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Background: Some preliminary research suggests higher rates of gastrointestinal disease in individuals with eating disorders (EDs). However, research is limited, and it remains unknown what etiologic factors account for observed associations. This was the first study to examine how EDs and dimensional ED symptoms (e.g. body dissatisfaction, binge eating) are phenotypically and etiologically associated with gastrointestinal disease in a large, population-based twin sample. Methods: Adult female (N = 2980) and male (N = 2903) twins from the Michigan State University Twin Registry reported whether they had a lifetime ED (anorexia nervosa, bulimia nervosa, or binge-eating disorder) and completed a measure of dimensional ED symptoms. We coded the presence/absence of lifetime gastrointestinal disease (e.g. inflammatory bowel disease) based on responses to questions regarding chronic illnesses and medications. We first examined whether twins with gastrointestinal disease had higher rates of EDs and ED symptoms, then used correlated factors twin models to investigate genetic and environmental contributions to the overlap between disorders. Results: Twins with gastrointestinal disease had significantly greater dimensional ED symptoms (β = 0.21, p < 0.001) and odds of a lifetime ED (OR 2.90, p = 0.001), regardless of sex. Shared genetic factors fully accounted for the overlap between disorders, with no significant sex differences in etiologic associations. Conclusions: Comorbidity between EDs and gastrointestinal disease may be explained by overlap in genetic influences, potentially including inflammatory genes implicated in both types of disorders. Screening for gastrointestinal disease in people with EDs, and EDs in those with gastrointestinal disease, is warranted. [ABSTRACT FROM AUTHOR]

Background: Are genetic risk factors for current depressive symptoms good proxies for genetic risk factors for syndromal major depression (MD)? Methods: In over 9000 twins from the population-based Virginia Adult Twin Study of Psychiatric and Substance Use Disorders, the occurrence of all nine DSM symptomatic criteria for MD in the last year was assessed at personal interview and then grouped by their temporal co-occurrence. The DSM criteria which occurred outside (OUT) v. inside of (IN) MD episodes were then separated. We calculated tetrachoric correlations for OUT and IN depressive criteria in monozygotic (MZ) and dizygotic (DZ) pairs and fitted univariate and bivariate ACE twin models using OpenMx. Results: The mean twin correlations (±95% CIs) for IN depressive criteria were substantially higher than for OUT depressive criteria in both MZ [+0.35 (0.32–0.38) v. 0.20 (0.17–0.24)] and DZ pairs [0.20 (0.17–0.24) v. 0.10 (0.04–0.16]. The mean IN–OUT cross-correlation in MZ and DZ pairs was modest [+0.15 (0.07–0.24) and +0.07 (0.03–0.12)]. The mean heritability estimates for the nine In v. Out depressive criteria was 0.31 (0.22–0.41) and 0.15 (0.08–0.21), in MZ and DZ pairs, respectively. The mean genetic correlation between the nine IN and OUT depressive criteria was +0.07 (−0.07 to 0.21). Conclusions: Depressive criteria occurring outside depressive episodes are less heritable than those occurring within. These two ways criteria can manifest are not closely genetically related. Current depressive symptoms – most of which are occurring outside of depressive episodes – are not, for genetic studies, good proxies for MD. [ABSTRACT FROM AUTHOR]

Background: Many studies aggregate prescription opioid misuse (POM) and heroin use into a single phenotype, but emerging evidence suggests that their genetic and environmental influences may be partially distinct. Methods: In total, 7164 individual twins (84.12% complete pairs; 59.81% female; mean age = 30.58 years) from the Australian Twin Registry reported their lifetime misuse of prescription opioids, stimulants, and sedatives, and lifetime use of heroin, cannabis, cocaine/crack, illicit stimulants, hallucinogens, inhalants, solvents, and dissociatives via telephone interview. Independent pathway models (IPMs) and common pathway models (CPMs) partitioned the variance of drug use phenotypes into general and drug-specific genetic (a), common environmental (c), and unique environmental factors (e). Results: An IPM with one general a and one general e factor and a one-factor CPM provided comparable fit to the data. General factors accounted for 55% (a = 14%, e = 41%) and 79% (a = 64%, e = 15%) of the respective variation in POM and heroin use in the IPM, and 25% (a = 12%, c = 8%, e = 5%) and 80% (a = 38%, c = 27%, e = 15%) of the respective variation in POM and heroin use in the CPM. Across both models, POM emerged with substantial drug-specific genetic influence (26–39% of total phenotypic variance; 69–74% of genetic variance); heroin use did not (0% of total phenotypic variance; 0% of genetic variance in both models). Prescription sedative misuse also demonstrated significant drug-specific genetic variance. Conclusions: Genetic variation in POM, but not heroin use, is predominantly drug-specific. Misuse of prescription medications that reduce experiences of subjective distress may be partially influenced by sources of genetic variation separate from illicit drug use. [ABSTRACT FROM AUTHOR]

Background: A moderate to high alcohol consumption is associated with a lower risk of cardiovascular disease (CVD) mortality in comparison with low consumption. The mechanisms underlying this association are not clear and have been suggested to be caused by residual confounding. The main objective of this study was to separate the familial and individual risk for CVD mortality and all-cause mortality related to alcohol consumption. This will be done by estimating the risk for CVD mortality and all-cause mortality in twin pairs discordant for alcohol consumption. Methods: Alcohol consumption was assessed at two time points using self-report questionnaires in the Norwegian Twin Registry. Data on CVD mortality was obtained from the Norwegian Cause of Death Registry. Exposure–outcome associations for all-cause mortality and mortality due to other causes than CVD were estimated for comparison. Results: Coming from a family with moderate to high alcohol consumption was protective against cardiovascular death (HR = 0.54, 95% CI 0.65–0.83). Moderate and high alcohol consumption levels were associated with a slightly increased risk of CVD mortality at the individual level (HR = 1.33, 95% CI 1.02–1.73). There was no association between alcohol consumption and all-cause mortality both at the familial nor at the individual level. Conclusions: The protective association of moderate to high alcohol consumption with a lower risk of CVD mortality was accounted for by familial factors in this study of twins. Early life genetic and environmental familial factors may mask an absence of health effect of moderate to high alcohol consumption on cardiovascular mortality. [ABSTRACT FROM AUTHOR]

Background: There is some evidence that autism spectrum disorder (ASD) frequently co-occurs with immune-mediated conditions including asthma. We aimed to explore the familial co-aggregation of ASD and asthma using different genetically informed designs. Methods: We first examined familial co-aggregation of asthma and ASD in individuals born in Sweden from 1992 to 2007 (n = 1 569 944), including their full- and half-siblings (n = 1 704 388 and 356 544 pairs) and full cousins (n = 3 921 890 pairs), identified using Swedish register data. We then applied quantitative genetic modeling to siblings (n = 620 994 pairs) and twins who participated in the Child and Adolescent Twin Study in Sweden (n = 15 963 pairs) to estimate the contribution of genetic and environmental factors to the co-aggregation. Finally, we estimated genetic correlations between traits using linkage disequilibrium score regression (LDSC). Results: We observed a within-individual association [adjusted odds ratio (OR) 1.33, 95% confidence interval (CI) 1.28–1.37] and familial co-aggregation between asthma and ASD, and the magnitude of the associations decreased as the degree of relatedness decreased (full-siblings: OR 1.44, 95% CI 1.38–1.50, maternal half-siblings: OR 1.28, 95% CI 1.18–1.39, paternal half-siblings: OR 1.05, 95% CI 0.96–1.15, full cousins: OR 1.06, 95% CI 1.03–1.09), suggesting shared familial liability. Quantitative genetic models estimated statistically significant genetic correlations between ASD traits and asthma. Using the LDSC approach, we did not find statistically significant genetic correlations between asthma and ASD (coefficients between −0.09 and 0.12). Conclusions: Using different genetically informed designs, we found some evidence of familial co-aggregation between asthma and ASD, suggesting the weak association between these disorders was influenced by shared genetics. [ABSTRACT FROM AUTHOR]

