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Sökning: WFRF:(Sundquist S)

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3.
  • Baekkeskov, S, et al. (författare)
  • Antibodies to a 64,000 Mr human islet cell antigen precede the clinical onset of insulin-dependent diabetes
  • 1987
  • Ingår i: Journal of Clinical Investigation. - 0021-9738. ; 79:3, s. 34-926
  • Tidskriftsartikel (refereegranskat)abstract
    • Antibodies in sera from newly diagnosed insulin-dependent diabetes mellitus (IDDM) patients are directed to a human islet cell protein of relative molecular mass (Mr) 64,000. Since IDDM seems to develop after a prodromal period of beta-cell autoimmunity, this study has examined whether 64,000 Mr antibodies could be detected in 14 individuals who subsequently developed IDDM and five first degree relatives who have indications of altered beta-cell function. Sera were screened by immunoprecipitation on total detergent lysates of human islets and positive sera retested on membrane protein preparations. Antibodies to the 64,000 Mr membrane protein were consistently detected in 11/14 IDDM patients, and in all 5 first degree relatives. 10 IDDM patients were already positive in the first samples, obtained 4-91 mo before the clinical onset of IDDM, whereas 1 patient progressed to a high 64,000 Mr immunoreactivity, at a time where a commencement of a decline in beta-cell function was detected. 64,000 Mr antibodies were detected before islet cell cytoplasmic antibodies (ICCA) in two patients. In the control groups of 21 healthy individuals, 36 patients with diseases of the thyroid and 5 SLE patients, the 64,000 Mr antibodies were detected in only one individual, who was a healthy sibling to an IDDM patient. These results suggest that antibodies against the Mr 64,000 human islet protein are an early marker of beta-cell autoimmunity and may be useful to predict a later development of IDDM.
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  • 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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  • Kendler, Kenneth S., et al. (författare)
  • Risk for psychiatric and substance use disorders as a function of transitions in Sweden's public educational system : a national study
  • 2024
  • Ingår i: Psychological Medicine. - 1469-8978. ; 54:1, s. 117-124
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: To clarify, in a national sample, associations between risk for seven psychiatric and substance use disorders and five key transitions in Sweden's public educational system. METHODS: Swedish-born individuals (1972-1995, N = 1 997 910) were followed through 12-31-2018, at mean age 34.9. We predicted, from these educational transitions, risk for major depression (MD), obsessive-compulsive disorder (OCD), bipolar disorder (BD), schizophrenia (SZ), anorexia nervosa (AN), alcohol use disorder (AUD), and drug use disorder (DUD), assessed from Swedish national registers, by Cox regression, censoring individuals with onsets ⩽17. We also predicted risk from the deviation of grades from family-genetic expectations (deviation 1) and from changes in grades from ages 16 to 19 (deviation 2). RESULTS: We observed four major risk patterns across transitions in our disorders: (i) MD and BD, (ii) OCD and SZ, (iii) AUD and DUD, and (iv) AN. Failing early educational transitions had the greatest impact on risk for OCD and SZ while for other disorders, not progressing from basic to upper high school had the largest effect. Completing vocational v. college-prep upper high school was strongly associated with risk for AUD and DUD, had little relation with MD, OCD, BD, and SZ risk, and was protective for AN. Deviation 1 predicted risk most strongly for SZ, AN, and MD. Deviation 2 predicted risk most strongly for SZ, AUD, and DUD. CONCLUSIONS: The pattern of educational transitions and within family and within person development deviations are strongly and relatively specifically associated with future risk for seven psychiatric and substance-use disorders.
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  • Kendler, K. S., et al. (författare)
  • The joint impact of cognitive performance in adolescence and familial cognitive aptitude on risk for major psychiatric disorders : a delineation of four potential pathways to illness
  • 2018
  • Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 23, s. 1076-1083
  • Tidskriftsartikel (refereegranskat)abstract
    • How do joint measures of premorbid cognitive ability and familial cognitive aptitude (FCA) reflect risk for a diversity of psychiatric and substance use disorders? To address this question, we examined, using Cox models, the predictive effects of school achievement (SA) measured at age 16 and FCA—assessed from SA in siblings and cousins, and educational attainment in parents—on risk for 12 major psychiatric syndromes in 1 140 608 Swedes born 1972–1990. Four developmental patterns emerged. In the first, risk was predicted jointly by low levels of SA and high levels of FCA—that is a level of SA lower than would be predicted from the FCA. This pattern was strongest in autism spectrum disorders and schizophrenia, and weakest in bipolar illness. In these disorders, a pathologic process seems to have caused cognitive functioning to fall substantially short of familial potential. In the second pattern, seen in the internalizing conditions of major depression and anxiety disorders, risk was associated with low SA but was unrelated to FCA. Externalizing disorders—drug abuse and alcohol use disorders—demonstrated the third pattern, in which risk was predicted jointly by low SA and low FCA. The fourth pattern, seen in eating disorders, was directly opposite of that observed in externalizing disorders with risk associated with high SA and high FCA. When measured together, adolescent cognitive ability and FCA identified four developmental patterns leading to diverse psychiatric disorders. The value of cognitive assessments in psychiatric research can be substantially increased by also evaluating familial cognitive potential.Molecular Psychiatry advance online publication, 18 April 2017; doi:10.1038/mp.2017.78.
