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BACKGROUND: Patients with idiopathic inflammatory myopathies (IIM) have an increased risk of cancer, but their cancer-related disease burden remains unclear. OBJECTIVES: To explore how cancer might impact the mortality of patients with IIM and examine the associated prognostic factors for cancer and death. METHODS: We identified patients with IIM diagnosed between 1998 and 2020 and ascertained their cancer and death records via linkage to the Swedish healthcare and population registers. Transition hazards from IIM diagnosis to cancer and death were estimated in multistate models using flexible parametric methods. We then predicted the probability of having cancer or death, and the duration of staying alive at a given time from IIM and cancer diagnoses from a crude model. We also explored prognostic factors for progression to cancer and death in a multivariable model. RESULTS: Of 1826 IIM patients, 310 (17%) were diagnosed with cancer before and 306 (17%) after IIM diagnosis. In patients diagnosed with cancer after IIM, the 5-year probability of death from cancer and from other causes was 31% and 18%, respectively, compared to 7% and 15% in patients without cancer after IIM. We reported several factors associated with risk of progression to cancer and death. Specifically, patients with first cancer after IIM who were older at IIM diagnosis, had cancer history, dermatomyositis and a cancer diagnosis within 1 year following IIM faced a greater cancer-specific mortality. CONCLUSION: We observed a substantial increase in mortality from cancer, compared to before, rather than other causes after a cancer diagnosis following IIM, suggesting an unmet medical need for effective cancer management in IIM patients. This finding, along with the identified prognostic factors, provides useful insight into future research directions for improving cancer management in IIM patients.
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BACKGROUND AND OBJECTIVES: Animal studies have suggested a link between benzodiazepine and related Z-drug (BZDR) use and immune dysfunction. Corresponding evidence in humans is limited and focuses mainly on pneumonia. This study aimed to assess the association of incident BZDR use with subsequent development of serious infections. METHODS: This Swedish register-based study included a population-based demographically matched cohort, a co-twin control cohort, and an active comparator cohort. Out of 7,362,979 individuals aged below 65 years who were BZDR naïve by 2007, 713,896 BZDR recipients with incident dispensation of any BZDRs between 2007 and 2019 were 1:1 matched to 713,896 nonrecipients from the general population; 9197 BZDR recipients were compared with their 9298 unexposed co-twins/co-multiples; and 434,900 BZDR recipients were compared with 428,074 incident selective serotonin reuptake inhibitor (SSRI) recipients. The outcomes were identified by the first inpatient or specialist outpatient diagnosis of serious infections in the National Patient Register, or death from any infections recorded as the underlying cause in the Cause of Death Register. Cox proportional hazards regression models were fitted and controlled for multiple confounders, including familial confounding and confounding by indication. To study a possible dose-response association, the cumulative dosage of BZDRs dispensed during the follow-up was estimated for each BZDR recipient and modeled as a time-varying exposure with dose categories in tertiles [≤ 20 defined daily doses (DDDs), > 20 DDDs ≤ 65, and > 65 DDDs). The risk of infections was assessed in BZDR recipients within each category of the cumulative BZDR dosage compared to their demographically matched nonrecipients. RESULTS: In the demographically matched cohort (average age at incident BZDR use 42.8 years, 56.9% female), the crude incidence rate of any serious infections in BZDR recipients and matched nonrecipients during 1-year follow-up was 4.18 [95% confidence intervals (CI) 4.13-4.23] and 1.86 (95% CI 1.83-1.89) per 100 person-years, respectively. After controlling for demographic, socioeconomic, clinical, and pharmacological confounders, BZDR use was associated with 83% relative increase in risk of any infections [hazard ratio (HR) 1.83, 95% CI 1.79-1.89]. The risk remained increased, although attenuated, in the co-twin cohort (HR 1.55, 95% CI 1.23-1.97) and active comparator cohort (HR 1.33, 95% CI 1.30-1.35). The observed risks were similar across different types of initial BZDRs and across individual BZDRs, and the risks increased with age at BZDR initiation. We also observed a dose-response association between cumulative BZDR dosage and risk of serious infections. CONCLUSIONS: BZDR initiation was associated with increased risks of serious infections, even when considering unmeasured familial confounding and confounding by indication. The exact pathways through which BZDRs may affect immune function, however, remain unclear. Further studies are needed to explore the neurobiological mechanisms underlying the association between BZDR use and serious infections, as it can lead to safer therapeutic strategies for patients requiring BZDR.
