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INTRODUCTION: Whether detailed genetic information contributes to risk stratification of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) remains uncertain. Pathogenic genetic variants in some genes seem to carry a higher risk for arrhythmia and earlier disease onset than others, but comparisons between variants in the same gene have not been done. Combined Annotation Dependent Depletion (CADD) score is a bioinformatics tool that measures the pathogenicity of each genetic variant. We hypothesized that a higher CADD score is associated with arrhythmic events and earlier age at ARVC manifestations in individuals carrying pathogenic or likely pathogenic genetic variants in plakophilin-2 (PKP2). METHODS: CADD scores were calculated using the data from pooled Scandinavian and North American ARVC cohorts, and their association with cardiac events defined as ventricular tachycardia/ventricular fibrillation (VT/VF) or syncope and age at definite ARVC diagnosis were assessed. RESULTS: In total, 33 unique genetic variants were reported in 179 patients (90 males, 71 probands, 96 with definite ARVC diagnosis at a median age of 35 years). Cardiac events were reported in 76 individuals (43%), of whom 53 had sustained VT/VF (35%). The CADD score was neither associated with age at cardiac events (HR 1.002, 95% CI: 0.953-1.054, p = 0.933) nor with age at definite ARVC diagnosis (HR 0.992, 95% CI: 0.947-1.039, p = 0.731). CONCLUSION: No correlation was found between CADD scores and clinical manifestations of ARVC, indicating that the score has no additional risk stratification value among carriers of pathogenic or likely pathogenic PKP2 genetic variants., Funding agencies: This work was supported by Region Östergötland (ALF) undergrant LIO-609681 and by FORSS (Medical Research Council ofSoutheast Sweden) under grant FORSS/572421 and FORSS/307961.Pyotr G. Platonov is supported by The Swedish Heart-Lung Foundation and governmental funding of clinical research (ALF). Henrik K. Jensen is supported by the Novo Nordisk Foundation (NNF18OC0031258). Wojciech Zareba is supported by NIH Grant(1R01HL116906) (Mechanisms, Genotypes and Clinical Phenotypes of Arrhythmogenic Cardiomyopathy).

Objective: Little is known about people who have been exposed to a suicide attempt by someone they know. The purpose of this study was to examine how many people have been exposed to a suicide attempt by someone they knew and whether the exposure was associated with general well-being and suicidal ideation. Method: A population-based online survey was conducted during 2019 in Denmark (n = 6,191). The associations between exposures to suicide attempt and general well-being (WHO-5) and suicidal ideation (Suicidal Ideation Attributes Scale) were examined using linear regression analyses. Results: Overall, 24.6% reported having experienced a suicide attempt by someone they knew. Of those, 46.5% had experienced a suicide attempt of a close relation and this group reported having been more affected by the event. Those exposed scored lower on general well-being (b: −3.0; 95% CI: −4.2 to −1.8; p > 0.001) and higher on suicidal ideation (b: 1.6; 95% CI: 1.3 - 1.9; p = 0.001) than those not exposed. Half of the exposed reported not having received sufficient support after the event. Conclusion: Suicide attempt affects a substantial share of the population, and it might be relevant to ensure that support is available for those exposed perceived to be in need of support.

Background: The suicide rate in first week after psychiatric discharge is alarmingly high. Although a risk assessment prior to discharge is standard praxis, it can be difficult to take into consideration the obstacles that patient will meet once discharged. A follow-up-visit during the first week after discharge is an opportunity to reevaluate whether a person may be at risk of suicide. Aim: To determine how many patients, of those who were assessed, were evaluated to be at elevated risk of suicide during the first week after psychiatric discharge and secondarily to identify predictors of this and predictors for receiving a follow-up visit during first week after discharge. Methods: All patients discharged between March 1st 2018 to January 17th 2019 were offered a home visit including a systematic risk assessment. Socio-demographics and clinical variables were obtained from medical records and logistic regression analyses were used to identify predictors of a higher suicide risk assessment as well as receiving a follow-up visit. Results: Information from 1905 discharges were included. Of these, 1,052 were seen in follow-up meetings. Risk assessments was conducted in a total of 567 discharge procedures, of which 28 (5%) had an elevated risk of suicide. A history of suicide attempt, suicide risk having been the reason for admission, a first diagnosis of a psychiatric disorder was associated with an elevated risk of suicide after discharge. Conclusion: Follow-up visits could serve as an important tool to identify people whose suicidal risk were overlooked at discharge or exposed to severe stressors after discharge.