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  • Kendler, Kenneth S., et al. (författare)
  • The protective effect of pregnancy on risk for drug abuse : A population, Co-relative, Co-spouse, and within-individual analysis
  • 2017
  • Ingår i: American Journal of Psychiatry. - : American Psychiatric Association Publishing. - 0002-953X .- 1535-7228. ; 174:10, s. 954-962
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The authors sought to determine whether pregnancy is an intrinsic motivator for cessation of drug abuse. Method: The authors conducted prospective cohort, corelative, co-spouse, and within-person analyses of registration for drug abuse during pregnancy among Swedish women born between 1980 and 1990 who gave birth between ages 20 and 35 (N=149,512). Drug abuse was assessed from medical, criminal, and pharmacy registries. Results: In the population, rates of drug abuse were lower during pregnancy (unadjusted odds ratio=0.67,95%CI=0.60, 0.74). Compared with population results, the negative association between pregnancy and drug abuse was moderately stronger in cousins (odds ratio=0.49,95%CI=0.39, 0.62) and substantially stronger in siblings (odds ratio=0.35, 95% CI=0.24, 0.51) discordant for pregnancy. The estimated odds ratio for drug abuse in pregnancy-discordant monozygotic twins was even stronger, at 0.17 (95% CI=0.10, 0.31). Within individuals, the odds ratio for drug abuse while pregnant compared with an equivalent prepregnancy interval was similar to that seen in pregnancy-discordant monozygotic twins, at 0.22 (95% CI=0.19, 0.26). Compared with cohabiting fathers, mothers had a greater reduction in risk for drug abuse during pregnancy (odds ratio=0.40, 95% CI=0.34, 0.47). Pregnancy was more protective in women with low parental education and without a cohabiting, actively drug-abusing father. Compared with prepregnancy baseline, withinindividual analyses indicate that risk for drug abuse is also substantially reduced in the postpartum period, for example, the odds ratio for postpartum days 0-242 was 0.13 (95% CI=0.11, 0.16). Conclusions: Risk for drug abuse in women is substantially reduced during pregnancy. Multiple analyses suggest that this association is largely causal, suggesting that pregnancy is indeed a strong intrinsic motivator for drug abuse cessation. Similar strong protective effects may be present in the immediate postpartum period. Our results have implications for our etiologic models of drug abuse and especially for contingency management programs seeking to reduce drug abuse risk.
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  • Long, E. C., et al. (författare)
  • The role of parent and offspring sex on risk for externalizing psychopathology in offspring with parental alcohol use disorder : a national Swedish study
  • 2018
  • Ingår i: Social Psychiatry and Psychiatric Epidemiology. - : Springer Science and Business Media LLC. - 0933-7954 .- 1433-9285. ; 53:12, s. 1381-1389
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: The substantial literature showing that offspring of parents with alcohol use disorder (AUD) is at increased risk for externalizing psychopathology rarely examines the differential effects of parental and offspring sex. This literature also has other important limitations, such as modest sample sizes and use of unrepresentative samples. Using a large, nationwide Swedish sample, we aim to investigate the roles of parental and offspring sex in externalizing psychopathology among offspring with parental AUD. Methods: AUD diagnosis and externalizing measures were obtained from national registries. Associations between outcomes and parental AUD were examined using logistic regressions. Parental and offspring sex effects were examined with interaction terms. Results: Risks for externalizing disorders were increased in sons and daughters with parental AUD, with significant differences between sons and daughters for criminal behavior; maternal AUD had a greater impact than paternal AUD (regardless of offspring sex), but having two parents with AUD increased risk for all outcomes substantially more than having one parent; and maternal AUD increased risk of drug abuse for daughters more than sons, while paternal AUD increased risk of AUD and criminal behavior for sons more than daughters. Conclusions: Offspring of parents with AUD are at increased risk for externalizing psychopathology. Maternal and paternal AUD differentially affected sons’ vs. daughters’ risks for AUD, drug abuse, and criminal behavior. The transmission of psychopathology within the externalizing spectrum appears to have sex-specific elements.
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  • Lönn, Sara L., et al. (författare)
  • The Impact of the Good Behavior Game on Risk for Drug Use Disorder in an Agent-Based Model of Southern Sweden
  • 2023
  • Ingår i: Journal of Studies on Alcohol and Drugs. - 1937-1888. ; 84:6, s. 863-873
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Drug use disorder (DUD) is aworldwide problem, and strategies to reduce its incidence are central to decreasing its burden. This investigation seeks to provide aproof of concept for the ability of agent-based modeling to predict the impact of the introduction of an effective school-based intervention, the Good Behavior Game (GBG), on reducing DUD in Scania, Sweden, primarilythrough increasing school achievement. Method: We modified anexisting agent-based simulation model of opioid use disorder to represent DUD inScania County, southernSweden. The model represents every individual in the population and is calibrated with the linked individual data from multiple sources including demographics, education, medical care, and criminal history. Risks for developing DUD were estimated from the population in Scania. Scenarios estimated the impact of introducing the GBG in schools located in disadvantaged areas. Results: The model accurately reflected the growth of DUD in Scania over amultiyear period and reproduced the levels of affected individuals in various socioeconomic strata over time. The GBG was estimated to improve school achievement and lower DUD registrations over time in males residing in disadvantaged areas by 10%, reflecting adecrease of 540 cases of DUD. Effects were considerably smaller in females. Conclusions: This work provides sup-portfor the impact of improvingschool achievement on long-termrisks of developing DUD. Italso demonstrated the value of using simulation modeling calibrated with data from areal population to estimate the impact of an intervention applied at apopulation level.
