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"Nordentoft, Merete"
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Suicide—turning the tide
2019
Suicide is a devastating public health problem, afflicting individuals, families, and societies. Fortunately, continuous striving by the World Health Organization to strengthen suicide prevention efforts is paying off. The annual number of suicide deaths decreased from 1 million to 800,000 worldwide during recent decades. A gloomy exception to this trend is the increasing rate of suicide in the United States (14.0 per 100,000 in 2017). But Denmark's experience offers some hope that prevention of suicide is possible. Why has its decline in suicide been steeper than in most other countries?
Journal Article
Cerebrospinal fluid markers of inflammation and infections in schizophrenia and affective disorders: a systematic review and meta-analysis
by
Nordentoft, Merete
,
Orlovska-Waast, Sonja
,
Michael Eriksen Benros
in
Affective disorders
,
Age composition
,
Albumin
2019
Infections and inflammatory processes have been associated with the development of schizophrenia and affective disorders; however, no study has yet systematically reviewed all available studies on cerebrospinal fluid (CSF) immune alterations. We aimed to systematically review the CSF immunological findings in schizophrenia spectrum and affective disorders. We identified all studies investigating CSF inflammatory markers in persons with schizophrenia or affective disorders published prior to March 23, 2017 searching PubMed, CENTRAL, EMBASE, Psychinfo, and LILACS. Literature search, data extraction and bias assessment were performed by two independent reviewers. Meta-analyses with standardized mean difference (SMD) including 95% confidence intervals (CI) were performed on case-healthy control studies. We identified 112 CSF studies published between 1942–2016, and 32 case-healthy control studies could be included in meta-analyses. Studies varied regarding gender distribution, age, disease duration, treatment, investigated biomarkers, and whether recruitment happened consecutively or based on clinical indication. The CSF/serum albumin ratio was increased in schizophrenia (1 study [54 patients]; SMD = 0.71; 95% CI 0.33–1.09) and affective disorders (4 studies [298 patients]; SMD = 0.41; 95% CI 0.23–0.60, I2 = 0%), compared to healthy controls. Total CSF protein was elevated in both schizophrenia (3 studies [97 patients]; SMD = 0.41; 95% CI 0.15–0.67, I2 = 0%) and affective disorders (2 studies [53 patients]; SMD = 0.80; 95% CI 0.39–1.21, I2 = 0%). The IgG ratio was increased in schizophrenia (1 study [54 patients]; SMD = 0.68; 95% CI 0.30–1.06), whereas the IgG Albumin ratio was decreased (1 study [32 patients]; SMD = −0.62; 95% CI −1.13 to −0.12). Interleukin-6 (IL-6) levels (7 studies [230 patients]; SMD = 0.55; 95% CI 0.35–0.76; I2 = 1%) and IL-8 levels (3 studies [95 patients]; SMD = 0.46; 95% CI 0.17–0.75, I2 = 0%) were increased in schizophrenia but not significantly increased in affective disorders. Most of the remaining inflammatory markers were not significantly different compared to healthy controls in the meta-analyses. However, in the studies which did not include healthy controls, CSF abnormalities were more common, and two studies found CSF dependent re-diagnosis in 3.2–6%. Current findings suggest that schizophrenia and affective disorders may have CSF abnormalities including signs of blood-brain barrier impairment and inflammation. However, the available evidence does not allow any firm conclusion since all studies showed at least some degree of bias and vastly lacked inclusion of confounding factors. Moreover, only few studies investigated the same parameters with healthy controls and high-quality longitudinal CSF studies are lacking, including impact of psychotropic medications, lifestyle factors and potential benefits of anti-inflammatory treatment in subgroups with CSF inflammation.
