| 1. |
- Amstadter, Ananda B., et al.
(författare)
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Testing Phenotypic Models of Posttraumatic Stress Disorder and Alcohol Use Disorder Comorbidity Using Longitudinal Registry Data
- 2023
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Ingår i: Journal of Studies on Alcohol and Drugs. - : Alcohol Research Documentation, Inc.. - 1937-1888 .- 1938-4114. ; 84:3, s. 378-388
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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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| 2. |
- Edwards, Alexis C., et al.
(författare)
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Time-specific and cumulative effects of exposure to parental externalizing behavior on risk for young adult alcohol use disorder
- 2017
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Ingår i: Addictive Behaviors. - : Elsevier BV. - 0306-4603. ; 72, s. 8-13
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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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| 3. |
- Karriker-Jaffe, Katherine J., et al.
(författare)
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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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Ingår i: Health and Place. - : Elsevier BV. - 1353-8292. ; 50, s. 16-26
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Tidskriftsartikel (refereegranskat)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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| 4. |
- Karriker-Jaffe, Katherine J., et al.
(författare)
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Young men's behavioral competencies and risk of alcohol use disorder in emerging adulthood : Early protective effects of parental education
- 2021
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Ingår i: Development and Psychopathology. - 0954-5794. ; 33:1, s. 135-148
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Tidskriftsartikel (refereegranskat)abstract
- We investigate how early exposure to parental externalizing behaviors (EB) may contribute to development of alcohol use disorders (AUD) in young adulthood, testing a developmental cascade model focused on competencies in three domains (academic, conduct, and work) in adolescence and emerging adulthood, and examining whether high parental education can buffer negative effects of parental EB and other early risk factors. We use data from 451,054 Swedish-born men included in the national conscript register. Structural equation models showed parental EB was associated with academic and behavioral problems during adolescence, as well as with lower resilience, more criminal behavior, and reduced social integration during emerging adulthood. These pathways led to elevated rates of AUD in emerging and young adulthood. Multiple groups analysis showed most of the indirect pathways from parental EB to AUD were present but buffered by higher parental education, suggesting early life experiences and competencies matter more for young men from lower socioeconomic status (SES) families than from higher SES families. Developmental competencies in school, conduct, and work are important precursors to the development of AUD by young adulthood that are predicted by parental EB. Occupational success may be an overlooked source of resilience for young men from low-SES families.
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| 5. |
- Kendler, Kenneth S., et al.
(författare)
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Predicting the Onset of Opioid Use Disorder in the Swedish General Population
- 2022
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Ingår i: Journal of Studies on Alcohol and Drugs. - : Alcohol Research Documentation, Inc.. - 1937-1888 .- 1938-4114. ; 83:3, s. 332-341
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Given the public health importance of opioid use disorder (OUD), we sought to understand better its risk predictors in the Swedish general population. Method: We examined the Swedish population, born 1950–1970 (n = 2,092,359), and followed through 2018. Using Cox, logistic, and co-sibling models, we explored associations between a wide range of putative risk factors and a first onset of OUD—assessed through medical, criminal, and pharmacy registers—in the entire cohort and in the cohort wherein prior cases of drug use disorder (DUD) were censored. Results: OUD was predicted by the following four risk factor domains: (a) externalizing syndromes, especially prior non-opioid DUD; (b) psychopathology; (c) psychosocial factors, including social class and immigrant and marital status; and (d) serious injuries and pain diagnoses. When predicting OUD as the first form of DUD, the importance of pain diagnoses as a predictor increased. Co-sibling analyses suggested that the association of some of these risk factors with OUD onset was likely largely causal, whereas others were a mixture of causal effects and familial confounding. An aggregate risk score from these individual risk factors had reasonable receiver operating characteristic (ROC) curve performance. Conclusions: OUD is a multifactorial syndrome for which risk can be meaningfully predicted by prior externalizing syndromes, internalizing and psychotic psychopathology, indicators of psychosocial status, and predictors of pain diagnoses. Some important differences were seen in the prediction of any OUD onset versus OUD onset as the first form of DUD. Much of the effect of these predictors appear, in co-sibling analyses, to likely reflect causal influences.