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  • Amstadter, Ananda B., et al. (författare)
  • Post-traumatic stress disorder and drug use disorder : examination of aetiological models in a Swedish population-based cohort
  • 2023
  • Ingår i: European Journal of Psychotraumatology. - 2000-8066. ; 14:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: There are two primary phenotypic models of comorbidity between post-traumatic stress disorder (PTSD) and drug use disorder (DUD), i.e. self-medication (PTSD precedes and causes DUD) and susceptibility (DUD precedes and causes PTSD). We sought to clarify the longitudinal relationship between PTSD and DUD, while examining sex differences. Method: We used approximately 23 years of longitudinal data from Swedish population registries to conduct two complementary statistical models: Cox proportional hazard models (N ≈ 1.5 million) and a cross-lagged panel model (N ≈ 3.8 million). Results: Cox proportional hazards models, adjusting for cohort and socioeconomic status, found strong evidence for the self-medication hypothesis, as PTSD predicted increased risk for DUD among both women [hazard ratio (HR) = 5.34, 95% confidence interval (CI) 5.18, 5.51] and men (HR = 3.65, 95% CI 3.54, 3.77), and moreover, that the PTSD to DUD association was significantly higher among women (interaction term 0.68, 95% CI 0.65, 0.71). The results of the susceptibility model were significant, but not as strong as the self-medication model. DUD predicted risk for PTSD among both women (HR = 2.43, 95% CI 2.38, 2.50) and men (HR = 2.55, 95% CI 2.50, 2.60), and HR was significantly higher in men (interaction term 1.05, 95% CI 1.02, 1.08). Investigating the pathways simultaneously in the cross-lagged model yielded support for both pathways of risk. The cross-paths instantiating the susceptibility model (0.10–0.22 in females, 0.12–0.19 in males) were mostly larger than those capturing the self-medication model (0.01–0.16 in females, 0.04–0.22 in males). Conclusions: We demonstrate that the relationship between PTSD and DUD is bidirectional, with evidence that future research should prioritize examining specific pathways of risk that may differ between men and women.
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  • Amstadter, Ananda B., et al. (författare)
  • Testing Phenotypic Models of Posttraumatic Stress Disorder and Alcohol Use Disorder Comorbidity Using Longitudinal Registry Data
  • 2023
  • Ingår i: Journal of Studies on Alcohol and Drugs. - : Alcohol Research Documentation, Inc.. - 1937-1888 .- 1938-4114. ; 84:3, s. 378-388
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Two predominant phenotypic models of causality exist to explain the high co-occurrence of posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD): the self-medication and susceptibility models. Population-based longitudinal studies that simultaneously examine both models are needed. Thus, the goal of the pres-ent study is to test these models using the Swedish National Registries. Method: Registries were used to conduct longitudinal Cox proportional hazard models (n ≈ 1.5 million) and cross-lagged panel models (N ≈ 3.8 million) with follow-up periods of ~23 years. Results: Covarying for cohort and socioeconomic status, Cox proportional hazards model results found strong support for the self-medication model. Results showed that PTSD predicted increased risk for AUD among both men (HR = 4.58 [4.42, 4.74]) and women (HR = 4.14 [3.99, 4.30]), significantly more so for men (interaction HR = 1.11 [1.05, 1.16]). Support was also found for the susceptibility model, although the effects were lower in magnitude than those for the self-medication model. AUD increased risk for PTSD among men (HR = 2.53 [2.47, 2.60]) and women (HR = 2.06 [2.01, 2.12]), and significantly more so for men (interaction term HR = 1.23 [1.18, 1.28]). Cross-lagged model results of simultaneously testing both models found support for bidirectionality. The PTSD-to-AUD paths and the AUD-to-PTSD paths were of modest effect for men and women. Conclusions: The results from both complementary statistical approaches demonstrate that the models of comorbidity are not mutually exclusive. Although the Cox model results evidenced more support for the self-medication pathway, the cross-lagged model results suggest that the prospective relationships between these disorders are nuanced across development. (J. Stud. Alcohol Drugs, 84, 378–388, 2023).
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  • Calling, Susanna, et al. (författare)
  • Coronary heart disease in mothers and fathers of adult children with alcohol use disorders
  • 2021
  • Ingår i: Addiction. - : Wiley. - 0965-2140 .- 1360-0443. ; 116:12, s. 3390-3397
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and aim: Having a family member with an alcohol use disorder (AUD) may negatively affect a person's health. Our aim was to study the long-term risk of coronary heart disease (CHD) in parents who have an offspring with AUD. Design: Cohort study with Cox regression models and co-sibling analyses. Setting: Sweden. Participants: From population registers, we selected all parent-offspring pairs in which the parent was born in Sweden between 1945 and 1965. Measurements: Baseline was set when the offspring was 15 years old and AUD was assessed from medical and criminal registers. The parents were followed for CHD during a mean follow-up of 18 years. Hazard ratios (HRs) in mothers and fathers were calculated and adjusted for potential confounders (year of birth, age at childbirth, sex of the child, parent' AUD, educational level, and marital status). Findings: In mothers, the adjusted HR for CHD was 1.24 (95% CI = 1.19–1.28) in relation to having a child with AUD. In fathers, the HR for CHD was lower than in mothers but still increased; the adjusted HR was 1.08 (95% CI = 1.05–1.12). In the co-sibling analyses, the HRs for mothers were similar to the HRs estimated from the population-based sample, but in fathers the association did not remain significant (HR = 0.98 [0.90–1.06]). Conclusions: In Sweden, there appears to be an association between having an offspring with alcohol use disorder and increased risk of developing coronary heart disease. For fathers, the association did not remain in co-sibling analyses.
