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Background: Attention-deficit/hyperactivity disorder (ADHD) has been associated with several autoimmune diseases (AD), both within individuals and across relatives, implying common underlying genetic or environmental factors in line with studies indicating that immunological mechanisms are key to brain development. To further elucidate the relationship between ADHD and autoimmunity we performed a population-wide familial co-aggregation study.Methods: We linked Swedish national registries, defined a birth cohort with their biological relatives and identified individuals diagnosed with ADHD and/or 13 ADs. The cohort included 5 178 225 individuals born between 1960 and 2010, of whom 118 927 (2.30%) had been diagnosed with ADHD. We then investigated the associations between ADHD and ADs within individuals and across relatives, with logistic regression and structural equation modelling.Results: Within individuals, ADHD was associated with a diagnosis of any of the 13 investigated ADs (adjusted odds ratio (OR) =1.34, 95% confidence interval (CI) = 1.30-1.38) as well as several specific ADs. Familial co-aggregation was observed. For example, ADHD was associated with any of the 13 ADs in mothers (OR = 1.29, 95% CI = 1.26-1.32), fathers (OR = 1.14, 95% CI = 1.11-1.18), full siblings (OR = 1.19, 95% CI = 1.15-1.22), aunts (OR = 1.12, 95% CI = 1.10-1.15), uncles (OR = 1.07, 95% CI = 1.05-1.10) and cousins (OR = 1.04, 95% CI = 1.03-1.06). Still, the absolute risks of AD among those with ADHD were low. The genetic correlation between ADHD and a diagnosis of any of the investigated ADs was 0.13 (95% CI = 0.09-0.17) and the environmental correlation was 0.02 (95% CI = -0.03-0.06).Conclusions: We found that ADHD and ADs co-aggregate among biological relatives, indicating that the relationship between ADHD and autoimmune diseases may in part be explained by shared genetic risk factors. The patterns of familial co-aggregation of ADHD and ADs do not readily support a role of maternal immune activation in the aetiology of ADHD. The findings have implications for aetiological models of ADHD. However, screening for autoimmunity among individuals with ADHD is not warranted. [ABSTRACT FROM AUTHOR]

The human sex ratio at birth (SRB), defined as the ratio between the number of newborn boys to the total number of newborns, is typically slightly greater than 1/2 (more boys than girls) and tends to vary across different geographical regions and time periods. In this large-scale study, we sought to validate previously-reported associations and test new hypotheses using statistical analysis of two very large datasets incorporating electronic medical records (EMRs). One of the datasets represents over half (∼ 150 million) of the US population for over 8 years (IBM Watson Health MarketScan insurance claims) while another covers the entire Swedish population (∼ 9 million) for over 30 years (the Swedish National Patient Register). After testing more than 100 hypotheses, we showed that neither dataset supported models in which the SRB changed seasonally or in response to variations in ambient temperature. However, increased levels of a diverse array of air and water pollutants, were associated with lower SRBs, including increased levels of industrial and agricultural activity, which served as proxies for water pollution. Moreover, some exogenous factors generally considered to be environmental toxins turned out to induce higher SRBs. Finally, we identified new factors with signals for either higher or lower SRBs. In all cases, the effect sizes were modest but highly statistically significant owing to the large sizes of the two datasets. We suggest that while it was unlikely that the associations have arisen from sex-specific selection mechanisms, they are still useful for the purpose of public health surveillance if they can be corroborated by empirical evidences. Author summary: The human sex ratio at birth (SRB), usually slightly greater than 1/2, have been reported to vary in response to a wide array of exogenous factors. In the literature, many such factors have been posited to be associated with higher or lower SRBs, but the studies conducted so far have focused on no more than a few factors at a time and used far smaller datasets, thus prone to generating spurious correlations. We performed a series of statistical tests on 2 large, country-wide health datasets representing the United States and Sweden to investigate associations between putative exogenous factors and the SRB, and were able to validate a set of previously-reported associations while also discovering new signals. We propose to interpret these results simply as public health indicators awaiting further empirical confirmation rather than as implicated in (adaptive) sexual selection mechanisms. [ABSTRACT FROM AUTHOR]

