| 11. |
- Homman, Lina E., et al.
(author)
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Gender and Direction of Effect of Alcohol Problems and Internalizing Symptoms in a Longitudinal Sample of College Students
- 2017
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In: Substance Use & Misuse. - : Taylor & Francis. - 1082-6084 .- 1532-2491. ; 52:4, s. 429-438
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Journal article (peer-reviewed)abstract
- Background: Alcohol problems and internalizing symptoms are consistently found to be associated but how they relate to each other is unclear. Objective: The present study aimed to address limitations in the literature of comorbidity of alcohol problems and internalizing symptoms by investigating the direction of effect between the phenotypes and possible gender differences in college students. Method: We utilized data from a large longitudinal study of college students from the United States (N = 2607). Three waves of questionnaire-based data were collected over the first two years of college (in 2011–2013). Cross-lagged models were applied to examine the possible direction of effect of internalizing symptoms and alcohol problems. Possible effects of gender were investigated using multigroup modeling. Results: There were significant correlations between alcohol problems and internalizing symptoms. A direction of effect was found between alcohol problems and internalizing symptoms but differed between genders. A unidirectional relationship varying with age was identified for males where alcohol problems initially predicted internalizing symptoms followed by internalizing symptoms predicting alcohol problems. For females, a unidirectional relationship existed wherein alcohol problems predicted internalizing symptoms. Conclusions/Importance: We conclude that the relationship between alcohol problems and internalizing symptoms is complex and differ between genders. In males, both phenotypes are predictive of each other, while in females the relationship is driven by alcohol problems. Importantly, our study examines a population-based sample, revealing that the observed relationships between alcohol problems and internalizing symptoms are not limited to individuals with clinically diagnosed mental health or substance use problems.
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| 12. |
- Karriker-Jaffe, Katherine J., et al.
(author)
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Alcohol Availability and Onset and Recurrence of Alcohol Use Disorder : Examination in a Longitudinal Cohort with Cosibling Analysis
- 2018
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In: Alcoholism: Clinical and Experimental Research. - : Wiley. - 0145-6008. ; 42:6, s. 1105-1112
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Journal article (peer-reviewed)abstract
- Background: Recent reviews of associations of alcohol availability with alcohol outcomes suggest findings are highly inconsistent and highlight a lack of longitudinal and causal evidence. Effect modification (moderation or statistical interaction), which could contribute to the inconsistent picture in the existing literature, has not been systematically assessed. We examined associations of alcohol availability with onset and recurrence of alcohol use disorder (AUD) using multilevel, longitudinal population data from Sweden and tested hypothesized effect modifiers to identify groups for whom increased alcohol availability may be particularly risky. We also employed cosibling models to assess potential causality for AUD onset by accounting for genetic and shared-environment confounders. Methods: Data come from all individuals born in Sweden between 1950 and 1975 who were registered in a residential neighborhood at the end of 2005 (N = 2,633,922). We used Cox proportional hazards models to investigate time to AUD onset and logistic regression to assess the odds of AUD recurrence over an 8-year period. Results: Living in a neighborhood with at least 1 alcohol outlet of any type was associated with a small increase in the likelihood of developing AUD, with an adjusted hazard ratio (HR) of 1.16 (95% CI: 1.13 to 1.19). Among people with a prior AUD registration, alcohol availability was not significantly associated with recurrence of AUD, with an adjusted odds ratio of 1.02 (95% CI: 1.00 to 1.05). Associations of alcohol availability with AUD onset varied according to sex, age, education, neighborhood deprivation, and urbanicity. HRs from the sibling models were similar to those in the general population models, with an adjusted HR = 1.19 (95% CI: 1.15 to 1.24). Conclusions: Effects varied among neighborhood residents, but greater alcohol availability was a risk factor for AUD onset (but not relapse) in all groups examined except women. Cosibling models suggest there may be a causal relationship of greater alcohol availability with adult-onset AUD.
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| 13. |
- Karriker-Jaffe, Katherine J., et al.
(author)
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Chains of risk for alcohol use disorder : Mediators of exposure to neighborhood deprivation in early and middle childhood
- 2018
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In: Health and Place. - : Elsevier BV. - 1353-8292. ; 50, s. 16-26
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Journal article (peer-reviewed)abstract
- Our goal was to test a cascade model to identify developmental pathways, or chains of risk, from neighborhood deprivation in childhood to alcohol use disorder (AUD) in young adulthood. Using Swedish general population data, we examined whether exposure to neighborhood deprivation during early and middle childhood was associated with indicators of social functioning in adolescence and emerging adulthood, and whether these were predictive of AUD. Structural equation models showed exposure to neighborhood deprivation was associated with lower school achievement during adolescence, poor social functioning during emerging adulthood, and the development of AUD for both males and females. Understanding longitudinal pathways from early exposure to adverse environments to later AUD can inform prevention and intervention efforts.
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| 14. |
- Karriker-Jaffe, Katherine J., et al.