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  • Calling, Susanna, et al. (författare)
  • Socioeconomic status and alcohol use disorders across the lifespan : A co-relative control study
  • 2019
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 14:10, s. 0224127-0224127
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: Alcohol use disorders (AUD) is well known to aggregate in families and is associated with socioeconomic status (SES). The objective was to study the effect of education, income and neighborhood SES in adulthood on AUD, and to explore whether the potential associations were confounded by shared familial factors, by using a co-relative control design. METHODS: Data on AUD was drawn from the Swedish inpatient and outpatient care registers; prescription drug register; and crime data. Through national population registers we collected information on income, education and neighborhood SES at age 25, 30, 35 and 40 years in all individuals born in Sweden between 1950 and 1980. Each sex-specific stratum consisted of approximately 750,000-1,200,000 individuals, who were followed for AUD for a mean follow-up time ranging between 10 and 15 years until the end of 2013. Cox proportional hazards models were used to investigate the risk of AUD as a function of income, education and neighborhood SES in the general population and in pairs of first cousins and full siblings within the same sex, who differed in their exposure to the SES measure. RESULTS: Higher educational level, higher income and higher neighborhood SES were all associated with a reduced risk for AUD for both males and females in all ages. The potentially protective effect remained but was attenuated when comparing pairs of first cousins and full siblings. CONCLUSIONS: High educational level and income in adulthood, as well as high neighborhood socioeconomic status, may represent protective factors against alcohol use disorders, even when shared familial factors, e.g. childhood socioeconomic status and genetic factors, have been taken into account.
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  • Chartier, Karen G., et al. (författare)
  • Triangulation of evidence on immigration and rates of alcohol use disorder in Sweden : Evidence of acculturation effects
  • 2023
  • Ingår i: Alcoholism: Clinical and Experimental Research. - : Wiley. - 0145-6008 .- 1530-0277. ; 47:1, s. 104-115
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: This study aimed to determine the robustness of the impact of immigration on risk for alcohol use disorder (AUD) using different measures, designs, and immigrant regional cohorts. Methods: The analytic sample included all individuals born between 1950 and 1990 and registered in Sweden from 1973 to 2017. Using Cox regression models, we examined the risk for AUD from Swedish nationwide registries in immigrants to Sweden from seven geographical regions: Africa, Asia and Oceania, Eastern Europe, Finland, Latin America and the Caribbean, Middle East/North Africa, and Western countries. We assessed greater exposure to Swedish culture, which we interpreted as increasing acculturation, by (i) comparing first-generation immigrants and their children with no and one native Swedish parent and (ii) examining age at immigration. The baseline comparison group was the native Swedish population. We also examined AUD risk in first-generation sibling pairs discordant for their age at immigration. Results: In nearly all immigrant cohorts in Sweden, increasing degrees of acculturation, as assessed by both our variables, were associated with rates of AUD that approached those of the Swedish population. These findings occurred in both men and women and both regional cohorts whose first-generation immigrants had lower and higher levels of AUD than native-born Swedes. For most cohorts, the rates of change with acculturation were greater in women than in men. In sibling pairs from most regions, the sibling who was younger at immigration had a higher rate of AUD. Conclusions: An examination of both sexes and two different proxies for acculturation provides consistent support for socio-cultural influences on AUD risk. Our co-sibling analyses suggest that a meaningful proportion of this effect is likely to be causal in nature.
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  • Chattopadhyay, S., et al. (författare)
  • Influence of family history on risk of second primary cancers and survival in patients with squamous cell skin cancer
  • 2020
  • Ingår i: British Journal of Dermatology. - : Oxford University Press (OUP). - 0007-0963 .- 1365-2133. ; 183:3, s. 488-494
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Patients with squamous cell skin cancer (SCC) have an excellent prognosis but second primary cancers (SPCs) weaken survival prospects. Family history is a known risk factor for cancer but whether it is a risk factor for SPC in patients with SCC is not known. Objectives: To quantify the risk of family history on SPCs in patients with SCC and estimate survival probabilities of patients with SPCs depending on family history. Methods: With 13 945 histologically verified SCCs, relative risks (RRs) were estimated for family history using a generalized regression model. For survival analysis, hazard ratios (HRs) were assessed using a multivariable Cox proportional-hazards model. Results: Family history of invasive SCC increased risk of second invasive SCC [RR = 42·92, 95% confidence interval (CI) 33·69–50·32] compared with risk without family history (RR 19·12, 95% CI 17·88–21·08). Family history of any nonskin cancer in invasive SCC increased risk of the same cancers to be diagnosed as SPC (RRFH = 1·48, 95% CI 1·35–1·61 vs. RRno FH = 1·40, 95% CI 1·32–1·48); significant increases were observed for seven different nonskin cancers. Most results were replicated for in situ SCC. SPC was deleterious for survival irrespective of family history; HR for patients with SPC was 4·28 (95% CI 3·83–4·72) vs. those without SPC (1·04). Conclusions: Family history of nonskin cancer was associated with approximately a doubling of risk for SPCs in patients with SCC. SPC increases the death rate in patients with SCC 3–4 times, irrespective of family history. Taking family history into account at SCC diagnosis may help prevention or early detection of SPCs. What's already known about this topic? Second primary cancers (SPCs) are frequently diagnosed in patients with invasive and in situ squamous cell carcinoma (SCC); some epidemiological studies suggest a link to immune dysfunction. Family history of cancer is a risk factor for practically all first primary cancers but whether it also influences risk of SPCs in patients with SCC is not known. The possible influence of family history on survival in patients with SCC remains to be established.
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18.
