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APOE ɛ4, the most significant genetic risk factor for Alzheimer disease (AD), may mask effects of other loci. We re-analyzed genome-wide association study (GWAS) data from the International Genomics of Alzheimer's Project (IGAP) Consortium in APOE ɛ4+ (10 352 cases and 9207 controls) and APOE ɛ4- (7184 cases and 26 968 controls) subgroups as well as in the total sample testing for interaction between a single-nucleotide polymorphism (SNP) and APOE ɛ4 status. Suggestive associations (P

Individuals with mental illness are at higher risk of severe COVID-19 outcomes. However, previous studies on the uptake of COVID-19 vaccination in this population have reported conflicting results. Using data from seven cohort studies (N = 325,298) included in the multinational COVIDMENT consortium, and the Swedish registers (N = 8,080,234), this study investigates the association between mental illness (defined using self-report measures, clinical diagnosis and prescription data) and COVID-19 vaccination uptake. Results from the COVIDMENT cohort studies were pooled using meta-analyses, the majority of which showed no significant association between mental illness and vaccination uptake. In the Swedish register study population, we observed a very small reduction in the uptake of both the first and second dose of a COVID-19 vaccine among individuals with vs. without mental illness; the reduction was however greater among those not using psychiatric medication. Here we show that uptake of the COVID-19 vaccine is generally high among individuals both with and without mental illness, however the lower levels of vaccination uptake observed among subgroups of individuals with unmedicated mental illness warrants further attention., (© 2024. The Author(s).)

Background: Childhood maltreatment (CM) has been indicated in adverse health outcomes across the lifespan, including severe infection-related outcomes. Yet, data are scarce on the potential role of CM in severe COVID-19-related outcomes as well as on mechanisms underlying this association., Methods: We included 151,427 individuals in the UK Biobank who responded to questions on the history of CM in 2016 and 2017 and were alive on January 31, 2020. Binomial logistic regression models were performed to estimate the association between a history of CM and severe COVID-19 outcomes (i.e. hospitalization or death due to COVID-19), as well as COVID-19 diagnosis and vaccination as secondary outcomes. We then explored the potential mediating roles of socio-economic status, lifestyle and pre-pandemic comorbidities, and the effect modification by polygenic risk score for severe COVID-19 outcomes., Results: The mean age of the study population at the start of the pandemic was 67.7 (SD = 7.72) years, and 56.5% were female. We found the number of CM types was associated with the risk of severe COVID-19 outcomes in a graded manner (p for trend  < 0.01). Compared to individuals with no history of CM, individuals exposed to any CM were more likely to be hospitalized or die due to COVID-19 (odds ratio [OR] = 1.54 [95%CI 1.31-1.81]), particularly after physical neglect (2.04 [1.57-2.62]). Largely comparable risk patterns were observed across groups of high vs. low genetic risks for severe COVID-19 outcomes (p for difference  > 0.05). Mediation analysis revealed that 50.9% of the association between CM and severe COVID-19 outcomes was explained by suboptimal socio-economic status, lifestyle, and pre-pandemic diagnosis of psychiatric disorders or other chronic medical conditions. In contrast, any CM exposure was only weakly associated with COVID-19 diagnosis (1.06 [1.01-1.12]) while significantly associated with not being vaccinated for COVID-19 (1.21 [1.13-1.29])., Conclusions: Our results add to the growing knowledge base indicating the role of childhood maltreatment in negative health outcomes across the lifespan, including severe COVID-19-related outcomes. The identified factors underlying this association represent potential intervention targets for mitigating the harmful effects of childhood maltreatment in COVID-19 and similar future pandemics., (© 2024. The Author(s).)

