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1.	Docherty, Anna R, et al. (författare) GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors. 2023 Ingår i: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 180:10, s. 723-738 Tidskriftsartikel (refereegranskat)abstract Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures.This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses.Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors.This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.
2.	Mullins, Niamh, et al. (författare) Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors 2022 Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 91:3, s. 313-327 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders.METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors.RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged.CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.
3.	Salvatore, Jessica E., et al. (författare) Parental alcohol use disorder and offspring marital outcomes 2019 Ingår i: Addiction. - : Wiley. - 0965-2140. ; 114:1, s. 81-91 Tidskriftsartikel (refereegranskat)abstract Aims: We tested whether parental alcohol use disorder (AUD) predicted adult offspring's likelihood of marriage and marriage to an AUD-affected spouse; whether effects differed as a function of the sex or number of affected parents; and whether they were robust to confounders. Design: Sex-stratified Cox and logistic regression models. Setting: Sweden. Participants: A total of 1 171 070 individuals (51.40% male) born 1965–75. Measurements: Obtained from legal, medical and pharmacy registries. Predictor was parent AUD. Outcomes were marriage and spouse AUD. Adjustments included offspring birth year and AUD; and parental education, marriage, divorce, criminal behavior and drug abuse. Findings: Male and female offspring of AUD-affected parents were more likely to marry at younger ages (< 25), illustrative unadjusted hazard ratio (HR)age 20 = 1.22 (1.17, 1.28) and 1.34 (1.20, 1.39) and were less likely to marry at older ages (> 25), HRage 30 = 0.79 (0.78, 0.81) and 0.82 (0.81, 0.84). Parental AUD was associated with higher odds of having an affected spouse for males and females, odds ratio (OR) = 1.47 (1.38, 1.57) and 1.63 (1.56, 1.70). Effects were more pronounced for those with two versus one AUD-affected parent and adjustments attenuated effects negligibly. Daughters of affected mothers (versus fathers) were more likely to have AUD-affected husbands, OR = 1.68 (1.54, 1.84) versus 1.56 (1.48, 1.64), while there was no difference in sons. Conclusions: In Sweden, parental alcohol use disorder (AUD) is associated with a higher probability of marriage at younger ages, a lower probability of marriage at older ages and a higher likelihood of marriage to an affected spouse compared with no parental AUD. Most of these effects become stronger when the number of AUD-affected parents increases from one to two, and most effects hold after controlling for parents’ socio-economic status, marital history, other externalizing disorders and offspring's own AUD status. Daughters of affected mothers are more likely to have an affected spouse.
4.	Crump, Casey, et al. (författare) Comparative risk of suicide by specific substance use disorders : A national cohort study 2021 Ingår i: Journal of Psychiatric Research. - : Elsevier BV. - 0022-3956. ; 144, s. 247-254 Tidskriftsartikel (refereegranskat)abstract Substance use disorders (SUDs) are important risk factors for suicide, yet little is known about how suicide risks vary by specific SUDs. We examined these risks for the first time in a large general population to facilitate comparisons across SUDs. A national cohort study was conducted of all 6,947,191 adults in Sweden. SUDs (opioid, sedative/hypnotic, hallucinogen, cannabis, amphetamine, cocaine, and alcohol use disorders) were identified using inpatient, outpatient, and crime data, and suicide deaths using nationwide death data with follow-up during 2003–2016. Cox regression was used to compute hazard ratios (HRs) for suicide death while adjusting for sociodemographic factors and psychiatric, SUD, and somatic comorbidities. Co-sibling analyses assessed for confounding by unmeasured shared familial (genetic and/or environmental) factors. In 79.8 million person-years of follow-up, 15,616 (0.2%) suicide deaths were identified. All SUDs were associated with significantly increased risks, with HRs ranging from 12- to 26-fold and 2.5- to 6.4-fold before and after adjusting for covariates, respectively. After adjusting for all covariates, opioid use disorder was the strongest risk factor (HR, 6.39; 95% CI, 5.53–7.38) (P ≤ 0.002 compared with any other SUD), followed by sedative/hypnotic use disorder (4.62; 4.06–5.27) (P ≤ 0.009 compared with any other SUD except opioid or hallucinogen). Most associations persisted after controlling for shared familial factors, consistent with causal effects. In this large national cohort, all SUDs were associated with significantly increased risks of suicide death, especially opioid and sedative/hypnotic use disorders. These findings may improve risk stratification and inform interventions to prevent suicide in the highest-risk subgroups with SUDs.