Journal Article
Should psychiatrists be more cautious about the long-term prophylactic use of antipsychotics?
by
Taylor, David
,
Nordentoft, Merete
,
Quattrone, Diego
in
Analysis
,
Antipsychotic Agents - administration & dosage
,
Antipsychotic Agents - adverse effects
2016
Patients who recover from an acute episode of psychosis are frequently prescribed prophylactic antipsychotics for many years, especially if they are diagnosed as having schizophrenia. However, there is a dearth of evidence concerning the long-term effectiveness of this practice, and growing concern over the cumulative effects of antipsychotics on physical health and brain structure. Although controversy remains concerning some of the data, the wise psychiatrist should regularly review the benefit to each patient of continuing prophylactic antipsychotics against the risk of side-effects and loss of effectiveness through the development of supersensitivity of the dopamine D2 receptor. Psychiatrists should work with their patients to slowly reduce the antipsychotic to the lowest dose that prevents the return of distressing symptoms. Up to 40% of those whose psychosis remits after a first episode should be able to achieve a good outcome in the long term either with no antipsychotic medication or with a very low dose.
Journal Article
European Psychiatric Association guidance on treatment of cognitive impairment in schizophrenia
by
Nordentoft, Merete
,
Nibbio, Gabriele
,
Gaebel, Wolfgang
in
Antipsychotics
,
Clinical trials
,
Cognition & reasoning
2022
BackgroundAlthough cognitive impairment is a core symptom of schizophrenia related to poorer outcomes in different functional domains, it still remains a major therapeutic challenge. To date, no comprehensive treatment guidelines for cognitive impairment in schizophrenia are implemented.MethodsThe aim of the present guidance paper is to provide a comprehensive meta-review of the current available evidence-based treatments for cognitive impairment in schizophrenia. The guidance is structured into three sections: pharmacological treatment, psychosocial interventions, and somatic treatments.ResultsBased on the reviewed evidence, this European Psychiatric Association guidance recommends an appropriate pharmacological management as a fundamental starting point in the treatment of cognitive impairment in schizophrenia. In particular, second-generation antipsychotics are recommended for their favorable cognitive profile compared to first-generation antipsychotics, although no clear superiority of a single second-generation antipsychotic has currently been found. Anticholinergic and benzodiazepine burdens should be kept to a minimum, considering the negative impact on cognitive functioning. Among psychosocial interventions, cognitive remediation and physical exercise are recommended for the treatment of cognitive impairment in schizophrenia. Noninvasive brain stimulation techniques could be taken into account as add-on therapy.ConclusionsOverall, there is definitive progress in the field, but further research is needed to develop specific treatments for cognitive impairment in schizophrenia. The dissemination of this guidance paper may promote the development of shared guidelines concerning the treatment of cognitive functions in schizophrenia, with the purpose to improve the quality of care and to achieve recovery in this population.
Journal Article
Childhood bullying involvement and later suicidality: longitudinal analyses from The Danish National Birth Cohort
by
Hawton, Keith
,
Campbell-Hansen, Lauren Marie
,
Nordentoft Merete
in
Adolescents
,
Bullying
,
Children
2026
BackgroundBullying involvement (victim or perpetrator role) in childhood is linked to later suicidality. However, findings are inconsistent, and sex may be a moderator. We investigated whether childhood bullying involvement was associated with suicidality in adolescence, and whether this association varied by sex.MethodsChildhood bullying involvement was collected from self-reports of children and parents during the 11-year follow-up of the Danish National Birth Cohorts (DNBC). Data on suicidal ideation (SI) and suicide attempts (SA) from the 18-year follow-up were supplemented with hospital records of SA from the National Patient Register. Associations were estimated using multinomial logistic regressions, while inverse probability weighting accounted for socioeconomic-related selection bias.Results11 705 boys and 17 292 girls were included. Adolescent boys exposed to bullying had increased risks of SI (adjusted relative risk ratio (aRRR): 1.6; 95% CI: 1.4 to 1.8) and SA (aRRR: 2.8; 95% CI: 2.0 to 3.8), while no increased risk was found among those who were perpetrators of bullying vs non-involved peers. Girl victims had increased risks (aRRR) of SI and SA of 1.6 (95% CI: 1.5 to 1.7) and 2.9 (95% CI: 2.5 to 3.5), respectively. Girl perpetrators had an increased risk of SA (aRRR: 2.3; 95% CI: 1.5 to 3.6). Sex significantly moderated the association between perpetration role and suicidality.ConclusionChildhood bullying was associated with a higher risk of suicidality during adolescence. Girl, but not boy, perpetrators had increased risk of SI and SA. These findings emphasise the importance of preventive interventions targeting bullying in childhood and its long-term effects, including possible differences in policies for boys and girls.