Importance: Exposure to adverse childhood experiences (ACEs) has consistently been associated with multiple negative mental health outcomes extending into adulthood. However, given that ACEs and psychiatric disorders cluster within families, it remains to be comprehensively assessed to what extent familial confounding contributes to associations between ACEs and clinically confirmed adult psychiatric disorders., Objective: To investigate whether associations between ACEs and adult mental health outcomes remain after adjusting for familial (genetic and environmental) confounding., Design, Setting, and Participants: This Swedish twin cohort study used a discordant twin pair design based on monozygotic (MZ) and dizygotic (DZ) twins. A total of 25 252 adult twins (aged 18-47 years) from the Swedish Twin Registry born between 1959 and 1998 were followed up from age 19 years until 2016, with a maximum follow-up time of 39 years. Data were analyzed from April 2022 to November 2023., Exposures: A total of 7 ACEs, including family violence, emotional abuse or neglect, physical neglect, physical abuse, sexual abuse, rape, and hate crime, were assessed with items from the Life Stressor Checklist-Revised in a web-based survey., Main Outcomes and Measures: Adult (ages >18 years) clinical diagnosis of psychiatric disorders (ie, depressive, anxiety, alcohol or drug misuse, or stress-related disorders) were obtained from the Swedish National Patient Register., Results: Of 25 252 twins included in the study (15 038 female [59.6%]; mean [SD] age at ACE assessment, 29.9 [8.7] years), 9751 individuals (38.6%) reported exposure to at least 1 ACE. A greater number of ACEs was associated with increased odds of any psychiatric disorder in the full cohort (odds ratio [OR] per additional ACE, 1.52; 95% CI, 1.48-1.57). The association remained but ORs per additional ACE were attenuated in DZ (1.29; 95% CI, 1.14-1.47) and MZ (1.20; 95% CI, 1.02-1.40) twin pairs. Individuals who were exposed to sexual abuse compared with those who were not exposed had increased odds of any clinically confirmed psychiatric disorder in all comparisons: full cohort (OR, 3.09; 95% CI, 2.68-3.56), DZ twin pairs (OR, 2.10; 95% CI, 1.33-3.32), and MZ twin pairs (1.80; 95% CI, 1.04-3.11)., Conclusions and Relevance: This study found that associations between ACEs and adult mental health outcomes remained after controlling for shared genetic and environmental factors, which was particularly evident after multiple ACEs or sexual abuse. These findings suggest that targeted interventions may be associated with reduced risks of future psychopathology.

Background: Coronavirus disease 2019 (COVID-19) caused major disruptions in healthcare services worldwide. Yet, little is known about the association between perceived disruption in healthcare services and socio-demographic factors, pre-existing health conditions as well as concurrent physical and psychological symptoms., Methods: Leveraging data from the Icelandic COVID-19 National Resilience Cohort, we performed a repeated measure analysis among 15 754 participants who responded to the question on perceived disruption in healthcare services from December 2020 to July 2021, to explore its association with socio-demographic factors, health indicators and conditions. Furthermore, we performed a longitudinal analysis among 7848 participants with two repeated measures to explore the association between timing and duration of perceived disruption in healthcare services and changes in depression, anxiety, sleep quality and somatic symptoms., Results: The prevalence of perceived disruption in healthcare services slightly decreased over time (P < 0.01). Perceived disruption in healthcare services was more prevalent among individuals with pre-existing health conditions, i.e. history of psychiatric disorders (prevalence ratio = 1.59, 95% confidence interval 1.48-1.72) and chronic somatic conditions [1.40 (1.30-1.52)]. However, no increase in the prevalence of perceived disruption in healthcare services was observed among individuals diagnosed with COVID-19 [0.99 (0.84-1.18)]. Moreover, we found that emerging perceived disruption in healthcare services was associated with an increase in symptoms of mental illness during the pandemic (βs 0.06-0.68)., Conclusions: A disruption in healthcare services during the COVID-19 pandemic was reported by vulnerable groups, while the Icelandic healthcare system managed to maintain accessible services to individuals with COVID-19., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Public Health Association.)

