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Background No prior twin study has explored the heritability of clinically diagnosed ADHD. Such studies are needed to resolve conflicting results regarding the importance of genetic effects for ADHD in adults. We aimed to estimate the relative contribution of genetic and environmental influences for clinically diagnosed ADHD across the life span with a specific focus on ADHD in adults. Method Information about zygosity and sex was obtained from 59,514 twins born between 1959 and 2001 included in the nation-wide population-based Swedish Twin Register. Clinical data of ADHD diagnosis was obtained from the Prescribed Drug (i.e., stimulant or non-stimulant medication for ADHD) and National Patient Registers (i.e., ICD-10 diagnosis of ADHD). Twin methods were applied to clinical data of ADHD diagnosis using structural equation modeling with monozygotic and dizygotic twins. Results The best-fitting model revealed a high heritability of ADHD (0.88; 95% CI, 0.83–0.92) for the entire sample. Shared environmental effects, on the other hand, were non-significant and of minimal importance. The heritability of ADHD in adults was also substantial (0.72; 95% CI, 0.56–0.84). Conclusion This study showed that the heritability of clinically diagnosed ADHD is high across the life span. Our finding of high heritability for clinically diagnosed ADHD in adults indicate that the previous reports of low heritability is best explained by rater effects and that gene-identification studies of ADHD in adults needs to consider pervasiveness (e.g., multiple raters) and developmentally (e.g., childhood onset criteria) informative data.

A strong genetic link between the extreme and the subthreshold variation of DSM-IV based assessments of ADHD symptoms was found. The data suggest that ADHD is best viewed as the quantitative extreme of genetic and environmental factors operating dimensionally throughout the distribution of ADHD symptoms, indicating that the same etiologic factors are involved in the full range of symptoms of inattention, hyperactivity and impulsivity.

Autistic-like traits and their association with mental health problems in two nationwide twin cohorts of children and adults.Lundström, Sebastian; Chang, Z; Kerekes, Nora; Gumpert, C H; Råstam, Maria; Gillberg, C; Lichtenstein, P; Anckarsäter, Henrik Link to publication Citation for published version (APA): Lundström, S., Chang, Z., Kerekes, N., Gumpert, C. H., Råstam, M., Gillberg, C., ... Anckarsäter, H. (2011). Autistic-like traits and their association with mental health problems in two nationwide twin cohorts of children and adults. Psychological Medicine, 41(11), 2423-2433. DOI: 10.1017/S0033291711000377General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal Background. Autistic-like traits (ALTs), that is restrictions in intuitive social interaction, communication and flexibility of interests and behaviors, were studied in two population-based Swedish twin studies, one in children and one in adults : (1) to examine whether the variability in ALTs is a meaningful risk factor for concomitant attention deficit hyperactivity disorder (ADHD), anxiety, conduct problems, depression and substance abuse, and (2) to assess whether common genetic and environmental susceptibilities can help to explain co-existence of ALTs and traits associated with such concomitant problems.Method. Two nationwide twin cohorts from Sweden (consisting of 11 222 children and 18 349 adults) were assessed by DSM-based symptom algorithms for autism. The twins were divided into six groups based on their degree of ALTs and the risk for concomitant mental health problems was calculated for each group. Genetic and environmental susceptibilities common to ALTs and the other problem types were examined using bivariate twin modeling.Results. In both cohorts, even the lowest degree of ALTs increased the risk for all other types of mental health problems, and these risk estimates increased monotonically with the number of ALTs. For all conditions, common genetic and environmental factors could be discerned. Overall, the phenotypic correlation between ALTs and the traits examined were less pronounced in adulthood than in childhood and less affected by genetic compared with environmental factors.Conclusions. Even low-grade ALTs are relevant to clinical psychiatry as they increase the risk for several heterotypical mental health problems. The association is influenced partly by common genetic and environmental susceptibilities. Attention to co-existing ALTs is warranted in research on a wide range of mental ...

SummaryBackgroundDepression increases the risk of a range of adverse outcomes including suicide, premature mortality, and self-harm, but associations with violent crime remain uncertain. We aimed to determine the risks of violent crime in patients with depression and to investigate the association between depressive symptoms and violent crime in a cohort of twins.MethodsWe conducted two studies. The first was a total population study in Sweden of patients with outpatient diagnoses of depressive disorders (n=47 158) between 2001 and 2009 and no lifetime inpatient episodes. Patients were age and sex matched to general population controls (n=898 454) and risk of violent crime was calculated. Additionally, we compared the odds of violent crime in unaffected half-siblings (n=15 534) and full siblings (n=33 516) of patients with the general population controls. In sensitivity analyses, we examined the contribution of substance abuse, sociodemographic factors, and previous criminality. In the second study, we studied a general population sample of twins (n=23 020) with continuous measures of depressive symptoms for risk of violent crime.FindingsDuring a mean follow-up period of 3·2 years, 641 (3·7%) of the depressed men and 152 (0·5%) of the depressed women violently offended after diagnosis. After adjustment for sociodemographic confounders, the odds ratio of violent crime was 3·0 (95% CI 2·8–3·3) compared with the general population controls. The odds of violent crime in half-siblings (adjusted odds ratio 1·2 [95% CI 1·1–1·4]) and full siblings (1·5, 95% CI 1·3–1·6) were significantly increased, showing some familial confounding of the association between depression and violence. However, the odds increase remained significant in individuals with depression after adjustment for familial confounding, and in those without substance abuse comorbidity or a previous violent conviction (all p<0·0001). In the twin study, during the mean follow-up time of 5·4 years, 88 violent crimes were recorded. Depressive symptoms were associated with increased risk of violent crime and a sensitivity analysis identified little difference in risk estimate when all crimes (violent and non-violent) was the outcome.InterpretationRisk of violent crime was increased in individuals with depression after adjustment for familial, sociodemographic and individual factors in two longitudinal studies. Clinical guidelines should consider recommending violence risk assessment in certain subgroups with depression.

