Alcohol use disorder, psychiatric comorbidities, marriage and divorce in a high-risk sample.

OBJECTIVE: To examine associations between alcohol use disorder (AUD), its psychiatric comorbidities, and their interactions, with marital outcomes in a diverse high-risk, genetically informative sample. METHOD: Participants included European ancestry (EA; n = 4,045) and African ancestry (AA; n = 1,550) individuals from the multigenerational Collaborative Study on the Genetics of Alcoholism (COGA) sample (56% female, Mage ∼ 41 years). Outcomes were lifetime marriage and divorce. Predictors included lifetime AUD, an alcohol problems polygenic score (PRS), and AUD comorbidities, including conduct or antisocial personality disorder (ASP), cannabis dependence/abuse (CAN), frequent tobacco use (TOB), and major depressive disorder (MDD). Mixed effect Cox models and generalized linear mixed effects models were fit. RESULTS: Among EA participants, those with AUD and CAN were less likely to marry (hazard ratios [HRs] 0.70-0.83, ps < 0.01). Among AA participants, those with AUD and TOB were less likely to marry (HRs 0.66-0.82, ps < 0.05) and those with MDD were more likely to marry (HR = 1.34, ps < 0.01). Among EA participants, AUD, CAN, TOB, and MDD were associated with higher odds of divorce (odds ratios [ORs] 1.59-2.21, ps < 0.01). Among AA participants, no predictors were significantly associated with divorce. Significant random effects indicated genetic and environmental influences on marriage, but only environmental factors on divorce. CONCLUSIONS: In a high-risk sample, AUD was associated with reduced likelihood of marriage in EA and AA individuals and increased risk of divorce in EA individuals. These associations were largely independent of comorbidities. Genetic and environmental background factors contributed to marriage, while only environmental background factors contributed to divorce. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Temporal trends in smoking and nicotine dependence in relation to co-occurring substance use in the United States, 2005-2016.

BACKGROUND: Despite an overall decline in tobacco use in the United States, secular trends of smoking and nicotine dependence with co-occurring substance use are not well characterized. METHODS: We examined self-reported tobacco and other substance use in 22,245 participants age 21-59 in the United States from six waves of the National Health and Nutrition Examination Survey (NHANES). Using Joinpoint regression, we assessed secular trends of smoking and nicotine dependence as a function of co-occurring use of alcohol, prescription opioids, marijuana/hashish, cocaine/heroin/methamphetamine, or other injection drug use. Multivariable logistic regressions were fitted to identify the potential risk factors. RESULTS: During 2005-2016, the prevalence of current smoking decreased (without co-occurring substance use: 17.0 %-12.7 %; with co-occurring use of one substance: 35.3 % to 24.6 %; with co-occurring use of two or more substances: 53.8 %-42.2 %), and moderate-to-severe nicotine dependence decreased as well (8.0 %-4.2 %, 16.0 %-8.8 %, and 23.9 %-15.7 %, respectively). Smoking and nicotine dependence were more likely in those with co-occurring use of one substance (current smoking: odds ratio [OR] = 2.22, 95 % confidence interval [CI] = 2.01-2.45); nicotine dependence: OR = 1.88, 95 % CI = 1.63-2.17) and in those with co-occurring use of two or more substances (current smoking: OR = 5.25, 95 % CI = 4.63-5.95; nicotine dependence: OR = 3.24, 95 % CI = 2.72-3.87). CONCLUSIONS: Co-occurring substance use was associated with smaller reductions in tobacco use, over time, and with increased odds of nicotine dependence. This suggests that co-occurring substance users should be regarded as a tobacco-related disparity group and prioritized for tobacco control interventions.

Timing of mortality in mothers with recurrent convictions for driving under the influence of alcohol and their children, from childbirth to child age 17.

BACKGROUND: We tested variation in the timing of child and maternal mortality associated with severe maternal AUD, as represented by recurrent arrests for driving under the influence of alcohol (rDUI). METHODS: rDUI mothers (N = 1614) and Controls with no alcohol-related driving offenses (N = 109,928) who gave birth in Missouri from 2000 to 2004 were identified using vital records. Propensity score matching adjusted for birth record measures including delayed prenatal care, smoking during pregnancy, relationship with reproductive partner [married/unmarried, paternity acknowledged/unacknowledged], partner DUI status from driving records, and for socioeconomic characteristics of maternal residential census tract at birth derived from census data. Survival analysis was used to test months from childbirth to child or maternal death as a function of lifetime rDUI status. RESULTS: Maternal rDUIs were associated with a consistently elevated probability of child mortality from birth through child age 17 after propensity score-adjustment (Hazard Ratio [HR] = 1.70, 95 % CI = 1.17-2.47). Maternal mortality was not elevated, relative to Controls, until child age 6-11 (HR = 1.58, 95 % CI = 1.05-2.35) and increased again from child age 12-17 (HR = 4.12, 95 % CI = 3.04-5.86). CONCLUSIONS: Severe maternal AUD, as characterized by rDUI, increases the risk for child mortality over that of Controls through age 17. Delays in rDUI maternal mortality until child age 6 may indicate a period when maternal referral for intervention to reduce harm to child and mother is likely to be especially effective.

