| 31. |
- Edwards, Alexis C., et al.
(författare)
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Early environmental influences contribute to covariation between internalizing symptoms and alcohol intoxication frequency across adolescence
- 2011
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Ingår i: Addictive Behaviours. - Oxford, United Kingdom : Elsevier. - 0306-4603 .- 1873-6327. ; 36:3, s. 175-182
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Tidskriftsartikel (refereegranskat)abstract
- The association between alcohol use and internalizing symptoms during adolescence varies across studies, and the causes underlying this association remain unclear. The current study examines the relationship between symptoms of anxiety and depression and intoxication frequency in a sample of Swedish twins assessed longitudinally from ages 13-14 to 19-20. The objectives of the study were to assess the stability of genetic and environmental influences on each trait across adolescence; to investigate whether these traits share genetic and/or environmental liabilities; and to explore quantitative changes in the shared liability over time. We found that the magnitude of genetic influences on internalizing symptoms remained relatively stable across adolescence, while their impact on intoxication frequency was dynamic. Symptoms of anxiety and depression were influenced by unique environmental factors, while both shared and unique environmental factors influenced intoxication frequency. Genetic and environmental innovation and attenuation were observed for both traits. While no significant genetic correlation was observed between traits, unique environmental factors did contribute to a shared liability. This environmental correlation was positive and moderate (r(E)=0.41) in the early assessment, but decreased and changed direction at later waves (r(E)=-.04 to -.01). The genetic and environmental factors underlying internalizing symptoms and intoxication frequency appear to be developmentally dynamic. Early environmental factors contribute to the association between these traits, but this shared liability diminishes across adolescence.
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| 32. |
- Edwards, Alexis C., et al.
(författare)
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Exposure to alcohol outlets and risk of suicidal behavior in a Swedish cohort of young adults
- 2023
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Ingår i: Alcoholism: Clinical and Experimental Research. - 0145-6008. ; 47:5, s. 930-939
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Tidskriftsartikel (refereegranskat)abstract
- Background: Greater alcohol accessibility, for example in the form of a high density of alcohol outlets or low alcohol taxation rates, may be associated with increased risk of suicidal behavior. However, most studies have been conducted at the aggregate level, and some have not accounted for potential confounders such as socioeconomic position or neighborhood quality. Methods: In a Swedish cohort of young adults aged 18 to 25, we used logistic regressions to evaluate whether living in a neighborhood that included bars, nightclubs, and/or government alcohol outlets was associated with risk of suicide attempt (SA) or suicide death (SD) during four separate 2-year observation periods. Neighborhoods were defined using pre-established nationwide designations. We conducted combined-sex and sex-stratified analyses, and included as covariates indicators of socioeconomic position, neighborhood deprivation, and aggregate genetic liability to suicidal behavior. Results: Risk of SA was increased in some subsamples of individuals living in a neighborhood with a bar or government alcohol outlet (odds ratios [ORs] = 1.05 to 1.15). Risk of SD was also higher among certain subsamples living in a neighborhood with a government outlet (ORs = 1.47 to 1.56), but lower for those living near a bar (ORs = 0.89 to 0.91). Significant results were driven by, but not exclusive to, the male subsample. Individuals with higher aggregate genetic risk for SA were more sensitive to the effects of a neighborhood government alcohol outlet, pooled across observation periods, in analyses of the sexes combined (relative excess risk due to interaction [RERI] = 0.05; 95% confidence intervals [CI] 0.01; 0.09) and in the male subsample (RERI = 0.06; 95% CI 0.001; 0.12). Conclusions: Although effect sizes are small, living in a neighborhood with bars and/or government alcohol outlets may increase suicidal behavior among young adults. Individuals with higher genetic liability for SA are slightly more susceptible to these exposures.
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| 33. |
- Edwards, Alexis C., et al.