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The impact of traumatic brain injury (TBI) on subsequent risk of schizophrenia (SCZ) or bipolar disorder (BD) remains contested. Possible genetic and environmental confounding effects have also been understudied. Therefore, we aim to investigate the impact of TBI on the risk of SCZ and BD and whether the effect varies by injury severity, age at injury, and sex. We identified 4,184 SCZ and 18,681 BD cases born between 1973 and 1998 in the Swedish National Registers. Case-control samples matched (1:5) on birth year, sex, and birthplace were created along with a family design study, with cases matched to non-case full siblings. TBI was associated with higher risk of SCZ and BD (IRR=1.33 for SCZ, IRR=1.78 for BD). The association remained significant in the sibling comparison study. Moderate or severe TBI was associated with higher risk for both SCZ and BD compared to mild TBI. Older age at injury was associated with higher risk of SCZ and BD, and the effect of TBI was stronger in women than men. Findings indicate that TBI is a risk factor for both SCZ and BD with differential impact by age, severity and sex and that this association cannot be explained by familial confounding alone.
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Transtorno Bipolar , Lesões Encefálicas Traumáticas , Sistema de Registros , Esquizofrenia , Humanos , Masculino , Esquizofrenia/epidemiologia , Transtorno Bipolar/epidemiologia , Feminino , Adulto , Lesões Encefálicas Traumáticas/epidemiologia , Suécia/epidemiologia , Estudos de Casos e Controles , Pessoa de Meia-Idade , Adulto Jovem , Fatores de Risco , Irmãos , Fatores Sexuais , Adolescente , Fatores EtáriosRESUMO
Background: Evidence for substance use-related problems in individuals with mild intellectual disability is sparse and mainly limited to selected psychiatric populations. We evaluated the risk of substance use-related problems in individuals with mild intellectual disability compared to the general population. Additionally, we have performed secondary sibling comparison analyses to account for familial confounding. Methods: We conducted a population-based cohort study of individuals born in Sweden between 1973 and 2003. A total of 18,307 individuals with mild intellectual disability were compared to 915,350 reference individuals from the general population and 18,996 full siblings of individuals with mild intellectual disability. Information on mild intellectual disability and substance use-related problems was obtained from several Swedish national and regional school and healthcare registers. Substance use-related problems were measured via corresponding diagnostic and legal codes and included alcohol use disorder, drug use disorder, alcohol-related somatic disease, conviction for a substance-related crime, and substance-related death. Results: Individuals with mild intellectual disability had a higher risk of any substance use-related problem compared to the general population (HR, 1.81; 95% CI, 1.72-1.91), both in males (HR, 1.76; 95% CI, 1.65-1.89) and females (HR, 1.89; 95% CI, 1.74-2.05). The risks of substance use-related problems were particularly elevated among individuals with mild intellectual disability and psychiatric comorbidities (HR, 2.21-8.24). The associations were attenuated in the sibling comparison models. Conclusions: Individuals with mild intellectual disability, especially those with psychiatric comorbidity, are at an elevated risk of substance use-related problems. Familial factors shared by full siblings contribute considerably to the association between mild intellectual disability and substance use-related problems.
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BACKGROUND: There is currently insufficient understanding of the health and behavior of children whose parents engage in criminal behavior. We examined associations between parental criminal convictions and wide range of offspring health, behavioral, and social outcomes by age 18 in a large, national sample, aiming to get a comprehensive picture of the risks among children of offending parents. METHODS: We studied 1,013,385 individuals born in Sweden between 1987 and 1995, and their parents. Using data from several longitudinal nationwide registers, we investigated parental convictions and 85 offspring outcomes until the end of 2013, grouped into birth-related conditions, psychiatric and somatic disorders, accidents and injuries, mortality, school achievement, violent victimization, and criminality. Cox proportional hazards regression and logistic regression models were used to examine the associations. The role of genetic factors in intergenerational associations was studied in children-of-siblings analyses. We also examined the co-occurrence of multiple outcomes using Poisson regression. RESULTS: A total of 223,319 (22.0%) individuals had one parent convicted and 31,241 (3.1%) had both parents convicted during the first 18 years of their life. The strongest associations were found between parental convictions and offspring behavioral problems, substance use disorders, poor school achievement, violent victimization, and criminality, with an approximately 2 to 2.5-fold increased risk in children with one convicted parent and 3- to 4-fold increased risk in children with two convicted parents. The risks were particularly elevated among children of incarcerated parents with a history of violent convictions. The associations appeared to be at least partly explained by genetic influences. Parental convictions were also associated with an increased likelihood of experiencing multiple outcomes. CONCLUSIONS: Our findings help to calibrate the risks of a wide range of adverse outcomes associated with parental convictions and may be used to guide prevention efforts and identify key areas for future research.