Background: Alcohol, cannabis, and nicotine use are highly comorbid and alarmingly prevalent in young adults. The hippocampus may be particularly sensitive to substance exposure. This remains largely untested in humans and familial risk may confound exposure effects. We extend prior work on alcohol and hippocampal volume in women by testing common and unique substance use effects and the potential moderating role of sex on hippocampal volume during emerging adulthood. A quasi-experimental cotwin control (CTC) design was used to separate familial risk from exposure consequences. Methods: In a population-based sample of 435 24-year-old same-sex twins (58% women), dimensional measures (e.g. frequency, amount) of alcohol, cannabis, and nicotine use across emerging adulthood were assessed. Hippocampal volume was assessed using MRI. Results: Greater substance use was significantly associated with lower hippocampal volume for women but not men. The same pattern was observed for alcohol, cannabis, and nicotine. CTC analyses provided evidence that hippocampal effects likely reflected familial risk and the consequence of substance use in general and alcohol and nicotine in particular; cannabis effects were in the expected direction but not significant. Within-pair mediation analyses suggested that the effect of alcohol use on the hippocampus may reflect, in part, comorbid nicotine use. Conclusions: The observed hippocampal volume deviations in women likely reflected substance-related premorbid familial risk and the consequences of smoking and, to a lesser degree, drinking. Findings contribute to a growing body of work suggesting heightened risk among women toward experiencing deleterious effects of substance exposure on the still-developing young adult hippocampus. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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 (N = 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. Results: 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). Conclusions: 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. [ABSTRACT FROM AUTHOR]

Background: Although mental wellbeing has been linked with positive health outcomes, including longevity and improved emotional and cognitive functioning, studies examining the underlying neural mechanisms of both subjective and psychological wellbeing have been sparse. We assessed whether both forms of wellbeing are associated with neural activity engaged during positive and negative emotion processing and the extent to which this association is driven by genetics or environment. Methods: We assessed mental wellbeing in 230 healthy adult monozygotic and dizygotic twins using a previously validated questionnaire (COMPAS-W) and undertook functional magnetic resonance imaging during a facial emotion viewing task. We used linear mixed models to analyse the association between COMPAS-W scores and emotion-elicited neural activation. Univariate twin modelling was used to evaluate heritability of each brain region. Multivariate twin modelling was used to compare twin pairs to assess the contributions of genetic and environmental factors to this association. Results: Higher levels of wellbeing were associated with greater neural activity in the dorsolateral prefrontal cortex, localised in the right inferior frontal gyrus (IFG), in response to positive emotional expressions of happiness. Univariate twin modelling showed activity in the IFG to have 20% heritability. Multivariate twin modelling suggested that the association between wellbeing and positive emotion-elicited neural activity was driven by common variance from unique environment (r = 0.208) rather than shared genetics. Conclusions: Higher mental wellbeing may have a basis in greater engagement of prefrontal neural regions in response to positive emotion, and this association may be modifiable by unique life experiences. [ABSTRACT FROM AUTHOR]

Background: Research has yielded evidence for genetic and environmental factors influencing the risk of schizophrenia. Numerous environmental factors have been identified; however, the individual effects are small. The additive and interactive effects of multiple risk factors are not well elucidated. Twin pairs discordant for schizophrenia offer a unique opportunity to identify factors that differ between patients and unaffected co-twins, who are perfectly matched for age, sex and genetic background. Methods: Register data were combined with clinical data for 216 twins including monozygotic (MZ) and dizygotic (DZ) proband pairs (one or both twins having a schizophrenia spectrum diagnosis) and MZ/DZ healthy control (HC) pairs. Logistic regression models were applied to predict (1) illness vulnerability (being a proband v. HC pair) and (2) illness status (being the patient v. unaffected co-twin). Risk factors included: A polygenic risk score (PRS) for schizophrenia, birth complications, birth weight, Apgar scores, paternal age, maternal smoking, season of birth, parental socioeconomic status, urbanicity, childhood trauma, estimated premorbid intelligence and cannabis. Results: The PRS [odds ratio (OR) 1.6 (1.1–2.3)], childhood trauma [OR 4.5 (2.3–8.8)], and regular cannabis use [OR 8.3 (2.1–32.7)] independently predicted illness vulnerability as did an interaction between childhood trauma and cannabis use [OR 0.17 (0.03–0.9)]. Only regular cannabis use predicted having a schizophrenia spectrum diagnosis between patients and unaffected co-twins [OR 3.3 (1.1–10.4)]. Conclusion: The findings suggest that several risk factors contribute to increasing schizophrenia spectrum vulnerability. Moreover, cannabis, a potentially completely avoidable environmental risk factor, seems to play a substantial role in schizophrenia pathology. [ABSTRACT FROM AUTHOR]

Background: Anxiety disorders are highly prevalent with an early age of onset. Understanding the aetiology of disorder emergence and recovery is important for establishing preventative measures and optimising treatment. Experimental approaches can serve as a useful model for disorder and recovery relevant processes. One such model is fear conditioning. We conducted a remote fear conditioning paradigm in monozygotic and dizygotic twins to determine the degree and extent of overlap between genetic and environmental influences on fear acquisition and extinction. Methods: In total, 1937 twins aged 22–25 years, including 538 complete pairs from the Twins Early Development Study took part in a fear conditioning experiment delivered remotely via the Fear Learning and Anxiety Response (FLARe) smartphone app. In the fear acquisition phase, participants were exposed to two neutral shape stimuli, one of which was repeatedly paired with a loud aversive noise, while the other was never paired with anything aversive. In the extinction phase, the shapes were repeatedly presented again, this time without the aversive noise. Outcomes were participant ratings of how much they expected the aversive noise to occur when they saw either shape, throughout each phase. Results: Twin analyses indicated a significant contribution of genetic effects to the initial acquisition and consolidation of fear, and the extinction of fear (15, 30 and 15%, respectively) with the remainder of variance due to the non-shared environment. Multivariate analyses revealed that the development of fear and fear extinction show moderate genetic overlap (genetic correlations 0.4–0.5). Conclusions: Fear acquisition and extinction are heritable, and share some, but not all of the same genetic influences. [ABSTRACT FROM AUTHOR]

Background: Psychopathic traits involve interpersonal manipulation, callous affect, erratic lifestyle, and antisocial behavior. Though adult psychopathic traits emerge from both genetic and environmental risk, no studies have examined etiologic associations between adult psychopathic traits and experiences of parenting in childhood, or the extent to which parenting practices may impact the heritability of adult psychopathic traits using a genetically-informed design. Methods: In total, 1842 adult twins from the community reported their current psychopathic traits and experiences of negative parenting during childhood. We fit bivariate genetic models to the data, decomposing the variance within, and the covariance between, psychopathic traits and perceived negative parenting into their genetic and environmental components. We then fit a genotype × environment interaction model to evaluate whether negative parenting moderated the etiology of psychopathic traits. Results: Psychopathic traits were moderately heritable with substantial non-shared environmental influences. There were significant associations between perceived negative parenting and three of four psychopathy facets (interpersonal manipulation, erratic lifestyle, antisocial tendencies, but not callous affect). These associations were attributable to a common non-shared environmental pathway and not to overlapping genetic effects. Additionally, we found that primarily shared environmental influences were stronger on psychopathic traits for individuals with a history of greater negative parenting. Conclusions: Utilizing a genetically-informed design, we found that both genetic and non-shared environmental factors contribute to the emergence of psychopathic traits. Moreover, perceptions of negative parenting emerged as a clear environmental influence on the development of interpersonal, lifestyle, and antisocial features of psychopathy. [ABSTRACT FROM AUTHOR]

Background: A dominant feature of anxiety disorders is familial aggregation. However, the underlying mechanisms of between- and within-generational anxiety resemblance remain poorly understood. By disentangling the genetic v. environmental sources of familial resemblance in anxiety, we can help prevent within-family transmission of anxiety disorders. Therefore, data from both parents and twins are needed to obtain unbiased and detailed estimations of genetic and environmental sources of similarity between family members. Methods: We examined data from 991 families with same-sex twins. Trait anxiety in twins was assessed via self-report and parent report, while parental trait anxiety was assessed via self-report. We established a nuclear twin family model and estimated genetic and environmental variances using two survey waves. Results: The results suggested that additive genetic (A), dominant genetic (D), and non-shared environmental (E) influences significantly contributed to trait anxiety, whereas familial environmental influences (F) and passive gene–environment correlations (rGE) did not. Sibling environmental influences (S) were only found in self-report data, and increased when genetic influences decreased from Wave 1 to Wave 2. Conclusions: Our study highlights the important role of broad heritability in intrafamilial trait anxiety similarity. Parent–child resemblance occurred primarily due to shared genetic makeup rather than direct environmental transmission. Sibling-specific environments, as the only source of shared environments, need further investigation. These findings have both theoretical and practical significance for anxiety disorders. Future research can expand our understanding by examining the gene–environment interplay and sex differences. [ABSTRACT FROM AUTHOR]