Social class discrimination as a predictor of first cigarette use and transition to nicotine use disorder in Black and White youth.

PURPOSE: To characterize the association of social class discrimination with the timing of first cigarette use and progression to DSM-IV nicotine dependence (ND) in Black and White youth, examining variation by race, parent vs. youth experiences of discrimination, socioeconomic status (SES), and stage of smoking. METHODS: Data were drawn from 1461 youth (55.2% Black, 44.8% White; 50.2% female) and mothers in a high-risk family study of alcohol use disorder and related conditions. Cox proportional hazard regression analyses were conducted, using youth's and mother's social class discrimination to predict first cigarette use and progression to ND, stratifying by race. Interactions between discrimination and SES indicators (parental education and household income) were tested. Adjusted models included psychiatric covariates. RESULTS: In the adjusted first cigarette use models, neither youth's nor mother's social class discrimination was a significant predictor among Black youth, but mother's discrimination was associated with increased risk [HR = 1.53 (1.18-1.99)] among White youth. In the adjusted ND models, mother's discrimination was associated with reduced ND risk for Black youth in middle-income families [HR = 0.29 (CI 0.13-0.63)], but neither youth's nor mother's discrimination predicted transition to ND among White youth. CONCLUSIONS: The observed race and smoking stage-specific effects suggest that social class discrimination is more impactful on early stages of smoking for White youth and later stages for Black youth. The robustness of links with mother's discrimination experiences further suggests the importance of considering family-level effects and the need to explore possible mechanisms, such as socialization processes.

A large-scale genome-wide association study meta-analysis of cannabis use disorder.

BACKGROUND: Variation in liability to cannabis use disorder has a strong genetic component (estimated twin and family heritability about 50-70%) and is associated with negative outcomes, including increased risk of psychopathology. The aim of the study was to conduct a large genome-wide association study (GWAS) to identify novel genetic variants associated with cannabis use disorder. METHODS: To conduct this GWAS meta-analysis of cannabis use disorder and identify associations with genetic loci, we used samples from the Psychiatric Genomics Consortium Substance Use Disorders working group, iPSYCH, and deCODE (20 916 case samples, 363 116 control samples in total), contrasting cannabis use disorder cases with controls. To examine the genetic overlap between cannabis use disorder and 22 traits of interest (chosen because of previously published phenotypic correlations [eg, psychiatric disorders] or hypothesised associations [eg, chronotype] with cannabis use disorder), we used linkage disequilibrium score regression to calculate genetic correlations. FINDINGS: We identified two genome-wide significant loci: a novel chromosome 7 locus (FOXP2, lead single-nucleotide polymorphism [SNP] rs7783012; odds ratio [OR] 1·11, 95% CI 1·07-1·15, p=1·84 × 10-9) and the previously identified chromosome 8 locus (near CHRNA2 and EPHX2, lead SNP rs4732724; OR 0·89, 95% CI 0·86-0·93, p=6·46 × 10-9). Cannabis use disorder and cannabis use were genetically correlated (rg 0·50, p=1·50 × 10-21), but they showed significantly different genetic correlations with 12 of the 22 traits we tested, suggesting at least partially different genetic underpinnings of cannabis use and cannabis use disorder. Cannabis use disorder was positively genetically correlated with other psychopathology, including ADHD, major depression, and schizophrenia. INTERPRETATION: These findings support the theory that cannabis use disorder has shared genetic liability with other psychopathology, and there is a distinction between genetic liability to cannabis use and cannabis use disorder. FUNDING: National Institute of Mental Health; National Institute on Alcohol Abuse and Alcoholism; National Institute on Drug Abuse; Center for Genomics and Personalized Medicine and the Centre for Integrative Sequencing; The European Commission, Horizon 2020; National Institute of Child Health and Human Development; Health Research Council of New Zealand; National Institute on Aging; Wellcome Trust Case Control Consortium; UK Research and Innovation Medical Research Council (UKRI MRC); The Brain & Behavior Research Foundation; National Institute on Deafness and Other Communication Disorders; Substance Abuse and Mental Health Services Administration (SAMHSA); National Institute of Biomedical Imaging and Bioengineering; National Health and Medical Research Council (NHMRC) Australia; Tobacco-Related Disease Research Program of the University of California; Families for Borderline Personality Disorder Research (Beth and Rob Elliott) 2018 NARSAD Young Investigator Grant; The National Child Health Research Foundation (Cure Kids); The Canterbury Medical Research Foundation; The New Zealand Lottery Grants Board; The University of Otago; The Carney Centre for Pharmacogenomics; The James Hume Bequest Fund; National Institutes of Health: Genes, Environment and Health Initiative; National Institutes of Health; National Cancer Institute; The William T Grant Foundation; Australian Research Council; The Virginia Tobacco Settlement Foundation; The VISN 1 and VISN 4 Mental Illness Research, Education, and Clinical Centers of the US Department of Veterans Affairs; The 5th Framework Programme (FP-5) GenomEUtwin Project; The Lundbeck Foundation; NIH-funded Shared Instrumentation Grant S10RR025141; Clinical Translational Sciences Award grants; National Institute of Neurological Disorders and Stroke; National Heart, Lung, and Blood Institute; National Institute of General Medical Sciences.