5.	Crump, Casey, et al. (författare) Health care utilization prior to suicide in adults with drug use disorders 2021 Ingår i: Journal of Psychiatric Research. - : Elsevier BV. - 0022-3956. ; 135, s. 230-236 Tidskriftsartikel (refereegranskat)abstract Drug use disorders (DUD) are associated with psychiatric illness and increased risks of suicide. We examined health care utilization prior to suicide in adults with DUD, which may reveal opportunities to prevent suicide in this high-risk population. A national cohort study was conducted of all 6,947,191 adults in Sweden, including 166,682 (2.4%) with DUD, who were followed up for suicide during 2002–2015. A nested case-control design examined health care utilization among persons with DUD who died by suicide and 10:1 age- and sex-matched controls from the general population. In 86.7 million person-years of follow-up, 15,662 (0.2%) persons died by suicide, including 1946 (1.2%) persons with DUD. Unadjusted and adjusted relative risks of suicide associated with DUD were 11.03 (95% CI, 10.62–11.46) and 2.84 (2.68–3.00), respectively. 30.4% and 52.3% of DUD cases who died by suicide had a health care encounter within 2 weeks or 3 months before the index date, respectively, compared with 5.9% and 24.3% of controls (unadjusted prevalence ratio and difference, <2 weeks: 5.20 [95% CI, 4.76–5.67] and 24.6 percentage points [22.5–26.6]; <3 months: 2.15 [2.05–2.26] and 27.9 [25.6–30.2]). However, after adjusting for psychiatric comorbidities, these differences were much attenuated. Among DUD cases, 72.5% of last encounters within 2 weeks before suicide were in outpatient clinics, mostly for non-psychiatric diagnoses. In this large national cohort, suicide among adults with DUD was often shortly preceded by outpatient clinic encounters. Clinical encounters in these settings are important opportunities to identify suicidality and intervene accordingly in patients with DUD.
6.	Crump, Casey, et al. (författare) Healthcare utilisation prior to suicide in persons with alcohol use disorder : National cohort and nested case-control study 2020 Ingår i: British Journal of Psychiatry. - : Royal College of Psychiatrists. - 0007-1250 .- 1472-1465. ; 217:6, s. 710-716 Tidskriftsartikel (refereegranskat)abstract Background Alcohol use disorder (AUD) is common and associated with increased risk of suicide. Aims To examine healthcare utilisation prior to suicide in persons with AUD in a large population-based cohort, which may reveal opportunities for prevention. Method A national cohort study was conducted of 6 947 191 adults in Sweden in 2002, including 256 647 (3.7%) with AUD, with follow-up for suicide through 2015. A nested case-control design examined healthcare utilisation among people with AUD who died by suicide and 10:1 age- and gender-matched controls. Results In 86.7 million person-years of follow-up, 15 662 (0.2%) persons died by suicide, including 2601 (1.0%) with AUD. Unadjusted and adjusted relative risks for suicide associated with AUD were 8.15 (95% CI 7.86-8.46) and 2.22 (95% CI 2.11-2.34). Of the people with AUD who died by suicide, 39.7% and 75.6% had a healthcare encounter <2 weeks or <3 months before the index date respectively, compared with 6.3% and 25.4% of controls (adjusted prevalence ratio (PR) and difference (PD), <2 weeks: PR = 3.86, 95% CI 3.50-4.25, PD = 26.4, 95% CI 24.2-28.6; <3 months: PR = 2.03, 95% CI 1.94-2.12, PD = 34.9, 95% CI 32.6-37.1). AUD accounted for more healthcare encounters within 2 weeks of suicide among men than women (P = 0.01). Of last encounters, 48.1% were in primary care and 28.9% were in specialty out-patient clinics, mostly for non-psychiatric diagnoses. Conclusions Suicide among persons with AUD is often shortly preceded by healthcare encounters in primary care or specialty out-patient clinics. Encounters in these settings are important opportunities to identify active suicidality and intervene accordingly in patients with AUD.
