Clarifying the relationship between physical injuries and risk for suicide attempt in a Swedish national sample.

INTRODUCTION: The Interpersonal-Psychological Theory of Suicide proposes that capability for suicide is acquired through exposure to painful and provocative events (PPEs). Although there is robust evidence for a positive association between aggregate measures of PPEs and risk for suicidal behavior, little is known about the contributions of physical injuries. The present study investigated the relationship between injuries and risk of subsequent suicide attempt (SA). METHODS: Data were from Swedish population-based registers. All individuals born in Sweden between 1970 and 1990 were included (N = 1,011,725 females and 1,067,709 males). We used Cox regression models to test associations between 10 types of injuries (eye injury; fracture; dislocation/sprain/strain; injury to nerves and spinal cord; injury to blood vessels; intracranial injury; crushing injury; internal injury; traumatic amputation; and other or unspecified injuries) and risk for later SA. Analyses were stratified by sex and adjusted for year of birth and parental education. Additional models tested for differences in the pattern of associations based on age group and genetic liability for SA. In co-relative models, we tested the association between each injury type and risk for SA in relative pairs of varying genetic relatedness to control for unmeasured familial confounders. RESULTS: All 10 injury types were associated with elevated risk for SA (hazard ratios [HRs] = 1.2-7.0). Associations were stronger in the first year following an injury (HRs = 1.8-7.0), but HRs remained above 1 more than 1 year after injury exposure (HRs = 1.2-2.6). The strength of associations varied across injury type, sex, age, and genetic liability for SA. For example, the magnitude of the association between crushing injury and risk for SA was larger in females than males, whereas other injuries showed a similar pattern of associations across sex. Moreover, there was evidence to support positive additive interaction effects between several injury types and aggregate genetic liability for SA (relative excess risk due to interaction [RERI] = 0.1-0.3), but the majority of these interactions became non-significant or changed direction after accounting for comorbid psychiatric and substance use disorders. In co-relative models, the pattern of associations differed by injury type, such that there was evidence to support a potential causal effect of eye injury, fracture, dislocation/sprain/strain, intracranial injury, and other and unspecified injuries on risk for SA. For the remaining injury types, HRs were not significantly different from 1 in monozygotic twins, which is consistent with confounding by familial factors. CONCLUSIONS: Injuries are associated with increased risk for subsequent SA, particularly in the first year following an injury. While genetic and familial environmental factors may partly explain these associations, there is also evidence to support a potential causal effect of several injury types on future risk for SA.

Patterns and predictors of alcohol misuse trajectories from adolescence through early midlife.

We took a multilevel developmental contextual approach and characterized trajectories of alcohol misuse from adolescence through early midlife, examined genetic and environmental contributions to individual differences in those trajectories, and identified adolescent and young adult factors associated with change in alcohol misuse. Data were from two longitudinal population-based studies. FinnTwin16 is a study of Finnish twins assessed at 16, 17, 18, 25, and 35 years (N = 5659; 52% female; 32% monozygotic). The National Longitudinal Study of Adolescent to Adult Health (Add Health) is a study of adolescents from the United States, who were assessed at five time points from 1994 to 2018 (N = 18026; 50% female; 64% White, 21% Black, 4% Native American, 7% Asian, 9% Other race/ethnicity). Alcohol misuse was measured as frequency of intoxication in FinnTwin16 and frequency of binge drinking in Add Health. In both samples, trajectories of alcohol misuse were best described by a quadratic growth curve: Alcohol misuse increased across adolescence, peaked in young adulthood, and declined into early midlife. Individual differences in these trajectories were primarily explained by environmental factors. Several adolescent and young adult correlates were related to the course of alcohol misuse, including other substance use, physical and mental health, and parenthood.

Mediational pathways between aggregate genetic liability and nonfatal suicide attempt: A Swedish population-based cohort.