Background: Few factor analyses and no network analyses have examined the structure of DSM phobic fears or tested the specificity of the relationship between panic disorder and agoraphobic fears. Methods: Histories of 21 lifetime phobic fears, coded as four-level ordinal variables (no fear to fear with major interference) were assessed at personal interview in 7514 adults from the Virginia Twin Registry. We estimated Gaussian Graphical Models on individual phobic fears; compared network structures of women and men using the Network Comparison Test; used community detection to determine the number and nature of groups in which phobic fears hang together; and validated the anticipated specific relationship between panic disorder and agoraphobia. Results: All networks were densely and positively inter-connected; networks of women and men were structurally similar. Our most frequent and stable solution identified four phobic clusters: (i) blood-injection, (ii) social-agoraphobia, (iii) situational, and (iv) animal-disease. Fear of public restrooms and of diseases clustered with animal and not, respectively, social and blood-injury phobias. When added to the network, the three strongest connections with lifetime panic disorder were all agoraphobic fears: being in crowds, going out of the house alone, and being in open spaces Conclusions: Using network analyses applied to a large epidemiologic twin sample, we broadly validated the DSM-IV typography but did not entirely support the distinction of agoraphobic and social phobic fears or the DSM placements for fears of public restrooms and diseases. We found strong support for the specificity of the relationship between panic disorder and agoraphobic fears. [ABSTRACT FROM AUTHOR]

Background: Previous research indicates that body dysmorphic disorder (BDD) is associated with risk of suicidality. However, studies have relied on small and/or specialist samples and largely focussed on adults, despite these difficulties commonly emerging in youth. Furthermore, the aetiology of the relationship remains unknown. Methods: Two independent twin samples were identified through the Child and Adolescent Twin Study in Sweden, at ages 18 (N = 6027) and 24 (N = 3454). Participants completed a self-report measure of BDD symptom severity. Young people and parents completed items assessing suicidal ideation/behaviours. Logistic regression models tested the association of suicidality outcomes with: (a) probable BDD, classified using an empirically derived cut-off; and (b) continuous scores of BDD symptoms. Bivariate genetic models examined the aetiology of the association between BDD symptoms and suicidality at both ages. Results: Suicidal ideation and behaviours were common among those with probable BDD at both ages. BDD symptoms, measured continuously, were linked with all aspects of suicidality, and associations generally remained significant after adjusting for depressive and anxiety symptoms. Genetic factors accounted for most of the covariance between BDD symptoms and suicidality (72.9 and 77.7% at ages 18 and 24, respectively), but with significant non-shared environmental influences (27.1 and 22.3% at ages 18 and 24, respectively). Conclusions: BDD symptoms are associated with a substantial risk of suicidal ideation and behaviours in late adolescence and early adulthood. This relationship is largely explained by common genetic liability, but non-shared environmental effects are also significant and could provide opportunities for prevention among those at high-risk. [ABSTRACT FROM AUTHOR]

Background: Despite abundant research on the potential causal influence of childhood maltreatment (CM) on psychological maladaptation in adulthood, almost none has implemented the discordant twin design as a means of examining the role of such experiences in later disordered gambling (DG) while accounting for genetic and family environmental confounds. The present study implemented such an approach to disentangle the potential causal and familial factors that may account for the association between CM and DG. Methods: Participants were 3750 twins from the Australian Twin Registry [Mage = 37.60 (s.d. = 2.31); 58% female]. CM and DG were assessed separately via two semi-structured telephone interviews. Random-intercept generalized linear mixed models were fit to the data; zygosity, sex, educational attainment, childhood psychiatric disorder, adult antisocial behavior, and alcohol use disorder (AUD) were included as covariates. Results: Neither quasi-causal nor familial effects of CM predicted DG after adjusting for covariates. Educational attainment appeared to reduce the risk of DG while AUD appeared to increase risk; evidence also emerged for familial effects of antisocial behavior on DG. Post-hoc analyses revealed a familial effect of CM on antisocial behavior, indicating that the association between CM and DG identified in unadjusted models and in prior studies may be accounted for by genetic and shared family environmental effects of antisociality. Conclusions: These findings add to the meager literature showing that CM does not exert a causal effect on DG, and present novel evidence that familial effects of antisocial behavior may account for the association between CM and DG identified in extant non-twin research. [ABSTRACT FROM AUTHOR]

Background: Depressive episodes experienced in unipolar (UD) and bipolar (BD) disorders are characterized by anhedonia and have been associated with abnormalities in reward processes related to reward valuation and error prediction. It remains however unclear whether these deficits are associated with familial vulnerability to mood disorders. Methods: In a functional magnetic resonance imaging study, we evaluated differences in the expected value (EV) and reward prediction error (RPE) signals in ventral striatum (VS) and prefrontal cortex between three groups of monozygotic twins: affected twins in remission for either UD or BD (n = 53), their high-risk unaffected co-twins (n = 34), and low-risk twins with no family history of mood disorders (n = 25). Results: Compared to low-risk twins, affected twins showed lower EV signal bilaterally in the frontal poles and lower RPE signal bilaterally in the VS, left frontal pole and superior frontal gyrus. The high-risk group did not show a significant change in the EV or RPE signals in frontostriatal regions, yet both reward signals were consistently lower compared with low-risk twins in all regions where the affected twins showed significant reductions. Conclusion: Our findings strengthen the notion that reduced valuation of expected rewards and reduced error-dependent reward learning may underpin core symptom of depression such as loss of interest in rewarding activities. The trend reduction in reward-related signals in unaffected co-twins warrants further investigation of this effect in larger samples and prospective follow-up to confirm possible association with increased familial vulnerability to mood disorders. [ABSTRACT FROM AUTHOR]

Background: Sleep apnea is one of the most common sleep disorders and it is related to multiple negative health consequences. Previous studies have shown that sleep apnea is influenced by genetic factors. However, studies have not investigated the genetic and environmental influences of symptoms of sleep apnea in young adults. Furthermore, the underpinnings of the relationship between apnea symptoms and internalizing/externalizing problems are unknown. The objectives of this study were to estimate the magnitude of: (1) genetic and environmental influences on self-reported apnea symptoms; (2) the relationship between self-reported apnea symptoms and internalizing/externalizing traits; (3) genetic and environmental influences on the associations between self-reported apnea symptoms, internalizing behaviors and externalizing behaviors. Methods: In a twin/sibling study, univariate and multivariate models were fitted to estimate both individual variance and sources of covariance between symptoms of sleep apnea and internalizing/externalizing behaviors. Results: Our results show that genetic influences account for 40% of the variance in sleep apnea symptoms. Moreover, there are modest associations between depression, anxiety and externalizing behaviors with apnea symptoms (ranging from r = 0.22–0.29). However, the origins of these associations differ. For example, whereas most of the covariation between symptoms of depression and sleep apnea can be explained by genes (95%), there was a larger role for the environment (53%) in the association between symptoms of anxiety and sleep apnea. Conclusions: Genetic factors explain a significant proportion of variance in symptoms of apnea and most of the covariance with depression. [ABSTRACT FROM AUTHOR]

Background: Attention-deficit hyperactivity disorder (ADHD) is associated with poorer cognitive functioning. We used a developmental, genetically-sensitive approach to examine intelligence quotient (IQ) from early childhood to young adulthood among those with different ADHD courses to investigate whether changes in ADHD were reflected in differences in IQ. We also examined executive functioning in childhood and young adulthood among different ADHD courses. Methods: Study participants were part of the Environmental Risk (E-Risk) Longitudinal Twin Study, a population-based birth cohort of 2232 twins. We assessed ADHD in childhood (ages 5, 7, 10 and 12) and young adulthood (age 18). We examined ADHD course as reflected by remission, persistence and late-onset. IQ was evaluated at ages 5, 12 and 18, and executive functioning at ages 5 and 18. Results: ADHD groups showed deficits in IQ across development compared to controls; those with persistent ADHD showed the greatest deficit, followed by remitted and late-onset. ADHD groups did not differ from controls in developmental trajectory of IQ, suggesting changes in ADHD were not reflected in IQ. All ADHD groups performed more poorly on executive functioning tasks at ages 5 and 18; persisters and remitters differed only on an inhibitory control task at age 18. Conclusions: Differences in ADHD course – persistence, remission and late-onset – were not directly reflected in changes in IQ. Instead, having ADHD at any point across development was associated with lower average IQ and poorer executive functioning. Our finding that individuals with persistent ADHD have poorer response inhibition than those who remitted requires replication. [ABSTRACT FROM AUTHOR]

