ABSTRACT
Mental disorders (MDs) are leading causes of disability and premature death worldwide, partly due to high comorbidity with cardiometabolic disorders (CMDs). Reasons for this comorbidity are still poorly understood. We leverage nation-wide health records and complete genealogies of Denmark and Sweden (n=17 million) to reveal the genetic and environmental contributions underlying the observed comorbidity between six MDs and 14 CMDs. Genetic factors contributed about 50% to the comorbidity of schizophrenia, affective disorders, and autism spectrum disorder with CMDs, whereas the comorbidity of attention-deficit/hyperactivity disorder and anorexia with CMDs was mainly or fully driven by environmental factors. These findings provide causal insight to guide clinical and scientific initiatives directed at achieving mechanistic understanding as well as preventing and alleviating the consequences of these disorders.
ABSTRACT
Background: Although the persistence of physical symptoms after SARS-CoV-2 infection is a major public health concern, evidence from large observational studies beyond one year post diagnosis remain scarce. We aimed to assess the prevalence of physical symptoms in relation to acute illness severity up to more than 2-years after diagnosis of COVID-19. Methods: This multinational study included 64,880 adult participants from Iceland, Sweden, Denmark, and Norway with self-reported data on COVID-19 and physical symptoms from April 2020 to August 2022. We compared the prevalence of 15 physical symptoms, measured by the Patient Health Questionnaire (PHQ-15), among individuals with or without a confirmed COVID-19 diagnosis, by acute illness severity, and by time since diagnosis. We additionally assessed the change in symptoms in a subset of Swedish adults with repeated measures, before and after COVID-19 diagnosis. Findings: During up to 27 months of follow-up, 34.5% participants (22,382/64,880) were diagnosed with COVID-19. Individuals who were diagnosed with COVID-19, compared to those not diagnosed, had an overall 37% higher prevalence of severe physical symptom burden (PHQ-15 score ≥15, adjusted prevalence ratio [PR] 1.37 [95% confidence interval [CI] 1.23-1.52]). The prevalence was associated with acute COVID-19 severity: individuals bedridden for seven days or longer presented with the highest prevalence (PR 2.25 [1.85-2.74]), while individuals never bedridden presented with similar prevalence as individuals not diagnosed with COVID-19 (PR 0.92 [0.68-1.24]). The prevalence was statistically significantly elevated among individuals diagnosed with COVID-19 for eight of the fifteen measured symptoms: shortness of breath, chest pain, dizziness, heart racing, headaches, low energy/fatigue, trouble sleeping, and back pain. The analysis of repeated measurements rendered similar results as the main analysis. Interpretation: These data suggest an elevated prevalence of some, but not all, physical symptoms during up to more than 2 years after diagnosis of COVID-19, particularly among individuals suffering a severe acute illness, highlighting the importance of continued monitoring and alleviation of these targeted core symptoms. Funding: This work was mainly supported by grants from NordForsk (COVIDMENT, grant number 105668 and 138929) and Horizon 2020 (CoMorMent, 847776). See Acknowledgements for further details on funding.
ABSTRACT
Background: Several psychiatric disorders have been associated with increased risk of cardiovascular disease (CVD), however, the role of familial factors and the main disease trajectories remain unknown. Methods: In this longitudinal cohort study, we identified a cohort of 900,240 patients newly diagnosed with psychiatric disorders during January 1, 1987 and December 31, 2016, their 1,002,888 unaffected full siblings, and 1:10 age- and sex-matched reference population from nationwide medical records in Sweden, who had no prior diagnosis of CVD at enrolment. We used flexible parametric models to determine the time-varying association between first-onset psychiatric disorders and incident CVD and CVD death, comparing rates of CVD among patients with psychiatric disorders to the rates of unaffected siblings and matched reference population. We also used disease trajectory analysis to identify main disease trajectories linking psychiatric disorders to CVD. Identified associations and disease trajectories of the Swedish cohort were validated in a similar cohort from nationwide medical records in Denmark (N = 875,634 patients, same criteria during January 1, 1969 and December 31, 2016) and in Estonian cohorts from the Estonian Biobank (N = 30,656 patients, same criteria during January 1, 2006 and December 31, 2020), respectively. Findings: During up to 30 years of follow-up of the Swedish cohort, the crude incidence rate of CVD was 9.7, 7.4 and 7.0 per 1000 person-years among patients with psychiatric disorders, their unaffected siblings, and the matched reference population. Compared with their siblings, patients with psychiatric disorders experienced higher rates of CVD during the first year after diagnosis (hazard ratio [HR], 1.88; 95% confidence interval [CI], 1.79-1.98) and thereafter (1.37; 95% CI, 1.34-1.39). Similar rate increases were noted when comparing with the matched reference population. These results were replicated in the Danish cohort. We identified several disease trajectories linking psychiatric disorders to CVD in the Swedish cohort, with or without mediating medical conditions, including a direct link between psychiatric disorders and hypertensive disorder, ischemic heart disease, venous thromboembolism, angina pectoris, and stroke. These trajectories were validated in the Estonian Biobank cohort. Interpretation: Independent of familial factors, patients with psychiatric disorders are at an elevated risk of subsequent CVD, particularly during first year after diagnosis. Increased surveillance and treatment of CVDs and CVD risk factors should be considered as an integral part of clinical management, in order to reduce risk of CVD among patients with psychiatric disorders. Funding: This research was supported by EU Horizon 2020 Research and Innovation Action Grant, European Research Council Consolidator grant, Icelandic Research fund, Swedish Research Council, US NIMH, the Outstanding Clinical Discipline Project of Shanghai Pudong, the Fundamental Research Funds for the Central Universities, and the European Union through the European Regional Development Fund; the Research Council of Norway; the South-East Regional Health Authority, the Stiftelsen Kristian Gerhard Jebsen, and the EEA-RO-NO-2018-0535.
