Center for Primary Health Care Research, Lund University, Jan Waldenströmsgata 35, CRC, building 28, floor 11, entrance 72, Malmö University Hospital, Malmö, S-205 02, Sweden. Electronic address: firstname.lastname@example.org.
The societal consequences of drug abuse (DA) are severe and well documented, the World Health Organization recommending tracking of population trends for effective policy responses in treatment of DA and delivery of health care services. However, to correctly identify possible sources of DA change, one must first disentangle three different time-related influences on the need for treatment due to DA: age effects, period effects and cohort effects.
We constructed our main Swedish national DA database (spanning four decades) by linking healthcare data from the Swedish Hospital Discharge Register to individuals, which included hospitalisations in Sweden for 1975-2010. All hospitalized DA cases were identified by ICD codes. Our Swedish national sample consisted of 3078,129 men and 2921,816 women. We employed a cross-classified multilevel logistic regression model to disentangle any net age, period and cohort effects on DA hospitalization rates.
We found distinct net age, period and cohort effects, each influencing the predicted probability of hospitalisation for DA in men and women. Peak age for DA in both sexes was 33-35 years; net period effects showed an increase in hospitalisation for DA from 1996 to 2001; and in birth cohorts 1968-1974, we saw a considerable reduction (around 75%) in predicted probability of hospitalisation for DA.
The use of hospital admissions could be regarded as a proxy of the population's health service use for DA. Our results may thus constitute a basis for effective prevention planning, treatment and other appropriate policy responses.
We tested the association between alcohol use disorder (AUD) and divorce; estimated the genetic and environmental influences on divorce; estimated how much genetic and environmental influences accounted for covariance between AUD and divorce; and estimated latent genetic and environmental correlations between AUD and divorce. We tested sex differences in these effects.
We identified twin and sibling pairs with AUD and divorce information in Swedish national registers. We described the association between AUD and divorce using tetrachorics and used twin and sibling models to estimate genetic and environmental influences on divorce, on the covariance between AUD and divorce and the latent genetic and environmental correlations between AUD and divorce.
A total of 670?836 individuals (53% male) born 1940-1965.
Life-time measures of AUD and divorce.
AUD and divorce were related strongly (males: rtet = +0.44, 95% CI = 0.43, 0.45; females rtet = +0.37, 95% CI = 0.36, 0.38). Genetic factors accounted for a modest proportion of the variance in divorce (males: 21.3%, 95% CI = 7.6, 28.5; females: 31.0%, 95% CI = 18.8, 37.1). Genetic factors accounted for most of the covariance between AUD and divorce (males: 52.0%, 95% CI = 48.8, 67.9; females: 53.74%, 95% CI = 17.6, 54.5), followed by non-shared environmental factors (males: 45.0%, 95% CI = 37.5, 54.9; females: 41.6%, 95% CI = 40.3, 60.2). Shared environmental factors accounted for a negligible proportion of the covariance (males: 3.0%, 95% CI = -3.0, 13.5; females: 4.75%, 95% CI = 0.0, 6.6). The AUD-divorce genetic correlations were high (males: rA = +0.76, 95% CI = 0.53, 0.90; females +0.52, 95% CI = 0.24, 0.67). The non-shared environmental correlations were modest (males: rE = +0.32, 95% CI = 0.31, 0.40; females: +0.27, 95% CI = 0.27, 0.36).
Divorce and alcohol use disorder are correlated strongly in the Swedish population, and the heritability of divorce is consistent with previous studies. Covariation between AUD and divorce results from overlapping genetic and non-shared environmental factors. Latent genetic and non-shared environmental correlations for alcohol use disorder and divorce are high and moderate.
Excess alcohol consumption and alcohol use disorders (AUDs) are associated with substantially increased mortality. Efforts to reduce this toll require an understanding of their causes.
To clarify the degree to which the excess mortality associated with AUDs arises (1) from the predispositions of the person who develops AUD (and which would likely be shared by close relatives) and (2) as a direct result of AUD itself.
A prospective cohort and co-relative design study involving all individuals born in Sweden from 1940 to 1965 who had neither died nor migrated prior to 1973 or age 15 years (N?=?2?821?036). They were followed up from January 1, 1973, until December 31, 2010. Alcohol use disorder was assessed from medical, criminal, and pharmacy registries. Half-siblings, full-siblings, and monozygotic twin pairs discordant for AUD were obtained from the Multi-Generation and Twin Register.
Death obtained from the Swedish Death registry.
Our cohort (1?447?887 males and 1?373?149 females) included 131?895 males and 42?163 females registered with AUD. The mean (SD) age at first AUD registration was 39 (13.4) years. We ascertained 127?347 and 76?325 deaths in the male and female subsamples, respectively. Controlling for sex, educational status, and year of birth, the mortality hazard ratio associated with AUD was 5.83 (95% CI, 5.76-5.90) and varied-with an inverted U-shaped function-by age. Examining the AUD-mortality association in the general population and in relative pairs discordant for AUD exposure demonstrated substantial familial confounding in early to mid-adulthood: the AUD-associated mortality hazard ratio was much lower in discordant close relatives than in the general population. In middle to late adulthood, evidence for familial confounding decreased with increasing evidence for a direct effect of AUD on elevated mortality. In the oldest age group (65-70 years), the mortality hazard ratios were similar across the population and all relative pairs, suggesting that the excess mortality was largely a result of having AUD. Adding years since onset of AUD to the model showed that both increasing age and increasing years of duration of AUD contributed to the reduction of familial confounding in the association between AUD and elevated mortality.