Background The association between suicide attempts (SAs) in parents and children is unclear, and risk indicators for intergenerational transmission remain undocumented. We aimed to assess this association, considering the child's developmental period at the time of parents' attempted suicide, and the parental relation. Methods Using a prospective cohort design, nationwide population data were linked to the Psychiatric Central Register and National Patient Register for all individuals aged 10 years or older living in Denmark between 1980 and 2016. We assessed incidence rate ratios (IRRs) and cumulative hazards for children's first SA. Results In a cohort of 4 419 651 children, 163 056 (3.7%) had experienced a parental SA. An SA was recorded among 6996 (4.3%) of the exposed children as opposed to 70112 (1.6%) in unexposed individuals. Higher rates were noted when a parental SA occurred during early childhood (0 ≤ age < 2) [IRR, 4.7; 95% confidence interval (CI) 4.2-5.4] v. late childhood (6 ≤ age < 13) (IRR, 3.6; 95% CI 3.4-3.8) when compared to those unexposed. Children exposed prior to age 2 had the highest rates of all sub-groups when reaching age 13-17 (IRR, 6.5; 95% CI 6.0-7.1) and 18-25 years (IRR, 6.8; 95% CI 6.2-7.4). Maternal SA (IRR, 3.4; 95% CI 3.2-3.5) was associated with higher rates than paternal (IRR, 2.8; 95% CI 2.7-2.9). Conclusion Parental SA was associated with children's own SA. Exposure during early developmental stages was associated with the highest rates. Early preventive efforts are warranted as is monitoring of suicide risk in the children from age 13.

Objective: The majority of individuals with suicidal ideation do not receive help, and every year close to 800,000 people die by suicide. This study aimed to investigate the effectiveness of a guided internet-based self-help program compared to a waiting list control group in reducing suicidal ideation.Methods: In a randomized controlled trial, 402 individuals with suicidal ideation were assigned to a guided internet-based self-help program or a waiting list control group from September 13, 2016, to September 2, 2018. The primary outcome was suicidal ideation measured with the Beck Scale for Suicide Ideation at postintervention (6 weeks after baseline).Results: Participants assigned to the internet-based self-help program experienced at postintervention a significant reduction on the primary outcome of suicidal ideation (mean difference: 2.91; 95% CI, 1.28 to 4.54; P = .0005, Cohen's d = 0.25) compared to the waiting list control group and on the secondary outcomes of hopelessness (mean difference: 1.98; 95% CI, 0.97 to 3.99) and worrying (mean difference: 5.19; 95% CI, 2.36 to 8.10). Six months later (follow-up), the difference between the groups remained significant for suicidal ideation, hopelessness, and worrying. A total of 28 (16.8%) of the participants in the intervention group reported negative effects from the internet-based self-help program.Conclusions: Internet-based self-help therapy was associated with a reduction in suicidal ideation at postintervention and 6-month follow-up. Some participants found it challenging to work with the therapeutic exercises, and we recommend that internet-based self-help therapy be implemented in mental health clinics or crisis lines, where support or online counseling is available.Trial Registration: ClinicalTrials.gov identifier: NCT02872610.

OBJECTIVE: Lyme borreliosis is a tick-borne infectious disease that may confer an increased risk of mental disorders, but previous studies have been hampered by methodological limitations, including small sample sizes. The authors used a nationwide retrospective cohort study design to examine rates of mental disorders following Lyme borreliosis.METHODS: Using Denmark's National Patient Register and the Psychiatric Central Research Register, and including all persons living in Denmark from 1994 through 2016 (N=6,945,837), the authors assessed the risk of mental disorders and suicidal behaviors among all individuals diagnosed with Lyme borreliosis in inpatient and outpatient hospital contacts (N=12,156). Incidence rate ratios (IRRs) were calculated by Poisson regression analyses.RESULTS: Individuals with Lyme borreliosis had higher rates of any mental disorder (IRR=1.28, 95% CI=1.20, 1.37), of affective disorders (IRR=1.42, 95% CI=1.27, 1.59), of suicide attempts (IRR=2.01, 95% CI=1.58, 2.55), and of death by suicide (IRR=1.75, 95% CI=1.18, 2.58) compared with those without Lyme borreliosis. The 6-month interval after diagnosis was associated with the highest rate of any mental disorder (IRR=1.96, 95% CI=1.53, 2.52), and the first 3 years after diagnosis was associated with the highest rate of suicide (IRR=2.41, 95% CI=1.25, 4.62). Having more than one episode of Lyme borreliosis was associated with increased incidence rate ratios for mental disorders, affective disorders, and suicide attempts, but not for death by suicide.CONCLUSIONS: Individuals diagnosed with Lyme borreliosis in the hospital setting had an increased risk of mental disorders, affective disorders, suicide attempts, and suicide. Although the absolute population risk is low, clinicians should be aware of potential psychiatric sequelae of this global disease.

