•Infectious mononucleosis is often associated with prolonged fatigue.•The association with depression was unclear since large-scale studies were lacking.•This prospective cohort study included 12,510 ...individuals with the infection.•Infectious mononucleosis was associated with a 40% increased risk for depression.•The increased risk was significant to the period one year or later after the infection.
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 nationwide registry data to investigate the association between infectious mononucleosis and subsequent depression in this first large-scale study.
Prospective cohort study using nationwide Danish registers covering all 1,440,590 singletons born (1977–2005) in Denmark by Danish born parents (21,830,542 person-years’ follow-up until 2016); where 12,510 individuals had a hospital contact with infectious mononucleosis. The main outcome measures were a diagnosis of major depressive disorder (ICD-8: 296.09, 298.09, 300.4; ICD-10: F32) requiring hospital contact.
Infectious mononucleosis was associated with a 40% increased hazard ratio (HR) for a subsequent depression diagnosis in the fully adjusted model (HR: 1.40, 95% CI: 1.26–1.56;n = 358), when compared to unexposed individuals. The increased risk of being diagnosed with depression was significant to the periods one to four years after the infectious mononucleosis diagnosis (HR: 1.40, 95% CI: 1.17–1.67;n = 121) and ≥ five years (HR: 1.40, 95% CI: 1.22–1.61;n = 207). We did not find any differences according to age (p = 0.61) nor sex (p = 0.30).
In this largest study to date, infectious mononucleosis in childhood or adolescence was associated with an increased risk of a subsequent depression. Our findings have important clinical implications and identifies youth with infectious mononucleosis as a group at high risk of later depression in young adulthood.
No medications have been indicated for the treatment of anorexia nervosa (AN). Nonetheless, individuals with AN are frequently treated pharmacologically. The present study maps nationwide ...pharmacotherapy two years before to five years after first AN diagnosis.
We identified all medication prescriptions in a national register-based study of patients with a first diagnosis of AN between 1998 and 2011, and age and gender matched controls (1:10). Medication classes were compared using odds ratios (OR) between patients and controls; between patients below and above 15 years; between patients with and without comorbidity; and between those diagnosed before or after 2005.
The odds of pharmacotherapy were increased in patients for all classes of medication except a small residual class. Highest odds were found for alimentary (OR 2.8, p < 0.001) and psychopharmacological (OR 5.5, p < 0.001) medication. The former peaked one year prior to first diagnosis and the latter one year after. Older patients had increased risk of almost all medication classes with cardiovascular medication showing a fivefold OR (p < 0.001). Patients with psychiatric comorbidity had a threefold OR for psychopharmacological medication (p < 0.001) compared to patients without psychiatric comorbidity. Calendar year showed few and small differences.
The extended use of all medication classes both prior to and after first diagnosis of AN highlights the severe cause and complexity of AN. The results encourage clinical caution of pharmacotherapy, highlight the need for pharmacotherapy guidelines for AN, and emphasize the urgency of research in pharmacotherapy in AN.
•Pharmacotherapy is common in the treatment of anorexia nervosa.•A three-fold increase of alimentary drugs peaks one year prior to first diagnosis.•A five-fold increase of psychopharmacotherapy peaks one year after first diagnosis.•Elevated pharmacotherapy reflects the complex treatment needs of patients.•Pharmacotherapy guidelines and research are urgently needed in anorexia nervosa.
In a study involving more than 5.9 million persons in a Danish registry, the presence of a mental disorder (in 11.8% of the population) was associated with subsequent medical conditions encompassing ...31 specific diagnoses, with hazard ratios that ranged from 0.82 to 3.62 and varied greatly over time.
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 1977–2016 and who had a hospital contact for ulcer with or without vagotomy. Follow‐up was until any diagnosis of mental disorders requiring hospital contact, emigration, death, or end of follow‐up on December 31, 2016, whichever came first. Data were analyzed using survival analysis and adjusted for sex, age, calendar year, ulcer type, and Charlson comorbidity index score.