7.	Crump, Casey, et al. (författare) Preterm birth, low fetal growth and risk of suicide in adulthood : A national cohort and co-sibling study 2021 Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 50:5, s. 1604-1614 Tidskriftsartikel (refereegranskat)abstract Background: Adverse perinatal exposures have been associated with psychiatric disorders and suicidal behaviours later in life. However, the independent associations of gestational age at birth or fetal growth with suicide death, potential sex-specific differences, and causality of these associations are unclear. Methods: A national cohort study was conducted of all 2 440 518 singletons born in Sweden during 1973-98 who survived to age 18 years, who were followed up through 2016. Cox regression was used to compute hazard ratios (HRs) for suicide death associated with gestational age at birth or fetal growth while mutually adjusting for these factors, sociodemographic characteristics and family history of suicide. Co-sibling analyses assessed the influence of unmeasured shared familial (genetic and/or environmental) factors. Results: In 31.2 million person-years of follow-up, 4470 (0.2%) deaths by suicide were identified. Early preterm birth (22-33 weeks) was associated with an increased risk of suicide among females [adjusted hazard ratio (HR), 1.97; 95% confidence interval CI), 1.29, 3.01; P = 0.002) but not males (0.90; 0.64, 1.28; P = 0.56), compared with full-term birth (39-41 weeks). Small for gestational age was associated with a modestly increased risk of suicide among females (adjusted HR, 1.27; 95% CI, 1.08, 1.51; P = 0.005) and males (1.14; 1.03, 1.27; P = 0.02). However, these associations were attenuated and non-significant after controlling for shared familial factors. Conclusions: In this large national cohort, preterm birth in females and low fetal growth in males and females were associated with increased risks of suicide death in adulthood. However, these associations appeared to be non-causal and related to shared genetic or prenatal environmental factors within families.
8.	Crump, Casey, et al. (författare) Response to Lao, Guan, Wang, et al. 2024 Ingår i: Journal of the National Cancer Institute. - 0027-8874. ; 116:5, s. 770-770 Tidskriftsartikel (refereegranskat)
9.	Crump, Casey, et al. (författare) Risks of alcohol and drug use disorders in prostate cancer survivors : a national cohort study 2023 Ingår i: JNCI CANCER SPECTRUM. - : Oxford University Press (OUP). - 2515-5091. ; 7:4 Tidskriftsartikel (refereegranskat)abstract Background: Prostate cancer (PC) survivors may potentially use substances to cope with psychological distress or poorly controlled physical symptoms. Little is known, however, about the long-term risks of alcohol use disorder (AUD) or drug use disorders in men with PC.Methods: A national cohort study was conducted in Sweden of 180 189 men diagnosed with PC between 1998 and 2017 and 1 801 890 age-matched population-based control men. AUD and drug use disorders were ascertained from nationwide records through 2018. Cox regression was used to compute hazard ratios (HRs) while adjusting for sociodemographic factors and prior psychiatric disorders. Subanalyses examined differences by PC treatment from 2005 to 2017.Results: Men with high-risk PC had increased risks of both AUD (adjusted HR = 1.44, 95% confidence interval [CI] = 1.33 to 1.57) and drug use disorders (adjusted HR = 1.93, 95% CI = 1.67 to 2.24). Their AUD risk was highest in the first year and was no longer significantly elevated 5 years after PC diagnosis, whereas their drug use disorders risk remained elevated 10 years after PC diagnosis (adjusted HR = 2.26, 95% CI = 1.45 to 3.52), particularly opioid use disorder (adjusted HR = 3.07, 95% CI = 1.61 to 5.84). Those treated only with androgen-deprivation therapy had the highest risks of AUD (adjusted HR = 1.91, 95% CI = 1.62 to 2.25) and drug use disorders (adjusted HR = 2.23, 95% CI = 1.70 to 2.92). Low- or intermediate-risk PC was associated with modestly increased risks of AUD (adjusted HR = 1.38, 95% CI = 1.30 to 1.46) and drug use disorders (adjusted HR = 1.19, 95% CI = 1.06 to 1.34).Conclusions: In this large cohort, men with PC had significantly increased risks of both AUD and drug use disorders, especially those with high-risk PC and treated only with androgen-deprivation therapy. PC survivors need long-term psychosocial support and timely detection and treatment of AUD and drug use disorders.