Marital status, partner acknowledgment of paternity, and neighborhood influences on smoking during first pregnancy: findings across race/ethnicity in linked administrative and census data.

BACKGROUND: Improving prediction of cigarette smoking during pregnancy (SDP), including differences by race/ethnicity and geography, is necessary for interventions to achieve greater and more equitable SDP reductions. METHODS: Using individual-level data on singleton first births, 2010-2017 (N = 182,894), in a US state with high SDP rates, we predicted SDP risk as a function of reproductive partner relationship (marital status, paternity acknowledgement), maternal and residential census tract sociodemographics, and census tract five-year SDP rate. RESULTS: SDP prevalence was 12.7% (white non-Hispanics, WNH), 6.8% (Black/African Americans, AA), 19.5% (Native American, NA), 4.7% (Hispanic, H), and 2.8% (Asian, AS). In WNH and AA, with similar trends in other groups, after adjustment for non-linear effects of maternal age and education and for census tract risk-factors, there was a consistent risk-ordering of SDP rates by reproductive partner relationship: married/with paternity acknowledged < unmarried/acknowledged < unmarried/unacknowledged < married/unacknowledged. Associations with census tract SDP rate, adjusted for maternal and census tract sociodemographics, were stronger for AA and H (OR 2.65-2.67) than for NA (OR = 1.91), WNH (OR = 1.75), or AS (NS). AA SDP was increased in tracts having a higher proportion of WNH residents and was reduced in comparison with WNH at every combination of age, education and partner relationship. CONCLUSIONS: Inattention to differences by race/ethnicity may obscure SDP risk factors. Despite marked race/ethnic differences in unmarried-partner cohabitation rates, failure to acknowledge paternity emerged as an important and consistent risk-predictor. Census-tract five-year SDP rates have heterogeneous origins, but the association of AA SDP risk with increased racial heterogeneity suggests an important influence of neighbor risk behaviors.

Eating disorders in a community-based sample of women with alcohol use disorder and nicotine dependence.

BACKGROUND: Studies consistently report a higher prevalence of substance use disorders (SUDs) among women with eating disorders than control women. However, limited research exists on the prevalence of eating disorder symptoms and diagnoses in women with SUDs, especially in community-based populations. We examined the prevalence of eating disorder symptoms and diagnosis by the presence or absence of lifetime alcohol use disorder (AUD) and/or nicotine dependence (ND) in a community-based sample of women. METHODS: 3756 women (median age = 22 years) from the Missouri Adolescent Female Twin Study completed a modified semi-structured interview assessing lifetime DSM-IV psychiatric disorders and SUDs. Logistic regression models adjusted for demographic characteristics and other psychopathology, and robust standard errors accounted for the non-independence of twin data. RESULTS: In general, women with comorbid AUD and ND had a higher prevalence of eating disorder symptoms and diagnoses than women with AUD or ND Only, who in turn had a higher prevalence than those without either SUD. After adjustment for covariates, women with AUD and ND had significantly greater risk of broad anorexia nervosa (RRR = 3.17; 99 % CI = 1.35, 7.44), purging disorder (2.59; 1.24, 5.43), and numerous eating disorder symptoms than women with neither disorder. Significant differences emerged between individuals with both AUD and ND versus women with AUD Only or ND Only for some eating disorder symptoms. CONCLUSIONS: Women with lifetime AUD or ND diagnoses are at high risk for eating disorder symptoms and diagnoses, underscoring the importance of assessing eating disorder symptoms among women with these disorders.