  • Cook, Won Kim, et al. (författare)
  • Drinking cultures and socioeconomic risk factors for alcohol and drug use disorders among first- and second-generation immigrants : A longitudinal analysis of Swedish population data
  • 2021
  • Ingår i: Drug and Alcohol Dependence. - : Elsevier BV. - 0376-8716. ; 226
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Few longitudinal studies investigate predictors of substance use incidence among immigrants. The current study describes substance use disorders in immigrants to Sweden, focusing on drinking culture in the country of origin and socioeconomic status (SES), and how these intersect with generational status to influence risk. Methods: Using pseudonymized Swedish population registry data, we track onset of alcohol use disorder and drug use disorder in a longitudinal study of 815,778 first-generation immigrants and 674,757 second-generation immigrants from 64 countries over a 6-year period. Cox regression analysis estimated risks of alcohol and drug use disorders in second-generation immigrants compared to first-generation, and moderation analyses assessed interactions of generational status with country-of-origin per capita alcohol consumption and SES. Results: Immigrants and second-generation immigrants originating from countries with high levels of alcohol consumption had higher risks for alcohol and drug use disorders. Immigrants with high SES had lower risks for alcohol and drug use disorders. The interaction between generational status and country-of-origin alcohol consumption was significant for drug use disorder (not for alcohol use disorder), with drug use disorder risk for second-generation immigrants being highest for those from countries with the lowest level of country-of-origin per capita alcohol consumption. The interaction between generational status and SES was significant for alcohol use disorder, with low-SES second-generation immigrants showing markedly higher risk than first-generation immigrants with comparable SES. Conclusions: Among immigrants in Sweden, second-generation immigrants are at increased risk of developing alcohol and drug use disorders, particularly if they have lower SES. Policy and community attention to these high-risk subgroups in immigrant communities is warranted.
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19.
  • 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.
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20.
  • 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.
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21.
  • 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.
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22.
  • 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.
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23.
  • 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.
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24.
  • 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.
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25.
  • 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. ; 149:6, s. 479-490
  • 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.
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26.
  • 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.
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27.
  • 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.
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28.
  • 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.
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29.
  • 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.
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30.
  • 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.
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31.
  • 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.
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32.
  • Edwards, A. C., et al. (författare)
  • Geographic proximity is associated with transmission of suicidal behaviour among siblings
  • 2019
  • Ingår i: Acta Psychiatrica Scandinavica. - : Wiley. - 0001-690X .- 1600-0447. ; 140:1, s. 30-38
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The aim of this study was to clarify the role of ‘contagion’, or social transmission, in risk of suicidal behaviour (SB) among siblings. Methods: We followed Swedish sibling pairs until one of them (S1; N = 111,848) was registered for a suicide attempt or completion. We tested the effect of geographic proximity between siblings on risk of a first SB registration of S1's sibling (S2). To control for familial confounding, we conducted complementary analyses of sibling trios (N = 701), comparing risk in different siblings as a function of their respective proximity to S1. Results: The best-fitting model across sibling pairs included an effect of distance between siblings (HR = 0.96, 95% CI = 0.93–0.99). Hazard ratios declined quickly up to 25 km and largely stabilized beyond 150 km. Across all pairs, a larger age difference between siblings was associated with reduced SB risk (HR = 0.96 95% CI = 0.93–0.98). Findings were consistent within the sibling trios. Conclusions: Consistent with the concept of suicide contagion, risk of suicidal behaviour subsequent to a sibling's suicide completion or attempt is higher as a function of sibling closeness. These findings are robust to potentially confounding familial factors.
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33.
  • 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.
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34.
  • 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.
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35.
  • Edwards, Alexis C., et al. (författare)
  • Shared genetic and environmental etiology between substance use disorders and suicidal behavior
  • 2023
  • Ingår i: Psychological Medicine. - 0033-2917. ; 53:6, s. 2380-2388
  • 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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36.
  • Edwards, Alexis C., et al. (författare)
  • Socioeconomic position indicators and risk of alcohol-related medical conditions : A national cohort study from Sweden
  • 2024
  • Ingår i: PLoS Medicine. - 1549-1277. ; 21:3
  • 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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37.
  • Edwards, Alexis C., et al. (författare)
  • Socioeconomic sequelae of drug abuse in a Swedish national cohort
  • 2020
  • Ingår i: Drug and Alcohol Dependence. - : Elsevier BV. - 0376-8716. ; 212
  • 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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38.
  • Edwards, Alexis C., et al. (författare)
  • The role of substance use disorders in the transition from suicide attempt to suicide death : a record linkage study of a Swedish cohort
  • 2024
  • Ingår i: Psychological Medicine. - 1469-8978. ; 54:1, s. 90-97
  • 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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39.
  • Edwards, Alexis C., et al. (författare)
  • Time-specific and cumulative effects of exposure to parental externalizing behavior on risk for young adult alcohol use disorder
  • 2017
  • Ingår i: Addictive Behaviors. - : Elsevier BV. - 0306-4603. ; 72, s. 8-13
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Previous studies indicate that parental externalizing behavior (EB) is a robust risk factor for alcohol use disorder (AUD) in their children, and that this is due to both inherited genetic liability and environmental exposure. However, it remains unclear whether the effects of exposure to parental EB vary as a function of timing and/or chronicity. Methods We identified biological parents with an alcohol use disorder, drug abuse, or criminal behavior, during different periods of their child's upbringing, using Swedish national registries. Logistic regression was used to determine whether the effect of parental EB exposure during different developmental periods differentially impacted children's risk for young adult AUD (ages 19–24). In addition, we tested how multiply affected parents and/or sustained exposure to affected parents impacted risk. Results While parental EB increased risk for young adult AUD, timing of exposure did not differentially impact risk. Having a second affected parent increased the risk of AUD additionally, and sustained exposure to parental EB across multiple periods resulted in a higher risk of young adult AUD than exposure in only one period. Conclusions In this well-powered population study, there was no evidence of “sensitive periods” of exposure to national registry-ascertained parental EB with respect to impact on young adult AUD, but sustained exposure was more pathogenic than limited exposure. These findings suggest developmental timing does not meaningfully vary the impact, but rather there is a pervasive risk for development of young adult AUD for children and adolescents exposed to parental EB.
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40.
