predisposition of schizophrenia spectrum psychosis (SZ) or bipolar disorder (BP), and whether indicators of disorganized caregiving are associated with the caregivers’ and children’s level of functioning as well as the children’s internali...

The substantial phenotypic heterogeneity in autism limits our understanding of its genetic etiology. To address this gap, here we investigated genetic differences between autistic individuals ( n max = 12,893) based on core and associated features of autism, co-occurring developmental disabilities and sex. We conducted a comprehensive factor analys...

Cognitive heterogeneity characterizes individuals with schizophrenia and bipolar disorder; however, little is known of cognitive heterogeneity within young children at familial high-risk of schizophrenia or bipolar disorder. This study aimed to investigate heterogeneity across social cognitive and language functions in children at familial high-ris...

PurposeTo investigate longitudinal trajectories of vocational recovery (VR) among individuals with severe mental illness (SMI) who participated in the Danish Individual Placement and Support (IPS) trial, and whether the IPS intervention, socio-demographic and disease-specific characteristics predicted trajectory membership.Methods In an observation...

Purpose We explored if patients with treatment-resistant depression (TRD) go through different states of labor market affiliation during their course of illness before they return to work or obtain early retirement as compared to patients without TRD. Methods All adults between 18 and 58 years with a first-time hospital contact due to depression i...

Social impairments are suggested as vulnerability markers for schizophrenia and bipolar disorder. Therefore, we investigated the development of social responsiveness and theory of mind (ToM) in children at familial high-risk of schizophrenia (FHR-SZ) or bipolar disorder (FHR-BP). This study is part of The Danish High Risk and Resilience Study, a lo...

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 (...

Background Children born to parents with severe mental illness are at increased risk of mental and behavioral difficulties during childhood. We aimed to investigate the occurrence of clinically significant behavioral difficulties in 7-year-old children of parents diagnosed with schizophrenia or bipolar disorder as well as in control children by usi...

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...

Rare coding variation has historically provided the most direct connections between gene function and disease pathogenesis. By meta-analysing the whole exomes of 24,248 schizophrenia cases and 97,322 controls, we implicate ultra-rare coding variants (URVs) in 10 genes as conferring substantial risk for schizophrenia (odds ratios of 3–50, P < 2.14 ×...

Background Hydrocephalus is one of the most common congenital disorders of the central nervous system and often displays psychiatric co-morbidities, in particular autism spectrum disorder. The disease mechanisms behind hydrocephalus are complex and not well understood, but some association with dysfunctional cilia in the brain ventricles and subara...

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...

Importance: Neurocognitive impairments exist in children at familial high risk (FHR) of schizophrenia and bipolar disorder. Studies on preadolescent developmental courses of neurocognition are important to describe shared and distinct neurodevelopmental pathways in these groups. Objective: To assess the development in specific neurocognitive fun...

This review summarises the current knowledge of the use of collaborative care (CC) in Denmark. CC is an evidence-based approach to the treatment of depression and anxiety in primary care services. An optimised treatment is needed in Denmark, and a Danish CC model called Collabri, later Collabri Flex, was developed and evaluated in randomised contro...

Background Asthma with severe exacerbation is one of the most common causes of hospitalization among young children. Exacerbations are typically triggered by respiratory infections, but the host factors causing recurrent infections and exacerbations in some children are poorly understood. As a result, current treatment options and preventive measur...

Objective: Stress-related disorders are common, associated with substantial individual suffering, and place a large economic burden on society. While treatment appears to be able to reduce symptoms, evidence of interventions to improve vocational outcomes is flimsy. Lack of integration of vocational rehabilitation and healthcare services has been...

Background Children born to parents with severe mental illness have gained more attention during the last decades because of increasing evidence documenting that these children constitute a population with an increased risk of developing mental illness and other negative life outcomes. Because of high-quality research with cohorts of offspring with...

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...

Objectives: Childhood trauma increases the risk of developing mental illness as does being born to parents with schizophrenia or bipolar disorder. We aimed to compare prevalence of lifetime childhood trauma among 11-year-old children at familial high risk of schizophrenia (FHR-SZ) or bipolar disorder (FHR-BP) compared with population-based control...

Background Functional outcomes are important measures in the overall clinical course of psychosis and individuals at clinical high-risk (CHR), however, prediction of functional outcome remains difficult based on clinical information alone. In the first part of this study, we evaluated whether a combination of biological and clinical variables could...

Background Suicidal behaviour runs in families, but the nature of transgenerational concordance needs elucidation. The aim of this study was to examine parent-to-child transmission by investigating whether presence and nature of parental suicidal behaviour was associated with suicidal behaviour in children. Methods We did a retrospective, nationwi...

Background Facing multiple risk factors, relative to single risk factor exposure early in life can have great implications for negative child development. Objective We aim to examine whether the prevalence of early risk factors is higher among children with familial high risk for schizophrenia or bipolar disorder compared to controls. Further, to...

Decades of research show that psychosocial treatments are effective for psychosis, yet they remain unimplemented as the American healthcare system relies primarily on pharmacological solutions instead. This book reviews the history and current state of research to provide a more nuanced understanding of the evidence for and barriers to psychosocial...

Attention deficit hyperactivity disorder (ADHD) is a prevalent childhood psychiatric disorder, with a major genetic component. Here we present a GWAS meta-analysis of ADHD comprising 38,691 individuals with ADHD and 186,843 controls. We identified 27 genome-wide significant loci, which is more than twice the number previously reported. Fine-mapping...

Background: . High-quality comprehensive data on short-/long-term physical/mental health effects of the COVID-19 pandemic are needed. Methods: . The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT) is an international, multi-language (n=30) project involving >230 investigators from 49 countries/territories/re...