Objective: The aims of the current study were to investigate the associations between two aspects of well-being satisfaction with life and vitality - and all-cause mortality, and examine the impact of potential confounding factors on the associations. Methods: Baseline satisfaction with life was assessed using the Satisfaction With Life Scale (n = 7058) and vitality was assessed using the Short-Form 36 vitality subscale (n = 6987). The study sample consisted of midlife participants from the Copenhagen Aging and Midlife Biobank (CAMB) study conducted from 2009 to 2011. Deaths (n = 312) in the study sample in the follow-up period (mean of 8.6 years) were assessed using Danish register data. The hazard ratios of all-cause mortality according to satisfaction with life and vitality scores adjusted for potential covariates were examined with proportional hazard regression. Results: A one standard deviation increase on the SWLS and the SF-36 vitality scale was associated with a 39% (HR = 0.61, 95% CI = 0.55 & ndash;0.67) and 40% (HR = 0.60, 95% CI = 0.54 & ndash;0.66) decreased risk of mortality respectively, after adjustment for baseline sociodemographic factors. The associations remained significant after separate adjustment for lifestyle (SWLS: HR = 0.67, SF-36 vitality: HR = 0.67), health (SWLS: HR = 0.65, SF-36 vitality: HR = 0.64), depressive symptoms (SWLS: HR = 0.72, SF-36 vitality: HR = 0.71) and social factors (SWLS: HR = 0.76, SF-36 vitality: HR = 0.69). Conclusions: Satisfaction with life and vitality are of predictive value for mortality, independently of sociodemographics, lifestyle, health, depressive symptoms, and social factors.

Aims We aimed to analyze whether people with substance-induced psychosis (SIP), both those who convert and do not convert to schizophrenia, have higher all-cause and cause-specific mortality when compared to the general population. Design Prospective cohort study. Setting Nationwide Danish registers. Participants/Cases We included all people born in Denmark, living in Denmark on their 15th birthday, and age 15 or more during the study period from January 1, 1994, and August 10, 2017. Measurements Exposure was categorized as: (i) neither SIP nor schizophrenia; (ii) SIP without preceding schizophrenia; (iii) SIP converted to schizophrenia; and (iv) schizophrenia without preceding SIP. Any SIP and substance-specific SIPS were examined regarding all-cause and cause-specific mortality. Findings The study included a total of 5 619 691 individuals. Compared to people with neither schizophrenia nor SIP, people with SIP without preceding schizophrenia had an increased risk of dying (hazard ratio [HR] = 6.23, 95% CI = 5.96-6.50), as had those with SIP converting to schizophrenia (HR = 9.77, 95% CI = 8.84-10.79) and those with only schizophrenia (HR = 3.07, 95% CI = 3.03-3.13). A similar pattern, albeit with higher HRs, was observed for suicides and accidental deaths. Other cause-specific-mortality groups also generally showed the same pattern, as did types of individual substances. Conclusions Substance-induced psychosis was strongly associated with an increased risk of both all-cause and cause-specific mortality, even among cases who did not convert to schizophrenia. This provides a strong rationale for monitoring people with previous diagnosis of substance-induced psychosis and developing and implementing interventions to reduce this excess mortality.

Associations of educational level and intelligence with age at onset and age at treatment of alcohol use disorders (AUD) are sparsely investigated; however, knowledge about these associations is important for an enhanced understanding of AUD. This study aimed to examine three measures of timing of AUD: estimated age at onset of alcohol problems, age at first registration in an outpatient alcohol clinic, and age at first AUD hospital diagnosis, and to estimate associations of educational level and intelligence with these measures of timing of AUD. The aim was investigated in a register-based study comprising 7,019 Danish men seeking outpatient AUD treatment. Data on educational level and intelligence were obtained from the Danish Conscription Database. Estimated age at onset of alcohol problems and age at first registration in an outpatient alcohol clinic were obtained from the Copenhagen Alcohol Cohort. Age at first AUD hospital diagnosis was retrieved from national Danish psychiatric registers. Among individuals with information on all measures of timing of AUD, 65.8% followed the developmental sequence: estimated age at onset of alcohol problems (M=32.08 years, SD=9.3), age at first registration in an outpatient alcohol clinic (M=39.89 years, SD=9.5), and age at first AUD hospital diagnosis (M=42.27 years, SD=12.4). Adjusted linear regression models revealed significant associations of high educational level and high intelligence with later onset and treatment of AUD, ranging from 0.97-1.28 years (p<0.0001) for educational level and from 0.16-0.20 years (p<0.0001) for intelligence. In conclusion, AUD develops sequentially. High educational level and intelligence were associated with later onset and treatment of AUD, but educational level explained most unique variance. This may indicate that in addition to cognitive factors reflected by both educational level and intelligence, non-cognitive factors only reflected by educational level also are important fo

