No prior twin study has explored the heritability of clinically diagnosed attention deficit hyperactivity disorder (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 lifespan with a specific focus on ADHD in adults.
Information on zygosity and sex was obtained from 59514 twins born between 1959 and 2001 included in the nationwide population-based Swedish Twin Registry. Clinical data for ADHD diagnoses (i.e. stimulant or non-stimulant medication for ADHD) were obtained from the Swedish Prescribed Drug Register (PDR) and from the National Patient Register (i.e. ICD-10 diagnosis of ADHD). Twin methods were applied to clinical data of ADHD diagnoses using structural equation modeling with monozygotic (MZ) and dizygotic (DZ) twins.
The best-fitting model revealed a high heritability of ADHD 0.88, 95% confidence interval (CI) 0.83-0.92 for the entire sample. However, shared environmental effects were non-significant and of minimal importance. The heritability of ADHD in adults was also substantial (0.72, 95% CI 0.56-0.84).
This study shows that the heritability of clinically diagnosed ADHD is high across the lifespan. Our finding of high heritability for clinically diagnosed ADHD in adults indicates that the previous reports of low heritability are best explained by rater effects, and that gene-identification studies of ADHD in adults need to consider pervasiveness (e.g. multiple raters) and developmentally (e.g. childhood-onset criteria) informative data.
IMPORTANCE: The frequency with which autism spectrum disorders (ASDs) are diagnosed has shown a marked increase in recent years. One suggestion is that this is partly because of secular changes in ...the environment, yet to our knowledge this hypothesis lacks evidence. OBJECTIVE: To assess whether the relative importance of genetic and environmental associations with ASD and autistic traits has changed over a 16-year and 26-year period. DESIGN, SETTING, AND PARTICIPANTS: A twin design was used to assess whether the heritability of ASD and autistic traits has changed over time. Data from 2 nationwide Swedish twin cohorts was used: the Swedish Twin Registry (STR; participants born between January 1982 and December 2008) and the Child and Adolescent Twin Study in Sweden (CATSS; participants born between January 1992 and December 2008). Autism spectrum disorder diagnoses were identified for twins in the STR, with follow-up to 2013. Questionnaires assigned screening diagnoses of ASD to CATSS participants and assessed autistic traits. Analyses were performed from September 1, 2018, to March 31, 2019. EXPOSURES: Each sample was divided into several birth cohorts covering 1982 to 1991 (for the STR only), 1992-1995, 1996-1999, 2000-2003, and 2004-2008. OUTCOMES: We assessed whether the genetric and environment variance underlying autistic traits changed across birth cohorts and examined whether the relative contribution of genetics and environment to liability for autism changed across birth cohorts. RESULTS: Data were available for 22 678 twin pairs (5922 female same-sex pairs 26.1%, 5563 male same-sex pairs 24.5%, and 11193 opposite-sex pairs 49.4%) in the STR and 15 280 pairs (4880 female same-sex pairs 31.9%, 5092 male same-sex pairs 33.3%, and 5308 opposite-sex pairs 34.7%) in CATSS. The heritability of ASD diagnoses in the STR ranged from 0.88 (95% CI, 0.74-0.96) to 0.97 (95% CI, 0.89-0.99). The heritability of screening diagnoses in CATSS varied from 0.75 (95% CI, 0.58-0.87) to 0.93 (95% CI, 0.84-0.98). Autistic traits showed a modest variance increase over time that was associated with increases in genetic and environmental variance, with the total variance increasing from 0.95 (95% CI, 0.92-0.98) to 1.17 (95% CI, 1.13-1.21) over time. CONCLUSIONS AND RELEVANCE: Weak evidence was found for changes in the genetic and environmental factors underlying ASD and autistic traits over time. Genetic factors played a consistently larger role than environmental factors. Environmental factors are thus unlikely to explain the increase in the prevalence of ASD.
Traumatic brain injury (TBI) is the leading cause of disability and mortality in children and young adults worldwide. It remains unclear, however, how TBI in childhood and adolescence is associated ...with adult mortality, psychiatric morbidity, and social outcomes.