Background: Adverse childhood experiences (ACEs) are well-known risk factors for schizophrenia and bipolar disorder., Aims: The aim was to study the associations between specific ACEs and psychological functioning in women with schizophrenia or bipolar disorder., Method: Among 29 367 women (mean age 44 years) from the Icelandic Stress-And-Gene-Analysis (SAGA) study, 534 (1.8%, mean age 40) reported having been diagnosed with schizophrenia or bipolar disorder, which were combined to 'severe mental disorders'. Participants reported on 13 types of ACEs, childhood deprivation and psychological functioning (defined as coping ability and current symptoms of depression, anxiety and sleep disturbances). Adjusted Poisson regression calculated prevalence ratios (PRs) between ACEs and severe mental disorders. Linear regression assessed the association between ACEs and psychological functioning among women with a severe mental disorder., Results: Women with a severe mental disorder reported more ACEs (mean 4.57, s.d. = 2.82) than women without (mean 2.51, s.d. = 2.34) in a dose-dependent manner (fully-adjusted PR = 1.23 per ACE, 95% CI 1.20-1.27). After mutual adjustment for other ACEs, emotional abuse, sexual abuse, mental illness of a household member, emotional neglect, bullying and collective violence were associated with severe mental disorders. Among women with severe mental disorders, a higher number of ACEs was associated with increased symptom burden of depression (β = 2.79, 95% CI = 1.19-4.38) and anxiety (β = 2.04, 95% CI = 0.99-3.09) including poorer sleep quality (β = 0.83, 95% CI = 0.07-1.59). Findings were similar for schizophrenia and bipolar disorder separately., Conclusion: Women with schizophrenia or bipolar disorder show a strong history of ACEs, which may interfere with their psychological functioning and, therefore, need to be addressed as part of their treatment, for example, with trauma-focused psychotherapy.

Emerging data suggest that certain adverse childhood experiences (ACEs) are associated with perinatal depression (PND). However, few studies have comprehensively assessed the cumulative number and types of ACEs and their association to PND. We conducted a cross-sectional analysis among 16,831 female participants from the Stress-And-Gene-Analysis (SAGA) cohort in Iceland, 2018. ACEs were surveyed with the World Health Organization ACE-International questionnaire, while PND symptoms were assessed using the Edinburgh Postnatal Depression Scale (lifetime version). We, while adjusting for confounding factors, estimated the prevalence ratio (PR) of PND in relation to total number of ACEs using the Poisson quasi-likelihood model and further performed analyses for type-specific ACEs. At a mean age of 44 years (SD ± 11.1), 6,201 (36.8%) participants had experienced probable PND. Total number of ACEs was positively associated with PND (PR 1.11 per ACE, 95% CI: 1.10-1.11), also among women without any psychiatric comorbidities (PR 1.13, 95% CI: 1.11-1.14). PRs increased in a dose-response manner with the number of ACEs (P for trend < 0.001); women that endorsed 5 or more ACEs were twice as likely to have experienced PND (PR 2.24, 95% CI: 2.09-2.41). All ACE types (n = 13) were associated with PND, with most pronounced association for emotional neglect by a guardian (PR 1.53, 95% CI: 1.47-1.59). Our findings suggest a positive association between number of ACEs and PND symptoms. If our results are confirmed with prospective data, healthcare providers need to be alert of the risk of PND among expecting mothers with history of ACEs., (© 2023. The Author(s).)

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., Competing Interests: OAA receives support from the NordForsk (grant number 105668 COVIDMENT) and the European Union’s Horizon 2020 Research and Innovation Programme (Grant 847776; CoMorMent). OAA declares receiving grants or contracts from NIH NIMN Award (R01MH123724-01, 1R01MH124839, 1R01MH129742, 1R01MH129858-01A1), Research Council of Norway (RCN grants 223273, 296030, 300309, 324252), the South-East Norway Health Authority (grant 2017-112, 2022-073), European Union’s Horizon 2020 Research and Innovation Programme (Grant 964874 REALMENT), EEA-RO-NO-2018-0535, and KG Jebsen Stiftelsen (grants SKGJ-MED-008 and SKGJ-MED-021). OAA receives consulting fees from Biogen, Cortechs.ai and Milken. OAA gets Speaker’s honorarium from Janssen, Lundbeck and Sunovion, and has a patent on Intranasal Administration (US20160310683 A1). OAA participated in advisory board as National PI for JANSSEN trial depression, MAPS trial PTSD and BI trial schizophrenia. OAA declares having stock at Cortechs.ai. RP receives grant of Excellence, Icelandic Research Fund. RP declares to be the vice president at UEMS Section of Internal Medicine, a board member of the Icelandic Society of Internal Medicine, and is the president of the Icelandic Transplantation Society. EF received a payment for keynote lecture from Astra Zeneca. SUJ is a leader in Metacognitive Therapy Institute Norwegian Branch. FF receives support from the NordForsk (grant number 105668 and 138929 COVIDMENT) and the Horizon 2020 (Grant 847776; CoMorMent). UAV receives support from the NordForsk (grant number 105668 and 138929 COVIDMENT) and the Horizon 2020 (Grant 847776; CoMorMent). AL declares to receive Fredrik and Ingrid Thuring Foundation. OBVP receives Independent Research Fund Denmark (0214-00127B). QS declares receiving support from the Outstanding Clinical Discipline Project of Shanghai Pudong (Grant No.: PWYgy2021-02) and the Fundamental Research Funds for the Central Universities. PFS declares receiving funding from the Swedish Research Council (Vetenskapsrådet, award D0886501). PFS also receives consulting fees, participating on a data safety monitoring board or advisory board, and holds stock or stock options, from Neumora Therapeutics. All other authors declare no competing interests., (© 2023 The Author(s).)