Despite recent progress in the genetics of suicidal behavior, the pathway by which genetic liability increases suicide attempt risk is unclear. We investigated the mediational pathways from family/genetic risk for suicide attempt (FGRSSA) to suicide attempt by considering the roles of psychiatric illnesses. In a Swedish cohort, we evaluated time to suicide attempt as a function of FGRSSA and the mediational effects of alcohol use disorder, drug use disorder, attention-deficit/hyperactivity disorder, major depression, anxiety disorder, bipolar disorder, and non-affective psychosis. Analyses were conducted by sex in three age periods: 15-25 years (Nfemales = 850,278 and Nmales = 899,366), 26-35 years (Nfemales = 800,189 and Nmales = 861,774), and 36-45 years (Nfemales = 498,285 and Nmales = 535,831). The association between FGRSSA and suicide attempt was mediated via psychiatric disorders. The highest mediation effects were observed for alcohol use disorder in males (15-25 years, HRtotal = 1.60 [1.59; 1.62], mediation = 14.4%), drug use disorder in females (25-36 years, HRtotal = 1.46 [1.44; 1.49], mediation = 11.2%), and major depression (25-36 years) in females (HRtotal = 1.46 [1.44; 1.49], mediation = 7%) and males (HRtotal = 1.50 [1.47;1.52], mediation = 4.7%). While the direct effect of FGRSSA was higher at ages of 15-25, the mediation via psychiatric disorders was more prominent in later adulthood. Our study informs about the psychiatric illnesses via which genetic liability operates to impact suicide attempt risk, with distinct contributions according to age and sex.

Divorce and risk of suicide attempt: a Swedish national study.

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.

Shared genetic and environmental etiology between substance use disorders and suicidal behavior.

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.

Clinical, environmental, and genetic risk factors for substance use disorders: characterizing combined effects across multiple cohorts.

Substance use disorders (SUDs) incur serious social and personal costs. The risk for SUDs is complex, with risk factors ranging from social conditions to individual genetic variation. We examined whether models that include a clinical/environmental risk index (CERI) and polygenic scores (PGS) are able to identify individuals at increased risk of SUD in young adulthood across four longitudinal cohorts for a combined sample of N = 15,134. Our analyses included participants of European (NEUR = 12,659) and African (NAFR = 2475) ancestries. SUD outcomes included: (1) alcohol dependence, (2) nicotine dependence; (3) drug dependence, and (4) any substance dependence. In the models containing the PGS and CERI, the CERI was associated with all three outcomes (ORs = 01.37-1.67). PGS for problematic alcohol use, externalizing, and smoking quantity were associated with alcohol dependence, drug dependence, and nicotine dependence, respectively (OR = 1.11-1.33). PGS for problematic alcohol use and externalizing were also associated with any substance dependence (ORs = 1.09-1.18). The full model explained 6-13% of the variance in SUDs. Those in the top 10% of CERI and PGS had relative risk ratios of 3.86-8.04 for each SUD relative to the bottom 90%. Overall, the combined measures of clinical, environmental, and genetic risk demonstrated modest ability to distinguish between affected and unaffected individuals in young adulthood. PGS were significant but added little in addition to the clinical/environmental risk index. Results from our analysis demonstrate there is still considerable work to be done before tools such as these are ready for clinical applications.

The effect of parental alcohol use on alcohol use disorder in young adulthood: Exploring the mediating roles of adolescent alcohol expectancies and consumption.

INTRODUCTION: Parental alcohol use and problems are risk factors for alcohol use disorder (AUD), and these effects may be mediated by adolescent alcohol expectancies and consumption. In the present study, we tested the direct effects of mothers' and fathers' alcohol consumption on young adult AUD, as well as the indirect effects through adolescent maximum alcohol use, alcohol consumption, and alcohol expectancies. METHODS: Participants were 5160 individuals (49.1% female) and their biological parents from the Avon Longitudinal Study of Parents and Children, a cohort study of children born in southwestern England during 1991 and 1992. Structural equation modeling (SEM) was used to test associations of mothers' and fathers' alcohol use (assessed when children were 12 years old) with age 24 AUD. Potential mediator variables included the maximum number of alcoholic drinks consumed within a 24-h period by age 13.5 and alcohol expectancies and alcohol consumption at ages 17 and 20. RESULTS: Higher maternal and paternal alcohol use were associated with higher levels of alcohol consumption at age 17. Greater alcohol consumption, in turn, was related to a more severe presentation of AUD. The overall indirect effects of mothers' (b = 0.033, 95% confidence interval [CI] = 0.006, 0.059) and fathers' drinking (b = 0.041, 95% CI = 0.018, 0.064) on AUD were modest but significant, and were primarily comprised of adolescent alcohol consumption rather than alcohol expectancies. CONCLUSIONS: Our findings underscore the importance of both mothers' and fathers' drinking for the development of alcohol use and problems across adolescence and young adulthood.