Alcohol sensitivity in women after undergoing bariatric surgery: a cross-sectional study.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), the most common bariatric surgeries performed worldwide, increase the risk to develop an alcohol use disorder. This might be due, in part, to surgery-related changes in alcohol pharmacokinetics. Another risk factor, unexplored within this population, is having a reduced subjective response to alcohol's sedative effects. OBJECTIVES: To assess whether the alcohol sensitivity questionnaire (ASQ), a simple self-report measure, could pinpoint reduced alcohol sensitivity in the bariatric population. SETTING: University medical centers in Missouri and Illinois. METHODS: Women who had RYGB (n = 16), SG (n = 28), or laparoscopic adjustable gastric banding surgery (n = 11) within the last 5 years completed the ASQ for both pre- and postsurgical timeframes, and 45 of them participated in oral alcohol challenge testing postsurgery. Blood alcohol concentration (BAC) and subjective stimulation and sedation were measured before and for 3.5 hours after drinking. RESULTS: In line with faster and higher peak BACs after RYGB and SG than laparoscopic adjustable gastric banding surgery (P < .001), postsurgery ASQ scores were more reduced from presurgery scores after RYGB/SG than after laparoscopic adjustable gastric banding surgery (-2.3 ± .3 versus -1.2 ± .2; P < .05). However, despite the dramatic changes in BAC observed when ingesting alcohol after RYGB/SG surgeries, which resulted in peak BAC that were approximately 50% above the legal driving limit, a third of these women felt almost no alcohol-related sedative effects. CONCLUSIONS: Although RYGB/SG dramatically increased sensitivity to alcohol in all participants, meaningful interindividual differences remained. The ASQ might help identify patients at increased risk to develop an alcohol use disorder after surgery.

Patterns of gambling and substance use initiation in African American and White adolescents and young adults.

The focus of the current investigation is to examine the temporal relationship of gambling onset and alcohol, tobacco, and cannabis initiation in adolescents and young adults (M age = 20.3 years) by examining the prevalence and pattern of onset for each substance and gambling pairing and the associated risk between gambling and each substance use. Data were drawn from the multiwave Missouri Family Study (n = 1,349) of African American (AA; n = 450) and White families (n = 317) enriched for risk for alcohol use disorder and includes those who were assessed for gambling behaviors and problems: AA (360 males, 390 females) and White (287 males, 312 females). Findings indicated racial differences in the overall prevalence of gambling behaviors and substance use as well as patterns of initiation-particularly within gambling/alcohol and gambling/tobacco for males. Survival models revealed some similarities as well as differences across race and gender groups in associations of gambling with initiation of substances, as well as substances with initiation of gambling. Alcohol use (AA males only) and cannabis use (AA males and White females) elevated the hazards of initiating gambling. In contrast, gambling significantly elevated the hazards of initiation alcohol across 3 of 4 groups and of cannabis use in AA males only. The results highlight some overlapping as well as distinct risk factors for both gambling and substance use initiation in this cohort enriched for vulnerability to alcohol use disorder (AUD). These findings have implications for integrating gambling prevention into existing substance use prevention and intervention efforts-particularly but not exclusively for young AA males. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Elevated maternal and child mortality among women with multiple DUI convictions compared with socio-demographically matched controls.

AIMS: To assess whether having multiple convictions for driving while under the influence of alcohol (MDUI) in women is a risk factor for maternal, infant and child mortality. DESIGN: Retrospective cohort design using record linkage, comparing women with MDUI convictions with propensity-matched women without alcohol-related driving offences ascertained through state records, on rates of maternal, infant and child mortality. SETTING: Missouri, United States. PARTICIPANTS: MDUI women (n = 1658) and women with no alcohol-related driving convictions (control, n = 184 252) who gave birth from 2000 to 2004. MEASUREMENTS: Data were obtained from state administrative records and US Census data. The outcomes were maternal, infant and child mortality. The input variable was presence or absence of MDUI convictions. Propensity-matching variables were maternal (smoking during pregnancy, delayed prenatal care, previous child deaths, age at birth, mother Missouri-born, education, pre-pregnancy obesity, marital status), reproductive partner (un-named partner, race/ethnicity, education, DUI status) and census tract (socio-economic advantage, urbanicity) characteristics. FINDINGS: Women with MDUI convictions had higher odds of maternal, infant and child mortality than propensity-matched controls [odds ratio (OR) = 2.65, 95% confidence interval (CI) = 2.07-3.40 and OR = 1.75, 95% CI = 1.17-2.61, respectively]. CONCLUSIONS: Having multiple convictions for driving under the influence of alcohol in women appears to be a risk factor for increased maternal, infant and child mortality.