Background: Psychoactive substance use is lower among married compared to divorced or unmarried men; yet, the nature of this effect remains unclear because becoming and staying married is potentially confounded with substance-related background familial and individual factors, like parental divorce and personality. The authors investigated the associations between marital status and substance use; how substance use changed across the transition to marriage; and whether marriage effects were likely to be causal. Method: The sample included 1790 adults from male–male twin pairs from a population-based registry. Measures of marital status and alcohol, tobacco, and cannabis use came from Life History Calendars. Data were analyzed using regression, co-twin comparison, and within-person models. The latter models are tools for quasi-causal inference that control for familial and individual-level confounders. Results: Married men used less alcohol, tobacco, and cannabis than men who were divorced/separated or single. In analyses of substance use across the transition to marriage, men reduced their alcohol and cannabis use both before and after marriage, but their tobacco use only after marriage. These effects were largely robust in co-twin and within-person analyses. Conclusions: Marriage was associated with substantial reductions in substance use compared to being divorced/separated or single, and these reductions began prior to marriage. The co-twin comparison and within-person models ruled out the alternative explanation that marriage effects were due to confounding background familial and individual factors. These results provide strong evidence that the social role expectations associated with marriage reduce psychoactive substance use. [ABSTRACT FROM AUTHOR]

Background: Social support has been shown to be associated with a reduced likelihood of developing psychotic experiences in the general population and even amongst those at high risk due to exposure to multiple forms of victimisation (poly-victimised). However, it is unclear whether this association is merely due to the confounding effects of shared environmental and genetic influences, or reverse causality. Therefore, we investigated whether social support has a unique environmentally mediated effect on adolescent psychotic experiences after accounting for familial factors, including genetic factors, and also prior psychopathology. Methods: Participants were from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally-representative cohort of 2232 UK-born twins. Adolescents were interviewed at age 18 about psychotic experiences and victimisation exposure since age 12, and their perceptions of social support. Prior childhood mental health problems and psychotic symptoms were assessed at age 12. The discordant twin method was used to disentangle the relative family-wide and unique-environmental effects of social support on psychotic experiences in the general population and among poly-victimised adolescents. Results: Perceived social support, particularly from friends, was found to have a unique environmentally mediated buffering effect on adolescent psychotic experiences in the whole sample and in the high-risk poly-victimised group. Conclusions: The protective effects of social support on adolescent psychotic experiences cannot be accounted for by shared environmental or genetic factors, nor by earlier psychopathology. Our findings suggest that early intervention programmes focused on increasing perceptions of social support have the potential to prevent the emergence of psychotic experiences amongst adolescents. [ABSTRACT FROM AUTHOR]

Background: Metabolic syndrome (MetS) is associated with reduced life expectancy in patients with affective disorders, however, whether MetS also plays a role before the onset of affective disorder is unknown. We aimed to investigate whether MetS, inflammatory markers or oxidative stress act as risk factors for affective disorders, and whether MetS is associated with increased inflammation and oxidative stress. Methods: We conducted a high-risk study including 204 monozygotic (MZ) twins with unipolar or bipolar disorder in remission or partial remission (affected), their unaffected co-twins (high-risk) and twins with no personal or family history of affective disorder (low-risk). Metabolic Syndrome was ascertained according to the International Diabetes Federation (IDF) criteria. Inflammatory markers and markers of oxidative stress were analyzed from fasting blood and urine samples, respectively. Results: The affected and the high-risk group had a significantly higher prevalence of MetS compared to the low-risk group (20% v. 15% v. 2.5%, p = 0.0006), even after adjusting for sex, age, smoking and alcohol consumption. No differences in inflammatory and oxidative markers were seen between the three groups. Further, MetS was associated with alterations in inflammatory markers, and oxidative stress was modestly correlated with inflammation. Conclusion: Metabolic syndrome is associated with low-grade inflammation and may act as a risk factor and a trait marker for affective disorders. If confirmed in longitudinal studies, this suggests the importance of early intervention and preventive approaches targeted towards unhealthy lifestyle factors that may contribute to later psychopathology. [ABSTRACT FROM AUTHOR]

Background: Causes of the comorbidity of substance misuse with anxiety-related and depressive disorders (anxiety/depression) remain poorly known. We estimated associations of substance misuse and anxiety/depression in the general population and tested them while accounting for genetic and shared environmental factors. Methods: We studied individuals born in Sweden 1968–1997 (n = 2 996 398) with follow-up in nationwide register data for 1997–2013. To account for familial effects, stratified analyses were conducted within siblings and twin pairs. Substance misuse was defined as ICD-10 alcohol or drug use disorder or an alcohol/drug-related criminal conviction. Three dimensions of ICD-10 anxiety and depressive disorders and a substance misuse dimension were identified through exploratory factor analysis. Results: Substance misuse was associated with a 4.5-fold (95% CI 4.50–4.58) elevated risk of lifetime generalized anxiety/depression, 4.7-fold (95% CI 4.63–4.82) elevated risk of panic disorder and agora/social phobia, and 2.9-fold elevated risk of phobias/OCD (95% CI 2.82–3.02) as compared to those without substance misuse. The associations were attenuated in within-family analyses but we found elevated risks in monozygotic twin pairs discordant for substance misuse as well as significant non-shared environmental correlations. The association between anxiety/depression and substance misuse was mainly driven by generalized anxiety/depression, whereas other anxiety/depression dimensions had minor or no independent associations with substance misuse. Conclusions: Substance misuse and anxiety/depression are associated at the population level, and these associations are partially explained by familial liabilities. Our findings indicate a common genetic etiology but are also compatible with a potential partially causal relationship between substance misuse and anxiety/depression. [ABSTRACT FROM AUTHOR]

Background: Prior work has robustly suggested that social processes in the neighborhood (i.e. informal social control, social cohesion, norms) influence child conduct problems (CP) and related outcomes, but has yet to consider how these community-level influences interact with individual-level genetic risk for CP. The current study sought to do just this, evaluating neighborhood-level social processes as etiologic moderators of child CP for the first time. Methods: We made use of two nested samples of child and adolescent twins within the Michigan State University Twin Registry (MSUTR): 5649 families who participated in in the Michigan Twins Project (MTP) and 1013 families who participated in the Twin Study of Behavioral and Emotional Development (TBED-C). The neighborhood social processes of informal social control, social cohesion, and norms were assessed using neighborhood sampling techniques, in which residents of each twin family's neighborhood reported on the social processes in their neighborhood. Standard biometric GxE analyses evaluated the extent to which they moderated the etiology of CP. Results: The 'no moderation' model provided the best fit to the data in nearly all cases, arguing against neighborhood social processes as etiologic moderators of youth CP. Conclusions: The neighborhood social processes evaluated here do not appear to exert their effects on child CP via etiologic moderation. The documented links between neighborhood social processes and child CP are thus likely to reflect a different etiologic process. Possibilities include environmental main effects of neighborhood social processes on child CP, or genotype-environment correlations. [ABSTRACT FROM AUTHOR]

Background: Internalizing and externalizing psychopathology factors explain much of the covariance among psychiatric conditions, especially at the level of genetic risk. However, few studies have examined internalizing and externalizing factors in middle-aged samples, especially their ability to predict later symptoms across midlife. The goals of the current study were (i) to quantify the genetic and environmental influences on internalizing and externalizing psychopathology in individuals in their early 40s, and (ii) examine the extent to which these genetic and environmental influences predict self-reported measures of internalizing and externalizing symptoms 15–20 years later. Method: 1484 male twins completed diagnostic interviews of psychopathology at mean age 41 and self-reported measures of anxiety, depression, substance use, and related variables at up to two time-points in late middle age (mean ages 56 and 62). Results: Structural equation modeling of the diagnostic interviews confirmed that internalizing and externalizing factors accounted for most of the genetic variance in individual disorders, with substantial genetic (ra = 0.70) and environmental (re = 0.77) correlations between the factors. Internalizing psychopathology at age 41 was correlated with latent factors capturing anxiety, depression, and/or post-traumatic stress symptoms at ages 56 (r = 0.51) and 62 (r = 0.43). Externalizing psychopathology at age 41 was correlated r = 0.67 with a latent factor capturing aggression, tobacco use, and alcohol use at age 56. Stability of both factors was driven by genetic influences. Conclusions: These findings demonstrate the considerable stability of internalizing and externalizing psychopathology symptoms across middle age, especially their genetic influences. Diagnostic interviews effectively predict self-reported symptoms and behaviors 15–20 years later. [ABSTRACT FROM AUTHOR]