Background: Little is known regarding the mental health impact of having a significant person (family member and/or close friend) with COVID-19 of different severity., Methods: The study included five prospective cohorts from four countries (Iceland, Norway, Sweden, and the UK) with self-reported data on COVID-19 and symptoms of depression and anxiety during March 2020-March 2022. We calculated prevalence ratios (PR) of depression and anxiety in relation to having a significant person with COVID-19 and performed a longitudinal analysis in the Swedish cohort to describe temporal patterns., Findings: 162,237 and 168,783 individuals were included in the analysis of depression and anxiety, respectively, of whom 24,718 and 27,003 reported a significant person with COVID-19. Overall, the PR was 1.07 (95% CI: 1.05-1.10) for depression and 1.08 (95% CI: 1.03-1.13) for anxiety in relation to having a significant person with COVID-19. The respective PRs for depression and anxiety were 1.15 (95% CI: 1.08-1.23) and 1.24 (95% CI: 1.14-1.34) if the patient was hospitalized, 1.42 (95% CI: 1.27-1.57) and 1.45 (95% CI: 1.31-1.60) if the patient was ICU-admitted, and 1.34 (95% CI: 1.22-1.46) and 1.36 (95% CI: 1.22-1.51) if the patient died. Individuals with a significant person with hospitalized, ICU-admitted, or fatal COVID-19 showed elevated prevalence of depression and anxiety during the entire year after the COVID-19 diagnosis., Interpretation: Family members and close friends of critically ill COVID-19 patients show persistently elevated prevalence of depressive and anxiety symptoms., Funding: This study was primarily supported by NordForsk (COVIDMENT, 105668) and Horizon 2020 (CoMorMent, 847776)., Competing Interests: AL received a grant from the Fredrik and Ingrid Thuring Foundation. DLM is a part-time employee of Optima Partners Ltd. EMF received payment for keynote lecture from Astra Zeneca. HA received a grant from the Research Council of Norway. PFS received a grant from the Swedish Research Council (Vetenskapsrådet, award D0886501) and is a consultant and shareholder Neumora Therapeutics for work not directly related to the topics of this paper. OAA received grants from NordForsk (Grant 105668) and the European Union’s Horizon2020 Research and Innovation Programme (Grant 847776; CoMorMent) for the current project and received grants from NIH NIMH, the Research Council of Norway, the South-East Regional Health Authority, Horizon2020, Stiftelsen Kristian Gerhard Jebsen, consulting fees from Biogen, Cortechs.ai and Milken, payment or honoraria from Janssen, Lundbeck and Sunovion, and reports patent Intranasal Administration, US20160310683 A1, participation on DSMB 21 board as PI, and stock options with Cortechs.ai. UAV received grants from NordForsk (Grants 138929 and 105668). FF received grants from NordForsk, the Swedish Research Council for Health, Working Life and Welfare, the Horizon2020 programme, Swedish Research Council, Swedish Cancer Society, US CDC, US NIH, and the European Research Council. The other authors declare no conflict of interest., (© 2023 The Author(s).)

Background: A growing literature, mostly based on selected populations, indicates that traumas may be associated with autoimmune diseases, yet few studies exist on adverse childhood experiences (ACEs) and multiple sclerosis (MS) in the general population., Objective: We assessed cross-sectional associations between self-reported ACEs and MS among Icelandic women in the population-based Stress-And-Gene-Analysis (SAGA) cohort., Methods: Participants (n = 27,870; mean age 44.9 years) answered a web-based survey that included the ACE-International Questionnaire and a question about MS diagnosis. Log-linear Poisson regression models estimated MS prevalence ratios and 95% confidence intervals for ACEs adjusted for covariates., Results: 214 women reported having been diagnosed with MS (crude prevalence = 7.7 per 1000). Compared to women without MS, women with MS reported more fatigue, body pain and bladder problems. The average cumulative number of ACEs was 2.1. After adjustment for age, education, childhood deprivation, smoking and depressive symptoms, MS prevalence did not increase with increasing ACEs exposure (PR = 1.00, 95% CI = 0.92, 1.09). Thirteen ACE categories, including abuse, neglect, household dysfunction and violence were not individually or independently associated with MS., Conclusion: Limited by self-reported data and cross-sectional design, results do not consistently support associations between ACEs in the development of MS among adult Icelandic women.