Journal Article
Outcomes of Nordic mental health systems: life expectancy of patients with mental disorders
2011
People with mental disorders evince excess mortality due to natural and unnatural deaths. The relative life expectancy of people with mental disorders is a proxy measure of effectiveness of social policy and health service provision.
To evaluate trends in health outcomes of people with serious mental disorders.
We examined nationwide 5-year consecutive cohorts of people admitted to hospital for mental disorders in Denmark, Finland and Sweden in 1987-2006. In each country the risk population was identified from hospital discharge registers and mortality data were retrieved from cause-of-death registers. The main outcome measure was life expectancy at age 15 years.
People admitted to hospital for a mental disorder had a two- to threefold higher mortality than the general population in all three countries studied. This gap in life expectancy was more pronounced for men than for women. The gap decreased between 1987 and 2006 in these countries, especially for women. The notable exception was Swedish men with mental disorders. In spite of the positive general trend, men with mental disorders still live 20 years less, and women 15 years less, than the general population.
During the era of deinstitutionalisation the life expectancy gap for people with mental disorders has somewhat diminished in the three Nordic countries. Our results support further development of the Nordic welfare state model, i.e. tax-funded community-based public services and social protection. Health promotion actions, improved access to healthcare and prevention of suicides and violence are needed to further reduce the life expectancy gap.
Journal Article
Excess Mortality, Causes of Death and Life Expectancy in 270,770 Patients with Recent Onset of Mental Disorders in Denmark, Finland and Sweden
by
Nordentoft, Merete
,
Hällgren, Jonas
,
Westman, Jeanette
in
Affective disorders
,
Analysis
,
Biology
2013
Excess mortality among patients with severe mental disorders has not previously been investigated in detail in large complete national populations.
To investigate the excess mortality in different diagnostic categories due to suicide and other external causes of death, and due to specific causes in connection with diseases and medical conditions.
In longitudinal national psychiatric case registers from Denmark, Finland, and Sweden, a cohort of 270,770 recent-onset patients, who at least once during the period 2000 to 2006 were admitted due to a psychiatric disorder, were followed until death or the end of 2006. They were followed for 912,279 person years, and 28,088 deaths were analyzed. Life expectancy and standardized cause-specific mortality rates were estimated in each diagnostic group in all three countries.
The life expectancy was generally approximately 15 years shorter for women and 20 years shorter for men, compared to the general population. Mortality due to diseases and medical conditions was increased two- to three-fold, while excess mortality from external causes ranged from three- to 77-fold. Mortality due to diseases and medical conditions was generally lowest in patients with affective disorders and highest in patients with substance abuse and personality disorders, while mortality due to suicide was highest in patients with affective disorders and personality disorders, and mortality due to other external causes was highest in patients with substance abuse.
These alarming figures call for action in order to prevent the high mortality.
Journal Article
A major role for common genetic variation in anxiety disorders
by
Nordentoft Merete
,
Hotopf, Matthew
,
Wan Cho Shing
in
Anxiety
,
Anxiety disorders
,
Brain-derived neurotrophic factor
2020
Anxiety disorders are common, complex psychiatric disorders with twin heritabilities of 30–60%. We conducted a genome-wide association study of Lifetime Anxiety Disorder (ncase = 25 453, ncontrol = 58 113) and an additional analysis of Current Anxiety Symptoms (ncase = 19 012, ncontrol = 58 113). The liability scale common variant heritability estimate for Lifetime Anxiety Disorder was 26%, and for Current Anxiety Symptoms was 31%. Five novel genome-wide significant loci were identified including an intergenic region on chromosome 9 that has previously been associated with neuroticism, and a locus overlapping the BDNF receptor gene, NTRK2. Anxiety showed significant positive genetic correlations with depression and insomnia as well as coronary artery disease, mirroring findings from epidemiological studies. We conclude that common genetic variation accounts for a substantive proportion of the genetic architecture underlying anxiety.