In a Swedish birth cohort between 1973 and 1985 of 1,143,470 individuals, we identified all those who had sustained at least one TBI (n = 104,290 or 9.1%) up to age 25 y and their unaffected siblings (n = 68,268) using patient registers. We subsequently assessed these individuals for the following outcomes using multiple national registries: disability pension, specialist diagnoses of psychiatric disorders and psychiatric inpatient hospitalisation, premature mortality (before age 41 y), low educational attainment (not having achieved secondary school qualifications), and receiving means-tested welfare benefits. We used logistic and Cox regression models to quantify the association between TBI and specified adverse outcomes on the individual level. We further estimated population attributable fractions (PAF) for each outcome measure. We also compared differentially exposed siblings to account for unobserved genetic and environmental confounding. In addition to relative risk estimates, we examined absolute risks by calculating prevalence and Kaplan-Meier estimates. In complementary analyses, we tested whether the findings were moderated by injury severity, recurrence, and age at first injury (ages 0-4, 5-9, 6-10, 15-19, and 20-24 y). TBI exposure was associated with elevated risks of impaired adult functioning across all outcome measures. After a median follow-up period of 8 y from age 26 y, we found that TBI contributed to absolute risks of over 10% for specialist diagnoses of psychiatric disorders and low educational attainment, approximately 5% for disability pension, and 2% for premature mortality. The highest relative risks, adjusted for sex, birth year, and birth order, were found for psychiatric inpatient hospitalisation (adjusted relative risk aRR = 2.0; 95% CI: 1.9-2.0; 6,632 versus 37,095 events), disability pension (aRR = 1.8; 95% CI: 1.7-1.8; 4,691 versus 29,778 events), and premature mortality (aRR = 1.7; 95% CI: 1.6-1.9; 799 versus 4,695 events). These risks were only marginally attenuated when the comparisons were made with their unaffected siblings, which implies that the effects of TBI were consistent with a causal inference. A dose-response relationship was observed with injury severity. Injury recurrence was also associated with higher risks-in particular, for disability pension we found that recurrent TBI was associated with a 3-fold risk increase (aRR = 2.6; 95% CI: 2.4-2.8) compared to a single-episode TBI. Higher risks for all outcomes were observed for those who had sustained their first injury at an older age (ages 20-24 y) with more than 25% increase in relative risk across all outcomes compared to the youngest age group (ages 0-4 y). On the population level, TBI explained between 2%-6% of the variance in the examined outcomes. Using hospital data underestimates milder forms of TBI, but such misclassification bias suggests that the reported estimates are likely conservative. The sibling-comparison design accounts for unmeasured familial confounders shared by siblings, including half of their genes. Thus, residual genetic confounding remains a possibility but will unlikely alter our main findings, as associations were only marginally attenuated within families.
Given our findings, which indicate potentially causal effects between TBI exposure in childhood and later impairments across a range of health and social outcomes, age-sensitive clinical guidelines should be considered and preventive strategies should be targeted at children and adolescents.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
AbstractObjectiveTo examine associations between gabapentinoids and adverse outcomes related to coordination disturbances (head or body injuries, or both and road traffic incidents or offences), ...mental health (suicidal behaviour, unintentional overdoses), and criminality.DesignPopulation based cohort study.SettingHigh quality prescription, patient, death, and crime registers, Sweden.Participants191 973 people from the Swedish Prescribed Drug Register who collected prescriptions for gabapentinoids (pregabalin or gabapentin) during 2006 to 2013.Main outcome measuresPrimary outcomes were suicidal behaviour, unintentional overdoses, head/body injuries, road traffic incidents and offences, and arrests for violent crime. Stratified Cox proportional hazards regression was conducted comparing treatment periods with non-treatment periods within an individual. Participants served as their own control, thus accounting for time invariant factors (eg, genetic and historical factors), and reducing confounding by indication. Additional adjustments were made by age, sex, comorbidities, substance use, and use of other antiepileptics.ResultsDuring the study period, 10 026 (5.2%) participants were treated for suicidal behaviour or died from suicide, 17 144 (8.9%) experienced an unintentional overdose, 12 070 (6.3%) had a road traffic incident or offence, 70 522 (36.7%) presented with head/body injuries, and 7984 (4.1%) were arrested for a violent crime. In within-individual analyses, gabapentinoid treatment was associated with increased hazards of suicidal behaviour and deaths from suicide (age adjusted hazard ratio 1.26, 95% confidence interval 1.20 to 1.32), unintentional overdoses (1.24, 1.19 to 1.28), head/body injuries (1.22, 1.19 to 1.25), and road traffic incidents and offences (1.13, 1.06 to 1.20). Associations with arrests for violent crime were less clear (1.04, 0.98 to 1.11). When the drugs were examined separately, pregabalin was associated with increased hazards of all outcomes, whereas gabapentin was associated with decreased or no statistically significant hazards. When stratifying on age, increased hazards of all outcomes were associated with participants aged 15 to 24 years.ConclusionsThis study suggests that gabapentinoids are associated with an increased risk of suicidal behaviour, unintentional overdoses, head/body injuries, and road traffic incidents and offences. Pregabalin was associated with higher hazards of these outcomes than gabapentin.
