Socioeconomic position indicators and risk of alcohol-related medical conditions: A national cohort study from Sweden.

BACKGROUND: Alcohol consumption contributes to excess morbidity and mortality in part through the development of alcohol-related medical conditions (AMCs, including alcoholic cardiomyopathy, hepatitis, cirrhosis, etc.). The current study aimed to clarify the extent to which risk for these outcomes differs as a function of socioeconomic position (SEP), as discrepancies could lead to exacerbated health disparities. METHODS AND FINDINGS: We used longitudinal Swedish national registries to estimate the individual and joint associations between 2 SEP indicators, educational attainment and income level, and risk of AMC based on International Classification of Diseases codes, while controlling for other sociodemographic covariates and psychiatric illness. We conducted Cox proportional hazards models in sex-stratified analyses (N = 1,162,679 females and N = 1,196,659 males), beginning observation at age 40 with follow-up through December 2018, death, or emigration. By the end of follow-up, 4,253 (0.37%) females and 11,183 (0.93%) males had received an AMC registration, corresponding to overall AMC incidence rates among females and males of 2.01 and 5.20, respectively. In sex-stratified models adjusted for birth year, marital status, region of origin, internalizing and externalizing disorder registrations, and alcohol use disorder (AUD) registration, lower educational attainment was associated with higher risk of AMC in both females (hazard ratios [HRs] = 1.40 to 2.46 for low- and mid-level educational attainment across 0 to 15 years of observation) and males (HRs = 1.13 to 1.48). Likewise, risk of AMC was increased for those with lower income levels (females: HRs = 1.10 to 5.86; males: HRs = 1.07 to 6.41). In secondary analyses, we further adjusted for aggregate familial risk of AUD by including family genetic risk scores for AUD (FGRSAUD), estimated using medical, pharmacy, and criminal registries in extended families, as covariates. While FGRSAUD were associated with risk of AMC in adjusted models (HR = 1.17 for females and HR = 1.21 for males), estimates for education and income level remained largely unchanged. Furthermore, FGRSAUD interacted with income level, but not education level, such that those at higher familial liability to AUD were more susceptible to the adverse effect of low income. Limitations of these analyses include the possibility of false negatives for psychiatric illness registrations, changes in income after age 40 that were not accounted for due to modeling restrictions, restriction to residents of a high-income country, and the inability to account for individual-level alcohol consumption using registry data. CONCLUSIONS: Using comprehensive national registry data, these analyses demonstrate that individuals with lower levels of education and/or income are at higher risk of developing AMC. These associations persist even when accounting for a range of sociodemographic, psychiatric, and familial risk factors. Differences in risk could contribute to further health disparities, potentially warranting increased screening and prevention efforts in clinical and public health settings.

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.

Alcohol use disorder and risk of specific methods of suicide death in a national cohort.

INTRODUCTION: Alcohol use disorder (AUD) is among the strongest correlates of suicide death, but it is unclear whether AUD status is differentially associated with risk of suicide by particular methods. METHODS: The authors used competing risks models to evaluate the association between AUD status and risk of suicide by poisoning, suffocation, drowning, firearm, instruments, jumping, or other means in a large Swedish cohort born 1932-1995 (total N = 6,581,827; 48.8% female). Data were derived from Swedish national registers, including the Cause of Death Register and a range of medical registers. RESULTS: After adjusting for sociodemographic factors and familial liability to suicidal behavior, AUD was positively associated with risk of suicide for each method evaluated (cumulative incidence differences: 0.006-1.040 for females, 0.046-0.680 for males), except the association with firearm suicide in females. AUD was most strongly associated with risk of suicide by poisoning. Sex differences in the effects of AUD and family liability were observed for some, but not all, methods. Furthermore, high familial liability for suicidal behavior exacerbated AUD's impact on risk for suicide by poisoning (both sexes) and suffocation and jumping (males only), while the inverse interaction was observed for firearm suicide (males only). CONCLUSIONS: AUD increases risk of suicide by all methods examined and is particularly potent with respect to risk of suicide by poisoning. Differences in risk related to sex and familial liability to suicidal behavior underscore AUD's nuanced role in suicide risk. Future research should investigate targeted means restriction effectiveness among persons with AUD.