Journal Article
European Psychiatric Association guidance on assessment of cognitive impairment in schizophrenia
by
Nordentoft, Merete
,
Gaebel, Wolfgang
,
Vita, Antonio
in
Assessment instruments
,
Clinical medicine
,
Clinical trials
2022
BackgroundImpairment in a wide range of cognitive abilities has been consistently reported in individuals with schizophrenia. Both neurocognitive and social cognitive deficits are thought to underlie severe functional disabilities associated with schizophrenia. Despite the key role in schizophrenia outcome, cognition is still poorly assessed in both research and clinical settings.MethodsIn this guidance paper, we provide a systematic review of the scientific literature and elaborate several recommendations for the assessment of cognitive functions in schizophrenia both in research settings and in real-world clinical practice.ResultsExpert consensus and systematic reviews provided guidance for the optimal assessment of cognitive functions in schizophrenia. Based on the reviewed evidence, we recommend a comprehensive and systematic assessment of neurocognitive and social cognitive domains in schizophrenia, in all phases of the disorder, as well as in subjects at risk to develop psychosis. This European Psychiatric Association guidance recommends not only the use of observer reports but also self-reports and interview-based cognitive assessment tools. The guidance also provides a systematic review of the state of the art of assessment in the first episode of psychosis patients and in individuals at risk for psychosis.ConclusionThe comprehensive review of the evidence and the recommendations might contribute to advance the field, allowing a better cognitive assessment, and avoiding overlaps with other psychopathological dimensions. The dissemination of this guidance paper may promote the development of shared guidelines concerning the assessment of cognitive functions in schizophrenia, with the purpose to improve the quality of care and to obtain recovery.
Journal Article
Life Expectancy and Death by Diseases of the Circulatory System in Patients with Bipolar Disorder or Schizophrenia in the Nordic Countries
by
Nordentoft, Merete
,
Hällgren, Jonas
,
Westman, Jeanette
in
Bipolar disorder
,
Bipolar Disorder - mortality
,
Cardiovascular diseases
2013
Excess mortality from diseases and medical conditions (natural death) in persons with psychiatric disorders has been extensively reported. Even in the Nordic countries with well-developed welfare systems, register based studies find evidence of an excess mortality. In recent years, cardiac mortality and death by diseases of the circulatory system has seen a decline in all the Nordic countries, but a recent paper indicates that women and men in Denmark, Finland, and Sweden, who had been hospitalised for a psychotic disorder, had a two to three-fold increased risk of dying from a cardiovascular disease. The aim of this study was to compare the mortality by diseases of the circulatory system among patients with bipolar disorder or schizophrenia in the three Nordic countries Denmark, Sweden, and Finland. Furthermore, the aim was to examine and compare life expectancy among these patients. Cause specific Standardized Mortality Rates (SMRs) were calculated for each specific subgroup of mortality. Life expectancy was calculated using Wiesler's method.
The SMR for bipolar disorder for diseases of the circulatory system was approximately 2 in all countries and both sexes. SMR was slightly higher for people with schizophrenia for both genders and in all countries, except for men in Denmark. Overall life expectancy was much lower among persons with bipolar disorder or schizophrenia, with life expectancy being from 11 to 20 years shorter.
Our data show that persons in the Nordic countries with schizophrenia or bipolar disorder have a substantially reduced life expectancy. An evaluation of the reasons for these increased mortality rates should be prioritized when planning healthcare in the coming years.
Journal Article