10.	Crump, Casey, et al. (författare) Risks of Depression and Suicide After Diagnosis With Heart Failure : A National Cohort Study 2022 Ingår i: JACC: Heart Failure. - : Elsevier BV. - 2213-1779. ; 10:11, s. 819-827 Tidskriftsartikel (refereegranskat)abstract Background: Heart failure (HF) has been associated with psychosocial distress, but other long-term mental health sequelae are unclear. Objectives: In this study, the authors sought to determine risks of major depression and suicide, susceptible time periods, and sex-specific differences after HF diagnosis in a large population-based cohort. Methods: A national cohort study was conducted of all 154,572 persons diagnosed with HF at ages 18-75 years during 2002-2017 in Sweden and 1,545,720 age- and sex-matched population-based control subjects who were followed up for major depression and suicide ascertained from nationwide inpatient, outpatient, and death records through 2018. Poisson regression was used to compute incidence rate ratios (IRRs) while adjusting for sociodemographic factors and comorbidities. Results: HF was associated with increased risks of major depression and death by suicide in both men and women, with highest risks in the first 3 months, then declining to modest risks at ≥12 months after HF diagnosis. Within 3 months after HF diagnosis, adjusted IRRs for new-onset major depression were 3.34 (95% CI: 3.04-3.68) in men and 2.78 (95% CI: 2.51-3.09) in women, and for suicide death were 4.47 (95% CI: 2.62-7.62) in men and 2.82 (95% CI: 1.11-7.12) in women. These risks were elevated regardless of age at HF diagnosis. HF was associated with significantly more depression cases in women (P < 0.001). Conclusions: In this large national cohort, HF was associated with substantially increased risks of depression and suicide in men and women, with highest risks occurring within 3 months after HF diagnosis. Men and women with HF need timely detection and treatment of depression and suicidality.
11.	Crump, Casey, et al. (författare) Risks of depression, anxiety, and suicide in partners of men with prostate cancer : a national cohort study 2024 Ingår i: Journal of the National Cancer Institute. - 0027-8874. ; 116:5, s. 745-752 Tidskriftsartikel (refereegranskat)abstract Background: A diagnosis of prostate cancer (PC) may cause psychosocial distress not only in a man but also in his intimate partner. However, long-term risks of depression, anxiety, or suicide in partners of men with PC are largely unknown. Methods: A national cohort study was conducted of 121 530 partners of men diagnosed with PC during 1998-2017 and 1 093 304 population-based controls in Sweden. Major depression, anxiety disorder, and suicide death were ascertained through 2018. Cox regression was used to compute hazard ratios (HRs) while adjusting for sociodemographic factors. Results: Partners of men with high-risk PC had increased risks of major depression (adjusted HR ¼ 1.34, 95% confidence interval [CI] ¼ 1.30 to 1.39) and anxiety disorder (adjusted HR ¼ 1.25, 95% CI ¼ 1.20 to 1.30), which remained elevated 10 or more years later. Suicide death was increased in partners of men with distant metastases (adjusted HR ¼ 2.38, 95% CI ¼ 1.08 to 5.22) but not other high-risk PC (adjusted HR ¼1.14, 95% CI ¼ 0.70 to 1.88). Among partners of men with high-risk PC, risks of major depression and anxiety disorder were highest among those 80 years of age or older (adjusted HR ¼ 1.73; 95% CI ¼ 1.53 to 1.96; adjusted HR ¼ 1.70, 95% CI ¼ 1.47 to 1.96, respectively), whereas suicide death was highest among those younger than 60 years of age (adjusted HR ¼ 7.55, 95% CI ¼ 2.20 to 25.89). In contrast, partners of men with low- or intermediate-risk PC had modestly or no increased risks of these outcomes. Conclusions: In this large cohort, partners of men with high-risk PC had increased risks of major depression and anxiety disorder, which persisted for 10 or more years. Suicide death was increased 2-fold in partners of men with distant metastases. Partners as well as men with PC need psychosocial support and close follow-up for psychosocial distress.