Objective: To compare suicide rates of people in prison and the general population in the Nordic countries. Methods: Data on deaths by suicide and person-years for people in prison and the general population were obtained for the Nordic countries during 2000–2016. Age-standardized rate ratios were calculated. Results: The suicide rate in the Nordic countries overall was 110.1 (95% CI = 98.1, 122.2) per 100,000 person-years for people in prison. A significant decline was noted for the suicide rate of people in prison between 2000 and 2016 (p< 0.0001). The age-standardized mortality ratio was 7.4 (95% CI = 5.9–8.2) for males and 17.8 (95% CI = 7.3–33.2) for females in Denmark, Iceland, and Norway. Conclusion: Despite a decreasing trend over time, excess suicide mortality was noted for people in prison.

Background: Depression and anxiety are heterogenous disorders often combined into one entity in studies. Few studies have compared trajectories of depression and anxiety among clinically ill. We aimed to identify specific trajectories of depression, and anxiety and predictors of trajectory membership. Methods: Latent growth mixture modelling was carried out on data from the IPS-MA trial (n = 261), a supported employment intervention for people with mood or anxiety, to identify trajectories of depression and anxiety. Logistic regression was used to estimate predictors for trajectory membership. Associations between trajectory class and remission of comorbid depression or anxiety and return to work were also tested. Results: We identified three trajectories of depression and anxiety symptoms respectively; moderate-decreasing (60%), moderate-stable (26%), and low-stable (14%) depression and mild-decreasing (59%), moderate-decreasing (33%), and moderate-stable (8%) anxiety. The depression model showed low precision in class separation (entropy 0.66), hence, predictors of class membership were not estimated. For anxiety, lower age and higher levels of depressive symptoms were associated with a less desirable trajectory. Remission of comorbid depressive symptoms after two years differed significantly between classes (p < 0.000). Fewer had returned to work in the two moderate classes compared to the mild-decreasing anxiety class. Limitations: Depression model not reliable. Only 80% of participants from original study included. Not able to distinguish between anxiety disorders. Conclusion: Trajectories of anxiety confirm that, even after two years, a rather large proportion in the moderate-stable class had symptoms of moderate anxiety, moderate comorbid depressive symptoms, and less probability of having returned to work. Trial registration: ClinicalTrials.govNCT01721824.

Objectives: The main objective of the current study was to investigate associations between two aspects of well-being–satisfaction with life and vitality–and incidence of and mortality from ischemic heart disease. Study design. The Copenhagen Aging and Midlife Biobank (CAMB) was conducted from 2009 to 2011 and was used as baseline data with 6750 individuals having complete information on The Satisfaction with Life Scale (SWLS) and 6652 individuals with complete information on the Short Form Health Survey (SF-36) vitality scale. Incidence of and mortality from ischemic heart disease were assessed using Danish register data and a total of 349 CAMB individuals were registered with either a diagnosis (n = 337) or had died (n = 12) from ischemic heart disease before the end of follow-up (31 December 2017). The hazard ratios of ischemic heart disease according to satisfaction with life and vitality scores were investigated using Cox proportional hazard regression adjusted for potential covariates. Results. A one standard deviation increase on the SWLS was associated with an 18% reduced risk of ischemic heart disease while a one standard deviation increase on the SF-36 vitality scale was associated with a 24% reduced risk of ischemic heart disease after adjustment for baseline socio-demographic factors. These associations remained when separately adjusting for lifestyle, objective health, and social factors, but became non-significant when adjusting for self-reported health. Conclusion. Our study indicates that both psychological and health-related components of wellbeing are important in relation to ischemic heart disease.