(author)
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Disparities in pharmacotherapy for alcohol use disorder in the context of universal health care : A Swedish register study
- 2017
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In: Addiction. - : Wiley. - 0965-2140. ; 112:8, s. 1386-1394
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Journal article (peer-reviewed)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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| 15. |
- Kendler, Kenneth S., et al.
(author)
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A developmental etiological model for drug abuse in men
- 2017
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In: Drug and Alcohol Dependence. - : Elsevier BV. - 0376-8716. ; 179, s. 220-228
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Journal article (peer-reviewed)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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| 16. |
- Kendler, Kenneth S., et al.
(author)
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A National Swedish Twin-Sibling Study of Alcohol Use Disorders
- 2016
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In: Twin Research and Human Genetics. - : Cambridge University Press (CUP). - 1832-4274 .- 1839-2628. ; 19:5, s. 430-437
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Journal article (peer-reviewed)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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| 17. |
- Kendler, Kenneth S, et al.
(author)
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A Swedish National Prospective and Co-relative Study of School Achievement at Age 16, and Risk for Schizophrenia, Other Nonaffective Psychosis, and Bipolar Illness.
- 2016
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In: Schizophrenia Bulletin. - : Oxford University Press (OUP). - 1745-1701 .- 0586-7614. ; 42:1, s. 77-86
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Journal article (peer-reviewed)abstract
- While cognitive ability is inversely associated with risk for schizophrenia (SZ), the association is less clear with other nonaffective psychoses (ONAP) and bipolar illness (BPI). Using national Swedish hospital registry data, we examined the prospective relationship between school achievement (SA) and development of SZ, ONAP, and BPI in 1800643 adolescents born 1972-1990. We used Cox proportional hazard and co-relative control models to predict onset of SZ, ONAP, and BPI from standardized SA scores at age 16. The hazard ratio (HRs; and 95% CIs) for first onset of SZ as a function of SA was 0.66 (0.64-0.68) for both sexes. For ONAP, the HRs equaled 0.66 (0.64-0.68) for males and 0.72 (0.70-0.75) for females. For BPI, parallel HRs were 0.81 (0.78-0.84) and 0.71 (0.70-0.73). The association between SA and risk was stronger in the lower vs the higher ranges of SA. In most analyses, moderate increases in risk were observed at the highest levels of SA, with the strongest evidence for females and risk of ONAP. Co-relative control analyses indicated that common genetic or familial-environmental effects only marginally confounded these associations. Consistent with prior studies, these results have 3 major implications for neurodevelopmental models: (1) adolescent cognitive deficits that increase risk are not the result of prodromal changes,( 2) individual specific environmental exposures are largely responsible for the association between low SA and psychosis risk, and (3) neurodevelopmental disturbances (as indicated by low SA) are not unique to SZ but also occur in ONAP and to a lesser degree BPI.
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| 18. |
- Kendler, Kenneth S, et al.
(author)
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A Swedish Population-Based Multivariate Twin Study of Externalizing Disorders.
- 2015
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In: Behavior Genetics. - : Springer Science and Business Media LLC. - 0001-8244 .- 1573-3297. ; 46:2, s. 183-192
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Journal article (peer-reviewed)abstract
- In epidemiological and twin populations, prior interview studies have identified an externalizing spectrum of disorders. Could this be detected utilizing objective registry data? In 20,603 twin pairs from the Swedish Twin Registry, we obtained information from national medical, criminal and pharmacy records on drug abuse (DA), criminal behavior (CB) and alcohol use disorders (AUD). Multivariate twin modeling was performed with the OpenMx package. A common pathway model with quantitative but not qualitative sex effects fit best with twin resemblance for the latent liability to externalizing syndromes due to both genetic and shared environmental factors. Heritability of the liability was higher in females (76 vs. 62 %) while shared environmental influences were considerably stronger in males (23 vs. 3 %). In both sexes, this latent liability was most strongly indexed by DA and least by CB. All three syndromes had specific genetic influences (especially CB and AUD in males, and CB in females) and specific shared environmental effects (especially DA and CB in males, and AUD in females). For DA, CB and AUD in men, and DA and AUD in women, at least 75 % of the genetic risk arose through the common factor. The best fit model assumed that genetic and environmental influences on these externalizing syndromes in males and females were the same. We identified, in registry data, a highly heritable externalizing spectrum. DA, CB and AUD share substantial genetic and modest to moderate shared environmental influences. The nature of the externalizing spectrum differed meaningfully between the sexes.
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| 19. |
- Kendler, Kenneth S., et al.