12.	Dahlman, Disa, et al. (författare) Socioeconomic correlates of incident and fatal opioid overdose among Swedish people with opioid use disorder 2021 Ingår i: Substance Abuse: Treatment, Prevention, and Policy. - : Springer Science and Business Media LLC. - 1747-597X. ; 16:1 Tidskriftsartikel (refereegranskat)abstract Background: Opioid overdose (OD) and opioid OD death are major health threats to people with opioid use disorder (OUD). Socioeconomic factors are underexplored potential determinants of opioid OD. In this study, we assessed socioeconomic and other factors and their associations with incident and fatal opioid OD, in a cohort consisting of 22,079 individuals with OUD. Methods: We performed a retrospective, longitudinal study based on Swedish national register data for the period January 2005–December 2017. We used Cox proportional hazard models to investigate the risk of incident and fatal opioid OD as a function of several individual, parental and neighborhood covariates. Results: Univariate analysis showed that several covariates were associated with incident and fatal opioid OD. In the multivariate analysis, incident opioid OD was associated with educational attainment (Hazard ratio [HR] 0.96; 95% confidence interval [CI] 0.94–0.97), having received social welfare (HR 1.31; 95% CI 1.22–1.39), and criminal conviction (HR 1.53; 95% CI 1.42–1.65). Fatal opioid OD was also associated with criminal conviction (HR 1.93; 95% CI 1.61–2.32). Conclusion: Individuals with low education and receipt of social welfare had higher risks of incident opioid OD and individuals with criminal conviction were identified as a risk group for both incident and fatal opioid OD. Our findings should raise attention among health prevention policy makers in general, and among decision-makers within the criminal justice system and social services in particular.
13.	Edwards, Alexis C., et al. (författare) Alcohol use disorder and non-fatal suicide attempt : findings from a Swedish National Cohort Study 2022 Ingår i: Addiction. - : Wiley. - 0965-2140 .- 1360-0443. ; 117:1, s. 96-105 Tidskriftsartikel (refereegranskat)abstract Background and Aims: Alcohol use disorder (AUD) is associated with increased risk of non-fatal suicide attempt. We aimed to measure the strength and mechanistic nature of the association between AUD and increased suicide attempt and determine any causal pathways and/or shared risk factors. Design: We used Cox proportional hazards models in population-level and co-relative analyses to evaluate the risk of first non-fatal suicide attempt as a function of previous AUD. Setting and Participants: We used continuously updated longitudinal nationwide Swedish registry data on native Swedes born from 1950 to 1970 (n = 2 229 619) and followed from age 15 until 2012. Measurements: AUD and suicide attempt were identified using International Classification of Diseases (ICD)-8, ICD-9, and ICD-10 codes. AUD was also identified using pharmacy and criminal records. Genetic and family environmental risks were derived based on relatedness via the Multi-Generation Register and shared residency via the Population and Housing Census and the Total Population Register. Findings: AUD was robustly associated with suicide attempt in crude models (hazard ratio [HR] = 15.24 [95% CI: 14.92, 15.56]). In models adjusted for sociodemographic factors and psychiatric comorbidity, the association was attenuated: for women, HRs declined gradually across time, ranging from 5.55 (3.72, 8.29) during the observation period that ranged from age 15 to 19 years to 1.77 (1.65, 1.90) at age 40 or older. For men, the corresponding figures were 6.12 (4.07, 9.19) and 1.83 (1.72, 1.94); in contrast to women, risk of suicide attempt among men increased from age 15 to 29 before declining. In co-relative models, a residual association remained, consistent with a causal path from AUD to suicide attempt. Conclusions: In Sweden, alcohol use disorder appears to be an important predictor of suicide attempt even in the context of other psychiatric disorders. The observed association is likely the result of features that jointly impact risk of alcohol use disorder and suicide attempts (genetic liability, psychiatric illness, and childhood stressors) and a potentially causal pathway, acting independently or in conjunction with one another.