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Objective: Avoidant restrictive food intake disorder (ARFID) is a feeding and eating disorder characterized by extremely restricted dietary variety and/or quantity resulting in serious consequences for physical health and psychosocial functioning. ARFID often co-occurs with neurodevelopmental conditions (NDCs) and psychiatric conditions, but previous data are mostly limited to small clinical samples examining a narrow range of conditions. Here, we examined NDCs and psychiatric conditions in a large, population-based group of children with ARFID. Method: In a sample of 30,795 children born 1992-2008 in Sweden, ARFID was assessed using parent reports and clinical diagnoses from national health registers. Parents further reported symptoms of NDCs and psychiatric conditions at child age 9 or 12 years. We conducted regressions for symptom scores and screening diagnoses (identified using validated cut offs) on ARFID and examined interactions with sex. Results: Children with ARFID had significantly increased odds of all 17 screening diagnoses with odds ratios ranging from 3.3 for visual hallucinations to 13.7 for autism (all p<.0001). The most common NDCs were oppositional defiant disorder (19.4%), ADHD (16.9%), tic disorders (14.8%), and autism (12.1%). Among psychiatric conditions, separation anxiety disorder (29.0%) and sleep problems (20.0%) had the highest prevalence. We did not find any sex-specific differences in co-occurring conditions. Conclusion: This study highlights the co-occurrence of a broad range of NDCs and psychiatric conditions with ARFID in a large, non-clinical cohort. Our findings underscore that children with ARFID face significant burden from multiple co-existing conditions which should be considered during assessment and treatment.
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BACKGROUND: Body dysmorphic disorder (BDD) is thought to be associated with considerable suicide risk. This nationwide cohort study quantified the risks of intentional self-harm-including nonsuicidal self-injuries and suicide attempts-and death by suicide in BDD. METHODS: Individuals with a validated ICD-10 diagnosis of BDD in the Swedish National Patient Register, registered between January 1, 1997, and December 31, 2020, were matched with 10 unexposed individuals (i.e., without BDD) from the general population on birth year, sex, and county of residence. Conditional Poisson regression models estimated incidence rate ratios and 95% CIs for intentional self-harm. Stratified Cox proportional hazards models estimated hazard ratios and 95% CIs for death by suicide. Models adjusted for sociodemographic variables and lifetime psychiatric comorbidities. RESULTS: Among 2833 individuals with BDD and 28,330 unexposed matched individuals, 466 (16.45%) and 1071 (3.78%), respectively, had at least 1 record of intentional self-harm during the study period (incidence rate ratio = 3.37; 95% CI, 3.02-3.76). In the BDD group, about two-thirds (n = 314; 67%) had their first recorded self-harm event before their first BDD diagnosis. A total of 17 (0.60%) individuals with BDD and 27 (0.10%) unexposed individuals died by suicide (hazard ratio = 3.47; 95% CI, 1.76-6.85). All results remained robust to additional adjustment for lifetime psychiatric comorbidities. A higher proportion of individuals with BDD who died by suicide had at least 1 previous record of intentional self-harm compared with unexposed individuals (52.94% vs. 22.22%; p = .036). CONCLUSIONS: BDD was associated with a 3-fold increased risk of intentional self-harm and death by suicide.
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Background: Avoidant restrictive food intake disorder (ARFID) is a feeding and eating disorder, characterized by limited variety and/or quantity of food intake impacting physical health and psychosocial functioning. Children with ARFID often present with a range of psychiatric and somatic symptoms, and therefore consult various pediatric subspecialties; large-scale studies mapping comorbidities are however lacking. To characterize health care needs of people with ARFID, we systematically investigated ARFID-related mental and somatic conditions in 616 children with ARFID and >30,000 children without ARFID. Methods: In a Swedish twin cohort, we identified the ARFID phenotype in 6-12-year-old children based on parent-reports and register data. From >1,000 diagnostic ICD-codes, we specified mental and somatic conditions within/across ICD-chapters, number of distinct per-person diagnoses, and inpatient treatment days between birth and 18th birthday (90 outcomes). Hazard ratios (HR) and incidence rate ratios (IRR) were calculated. Findings: Relative risks of neurodevelopmental, gastrointestinal, endocrine/metabolic, respiratory, neurological, and allergic disorders were substantially increased in ARFID (e.g., autism HR[CI95%]=9.7[7.5-12.5], intellectual disability 10.3[7.6-13.9], gastroesophageal reflux disease 6.7[4.6-9.9], pituitary conditions 5.6[2.7-11.3], chronic lower respiratory diseases 4.9[2.4-10.1], epilepsy 5.8[4.1-8.2]). ARFID was not associated with elevated risks of autoimmune illnesses and obsessive-compulsive disorder. Children with ARFID had a significantly higher number of distinct mental diagnoses (IRR[CI95%]=4.7[4.0-5.4]) and longer duration of hospitalizations (IRR[CI95%]=5.5[1.7-17.6]) compared with children without ARFID. Children with ARFID were diagnosed earlier with a mental condition than children without ARFID. No sex-specific differences emerged. Interpretation: This study yields the broadest and most detailed evidence of co-existing mental and somatic conditions in the largest sample of children with ARFID to date. Findings suggest a complex pattern of health needs in youth with ARFID, underscoring the critical importance of attention to the illness across all pediatric specialties. Funding: Fredrik and Ingrid Thurings Foundation, Mental Health Foundation.