Results
During the study period, 113,086 individuals had a hospital contact for ulcer. Of these, 5,408 were exposed to vagotomy where 375 (6.9%) subsequently developed a mental disorder. Vagotomy overall was not associated with mental disorders (HR: 1.10; 95%CI: 0.99–1.23), compared to individuals with ulcer not exposed to vagotomy. However, truncal vagotomy was associated with an increased HR of 1.22 (95%CI: 1.06–1.41) for mental disorders, whereas highly selective vagotomy was not associated with mental disorders (HR: 0.98; 95%CI: 0.84–1.15). Truncal vagotomy was also associated with higher risk of mental disorders when compared to highly selective vagotomy (p = 0.034).
Conclusions
Overall, vagotomy did not increase the risk of mental disorders; however, truncal vagotomy specifically was associated with a small risk increase in mental disorders, whereas no association was found for highly selective vagotomy. Thus, the vagus nerve does not seem to have a major impact on the development of mental disorders.
About 20% of individuals with anorexia nervosa (AN) remain chronically ill. Therefore, early identification of poor outcome could improve care. Genetic research has identified regions of the genome ...associated with AN. Patients with anorexia nervosa were identified via the Swedish eating disorder quality registers Stepwise and Riksät and invited to participate in the Anorexia Nervosa Genetics Initiative. First, we associated genetic information longitudinally with eating disorder severity indexed by scores on the Clinical Impairment Assessment (CIA) in 2843 patients with lifetime AN with or without diagnostic migration to other forms of eating disorders followed for up to 16 years (mean = 5.3 years). Second, we indexed the development of a severe and enduring eating disorder (SEED) by a high CIA score plus a follow-up time ≥5 years. We associated individual polygenic scores (PGSs) indexing polygenic liability for AN, schizophrenia, and body mass index (BMI) with severity and SEED. After multiple testing correction, only the BMI PGS when calculated with traditional clumping and p value thresholding was robustly associated with disorder severity (β
= 1.30; 95% CI: 0.72, 1.88; p = 1.2 × 10
) across all p value thresholds at which we generated the PGS. However, using the alternative PGS calculation method PRS-CS yielded inconsistent results for all PGS. The positive association stands in contrast to the negative genetic correlation between BMI and AN. Larger discovery GWASs to calculate PGS will increase power, and it is essential to increase sample sizes of the AN GWASs to generate clinically meaningful PGS as adjunct risk prediction variables. Nevertheless, this study provides the first evidence of potential clinical utility of PGSs for eating disorders.
The predictive performance of polygenic scores (PGS) is largely dependent on the number of samples available to train the PGS. Increasing the sample size for a specific phenotype is expensive and ...takes time, but this sample size can be effectively increased by using genetically correlated phenotypes. We propose a framework to generate multi-PGS from thousands of publicly available genome-wide association studies (GWAS) with no need to individually select the most relevant ones. In this study, the multi-PGS framework increases prediction accuracy over single PGS for all included psychiatric disorders and other available outcomes, with prediction R
increases of up to 9-fold for attention-deficit/hyperactivity disorder compared to a single PGS. We also generate multi-PGS for phenotypes without an existing GWAS and for case-case predictions. We benchmark the multi-PGS framework against other methods and highlight its potential application to new emerging biobanks.
To ascertain the association and coaggregation of eating disorders and childhood-onset type 1 diabetes in families.
Using population samples from national registers in Sweden (
= 2,517,277) and ...Demark (
= 1,825,920), we investigated the within-individual association between type 1 diabetes and eating disorders and their familial coaggregation among full siblings, half siblings, full cousins, and half cousins. On the basis of clinical diagnoses, we classified eating disorders into any eating disorder (AED), anorexia nervosa (AN) and atypical AN, and other eating disorder (OED). Associations were determined with hazard ratios (HRs) with 95% CIs from Cox regressions.
Swedish and Danish individuals with a type 1 diabetes diagnosis had a greater risk of receiving an eating disorder diagnosis (HR 95% CI Sweden: AED 2.02 1.80-2.27, AN 1.63 1.36-1.96, OED 2.34 2.07-2.63; Denmark: AED 2.19 1.84-2.61, AN 1.78 1.36-2.33, OED 2.65 2.20-3.21). We also meta-analyzed the results: AED 2.07 (1.88-2.28), AN 1.68 (1.44-1.95), OED 2.44 (2.17-2.72). There was an increased risk of receiving an eating disorder diagnosis in full siblings in the Swedish cohort (AED 1.25 1.07-1.46, AN 1.28 1.04-1.57, OED 1.28 1.07-1.52); these results were nonsignificant in the Danish cohort.