Background: Parental characteristics and practices predict borderline personality disorder (BPD) symptoms in children. However, it is difficult to disentangle whether these effects are genetically or environmentally mediated. The present study examines the contributions of genetic and environmental influences by comparing the effects of familial risk factors (i.e. parental psychopathology and borderline traits, maladaptive parenting, marital discord) on child BPD traits in genetically related (biological) and non-related (adoptive) families. Methods: Data are from 409 adoptive and 208 biological families who participated in the Siblings Interaction and Behavior Study (SIBS) and 580 twin families the Minnesota Twin Family Study (MTFS). Parent characteristics and practices included parental psychopathology (measured via structured clinical interviews), parental BPD traits, parenting behaviors, and marital discord. A series of multi-level regression models were estimated to examine the relationship of familial risk factors to child BPD traits and to test whether children's adoptive status moderated the association. Results: Symptom counts of parents' conduct disorder, adult antisocial behavior, nicotine, alcohol, and illicit drug dependence, and paternal BPD traits substantially predicted child BPD traits only in biological offspring, implying genetic transmission. Maternal BPD traits and both maternal and paternal conflict, lack of regard, and lack of involvement predicted offspring BPD traits regardless of the adoptive status, implying environmental transmission. Conclusions: Parental externalizing psychopathology and father's BPD traits contribute genetic risk for offspring BPD traits, but mothers' BPD traits and parents' poor parenting constitute environmental risks for the development of these offspring traits. [ABSTRACT FROM AUTHOR]

Background: Social attention ability is crucial for human adaptive social behaviors and interpersonal communications, and the malfunction of which has been implicated in autism spectrum disorder (ASD), a highly genetic neurodevelopmental disorder marked by striking social deficits. Methods: Using a classical twin design, the current study investigated the genetic contribution to individual variation in social and non-social attention abilities, and further probed their potential genetic linkage. Moreover, individual autistic traits were further measured in an independent group of non-twin participants to examine the hypothetical link between the core social attention ability and ASD. Results: We found reliable genetic influences on the social attentional effects induced by two distinct cues (eye gaze and walking direction), with 91% of their covariance accounted for by common genetic effects. However, no evidence of heritability or shared genetic effects was observed for the attentional effect directed by a non-social cue (i.e. arrow direction) and its correlation with the social attention ability. Remarkably, one's autistic traits could well predict his/her heritable core social attention ability extracted from the conventional social attentional effect. Conclusions: These findings together suggest that human social attention ability is supported by unique genetic mechanisms that can be shared across different social, but not non-social, processing. Moreover, they also encourage the identification of 'social attention genes' and highlight the critical role of the core human social attention ability in seeking the endophenotypes of social cognitive disorders including ASD. [ABSTRACT FROM AUTHOR]

Background: Vulnerability to depression can be measured in different ways. We here examine how genetic risk factors are inter-related for lifetime major depression (MD), self-report current depressive symptoms and the personality trait Neuroticism. Method: We obtained data from three population-based adult twin samples (Virginia n = 4672, Australia #1 n = 3598 and Australia #2 n = 1878) to which we fitted a common factor model where risk for 'broadly defined depression' was indexed by (i) lifetime MD assessed at personal interview, (ii) depressive symptoms, and (iii) neuroticism. We examined the proportion of genetic risk for MD deriving from the common factor v. specific to MD in each sample and then analyzed them jointly. Structural equation modeling was conducted in Mx. Results: The best fit models in all samples included additive genetic and unique environmental effects. The proportion of genetic effects unique to lifetime MD and not shared with the broad depression common factor in the three samples were estimated as 77, 61, and 65%, respectively. A cross-sample mega-analysis model fit well and estimated that 65% of the genetic risk for MD was unique. Conclusion: A large proportion of genetic risk factors for lifetime MD was not, in the samples studied, captured by a common factor for broadly defined depression utilizing MD and self-report measures of current depressive symptoms and Neuroticism. The genetic substrate for MD may reflect neurobiological processes underlying the episodic nature of its cognitive, motor and neurovegetative manifestations, which are not well indexed by current depressive symptom and neuroticism. [ABSTRACT FROM AUTHOR]

Background: Prior work has indicated both theoretical and empirical overlap between social and physical aggression. The extent to which their covariance can be explained by the same underlying genetic or environmental factors, however, remains unclear. It is also uncertain whether or how the origins of their covariance might vary across sex. The current study sought to fill these gaps in the literature. Methods: We examined maternal and teacher reports of youth physical and social aggression in over 1000 6–10 years old (mean age = 8.02 years) twin pairs from the Michigan State University Twin Registry. We made use of the bivariate correlated factors model to clarify the origins of their association. We further tested both sex difference and no-sex difference versions of that model to determine whether there are sex differences in the association between social and physical aggression, as often assumed. Results: The covariation between social and physical aggression was due to overlapping genetic factors and common environmental conditions. Specifically, 50–57% of the genetic factors, 74–100% of the shared environmental factors, and 28–40% of the unique environmental factors influencing physical aggression also influenced social aggression according to both mother and teacher reports. These shared etiological factors did not differ across sex. Conclusions: These findings argue against the common assumption that social aggression is the 'female version' of male physical aggression, and instead suggest that social aggression may be best conceptualized as a form of antisocial behavior that shares developmental pathways with other manifestations of externalizing pathology. [ABSTRACT FROM AUTHOR]

Background: Bipolar disorder is a highly heritable mental illness that transmits intergeneratively. Previous studies supported that first-degree relatives (FDRs), such as parents, offspring, and siblings, of patients with bipolar disorder, had a higher risk of bipolar disorder. However, whether FDRs of bipolar patients have an increased risk of schizophrenia, major depressive disorder (MDD), autism spectrum disorder (ASD), and attention deficit hyperactivity disorder (ADHD) remains unclear. Methods: Among the entire population in Taiwan, 87 639 patients with bipolar disorder and 188 290 FDRs of patients with bipolar disorder were identified in our study. The relative risks (RRs) of major psychiatric disorders were assessed among FDRs of patients with bipolar disorder. Results: FDRs of patients with bipolar disorder were more likely to have a higher risk of major psychiatric disorders, including bipolar disorder (RR 6.12, 95% confidence interval (CI) 5.95–6.30), MDD (RR 2.89, 95% CI 2.82–2.96), schizophrenia (RR 2.64, 95% CI 2.55–2.73), ADHD (RR 2.21, 95% CI 2.13–2.30), and ASD (RR 2.10, 95% CI 1.92–2.29), than the total population did. These increased risks for major psychiatric disorders were consistent across different familial kinships, such as parents, offspring, siblings, and twins. A dose-dependent relationship was also found between risk of each major psychiatric disorder and numbers of bipolar patients. Conclusions: Our study was the first study to support the familial coaggregation of bipolar disorder with other major psychiatric disorders, including schizophrenia, MDD, ADHD, and ASD, in a Taiwanese (non-Caucasian) population. Given the elevated risks of major psychiatric disorders, the public health government should pay more attention to the mental health of FDRs of patients with bipolar disorder. [ABSTRACT FROM AUTHOR]

Background: Normative and pathological personality traits have rarely been integrated into a joint large-scale structural analysis with psychiatric disorders, although a recent study suggested they entail a common individual differences continuum. Methods: We explored the joint factor structure of 11 psychiatric disorders, five personality-disorder trait domains (DSM-5 Section III), and five normative personality trait domains (the 'Big Five') in a population-based sample of 2796 Norwegian twins, aged 19‒46. Results: Three factors could be interpreted: (i) a general risk factor for all psychopathology, (ii) a risk factor specific to internalizing disorders and traits, and (iii) a risk factor specific to externalizing disorders and traits. Heritability estimates for the three risk factor scores were 48% (95% CI 41‒54%), 35% (CI 28‒42%), and 37% (CI 31‒44%), respectively. All 11 disorders had uniform loadings on the general factor (congruence coefficient of 0.991 with uniformity). Ignoring sign and excluding the openness trait, this uniformity of factor loadings held for all the personality trait domains and all disorders (congruence 0.983). Conclusions: Based on our findings, future research should investigate joint etiologic and transdiagnostic models for normative and pathological personality and other psychopathology. [ABSTRACT FROM AUTHOR]

Available twin-family data on sex differences in antisocial behavior (ASB) simultaneously suggest that ASB is far more prevalent in males than in females, and that its etiology (i.e. the effects of genes, environments, hormones, culture) does not differ across sex. This duality presents a conundrum: How do we make sense of mean sex differences in ASB if not via differences in genes, environments, hormones, and/or cultures? The current selective review and critique explores possible contributions to these seemingly incompatible sets of findings. We asked whether the presence of sex differences in behavior could be smaller than is typically assumed, or confined to a specific set of behaviors. We also asked whether there might be undetected differences in etiology across sex in twin-family studies. We found little evidence that bias or measurement invariance across sex account for phenotypic sex differences in ASB, but we did identify some key limitations to current twin-family approaches. These included the questionable ability of qualitative sex difference analyses to detect gender norms and prenatal exposure to testosterone, and concerns regarding specific analytic components of quantitative sex difference analyses. We conclude that the male preponderance in ASB is likely to reflect a true sex difference in observed behavior. It was less clear, however, that the genetic and environmental contributions to ASB are indeed identical across sex, as argued by prior twin-family studies. It is our hope that this review will inspire the development of new, genetically-informed methods for studying sex differences in etiology. [ABSTRACT FROM AUTHOR]

