The role of parent and offspring sex on risk for externalizing psychopathology in offspring with parental alcohol use disorder: a national Swedish study.

PURPOSE: The substantial literature showing that offspring of parents with alcohol use disorder (AUD) is at increased risk for externalizing psychopathology rarely examines the differential effects of parental and offspring sex. This literature also has other important limitations, such as modest sample sizes and use of unrepresentative samples. Using a large, nationwide Swedish sample, we aim to investigate the roles of parental and offspring sex in externalizing psychopathology among offspring with parental AUD. METHODS: AUD diagnosis and externalizing measures were obtained from national registries. Associations between outcomes and parental AUD were examined using logistic regressions. Parental and offspring sex effects were examined with interaction terms. RESULTS: Risks for externalizing disorders were increased in sons and daughters with parental AUD, with significant differences between sons and daughters for criminal behavior; maternal AUD had a greater impact than paternal AUD (regardless of offspring sex), but having two parents with AUD increased risk for all outcomes substantially more than having one parent; and maternal AUD increased risk of drug abuse for daughters more than sons, while paternal AUD increased risk of AUD and criminal behavior for sons more than daughters. CONCLUSIONS: Offspring of parents with AUD are at increased risk for externalizing psychopathology. Maternal and paternal AUD differentially affected sons' vs. daughters' risks for AUD, drug abuse, and criminal behavior. The transmission of psychopathology within the externalizing spectrum appears to have sex-specific elements.

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.

Parental substance use disorder and risk of intellectual disability in offspring in Sweden: a national register study.

Background: Intellectual disability (ID) is a disorder with unknown aetiology in many cases. Maternal alcohol use is a known risk factor for ID, but less is known about the importance of maternal and paternal substance use disorder (SUD) and risk of ID in offspring. Methods: Data from multiple nationwide registers were used to create a cohort of children born from January 01, 1978 to December 31, 2002. All participants were born in Sweden, had available parental identification information and did not emigrate or die before age 12 (n = 1,940,820). Logistic regression modelling was performed with exposure defined as having a parent who received any SUD diagnosis, including alcohol use disorder (AUD) and drug use disorder (DUD). The outcome was registration of diagnosis of any form of ID. First, we analysed the risk of ID if parental SUD was registered prior to childbirth with stepwise adjustment of multiple covariates. Second, the effect of timing of SUD diagnosis in relation to childbirth was analysed. Findings: Of 37,410 offspring with parental SUD registered prior to birth, 3.0% (n = 1110) had any form of ID compared to 1.2% (n = 23,168) of those 1,903,410 individuals without parental SUD prior birth. Parental SUD prior birth was associated with an increased risk of any form of ID (Odds Ratio [OR]: 2.3 [2.2-2.5]), with ORs similar for maternal (OR: 2.3 [2.1-2.5]) and paternal SUD (OR: 2.3 [2.1-2.5]). These ORs were reduced but remained statistically significant after adjusting for parental education, migration, psychiatric comorbidity, and co-parent SUD (OR parental SUD: 1.6 [1.5-1.8]; OR maternal SUD: 1.4 [1.2-1.5]; OR paternal SUD: 1.6 [1.5-1.7]). Parental SUD was associated with increased risk of ID in offspring irrespective of timing of diagnosis, but if mothers or fathers were diagnosed with AUD during pregnancy (OR maternal AUD: 5.0 [3.1-8.2]; OR paternal AUD: 2.8 [2.2-3.6]), the risk was significantly greater than if the AUD diagnosis was first registered after childbirth (OR maternal AUD: 1.9 [1.8-2.0]; OR paternal AUD: 1.6 [1.6-1.7]). Interpretation: Both paternal and maternal SUD were associated with an increased risk of ID in offspring, with greatest risk observed when AUD was diagnosed during pregnancy. Possible mechanisms may involve shared genetic and environmental factors, including toxic effects from alcohol intake. These findings have clinical implications in suggesting that parental SUD in either parent represents a possibly modifiable risk factor to consider when developing prevention, diagnostics and treatment programs for children with ID. Funding: Stockholm County Council, the Research Council of the Swedish Alcohol Retailing Monopoly, Fredrik and Ingrid Thurings stiftelse, Academy of Finland, the Swedish Research Council and the Swedish Research Council for Health, Working Life and Welfare, Nordforsk by the Nordic Council of Ministers and the Polish Medical Research Agency.

