We sought to evaluate whether the timing of co-occurrence of psychiatric disorder groups provides evidence for one disorder group predisposing individuals to subsequent onset of other disorder groups ...above and beyond a common liability model. Data were drawn from the 2012–2013 National Epidemiologic Survey on Alcohol and Related Conditions-III (n = 36,309). We identified statistically significant sequences of the age of onset of mood, anxiety, and substance use disorders (SUD) using a novel method distinguishing significant sequences from patterns expected only due to correlations induced by common liability among disorders. At every age, the lifetime probability of the three disorder groups was positively correlated consistent with a common liability model, but using a sequence analysis that accounts for different population level age of onset patterns and age specific correlations due to common liability, only SUD was more likely to precede mood disorders than expected (4.0% vs 3.3%, p < .001). Onsets within the same year of mood and anxiety disorders (21.5%) occurred over 6 times more commonly than expected by chance. SUD and mood disorders onsets occurred during the same year (9.0%) twice as commonly as expected, whereas SUD and anxiety disorder onsets did not occur in the same year significantly more commonly than expected. These results suggest that above and beyond common liabilities to comorbid mood, anxiety, and SUD disorders across the lifespan, SUDs predispose individuals for future onset of mood disorders, but not the reverse. Frequent simultaneous onset of psychiatric disorders further supports shared underlying vulnerabilities across disorder groups.
Why do potentially traumatic events (PTEs) and substance use (SU) so commonly co-occur during adolescence? Causal hypotheses developed from the study of posttraumatic stress disorder (PTSD) and ...substance use disorder (SUD) among adults have not yet been subject to rigorous theoretical analysis or empirical tests among adolescents with the precursors to these disorders: PTEs and SU. Establishing causality demands accounting for various factors (e.g. genetics, parent education, race/ethnicity) that distinguish youth endorsing PTEs and SU from those who do not, a step often overlooked in previous research.
We leveraged nationwide data from a sociodemographically diverse sample of youth (N = 11,468) in the Adolescent Brain and Cognitive Development Study. PTEs and substance use prevalence were assessed annually. To account for the many pre-existing differences between youth with and without PTE/SU (i.e. confounding bias) and provide rigorous tests of causal hypotheses, we linked within-person changes in PTEs and SU (alcohol, cannabis, nicotine) across repeated measurements and adjusted for time-varying factors (e.g. age, internalizing symptoms, externalizing symptoms, and friends' use of substances).
Before adjusting for confounding using within-person modeling, PTEs and SU exhibited significant concurrent associations (βs = .46-1.26, ps < .05) and PTEs prospectively predicted greater SU (βs = .55-1.43, ps < .05) but not vice versa. After adjustment for confounding, the PTEs exhibited significant concurrent associations for alcohol (βs = .14-.23, ps < .05) and nicotine (βs = .16, ps < .05) but not cannabis (βs = -.01, ps > .05) and PTEs prospectively predicted greater SU (βs = .28-.55, ps > .05) but not vice versa.
When tested rigorously in a nationwide sample of adolescents, we find support for a model in which PTEs are followed by SU but not for a model in which SU is followed by PTEs. Explanations for why PTSD and SUD co-occur in adults may need further theoretical analysis and adaptation before extension to adolescents.
Bipolar disorder (BD) is an overarching diagnostic class defined by the presence of at least one prior manic episode (BD I) or both a prior hypomanic episode and a prior depressive episode (BD II). ...Traditionally, BD II has been conceptualized as a less severe presentation of BD I, however, extant literature to investigate this claim has been mixed.
We apply genomic structural equation modeling (Genomic SEM) to investigate divergent genetic pathways across BD's two major subtypes using the most recent GWAS summary statistics from the PGC. We begin by identifying divergences in genetic correlations across 98 external traits using a Bonferroni-corrected threshold. We also use a theoretically informed follow-up model to examine the extent to which the genetic variance in each subtype is explained by schizophrenia and major depression. Lastly, transcriptome-wide SEM (T-SEM) was used to identify neuronal gene expression patterns associated with BD subtypes.
BD II was characterized by significantly larger genetic overlap across non-psychiatric medical and internalizing traits (e.g. heart disease, neuroticism, insomnia), while stronger associations for BD I were absent. Consistent with these findings, follow-up modeling revealed a substantial major depression component for BD II. T-SEM results revealed 35 unique genes associated with shared risk across BD subtypes.
Divergent patterns of genetic relationships across external traits provide support for the distinction of the bipolar subtypes. However, our results also challenge the illness severity conceptualization of BD given stronger genetic overlap across BD II and a range of clinically relevant traits and disorders.
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.
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 (
= 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.
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).
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.