Suicide is a major public health concern globally. Accurately predicting suicidal behavior remains challenging. This study aimed to use machine learning approaches to examine the potential of the ...Swedish national registry data for prediction of suicidal behavior.
The study sample consisted of 541,300 inpatient and outpatient visits by 126,205 Sweden-born patients (54% female and 46% male) aged 18 to 39 (mean age at the visit: 27.3) years to psychiatric specialty care in Sweden between January 1, 2011 and December 31, 2012. The most common psychiatric diagnoses at the visit were anxiety disorders (20.0%), major depressive disorder (16.9%), and substance use disorders (13.6%). A total of 425 candidate predictors covering demographic characteristics, socioeconomic status (SES), electronic medical records, criminality, as well as family history of disease and crime were extracted from the Swedish registry data. The sample was randomly split into an 80% training set containing 433,024 visits and a 20% test set containing 108,276 visits. Models were trained separately for suicide attempt/death within 90 and 30 days following a visit using multiple machine learning algorithms. Model discrimination and calibration were both evaluated. Among all eligible visits, 3.5% (18,682) were followed by a suicide attempt/death within 90 days and 1.7% (9,099) within 30 days. The final models were based on ensemble learning that combined predictions from elastic net penalized logistic regression, random forest, gradient boosting, and a neural network. The area under the receiver operating characteristic (ROC) curves (AUCs) on the test set were 0.88 (95% confidence interval CI = 0.87-0.89) and 0.89 (95% CI = 0.88-0.90) for the outcome within 90 days and 30 days, respectively, both being significantly better than chance (i.e., AUC = 0.50) (p < 0.01). Sensitivity, specificity, and predictive values were reported at different risk thresholds. A limitation of our study is that our models have not yet been externally validated, and thus, the generalizability of the models to other populations remains unknown.
By combining the ensemble method of multiple machine learning algorithms and high-quality data solely from the Swedish registers, we developed prognostic models to predict short-term suicide attempt/death with good discrimination and calibration. Whether novel predictors can improve predictive performance requires further investigation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Researchers have identified environmental risks that predict subsequent psychological and medical problems. Based on these correlational findings, researchers have developed and tested complex ...developmental models and have examined biological moderating factors (e.g., gene-environment interactions). In this context, we stress the critical need for researchers to use family-based, quasi-experimental designs when trying to integrate genetic and social science research involving environmental variables because these designs rigorously examine causal inferences by testing competing hypotheses. We argue that sibling comparison, offspring of twins or siblings, in vitro fertilization designs, and other genetically informed approaches play a unique role in bridging gaps between basic biological and social science research. We use studies on maternal smoking during pregnancy to exemplify these principles.
Intimate partner violence (IPV) against women is associated with a wide range of adverse outcomes. Although mental disorders have been linked to an increased risk of perpetrating IPV against women, ...the direction and magnitude of the association remain uncertain. In a longitudinal design, we examined the association between mental disorders and IPV perpetrated by men towards women in a population-based sample and used sibling comparisons to control for factors shared by siblings, such as genetic and early family environmental factors.