Principal Component Analysis Reduces Collider Bias in Polygenic Score Effect Size Estimation.

In this study, we test principal component analysis (PCA) of measured confounders as a method to reduce collider bias in polygenic association models. We present results from simulations and application of the method in the Collaborative Study of the Genetics of Alcoholism (COGA) sample with a polygenic score for alcohol problems, DSM-5 alcohol use disorder as the target phenotype, and two collider variables: tobacco use and educational attainment. Simulation results suggest that assumptions regarding the correlation structure and availability of measured confounders are complementary, such that meeting one assumption relaxes the other. Application of the method in COGA shows that PC covariates reduce collider bias when tobacco use is used as the collider variable. Application of this method may improve PRS effect size estimation in some cases by reducing the effect of collider bias, making efficient use of data resources that are available in many studies.

Exploring the relationships between adolescent alcohol misuse and later life health outcomes.

BACKGROUND: We sought to clarify the impact of adolescent alcohol misuse on adult physical health and subjective well-being. To do so, we investigated both the direct associations between adolescent alcohol misuse and early midlife physical health and life satisfaction and the indirect effects on these outcomes attributable to subsequent alcohol problems. METHOD: The sample included 2733 twin pairs (32% monozygotic; 52% female) from the FinnTwin16 study. Adolescent alcohol misuse was a composite of frequency of drunkenness, frequency of alcohol use, and alcohol problems at ages 16, 17, and 18.5. The early midlife outcomes included somatic symptoms, self-rated health, and life satisfaction at age 34. The mediators examined as part of the indirect effect analyses included alcohol problems from the Rutgers Alcohol Problem Index at ages 24 and 34. Serial mediation and co-twin comparison models were applied and included covariates from adolescence and early midlife. RESULTS: There were weak direct associations between adolescent alcohol misuse and early midlife physical health and life satisfaction. However, there was stronger evidence for indirect effects, whereby young adult and early midlife alcohol problems serially mediated the relationship between adolescent alcohol misuse and early midlife somatic symptoms (ß = 0.03, 95% CI [0.03, 0.04]), self-rated health (ß = -0.02, 95% CI [-0.03, -0.01]), and life satisfaction (ß = -0.03, CI [-0.04, -0.02]). These serial mediation effects were robust in co-twin comparison analyses. CONCLUSIONS: These results provide evidence that alcohol problems are a primary driver linking adolescent alcohol misuse and poor health outcomes across the lifespan.

Patterns and Correlates of Polysubstance Use Among Individuals With Severe Alcohol Use Disorder.

AIM: The present study examined patterns and correlates of polysubstance use among individuals with severe alcohol use disorder (AUD). METHODS: Participants were 2785 individuals (63% female; mean age = 43 years, range = 18-78 years) from the Genes, Addiction and Personality Study. All participants met lifetime criteria for severe AUD (6+ symptoms). We used latent class analysis to identify patterns of frequency of lifetime use for cigarettes, marijuana, cocaine, stimulants, sedatives, opioids and hallucinogens. A variety of demographic and behavioral correlates of latent class membership were tested in univariable and multivariable models. RESULTS: A five-class solution was selected: extended range polysubstance use (24.5%); cigarette and marijuana use (18.8%); 'testers,' characterized by high probabilities of smoking 100 or more cigarettes, using marijuana 6+ times, and trying the remaining substances 1-5 times (12.3%); moderate range polysubstance use (17.1%) and minimal use (reference class; 27.3%). In univariable analyses, all potential correlates were related to latent class membership. In the multivariable model, associations with gender, race/ethnicity, age of onset for alcohol problems, dimensions of impulsivity, depressive symptoms, antisocial behavior and family history density of alcohol problems remained significant, though the pattern and strength of associations differed across classes. For instance, sensation-seeking, lack of premeditation and family history were uniquely associated with membership in the extended range polysubstance use class. CONCLUSION: Patterns of polysubstance use are differentially related to demographic and behavioral factors among individuals with severe AUD. Assessing use across multiple substances may inform the selection of targets for treatment and prevention.