Background: 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.Methods and Findings: 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.Conclusions: 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. [ABSTRACT FROM AUTHOR]

Background: Fertility in men with hypospadias may be affected due to anatomical, surgical, or etiological factors and associated conditions. Fertility is further influenced by psychosocial and genetic factors, often shared within families. Objective: To evaluate fertility in men born with hypospadias and assess confounding by familial factors. Materials and methods: A population‐based cohort of 1.2 million men born in Sweden 1964‐1998, identified through national demographic and healthcare registers. Associations between hypospadias and (a) being a biological father, (b) conceiving through ART, and (c) diagnosis of male infertility were investigated in the full cohort with logistic regression models and Cox proportional hazard models, expressed as odds ratios (ORs) and hazard ratios (HRs), respectively, with 95% confidence intervals (CIs). A stratified proportional hazard model, conditional on sibling group, was used to control for shared familial confounding. Results: Men with hypospadias, as a whole group, had a lower probability of having biological children (adjusted HR 0.87, 95% CI 0.83‐0.92). A significant association was present in both distal (adjusted HR 0.90, 95% CI 0.85‐0.96) and proximal hypospadias (HR 0.59, 95% CI 0.42‐0.81). Men with hypospadias more often became fathers through ART, regardless of concomitant cryptorchidism. The initial association between hypospadias and the diagnosis of infertility disappeared in sensitivity analyses excluding cryptorchidism. Discussion: Men with hypospadias displayed lower birthrates as compared to their brothers and the general population. Mere birthrates may, however, be a questionable measure of fertility in a population using family planning. However, men with hypospadias were also at higher risk of reproducing through ART and did more often receive a diagnosis of male infertility. Altogether, these findings indicate impaired fertility in men with hypospadias. Conclusions: Fertility in men with hypospadias is impaired, as shown by lower birthrates, increased use of ART and higher risk of receiving a diagnosis of male infertility. [ABSTRACT FROM AUTHOR]

Background: Attention‐deficit/hyperactivity disorder (ADHD) is often associated with other neurodevelopmental disorders (NDs) and with risky behaviors and adverse health outcomes, including injuries. Treatment with ADHD medication has been associated with reduced risk of injuries. However, it is unknown whether the association is present in individuals with co‐occurring NDs. The aim of the present study was to estimate the association between ADHD medication use and unintentional injuries in Sweden in children and adolescents with ADHD, including those with co‐occurring NDs. Methods: Using a linkage of several national registers via the unique personal identification number, we identified individuals with a diagnosis of ADHD and of other NDs, including autism spectrum disorder, intellectual disability, communication disorders, learning disorders and motor disorders. The primary outcome was unintentional injuries. Secondary outcome was traumatic brain injury (TBI). Individuals were followed from January 1st 2006 or their 5th birthday or the date of the first unintentional injury, whichever came last, to December 31st 2013 or their 18th birthday or death, whichever came first. We compared the rate of injuries during periods on‐treatment with the rate of injuries during periods off‐treatment within the same individual using stratified Cox regression to calculate hazard ratio (HR) with 95% confidence intervals (CIs). Results: For children and adolescents with ADHD (N = 9,421) the rate of any unintentional injuries (HR = 0.85; 95% CI = 0.78–0.92) and TBIs (HR = 0.27; 95% CIs = 0.20–0.38) during medicated periods was lower than during non‐medicated periods. Similar results were found among individuals with co‐occurring NDs (N = 2,986), for unintentional injuries (HR = 0.88; 95% CI = 0.77–1.01) and for TBIs (HR = 0.27; 95% CI = 0.16–0.44). Conclusions: Beneficial effects of ADHD medication may extend beyond reduction of ADHD core symptoms to prevention of unintentional injuries in children and adolescents, including individuals with co‐occurring NDs. [ABSTRACT FROM AUTHOR]