14.	Edwards, Alexis C., et al. (författare) Alcohol use disorder and risk of specific methods of suicide death in a national cohort 2024 Ingår i: Acta Psychiatrica Scandinavica. - 0001-690X. Tidskriftsartikel (refereegranskat)abstract Introduction: Alcohol use disorder (AUD) is among the strongest correlates of suicide death, but it is unclear whether AUD status is differentially associated with risk of suicide by particular methods. Methods: The authors used competing risks models to evaluate the association between AUD status and risk of suicide by poisoning, suffocation, drowning, firearm, instruments, jumping, or other means in a large Swedish cohort born 1932–1995 (total N = 6,581,827; 48.8% female). Data were derived from Swedish national registers, including the Cause of Death Register and a range of medical registers. Results: After adjusting for sociodemographic factors and familial liability to suicidal behavior, AUD was positively associated with risk of suicide for each method evaluated (cumulative incidence differences: 0.006–1.040 for females, 0.046–0.680 for males), except the association with firearm suicide in females. AUD was most strongly associated with risk of suicide by poisoning. Sex differences in the effects of AUD and family liability were observed for some, but not all, methods. Furthermore, high familial liability for suicidal behavior exacerbated AUD's impact on risk for suicide by poisoning (both sexes) and suffocation and jumping (males only), while the inverse interaction was observed for firearm suicide (males only). Conclusions: AUD increases risk of suicide by all methods examined and is particularly potent with respect to risk of suicide by poisoning. Differences in risk related to sex and familial liability to suicidal behavior underscore AUD's nuanced role in suicide risk. Future research should investigate targeted means restriction effectiveness among persons with AUD.
15.	Edwards, Alexis C., et al. (författare) Alcohol Use Disorder and Risk of Suicide in a Swedish Population-Based Cohort 2020 Ingår i: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 177:7, s. 627-634 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: The authors examined the association between alcohol use disorder (AUD) and risk of suicide, before and after accounting for psychiatric comorbidity, and assessed the extent to which the observed association is due to a potentially causal mechanism or genetic and familial environmental confounding factors that increase risk for both. METHODS: Longitudinal population-wide Swedish medical, criminal, and pharmacy registries were used to evaluate the risk of death by suicide as a function of AUD history. Analyses employed prospective cohort and co-relative designs, including data on 2,229,880 native Swedes born between 1950 and 1970 and observed from age 15 until 2012. RESULTS: The lifetime rate of suicide during the observation period was 3.54% for women and 3.94% for men with AUD, compared with 0.29% and 0.76% of women and men, respectively, without AUD. In adjusted analyses, AUD remained robustly associated with suicide: hazard ratios across observation periods ranged from 2.61 to 128.0 among women and from 2.44 to 28.0 among men. Co-relative analyses indicated that familial confounding accounted for some, but not all, of the observed association. A substantial and potentially causal relationship remained after accounting for a history of other psychiatric diagnoses. CONCLUSIONS: AUD is a potent risk factor for suicide, with a substantial association persisting after accounting for confounding factors. These findings underscore the impact of AUD on suicide risk, even in the context of other mental illness, and implicate the time frame shortly after a medical or criminal AUD registration as critical for efforts to reduce alcohol-related suicide.
16.	Edwards, Alexis C., et al. (författare) Associations between Divorce and Onset of Drug Abuse in a Swedish National Sample 2018 Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 187:5, s. 1010-1018 Tidskriftsartikel (refereegranskat)abstract Rates of drug abuse are higher among divorced individuals than among those who are married, but it is not clear whether divorce itself is a risk factor for drug abuse or whether the observed association is confounded by other factors. We examined the association between divorce and onset of drug abuse in a population-based Swedish cohort born during 1965-1975 (n = 651,092) using Cox proportional hazards methods, with marital status as a time-varying covariate. Potential confounders (e.g., demographics, adolescent deviance, and family history of drug abuse) were included as covariates. Parallel analyses were conducted for widowhood and drug-Abuse onset. In models with adjustments, divorce was associated with a substantial increase in risk of drug-Abuse onset in both sexes (hazard ratios > 5). Co-relative analyses (among biological relatives) were consistent with a partially causal role of divorce on drug-Abuse onset. Widowhood also increased risk of drug-Abuse onset, although to a lesser extent. Divorce is a potent risk factor for onset of drug abuse, even after adjusting for deviant behavior in adolescence and family history of drug abuse. The somewhat less-pronounced association with widowhood, particularly among men, suggests that the magnitude of association between divorce and drug abuse may not be generalizable to the end of a relationship.