The interaction of sociodemographic risk factors and measures of nicotine dependence in predicting maternal smoking during pregnancy.

BACKGROUND: Understanding differences in nicotine dependence assessments' ability to predict smoking cessation is complicated by variation in quit attempt contexts. Pregnancy reduces this variation, as each pregnant smoker receives the same strong cessation incentive. Cigarette smoking during pregnancy (SDP) provides a powerful paradigm for analyzing the interplay between nicotine dependence measures and sociodemographics in predicting cessation failure. METHODS: Data from a female twin cohort (median birth year 1980), assessed in teens and early twenties, were merged with birth records to identify those with smoking history who experienced childbirth (N = 1657 births, N = 763 mothers). Logistic regression predicting SDP, as a function of birth record sociodemographic variables, generated a sociodemographic risk-score. Further analysis incorporated the risk-score with data from research interviews on DSM-IV-Nicotine Dependence symptom count, Heaviness of Smoking Index. RESULTS: Low maternal educational level, younger age at childbirth, and being unmarried all contributed risk for SDP. In addition to sociodemographic risk-score, the best predictors of SDP included HSI-score (OR:1.51), their two-way interaction (OR:0.39; reduced impact of dependence at intermediate-high sociodemographic risk), history of ≥ two failed quit attempts (OR:1.38), and a dummy variable for prior pregnancy at time of assessment (OR:1.82). DSM-IV-Nicotine Dependence symptoms underperformed the Heaviness of Smoking Index and did not improve prediction when added to the best model. CONCLUSIONS: The 2-item Heaviness of Smoking Index measure and report of ≥ two failed quit attempts performed best for predicting SDP. The contribution of either nicotine dependence measure to SDP risk was diminished at increased levels of sociodemographic risk.

Risk Factors Associated With Gambling Involvement among a National Sample of African American and European American Young Adults.

In the current research, we examined the association of key risk and protective factors for gambling involvement from the domains of family environment, conduct problems/delinquency, substance use, and depressive psychopathology in a nationally representative sample. The sample was comprised of 13,291 young adults (ages 18-26; Meanage = 22.8) self-identifying as European American (n=9,939) or African American (n=3,335) who participated in Wave III (n = 15,170) of the restricted-use National Longitudinal Study of Adolescent to Adult Health. We used separate logistic regressions to study participation in specific gam bling categories (lottery games, casino-type games, other games). Childhood neglect, physical discipline, and current alcohol use was associated across each of the three gam bling categories. Our results also revealed differences between European American and African American subjects. Current cannabis use was associated with all three categories among African Americans, while current cigarette use was associated among European Americans for lottery games, and depression (female) was associated with other games. We also applied multinomial logistic regression to study gambling involvement based on the number of gam bling categories that the participant engaged in 2 or more (referent), only 1, or none at all. Our results revealed that delinquency/conduct symptoms (AOR=0.83) along with cannabis use (African American; AOR =0.66), cigarette use (European American; AOR =0.83), current alcohol use (AOR=0.66) were associated with gambling in two categories vs. gambling in one category. Childhood physical discipline (AOR=0.75) and childhood neglect (AOR=0.75) were associated with gam bling in two categories vs. no gambling. Further are needed to investigate the developmental pathways leading to increased gam bling involvement among African American and European American adolescents and young adults.

Impact of adherence to antidepressants on long-term prescription opioid use cessation.

BACKGROUND: Depression contributes to persistent opioid analgesic use (OAU). Treating depression may increase opioid cessation. Aims To determine if adherence to antidepressant medications (ADMs) v. non-adherence was associated with opioid cessation in patients with a new depression episode after >90 days of OAU. METHOD: Patients with non-cancer, non-HIV pain (n = 2821), with a new episode of depression following >90 days of OAU, were eligible if they received ≥1 ADM prescription from 2002 to 2012. ADM adherence was defined as >80% of days covered. Opioid cessation was defined as ≥182 days without a prescription refill. Confounding was controlled by inverse probability of treatment weighting. RESULTS: In weighted data, the incidence rate of opioid cessation was significantly (P = 0.007) greater in patients who adhered v. did not adhered to taking antidepressants (57.2/1000 v. 45.0/1000 person-years). ADM adherence was significantly associated with opioid cessation (odds ratio (OR) = 1.24, 95% CI 1.05-1.46). CONCLUSIONS: ADM adherence, compared with non-adherence, is associated with opioid cessation in non-cancer pain. Opioid taper and cessation may be more successful when depression is treated to remission. Declaration of interest None.