  • Eriksson, S., et al. (författare)
  • Genetic analysis of insect bite hypersensitivity (summer eczema) in Icelandic horses
  • 2008
  • Ingår i: Animal. - 1751-7311. ; 2:3, s. 360-365
  • Tidskriftsartikel (refereegranskat)abstract
    • There is a lack of knowledge about the genetic background of eczema due to insect bite hypersensitivity, also called summer eczema, in horses. The condition is known in several horse breeds and countries and it causes reduced welfare of the horse and economic losses to the owner The aim of this study was to estimate genetic parameters for summer eczema in Swedish-born Icelandic horses. A questionnaire was sent to owners of horses sired by stallions with more than 50 offspring born in Sweden between 1991 and 2001. Variance components of summer eczema classified as healthy, mild, moderate or severe were estimated using the threshold methodology with sire models. In addition, summer eczema was analysed as a binary trait (healthy v. affected). The analyses included 1250 horses sired by 33 stallions. The prevalence of summer eczema was 8%, with a range of 0% to 30% in different paternal half-sib groups. Offspring of dams suffering from eczema had a higher risk of developing eczema. The heritability for severity of summer eczema was estimated at 0.3 (s.d. < 0.2) with a threshold sire model. In contrast to the age of the horse, different geographic areas and gender were significantly associated with severity of the eczema. We conclude that genetic selection could decrease the prevalence of summer eczema among Swedish-born Icelandic horses. The amount and quality of data are, however crucial for the possibility to introduce a genetic evaluation of summer eczema. The symptoms should be classified in several classes according to severity, and this classification could be made by the horse owner.
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41.
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42.
  • Ji, Jianguang, et al. (författare)
  • Incidence of Cancer in Patients With Schizophrenia and Their First-Degree Relatives: A Population-Based Study in Sweden.
  • 2013
  • Ingår i: Schizophrenia Bulletin. - : Oxford University Press (OUP). - 1745-1701 .- 0586-7614. ; 39:3, s. 527-536
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Previous studies of the association between schizophrenia and cancer have produced conflicting results, probably because of the failure to control for confounding factors. Objective: To test if the possible association between schizophrenia and cancer is genetic by investigating the incidence of cancer in patients with schizophrenia and their relatives. Design: Retrospective cohort study with follow-up between 1965 and 2008. Estimated smoking rates were used to adjust the incidence rates of smoking-related cancers. Participants: The entire Swedish population.Main outcome measures:Risk of overall cancer and 34 site-/type-specific cancers.Results:A total of 59 233 patients in Sweden with schizophrenia were identified, of whom 6137 developed cancer during the study period, giving a decreased standardized incidence ratio (SIR) of 0.79 (95% CI 0.77-0.81). The decrease was more pronounced (SIR 0.40, 95% CI 0.38-0.43) before the first diagnosis of schizophrenia. The overall risk was significantly reduced among their unaffected parents (SIR 0.96, 95% CI 0.94-0.98) and siblings (SIR 0.92, 95% CI 0.89-0.96). Sex-stratified analyses indicated different incidence rates between males and females, with female patients having higher cancer risks than the general population. Conclusions: The significantly decreased incidences of cancers in patients diagnosed with schizophrenia and their unaffected relatives suggest that familiar/genetic factors contributing to schizophrenia may protect against the development of cancer, especially for those cancer sites observed in both settings. The increased risk of breast, cervical, and endometrial cancers after the first diagnosis of schizophrenia could be attributed to nongenetic factors such as antipsychotics administration, which may justify preventive medical screening.
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43.
  • Jönsson, Lena S, et al. (författare)
  • Is acculturation associated with physical activity among female immigrants in Sweden?
  • 2013
  • Ingår i: Journal of Public Health. - : Oxford University Press (OUP). - 1741-3850 .- 1741-3842. ; 35:2, s. 270-277
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Immigrant women in Sweden have lower levels of leisure time physical activity (LTPA) than Swedish-born women. The reasons are unclear, although acculturation has been suggested to play a role. METHODS: We used a cross-sectional study design to investigate the association between LTPA and two indicators of acculturation: (i) language proficiency (ability to understand news reports on the radio and television) and (ii) age at the time of migration, and if there existed a modifying effect on these hypothesized associations. The study sample consisted of 1651 women, aged 18-65, living in Sweden and born in Finland, Chile or Iraq. A postal questionnaire (translated into the women's native language) was used to collect the variables. The International Physical Activity Questionnaire was used to assess LTPA. Data were collected in 2002-05 and analyzed in 2009-10. A partial-proportional odds model was used for the analysis. RESULTS: Increased language proficiency was associated with increased LTPA [odds ratio (OR) = 2.31, 95% confidence interval (CI) = 1.57-3.41]. Country of birth modified the association. Furthermore, younger age at migration was associated with increased LTPA (OR = 1.44, 95% CI = 1.01-2.03). CONCLUSIONS: Increased language proficiency has the potential to be an important health-promoting factor among immigrant women.
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44.