Background: The association between cardiovascular disease (CVD) and selected psychiatric disorders has frequently been suggested while the potential role of familial factors and comorbidities in such association has rarely been investigated., Methods: We identified 869,056 patients newly diagnosed with CVD from 1987 to 2016 in Sweden with no history of psychiatric disorders, and 910,178 full siblings of these patients as well as 10 individually age- and sex-matched unrelated population controls ( N = 8,690,560). Adjusting for multiple comorbid conditions, we used flexible parametric models and Cox models to estimate the association of CVD with risk of all subsequent psychiatric disorders, comparing rates of first incident psychiatric disorder among CVD patients with rates among unaffected full siblings and population controls., Results: The median age at diagnosis was 60 years for patients with CVD and 59.2% were male. During up to 30 years of follow-up, the crude incidence rates of psychiatric disorder were 7.1, 4.6, and 4.0 per 1000 person-years for patients with CVD, their siblings and population controls. In the sibling comparison, we observed an increased risk of psychiatric disorder during the first year after CVD diagnosis (hazard ratio [HR], 2.74; 95% confidence interval [CI], 2.62-2.87) and thereafter (1.45; 95% CI, 1.42-1.48). Increased risks were observed for all types of psychiatric disorders and among all diagnoses of CVD. We observed similar associations in the population comparison. CVD patients who developed a comorbid psychiatric disorder during the first year after diagnosis were at elevated risk of subsequent CVD death compared to patients without such comorbidity (HR, 1.55; 95% CI, 1.44-1.67)., Conclusions: Patients diagnosed with CVD are at an elevated risk for subsequent psychiatric disorders independent of shared familial factors and comorbid conditions. Comorbid psychiatric disorders in patients with CVD are associated with higher risk of cardiovascular mortality suggesting that surveillance and treatment of psychiatric comorbidities should be considered as an integral part of clinical management of newly diagnosed CVD patients., Funding: This work was supported by the EU Horizon 2020 Research and Innovation Action Grant (CoMorMent, grant no. 847776 to UV, PFS, and FF), Grant of Excellence, Icelandic Research Fund (grant no. 163362-051 to UV), ERC Consolidator Grant (StressGene, grant no. 726413 to UV), Swedish Research Council (grant no. D0886501 to PFS), and US NIMH R01 MH123724 (to PFS)., Competing Interests: QS, HS, TA, JY, DL, JJ, JB, LY, PS, AS, WY, KF, FF, UV No competing interests declared, (© 2022, Shen et al.)

Study Objectives: To date, few studies have assessed sleep problems among women residing in Subarctic regions. Therefore, the aim of this large-scale population-based study was to assess the prevalence of severe sleep problems and associated factors among Icelandic women, living at 63-66°N., Methods: Participants were 29 681 women (18-69 years old) who took part in the Icelandic Stress-And-Gene-Analysis study in 2018-2019. Background information, health-related behavior, and mental health symptoms were assessed with an online questionnaire. The Pittsburgh Sleep Quality Index (PSQI) was used to assess severe sleep problems during the past month. Adjusting for age, marital status, number of children, education, personal income, work schedule, region, and response period, we used modified Poisson log-linear models to obtain prevalence ratios (PRs) with 95% confidence intervals (CIs)., Results: Overall, 24.2% of women reported severe sleep problems (PSQI >10). Women responding in the winter presented with an overall higher prevalence of severe sleep problems, compared to those responding in the summer (PR 1.21; 95% CI, 1.15 to 1.28). Severe sleep problems were more prevalent among young and late-midlife women, those who were single, had children, socio-economic challenges, worked shifts, and flexible hours. Furthermore, obesity, suboptimal health behaviors, excessive screen time, and mental health problems were associated with severe sleep problems., Conclusion: Severe sleep problems are more common among women in Subarctic regions than elsewhere, particularly during winter. These findings motivate the development of preventive strategies and interventions for women in the Subarctic who suffer from sleep problems., (© Sleep Research Society 2022. Published by Oxford University Press on behalf of the Sleep Research Society.)