Background: Gambling disorder (GD), recognized in Diagnostic and Statistical Manual of Mental Disorders, Version 5 (DSM-5) as a behavioral addiction, is associated with a range of adverse outcomes. However, there has been little research on the genetic and environmental influences on the development of this disorder. This study reports results from the largest twin study of GD conducted to date. Methods: Replication and combined analyses were based on samples of 3292 (mean age 31.8, born 1972–79) and 4764 (mean age 37.7, born 1964–71) male, female, and unlike-sex twin pairs from the Australian Twin Registry. Univariate biometric twin models estimated the proportion of variation in the latent GD liability that could be attributed to genetic, shared environmental, and unique environmental factors, and whether these differed quantitatively or qualitatively for men and women. Results: In the replication study, when using a lower GD threshold, there was evidence for significant genetic (60%; 95% confidence interval (CI) 45–76%) and unique environmental (40%; 95% CI 24–56%), but not shared environmental contributions (0%; 95% CI 0–0%) to GD liability; this did not significantly differ from the original study. In the combined analysis, higher GD thresholds (such as one consistent with DSM-5 GD) and a multiple threshold definitions of GD yielded similar results. There was no evidence for quantitative or qualitative sex differences in the liability for GD. Conclusions: Twin studies of GD are few in number but they tell a remarkably similar story: substantial genetic and unique environmental influences, with no evidence for shared environmental contributions or sex differences in GD liability. [ABSTRACT FROM AUTHOR]

Background: The Triarchic Psychopathy Measure (TriPM) provides Disinhibition, Boldness, and Meanness scales for assessing the three trait domains of the triarchic model. Here we examined the genetic and environmental etiology of these three domains, including evaluation of potential sex differences. Methods: A total of 1016 men and women ages 19–20 years were drawn from the University of Southern California Risk Factors for Antisocial Behavior twin study. Results: Scores for the three TriPM scales were correlated to differing degrees, with the strongest phenotypic correlation between Disinhibition and Meanness. No sex differences were found in the genetic and environmental influences underlying these three domains, suggesting that the same genes and life experiences contribute to these traits in young men and women. For TriPM Disinhibition and Boldness, genetic factors explained about half or less of the variance, with the rest of the variance being explained by non-shared environmental factors. For TriPM Meanness, on the other hand, genetic, shared environmental, and non-shared environmental factors accounted for the variance. The phenotypic correlation between Disinhibition and Meanness was explained in part by common genes (26%), with the remainder attributable about equally to common shared (39%), and non-shared environmental influences (35%). Conclusions: These findings contribute to our understanding of psychopathic personality traits by demonstrating the importance of heritable factors for disinhibition and boldness facets of psychopathy, and the importance of shared environmental influences for the meanness facet. [ABSTRACT FROM AUTHOR]

Background: Can the structure of genetic and environmental influences on normative personality traits (NPTs), abnormal personality traits (APTs), and DSM-IV criteria for personality disorders (PD) fit a high or low congruence model positing, respectively, close or more limited etiologic continuity? Method: Exploratory factor analysis was applied to transformed correlation matrices from Cholesky twin decompositions obtained in OpenMx. In 2801 adult twins from the Norwegian Institute of Public Health Twin Panel, NPTs and APTs were assessed by self-report using the Big Five Inventory (BFI) and PID-5-Norwegian Brief Form (PID-5-NBF), respectively. PDs were assessed at interview using the Structured Interview for DSM-IV Personality (SIDP-IV). Results: The best model yielded three genetic and three unique environmental factors. Genetic factors were dominated, respectively, by (i) high loadings on nearly all PDs and NPT/APT neuroticism and compulsivity, (ii) negative loadings on NPT agreeableness/conscientiousness and positive loadings on APT/PD measures of antisocial traits, and (iii) negative loadings on NPT extraversion and histrionic PD, and positive loadings on APT detachment and schizoid/avoidant PD. Unique environmental factors were dominated, by (i) high loadings on all PDs, (ii) high loadings on all APT dimensions and NPT neuroticism, and (iii) negative loadings on NPT extraversion and positive loadings on NPT detachment/avoidant PD. Conclusions: Two genetic and one environmental common factor were consistent with a high congruence model while one genetic and two environmental factors were more supportive of a low congruence model. The relationship between genetic and environmental influences on personality assessed by NPTs, APTs, and PDs is complex and does not fit easily into a low or high congruence model. [ABSTRACT FROM AUTHOR]

Background: Identification of endophenotypes can improve prevention, detection and development of new treatments. We therefore investigated whether aberrant affective cognition constitutes an endophenotype for affective disorders by being present in monozygotic (MZ) twins with unipolar or bipolar disorder in partial remission (i.e. affected) and their unaffected co-twins (i.e. high-risk) relative to twins with no family history of affective disorder (i.e. low-risk). Methods: We conducted an assessor blind cross-sectional study from 2014 to 2017 of MZ twins using Danish population-based registers in recruitment. Twins attended one test session involving neurocognitive testing, clinical ratings and questionnaires. Main outcomes were attention to and recognition of emotional facial expressions, the memory of emotional self-referential words, emotion regulation and coping strategies. Results: Participants were 103 affected, 44 high-risk and 36 low-risk MZ twins. Groups were demographically well-balanced and showed comparable non-affective cognitive performance. We observed no aberrant affective cognition in affected and high-risk relative to low-risk twins. However, high-risk twins displayed attentional avoidance of emotional faces (p s ⩽ 0.009) and more use of task-oriented coping strategies (p = 0.01) compared with affected twins. In contrast did affected twins show more emotion-oriented coping than high- and low-risk twins (p s ⩽ 0.004). Conclusions: Our findings provide no support of aberrant affective cognition as an endophenotype for affective disorders. High-risk twins' attentional avoidance of emotional faces and greater use of task-oriented coping strategies may reflect compensatory mechanisms. [ABSTRACT FROM AUTHOR]

Background: Maternal smoking during pregnancy (MSDP) has been linked to offspring's externalizing problems. It has been argued that socio-demographic factors (e.g. maternal age and education), co-occurring environmental risk factors, or pleiotropic genetic effects may account for the association between MSDP and later outcomes. This study provides a comprehensive investigation of the association between MSDP and a single harmonized component of externalizing: aggressive behaviour, measured throughout childhood and adolescence. Methods: Data came from four prospective twin cohorts – Twins Early Development Study, Netherlands Twin Register, Childhood and Adolescent Twin Study of Sweden, and FinnTwin12 study – who collaborate in the EU-ACTION consortium. Data from 30 708 unrelated individuals were analysed. Based on item level data, a harmonized measure of aggression was created at ages 9–10; 12; 14–15 and 16–18. Results: MSDP predicted aggression in childhood and adolescence. A meta-analysis across the four samples found the independent effect of MSDP to be 0.4% (r = 0.066), this remained consistent when analyses were performed separately by sex. All other perinatal factors combined explained 1.1% of the variance in aggression across all ages and samples (r = 0.112). Paternal smoking and aggressive parenting strategies did not account for the MSDP-aggression association, consistent with the hypothesis of a small direct link between MSDP and aggression. Conclusions: Perinatal factors, including MSDP, account for a small portion of the variance in aggression in childhood and adolescence. Later experiences may play a greater role in shaping adolescents' aggressive behaviour. [ABSTRACT FROM AUTHOR]

Background: Genetic influences on alcohol involvement are likely to vary as a function of the 'alcohol environment,' given that exposure to alcohol is a necessary precondition for genetic risk to be expressed. However, few gene–environment interaction studies of alcohol involvement have focused on characteristics of the community-level alcohol environment. The goal of this study was to examine whether living in a community with more alcohol outlets would facilitate the expression of the genetic propensity to drink in a genetically-informed national survey of United States young adults. Methods: The participants were 2434 18–26-year-old twin, full-, and half-sibling pairs from Wave III of the National Longitudinal Study of Adolescent to Adult Health. Participants completed in-home interviews in which alcohol use was assessed. Alcohol outlet densities were extracted from state-level liquor license databases aggregated at the census tract level to derive the density of outlets. Results: There was evidence that the estimates of genetic and environmental influences on alcohol use varied as a function of the density of alcohol outlets in the community. For example, the heritability of the frequency of alcohol use for those residing in a neighborhood with ten or more outlets was 74% (95% confidence limits = 55–94%), compared with 16% (95% confidence limits = 0–34%) for those in a neighborhood with zero outlets. This moderating effect of alcohol outlet density was not explained by the state of residence, population density, or neighborhood sociodemographic characteristics. Conclusions: The results suggest that living in a neighborhood with many alcohol outlets may be especially high-risk for those individuals who are genetically predisposed to frequently drink. [ABSTRACT FROM AUTHOR]