Using Swedish nationwide registries, we identified men from 9 diagnostic groups over 1998-2013, with sample sizes ranging from 9,529 with autism to 88,182 with depressive disorder. We matched individuals by age and sex to general population controls (ranging from 186,017 to 1,719,318 controls), and calculated the hazard ratios of IPV against women. We also estimated the hazard ratios of IPV against women in unaffected full siblings (ranging from 4,818 to 37,885 individuals) compared with the population controls. Afterwards, we compared the hazard ratios for individuals with psychiatric diagnoses with those for siblings using the ratio of hazard ratios (RHR). In sensitivity analyses, we examined the contribution of previous IPV against women and common psychiatric comorbidities, substance use disorders and personality disorders. The average follow-up time across diagnoses ranged from 3.4 to 4.8 years. In comparison to general population controls, all psychiatric diagnoses studied except autism were associated with an increased risk of IPV against women in men, with hazard ratios ranging from 1.5 (95% CI 1.3-1.7) to 7.7 (7.2-8.3) (p-values < 0.001). In sibling analyses, we found that men with depressive disorder, anxiety disorder, alcohol use disorder, drug use disorder, attention deficit hyperactivity disorder, and personality disorders had a higher risk of IPV against women than their unaffected siblings, with RHR values ranging from 1.7 (1.3-2.1) to 4.4 (3.7-5.2) (p-values < 0.001). Sensitivity analyses showed higher risk of IPV against women in men when comorbid substance use disorders and personality disorders were present, compared to risk when these comorbidities were absent. In addition, increased IPV risk was also found in those without previous IPV against women. The absolute rates of IPV against women ranged from 0.1% to 2.1% across diagnoses over 3.4 to 4.8 years. Individuals with alcohol use disorders (1.7%, 1,406/82,731) and drug use disorders (2.1%, 1,216/57,901) had the highest rates. Our analyses were restricted to IPV leading to arrest, suggesting that the applicability of our results may be limited to more severe forms of IPV perpetration.
Our results indicate that most of the studied mental disorders are associated with an increased risk of perpetrating IPV towards women, and that substance use disorders, as principal or comorbid diagnoses, have the highest absolute and relative risks. The findings support the development of IPV risk identification and prevention services among men with substance use disorders as an approach to reduce the prevalence of IPV.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Recent research suggests that having a newborn child is associated with substantially reduced risk for maternal suicide. We studied postpartum suicides in a national cohort of mothers and the role of ...mental disorder, self-harm and delivery related factors.
We used a nested case-control design with data from Swedish registries. The cohort consisted of all women given birth in Sweden 1974-2009. Mothers who died by suicide during follow-up were considered cases (n = 1,786) and risk of suicide was estimated with proximity to delivery as the explanatory variable. In a second step, association between suicide during the first year following delivery (n = 145) and mental disorder, self-harm and delivery related variables risk factors were analyzed.
The first postpartum year was associated with a lower risk of suicide, compared to later (RR 0.80, 95%CI 0.66-0.96), which was unaltered after adjustment for socio-economic status and history of self-harm (aRR 0.82, 95%CI 0.68-0.99). Compared to living mothers, suicide victims of the postpartum year more often had affective disorders (aRR 133.94, 95%CI 45.93-390.61), psychotic disorders (aRR 83.69, 95%CI 36.99-189.31) and history of self-harm (aRR 47.56, 95%CI 18.24-124.02). The aRR of stillbirth was 2.66 (95%CI 0.63-11.30).
