| 1. |
- Mullins, Niamh, et al.
(author)
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GWAS of Suicide Attempt in Psychiatric Disorders and Association With Major Depression Polygenic Risk Scores
- 2019
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In: American Journal of Psychiatry. - : American Psychiatric Association Publishing. - 0002-953X .- 1535-7228. ; 176:8, s. 651-660
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Journal article (peer-reviewed)abstract
- Objective: More than 90% of people who attempt suicide have a psychiatric diagnosis; however, twin and family studies suggest that the genetic etiology of suicide attempt is partially distinct from that of the psychiatric disorders themselves. The authors present the largest genome-wide association study (GWAS) on suicide attempt, using cohorts of individuals with major depressive disorder, bipolar disorder, and schizophrenia from the Psychiatric Genomics Consortium.Methods: The samples comprised 1,622 suicide attempters and 8,786 nonattempters with major depressive disorder; 3,264 attempters and 5,500 nonattempters with bipolar disorder; and 1,683 attempters and 2,946 nonattempters with schizophrenia. A GWAS on suicide attempt was performed by comparing attempters to nonattempters with each disorder, followed by a meta-analysis across disorders. Polygenic risk scoring was used to investigate the genetic relationship between suicide attempt and the psychiatric disorders.Results: Three genome-wide significant loci for suicide attempt were found: one associated with suicide attempt in major depressive disorder, one associated with suicide attempt in bipolar disorder, and one in the meta-analysis of suicide attempt in mood disorders. These associations were not replicated in independent mood disorder cohorts from the UK Biobank and iPSYCH. No significant associations were found in the meta-analysis of all three disorders. Polygenic risk scores for major depression were significantly associated with suicide attempt in major depressive disorder (R2=0.25%), bipolar disorder (R2=0.24%), and schizophrenia (R2=0.40%).Conclusions: This study provides new information on genetic associations and demonstrates that genetic liability for major depression increases risk for suicide attempt across psychiatric disorders. Further collaborative efforts to increase sample size may help to robustly identify genetic associations and provide biological insights into the etiology of suicide attempt.
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| 2. |
- Edwards, Alexis C., et al.
(author)
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Protective Effects of Pregnancy on Risk of Alcohol Use Disorder
- 2019
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In: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 176:2, s. 138-145
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Journal article (peer-reviewed)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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| 3. |
- Kendler, Kenneth S., et al.
(author)
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The protective effect of pregnancy on risk for drug abuse : A population, Co-relative, Co-spouse, and within-individual analysis
- 2017
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In: American Journal of Psychiatry. - : American Psychiatric Association Publishing. - 0002-953X .- 1535-7228. ; 174:10, s. 954-962
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Journal article (peer-reviewed)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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| 4. |
- Baker, Jessica H., et al.
(author)
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Associations Between Alcohol Involvement and Drive for Thinness and Body Dissatisfaction in Adolescent Twins : A Bivariate Twin Study
- 2018
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In: Alcoholism. - : Wiley-Blackwell. - 0145-6008 .- 1530-0277. ; 42:11, s. 2214-2223
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Journal article (peer-reviewed)abstract
- BACKGROUND: Alcohol involvement has familial associations with bulimic symptoms (i.e., binge eating, inappropriate compensatory behaviors), with several studies indicating a genetic overlap between the two. It is unclear whether overlapping familial risk with alcohol involvement extends to other eating disorder symptoms. Understanding the genetic overlap between alcohol involvement and other eating disorder symptoms may aid in more targeted interventions for comorbid alcohol use-eating disorder symptoms. Thus, we investigated associations between alcohol involvement and 2 core eating disorder symptoms: drive for thinness and body dissatisfaction in adolescent female and male twins.METHODS: We assessed 3 levels of alcohol involvement: alcohol use in the last month, having ever been intoxicated, and alcohol intoxication frequency via self-report. The Eating Disorder Inventory-II assessed drive for thinness and body dissatisfaction. Sex-specific biometrical twin modeling examined the genetic overlap between alcohol involvement and eating disorder symptoms.RESULTS: Phenotypic associations between alcohol involvement, drive for thinness, and body dissatisfaction were significantly greater in girls compared with boys. A majority of the associations between alcohol involvement, drive for thinness, and body dissatisfaction in girls, but not boys, met our threshold for twin modeling (phenotypic r > 0.20). Moderate genetic correlations were observed between the 3 aspects of alcohol involvement and drive for thinness. Moderate genetic correlations were observed between alcohol use and intoxication frequency and body dissatisfaction.CONCLUSIONS: Together with the literature on alcohol involvement and bulimic symptoms, these findings suggest a generalized association between alcohol involvement and eating disorder symptoms in girls, whereas this association may be symptom specific in boys. Genetic correlations indicate that the amount and direction of this genetic overlap differs across specific symptoms. When intervening on comorbid alcohol involvement and eating disorder symptoms, it may be important to target-specific eating disorder symptoms.
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| 5. |
- Baker, Jessica H., et al.