Excess mortality associated with AUD arises both from the predispositions of the person who develops AUD and the direct result of having AUD. The effect of predisposition is more prominent early in the life course and in the early years of AUD. The direct effect of AUD becomes progressively more important later in life and with longer duration of AUD. These results have implications for interventions seeking to reduce the elevated AUD-associated mortality.
Alcohol use disorder (AUD) runs strongly in families. It is unclear to what extent the cross-generational transmission of AUD results from genetic vs environmental factors.
To determine to what extent genetic and environmental factors contribute to the risk for AUD.
Follow-up in 8 public data registers of adoptees, their biological and adoptive relatives, and offspring and parents from stepfamilies and not-lived-with families in Sweden. In this cohort study, subtypes of AUD were assessed by latent class analysis. A total of 18,115 adoptees (born 1950-1993) and 171,989 and 107,696 offspring of not-lived-with parents and stepparents, respectively (born 1960-1993).
Alcohol use disorder recorded in medical, legal, or pharmacy registry records.
Alcohol use disorder in adoptees was significantly predicted by AUD in biological parents (odds ratio, 1.46; 95% CI, 1.29-1.66) and siblings (odds ratio, 1.94; 95% CI, 1.55-2.44) as well as adoptive parents (odds ratio, 1.40; 95% CI, 1.09-1.80). Genetic and environmental risk indices created from biological and adoptive relatives acted additively on adoptee AUD liability. Results from biological and adoptive relatives were replicated and extended from examinations of, respectively, not-lived-with parents and stepparents. Multivariate models in these families showed that AUD in offspring was significantly predicted by AUD, drug abuse, psychiatric illness, and crime in not-lived-with parents and by AUD, drug abuse, crime, and premature death in stepparents. Latent class analyses of adoptees and offspring of not-lived-with parents with AUDs revealed 3 AUD classes characterized by (1) female preponderance and high rates of psychiatric illness, (2) mild nonrecurrent symptoms, and (3) early-onset recurrence, drug abuse, and crime. These classes had distinct genetic signatures in the patterns of risk for various disorders in their not-lived-with parents and striking differences in the rates of recorded mood disorders.
Parent-offspring transmission of AUD results from both genetic and environmental factors. Genetic risk for AUD reflects both a specific liability to AUD and to other externalizing disorders. Environmental risk reflects features of both parental psychopathology and other aspects of the rearing environment. Alcohol use disorder is a heterogeneous syndrome and meaningful subtypes emerged from latent class analysis, which were validated by patterns of disorders in biological parents and specific psychiatric comorbidities. The general population contains informative family constellations that can complement more traditional adoption designs in clarifying the sources of parent-offspring resemblance.
Cites: Arch Gen Psychiatry. 1992 Aug;49(8):599-6081637250
Cites: Arch Gen Psychiatry. 1994 Jan;51(1):8-198279933
These three studies examined the hypothesis that prenatal exposure to sex hormones influences twins' risk for eating disorders based on co-twin sex, such that individuals with a female co-twin would be more likely than individuals with a male co-twin to meet diagnostic criteria for an eating disorder.
Male and female twins from the United States (N=2607), Norway (N=2796) and Sweden (N=16,458) with known co-twin sex and zygosity were assessed for eating disorders.
In the U.S. and Swedish samples, sex was significantly associated with eating disorder diagnoses, and although co-twin sex was not associated with eating disorders overall, it was associated with broadly defined bulimia nervosa in the Swedish sample. The effects for bulimia were not sustained when monozygotic twins were excluded, suggesting that the effects of prenatal sex hormones play a minor role in influencing eating disorders. Sex and co-twin sex were not associated with eating disorders in the Norwegian sample.
The prenatal sex hormone hypothesis, which proposes that prenatal hormone exposure is associated with later eating disorder symptomatology, was not supported in these three population-based twin samples.
Cites: Arch Gen Psychiatry. 2008 Mar;65(3):329-3618316679
Cohort studies suggest that the relationship between major depression (MD) and Type 2 diabetes (T2DM) is bidirectional. However, this association may be confounded by shared genetic or environmental factors. The objective of this study was to use a twin design to investigate the association between MD and T2DM.
Data come from the Screening Across the Lifespan Twin Study, a sample of monozygotic and dizygotic twins 40 years or older sampled from the Swedish Twin Registry (n = 37,043). MD was assessed by using the Composite International Diagnostic Inventory. Structural equation twin modeling and Cox proportional hazards modeling were used to assess the relationship between MD and T2DM.