We found only a weak negative association between childbirth during the preceding year and suicide, when using mothers as controls. A severe mental disorder after delivery and a history of self-harm was strongly associated with increased risk of suicide in the postpartum year and may inform the clinical assessment postpartum.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
IMPORTANCE Studies have shown that attention-deficit/hyperactivity disorder (ADHD) is associated with transport accidents, but the magnitude of the association remains unclear. Most important, it is ...also unclear whether ADHD medication reduces this risk. OBJECTIVES To estimate the association between ADHD and the risk of serious transport accidents and to explore the extent to which ADHD medication influences this risk among patients with ADHD. DESIGN, SETTING, AND PARTICIPANTS In total, 17 408 patients with a diagnosis of ADHD were observed from January 1, 2006, through December 31, 2009, for serious transport accidents documented in Swedish national registers. The association between ADHD and accidents was estimated with Cox proportional hazards regression. To study the effect of ADHD medication, we used stratified Cox regression to compare the risk of accidents during the medication period with the risk during the nonmedication period within the same patients. MAIN OUTCOMES AND MEASURES Serious transport accident, identified as an emergency hospital visit or death due to transport accident. RESULTS Compared with individuals without ADHD, male patients with ADHD (adjusted hazard ratio, 1.47; 95% CI, 1.32-1.63) and female patients with ADHD (1.45; 1.24-1.71) had an increased risk of serious transport accidents. In male patients with ADHD, medication was associated with a 58% risk reduction (hazard ratio, 0.42; 95% CI, 0.23-0.75), but there was no statistically significant association in female patients. Estimates of the population-attributable fractions suggested that 41% to 49% of the accidents in male patients with ADHD could have been avoided if they had been receiving treatment during the entire follow-up. CONCLUSIONS AND RELEVANCE Attention-deficit/hyperactivity disorder is associated with an increased risk of serious transport accidents, and this risk seems to be possibly reduced by ADHD medication, at least among male patients. This should lead to increased awareness among clinicians and patients of the association between serious transport accidents and ADHD medication.
IMPORTANCE Advancing paternal age is associated with increased genetic mutations during spermatogenesis, which research suggests may cause psychiatric morbidity in the offspring. The effects of ...advancing paternal age at childbearing on offspring morbidity remain unclear, however, because of inconsistent epidemiologic findings and the inability of previous studies to rigorously rule out confounding factors. OBJECTIVE To examine the associations between advancing paternal age at childbearing and numerous indexes of offspring morbidity. DESIGN, SETTING, AND PARTICIPANTS We performed a population-based cohort study of all individuals born in Sweden in 1973-2001 (N = 2 615 081), with subsets of the data used to predict childhood or adolescent morbidity. We estimated the risk of psychiatric and academic morbidity associated with advancing paternal age using several quasi-experimental designs, including the comparison of differentially exposed siblings, cousins, and first-born cousins. EXPOSURE Paternal age at childbearing. MAIN OUTCOMES AND MEASURES Psychiatric (autism, attention-deficit/hyperactivity disorder, psychosis, bipolar disorder, suicide attempt, and substance use problem) and academic (failing grades and low educational attainment) morbidity. RESULTS In the study population, advancing paternal age was associated with increased risk of some psychiatric disorders (eg, autism, psychosis, and bipolar disorders) but decreased risk of the other indexes of morbidity. In contrast, the sibling-comparison analyses indicated that advancing paternal age had a dose-response relationship with every index of morbidity, with the magnitude of the associations being as large or larger than the estimates in the entire population. Compared with offspring born to fathers 20 to 24 years old, offspring of fathers 45 years and older were at heightened risk of autism (hazard ratio HR = 3.45; 95% CI, 1.62-7.33), attention-deficit/hyperactivity disorder (HR = 13.13; 95% CI, 6.85-25.16), psychosis (HR = 2.07; 95% CI, 1.35-3.20), bipolar disorder (HR = 24.70; 95% CI, 12.12-50.31), suicide attempts (HR = 2.72; 95% CI, 2.08-3.56), substance use problems (HR = 2.44; 95% CI, 1.98-2.99), failing a grade (odds ratio OR = 1.59; 95% CI, 1.37-1.85), and low educational attainment (OR = 1.70; 95% CI, 1.50-1.93) in within-sibling comparisons. Additional analyses using several quasi-experimental designs obtained commensurate results, further strengthening the internal and external validity of the findings. CONCLUSIONS AND RELEVANCE Advancing paternal age is associated with increased risk of psychiatric and academic morbidity, with the magnitude of the risks being as large or larger than previous estimates. These findings are consistent with the hypothesis that new genetic mutations that occur during spermatogenesis are causally related to offspring morbidity.
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