(author)
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Illicit Drug Use, Cigarette Smoking, and Eating Disorder Symptoms : Associations in an Adolescent Twin Sample
- 2018
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In: Journal of Studies on Alcohol and Drugs. - : Alcohol Research Documentation. - 1937-1888 .- 1938-4114. ; 79:5, s. 720-724
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Journal article (peer-reviewed)abstract
- Objective: Twin studies have shown that genetic factors in part explain the established relation between alcohol use (i.e., problematic use or abuse/dependence) and eating disorder symptoms in adolescent and adult females. However, studies have yet to elucidate if there are similar shared genetic factors between other aspects of substance involvement, such as illicit drug use and repeated cigarette smoking.Method: For those sex-specific phenotypic correlations above our threshold of.20, we used a behavioral genetic design to examine potential shared genetic overlap between self-reported lifetime illicit drug use and repeated cigarette smoking and the eating disorder symptoms of drive for thinness (DT), bulimia (BU), and body dissatisfaction (BD), as assessed with the Eating Disorder Inventory-II in 16- to 17-year-old female and male twin pairs.Results: Only phenotypic correlations with illicit drug use met our threshold for twin modeling. Small to moderate genetic correlations were observed between illicit drug use and BU in both girls and boys and between illicit drug use and in girls.Conclusions: Similar etiological factors are at play in the overlap between illicit drug use and certain eating disorder symptoms in girls and boys during adolescence, such that genetic factors are important for covariance. Specifically, illicit drug use was associated with bulimia nervosa symptoms in girls and boys, which parallels previous substance use research finding a genetic overlap between alcohol use and bulimia nervosa symptoms. Future research should prospectively examine developmental trajectories to further understand the etiological overlap between substance involvement and eating disorder symptoms.
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| 6. |
- Baker, Jessica H., et al.
(author)
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Shared Familial Risk Between Bulimic Symptoms and Alcohol Involvement During Adolescence
- 2017
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In: Journal of Abnormal Psychology. - : American Psychological Association. - 0021-843X .- 1939-1846. ; 126:5, s. 506-518
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Journal article (peer-reviewed)abstract
- Twin studies show the established relation between bulimic symptoms and problematic alcohol involvement in adult females is partly due to shared familial factors, specifically shared genetic effects. However, it is unclear if similar shared etiological factors exist during adolescence or in males. We examined the familial overlap (i.e., genetic and common environmental correlations) between bulimic symptoms and various levels of alcohol involvement in 16- to 17-year-old female and male same-sex twin pairs using sex-specific biometrical twin modeling. Bulimic symptoms were assessed with the Eating Disorder Inventory-2. Alcohol involvement included alcohol use in the last month, having ever been intoxicated, and alcohol intoxication frequency. Results revealed 3 distinct patterns. First, in general, phenotypic correlations indicated statistically similar associations between bulimic symptoms and alcohol involvement in girls and boys. Second, common environmental overlap was significant for the bivariate associations including having ever been intoxicated. Third, moderate genetic correlations were observed between all bulimic symptoms and alcohol involvement in girls and moderate common environmental correlations were observed in boys for the more risky/deviant levels of involvement. Similar to adults, there is familial overlap between bulimic symptoms and alcohol involvement in adolescent girls and boys. These results could inform symptom-and sex-specific, developmentally targeted prevention and intervention programs for the comorbidity between bulimic symptoms and alcohol involvement.
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| 7. |
- Calling, Susanna, et al.
(author)
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Socioeconomic status and alcohol use disorders across the lifespan : A co-relative control study
- 2019
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 14:10, s. 0224127-0224127
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Journal article (peer-reviewed)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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| 8. |
- Drislane, Laura E., et al.
(author)
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A triarchic model analysis of the youth psychopathic traits inventory
- 2015
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In: Journal of Personality Disorders. - : Guilford Publications. - 0885-579X .- 1943-2763. ; 29:1, s. 15-41
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Journal article (peer-reviewed)abstract
- The Triarchic model of psychopathy characterizes this complex condition in terms of distinct phenotypic constructs of boldness, meanness, and disinhibition. The current study evaluated the coverage of these constructs provided by a well-established inventory for assessing psychopathy in adolescents, the Youth Psychopathic Traits Inventory (YPI). A consensus rating approach was used to identify YPI items relevant to each Triarchic model construct, and convergent and discriminant validity of the resulting YPI-Triarchic scales were examined in relation to criterion measures consisting of scores on other psychopathy measures and relevant personality trait variables (N = 618, M age = 18.8). The YPI-Triarchic scales showed good internal consistency and exhibited properties largely consistent with predictions based on the Triarchic model, aside from somewhat greater than expected covariance between boldness and other facet scales. Findings are discussed in terms of their implications for interpreting scores on the YPI and for investigating distinctive components of psychopathy in youth.
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| 9. |
- Edwards, Alexis C., et al.
(author)
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Associations between Divorce and Onset of Drug Abuse in a Swedish National Sample
- 2018
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In: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 187:5, s. 1010-1018
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Journal article (peer-reviewed)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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| 10. |
- Edwards, Alexis C., et al.
(author)
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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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In: Addictive Behaviors. - : Elsevier BV. - 0306-4603. ; 72, s. 8-13
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Journal article (peer-reviewed)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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