Background: A recent family study of young adult males suggests a shared familial liability between attention-deficit/hyperactivity disorder (ADHD) and high body mass index (BMI), and a genome-wide meta-analysis reported a genetic correlation of 0.26 between ADHD and BMI. To date, it is unclear whether these findings generalize to the relationship between ADHD and clinically diagnosed obesity. Method: By linking the Swedish national registers, we identified 25 38 127 individuals born between 1973 and 2000, together with their siblings and cousins. The risk of clinical obesity in individuals with ADHD was compared with the risk in those without ADHD. The relative contributions of genetic and environmental factors to the association between ADHD and clinical obesity were examined via assessment of the familial co-aggregation of the two conditions and quantitative genetic analysis. Results: Individuals with ADHD were at an increased risk of clinical obesity compared with those without (risk difference 3.73%, 95% confidence interval (CI) 3.55–3.90%; risk ratio 3.05, 95% CI 2.95–3.15). Familial co-aggregation of ADHD and clinical obesity was detected and the strength of the co-aggregation decreased by decreasing genetic relatedness. The correlation between the liabilities to ADHD and clinical obesity can be entirely attributed to their genetic correlation (r g 0.30, 95% CI 0.17–0.44). Conclusion: The association between ADHD and clinical obesity in adolescence and young adulthood can be entirely attributed to genetic underpinnings shared by the two conditions. Children with ADHD should be monitored for weight gain so that preventive measures can be taken for those on a suboptimal trajectory. [ABSTRACT FROM AUTHOR]

Background Despite meta-analytic evidence for the association between attention-deficit/hyperactivity disorder ( ADHD) and overweight/obesity, the mechanisms underlying the association are yet to be fully understood. Methods By linking multiple Swedish national and regional registers, we identified 472,735 index males born during 1973-1992, with information on body weight and height directly measured before they were conscripted for military service. We further identified 523,237 full siblings born during 1973-2002 for the index males. All individuals were followed up from their third birthday to December 31, 2009 for ADHD diagnosis. Logistic regression models were used to estimate the association between overweight/obesity in index males and ADHD in their full siblings. Results Siblings of index males with overweight/obesity had increased risk for ADHD (overweight: OR = 1.14, 95% CI = 1.05-1.24; obesity: OR = 1.42, 95% CI = 1.24-1.63), compared with siblings of index males with normal weight. The results were adjusted for birth year of the index male and sex of the sibling. After further adjustment for ADHD status of the index male, the familial coaggregation remained significant (overweight: OR = 1.13, 95% CI = 1.04-1.22; obesity: OR = 1.38, 95% CI = 1.21-1.57). The results were similar across sex of the siblings. Conclusions Attention-deficit/hyperactivity disorder and overweight/obesity share familial risk factors, which are not limited to those causing overweight/obesity through the mediation of ADHD. Future research aiming at identifying family-wide environmental risk factors as well as common pleiotropic genetic variants contributing to both traits is warranted. [ABSTRACT FROM AUTHOR]

Background Attention-deficit/hyperactivity disorder ( ADHD) aggregates in families. To date, the strength, pattern, and characteristics of the familial aggregation have not been thoroughly assessed in a population-based family sample. Methods In this cohort study, we identified relative pairs of twins, full and half-siblings, and full and half cousins from 1,656,943 unique individuals born in Sweden between 1985 and 2006. The relatives of index persons were followed from their third birthday to 31 December 2009 for ADHD diagnosis. Birth year adjusted hazard ratio ( HR), that is, the rate of ADHD in relatives of ADHD-affected index persons compared with the rate of ADHD in relatives of unaffected index persons, was estimated in the different types of relatives using Cox proportional hazards model. Results During the follow-up, 31,865 individuals were diagnosed with ADHD (male to female ratio was 3.7). The birth year adjusted HRs were as follows: 70.45 for monozygotic twins; 8.44 for dizygotic twins; 8.27 for full siblings; 2.86 for maternal half-siblings; 2.31 for paternal half-siblings; 2.24 for full cousins; 1.47 for half cousins. Maternal half-siblings had significantly higher HR than in paternal half-siblings. The HR did not seem to be affected by index person's sex. Full siblings of index persons with ADHD diagnosis present at age 18 or older had a higher rate of ADHD ( HR: 11.49) than full siblings of index persons with ADHD diagnosis only before age 18 ( HR: 4.68). Conclusions Familial aggregation of ADHD increases with increasing genetic relatedness. The familial aggregation is driven by not only genetic factors but also a small amount of shared environmental factors. Persistence of ADHD into adulthood indexes stronger familial aggregation of ADHD. [ABSTRACT FROM AUTHOR]