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This cohort study estimates the heritability of clinically diagnosed obsessive-compulsive disorder in a sample of twins.
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Doenças em Gêmeos , Transtorno Obsessivo-Compulsivo , Humanos , Transtorno Obsessivo-Compulsivo/genética , Transtorno Obsessivo-Compulsivo/diagnóstico , Masculino , Feminino , Doenças em Gêmeos/genética , Doenças em Gêmeos/diagnóstico , Adulto , Gêmeos Monozigóticos/genética , Gêmeos Dizigóticos/genética , Predisposição Genética para Doença/genéticaRESUMO
BACKGROUND: Type 1 diabetes in children is known to be highly heritable, but much less is known about the heritability of adult-onset type 1 diabetes. Thus, our objective was to compare the familial aggregation and heritability of type 1 diabetes in adults and children. METHODS: This Swedish nationwide register-based cohort study included individuals born from Jan 1, 1982, to Dec 31, 2010, identified through the Medical Birth Register who were linked to their parents, full siblings, half siblings, and cousins through the Multi-Generation Register (MGR). We excluded multiple births, deaths within the first month of life, individuals who could not be linked to MGR, or individuals with contradictory information on sex. Information on diagnoses of type 1 diabetes was retrieved by linkages to the National Diabetes Register and National Patient Register (1982-2020). Individuals with inconsistent records of diabetes type were excluded. We estimated the cumulative incidence and hazard ratios (HRs) of type 1 diabetes in adults (aged 19-30 years) and children (aged 0-18 years) by family history of type 1 diabetes and the heritability of adult-onset and childhood-onset type 1 diabetes based on tetrachoric correlations, using sibling pairs. FINDINGS: 2 943 832 individuals were born in Sweden during the study period, 2 832 755 individuals were included in the analysis of childhood-onset type 1 diabetes and 1 805 826 individuals were included in the analysis of adult-onset type 1 diabetes. 3240 cases of adult-onset type 1 diabetes (median onset age 23·4 years [IQR 21·1-26·2]; 1936 [59·7%] male and 1304 [40·2%] female) and 17 914 cases of childhood-onset type 1 diabetes (median onset age 9·8 years [6·2-13·3]; 9819 [54·8%] male and 8095 [45·2%] female) developed during follow-up. Having a first-degree relative with type 1 diabetes conferred an HR of 7·21 (95% CI 6·28-8·28) for adult-onset type 1 diabetes and 9·92 (9·38-10·50) for childhood-onset type 1 diabetes. The HR of developing type 1 diabetes before the age 30 years was smaller if a first-degree relative developed type 1 diabetes during adulthood (6·68 [6·04-7·39]) rather than during childhood (10·54 [9·92-11·19]). Similar findings were observed for type 1 diabetes in other relatives. Heritability was lower for adult-onset type 1 diabetes (0·56 [0·45-0·66]) than childhood-onset type 1 diabetes (0·81 [0·77-0·85]). INTERPRETATION: Adult-onset type 1 diabetes seems to have weaker familial aggregation and lower heritability than childhood-onset type 1 diabetes. This finding suggests a larger contribution of environmental factors to the development of type 1 diabetes in adults than in children and highlights the need to identify and intervene on such factors. FUNDING: Swedish Research Council, the Swedish Research Council for Health, Working Life and Welfare, Swedish Diabetes Foundation, and the China Scholarship Council.