Background Exposure to inadequate home environment may put the healthy development of familial high-risk children at risk. This study aimed to investigate associations between risk factors and an adequate home environment of children having a parent diagnosed with schizophrenia or bipolar disorder. Methods From a cohort of 522 children, data from...

Introduction Anxiety disorders have a high lifetime prevalence, early-onset and long duration or chronicity. Exposure therapy is considered one of the most effective elements in cognitive behavioural therapy (CBT) for anxiety, but in vivo exposure can be challenging to access and control, and is sometimes rejected by patients because they consider...

Genome-wide association studies (GWASs) have revolutionized human genetics, allowing researchers to identify thousands of disease-related genes and possible drug targets. However, case-control status does not account for the fact that not all controls may have lived through their period of risk for the disorder of interest. This can be quantified b...

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...

Human behaviour is complex and multifaceted, and is studied by a broad range of disciplines across the social and natural sciences. To mark our 5th anniversary, we asked leading scientists in some of the key disciplines that we cover to share their vision of the future of research in their disciplines. Our contributors underscore how important it i...

Objective Children with familial high-risk of schizophrenia (FHR-SZ) or bipolar disorder (FHR-BP) are frequently affected in a range of domains known to be precursors of severe mental illness. No previous studies have gathered known precursors to examine whether they distribute evenly across familial high risk (FHR) children or if they cluster amon...

Background Studies of neurocognitive heterogeneity in young children at familial high-risk of bipolar disorder (FHR-BP) or schizophrenia (FHR-SZ) are important to investigate inter-individual neurocognitive differences. We aimed to identify neurocognitive subgroups, describe prevalence of FHR-BP or FHR-SZ children herein, and examine risk ratios (R...

Febrile seizures represent the most common type of pathological brain activity in young children and are influenced by genetic, environmental and developmental factors. In a minority of cases, febrile seizures precede later development of epilepsy. We conducted a genome-wide association study of febrile seizures in 7635 cases and 83 966 controls id...

Objective: To estimate phenotypic and familial association between early-life injuries and attention-deficit/hyperactivity disorder (ADHD) and the genetic contribution to the association using polygenic risk score for ADHD (PRS-ADHD) and genetic correlation analyses. Methods: Children born in Denmark between 1995-2010 (n = 786,543) were followed f...

Background . High-quality comprehensive data on short-/long-term physical/mental health effects of the COVID-19 pandemic are needed. Methods . The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT) is an international, multi-language (n=30) project involving >230 investigators from 49 countries/territories/regi...

Understanding longitudinal cognitive performance in individuals at ultra-high risk for psychosis (UHR) is important for informing theoretical models and treatment. A vital step in this endeavor is to determine whether there are UHR subgroups that have similar patterns of cognitive change over time. The aims were to: i) identify latent class traject...

Objective People with schizophrenia and bipolar disorder are at increased risk of having comorbid somatic illness. This is partly due to lack of physical activity, which may originate from childhood. Sleep disturbances are associated with schizophrenia and bipolar disorder. We aimed to assess physical activity and sleep in children at familial high...

Objective The aim of this study was to investigate an integrated mental healthcare and vocational rehabilitation intervention to improve and hasten the process of return-to-work of people on sick leave with anxiety and depression. Methods In this three-arm, randomised trial, participants were assigned to (1) integrated intervention (INT), (2) impr...

Background Children at familial high‐risk of schizophrenia and bipolar disorder have an elevated prevalence of mental disorders but studies of children within a narrow age range are lacking and there are few conjoint studies of these two groups. Knowledge on their mental health is important for prevention and early intervention. Methods The author...

Objective There are concerns that asylum-seekers are at increased risk of suicide attempt and suicide mortality. Yet, largescale nationwide studies are limited. Our aim was to examine whether asylum-seekers in Denmark had higher rates of suicide attempt and suicide when compared to the general population. Methods A retrospective cohort design was...

Cognitive impairments are strongly associated with schizophrenia (SZ) and bipolar disorder (BP) with executive functions (EF) impairments as a likely key feature. Studies of everyday behavior rated EF in young children at familial high risk of SZ (FHR-SZ) are scarce and, to our knowledge, non-existent in young children at familial high risk of BP (...

Background The association between autism spectrum disorder and hydrocephalus is not well understood, despite demonstrated links between autism spectrum disorder and cerebrospinal fluid abnormalities. Based on the hypothesis that autism spectrum disorder and hydrocephalus may, at least in some cases, be two manifestations of a shared congenital bra...

Background The home environment has a major impact on child development. Parental severe mental illness can pose a challenge to the home environment of a child. We aimed to examine the home environment of children of parents with schizophrenia or bipolar disorder and controls longitudinally through at-home assessments. Methods Assessments were con...

Importance Although the association between several recurrent genomic copy number variants (CNVs) and mental disorders has been studied for more than a decade, unbiased, population-based estimates of the prevalence, disease risks and trajectories, fertility, and mortality to contrast chromosomal abnormalities and advance precision health care are l...

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 Language plays a major role in human behavior. For this reason, neurodevelopmental and psychiatric disorders in which linguistic ability is impaired could have a big impact on the individual’s social interaction and general wellbeing. Such disorders tend to have a strong genetic component, but most past studies examined mostly the lingui...

Background: Reviews of camera surveillance systems have demonstrated ambivalent behaviors among people who die by railway suicide. Yet, only few preventive measures have been evaluated. Aims: We aimed to review incidents of suicidal behavior at a Danish railway station, install preventive measures, and monitor subsequent calls to a telephone helpli...