Sleeve gastrectomy surgery: when 2 alcoholic drinks are converted to 4.

BACKGROUND: While it is well established that Roux-en-Y gastric bypass (RYGB) causes a rapid and heightened peak blood alcohol concentration (BAC), results from previous studies on the effects of sleeve gastrectomy (SG) on alcohol pharmacokinetics are conflicting. Data from 2 studies found SG did not affect BAC, whereas another study found SG caused a heightened peak BAC after alcohol ingestion. Moreover, these 3 studies estimated BAC from breathalyzers, which might not reliably estimate peak BAC. OBJECTIVES: The aims of this study were to evaluate (1) the effect of SG, relative to RYGB and a presurgery group, on alcohol pharmacokinetics and subjective effects, and (2) whether breathalyzers are reliable in this population. SETTING: Single-center prospective nonrandomized trial. METHODS: We performed alcohol challenge tests in 11 women who had SG surgery 1.9 ± .1 years ago (body mass index = 35.1 ± 6.6 kg/m2), 8 women who had RYGB surgery 2.2 ± .4 years ago (body mass index = 30.0 ± 5.2 kg/m2), and 9 women who were scheduled for bariatric surgery (body mass index = 44.1 ± 4.0 kg/m2). BACs were estimated from breath samples and measured by gas chromatography at various times after consuming approximately 2 standard drinks. RESULTS: BAC increased faster, peak BAC was approximately 2-fold higher, and feelings of drunkenness were heightened in both SG and RYGB groups relative to the presurgery group (P values<.001). BAC estimated from breath samples underestimated BAC by 27% (standard deviation = 13%) and missed peak BACs postsurgery. CONCLUSIONS: SG, similar to RYGB, causes marked alterations in the response to alcohol ingestion manifested by a faster and higher peak BAC. The breathalyzer is invalid to assess effects of gastric surgeries on pharmacokinetics of ingested alcohol.

Associations of parental alcohol use disorders and parental separation with offspring initiation of alcohol, cigarette and cannabis use and sexual debut in high-risk families.

BACKGROUND AND AIMS: Parental alcohol use disorders (AUDs) and parental separation are associated with increased risk for early use of alcohol in offspring, but whether they increase risks for early use of other substances and for early sexual debut is under-studied. We focused on associations of parental AUDs and parental separation with substance initiation and sexual debut to (1) test the strength of the associations of parental AUDs and parental separation with time to initiation (age in years) of alcohol, tobacco and cannabis use and sexual debut and (2) compare the strength of association of parental AUD and parental separation with initiation. DESIGN: Prospective adolescent and young adult cohort of a high-risk family study, the Collaborative Study on the Genetics of Alcoholism (COGA). SETTING: Six sites in the United States. PARTICIPANTS: A total of 3257 offspring (aged 14-33 years) first assessed in 2004 and sought for interview approximately every 2 years thereafter; 1945 (59.7%) offspring had a parent with an AUD. MEASUREMENTS: Diagnostic interview data on offspring substance use and sexual debut were based on first report of these experiences. Parental life-time AUD was based on their own self-report when parents were interviewed (1991-2005) for most parents, or on offspring and other family member reports for parents who were not interviewed. Parental separation was based on offspring reports of not living with both biological parents most of the time between ages 12 and 17 years. FINDINGS: Parental AUDs were associated with increased hazards for all outcomes, with cumulative hazards ranging from 1.19 to 2.71. Parental separation was also an independent and consistent predictor of early substance use and sexual debut, with hazards ranging from 1.19 to 2.34. The strength of association of parental separation with substance initiation was equal to that of having two AUD-affected parents, and its association with sexual debut was stronger than the association of parental AUD in one or both parents. CONCLUSIONS: Parental alcohol use disorders (AUDs) and parental separation are independent and consistent predictors of increased risk for early alcohol, tobacco and cannabis use and sexual debut in offspring from families with a high risk of parental AUDs.

Single Motherhood, Alcohol Dependence, and Smoking During Pregnancy: A Propensity Score Analysis.