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Idade de Início , Diabetes Mellitus Tipo 1 , Sistema de Registros , Humanos , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/epidemiologia , Suécia/epidemiologia , Adulto , Masculino , Criança , Feminino , Adolescente , Pré-Escolar , Adulto Jovem , Estudos de Coortes , Lactente , Recém-Nascido , Predisposição Genética para Doença , IncidênciaRESUMO
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 25â¯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 25â¯252 twins included in the study (15â¯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.
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Experiências Adversas da Infância , Transtornos Mentais , Humanos , Adulto , Feminino , Masculino , Experiências Adversas da Infância/estatística & dados numéricos , Suécia/epidemiologia , Pessoa de Meia-Idade , Adulto Jovem , Adolescente , Transtornos Mentais/epidemiologia , Transtornos Mentais/psicologia , Sistema de Registros/estatística & dados numéricos , Estudos de Coortes , Gêmeos Monozigóticos/psicologia , Gêmeos Dizigóticos/psicologia , Gêmeos Dizigóticos/estatística & dados numéricos , Saúde Mental/estatística & dados numéricosRESUMO
Importance: Attention-deficit/hyperactivity disorder (ADHD) is associated with increased risks of adverse health outcomes including premature death, but it is unclear whether ADHD pharmacotherapy influences the mortality risk. Objective: To investigate whether initiation of ADHD pharmacotherapy was associated with reduced mortality risk in individuals with ADHD. Design, Setting, and Participants: In an observational nationwide cohort study in Sweden applying the target trial emulation framework, we identified individuals aged 6 through 64 years with an incident diagnosis of ADHD from 2007 through 2018 and no ADHD medication dispensation prior to diagnosis. Follow-up started from ADHD diagnosis until death, emigration, 2 years after ADHD diagnosis, or December 31, 2020, whichever came first. Exposures: ADHD medication initiation was defined as dispensing of medication within 3 months of diagnosis. Main Outcomes and Measures: We assessed all-cause mortality within 2 years of ADHD diagnosis, as well as natural-cause (eg, physical conditions) and unnatural-cause mortality (eg, unintentional injuries, suicide, and accidental poisonings). Results: Of 148â¯578 individuals with ADHD (61â¯356 females [41.3%]), 84â¯204 (56.7%) initiated ADHD medication. The median age at diagnosis was 17.4 years (IQR, 11.6-29.1 years). The 2-year mortality risk was lower in the initiation treatment strategy group (39.1 per 10â¯000 individuals) than in the noninitiation treatment strategy group (48.1 per 10â¯000 individuals), with a risk difference of -8.9 per 10â¯000 individuals (95% CI, -17.3 to -0.6). ADHD medication initiation was associated with significantly lower rate of all-cause mortality (hazard ratio [HR], 0.79; 95% CI, 0.70 to 0.88) and unnatural-cause mortality (2-year mortality risk, 25.9 per 10â¯000 individuals vs 33.3 per 10â¯000 individuals; risk difference, -7.4 per 10â¯000 individuals; 95% CI, -14.2 to -0.5; HR, 0.75; 95% CI, 0.66 to 0.86), but not natural-cause mortality (2-year mortality risk, 13.1 per 10â¯000 individuals vs 14.7 per 10â¯000 individuals; risk difference, -1.6 per 10â¯000 individuals; 95% CI, -6.4 to 3.2; HR, 0.86; 95% CI, 0.71 to 1.05). Conclusions and Relevance: Among individuals diagnosed with ADHD, medication initiation was associated with significantly lower all-cause mortality, particularly for death due to unnatural causes.
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Transtorno do Deficit de Atenção com Hiperatividade , Estimulantes do Sistema Nervoso Central , Adolescente , Adulto , Criança , Feminino , Humanos , Adulto Jovem , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/mortalidade , Estudos de Coortes , Mortalidade Prematura , Suécia/epidemiologia , Pessoa de Meia-Idade , Masculino , Estimulantes do Sistema Nervoso Central/uso terapêuticoRESUMO
BACKGROUND: Lower autonomic arousal is a well-known correlate of criminal offending and other risk-taking behaviors in men, but few studies have investigated this association in women. AIM: To test associations between autonomic arousal and criminal offending as well as unintentional injuries among female conscripts. METHODS: All women born 1958-1994 in Sweden who participated in voluntary military conscription (n = 12,499) were identified by linking Swedish population-based registers. Predictors were resting heart rate (RHR) and systolic blood pressure (SBP). Covariates were height, weight, and physical energy capacity. Main outcomes were criminal convictions (any, violent, and non-violent) from the National Crime Register. Secondary outcome was unintentional injuries requiring medical treatment or causing death. We used survival analyses to test for associations between predictors and outcomes. RESULTS: Low RHR, relative to high RHR, was associated with an increased risk of any criminal conviction, non-violent criminal convictions, and unintentional injuries. Low SBP, relative to high SBP, was associated with an increased risk of violent criminal convictions. CONCLUSIONS: Results support lower autonomic arousal, particularly lower RHR, as a correlate of criminal offending among women that warrants further examination, as the reported findings have potential implications for the prediction of future female crime.