Patients with type 1 diabetes are at a higher risk of subsequent eating disorders; however, there is conflicting support for the relationship between having a sibling with type 1 diabetes and an eating disorder diagnosis. Diabetes health care teams should be vigilant about disordered eating behaviors in children and adolescents with type 1 diabetes.
Previous studies have shown associations between maternal infections during pregnancy and increased risks of schizophrenia and autism spectrum disorder in the offspring. However, large-scale studies ...investigating an association between parental infections both during and outside the pregnancy period and the risk of any mental disorder in the child are lacking.
A nationwide Danish cohort study identified 1,206,600 children born between 1996 and 2015 and followed them to a maximum of 20 years of age. Exposure included all maternal and paternal infections treated with anti-infective agents or hospital contacts before, during, or after pregnancy. The main outcome was a diagnosis of any mental disorder in the child. Hazard ratios (HRs) were calculated using Cox regression analysis.
Maternal infections during pregnancy treated with anti-infective agents (n = 567,016) increased the risk of mental disorders (n = 70,037) in the offspring (HR, 1.09; 95% confidence interval CI, 1.06–1.12), which was more elevated (p < .001) than after paternal infections (n = 350,835; HR, 1.01; 95% CI, 0.98–1.03). Maternal hospital contacts for infections (n = 39,753) conferred an increased HR of 1.21 (95% CI, 1.14–1.28), which was not significantly (p = .08) different from the risk after paternal infections (n = 8559; HR, 1.07; 95% CI, 0.95–1.20). The increased risks observed during pregnancy were not different from the similarly increased risks for maternal and paternal infections before and after pregnancy. The risk of mental disorders increased in a dose-response relationship with the number of maternal infections treated with anti-infective agents, particularly during and after pregnancy (both p < .001).
Maternal infections were associated with an increased risk of mental disorder in the offspring; however, there were similar estimates during and outside the pregnancy period.
Purpose
We explored associations between clinical factors, including eating disorder psychopathology and more general psychopathology, and involuntary treatment in patients with anorexia nervosa. Our ...intention was to inform identification of patients at risk of involuntary treatment.
Methods
This was a retrospective cohort study combining clinical data from a specialized eating disorder hospital unit in Denmark with nationwide Danish register-based data. A sequential methodology yielding two samples (212 and 278 patients, respectively) was adopted. Descriptive statistics and regression analyses were used to explore associations between involuntary treatment and clinical factors including previous involuntary treatment, patient cooperation, and symptom-level psychopathology (Eating Disorder Inventory-2 (EDI-2) and Symptom Checklist-90-Revised (SCL-90-R)).
Results
Somatization (SCL-90-R) (OR = 2.60, 95% CI 1.16–5.81) and phobic anxiety (SCL-90-R) (OR = 0.43, 95% CI 0.19–0.97) were positively and negatively, respectively, associated with the likelihood of involuntary treatment. Furthermore, somatization (HR = 1.77, 95% CI 1.05–2.99), previous involuntary treatment (HR = 5.0, 95% CI 2.68–9.32), and neutral (HR = 2.92, 95% CI 1.20–7.13) or poor (HR = 3.97, 95% CI 1.49–10.59) patient cooperation were associated with decreased time to involuntary treatment. Eating disorder psychopathology measured by the EDI-2 was not significantly associated with involuntary treatment.
Conclusions
Clinical questionnaires of psychopathology appear to capture specific domains relevant to involuntary treatment. Poor patient cooperation and previous involuntary treatment being associated with shorter time to involuntary treatment raise important clinical issues requiring attention. Novel approaches to acute anorexia nervosa care along with unbiased evaluation upon readmission could mitigate the cycle of repeat admissions with involuntary treatment.
Level of evidence
Level III, cohort study.
PDF