Background There are persistent concerns of long-term effects of stimulant ADHD medication on the development of substance abuse. Methods Using Swedish national registers, we studied all individuals born 1960–1998 and diagnosed with ADHD (26,249 men and 12,504 women). We investigated the association between stimulant ADHD medication in 2006 and substance abuse during 2009. Substance abuse was indexed by substance-related death, crime, or hospital visits. Results ADHD medication was not associated with increased rate of substance abuse. Actually, the rate during 2009 was 31% lower among those prescribed ADHD medication in 2006, even after controlling for medication in 2009 and other covariates (hazard ratio: 0.69; 95% confidence interval: 0.57–0.84). Also the longer duration of medication, the lower the rate of substance abuse. Similar risk reductions were suggested among children and when investigating the association between stimulant ADHD medication and concomitant short-term abuse. Conclusions We found no indication of increased risks of substance abuse among individuals prescribed stimulant ADHD medication; if anything, the data suggested a long-term protective effect on substance abuse. Although stimulant ADHD medication does not seem to increase the risk for substance abuse, clinicians should remain alert to the potential problem of stimulant misuse and diversion in ADHD patients.

SummaryBackgroundReoffending and presence of psychiatric disorders are common in prisoners worldwide. However, whether psychiatric disorders are risk factors for reoffending is still unknown. We aimed to examine the association between psychiatric disorders, including substance use disorder, and violent reoffending.MethodsWe did a longitudinal cohort study of 47 326 prisoners who were imprisoned since Jan 1, 2000, and released before Dec 31, 2009, in Sweden. We obtained data for diagnosed psychiatric disorders from both inpatient and outpatient registers, and sociodemographic and criminological factors from other population-based registers. We calculated hazard ratios (HRs) for violent reoffending with Cox regression. To control for potential familial confounding, we compared sibling prisoners with and without psychiatric disorders. We calculated population attributable fraction to assess the population effect.FindingsDiagnosed psychiatric disorders were associated with an increased hazard of violent reoffending in male (adjusted HR 1·63 [95% CI 1·57–1·70]) and female (2·02 [1·54–2·63]) prisoners, and these associations were independent of measured sociodemographic and criminological factors, and, in men, remained substantial after adjustment for unmeasured familial factors (2·01 [1·66–2·43]). However, findings differed between individual diagnoses and sex. We found some evidence of stronger effects on violent reoffending of alcohol and drug use disorders and bipolar disorder than of other psychiatric disorders. Alcohol use disorder seemed to have a greater effect in women than in men (women 2·08 [1·66–2·60]; men 1·63 [1·56–1·71]). The overall effects of psychiatric disorders did not differ with severity of crime. The hazard of violent reoffending increased in a stepwise way with the number of diagnosed psychiatric disorders. Assuming causality, up to 20% (95% CI 19–22) of violent reoffending in men and 40% (27–52) in women was attributable to the diagnosed psychiatric disorders that we investigated.InterpretationCertain psychiatric disorders are associated with a substantially increased hazard of violent reoffending. Because these disorders are prevalent and mostly treatable, improvements to prison mental health services could counteract the cycle of reoffending and improve both public health and safety. National violence prevention strategies should consider the role of prison health.FundingWellcome Trust, Swedish Research Council, and Swedish Research Council for Health, Working Life and Welfare.

Objective Substance use disorders are major contributors to excess mortality among individuals with attention-deficit/hyperactivity disorder (ADHD), yet associations between pharmacological ADHD treatment and substance-related problems remain unclear. This study investigated concurrent and long-term associations between ADHD medication treatment and substance-related events. Method The authors analyzed 2005–2014 commercial healthcare claims from 2 993 887 (47.2% female) adolescent and adult ADHD patients. Within-individual analyses compared the risk of substance-related events (i.e., substance-use-disorder-related emergency-department visits) during months in which patients received prescribed stimulant medication or atomoxetine relative to that during months in which they did not. Results In adjusted within-individual comparisons, relative to periods in which they did not receive ADHD medication, male patients had 35% lower odds of concurrent substance-related events when receiving medication (odds ratio [OR] = 0.65, 95% CI, 0.64–0.67), and female patients had 31% lower odds of concurrent substance-related events (OR = 0.69, 95% CI, 0.67–0.71). Moreover, male patients had 19% lower odds of substance-related events two years after medication periods (OR = 0.81, 95% CI, 0.78–0.85), and female patients had 14% lower odds of substance-related events two years after medication periods (OR = 0.86, 95% CI, 0.82–0.91). Sensitivity analyses supported most findings but were less consistent for long-term associations among women. Conclusions These results provide evidence that receiving ADHD medication is unlikely to be associated with greater risk of substance-related problems in adolescence or adulthood. Rather, medication was associated with lower concurrent risk of substance-related events and, at least among men, lower long-term risk of future substance-related events.