Background Maternal Smoking During Pregnancy ( SDP) has consistently been associated with increased risk of attention-deficit/hyperactivity disorder ( ADHD) in offspring, but recent studies indicate that this association might be due to unmeasured familial confounding. Methods A total of 813,030 individuals born in Sweden between 1992 and 2000 were included in this nationwide population-based cohort study. Data on maternal SDP and ADHD diagnosis were obtained from national registers and patients were followed up from the age of 3 to the end of 2009. Hazard Ratios ( HRs) were estimated using stratified Cox regression models. Cousin and sibling data were used to control for unmeasured familial confounding. Results At the population level maternal SDP predicted ADHD in offspring ( HRModerate SDP = 1.89; HRHigh SDP = 2.50). This estimate gradually attenuated toward the null when adjusting for measured confounders ( HRModerate SDP = 1.62; HRHigh SDP = 2.04), unmeasured confounders shared within the extended family (i.e., cousin comparison) ( HRModerate SDP = 1.45; HRHigh SDP = 1.69), and unmeasured confounders within the nuclear family (i.e., sibling comparison) ( HRModerate SDP = 0.88; HRHigh SDP = 0.84). Conclusions Our results suggest that the association between maternal SDP and offspring ADHD are due to unmeasured familial confounding. [ABSTRACT FROM AUTHOR]

Seasonal affective disorder (SAD) famously follows annual cycles, with incidence elevation in the fall and spring. Should some version of cyclic annual pattern be expected from other psychiatric disorders? Would annual cycles be similar for distinct psychiatric conditions? This study probes these questions using 2 very large datasets describing the health histories of 150 million unique U.S. citizens and the entire Swedish population. We performed 2 types of analysis, using "uncorrected" and "corrected" observations. The former analysis focused on counts of daily patient visits associated with each disease. The latter analysis instead looked at the proportion of disease-specific visits within the total volume of visits for a time interval. In the uncorrected analysis, we found that psychiatric disorders' annual patterns were remarkably similar across the studied diseases in both countries, with the magnitude of annual variation significantly higher in Sweden than in the United States for psychiatric, but not infectious diseases. In the corrected analysis, only 1 group of patients—11 to 20 years old—reproduced all regularities we observed for psychiatric disorders in the uncorrected analysis; the annual healthcare-seeking visit patterns associated with other age-groups changed drastically. Analogous analyses over infectious diseases were less divergent over these 2 types of computation. Comparing these 2 sets of results in the context of published psychiatric disorder seasonality studies, we tend to believe that our uncorrected results are more likely to capture the real trends, while the corrected results perhaps reflect mostly artifacts determined by dominantly fluctuating, health-seeking visits across a given year. However, the divergent results are ultimately inconclusive; thus, we present both sets of results unredacted, and, in the spirit of full disclosure, leave the verdict to the reader. Should we expect psychiatric disorders to show a cyclic annual pattern? This study reveals that psychiatric diseases' annual patterns were remarkably similar across the studied diseases in both the US and Sweden, with the magnitude of annual variation significantly higher in Sweden than in the US for psychiatric, but not infectious, diseases. [ABSTRACT FROM AUTHOR]