(författare)
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Genetic and environmental influences on the progression from alcohol use disorder to alcohol-related medical conditions
- 2021
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Ingår i: Alcoholism: Clinical and Experimental Research. - : Wiley. - 0145-6008 .- 1530-0277. ; 45:12, s. 2528-2535
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Tidskriftsartikel (refereegranskat)abstract
- Background: Medical conditions related to alcohol use disorders (AUD) represent a substantial public health concern. However, only a subset of individuals with AUD develop these conditions and the extent to which genetic and environmental factors that are shared with AUD, versus those distinct from it, contribute to this progression has not yet been determined. Methods: Using data from Swedish national registries for a cohort born from 1932 to 1970 (N = 1,319,214, 48.9% women), we conducted twin-sibling biometric model fitting to examine the genetic and environmental sources of variance that contribute to the liability to alcohol-related medical conditions (AMC). Progression to AMC, determined using medical registry data, was contingent on an AUD registration, which was determined using medical and criminal registry data. Results: We identified AUD registrations in 3.2% of women and 9.2% of men. Among individuals with an AUD registration, 14.4% of women and 15.4% of men had an AMC registration. In the final models, we constrained the beta pathway from AUD to AMC and the genetic and unique environmental paths to be equal across sexes. The beta path was estimated at 0.59. AMC was modestly heritable in women (A = 0.32) and men (A = 0.30). The proportion of total heritability unique to AMC was 39.6% among women and 41.3% among men. A higher proportion of total environmental variance was unique to AMC: 76.7% for women and 77.2% for men. In a sensitivity analysis limited to liver-related AMC, we observed similar results, with a slightly lower beta path from AUD to AMC (0.46) and higher proportions of AMC-specific genetic (70.0% in women; 71.7% in men) and environmental (84.5% in both sexes) variance. Conclusions: A moderate-to-substantial proportion of genetic and environmental variance that contributes to AMC risk is not shared with AUD, underscoring the need for additional gene identification efforts for AMC. Furthermore, the prominent influence of environmental factors specific to AMC provides a promising area for the identification of prevention targets. We did not observe significant sex differences in the etiology of AMC, although follow-up is warranted in other well-powered studies.
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| 34. |
- Edwards, Alexis C., et al.
(författare)
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Genetic differences between suicide deaths and deaths of undetermined intent
- 2023
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Ingår i: Suicide and Life-Threatening Behavior. - : Wiley. - 0363-0234 .- 1943-278X. ; 53:1, s. 100-109
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Few, if any, prior studies have considered whether undetermined intent (UDI) deaths and suicide deaths differ with respect to genetic liability for suicidal behavior or psychopathology. Methods: The authors used Swedish national registry data to identify suicide deaths (N = 31,835) and UDI deaths (N = 10,623); sociodemographic covariates; and registrations for psychopathology. Family genetic risk scores (FGRS) were derived for each form of psychopathology. The authors used LASSO models to assess genetic and phenotypic differences across outcomes. Results: In the multivariate LASSO regressions, higher FGRS for major depression, bipolar disorder, and suicide death were associated with lower odds of UDI relative to unambiguous suicide (OR = 0.91–0.95), while those for alcohol and drug use disorders, ADHD, and criminal behavior were associated with higher odds of UDI relative to unambiguous suicide (OR = 1.04–1.12). When the corresponding phenotypic registration status for these outcomes was included in a subsequent model, the associations were attenuated and of small magnitude, but many remained different from OR = 1. Conclusions: Aggregate genetic differences between unambiguous suicide decedents and UDI deaths are small, particularly when accounting for psychiatric comorbidity, but in some cases, statistically significant. These findings suggest that different analytic treatment of UDI deaths may be warranted depending on the research question. Replication in other samples, and using molecular genetic data, is necessary.
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| 35. |
- Edwards, Alexis C., et al.