17.	Edwards, Alexis C., et al. (författare) Divorce and risk of suicide attempt : A Swedish national study Ingår i: Psychological Medicine. - 0033-2917. Tidskriftsartikel (refereegranskat)abstract Background Prior research has reported an association between divorce and suicide attempt. We aimed to clarify this complex relationship, considering sex differences, temporal factors, and underlying etiologic pathways. Methods We used Swedish longitudinal national registry data for a cohort born 1960-1990 that was registered as married between 1978 and 2018 (N = 1 601 075). We used Cox proportional hazards models to estimate the association between divorce and suicide attempt. To assess whether observed associations were attributable to familial confounders or potentially causal in nature, we conducted co-relative analyses. Results In the overall sample and in sex-stratified analyses, divorce was associated with increased risk of suicide attempt (adjusted hazard ratios [HRs] 1.66-1.77). Risk was highest in the year immediately following divorce (HRs 2.20-2.91) and declined thereafter, but remained elevated 5 or more years later (HRs 1.41-1.51). Divorcees from shorter marriages were at higher risk for suicide attempt than those from longer marriages (HRs 3.33-3.40 and 1.20-1.36, respectively). In general, HRs were higher for divorced females than for divorced males. Co-relative analyses suggested that familial confounders and a causal pathway contribute to the observed associations. Conclusions The association between divorce and risk of suicide attempt is complex, varying as a function of sex and time-related variables. Given evidence that the observed association is due in part to a causal pathway from divorce to suicide attempt, intervention or prevention efforts, such as behavioral therapy, could be most effective early in the divorce process, and in particular among females and those whose marriages were of short duration.
18.	Edwards, Alexis C., et al. (författare) Early environmental influences contribute to covariation between internalizing symptoms and alcohol intoxication frequency across adolescence 2011 Ingår i: Addictive Behaviours. - Oxford, United Kingdom : Elsevier. - 0306-4603 .- 1873-6327. ; 36:3, s. 175-182 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.
19.	Edwards, Alexis C., et al. (författare) Exposure to alcohol outlets and risk of suicidal behavior in a Swedish cohort of young adults 2023 Ingår i: Alcoholism: Clinical and Experimental Research. - 0145-6008. ; 47:5, s. 930-939 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.
20.	Edwards, Alexis C., et al. (författare) Genetic and environmental influences on the progression from alcohol use disorder to alcohol-related medical conditions 2021 Ingår i: Alcoholism: Clinical and Experimental Research. - : Wiley. - 0145-6008 .- 1530-0277. ; 45:12, s. 2528-2535 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.
21.	Edwards, Alexis C., et al. (författare) Genetic differences between suicide deaths and deaths of undetermined intent 2023 Ingår i: Suicide and Life-Threatening Behavior. - : Wiley. - 0363-0234 .- 1943-278X. ; 53:1, s. 100-109 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.