  • Karriker-Jaffe, Katherine J., et al. (författare)
  • Disparities in pharmacotherapy for alcohol use disorder in the context of universal health care : A Swedish register study
  • 2017
  • Ingår i: Addiction. - : Wiley. - 0965-2140. ; 112:8, s. 1386-1394
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and aims: Pharmacotherapy can be an important part of the continuum of care for alcohol use disorder (AUD). The Swedish universal health-care system emphasizes provision of care to marginalized groups. The primary aim was to test associations of neighborhood deprivation and disadvantaged social status with receipt of AUD pharmacotherapy in this context. Design: Data from linked population registers were used to follow an open cohort over 7 years. Setting: Sweden. Participants: Alcohol-related ICD-10 codes reported for all hospitalizations in the Swedish Hospital Discharge Register and all clinic/office visits in the Outpatient Care Register between 2005 and 2012 were used to identify 62549 cases with AUD. Measurements: The primary outcome was any AUD pharmacotherapy (naltrexone, disulfiram, acamprosate, nalmefene) picked up by patients between 2005 and 2012 (versus none), based on the Swedish Prescribed Drug Register. Neighborhood deprivation was defined using aggregated data from the Total Population Register; indicators of disadvantaged social status (income, education, country of origin) also came from this source. Findings: Approximately half the cases (53.7%) picked up one or more AUD pharmacotherapy prescriptions. In adjusted models, people living in neighborhoods with moderate [odds ratio (OR) = 0.90, 95% confidence interval (CI) = 0.86, 0.95] or high levels of deprivation (OR = 0.75, 95% CI = 0.70, 0.79) compared with low deprivation, those with lower incomes (for example, lowest quartile: OR = 0.70, 95% CI = 0.66, 0.73 compared with highest) and less education (for example, < 10 years: OR = 0.82, 95% CI = 0.78, 0.85 compared with 12+ years) and people born outside Sweden (OR = 0.74, 95% CI = 0.71, 0.78 compared with Swedish-born) were significantly less likely to pick up a prescription for AUD pharmacotherapy during the study period. Conclusions: There appear to be socio-economic disparities in the receipt of pharmacotherapy for alcohol use disorder in Sweden.
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45.
  • Kendler, Kenneth S., et al. (författare)
  • A developmental etiological model for drug abuse in men
  • 2017
  • Ingår i: Drug and Alcohol Dependence. - : Elsevier BV. - 0376-8716. ; 179, s. 220-228
  • Tidskriftsartikel (refereegranskat)abstract
    • Background We attempt to develop a relatively comprehensive structural model of risk factors for drug abuse (DA) in Swedish men that illustrates developmental and mediational processes. Methods We examined 20 risk factors for DA in 48,369 men undergoing conscription examinations in 1969–70 followed until 2011 when 2.34% (n = 1134) of them had DA ascertained in medical, criminal and pharmacy registries. Risk factors were organized into four developmental tiers reflecting i) birth, ii) childhood/early adolescence, iii) late adolescence, and iv) young adulthood. Structural equational model fitting was performed using Mplus. Results The best fitting model explained 47.8% of the variance in DA. The most prominent predictors, in order, were: early adolescent externalizing behavior, early adult criminal behavior, early adolescent internalizing behavior, early adult unemployment, early adult alcohol use disorder, and late adolescent drug use. Two major inter-connecting pathways emerged reflecting i) genetic/familial risk and ii) family dysfunction and psychosocial adversity. Generated on a first and tested on a second random half of the sample, a model from these variables predicted DA with an ROC area under the curve of 83.6%. Fifty-nine percent of DA cases arose from subjects in the top decile of risk. Conclusions DA in men is a highly multifactorial syndrome with risk arising from familial-genetic, psychosocial, behavioral and psychological factors acting and interacting over development. Among the multiple predisposing factors for DA, a range of psychosocial adversities, externalizing psychopathology and lack of social constraints in early adulthood are predominant.
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46.
  • Kendler, K. S., et al. (författare)
  • A developmental model for alcohol use disorders in Swedish men
  • 2016
  • Ingår i: Psychological Medicine. - 0033-2917. ; 46:13, s. 2759-2770
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Alcohol use disorder (AUD) is a classic multifactorial syndrome and it is critical to understand the diversity of the relevant risk factors and how they inter-relate over development. Method: We examined 21 risk factors for AUD in four developmental tiers reflecting (i) birth, (ii) childhood and early adolescence, (iii) late adolescence, and (iv) early adulthood in 47 414 Swedish men of whom 3907 (8.2%) were registered for AUD at or after age 25 with a mean length of follow-up of 33.9 (6.6) years. Structural equational model fitting was performed using Mplus. Results: The best-fitting model provided a good fit to the data and explained 23.4% of the variance in AUD. The five strongest predictors were: externalizing behaviors, criminal behavior, father's alcohol consumption, genetic risk, and low educational attainment. Two developmentally early familial/genetic risk factors had substantial direct paths to AUD: father's alcohol consumption and genetic liability. Other broad developmental pathways to risk for AUD were evident: externalizing, psychosocial and internalizing. Overall, the externalizing pathway to AUD was the strongest. However, these pathways were substantially interwoven over time such that risk factors from one domain were commonly predicted by and/or predicted risk factors from the other broad domains of risk. Conclusion: AUD in men is an etiologically complex syndrome influenced by familial-genetic, psychosocial, internalizing, and especially externalizing risk factors that act and interact over development and have complicated mediational pathways.
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47.
  • Kendler, Kenneth S., et al. (författare)
  • A distinctive profile of family genetic risk scores in a Swedish national sample of cases of fibromyalgia, irritable bowel syndrome, and chronic fatigue syndrome compared to rheumatoid arthritis and major depression
  • 2023
  • Ingår i: Psychological Medicine. - 0033-2917. ; 53:9, s. 3879-3886
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Functional somatic disorders (FSD) feature medical symptoms of unclear etiology. Attempts to clarify their origin have been hampered by a lack of rigorous research designs. We sought to clarify the etiology of the FSD by examining the genetic risk patterns for FSD and other related disorders. Methods This study was performed in 5 829 186 individuals from Swedish national registers. We quantified familial genetic risk for FSD, internalizing disorders, and somatic disorders in cases of chronic fatigue syndrome (CFS), fibromyalgia (FM), and irritable bowel syndrome (IBS), using a novel method based on aggregate risk in first to fifth degree relatives, adjusting for cohabitation. We compared these profiles with those of a prototypic internalizing psychiatric - major depression (MD) - and a somatic/autoimmune disorder: rheumatoid arthritis (RA). Results Patients with FM carry substantial genetic risks not only for FM, but also for pain syndromes and internalizing, autoimmune and sleep disorders. The genetic risk profiles for IBS and CFS are also widely distributed although with lower average risks. By contrast, genetic risk profiles of MD and RA are much more restricted to related conditions. Conclusion Patients with FM have a relatively unique family genetic risk score profile with elevated genetic risk across a range of disorders that differs markedly from the profiles of a classic autoimmune disorder (RA) and internalizing disorder (MD). A similar less marked pattern of genetic risks was seen for IBS and CFS. FSD arise from a distinctive pattern of genetic liability for a diversity of psychiatric, autoimmune, pain, sleep, and functional somatic disorders.