(författare)
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Military service and risk of subsequent drug use disorders among Swedish men
- 2023
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Ingår i: Social Psychiatry and Psychiatric Epidemiology. - : Springer Science and Business Media LLC. - 0933-7954 .- 1433-9285. ; 58:7, s. 1039-1048
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Environmental factors contribute substantially to risk for drug use disorders (DUD). The current study applies multiple methods to empirically test whether military service is associated with subsequent DUD, as previous findings are inconsistent. Methods: Longitudinal Swedish national registry data on a cohort of male conscripts born 1972–1987 (maximum N = 485,900) were used to test the association between military service and subsequent registration for DUD. Cox proportional hazard models were used in preliminary analyses, followed by three methods that enable causal inference: propensity score models, co-relative models, and instrumental variable analysis. Results: Across all methods, military service was causally associated with lower risk of DUD. Hazard ratios ranged from HR = 0.43 (95% confidence intervals [CI] 0.37; 0.50) in the instrumental variable analysis to 0.77 (0.75; 0.79) in the multivariate propensity score matching analysis. This effect diminished across time. In the model including a propensity score, HRs remained below 1 across the observation period, while confidence intervals included 1 after ~ 11 years in the co-relative analysis and after ~ 21 years in the instrumental variable analysis. Conclusions: In this cohort of Swedish men, complementary methods indicate that military service conferred substantial but time-limited protection against subsequent DUD. The observed effect could be due to reduced opportunity for substance use during service, social cohesion experienced during and after service, and/or socioeconomic advantages among veterans. Additional research is necessary to clarify these protective mechanisms and determine how other environmental contexts can provide similar benefits.
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| 36. |
- Edwards, Alexis C., et al.
(författare)
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Oral contraceptive use and risk of suicidal behavior among young women
- 2022
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Ingår i: Psychological Medicine. - 0033-2917. ; 52:9, s. 1710-1717
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Tidskriftsartikel (refereegranskat)abstract
- Background. Oral contraceptive use has been previously associated with an increased risk of suicidal behavior in some, but not all, samples. The use of large, representative, longitudinally-assessed samples may clarify the nature of this potential association. Methods. We used Swedish national registries to identify women born between 1991 and 1995 (N = 216 702) and determine whether they retrieved prescriptions for oral contraceptives. We used Cox proportional hazards models to test the association between contraceptive use and first observed suicidal event (suicide attempt or death) from age 15 until the end of follow-up in 2014 (maximum age 22.4). We adjusted for covariates, including mental illness and parental history of suicide. Results. In a crude model, use of combination or progestin-only oral contraceptives was positively associated with suicidal behavior, with hazard ratios (HRs) of 1.73-2.78 after 1 month of use, and 1.25-1.82 after 1 year of use. Accounting for sociodemographic, parental, and psychiatric variables attenuated these associations, and risks declined with increasing duration of use: adjusted HRs ranged from 1.56 to 2.13 1 month beyond the initiation of use, and from 1.19 to 1.48 1 year after initiation of use. HRs were higher among women who ceased use during the observation period. Conclusions. Young women using oral contraceptives may be at increased risk of suicidal behavior, but risk declines with increased duration of use. Analysis of former users suggests that women susceptible to depression/anxiety are more likely to cease hormonal contraceptive use. Additional studies are necessary to determine whether the observed association is attributable to a causal mechanism.
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| 37. |
- Edwards, Alexis C., et al.