Background: Prior research has documented shared heritable contributions to non-suicidal self-injury (NSSI) and suicidal ideation (SI) as well as NSSI and suicide attempt (SA). In addition, trauma exposure has been implicated in risk for NSSI and suicide. Genetically informative studies are needed to determine common sources of liability to all three self-injurious thoughts and behaviors, and to clarify the nature of their associations with traumatic experiences. Methods: Multivariate biometric modeling was conducted using data from 9526 twins [59% female, mean age = 31.7 years (range 24–42)] from two cohorts of the Australian Twin Registry, some of whom also participated in the Childhood Trauma Study and the Nicotine Addiction Genetics Project. Results: The prevalences of high-risk trauma exposure (HRT), NSSI, SI, and SA were 24.4, 5.6, 27.1, and 4.6%, respectively. All phenotypes were moderately to highly correlated. Genetic influences on self-injurious thoughts and behaviors and HRT were significant and highly correlated among men [ r G = 0.59, 95% confidence interval (CI) (0.37–0.81)] and women [ r G = 0.56 (0.49–0.63)]. Unique environmental influences were modestly correlated in women [ r E = 0.23 (0.01–0.45)], suggesting that high-risk trauma may confer some direct risk for self-injurious thoughts and behaviors among females. Conclusions: Individuals engaging in NSSI are at increased risk for suicide, and common heritable factors contribute to these associations. Preventing trauma exposure may help to mitigate risk for self-harm and suicide, either directly or indirectly via reductions in liability to psychopathology more broadly. In addition, targeting pre-existing vulnerability factors could significantly reduce risk for life-threatening behaviors among those who have experienced trauma. [ABSTRACT FROM AUTHOR]

Background: Existing evidence for gene × environment interaction (G × E) in neuroticism largely relies on candidate gene studies, although neuroticism is highly polygenic. This study aimed to investigate the long-term associations between polygenic risk scores for neuroticism (PRSN), objective childhood adversity and their interplay on emotional health aspects such as neuroticism itself, depressive symptoms, anxiety symptoms, loneliness and life satisfaction. Methods: The sample consisted of reared-apart (TRA) and reared-together (TRT) middle- and old age twins (N = 699; median age at separation = 2). PRSN were created under nine p value cut-off thresholds (p T-s) and the p T with the highest degree of neuroticism variance explained was chosen for subsequent analyses. Linear regressions were used to assess the associations between PRSN, childhood adversity (being reared apart) and emotional health. G × E was further investigated using a discordant twin design. Results: PRSN explained up to 1.7% (p T < 0.01) of phenotypic neuroticism in the total sample. Analyses across two separation groups revealed substantial heterogeneity in the variance explained by PRSN; 4.3% was explained in TRT, but almost no effect was observed in TRA. Similarly, PRSN explained 4% and 1.7% of the variance in depressive symptoms and loneliness, respectively, only in TRT. A significant G × E interaction was identified for depressive symptoms. Conclusions: By taking advantage of a unique sample of adopted twins, we demonstrated the presence of G × E in neuroticism and emotional health using PRSN and childhood adversity. Our results may indicate that genome-wide association studies are detecting genetic main effects associated with neuroticism, but not those susceptible to early environmental influences. [ABSTRACT FROM AUTHOR]

Background: Social aggression is a form of antisocial behavior in which social relationships and social status are used to damage reputations and inflict emotional harm on others. Despite extensive research examining the prevalence and consequences of social aggression, only a few studies have examined its genetic–environmental etiology, with markedly inconsistent results. Method: We estimated the etiology of social aggression using the nuclear twin family (NTF) model. Maternal-report, paternal-report, and teacher-report data were collected for twin social aggression (N = 1030 pairs). We also examined the data using the classical twin (CT) model to evaluate whether its strict assumptions may have biased previous heritability estimates. Results: The best-fitting NTF model for all informants was the ASFE model, indicating that additive genetic, sibling environmental, familial environmental, and non-shared environmental influences significantly contribute to the etiology of social aggression in middle childhood. However, the best-fitting CT model varied across informants, ranging from AE and ACE to CE. Specific heritability estimates for both NTF and CT models also varied across informants such that teacher reports indicated greater genetic influences and father reports indicated greater shared environmental influences. Conclusions: Although the specific NTF parameter estimates varied across informants, social aggression generally emerged as largely additive genetic (A = 0.15–0.77) and sibling environmental (S = 0.42–0.72) in origin. Such findings not only highlight an important role for individual genetic risk in the etiology of social aggression, but also raise important questions regarding the role of the environment. [ABSTRACT FROM AUTHOR]

Background: The genetic component of Cannabis Use Disorder may overlap with influences acting more generally on early stages of cannabis use. This paper aims to determine the extent to which genetic influences on the development of cannabis abuse/dependence are correlated with those acting on the opportunity to use cannabis and frequency of use. Methods: A cross-sectional study of 3303 Australian twins, measuring age of onset of cannabis use opportunity, lifetime frequency of cannabis use, and lifetime DSM-IV cannabis abuse/dependence. A trivariate Cholesky decomposition estimated additive genetic (A), shared environment (C) and unique environment (E) contributions to the opportunity to use cannabis, the frequency of cannabis use, cannabis abuse/dependence, and the extent of overlap between genetic and environmental factors associated with each phenotype. Results: Variance components estimates were A = 0.64 [95% confidence interval (CI) 0.58–0.70] and E = 0.36 (95% CI 0.29–0.42) for age of opportunity to use cannabis, A = 0.74 (95% CI 0.66–0.80) and E = 0.26 (95% CI 0.20–0.34) for cannabis use frequency, and A = 0.78 (95% CI 0.65–0.88) and E = 0.22 (95% CI 0.12–0.35) for cannabis abuse/dependence. Opportunity shares 45% of genetic influences with the frequency of use, and only 17% of additive genetic influences are unique to abuse/dependence from those acting on opportunity and frequency. Conclusions: There are significant genetic contributions to lifetime cannabis abuse/dependence, but a large proportion of this overlaps with influences acting on opportunity and frequency of use. Individuals without drug use opportunity are uninformative, and studies of drug use disorders must incorporate individual exposure to accurately identify aetiology. [ABSTRACT FROM AUTHOR]

The article cites a research study that examines the role of trauma exposure and posttraumatic stress disorder (PTSD) in the development of obesity in veterans. Recent studies have indicated that PTSD may be associated with obesity among men over the age of 60. Some studies have claimed that genetic liability may predispose some individuals to trauma exposure, PTSD and obesity.

Background: Using a longitudinal twin design and a latent growth curve/autoregressive approach, this study examined the genetic–environmental architecture of substance use across adolescence. Methods: Self-reports of substance use (i.e. alcohol, marijuana) were collected at ages 13, 14, 15, and 17 years from 476 twin pairs (475 boys, 477 girls) living in the Province of Quebec, Canada. Substance use increased linearly across the adolescent years. Results: ACE modeling revealed that genetic, as well as shared and non-shared environmental factors explained the overall level of substance use and that these same factors also partly accounted for growth in substance use from age 13 to 17. Additional genetic factors predicted the growth in substance use. Finally, autoregressive effects revealed age-specific non-shared environmental influences and, to a lesser degree, age-specific genetic influences, which together accounted for the stability of substance use across adolescence. Conclusions: The results support and expand the notion that genetic and environmental influences on substance use during adolescence are both developmentally stable and developmentally dynamic. [ABSTRACT FROM AUTHOR]

The article presents a study which examines the association between obesity, post-traumatic stress disorder (PTSD), and combat exposure in male veterans. Procedures of the study which involved male twins who were born between 1939 and 1957 and served in the U.S. military between 1964 and 1975 are offered. Results of the study which indicate the link between combat exposure and stress with and increased likelihood of obesity and weight gains are discussed.