OBJECTIVE: Few studies linking single motherhood and maternal smoking during pregnancy consider correlated risk from problem substance use beyond history of smoking and concurrent use of alcohol. In the present study, we used propensity score methods to examine whether the risk of smoking during pregnancy associated with single motherhood is the result of potential confounders, including alcohol dependence. METHOD: Data were drawn from mothers participating in a birth cohort study of their female like-sex twin offspring (n = 257 African ancestry; n = 1,711 European or other ancestry). We conducted standard logistic regression models predicting smoking during pregnancy from single motherhood at twins' birth, followed by propensity score analyses comparing single-mother and two-parent families stratified by predicted probability of single motherhood. RESULTS: In standard models, single motherhood predicted increased risk of smoking during pregnancy in European ancestry but not African ancestry families. In propensity score analyses, rates of smoking during pregnancy were elevated in single-mother relative to two-parent European ancestry families across much of the spectrum a priori risk of single motherhood. Among African ancestry families, within-strata comparisons of smoking during pregnancy by single-mother status were nonsignificant. CONCLUSIONS: These findings highlight single motherhood as a unique risk factor for smoking during pregnancy in European ancestry mothers, over and above alcohol dependence. Additional research is needed to identify risks, beyond single motherhood, associated with smoking during pregnancy in African ancestry mothers.

Major depressive disorder, suicidal thoughts and behaviours, and cannabis involvement in discordant twins: a retrospective cohort study.

BACKGROUND: Early and frequent cannabis use are associated with an increased likelihood of major depressive disorder (MDD) as well as suicidal thoughts and behaviours. We identify associations between aspects of cannabis use, MDD, and suicidal thoughts and behaviours and examine whether such associations persist after accounting for those predisposing factors, including genetic liability and early family environment, that are shared by identical twins who are discordant for cannabis exposure. Any residual association in such identical pairs might be indicative of individual-specific pathways that might be of a causal nature. METHODS: We did a logistic regression analysis of cannabis use from retrospective data on same-sex male and female twin pairs drawn from 3 studies that had recruited twins from the Australian Twin Registry, 1992-93 (sample 1), 1996-2000 (sample 2), and 2005-09 (sample 3). We studied associations between early use and frequent use of cannabis and MDD, suicidal ideation (ever and persistent), and suicide plan and attempt in the full sample as well as in pairs of monozygotic and dizygotic twins that were discordant for each measure of cannabis involvement at a single timepoint. Significant monozygotic associations were further adjusted for covariates, such as early alcohol or nicotine use, early dysphoric or anhedonic mood, conduct disorder, and childhood sexual abuse. Interactions between each cannabis measure and sex, sample or study effects, and birth year category were also examined as covariates. FINDINGS: In 13 986 twins (6181 monozygotic and 7805 dizygotic), cannabis use ranged from 1345 (30·4%) of 4432 people in sample 1 to 2275 (69·0%) of 3299 in sample 3. Mean age of first cannabis use ranged from 17·9 years (SD 3·3) in sample 3 to 21·1 years (5·2) in sample 1, and frequent use (≥100 times) was reported by 214 (15·9%) of 1345 users in sample 1 and 499 (21·9%) of 2275 in sample 3. The prevalence of suicidal ideation ranged from 1102 (24·9%) of 4432 people in sample 1 to 1644 (26·3%) of 6255 people in sample 2 and 865 (26·2%) of 3299 people in sample 3. Prevalence of MDD ranged from 901 (20·3%) people in sample 1 to 1773 (28·3%) in sample 2. The monozygotic twin who used cannabis frequently was more likely to report MDD (odds ratio 1·98, 95% CI 1·11-3·53) and suicidal ideation (2·47, 1·19-5·10) compared with their identical twin who had used cannabis less frequently, even after adjustment for covariates. For early cannabis use, the monozygotic point estimate was not significant but could be equated to the significant dizygotic estimate, suggesting a possible association with suicidal ideation. INTERPRETATION: The increased likelihood of MDD and suicidal ideation in frequent cannabis users cannot be solely attributed to common predisposing factors. FUNDING: National Institute on Drug Abuse, National Institutes of Health, Australian National Health and Medical Research Council.

The Influence of Paternal Separation, Paternal History of Alcohol Use Disorder Risk, and Early Substance Use on Offspring Educational Attainment by Young Adulthood.