(författare)
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Shared genetic and environmental etiology between substance use disorders and suicidal behavior
- 2023
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Ingår i: Psychological Medicine. - 0033-2917. ; 53:6, s. 2380-2388
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Tidskriftsartikel (refereegranskat)abstract
- Background Previous studies have demonstrated substantial associations between substance use disorders (SUD) and suicidal behavior. The current study empirically assesses the extent to which shared genetic and/or environmental factors contribute to associations between alcohol use disorders (AUD) or drug use disorders (DUD) and suicidal behavior, including attempts and death. Methods The authors used Swedish national registry data, including medical, pharmacy, criminal, and death registrations, for a large cohort of twins, full siblings, and half siblings (N = 1 314 990) born 1960-1980 and followed through 2017. They conducted twin-sibling modeling of suicide attempt (SA) or suicide death (SD) with AUD and DUD to estimate genetic and environmental correlations between outcomes. Analyses were stratified by sex. Results Genetic correlations between SA and SUD ranged from rA = 0.60-0.88; corresponding shared environmental correlations were rC = 0.42-0.89 but accounted for little overall variance; and unique environmental correlations were rE = 0.42-0.57. When replacing attempt with SD, genetic and shared environmental correlations with AUD and DUD were comparable (rA = 0.48-0.72, rC = 0.92-1.00), but were attenuated for unique environmental factors (rE = -0.01 to 0.31). Conclusions These findings indicate that shared genetic and unique environmental factors contribute to comorbidity of suicidal behavior and SUD, in conjunction with previously reported causal associations. Thus, each outcome should be considered an indicator of risk for the others. Opportunities for joint prevention and intervention, while limited by the polygenic nature of these outcomes, may be feasible considering moderate environmental correlations between SA and SUD.
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| 38. |
- Edwards, Alexis C., et al.
(författare)
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Socioeconomic position indicators and risk of alcohol-related medical conditions : A national cohort study from Sweden
- 2024
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Ingår i: PLoS Medicine. - 1549-1277. ; 21:3
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Tidskriftsartikel (refereegranskat)abstract
- Background AAUlco:hPollecaosencsounmfirpmtitohnatcaollnhteraibduintegsletvoelesxacreersesprmesoernbtiedditcyorarnedctmly:ortality in part through the development of alcohol-related medical conditions (AMCs, including alcoholic cardiomyopathy, hepatitis, cirrhosis, etc.). The current study aimed to clarify the extent to which risk for these outcomes differs as a function of socioeconomic position (SEP), as discrepancies could lead to exacerbated health disparities. Methods and findings We used longitudinal Swedish national registries to estimate the individual and joint associations between 2 SEP indicators, educational attainment and income level, and risk of AMC based on International Classification of Diseases codes, while controlling for other sociodemographic covariates and psychiatric illness. We conducted Cox proportional hazards models in sex-stratified analyses (N = 1,162,679 females and N = 1,196,659 males), beginning observation at age 40 with follow-up through December 2018, death, or emigration. By the end of follow-up, 4,253 (0.37%) females and 11,183 (0.93%) males had received an AMC registration, corresponding to overall AMC incidence rates among females and males of 2.01 and 5.20, respectively. In sex-stratified models adjusted for birth year, marital status, region of origin, internalizing and externalizing disorder registrations, and alcohol use disorder (AUD) registration, lower educational attainment was associated with higher risk of AMC in both females (hazard ratios [HRs] = 1.40 to 2.46 for low- and mid-level educational attainment across 0 to 15 years of observation) and males (HRs = 1.13 to 1.48). Likewise, risk of AMC was increased for those with lower income levels (females: HRs = 1.10 to 5.86; males: HRs = 1.07 to 6.41). In secondary analyses, we further adjusted for aggregate familial risk of AUD by including family genetic risk scores for AUD (FGRSAUD), estimated using medical, pharmacy, and criminal registries in extended families, as covariates. While FGRSAUD were associated with risk of AMC in adjusted models (HR = 1.17 for females and HR = 1.21 for males), estimates for education and income level remained largely unchanged. Furthermore, FGRSAUD interacted with income level, but not education level, such that those at higher familial liability to AUD were more susceptible to the adverse effect of low income. Limitations of these analyses include the possibility of false negatives for psychiatric illness registrations, changes in income after age 40 that were not accounted for due to modeling restrictions, restriction to residents of a high-income country, and the inability to account for individual-level alcohol consumption using registry data. Conclusions Using comprehensive national registry data, these analyses demonstrate that individuals with lower levels of education and/or income are at higher risk of developing AMC. These associations persist even when accounting for a range of sociodemographic, psychiatric, and familial risk factors. Differences in risk could contribute to further health disparities, potentially warranting increased screening and prevention efforts in clinical and public health settings.