Approximately 19% of respondents had a history of MD and 5% had a history of T2DM. MD was associated with 32% increased likelihood of T2DM (95% confidence interval = 1.00-1.80) among twins aged 40 to 55 years, even after accounting for genetic risk, but was not associated with T2DM among twins older than 55 years. T2DM was associated with 33% increased likelihood of MD (95% confidence interval = 1.02-1.72) among younger, but not older twins. Cholesky decomposition twin modeling indicated that common unique environmental factors contribute to the association between MD and T2DM.
Environmental factors that are unique to individuals (i.e., not shared within families) but common to both MD and T2DM contribute to their co-occurrence in midlife. However, we cannot exclude the possibility of bidirectional causation as an alternate explanation. It is likely that multiple processes are operating to effect the relation between psychiatric and medical conditions in midlife.
Cites: Am J Public Health. 2010 May;100(5):933-919846689
Using Swedish nationwide registry data, the authors investigated the correlation of genetic and environmental risk factors in the etiology of drug abuse as ascertained from medical and criminal registries by modeling twin and sibling data. Medical drug abuse was defined using public inpatient and outpatient records, while criminal drug abuse was ascertained through legal records. Twin, full and half sibling pairs were obtained from the national twin and genealogical registers. Information about sibling pair residence within the same household was obtained from Statistics Sweden. Standard bivariate genetic structural equation modeling was applied to the population-based data on drug abuse ascertained through medical and crime registries, using OpenMx. Analyses of all possible pairs of twins (MZ: N = 4482; DZ: N = 9838 pairs), full- (N = 1,278,086) and half-siblings (paternal: N = 7767; maternal N = 70,553) who grew up together suggested that factors explaining familial resemblance for drug abuse as defined through medical or criminal registries were mostly the same. Results showed substantial heritability and moderate contributions of shared environmental factors to drug abuse; both were higher in males versus females, and higher for drug abuse ascertained through criminal than medical records. Because of the low prevalence of both assessments of drug abuse, having access to population data was crucial to obtain stable estimates. Using objective registry data, the authors found that drug abuse-whether ascertained through medical versus criminal records-was highly heritable. Furthermore, shared environmental factors contributed significantly to the liability of drug abuse. Genetic and shared environmental risk factors for these two forms of drug abuse were highly correlated.
Cites: Proc Assoc Am Physicians. 1999 Mar-Apr;111(2):109-1810220805
Cites: Am J Psychiatry. 2014 Feb;171(2):209-1724077613
Correlational studies consistently report relationships between childhood trauma (CT) and most personality disorder (PD) criteria and diagnoses. However, it is not clear whether CT is directly related to PDs or whether common familial factors (i.e., shared environment and/or genetic factors) better account for that relationship. The current study used a cotwin control design to examine support for a direct effect of CT on PD criterion counts. Participants were from the Norwegian Twin Registry (N = 2,780), including a subset (n = 898) of twin pairs (449 pairs, 45% monozygotic [MZ]) discordant for CT meeting DSM-IV Posttraumatic Stress Disorder Criterion A. All participants completed the Norwegian version of the Structured Interview for DSM-IV Personality. Significant associations between CT and all PD criterion counts were detected in the general sample; however, the magnitude of observed effects was small, with CT accounting for no more than approximately 1% of variance in PD criterion counts. A significant, yet modest, interactive effect was detected for sex and CT on Schizoid and Schizotypal PD criterion counts, with CT being related to these disorders among women but not men. After common familial factors were accounted for in the discordant twin sample, CT was significantly related to Borderline and Antisocial PD criterion counts, but no other disorders; however, the magnitude of observed effects was quite modest (r2 = .006 for both outcomes), indicating that the small effect observed in the full sample is likely better accounted for by common genetic and/or environmental factors. CT does not appear to be a key factor in PD etiology.
Alcohol Use Disorder (AUD) is clinically heterogeneous. Using a large epidemiological sample ascertained via public registries, is it possible to identify clinical and historical features of AUD that reflect familial risk?
Using registration in national medical, legal or pharmacy registries, we identified four kinds of relative pairs (n=683,223) starting with a proband with AUD: cousins, half-siblings, full-siblings and monozygotic cotwins. Using linear hazard regression, we examined the interaction between five clinical/historical features of AUD in the proband and risk for AUD in these relatives.
Increased risk for AUD in relatives was predicted by the proband's early age at first registration, total number of registrations, recurrence, history of drug abuse and ascertainment in the medical versus the legal or pharmacy registry. In multivariate models, age at first registration, number of registrations, recurrence and history of drug abuse remained significant and in aggregate strongly predicted the risk for AUD in relatives. The risk for AUD in siblings of AUD probands in the highest decile of genetic risk predicted by these four indices was more than twice as great as that predicted in siblings of probands in the lowest risk decile.
In an epidemiological sample, familial risk for AUD can be assessed by simple clinical and historical variables.
Cites: J Stud Alcohol. 1979;40(1):89-116376949
Cites: Behav Genet. 2016 Mar;46(2):183-9226494460
Cites: Arch Gen Psychiatry. 2007 Nov;64(11):1313-2017984400
Cites: Methods Mol Biol. 2011;675:215-2020949391
Cites: N Engl J Med. 1994 Apr 14;330(15):1041-68127331