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| 6. |
- Kendler, Kenneth S., et al.
(författare)
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Risk factors for the development of opioid use disorder after first opioid prescription : a Swedish national study
- 2023
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Ingår i: Psychological Medicine. - 0033-2917. ; 53:13, s. 6223-6231
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Tidskriftsartikel (refereegranskat)abstract
- Background We need to better understand the frequency and predictors of opioid use disorder (OUD) after first opioid prescription (OP). Methods We followed 1 516 392 individuals from the Swedish population born 1980-2000, from 1 July 2007, until 31 Dec 2017. We examined putative risk predictors with univariable and multivariable Cox Models and the potential causal effects of predictors by propensity score and co-sibling analyses. Result Of the individuals in our cohort, 24.8% (375 404) received a first OP, of whom 3034 (0.90%) developed a subsequent first OUD. The hazard ratio (HR) (± 95% CIs) for OUD after OP equaled 7.10 (6.75-7.46), with a mean time to onset of 3.41 (2.39) years. The strongest putative risk factors for development of OUD after OP were prior psychiatric and substance use disorders, criminal behavior, parental divorce/death, poor school performance, current community deprivation, divorce, and male sex. Few predictors differed across sexes. OP renewal was associated with a HR of 3.66 (3.41-3.93) for OUD. Co-sibling and propensity score analyses suggested that at least a moderate proportion of the risk factor-OUD association was likely causal. A risk score to predict OUD after OP had an AUC of 0.85, where nearly 60% of cases scoring in the top decile. Conclusions In a general population sample, an OP represents a substantial risk factor for subsequent OUD. Many of the risk factors for OUD after OP can be readily assessed at the time of potential OP, permitting clinicians to evaluate the risk of iatrogenic OUD.
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| 7. |
- Kendler, Kenneth S., et al.
(författare)
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The actions and interactions of family genetic risk scores for alcohol use disorder and major depression on the risk for these two disorders
- 2022
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Ingår i: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics. - : Wiley. - 1552-4841 .- 1552-485X. ; 189:5, s. 128-138
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Tidskriftsartikel (refereegranskat)abstract
- We know little about how genetic risk factors for two disorders jointly act and interact in predisposing to illness. Therefore, in the Swedish population, born 1970–1990 (n = 2,116,082) and followed through 2015, we examine, using additive Cox models, the impact of the family genetic risk scores (FGRS) for alcohol use disorder (AUD) and major depression (MD), their interaction with each other and with the relevant comorbid disorder on risk for AUD and MD. FGRS scores are constructed using rates of illness in first-fourth degree relatives. FGRS for AUD and MD interacted in predicting of both disorders and one FRGS (e.g., for AUD) interacted with the phenotype of MD to predict that disorder (e.g., AUD). These FGRS interactions were not substantially attenuated by adding interactions with the disorders. These results replicated across sexes. In predicting risk for a given disorder, we rarely consider genetic liabilities for other disorders. But such effects were here significant and interactive. Furthermore, the primary disorder genetic risk interacts with comorbid disorders. The pathways to risk for disorders from their and other disorders' genetic liability may be more complex than commonly considered.
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| 8. |
- Kendler, Kenneth S., et al.