OBJECTIVE: To describe the prevalence of lifetime psychiatric hospital diagnoses among men registered in an outpatient alcohol clinic and compare the prevalence with matched controls. To assess temporality of alcohol use disorder (AUD) diagnoses and another psychiatric hospital diagnosis and examine the prevalence of lifetime psychiatric hospital diagnoses according to this temporal order.METHODS: The study included 8,412 Danish men registered in an outpatient alcohol clinic, and 8,412 unregistered controls from the Danish Conscription Database matched on birth date, lifespan, intelligence and draft board district. Information on first outpatient AUD treatment was retrieved from the Copenhagen Alcohol Cohort. Information on lifetime psychiatric hospital diagnoses was retrieved from national Danish psychiatric registers and based on the International Classification of Diseases the 8th and 10th Revisions. Prevalence estimates of lifetime psychiatric hospital diagnoses were compared with odds ratios (OR) between men registered in an outpatient alcohol clinic and the control population.RESULTS: Among men registered in an outpatient alcohol clinic, 66.6% had a lifetime psychiatric hospital diagnosis. In total, 8.6% had neuroses and anxiety disorders, while 25.3% had personality disorders. The OR of a lifetime psychiatric hospital diagnosis was 9.77 (95%CI: 8.87-10.75) when comparing men registered in an outpatient alcohol clinic with the control population. Among men with a lifetime psychiatric hospital diagnosis, 42.8% was registered with another psychiatric hospital diagnosis before registration with an AUD diagnosis.CONCLUSION: Among men with a lifetime psychiatric hospital diagnosis, AUD is rarely diagnosed without psychiatric comorbidity at first-time admissions to psychiatric hospital departments.

Background: Existing research indicates that spending time in nature is associated with diverse aspects of children's health and wellbeing. Although fundamental to later life chances and health, no systematic reviews, to our knowledge, have focused specifically on the effects of interaction with nature on socioemotional functioning in childhood. Objectives: Amongst children, what is the consistency of associations between the availability of or spending time in nature on socioemotional function and development? Furthermore, which child behaviours and states independently associate with socioemotional function and availability of or spending time in nature, and what is the consistency of associations between these behaviours and states and contact with nature? Data sources: Embase, Environment Complete, MEDLINE, and APA PsycINFO. Eligible studies were backward and forward snowball-searched. Study eligibility criteria: Studies investigating effects of, or associations between, availability of or interaction with nature on socioemotional or proximal outcomes in children under the age of 12 years were included in this review. Study appraisal and synthesis methods: The internal validity of studies investigating socioemotional outcomes were based on assessments of elements of study design, conduct, and reporting to identify potential issues related to confounding or other biases. The number of analyses indicating positive, negative, and non-significant associations between availability or interaction with green space and the outcomes were summed. Results: A total of 223 eligible full-texts, of which 43 pertained to socioemotional outcomes and 180 to proximal outcomes, met eligibility criteria. Positive associations between availability of and spending time in green space were found with children's intra- and interpersonal socioemotional function and development. Proportions of positive finding

Objective: Little is known about people who have been exposed to a suicide attempt by someone they know. The purpose of this study was to examine how many people have been exposed to a suicide attempt by someone they knew and whether the exposure was associated with general well-being and suicidal ideation. Method: A population-based online survey was conducted during 2019 in Denmark (n = 6,191). The associations between exposures to suicide attempt and general well-being (WHO-5) and suicidal ideation (Suicidal Ideation Attributes Scale) were examined using linear regression analyses. Results: Overall, 24.6% reported having experienced a suicide attempt by someone they knew. Of those, 46.5% had experienced a suicide attempt of a close relation and this group reported having been more affected by the event. Those exposed scored lower on general well-being (b: −3.0; 95% CI: −4.2 to −1.8; p > 0.001) and higher on suicidal ideation (b: 1.6; 95% CI: 1.3 – 1.9; p = 0.001) than those not exposed. Half of the exposed reported not having received sufficient support after the event. Conclusion: Suicide attempt affects a substantial share of the population, and it might be relevant to ensure that support is available for those exposed perceived to be in need of support.

Education has been suggested to be possibly the most consistent, robust, and durable method available for raising intelligence, but little is known about the genetic and environmental interplay underlying this association. Therefore, we investigated how school achievement, as measured by grade point average in lower secondary school at 15 years of age, moderated intelligence variation in young adulthood. The sample consisted of all Danish male twin pairs who had left lower secondary school since 2002 and appeared, typically at age 18, before a draft board through 2015 (N = 2660). Shared environmental variance unique to intelligence (10% of total variance) was found to be greater among individuals with poor school achievement. However, school achievement did not moderate the genetic influences or the non-shared environmental influences on intelligence. We discuss the implications of this in light of the constraints imposed by the statistical models we used.

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