Numerous epidemiological studies have reported a positive association between major depression (MD) and regular tobacco use (RU) or nicotine dependence (ND). However, few have used a genetically ...informative design to assess whether these traits share a common genetic and/or environmental liability.
We assessed MD, RU and ND in same-sex twins from the population-based Swedish Twin Registry. In males, we examined both cigarette use and snus (smokeless tobacco) use. We used structural equation modeling to examine the relationship between MD, RU, and ND given RU.
The results suggest modest correlations between MD and RU, and between MD and ND. In males, the liability shared between MD and RU is solely genetic for both cigarettes and snus, while MD and ND share both genetic and unique environmental influences. The continuation to ND given RU differed considerably between cigarette and snus users. In females, both MD-RU and MD-ND relationships are partially attributable to genetic and unique environmental correlations.
The relationship among MD, RU and ND is at least partially attributable to shared genetic and environmental risk factors. The genetic and environmental correlations between traits are modest. The nature of the shared liability differs by sex, and in males, by the type of tobacco product used. Differences between previous reports and results presented in the current study are suggestive of population differences in how MD and tobacco use inter-relate.
Abstract Background The nature of the relationship between major depression (MD) and phenotypes related to smoking behavior, including nicotine dependence (ND), is complicated. We present results ...from analyses comparing models wherein MD and ND are influenced by a shared latent factor to one in which causal pathways between phenotypes are examined. Method Data were collected for 2906 adult male twins from a population-based sample. Structural equation modeling was used to derive path estimates for shared liability and causal models. MD was assessed according to DSM-III-R diagnostic criteria; ND was assessed using the Fagerstrom Test for Nicotine Dependence (FTND). Results The best fitting shared liability model included genetic, but not environmental, influences shared between MD and FTND; a small proportion of these shared influences were also common to smoking initiation. The best fitting causal model included a unidirectional causal path from FTND to MD, with no direct genetic correlation between MD and smoking initiation. Model fit statistics indicated that these models provided nearly identical fits to the data, with the causal model providing a slightly superior AIC value. Conclusions The phenotypic association between MD and FTND is likely due to both a causal relationship, wherein increasing levels of nicotine dependence increase one's risk for depression, and to a shared genetic liability between the two. Limitations This sample consists of Caucasian males born in Virginia, and findings might not be generalizable to others. Statistical power was less than ideal.
This joint report includes economic national reports on the taxation of partnership in the Nordic countries, except Denmark. The general contents of these reports are summarized and thoroughly ...analyzed in Anna Holst Birket-Smith’s General report, published in this issue of the NTaxJ. For additional information, details on legislative measures etc. we find it important, however, to also publish the national reports in full length. We hope you will find it valuable as well. The respective national reports appear in alphabetic order, in regard to the country which regulation is presented. Name of the country reporter and contact information are presented in the beginning of each report.
This joint report includes the five legal national reports on the taxation of partnership in the Nordic countries. The general contents of these reports are summarized and thoroughly analyzed in ...Liselotte Madsen’s General report, published in this issue of the NTaxJ. For additional information, details on legislative measures etc. we find it important, however, to also publish the national reports in full length. We hope you will find it valuable as well.
The respective national reports appear in alphabetic order, in regard to the country which regulation is presented. Name of the country reporter and contact information are presented in the beginning of each report.
Depressive symptoms and alcohol use are frequently positively associated during adolescence. This study aimed to assess the heritability of each phenotype across adolescence; to assess potential ...shared liabilities; to examine changes in the nature of shared liabilities across adolescence; and to investigate potential causal relationships between depressive symptoms and alcohol use. We studied a longitudinally assessed sample of adolescent Finnish twins (N = 1,282) to test hypotheses about genetic and environmental influences on these phenotypes within and across ages, using data from assessments at ages 12, 14, and 17.5 years. The heritability of depressive symptoms is consistent across adolescence (~40–50%), with contributions from common and unique environmental factors. The heritability of alcohol use varies across time (a
2
= .25–.44), and age 14 alcohol use is heavily influenced by shared environmental factors. Genetic attenuation and innovation were observed across waves. Modest to moderate genetic (r
A
= .26–.59) and environmental (r
C
= .30–.63) correlations between phenotypes exist at all ages, but decrease over time. Tests for causal relationships between traits differed across ages and sexes. Intrapair MZ difference tests provided evidence for reciprocal causation in girls at ages 14 and 17.5. Formal causal models suggested significant causal relationships between the variables in both boys and girls. The association between depressive symptoms and alcohol use during adolescence is likely due to a combination of shared genetic and environmental influences and causal influences. These influences are also temporally dynamic, complicating efforts to understand factors contributing to the relationship between these outcomes.
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