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48.
  • Kendler, K. S., et al. (författare)
  • A latent class analysis of drug abuse in a national Swedish sample
  • 2013
  • Ingår i: Psychological Medicine. - 1469-8978. ; 43:10, s. 2169-2178
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. Drug abuse (DA) is a clinically heterogeneous syndrome. Using medical, legal, death and pharmacy records covering the entire population of Sweden, could we uncover meaningful subtypes of DA? Method. We performed a latent class analysis (LCA) on all individuals in Sweden born 1950-1993 who were registered with DA or its consequences (n=192 501) and then validated these classes using demographics, patterns of co-morbidity with alcohol use disorder (AUD), non-DA crime and psychiatric illness, and the pattern of aggregation and co-aggregation in sibling pairs. Results. The best-fit LCA had six classes : (1) low-frequency pure criminal, (2) high-frequency medical criminal, (3) low-frequency pure medical, (4) high-frequency medical, (5) prescription and (6) death. Each class had a distinct pattern of demographic features and co-morbidity and aggregated within sibling pairs with at least moderate specificity. For example, class 2 was characterized by early age at registration, low educational attainment, high male preponderance, high rates of AUDs, strong resemblance within sibling pairs [odds ratio (OR) 12.6] and crime and the highest risk for DA in siblings (20.0 %). By contrast, class 5 had a female preponderance, late age at registration, low rates of crime and AUDs, high rates of psychiatric illness, high familiality within sibling pairs (OR 14.7) but the lowest observed risk for DA in siblings (8.9 %). Conclusions. DA as assessed by public records is a heterogeneous syndrome. Familial factors contribute substantially to this heterogeneity. Advances in our understanding of etiological processes leading to DA will be aided by a consideration of this heterogeneity.
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49.
  • Kendler, Kenneth S., et al. (författare)
  • A National Swedish Twin-Sibling Study of Alcohol Use Disorders
  • 2016
  • Ingår i: Twin Research and Human Genetics. - : Cambridge University Press (CUP). - 1832-4274 .- 1839-2628. ; 19:5, s. 430-437
  • Tidskriftsartikel (refereegranskat)abstract
    • The relationship between the genetic and environmental risk factors for alcohol use disorders (AUD) detected in Swedish medical, pharmacy, and criminal registries has not been hitherto examined. Prior twin studies have varied with regard to the detection of shared environmental effects and sex differences in the etiology of AUD. In this report, structural equation modeling in OpenMx was applied to (1) the three types of alcohol registration in a population-based sample of male–male twins and reared-together full and half siblings (total 208,810 pairs), and (2) AUD, as a single diagnosis, in male–male, female–female, and opposite-sex (OS) twins and reared-together full and half siblings (total 787,916 pairs). An independent pathway model fit best to the three forms of registration and indicated that between 70% and 92% of the genetic and 63% and 98% of the shared environmental effects were shared in common with the remainder unique to each form of AUD registration. Criminal registration had the largest proportion of unique genetic and environmental factors. The best fit model for AUD estimated the heritability to be 22% and 57%, respectively, in females and males. Both shared (12% vs. 6%) and special twin environment (29% vs. 2%) were substantially more important in females versus males. In conclusion, AUD ascertained from medical, pharmacy, and criminal Swedish registries largely share the same genetic and environmental risk factors. Large sex differences in the etiology of AUD were seen in this sample, with substantially stronger familial environmental and weaker genetic effects in females versus males.
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50.
  • Kendler, K S, et al. (författare)
  • A novel sibling-based design to quantify genetic and shared environmental effects : application to drug abuse, alcohol use disorder and criminal behavior
  • 2016
  • Ingår i: Psychological Medicine. - 1469-8978. ; 46:8, s. 1639-1650
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Twin studies have been criticized for upwardly biased estimates that might contribute to the missing heritability problem.METHOD: We identified, from the general Swedish population born 1960-1990, informative sibships containing a proband, one reared-together full- or half-sibling and a full-, step- or half-sibling with varying degrees of childhood cohabitation with the proband. Estimates of genetic, shared and individual specific environment for drug abuse (DA), alcohol use disorder (AUD) and criminal behavior (CB), assessed from medical, legal or pharmacy registries, were obtained using Mplus.RESULTS: Aggregate estimates of additive genetic effects for DA, AUD and CB obtained separately in males and females varied from 0.46 to 0.73 and agreed with those obtained from monozygotic and dizygotic twins from the same population. Of 54 heritability estimates from individual classes of informative sibling trios (3 syndromes × 9 classes of trios × 2 sexes), heritability estimates from the siblings were lower, tied and higher than those from obtained from twins in 26, one and 27 comparisons, respectively. By contrast, of 54 shared environmental estimates, 33 were lower than those found in twins, one tied and 20 were higher.CONCLUSIONS: With adequate information, human populations can provide many methods for estimating genetic and shared environmental effects. For the three externalizing syndromes examined, concerns that heritability estimates from twin studies are upwardly biased or were not generalizable to more typical kinds of siblings were not supported. Overestimation of heritability from twin studies is not a likely explanation for the missing heritability problem.
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