(författare)
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The causal nature of the association between resting pulse in late adolescence and risk for internalizing and externalizing disorders : A co-relative analysis in a national male Swedish sample
- 2021
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Ingår i: Psychological Medicine. - 0033-2917. ; 51:11, s. 1822-1828
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundResting pulse is robustly and inversely associated with the risk for externalizing disorders and may be positively associated with internalizing disorders. We know little about the causal nature of these associations.MethodsWe examined resting pulse at conscription examination in 369 301 males born 1960-80 with a mean (s.d.) follow-up of 29.1 (7.7) years. From pulse rates, we predicted, using Cox models, the risk for criminal behavior (CB), drug abuse (DA), alcohol use disorder (AUD), major depression (MD), and anxiety disorders (AD), assessed from medical, criminal, and pharmacy registries. Co-relative analyses were conducted on the general population, cousin, half-sibling, full-sibling, and monozygotic pairs discordant for the outcome. Twin/sibling modeling for pulse was performed using OpenMX.ResultsFamilial resemblance for pulse resulted entirely from genetic factors. In the general population, the risk for externalizing disorders (CB, DA, and AUD) and internalizing disorders (MD and AD) were, respectively, significantly associated with low and high resting pulse rate. For CB, DA, and AUD, co-relative analyses showed that the inverse association with pulse resulted entirely from familial common causes (aka 'confounders'). By contrast, co-relative analyses found that the association between higher pulse and MD and AD resulted from direct causal effects.ConclusionsResting pulse has a negative and positive association with, respectively, the risk for externalizing and for internalizing disorders. Co-relative analyses indicate that the nature of these associations differ, suggesting that elevated pulse appears to directly increase the risk for internalizing disorders while the reduced pulse is a risk index for underlying traits that predispose to externalizing disorders.
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| 9. |
- Kendler, Kenneth S., et al.
(författare)
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The joint effects of genetic liability and the death of close relatives on risk for major depression and alcohol use disorder in a Swedish national sample
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Ingår i: Psychological Medicine. - 0033-2917.
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Tidskriftsartikel (refereegranskat)abstract
- Background. To determine whether genetic risk factors for major depression (MD) and alcohol use disorder (AUD) interact with a potent stressor – death of spouse, parent, and sibling – in predicting episodes of, respectively, MD and AUD. Methods. MD and AUD registrations were assessed from national Swedish registries. In individuals born in Sweden 1960–1970, we identified 7586, 388 459, and 34 370 with the loss of, respectively, a spouse, parent, and sibling. We started following subjects at age 18 or the year 2002 with end of follow-up in 2018. We examined time to event – a registration for MD within 6 months or AUD within a year – on an additive scale, using the Nelson–Aalen estimator. Genetic risk was assessed by the Family Genetic Risk Score (FGRS). Results. In separate models controlling for the main effects of death of spouse, parent, and sibling, FGRS, and sex, significant interactions were seen in all analyses between genetic risk for MD and death of relative in prediction of subsequent MD registration. A similar pattern of results, albeit with weaker interaction effects, was seen for genetic risk for AUD and risk for AUD registration. Genetic risk for bipolar disorder (BD) and anxiety disorders (AD) also interacted with event exposure in predicting MD. Conclusions. Genetic risk for both MD and AUD act in part by increasing the sensitivity of individuals to the pathogenic effects of environmental stressors. For prediction of MD, similar effects are also seen for genetic risk for AD and BD.
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| 10. |
- Long, Elizabeth C., et al.
(författare)
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A National Swedish Longitudinal Twin-Sibling Study of alcohol use disorders among males
- 2017
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Ingår i: Addiction. - : Wiley. - 0965-2140. ; 112:8, s. 1378-1385
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To examine whether genetic influences on the development of alcohol use disorders (AUD) among men during emerging adulthood through mid-adulthood are stable or dynamic. Design: A twin study modeling developmental changes in the genetic and environmental influences on AUD during three age periods (18-25, 26-33 and 33-41) as a Cholesky decomposition. Setting: Sweden. Participants: Swedish male twin pairs (1532 monozygotic and 1940 dizygotic) and 66033 full male sibling pairs born less than 2 years apart. Measurements: AUD was identified based on Swedish medical and legal registries. Findings: The best-fitting model included additive genetic and unique environmental factors, with no evidence for shared environmental factors. Although the total heritability was stable over time, there were two major genetic factors contributing to AUD risk, one beginning at ages 18-25 with a modest decline in importance over time [0.84; confidence interval (CI) = 0.83-0.88], and another of less impact beginning at ages 26-33 with a modest increase in importance by ages 33-41 (0.31; CI = 0.05-0.47). Conclusions: The heritability of alcohol use disorders among Swedish men appears to be stable among three age periods: 18-25 years, 26-33 years, and 33-41 years. Two sets of genetic risk factors contribute to alcohol use disorders risk, with one originating during the ages 18-25 years and another coming online at 26-33 years, providing support for the developmentally dynamic hypothesis.
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