22.	Edwards, Alexis C., et al. (författare) Long-term Risks of Depression and Suicide Among Men with Prostate Cancer : A National Cohort Study 2023 Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 84:3, s. 263-272 Tidskriftsartikel (refereegranskat)abstract Background: A diagnosis of prostate cancer (PC) may cause psychosocial distress that worsens quality of life; however, long-term mental health outcomes are unclear.Objective: To determine the long-term risks of major depression and death by suicide in a large population-based cohort. Design, setting, and participants: This was a national cohort study of 180 189 men diagnosed with PC during 1998-2017 and 1 801 890 age-matched, population-based, control men in Sweden.Outcome measurements and statistical analysis: Major depression and death by suicide were ascertained from nationwide outpatient, inpatient, and death records up to 2018. Cox regression was used to compute hazard ratios (HRs) adjusted for sociodemographic factors and comorbidities. Subanalyses assessed differences by PC treatment during 2005-2017.Results and limitations: Men diagnosed with high-risk PC had higher relative rates of major depression (adjusted HR [aHR] 1.82, 95% confidence interval [CI] 1.75-1.89) and death by suicide (aHR 2.43, 95% CI 2.01-2.95). These associations persisted for >= 10 yr after PC diagnosis. The relative increase in major depression was lower among those treated with radiation (aHR 1.44, 95% CI 1.31-1.57) or surgery (aHR 1.60, 95% CI 1.311.95) in comparison to androgen deprivation therapy (ADT) alone (aHR 2.02, 95% CI 1.89-2.16), whereas the relative rate of suicide death was higher only among those treated solely with ADT (aHR 2.83, 95% CI 1.80-4.43). By contrast, men with low- or intermediate-risk PC had a modestly higher relative rate of major depression (aHR 1.19, 95% CI 1.16-1.23) and higher relative rate of suicide death at 3-12 mo after PC diagnosis (aHR 1.88, 95% CI 1.11-3.18) but not across the entire follow-up period aHR 1.02, 95% CI 0.84-1.25). This study was limited to Sweden and will need replication in other populations.Conclusions: In this large cohort, high-risk PC was associated with substantially higher relative rates of major depression and death by suicide, which persisted for >= 10 yr after PC diagnosis. PC survivors need close follow-up for timely detection and treatment of psychosocial distress. Patient summary: In a large Swedish population, men with aggressive prostate cancer had higher long-term relative rates of depression and suicide. (c) 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.
23.	Edwards, Alexis C., et al. (författare) Military service and risk of subsequent drug use disorders among Swedish men 2023 Ingår i: Social Psychiatry and Psychiatric Epidemiology. - : Springer Science and Business Media LLC. - 0933-7954 .- 1433-9285. ; 58:7, s. 1039-1048 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.
24.	Edwards, Alexis C., et al. (författare) Oral contraceptive use and risk of suicidal behavior among young women 2022 Ingår i: Psychological Medicine. - 0033-2917. ; 52:9, s. 1710-1717 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.
25.	Edwards, Alexis C., et al. (författare) Protective Effects of Pregnancy on Risk of Alcohol Use Disorder 2019 Ingår i: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 176:2, s. 138-145 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE:: The authors sought to clarify the etiology of the association between pregnancy and reduced risk of alcohol use disorder. METHODS:: The authors used data from longitudinal population-wide Swedish medical, pharmacy, and criminal registries to evaluate whether rates of alcohol use disorder are lower during pregnancy. They compared pregnant women born between 1975 and 1992 (N=322,029) with matched population controls, with female relatives discordant for pregnancy, and with pre- and postpregnancy periods within individuals. They further compared rates of alcohol use disorder between pregnant women and their partners. RESULTS:: Pregnancy was inversely associated with alcohol use disorder across all analyses (odds ratios, 0.17-0.32). In co-relative analyses, the strength of the association increased among more closely related individuals. Within individuals, rates of alcohol use disorder were substantially decreased during pregnancy relative to the prepregnancy period (odds ratios, 0.25-0.26), and they remained reduced during postpartum periods (odds ratios, 0.23-0.31). Results were similar for second pregnancies (odds ratio, 0.23). The partners of pregnant women also exhibited reductions in alcohol use disorder (odds ratio, 0.45). Among women who became pregnant at earlier ages and those with a history of criminal behavior, the negative association between pregnancy and alcohol use disorder was especially pronounced, but no moderation was observed for a personal or maternal parental history of alcohol use disorder. CONCLUSIONS:: The findings suggest that pregnancy plays a critical, and likely causal, motivational role in reducing alcohol use disorder risk among women and, to a lesser extent, their partners. These results extend our understanding of the relationship between pregnancy and alcohol use, demonstrating that even a severe condition such as alcohol use disorder is subject to the protective effects of pregnancy.

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