Persons with mental disorders are at a higher risk than the general population for the subsequent development of certain medical conditions.
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 through 2016, for a total of 83.9 million person-years. We assessed 10 broad types of mental disorders and 9 broad categories of medical conditions (which encompassed 31 specific conditions). We used Cox regression models to calculate overall hazard ratios and time-dependent hazard ratios for pairs of mental disorders and medical conditions, after adjustment for age, sex, calendar time, and previous mental disorders. Absolute risks were estimated with the use of competing-risks survival analyses.
A total of 698,874 of 5,940,299 persons (11.8%) were identified as having a mental disorder. The median age of the total population was 32.1 years at entry into the cohort and 48.7 years at the time of the last follow-up. Persons with a mental disorder had a higher risk than those without such disorders with respect to 76 of 90 pairs of mental disorders and medical conditions. The median hazard ratio for an association between a mental disorder and a medical condition was 1.37. The lowest hazard ratio was 0.82 for organic mental disorders and the broad category of cancer (95% confidence interval CI, 0.80 to 0.84), and the highest was 3.62 for eating disorders and urogenital conditions (95% CI, 3.11 to 4.22). Several specific pairs showed a reduced risk (e.g., schizophrenia and musculoskeletal conditions). Risks varied according to the time since the diagnosis of a mental disorder. The absolute risk of a medical condition within 15 years after a mental disorder was diagnosed varied from 0.6% for a urogenital condition among persons with a developmental disorder to 54.1% for a circulatory disorder among those with an organic mental disorder.
Most mental disorders were associated with an increased risk of a subsequent medical condition; hazard ratios ranged from 0.82 to 3.62 and varied according to the time since the diagnosis of the mental disorder. (Funded by the Danish National Research Foundation and others; COMO-GMC ClinicalTrials.gov number, NCT03847753.).
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.
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.
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.
•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.
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.
A subgroup of patients with anorexia nervosa (AN) undergoing involuntary treatment (IT) seems to account for most of the IT events. Little is known about these patients and their treatment including ...the temporal distribution of IT events and factors associated with subsequent utilization of IT. Hence, this study explores (1) utilization patterns of IT events, and (2) factors associated with subsequent utilization of IT in patients with AN.
In this nationwide Danish register-based retrospective exploratory cohort study patients were identified from their first (index) hospital admission with an AN diagnosis and followed up for 5 years. We explored data on IT events including estimated yearly and total 5-year rates, and factors associated with subsequent increased IT rates and restraint, using regression analyses and descriptive statistics.
IT utilization peaked in the initial few years starting at or following the index admission. A small percentage (1.0%) of patients accounted for 67% of all IT events. The most frequent measures reported were mechanical and physical restraint. Factors associated with subsequent increased IT utilization were female sex, lower age, previous admissions with psychiatric disorders before index admission, and IT related to those admissions. Factors associated with subsequent restraint were lower age, previous admissions with psychiatric disorders, and IT related to these.
High IT utilization in a small percentage of individuals with AN is concerning and can lead to adverse treatment experiences. Exploring alternative approaches to treatment that reduce the need for IT is an important focus for future research.
The vitamin D binding protein (DBP), encoded by the group-specific component (GC) gene, is a component of the vitamin D system. In a genome-wide association study of DBP concentration in 65,589 ...neonates we identify 26 independent loci, 17 of which are in or close to the GC gene, with fine-mapping identifying 2 missense variants on chromosomes 12 and 17 (within SH2B3 and GSDMA, respectively). When adjusted for GC haplotypes, we find 15 independent loci distributed over 10 chromosomes. Mendelian randomization analyses identify a unidirectional effect of higher DBP concentration and (a) higher 25-hydroxyvitamin D concentration, and (b) a reduced risk of multiple sclerosis and rheumatoid arthritis. A phenome-wide association study confirms that higher DBP concentration is associated with a reduced risk of vitamin D deficiency. Our findings provide valuable insights into the influence of DBP on vitamin D status and a range of health outcomes.
The Eating Disorders Genetics Initiative (EDGI) is an international investigation exploring the role of genes and environment in anorexia nervosa, bulimia nervosa, and binge-eating disorder.
A total ...of 14,500 individuals with eating disorders and 1500 controls will be included from the United States (US), Australia (AU), New Zealand (NZ), and Denmark (DK). In the US, AU, and NZ, participants will complete comprehensive online phenotyping and will submit a saliva sample for genotyping. In DK, individuals with eating disorders will be identified by the National Patient Register, and genotyping will occur using bloodspots archived from birth. A genome-wide association study will be conducted within EDGI and via meta-analysis with other data from the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED).
EDGI represents the largest genetic study of eating disorders ever to be conducted and is designed to rapidly advance the study of the genetics of the three major eating disorders (anorexia nervosa, bulimia nervosa, and binge-eating disorder). We will explicate the genetic architecture of eating disorders relative to each other and to other psychiatric and metabolic disorders and traits. Our goal is for EDGI to deliver "actionable" findings that can be transformed into clinically meaningful insights.
EDGI is a registered clinical trial: clinicaltrials.gov NCT04378101 .
Anxiety and depression symptoms are common in individuals with eating disorders. To study these co-occurrences, we need high-quality self-report questionnaires. The 19-item self-rated Comprehensive ...Psychopathological Rating Scale for Affective Syndromes (CPRS-S-A) is not validated in patients with eating disorders. We tested its factor structure, invariance, and differences in its latent dimensions.
Patients were registered by 45 treatment units in the Swedish nationwide Stepwise quality assurance database for specialised eating disorder care (n = 9509). Patients self-reported their anxiety and depression symptoms on the CPRS-S-A. Analyses included exploratory and confirmatory factor analyses (CFA) in split samples, and testing of invariance and differences in subscales across eating disorder types.
Results suggested a four-factor solution: Depression, Somatic and fear symptoms, Disinterest, and Worry. Multigroup CFA indicated an invariant factor structure. We detected the following differences: Patients with anorexia nervosa binge-eating/purging subtype scored the highest and patients with unspecified feeding and eating disorders the lowest on all subscales. Patients with anorexia nervosa or purging disorder show more somatic and fear symptoms than individuals with either bulimia nervosa or binge-eating disorder.
Our four-factor solution of the CPRS-S-A is suitable for patients with eating disorders and may help to identify differences in anxiety and depression dimensions amongst patients with eating disorders.
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