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| 39. |
- Edwards, Alexis C., et al.
(författare)
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Socioeconomic sequelae of drug abuse in a Swedish national cohort
- 2020
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Ingår i: Drug and Alcohol Dependence. - : Elsevier BV. - 0376-8716. ; 212
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Tidskriftsartikel (refereegranskat)abstract
- Background: Drug abuse is frequently associated with negative sequelae such as reduced socioeconomic functioning. The extent to which these associations are attributable to a causal role of the disorder versus confounding factors that increase risk for both drug abuse and negative socioeconomic outcomes is unclear. Methods: Drug abuse cases were identified using Swedish national medical, pharmacy, and criminal registers. Applying Cox proportional hazard models, we tested the association between drug abuse and four outcomes: early retirement, social assistance, unemployment, and income at age 50. We used co-relative models to determine whether familial confounding factors accounted for observed associations. Results: In models adjusted for birth year, education, and early onset externalizing behavior, drug abuse was strongly associated with early retirement (hazard ratios [HR] = 5.13–6.28), social assistance (HR = 6.74–7.89), and income at age 50 (beta = −0.19 to −0.12); it was more modestly associated with unemployment (HR = 1.05–1.20). For social assistance and income (both sexes), and early retirement (women only), a model in which the association was partly attributable to familial factors fit the data well; residual associations support a partially causal role of drug abuse. For unemployment and early retirement among men, there was little evidence of familial confounding. Conclusions: The negative socioeconomic sequelae of drug abuse are likely due in part to familial confounding factors in conjunction with a causal relationship and/or unmeasured non-familial confounders. Relative contributions from distinct mechanisms differed across socioeconomic outcomes, which could have implications for understanding the potential impact of prevention and intervention efforts.
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| 40. |
- Edwards, Alexis C., et al.
(författare)
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The role of substance use disorders in the transition from suicide attempt to suicide death : a record linkage study of a Swedish cohort
- 2024
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Ingår i: Psychological Medicine. - 1469-8978. ; 54:1, s. 90-97
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Suicidal behavior and substance use disorders (SUDs) are important public health concerns. Prior suicide attempts and SUDs are two of the most consistent predictors of suicide death, and clarifying the role of SUDs in the transition from suicide attempt to suicide death could inform prevention efforts. METHODS: We used national Swedish registry data to identify individuals born 1960-1985, with an index suicide attempt in 1997-2017 (N = 74 873; 46.7% female). We assessed risk of suicide death as a function of registration for a range of individual SUDs. We further examined whether the impact of SUDs varied as a function of (i) aggregate genetic liability to suicidal behavior, or (ii) age at index suicide attempt. RESULTS: In univariate models, risk of suicide death was higher among individuals with any SUD registration [hazard ratios (HRs) = 2.68-3.86]. In multivariate models, effects of specific SUDs were attenuated, but remained elevated for AUD (HR = 1.86 95% confidence intervals 1.68-2.05), opiates [HR = 1.58 (1.37-1.82)], sedatives [HR = 1.93 (1.70-2.18)], and multiple substances [HR = 2.09 (1.86-2.35)]. In secondary analyses, the effects of most, but not all, SUD were exacerbated by higher levels of genetic liability to suicide death, and among individuals who were younger at their index suicide attempt. CONCLUSIONS: In the presence of a strong predictor of suicide death - a prior attempt - substantial predictive power is still attributable to SUDs. Individuals with SUDs may warrant additional suicide screening and prevention efforts, particularly in the context of a family history of suicidal behavior or early onset of suicide attempt.
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