Associations between polygenic liability to psychopathology and non-suicidal versus suicidal self-injury.

Little is known about how non-suicidal and suicidal self-injury are differentially genetically related to psychopathology and related measures. This research was conducted using the UK Biobank Resource, in participants of European ancestry (N = 2320 non-suicidal self-injury [NSSI] only; N = 2648 suicide attempt; 69.18% female). We compared polygenic scores (PGS) for psychopathology and other relevant measures within self-injuring individuals. Logistic regressions and likelihood ratio tests (LRT) were used to identify PGS that were differentially associated with these outcomes. In a multivariable model, PGS for anorexia nervosa (odds ratio [OR] = 1.07; 95% confidence intervals [CI] 1.01; 1.15) and suicidal behavior (OR = 1.06; 95% CI 1.00; 1.12) both differentiated between NSSI and suicide attempt, while the PGS for other phenotypes did not. The LRT between the multivariable and base models was significant (Chi square = 11.38, df = 2, p = 0.003), and the multivariable model explained a larger proportion of variance (Nagelkerke's pseudo-R2 = 0.028 vs. 0.025). While NSSI and suicidal behavior are similarly genetically related to a range of mental health and related outcomes, genetic liability to anorexia nervosa and suicidal behavior is higher among those reporting a suicide attempt than those reporting NSSI-only. Further elucidation of these distinctions is necessary, which will require a nuanced assessment of suicidal versus non-suicidal self-injury in large samples.

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.

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.

A Swedish population-based study to evaluate the usefulness of resting heart rate in the prediction of suicidal behavior among males.

INTRODUCTION: Resting heart rate has been distinctly related to both internalizing (high pulse) and externalizing (low pulse) disorders. We aimed to explore the associations between resting heart rate and suicidal behavior (nonfatal suicide attempt [SA] and suicide death [SD]) and evaluate if such associations exist beyond the effects of internalizing/externalizing symptomatology. METHOD: We used Cox proportional hazards models to evaluate the associations between resting heart rate (age 19) and later SA/SD in 357,290 Swedish men. Models were controlled for internalizing disorders, externalizing disorders, and resilience (the ability to deal with adversity). Co-relative analysis (comparing pairs of different genetic relatedness) was used to control for unmeasured family confounders and improve causal inference. RESULTS: In baseline models, low resting heart rate was associated with SA (HR = 0.96; 95% CI: 0.95,0.98) and high resting heart rate with SD (HR = 1.04; 95% CI: 1.002,1.07). The association with SA remained after adjustment for all confounders (HR = 0.98). However, the association with SD did not persist after controlling for covariates. Co-relative analysis did not support causal associations. CONCLUSIONS: Our findings raise interesting etiological questions for the understanding of suicidal behaviors but do not support the usefulness of resting heart rate in suicide prediction.

Risk of depression in persons with Alzheimer's disease: A national cohort study.

INTRODUCTION: Depression is a risk factor and possible prodromal symptom of Alzheimer's disease (AD), but little is known about subsequent risk of developing depression in persons with AD. METHODS: National matched cohort study was conducted of all 129,410 persons diagnosed with AD and 390,088 with all-cause dementia during 1998-2017 in Sweden, and 3,900,880 age- and sex-matched controls without dementia, who had no prior depression. Cox regression was used to compute hazard ratios (HRs) for major depression through 2018. RESULTS: Cumulative incidence of major depression was 13% in persons with AD and 3% in controls. Adjusting for sociodemographic factors and comorbidities, risk of major depression was greater than two-fold higher in women with AD (HR, 2.21; 95% confidence interval [CI], 2.11-2.32) or men with AD (2.68; 2.52-2.85), compared with controls. Similar results were found for all-cause dementia. DISCUSSION: Persons diagnosed with AD or related dementias need close follow-up for timely detection and treatment of depression. Highlights: In a large cohort, women and men with AD had >2-fold subsequent risk of depression.Risks were highest in the first year (>3-fold) but remained elevated ≥3 years later.Risk of depression was highest in persons aged ≥85 years at AD diagnosis.Persons with AD need close follow-up for detection and treatment of depression.

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.