The role of adolescent social relationships in promoting alcohol resistance: Interrupting the intergenerational transmission of alcohol misuse.

Genetic factors contribute to the intergenerational transmission of alcohol misuse, but not all individuals at high genetic risk develop problems. The present study examined adolescent relationships with parents, peers, and romantic partners as predictors of realized resistance, defined as high biological risk for disorder combined with a healthy outcome, to alcohol initiation, heavy episodic drinking, and alcohol use disorder (AUD). Data were from the Collaborative Study on the Genetics of Alcoholism (N = 1,858; 49.9% female; mean age at baseline = 13.91 years). Genetic risk, indexed using family history density and polygenic risk scores for alcohol problems and AUD, was used to define alcohol resistance. Adolescent predictors included parent-child relationship quality, parental monitoring, peer drinking, romantic partner drinking, and social competence. There was little support for the hypothesis that social relationship factors would promote alcohol resistance, with the exception that higher father-child relationship quality was associated with higher resistance to alcohol initiation ( ß ^ = - 0.19 , 95% CI = -0.35, -0.03). Unexpectedly, social competence was associated with lower resistance to heavy episodic drinking ( ß ^ = 0.10 , 95% CI = 0.01, 0.20). This pattern of largely null effects underscores how little is known about resistance processes among those at high genetic risk for AUD.

Associations of Alcohol Consumption With Epigenome-Wide DNA Methylation and Epigenetic Age Acceleration: Individual-Level and Co-twin Comparison Analyses.

BACKGROUND: DNA methylation may play a role in the progression from normative to problematic drinking and underlie adverse health outcomes associated with alcohol misuse. We examined the association between alcohol consumption and DNA methylation patterns using 3 approaches: a conventional epigenome-wide association study (EWAS); a co-twin comparison design, which controls for genetic and environmental influences that twins share; and a regression of age acceleration, defined as a discrepancy between chronological age and DNA methylation age, on alcohol consumption. METHODS: Participants came from the Finnish Twin Cohorts (FinnTwin12/FinnTwin16; N = 1,004; 55% female; average age = 23 years). Individuals reported the number of alcoholic beverages consumed in the past week, and epigenome-wide DNA methylation was assessed in whole blood using the Infinium HumanMethylation450 BeadChip. RESULTS: In the EWAS, alcohol consumption was significantly related to methylation at 24 CpG sites. When evaluating whether differences between twin siblings (185 monozygotic pairs) in alcohol consumption predicted differences in DNA methylation, co-twin comparisons replicated 4 CpG sites from the EWAS and identified 23 additional sites. However, when we examined qualitative differences in drinking patterns between twins (heavy drinker vs. light drinker/abstainer or moderate drinker vs. abstainer; 44 pairs), methylation patterns did not significantly differ within twin pairs. Finally, individuals who reported higher alcohol consumption also exhibited greater age acceleration, though results were no longer significant after controlling for genetic and environmental influences shared by co-twins. CONCLUSIONS: Our analyses offer insight into the associations between epigenetic variation and levels of alcohol consumption in young adulthood.

Predicting Alcohol Dependence Symptoms by Young Adulthood: A Co-Twin Comparisons Study.