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Criminosos , Masculino , Humanos , Feminino , Violência , Fatores de Risco , Crime , Nível de Alerta , Suécia/epidemiologiaRESUMO
Epigenetics plays an important role in the aging process, but it is unclear whether epigenetic factors also influence frailty, an age-related state of physiological decline. In this study, we performed a meta-analysis of epigenome-wide association studies in four samples drawn from the Swedish Adoption/Twin Study of Aging (SATSA) and the Longitudinal Study of Aging Danish Twins (LSADT) to explore the association between DNA methylation and frailty. Frailty was defined using the frailty index (FI), and DNA methylation levels were measured in whole blood using Illumina's Infinium HumanMethylation450K and MethylationEPIC arrays. In the meta-analysis consisting of a total of 829 participants, we identified 589 CpG sites that were statistically significantly associated with either the continuous or categorical FI (false discovery rate <0.05). Many of these CpGs have previously been associated with age and age-related diseases. The identified sites were also largely directionally consistent in a longitudinal analysis using mixed-effects models in SATSA, where the participants were followed up to a maximum of 20 years. Moreover, we identified three differentially methylated regions within the MGRN1, MIR596, and TAPBP genes that have been linked to neuronal aging, tumor growth, and immune functions. Furthermore, our meta-analysis results replicated 34 of the 77 previously reported frailty-associated CpGs at p < 0.05. In conclusion, our findings demonstrate robust associations between frailty and DNA methylation levels in 589 novel CpGs, previously unidentified for frailty, and strengthen the role of neuronal/brain pathways in frailty.
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Metilação de DNA , Epigenoma , Fragilidade , Humanos , Fragilidade/genética , Epigenoma/genética , Masculino , Feminino , Metilação de DNA/genética , Idoso , Estudo de Associação Genômica Ampla , Estudos de Coortes , Ilhas de CpG/genética , Envelhecimento/genética , Estudos Longitudinais , Epigênese Genética , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: Little is known about shared origins between inflammatory bowel disease (IBD) and allergic diseases (asthma, allergic rhinitis, and eczema). We aimed to expand current knowledge on the etiological sources of comorbidities between these disorders using a range of genetically informed methods. METHODS: Within-individual and familial co-aggregation analysis was applied to 2â 873â 445 individuals born in Sweden from 1987 to 2014 and their first- and second-degree relatives. Quantitative genetic modeling was applied to 38â 723 twin pairs to decompose the genetic and environmental sources for comorbidity. Polygenic risk score analysis between IBD and allergic diseases was conducted in 48â 186 genotyped twins, and linkage disequilibrium score regression was applied using publicly available data to explore the genetic overlap. RESULTS: IBD was associated with asthma (adjusted odds ratio [aOR], 1.35; 95% confidence interval [CI], 1.30 to 1.40), allergic rhinitis (aOR, 1.27; 95% CI, 1.20 to 1.34), and eczema (aOR, 1.47; 95% CI, 1.38 to 1.56), with similar estimates for ulcerative colitis or Crohn's disease. The ORs for familial co-aggregation decreased with decreasing genetic relatedness. Quantitative genetic modeling revealed little evidence of common genetic factors between IBD and allergic diseases (eg, IBD and allergic rhinitis; genetic correlation raâ =â 0.06; 95% CI, -0.03 to 0.15) but did reveal some evidence of unique environmental factors between IBD and eczema (reâ =â 0.16; 95% CI, 0.00 to 0.32). Molecular genetic analyses were similarly null for IBD and allergic diseases, except for a slight association between Crohn's disease polygenic risk score and eczema (OR, 1.09; 95% CI, 1.06 to 1.12). CONCLUSIONS: We found little evidence to support a shared origin between IBD and any allergic disease but weak evidence for shared genetic and unique environmental components for IBD and eczema.
Comorbidities between inflammatory bowel disease (IBD) with asthma and allergic diseases have been documented, but shared origin remains unknown. Using multiple genetically informed approaches, we found little evidence of a shared origin explaining the comorbidities of IBD with asthma and allergic rhinitis but weak evidence for IBD and eczema.