Background: Long-term mental and physical health consequences of COVID-19 (long COVID) are a persistent public health concern. Little is still known about the long-term mental health of non-hospitalised patients with COVID-19 with varying illness severities. Our aim was to assess the prevalence of adverse mental health symptoms among individuals diagnosed with COVID-19 in the general population by acute infection severity up to 16 months after diagnosis., Methods: This observational follow-up study included seven prospectively planned cohorts across six countries (Denmark, Estonia, Iceland, Norway, Sweden, and the UK). Participants were recruited from March 27, 2020, to Aug 13, 2021. Individuals aged 18 years or older were eligible to participate. In a cross-sectional analysis, we contrasted symptom prevalence of depression, anxiety, COVID-19-related distress, and poor sleep quality (screened with validated mental health instruments) among individuals with and without a diagnosis of COVID-19 at entry, 0-16 months from diagnosis. In a cohort analysis, we further used repeated measures to estimate the change in mental health symptoms before and after COVID-19 diagnosis., Findings: The analytical cohort consisted of 247 249 individuals, 9979 (4·0%) of whom were diagnosed with COVID-19 during the study period. Mean follow-up was 5·65 months (SD 4·26). Participants diagnosed with COVID-19 presented overall with a higher prevalence of symptoms of depression (prevalence ratio [PR] 1·18 [95% CI 1·03-1·36]) and poorer sleep quality (1·13 [1·03-1·24]) but not symptoms of anxiety (0·97 [0·91-1·03]) or COVID-19-related distress (1·05 [0·93-1·20]) compared with individuals without a COVID-19 diagnosis. Although the prevalence of depression and COVID-19-related distress attenuated with time, individuals diagnosed with COVID-19 but never bedridden due to their illness were consistently at lower risk of depression (PR 0·83 [95% CI 0·75-0·91]) and anxiety (0·77 [0·63-0·94]) than those not diagnosed with COVID-19, whereas patients who were bedridden for more than 7 days were persistently at higher risk of symptoms of depression (PR 1·61 [95% CI 1·27-2·05]) and anxiety (1·43 [1·26-1·63]) than those not diagnosed throughout the study period., Interpretation: Severe acute COVID-19 illness-indicated by extended time bedridden-is associated with long-term mental morbidity among recovering individuals in the general population. These findings call for increased vigilance of adverse mental health development among patients with a severe acute disease phase of COVID-19., Funding: Nordforsk, Horizon2020, Wellcome Trust, and Estonian Research Council., Competing Interests: Declaration of interests OAA has received a grant to their institution from Nordforsk and Research Council of Norway for the present manuscript. OAA has also received a grant to the institution for an entity other than the present manuscript from South East Norway Health Authority, KG Jebsen Stiftelsen, and National Institutes of Health, EU. OAA has received royalties for a textbook in psychiatry, consulting fees from HealthLytix and Milken Institute, payment for lectures from Sunovion and Lundbeck, and payment for expert testimony from the Norwegian Court. Outside of this work, OAA has a patent for a devise for nasal delivery. OAA has participated at his institution on boards for local principal investigator Clinical Trial Janssen, local principal investigator Clinical Trial MAPS, and local principal investigator Clinical Trial Boehringer. UAV has received grants for the current work from Nordforsk and Horizon2020 as well as grants outside the current work from the Icelandic Research Fund, Swedish Research Council, Swedish Cancer Society, and the European Research Council. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Childhood abuse and neglect have been associated with premenstrual disorders (PMDs), including premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD). However, the associations of other adverse childhood experiences (ACEs) and the cumulative number of ACEs with PMDs remain to be explored., Methods: To evaluate the associations of the cumulative number and types of ACEs with PMDs, we conducted a cross-sectional analysis with a subsample of menstruating women within the Stress-And-Gene-Analysis (SAGA) cohort, assessed for PMDs and ACEs (N=11,973). The cumulative and individual exposure of 13 types of ACEs was evaluated by a modified ACE-International Questionnaire. A modified version of the Premenstrual Symptom Screening Tool was used to identify probable cases of PMDs, further sub-grouped into PMS and PMDD. Prevalence ratios (PRs) of PMDs in relation to varying ACEs were estimated using Poisson regression., Results: At a mean age of 34.0 years (standard deviation (SD) 9.1), 3235 (27%) met the criteria of probable PMDs, including 2501 (21%) for PMS and 734 (6%) for PMDD. The number of ACEs was linearly associated with PMDs (fully-adjusted PR 1.12 per ACE, 95% CI 1.11-1.13). Specifically, the PR for PMDs was 2.46 (95% CI 2.21-2.74) for women with 4 or more ACEs compared with women with no ACEs. A stronger association was observed for probable PMDD compared to PMS (p for difference <0.001). The associations between ACEs and PMDs were stronger among women without PTSD, anxiety, or depression, and without childhood deprivation and were stronger among women a lower level of social support (p for interaction<0.001). All types of ACEs were positively associated with PMDs (PRs ranged from 1.11 to 1.51); the associations of sexual abuse, emotional neglect, family violence, mental illness of a household member, and peer and collective violence were independent of other ACEs., Conclusions: Our findings suggest that childhood adverse experiences are associated with PMDs in a dose-dependent manner. If confirmed by prospective data, our findings support the importance of early intervention for girls exposed to ACEs to minimize risks of PMDs and other morbidities in adulthood., (© 2022. The Author(s).)