Co-twin comparisons address familial confounding by controlling for genetic and environmental influences that twin siblings share. We applied the co-twin comparison design to investigate associations of adolescent factors with alcohol dependence (AD) symptoms. Participants were 1286 individuals (581 complete twin pairs; 42% monozygotic; and 54% female) from the FinnTwin12 study. Predictors included adolescent academic achievement, substance use, externalizing problems, internalizing problems, executive functioning, peer environment, physical health, relationship with parents, alcohol expectancies, life events, and pubertal development. The outcome was lifetime AD clinical criterion count, as measured in young adulthood. We examined associations of each adolescent domain with AD symptoms in individual-level and co-twin comparison analyses. In individual-level analyses, adolescents with higher levels of substance use, teacher-reported externalizing problems at age 12, externalizing problems at age 14, self- and co-twin-reported internalizing problems, peer deviance, and perceived difficulty of life events reported more symptoms of AD in young adulthood (ps < .044). Conversely, individuals with higher academic achievement, social adjustment, self-rated health, and parent-child relationship quality met fewer AD clinical criteria (ps < .024). Associations between adolescent substance use, teacher-reported externalizing problems, co-twin-reported internalizing problems, peer deviance, self-rated health, and AD symptoms were of a similar magnitude in co-twin comparisons. We replicated many well-known adolescent correlates of later alcohol problems, including academic achievement, substance use, externalizing and internalizing problems, self-rated health, and features of the peer environment and parent-child relationship. Furthermore, we demonstrate the utility of co-twin comparisons for understanding pathways to AD. Effect sizes corresponding to the associations between adolescent substance use, teacher-reported externalizing problems, co-twin-reported internalizing problems, peer deviance, and self-rated health were not significantly attenuated (p value threshold = .05) after controlling for genetic and environmental influences that twin siblings share, highlighting these factors as candidates for further research.

Characterization of Service Use for Alcohol Problems Across Generations and Sex in Adults With Alcohol Use Disorder.

BACKGROUND: There are gaps in the literature on service use (help-seeking and treatment utilization) for alcohol problems among those with alcohol use disorder (AUD). First, policy changes and cultural shifts (e.g., insurance) related to AUD have occurred over the last few decades, making it important to study generational differences. Second, multiple studies have found that females receive fewer services than males, and exploring whether these sex differences persist across generations can inform public health and research endeavors. The current study examined service use for alcohol problems among individuals with AUD. The aims were as follows: (i) to describe service use for alcohol problems; (ii) to assess generational differences (silent [b. 1928 to 1945], boomer [b. 1946 to 1964], generation X [b. 1965 to 1980], millennial [b. 1981 to 1996]) in help-seeking and treatment utilization; and (iii) to examine sex differences across generations. METHODS: Data were from affected family members of probands who participated in the Collaborative Study on the Genetics of Alcoholism (N = 4,405). First, frequencies for service use variables were calculated across generations. Pearson chi-square and ANOVA were used to test for differences in rates and types of service use across generations, taking familial clustering into account. Next, Cox survival modeling was used to assess associations of generation and sex with time to first help-seeking and first treatment for AUD, and time from first onset of AUD to first help-seeking and first treatment. Interactions between generation and sex were tested within each Cox regression. RESULTS: Significant hazards were found in all 4 transitions. Overall, younger generations used services earlier than older generations, which translated into higher likelihoods of these behaviors. Regardless of generation, younger females were less likely to use services than males. CONCLUSIONS: There are generational and sex differences in service use for alcohol problems among individuals with AUD. Policy and clinical implications are discussed.

Investigating Associations of Substance Use and Dependence With Planned Versus Unplanned Suicide Attempt.

OBJECTIVE: The present analyses investigated substance use and dependence as correlates of past-year suicide attempt and of unplanned versus planned suicide attempt in a nationally representative sample. METHOD: Participants were 214,505 adults (52% female; 64% White, 12% Black, <1% Native American, <1% Pacific Islander, 6% Asian, 16% Hispanic, 2% multiracial) from the 2015-2019 National Surveys on Drug Use and Health. Four logistic regression models were constructed. Models 1 and 2 examined substance use and dependence, respectively, as correlates of suicide attempt. Models 3 and 4 evaluated whether substance use and dependence were related to suicide attempt in the absence of a plan. RESULTS: In Models 1 and 2, higher cigarette smoking and marijuana use; any use of opioids, sedatives, and hallucinogens; and greater dependence on nicotine, alcohol, marijuana, and any illicit or prescription drug were associated with elevated risk for suicide attempt. Associations with cigarette smoking, sedative use, and dependence on nicotine, alcohol, and any illicit or prescription drug remained statistically significant in sensitivity analyses limited to individuals with suicidal ideation. In Models 3 and 4, substance use and dependence were unrelated to risk for unplanned (vs. planned) suicide attempt. CONCLUSIONS: Although substance-related outcomes are consistently associated with suicide attempt, there was little evidence that substance use and dependence are related to risk for unplanned versus planned suicidal behavior.