(author)
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Academic Achievement and Drug Abuse Risk Assessed Using Instrumental Variable Analysis and Co-relative Designs
- 2018
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In: JAMA Psychiatry. - : American Medical Association (AMA). - 2168-622X .- 2168-6238. ; 75:11, s. 1182-1188
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Journal article (peer-reviewed)abstract
- Importance: Low academic achievement (AA) in childhood and adolescence is associated with increased substance use. Empirical evidence, using longitudinal epidemiologic data, may provide support for interventions to improve AA as a means to reduce risk of drug abuse (DA). Objective: To clarify the nature of the association between adolescent AA and risk of DA by using instrumental variable and co-relative analysis designs. Design, Setting, and Participants: This study, assessing nationwide data from individuals born in Sweden between 1971 and 1982, used instrumental variable and co-relative analyses of the association between AA and DA. The instrument was month of birth. Co-relative analyses were conducted in pairs of cousins (263222 pairs), full siblings (154295), and monozygotic twins (1623) discordant for AA, with raw results fitted to a genetic model. The AA-DA association was modeled using Cox regression. Data analysis was conducted from October 2017 to January 2018. Exposures: Academic achievement assessed at 16 years of age (for instrumental variable analyses), and estimated discordance in AA in pairs of monozygotic twins (for co-relative analyses). Main Outcomes and Measures: Drug abuse registration in national medical, criminal, or pharmacy registries. Results: This instrumental variable analysis included 934462 participants (478341 males and 456121 females) with a mean (SD) age of 34.7 (4.3) years at a mean follow-up of 19 years. Earlier month of birth was associated with a linear effect on AA, with the regression coefficient per month equaling -0.0225 SDs (95% CI, -0.0231 to -0.0219). Controlling for AA, month of birth had no association with risk of DA (hazard ratio [HR], 1.000; 95% CI, 0.997-1.004). Lower AA had a significant association with risk of subsequent DA registration (HR per SD, 2.33; 95% CI, 2.30-2.35). Instrumental variable analysis produced a substantial but modestly attenuated association (HR, 2.04; 95% CI, 1.75-2.33). Controlling for modest associations between month of birth and parental educational status and DA risk reduced the association to a HR of 1.92 (95% CI, 1.67-2.22). The genetic model applied to the results of co-relative analyses fitted the observed data well and estimated the AA-DA association in monozygotic twins discordant for AA to equal a HR of 1.79 (95% CI, 1.64-1.92). Conclusions and Relevance: Two different methodological approaches with divergent assumptions both produced results consistent with the hypothesis that the significant association observed between AA at 16 years of age and risk of DA into middle adulthood may be causal. These results provide empirical support for efforts to improve AA as a means to reduce risk of DA.
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| 20. |
- Kendler, Kenneth S., et al.
(author)
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Alcohol use disorder and mortality across the lifespan : a longitudinal cohort and co-relative analysis
- 2016
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In: JAMA Psychiatry. - : American Medical Association (AMA). - 2168-622X. ; 73:6, s. 575-581
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Journal article (peer-reviewed)abstract
- Importance: Excess alcohol consumption and alcohol use disorders (AUDs) are associated with substantially increased mortality. Efforts to reduce this toll require an understanding of their causes. Objective: To clarify the degree to which the excess mortality associated with AUDs arises (1) from the predispositions of the person who develops AUD (and which would likely be shared by close relatives) and (2) as a direct result of AUD itself. Design, Setting, and Participants: A prospective cohort and co-relative design study involving all individuals born in Sweden from 1940 to 1965 who had neither died nor migrated prior to 1973 or age 15 years (N = 2 821 036). They were followed up from January 1, 1973, until December 31, 2010. Alcohol use disorder was assessed from medical, criminal, and pharmacy registries. Half-siblings, full-siblings, and monozygotic twin pairs discordant for AUD were obtained from the Multi-Generation and Twin Register. Main Outcome and Measure: Death obtained from the Swedish Death registry. Results: Our cohort (1 447 887 males and 1 373 149 females) included 131 895 males and 42 163 females registered with AUD. The mean (SD) age at first AUD registration was 39 (13.4) years.We ascertained 127 347 and 76 325 deaths in the male and female subsamples, respectively. Controlling for sex, educational status, and year of birth, the mortality hazard ratio associated with AUD was 5.83 (95%CI, 5.76-5.90) and varied-with an inverted U-shaped function-by age. Examining the AUD-mortality association in the general population and in relative pairs discordant for AUD exposure demonstrated substantial familial confounding in early to mid-adulthood: the AUD-associated mortality hazard ratio was much lower in discordant close relatives than in the general population. In middle to late adulthood, evidence for familial confounding decreased with increasing evidence for a direct effect of AUD on elevated mortality. In the oldest age group (65-70 years), the mortality hazard ratios were similar across the population and all relative pairs, suggesting that the excess mortality was largely a result of having AUD. Adding years since onset of AUD to the model showed that both increasing age and increasing years of duration of AUD contributed to the reduction of familial confounding in the association between AUD and elevated mortality. Conclusions and Relevance: Excess mortality associated with AUD arises both from the predispositions of the person who develops AUD and the direct result of having AUD. The effect of predisposition is more prominent early in the life course and in the early years of AUD. The direct effect of AUD becomes progressively more important later in life and with longer duration of AUD. These results have implications for interventions seeking to reduce the elevated AUD-associated mortality.
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