Background: Lesbian, gay, and bisexual (LGB) individuals report higher levels of depression and anxiety than heterosexual people. Genetic factors may be a ‘common cause’ of sexual minority status and psychological distress. Alternatively, these may be correlated because of non-genetic environmental factors (e.g. minority stressors). This study investigated minority stressors and distress in monozygotic twins discordant for sexual minority status. This design provides a test of the role of non-shared environmental factors while minimizing differences due to genetics. Methods: Thirty-eight twin pairs in which one was heterosexual and the other was LGB completed a survey. Differences between twin pairs in minority stressors, rumination, psychological distress, and gender non-conformity were examined. Associations between these variables were also tested. Results: Although there were no significant group differences for distress, LGB twins had higher rumination, a vulnerability factor for distress, than heterosexual co-twins. LGB twins also had higher scores than heterosexual co-twins on expectations of rejection, active concealment, self-stigma, prejudice events, childhood gender non-conformity, and lower scores on sexual orientation disclosure. Differences between twin pairs in rumination were positively associated with differences in acceptance concerns and self-stigma. Finally, self-stigma was positively associated with rumination in the full sample of heterosexual co-twins and microaggressions were positively associated with rumination when looking at exclusively heterosexual co-twins. Conclusions: These results support environmental factors as a causal explanation for disparities in rumination between LGB and heterosexual individuals. These factors likely include minority stressors. Rumination may also be associated with minority stressors in heterosexual MZ co-twins of LGB individuals. [ABSTRACT FROM AUTHOR]

Background: Although there is extensive evidence that problematic alcohol use is associated with smaller hippocampal volume, the typical cross-sectional study design cannot determine whether hippocampal deviations reflect pre-existing liability toward problematic alcohol use or instead reflect an alcohol exposure-related effect. We used the co-twin control study design, which capitalizes upon differences within a twin pair in levels of drinking, to differentiate pre-existing liability from an effect of alcohol exposure. Methods: The sample included 100 female twins, prospectively assessed from ages 11 to 24. Problematic alcohol use was assessed dimensionally and included indicators of quantity, frequency, and density of alcohol use and intoxication. Hippocampal volume was assessed using magnetic resonance imaging. Results: Problematic alcohol use (proximal and cumulative) was associated with significantly smaller left and right hippocampal volume. Follow-up co-twin control analyses that partitioned individual-level alcohol effects into pre-existing, familial liability and non-shared alcohol exposure-related effects indicated that this association reflected alcohol exposure. Greater alcohol using twins had smaller hippocampal volume relative to lesser alcohol using co-twins, beyond effects of their shared genetic and environmental liability toward problematic alcohol use. Results held accounting for recent alcohol use, other substance use, externalizing and internalizing psychopathology, personality traits, trauma exposure, and menstrual phase. Conclusions: The association between problematic alcohol use and smaller hippocampal volume likely reflects an alcohol exposure-related effect. Differentiating pre-existing brain deviations that confer risk for problematic alcohol use from those that reflect effects of alcohol on the brain will inform etiological models of addiction and further prevention and intervention efforts. [ABSTRACT FROM AUTHOR]

BackgroundPrevious research has shown relatively diminished medial prefrontal cortex activation and heightened psychophysiological responses during the recollection of personal events in post-traumatic stress disorder (PTSD), but the origin of these abnormalities is unknown. Twin studies provide the opportunity to determine whether such abnormalities reflect familial vulnerabilities, result from trauma exposure, or are acquired characteristics of PTSD.MethodsIn this case–control twin study, 26 male identical twin pairs (12 PTSD; 14 non-PTSD) discordant for PTSD and combat exposure recalled and imagined trauma-unrelated stressful and neutral life events using a standard script-driven imagery paradigm during functional magnetic resonance imaging and concurrent skin conductance measurement.ResultsDiminished activation in the medial prefrontal cortex during Stressful v. Neutral script-driven imagery was observed in the individuals with PTSD, relative to other groups.ConclusionsDiminished medial prefrontal cortex activation during Stressful v. Neutral script-driven imagery may be an acquired characteristic of PTSD. If replicated, this finding could be used prospectively to inform diagnosis and the assessment of treatment response. [ABSTRACT FROM AUTHOR]

Background: Associations between parenting and child outcomes are often interpreted as reflecting causal, social influences. However, such associationsmay be confounded by genes common to children and their biological parents. To the extent that these shared genes influence behaviours in both generations, a passive genetic mechanismmay explain links between them. Here we aim to quantify the relative importance of passive genetic v. social mechanisms in the intergenerational association between parent-offspring relationship quality and offspring internalizing problems in adolescence. Methods: We used a Children-of-Twins (CoT) designwith data fromthe parent-based Twin andOffspring Study of Sweden (TOSS) sample [909 adult twin pairs and their offspring; offspringmean age 15.75 (2.42) years], and the child-based Swedish Twin Study of CHild and Adolescent Development (TCHAD) sample [1120 adolescent twin pairs; mean age 13.67 (0.47) years]. A composite of parent-report measures (closeness, conflict, disagreements, expressions of affection) indexed parent- offspring relationship quality in TOSS, and offspring self-reported internalizing symptoms were assessed using the Child Behavior Checklist (CBCL) in both samples. Results: A social transmissionmechanism explained the intergenerational association [r = 0.21 (0.16-0.25)] in our best-fitting model. Apassive genetic transmission pathwaywas not found to be significant, indicating that parental genetic influences on parent-offspring relationship quality and offspring genetic influences on their internalizing problemswere non-overlapping. Conclusion: These results indicate that this intergenerational association is a product of social interactions between children and parents, within which bidirectional effects are highly plausible. Results fromgenetically informative studies of parentingrelated effects should be used to help refine early parenting interventions aimed at reducing risk for psychopathology. [ABSTRACT FROM AUTHOR]

BackgroundCan core genetic liabilities for suicidal behavior be indexed using psychological and neural indicators combined? The current work addressed this question by examining phenotypic and genetic associations of two biobehavioral traits, threat sensitivity (THT) and disinhibition (DIS) – operationalized as psychoneurometric variables (i.e., composites of psychological-scale and neurophysiological measures) – with suicidal behaviors in a sample of adult twins.MethodsParticipants were 444 identical and fraternal twins recruited from an urban community. THT was assessed using a psychological-scale measure of fear/fearlessness combined with physiological indicators of reactivity to aversive pictures, and DIS was assessed using scale measures of disinhibitory tendencies combined with indicators of brain response from lab performance tasks. Suicidality was assessed using items from structured interview and questionnaire protocols.ResultsTHT and DIS each contributed uniquely to prediction of suicidality when assessed psychoneurometrically (i.e., as composites of scale and neurophysiological indicators). In addition, these traits predicted suicidality interactively, with participants high on both reporting the greatest degree of suicidal behaviors. Biometric (twin-modeling) analyses revealed that a high percentage of the predictive association for each psychoneurometric trait (83% for THT, 68% for DIS) was attributable to genetic variance in common with suicidality.ConclusionsFindings indicate that psychoneurometric assessments of biobehavioral traits index genetic liability for suicidal behavior, and as such, can serve as innovative targets for research on core biological processes contributing to severe psychopathology, including suicidal proclivities and actions. [ABSTRACT FROM PUBLISHER]

BackgroundPrior research demonstrated that attention-deficit hyperactivity disorder (ADHD) is associated with binge-eating behavior, binge-eating disorder (BED), and bulimia nervosa (BN). The aim of this study was to investigate these associations in an adult twin population, and to determine the extent to which ADHD symptoms and binge-eating behavior share genetic and environmental factors.MethodsWe used self-reports of current ADHD symptoms and lifetime binge-eating behavior and associated characteristics from a sample of over 18 000 adult twins aged 20–46 years, from the population-based Swedish Twin Registry. Mixed-effects logistic regression was used to examine the association between ADHD and lifetime binge-eating behavior, BED, and BN. Structural equation modeling was used in 13 773 female twins to determine the relative contribution of genetic and environmental factors to the association between ADHD symptoms and binge-eating behavior in female adult twins.ResultsADHD symptoms were significantly associated with lifetime binge-eating behavior, BED, and BN. The heritability estimate for current ADHD symptoms was 0.42 [95% confidence interval (CI) 0.41–0.44], and for lifetime binge-eating behavior 0.65 (95% CI 0.54–0.74). The genetic correlation was estimated as 0.35 (95% CI 0.25–0.46) and the covariance between ADHD and binge-eating behavior was primarily explained by genetic factors (91%). Non-shared environmental factors explained the remaining part of the covariance.ConclusionsThe association between adult ADHD symptoms and binge-eating behavior in females is largely explained by shared genetic risk factors. [ABSTRACT FROM PUBLISHER]