Background: Adverse childhood experiences (ACEs) have consistently been associated with elevated risk of multiple adverse health outcomes, yet their contribution to coping ability and psychiatric resilience in adulthood is unclear., Methods: Cross-sectional data were derived from the ongoing Stress-And-Gene-Analysis cohort, representing 30% of the Icelandic nationwide female population, 18-69 years. Participants in the current study were 26,198 women with data on 13 ACEs measured with the ACE-International Questionnaire. Self-reported coping ability was measured with the Connor-Davidson Resilience Scale and psychiatric resilience was operationalized as absence of psychiatric morbidity. Generalized linear regression assuming normal or Poisson distribution were used to assess the associations of ACEs with coping ability and psychiatric resilience controlling for multiple confounders., Results: Number of ACEs was inversely associated with adult resilience in a dose-dependent manner; every 1SD unit increase in ACE scores was associated with both lower levels of coping ability ( β = -0.14; 95% CI-0.15,-0.13) and lower psychiatric resilience ( β = -0.28; 95% CI-0.29,-0.27) in adulthood. Compared to women with 0 ACEs, women with ≥5 ACEs had 36% lower prevalence of high coping ability (PR = 0.64, 95% CI 0.59,0.70) and 58% lower prevalence of high psychiatric resilience (PR = 0.42; 95% CI 0.39,0.45). Specific ACEs including emotional neglect, bullying, sexual abuse and mental illness of household member were consistently associated with reduced adult resilience. We observed only slightly attenuated associations after controlling for adult socioeconomic factors and social support in adulthood., Conclusions: Cumulative ACE exposure is associated with lower adult resilience among women, independent of adult socioeconomic factors and social support, indicating that adult resilience may be largely determined in childhood., Funding: This work was supported by the European Research Council (Consolidator grant; UAV, grant number 726413), and the Icelandic Center for Research (Grant of excellence; UAV, grant number 163362-051). HBD was supported by a doctoral grant from the University of Iceland Research Fund., Competing Interests: HD, TA, ET, KF, FF, GT, HR, QY, KC, BK, TH, DL, HS, JJ, AH, UV No competing interests declared, (© 2022, Daníelsdóttir et al.)

Background: The rate of labor induction has risen steeply throughout the world. This project aimed to estimate changes in the rates of adverse maternal and neonatal outcomes in Iceland between 1997 and 2018, and to assess whether the changes can be explained by an increased rate of labor induction., Methods: Singleton live births, occurring between 1997 and 2018, that did not start by prelabor cesarean, were identified from the Icelandic Medical Birth Register (n = 85 971). Rates of intrapartum cesarean birth (CB), obstetric emergencies, and neonatal outcomes were calculated, and adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) were estimated with log-binomial regression (reference: 1997-2001). Adjustments were made for: (a) maternal characteristics, and (b) labor induction and gestational age., Results: The rate of labor induction increased from 13.6% in the period 1997-2001 to 28.1% in the period 2014-2018. The rate of intrapartum CB decreased between the periods of 1997-2001 and 2014-2018 for both primiparous (aRR 0.76, 95% CI: 0.69 to 0.84) and multiparous women (aRR 0.55, 95% CI: 0.49 to 0.63). The rate of obstetric emergencies and adverse neonatal outcomes also decreased between these time periods. Adjusting for labor induction did not attenuate these associations., Conclusions: The rates of adverse maternal outcomes and adverse neonatal outcomes decreased over the study period. However, there was no evidence that this decrease could be explained by the increased rate of labor induction., (© 2021 Wiley Periodicals LLC.)