Personality correlates of past-year alcohol use in individuals with severe alcohol use disorder and a lifetime history of involvement in Alcoholics Anonymous.

BACKGROUND: Alcohol Use Disorder (AUD) is a highly impairing condition with important public health impacts. Despite the availability of treatment options for AUD, research shows that few people receive treatment, and even fewer can maintain abstinence/low drinking levels. This study investigated the role of personality traits in current alcohol use among individuals with severe AUD who ever attended Alcoholics Anonymous (AA), a widespread and easily accessible self-help group for alcohol problems. METHODS: Univariable and multivariable regressions were performed separately in females and males with alcohol consumption as an outcome. Socioeconomic factors, genetic liability, and psychopathology were included as covariates. RESULTS: Results from the multivariable model indicated that in females who attended AA, higher alcohol use was related to both positive and negative urgency as well as low sensation seeking, while in males, higher alcohol use was related to positive urgency. Results also indicated an important role of younger age and lower educational levels in higher alcohol use in both sexes. Moreover, single males and those with lower AUD severity were at higher risk of using alcohol in the past year. CONCLUSIONS: These findings highlighted sex-specific correlates of drinking in individuals with AUD who engaged in self-help groups. Findings may be useful to improve treatment options, as personality encompasses modifiable traits that can be targeted in psychological interventions.

Risk of suicidal behavior as a function of alcohol use disorder typologies: A Swedish population-based study.

BACKGROUND AND AIMS: Alcohol use disorder (AUD) is one of the strongest predictors of suicidal behavior. Here, we measured risk of suicide attempt and death as a function of AUD typologies. DESIGN: We used AUD typologies from previous latent class analysis: (i) externalizing subtype (characterized by externalizing symptomatology and early age of onset; individuals in this group have lower education and higher familial/social difficulties); (ii) subtype described by minimal psychopathology; and (iii) internalizing subtype (characterized by internalizing symptomatology and later age of onset; individuals in this group have higher education). We used class membership to predict distal outcomes (attempt and death) and performed regressions to evaluate whether differences in suicidal behavior were explained by the group characteristics (sex, age of onset, number and type of AUD registrations, familial/genetic risk for AUD, externalizing and internalizing behaviors, socio-economic indicators, marital status and childhood family status). We also evaluated the effect of suicide attempt prior to AUD. SETTING AND PARTICIPANTS: Based on longitudinal Swedish registry data, we included 217 074 individuals with AUD born 1950-80. MEASUREMENTS: Suicide attempts were identified using medical registers and deaths using the mortality register. FINDINGS: Individuals with the externalizing subtype had higher risks of suicidal behavior than other groups [attempt: externalizing versus minimal psychopathology: odds ratio (OR) = 1.35, 95% confidence interval (CI) = 1.35, 1.35; externalizing versus internalizing: OR = 1.47, 95% CI = 1.46, 1.48; death: externalizing versus minimal psychopathology: OR = 1.57, 95% CI = 1.57, 1.58; externalizing versus internalizing: OR = 1.99, 95% CI = 1.93, 2.06]. Individuals with minimal psychopathology had higher risks than those with internalizing symptomatology (attempt: OR = 1.09, 95% CI = 1.08, 1.10, death: OR = 1.26, 95% CI = 1.23, 1.30). These differences were explained by age at registration and were related to the number of registrations, sex, education, family disruption and suicide attempt prior to AUD. CONCLUSIONS: Among people in Sweden, considering alcohol use disorder (AUD) heterogeneity appears to be a meaningful way to evaluate suicide risk. The highest risk of suicide attempt and death occurs in the externalizing subtype of AUD, followed by the minimal psychopathology subtype, and then the internalizing subtype.

Divorce, genetic risk, and suicidal thoughts and behaviors in a sample with recurrent major depressive disorder.