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BACKGROUND AND HYPOTHESIS: Recent research showed that young people who presented to hospital with self-harm in Finland had a significantly elevated risk of later psychosis. We investigated the prospective relationship between hospital presentation for self-harm and risk of psychosis in an unprecedentedly large national Swedish cohort. STUDY DESIGN: We used inpatient and outpatient healthcare registers to identify all individuals born between 1981 and 1993 who were alive and living in Sweden on their 12th birthday and who presented to hospital one or more times with self-harm. We compared them with a matched cohort, followed up for up to 20 years, and compared the cumulative incidence of psychotic disorders. Furthermore, we examined whether the strength of the relationship between hospital presentation for self-harm and later psychosis changed over time by examining for cohort effects. STUDY RESULTS: In total, 28 908 (2.0%) individuals presented to hospital with self-harm without prior psychosis diagnosis during the follow-up. For individuals who presented to hospital with self-harm, the cumulative incidence of diagnosed psychosis was 20.7% at 20 years follow-up (hazard radioâ =â 13.9, 95% CI 13.3-14.6, P-value <5â ×â 10-308). There was no evidence of a dilution of the effect over time: while the incidence of hospital self-harm presentation increased, this did not result in an attenuation over time of the strength of the relationship between hospital self-harm presentation and subsequent psychosis. CONCLUSIONS: Individuals who present to hospital with self-harm in their teens and 20s represent an important risk group for psychosis prediction and prevention.
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Transtornos Psicóticos , Sistema de Registros , Comportamento Autodestrutivo , Humanos , Suécia/epidemiologia , Transtornos Psicóticos/epidemiologia , Comportamento Autodestrutivo/epidemiologia , Sistema de Registros/estatística & dados numéricos , Masculino , Feminino , Adulto , Adulto Jovem , Adolescente , Estudos Prospectivos , Hospitalização/estatística & dados numéricos , Incidência , Seguimentos , RiscoRESUMO
OBJECTIVE: Most mental disorders, when examined individually, are associated with an increased risk of cardiometabolic complications. However, these associations might be attributed to a general liability to psychopathology or confounded by unmeasured familial factors. The authors investigated the association between psychiatric conditions in young adulthood and the risk of cardiometabolic complications in middle adulthood, up to 40 years later. METHODS: This cohort study (N=672,823) identified all individuals and their siblings born in Sweden between 1955 and 1962 and followed the cohort through 2013. Logistic regression models were used to estimate the bivariate associations between 10 psychiatric conditions or criminal convictions and five cardiometabolic complications in individuals. A general factor model was used to identify general, internalizing, externalizing, and psychotic factors based on the comorbidity among psychiatric conditions and criminal convictions. The cardiometabolic complications were then regressed on the latent general factor and three uncorrelated specific factors within a structural equation modeling framework in individuals and across sibling pairs. RESULTS: Each psychiatric condition significantly increased the risk of cardiometabolic complications. These associations appeared nonspecific, as multivariate models indicated that most were attributable to the general factor of psychopathology, rather than to specific psychiatric conditions. There were no or only small associations between individuals' general psychopathology and their siblings' cardiometabolic complications. The same pattern was evident for the specific internalizing and psychotic factors. CONCLUSIONS: Associations between mental disorders in early life and later long-term risk of cardiometabolic complications appeared to be attributable to a general liability to psychopathology. Familial coaggregation analyses suggested that the elevated risk could not be attributed to confounders shared within families. One possibility is that lifestyle-based interventions may reduce the risk of later cardiometabolic complications for patients with several mental disorders.