Role of parental divorce and discord in the intergenerational transmission of alcohol use disorder.

BACKGROUND: Alcohol use disorder (AUD) has a strong familial component, and is associated with divorce and relationship discord. The purpose of this study was to test whether exposure to parental divorce and parental relationship discord contributes to the intergenerational transmission of AUD. METHODS: The sample included N = 9005 adult twins (43% female) from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders. Participant AUD diagnoses were derived from structured clinical interviews based on DSM-IV alcohol dependence. Participants also reported on parental divorce and parental AUD. In addition, direct psychiatric interview data and measures of relationship discord were available for a subsample of parents of female-female twin pairs (855 mothers, 617 fathers). Indirect effects models were fit and tested using a robust maximum likelihood estimator with Monte Carlo integration. RESULTS: Path and structural equation modeling results provided strong support for the intergenerational transmission of AUD, and indicated that parental AUD had indirect effects on offspring AUD through exposure to parental divorce and parental relationship discord. Effects were consistent across males and females. CONCLUSIONS: In a population-based adult twin sample, exposure to parental divorce and relationship discord appears to be important for understanding the intergenerational transmission of AUD. These effects are broadly consistent with the idea of genetic nurturance, whereby parents transmit genetic risk for alcohol use disorder to their children indirectly via heritable aspects of the home environment. Ultimately, this etiological information could bolster engagement with skills-based therapeutic efforts used in substance-related preventive interventions for divorced or distressed families.

Parental alcohol use disorder and offspring marital outcomes.

AIMS: We tested whether parental alcohol use disorder (AUD) predicted adult offspring's likelihood of marriage and marriage to an AUD-affected spouse; whether effects differed as a function of the sex or number of affected parents; and whether they were robust to confounders. DESIGN: Sex-stratified Cox and logistic regression models. SETTING: Sweden. PARTICIPANTS: A total of 1 171 070 individuals (51.40% male) born 1965-75. MEASUREMENTS: Obtained from legal, medical and pharmacy registries. Predictor was parent AUD. Outcomes were marriage and spouse AUD. Adjustments included offspring birth year and AUD; and parental education, marriage, divorce, criminal behavior and drug abuse. FINDINGS: Male and female offspring of AUD-affected parents were more likely to marry at younger ages (< 25), illustrative unadjusted hazard ratio (HR)age 20  = 1.22 (1.17, 1.28) and 1.34 (1.20, 1.39) and were less likely to marry at older ages (> 25), HRage 30  = 0.79 (0.78, 0.81) and 0.82 (0.81, 0.84). Parental AUD was associated with higher odds of having an affected spouse for males and females, odds ratio (OR) = 1.47 (1.38, 1.57) and 1.63 (1.56, 1.70). Effects were more pronounced for those with two versus one AUD-affected parent and adjustments attenuated effects negligibly. Daughters of affected mothers (versus fathers) were more likely to have AUD-affected husbands, OR = 1.68 (1.54, 1.84) versus 1.56 (1.48, 1.64), while there was no difference in sons. CONCLUSIONS: In Sweden, parental alcohol use disorder (AUD) is associated with a higher probability of marriage at younger ages, a lower probability of marriage at older ages and a higher likelihood of marriage to an affected spouse compared with no parental AUD. Most of these effects become stronger when the number of AUD-affected parents increases from one to two, and most effects hold after controlling for parents' socio-economic status, marital history, other externalizing disorders and offspring's own AUD status. Daughters of affected mothers are more likely to have an affected spouse.