Objective: To test if patients recovering from COVID-19 are at increased risk of mental morbidities and to what extent such risk is exacerbated by illness severity., Design: Population-based cross-sectional study., Setting: Iceland., Participants: A total of 22 861 individuals were recruited through invitations to existing nationwide cohorts and a social media campaign from 24 April to 22 July 2020, of which 373 were patients recovering from COVID-19., Main Outcome Measures: Symptoms of depression (Patient Health Questionnaire), anxiety (General Anxiety Disorder Scale) and posttraumatic stress disorder (PTSD; modified Primary Care PTSD Screen for DSM-5) above screening thresholds. Adjusting for multiple covariates and comorbidities, multivariable Poisson regression was used to assess the association between COVID-19 severity and mental morbidities., Results: Compared with individuals without a diagnosis of COVID-19, patients recovering from COVID-19 had increased risk of depression (22.1% vs 16.2%; adjusted relative risk (aRR) 1.48, 95% CI 1.20 to 1.82) and PTSD (19.5% vs 15.6%; aRR 1.38, 95% CI 1.09 to 1.75) but not anxiety (13.1% vs 11.3%; aRR 1.24, 95% CI 0.93 to 1.64). Elevated relative risks were limited to patients recovering from COVID-19 that were 40 years or older and were particularly high among individuals with university education. Among patients recovering from COVID-19, symptoms of depression were particularly common among those in the highest, compared with the lowest tertile of influenza-like symptom burden (47.1% vs 5.8%; aRR 6.42, 95% CI 2.77 to 14.87), among patients confined to bed for 7 days or longer compared with those never confined to bed (33.3% vs 10.9%; aRR 3.67, 95% CI 1.97 to 6.86) and among patients hospitalised for COVID-19 compared with those never admitted to hospital (48.1% vs 19.9%; aRR 2.72, 95% CI 1.67 to 4.44)., Conclusions: Severe disease course is associated with increased risk of depression and PTSD among patients recovering from COVID-19., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Background: There is increasing evidence that retinal microvascular diameters are associated with cardiovascular and cerebrovascular conditions. The shared genetic effects of these associations are currently unknown. The aim of this study was to increase our understanding of the genetic factors that mediate retinal vessel size., Methods and Results: This study extends previous genome-wide association study results using 24 000+ multiethnic participants from 7 discovery cohorts and 5000+ subjects of European ancestry from 2 replication cohorts. Using the Illumina HumanExome BeadChip, we investigate the association of single-nucleotide polymorphisms and variants collectively across genes with summary measures of retinal vessel diameters, referred to as the central retinal venule equivalent and the central retinal arteriole equivalent. We report 4 new loci associated with central retinal venule equivalent, one of which is also associated with central retinal arteriole equivalent. The 4 single-nucleotide polymorphisms are rs7926971 in TEAD1 (P=3.1×10(-) (11); minor allele frequency=0.43), rs201259422 in TSPAN10 (P=4.4×10(-9); minor allele frequency=0.27), rs5442 in GNB3 (P=7.0×10(-10); minor allele frequency=0.05), and rs1800407 in OCA2 (P=3.4×10(-8); minor allele frequency=0.05). The latter single-nucleotide polymorphism, rs1800407, was also associated with central retinal arteriole equivalent (P=6.5×10(-12)). Results from the gene-based burden tests were null. In phenotype look-ups, single-nucleotide polymorphism rs201255422 was associated with both systolic (P=0.001) and diastolic blood pressures (P=8.3×10(-04))., Conclusions: Our study expands the understanding of genetic factors influencing the size of the retinal microvasculature. These findings may also provide insight into the relationship between retinal and systemic microvascular disease., (© 2015 American Heart Association, Inc.)