OBJECTIVE: This study aimed to determine the associations among paternal alcohol problems, separation, and educational attainment in European American and African American offspring and whether offspring early alcohol/tobacco/marijuana use influenced these associations. METHOD: Families with offspring ages 13-19 years at intake were selected from state birth records and screened by telephone to determine high-risk or low-risk status (with/without paternal heavy drinking). Families of men with two or more driving-under-the-influence offenses were added as a very-high-risk group. Data from 340 African American and 288 European American offspring who were not enrolled in school at their last interview were analyzed. Educational attainment was modeled as less than high school, high school only (reference category), and some college or higher. Separation was defined as offspring report of not having lived continuously in the same household with their biological father from birth to age 14. Analyses were stratified by race. RESULTS: In European Americans, neither family risk status nor early alcohol/tobacco/marijuana use was associated with educational outcomes. However, paternal separation significantly elevated the likelihood of not completing high school in all models (relative risk ratios [RRRs] = 6.0-8.1, p <.001). For African American offspring, likelihoods of high school noncompletion were elevated marginally for paternal separation in only one model, but significantly for early marijuana use (RRRs = 2.8-3.2, p < .05). Very-high-risk status significantly reduced the likelihood of post-high school education in an adjusted model (RRR = 0.4, p < .05). CONCLUSIONS: High school noncompletion was significantly associated with paternal separation in European Americans and with early marijuana use in African American offspring. In addition, very-high-risk status reduced the likelihood of post-high school education in African American offspring only, suggesting that research with ethnically diverse samples yields important differences when examining outcomes of both separation and substance use on offspring education.

Reciprocal relationships between substance use and disorders and suicidal ideation and suicide attempts in the Collaborative Study of the Genetics of Alcoholism.

BACKGROUND: Substance use and misuse and suicidal thoughts and behaviors tend to co-occur. The purpose of this study was to examine whether (a) suicidal ideation and attempt are related to onset of alcohol, nicotine and cannabis use and dependence; (b) early use of alcohol, nicotine and cannabis is associated with onset of suicidal ideation and attempt; and (c) whether these associations persist while controlling for covariates, such as family history of alcohol problems, major depression and other internalizing and externalizing disorders. METHODS: The prospective cohort of the Collaborative Study of the Genetics of Alcoholism (COGA; N=3277) was used. Cross-sectional and discrete time logistic regression (i.e. survival) analyses examined associations between suicidal ideation and attempt and onset of alcohol, nicotine and cannabis use and dependence. Survival models also examined whether individual early substance use was related to onset of ideation and attempt. RESULTS: Ideation was related to 0.71-0.77 odds of onset of subsequent alcohol, nicotine and cannabis use. Attempt was associated with 1.44-1.61 odds of later alcohol, nicotine and cannabis dependence, even after accounting for covariates. Evidence for early substance use being related to subsequent onset of ideation or attempt was limited. Several sex and race differences emerged. LIMITATIONS: The sample was ascertained for family history of alcoholism; not all participants had been followed up allowing for censored observations; reporting bias. CONCLUSION: Suicide attempts are associated with increased likelihood of onset of substance dependence.

Comparison of Parent, Peer, Psychiatric, and Cannabis Use Influences Across Stages of Offspring Alcohol Involvement: Evidence from the COGA Prospective Study.

BACKGROUND: All stages of development of alcohol use disorder (AUD) have not been equally studied. While initiation of drinking has been given considerable attention, other stages have not been as thoroughly investigated. It is not clear whether the same factors are associated consistently across early and late transitions in AUD involvement. High-risk family samples that are enriched for AUD vulnerability and transitions in AUD development offer an opportunity to examine influences across multiple stages of AUD development. METHODS: Data from adolescents and young adults from high-risk families were used to study 4 transitions in AUD development-time to first drink, first drink to first problem, first drink to first diagnosis, and first problem to first diagnosis. Cox modeling was used to compare associations of parental AUD, parental separation, peer substance use, offspring ever-use of cannabis, trauma exposures, and internalizing and externalizing psychopathology across transitions. RESULTS: Hazards of most transitions were elevated for those who had ever used cannabis, those who attributed substance use to their peers, those with externalizing disorders, and those with parents with AUD. Many risk factors were linked to early initiation of alcohol, particularly cannabis use. Internalizing disorders were associated with later stages. Nonassaultive trauma was associated only with early initiation; assaultive trauma was not associated with any transition. CONCLUSIONS: In this large, ethnically diverse sample of high-risk youth, significant influences across transitions were fairly consistent, with externalizing disorders and cannabis ever-use elevating the likelihood of each stage, and peer and parental (and especially maternal AUD) influences linked to initiation and some later stages. Finally, in light of the increasingly permissive legal and social stances toward cannabis in the United States, the marked elevations of all alcohol outcomes observed for cannabis use underscore the importance of studying the underpinnings of this relationship.