BACKGROUND: Theories of risk for suicidal thoughts and behaviors (STB) implicate both interpersonal and biological factors. Divorce/separation and aggregate genetic liability are robustly associated with STB, but have seldom been evaluated in conjunction with one another. Furthermore, whether these factors are effective predictors in high-risk populations is not clear. METHODS: Analyses were conducted in a sample of Han Chinese women with severe recurrent major depressive disorder (maximum N = 4380). Logistic regressions were used to evaluate the associations between divorce/separation and polygenic scores (PGS) for suicidal ideation or behavior with STB. Where appropriate, additive interactions between divorce and PGS were tested. RESULTS: Divorce/separation was significantly associated with increased risk of suicidal ideation, plans, and attempts (odds ratios = 1.28-1.61). PGS for suicidal ideation were not associated with STB, while PGS for suicidal behavior were associated with ideation and plans (odds ratios = 1.08-1.09). There were no significant interactions between divorce/separation and PGS. CONCLUSIONS: Consistent with theories of suicidality, the disruption or end of an important interpersonal relationship is an indicator of risk for STB. Aggregate genetic liability for suicidal behavior more modestly contributes to risk, but does not exacerbate the negative impact of divorce. Thus, even within a high-risk sample, interpersonal and biological exposures distinguish between those who do and do not experience STB, and could motivate targeted screening. Further research is necessary to evaluate whether and how the context of divorce contributes to variation in its effect on STB risk.

Personality correlates of past-year alcohol use in individuals with severe alcohol use disorder and a lifetime history of involvement in alcoholics anonymous.

BACKGROUND: Alcohol use disorder (AUD) is a highly impairing condition with important public health impacts. Despite the availability of treatment options for AUD, research shows that few people receive treatment, and even fewer can maintain abstinence/low-drinking levels. This study investigated the role of personality traits in past-year alcohol use among individuals with severe AUD who ever attended Alcoholics Anonymous (AA), a widespread and easily accessible self-help group for alcohol problems. METHODS: Univariable and multivariable regressions were performed separately in females and males with alcohol consumption as an outcome. Socioeconomic factors, genetic liability, and psychopathology were included as covariates in the analyses. RESULTS: Results from the multivariable model indicated that in females who attended AA, greater alcohol use was related to both positive and negative urgency and low sensation seeking, while in males, greater alcohol use was related to positive urgency. Results also showed that, in both sexes, younger age and lower educational levels were associated with greater alcohol use. Moreover, single males and individuals with lower AUD severity were at higher risk of using alcohol in the past year. CONCLUSIONS: These findings highlight sex-specific correlates of drinking in individuals with AUD who engaged in self-help groups. These findings may help to improve treatment options, as personality encompasses modifiable traits that can be targeted in psychological interventions.

Shared genetic liability for alcohol consumption, alcohol problems, and suicide attempt: Evaluating the role of impulsivity.

Heavy drinking and diagnosis with alcohol use disorder (AUD) are consistently associated with risk for suicide attempt (SA). Though the shared genetic architecture among alcohol consumption and problems (ACP) and SA remains largely uncharacterized, impulsivity has been proposed as a heritable, intermediate phenotype for both alcohol problems and suicidal behavior. The present study investigated the extent to which shared liability for ACP and SA is genetically related to five dimensions of impulsivity. Analyses incorporated summary statistics from genome-wide association studies of alcohol consumption (N = 160,824), problems (N = 160,824), and dependence (N = 46,568), alcoholic drinks per week (N = 537,349), suicide attempt (N = 513,497), impulsivity (N = 22,861), and extraversion (N = 63,030). We used genomic structural equation modeling (Genomic SEM) to, first, estimate a common factor model with alcohol consumption, problems, and dependence, drinks per week, and SA included as indicators. Next, we evaluated the correlations between this common genetic factor and five factors representing genetic liability to negative urgency, positive urgency, lack of premeditation, sensation-seeking, and lack of perseverance. Common genetic liability to ACP and SA was significantly correlated with all five impulsive personality traits examined (rs = 0.24-0.53, ps < 0.002), and the largest correlation was with lack of premeditation, though supplementary analyses suggested that these findings were potentially more strongly influenced by ACP than SA. These analyses have potential implications for screening and prevention: Impulsivity can be comprehensively assessed in childhood, whereas heavy drinking and suicide attempt are quite rare prior to adolescence. Our findings provide preliminary evidence that features of impulsivity may serve as early indicators of genetic risk for alcohol problems and suicidality.