Assuntos
Transtornos Mentais , Humanos , Suécia/epidemiologia , Transtornos Mentais/epidemiologia , Transtornos Mentais/genética , Masculino , Feminino , Adulto , Estudos Longitudinais , Pessoa de Meia-Idade , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/epidemiologia , Adulto Jovem , Irmãos/psicologia , Comorbidade , Fatores de RiscoRESUMO
OBJECTIVE: To estimate the risk of all cause and cause specific mortality in people with obsessive-compulsive disorder (OCD) compared with matched unaffected people from the general population and with their unaffected siblings. DESIGN: Population based matched cohort and sibling cohort study. SETTING: Register linkage in Sweden. PARTICIPANTS: Population based cohort including 61 378 people with OCD and 613 780 unaffected people matched (1:10) on sex, birth year, and county of residence; sibling cohort consisting of 34 085 people with OCD and 47 874 unaffected full siblings. Cohorts were followed up for a median time of 8.1 years during the period from 1 January 1973 to 31 December 2020. MAIN OUTCOME MEASURES: All cause and cause specific mortality. RESULTS: 4787 people with OCD and 30 619 unaffected people died during the study period (crude mortality rate 8.1 and 5.1 per 1000 person years, respectively). In stratified Cox proportional hazards models adjusted for birth year, sex, county, migrant status (born in Sweden versus abroad), and sociodemographic variables (latest recorded education, civil status, and family income), people with OCD had an increased risk of all cause mortality (hazard ratio 1.82, 95% confidence interval 1.76 to 1.89) and mortality due to natural causes (1.31, 1.27 to 1.37) and unnatural causes (3.30, 3.05 to 3.57). Among the natural causes of death, those due to endocrine, nutritional, and metabolic diseases, mental and behavioural disorders, and diseases of the nervous, circulatory, respiratory, digestive, and genitourinary systems were higher in the OCD cohort. Conversely, the risk of death due to neoplasms was lower in the OCD cohort compared with the unaffected cohort. Among the unnatural causes, suicide showed the highest hazard ratio, followed by accidents. The results were robust to adjustment for psychiatric comorbidities and familial confounding. CONCLUSIONS: Non-communicable diseases and external causes of death, including suicides and accidents, were major contributors to the risk of mortality in people with OCD. Better surveillance, prevention, and early intervention strategies should be implemented to reduce the risk of fatal outcomes in people with OCD.
Assuntos
Transtorno Obsessivo-Compulsivo , Suicídio , Feminino , Humanos , Estudos de Coortes , Irmãos , Causas de Morte , Fatores de Risco , Transtorno Obsessivo-Compulsivo/epidemiologia , Transtorno Obsessivo-Compulsivo/psicologia , Suécia/epidemiologiaRESUMO
Importance: Antidepressants are increasingly prescribed to pediatric patients with unipolar depression, but little is known about the risk of treatment-emergent mania. Previous research suggests pediatric patients may be particularly vulnerable to this adverse outcome. Objective: To estimate whether pediatric patients treated with antidepressants have an increased incidence of mania/hypomania compared with patients not treated with antidepressants and to identify patient characteristics associated with the risk of mania/hypomania. Design, Setting, and Participants: In a cohort study applying the target trial emulation framework, nationwide inpatient and outpatient care in Sweden from July 1, 2006, to December 31, 2019, was evaluated. Follow-up was conducted for 12 and 52 weeks after treatment initiation, with administrative follow-up ending December 31, 2020. Data were analyzed between May 1, 2022, and June 28, 2023. Individuals aged 4 to 17 years with a diagnosis of depression, but without a prior diagnosis of mania/hypomania, bipolar disorder, or psychosis or treatment with mood stabilizer (lithium, valproate, or carbamazepine), prescriptions were included. Exposures: The treatment group included patients who initiated any antidepressant medication within 90 days of diagnosis. The control group included patients who did not initiate antidepressants within 90 days. Main Outcomes and Measures: Diagnosis of mania/hypomania or initiation of mood stabilizer therapy. Incidences were estimated with Kaplan-Meier estimator, and inverse probability of treatment weighting was used to adjust for group differences at baseline. Results: The cohort included 43â¯677 patients (28 885 [66%] girls); 24â¯573 in the treatment group and 19â¯104 in the control group. The median age was 15 (IQR, 14-16) years. The outcome occurred in 96 individuals by 12 weeks and in 291 by 52 weeks. The cumulative incidence of mania was 0.26% (95% CI, 0.19%-0.33%) in the treatment group and 0.20% (95% CI, 0.13%-0.27%) in the control group at 12 weeks, with a risk difference of 0.06% (95% CI, -0.04% to 0.16%). At 52 weeks, the cumulative incidence was 0.79% (95% CI, 0.68%-0.91%) in the treatment group and 0.52% (95% CI, 0.40%-0.63%) in the control group (risk difference, 0.28%; 95% CI, 0.12%-0.44%). Hospitalizations, parental bipolar disorder, and use of antipsychotics and antiepileptics were the most important predictors of mania/hypomania by 12 weeks. Conclusion: This cohort study found no evidence of treatment-emergent mania/hypomania by 12 weeks in children and adolescents. This corresponds to the time frame for antidepressants to exert their psychotropic effect. A small risk difference was found only with longer follow-up. Certain patient characteristics were associated with mania/hypomania, which warrants clinical attention.