Background: Attention-deficit/hyperactivity disorder (ADHD) has been associated with an increased risk of tobacco smoking, and more difficulties with smoking cessation compared to non-ADHD individuals. Women with ADHD may therefore show elevated rates of smoking during pregnancy. Aims: To examine the association between ADHD and smoking habits among pregnant women in Sweden and Norway. Methods: Women pregnant for the first time were identified in Sweden (n = 622,037), and Norway (n = 293,383), of which 1.2% (n = 7,444), and 1.7% (n = 4,951) were defined as having ADHD, respectively. Data on smoking habits were collected early and late in pregnancy. Results: In Sweden, ADHD was associated with an increased risk of smoking early in pregnancy, adjusted risk ratio (adjRR) 2.69 (95% confidence interval, 2.58–2.81), and late in pregnancy, adjRR 2.95 (2.80–3.10). Similar findings were observed in the Norwegian data, early in pregnancy, adjRR 2.31 (2.21–2.40), and late in pregnancy, adjRR 2.56 (2.42–2.70). Women with ADHD were more likely to continue smoking during pregnancy, compared to women without ADHD, both in Sweden adjRR 1.13 (1.10–1.17), and in Norway, adjRR 1.16 (1.12–1.20). Having a sibling diagnosed with ADHD was associated with an increased risk of smoking early and late in pregnancy, in both Sweden and Norway. Conclusions: Women with ADHD are considerably more likely to smoke early and late in (their first) pregnancy and are less likely to stop smoking between the two time points. Smoking, early and late in pregnancy, co-aggregates in families with ADHD. Smoking prevention and intervention programs should be targeted towards women with ADHD, specifically during their childbearing years, to ensure better mother and child outcomes. [ABSTRACT FROM AUTHOR]

Background: Meta‐analyses suggest an association between autism spectrum disorder (ASD) and obesity, but the factors underlying this association remain unclear. This study investigated the association between ASD and obesity stratified on intellectual disability (ID). In addition, in order to gain insight into possible shared etiological factors, the potential role of shared familial liability was examined. Method: We studied a cohort of 3,141,696 individuals by linking several Swedish nationwide registers. We identified 35,461 individuals with ASD and 61,784 individuals with obesity. Logistic regression models were used to estimate the association between ASD and obesity separately by ID and sex and by adjusting for parental education, psychiatric comorbidity, and psychotropic medication. Potential shared familial etiologic factors were examined by comparing the risk of obesity in full siblings, maternal and paternal half‐siblings, and full‐ and half‐cousins of individuals with ASD to the risk of obesity in relatives of individuals without ASD. Results: Individuals with ASD + ID (OR = 3.76 [95% CI, 3.38–4.19]) and ASD−ID (OR = 3.40 [95% CI, 3.23–3.58]) had an increased risk for obesity compared with individuals without ASD. The associations remained statistically significant when adjusting for parental education, psychiatric comorbidity, and medication. Sex‐stratified analyses indicated a higher relative risk for males compared with females, with statistically significant interaction effects for ASD−ID, but not for ASD+ID in the fully adjusted model. First‐degree relatives of individuals with ASD+ID and ASD−ID had an increased risk of obesity compared with first‐degree relatives of individuals without ASD. The obesity risk was similar in second‐degree relatives of individuals with ASD+ID but was lower for and ASD−ID. Full cousins of individuals with ASD+ID had a higher risk compared with half‐cousins of individuals with ASD+ID). A similar difference in the obesity risk between full cousins and half‐cousins was observed for ASD−ID. Conclusions: Individuals with ASD and their relatives are at increased risk for obesity. The risk might be somewhat higher for males than females. This warrants further studies examining potential common pleiotropic genetic factors and shared family‐wide environmental factors for ASD and obesity. Such research might aid in identifying specific risks and underlying mechanisms in common between ASD and obesity. [ABSTRACT FROM AUTHOR]

Background: Previous studies are inconclusive concerning the association between maternal pre-pregnancy overweight/obesity and risk of attention-deficit/hyperactivity disorder (ADHD) in offspring. We therefore conducted a systematic review and meta-analysis to clarify this association. To address the variation in confounding adjustment between studies, especially inadequate adjustment of unmeasured familial confounding in most studies, we further performed cousin and sibling comparisons in a nationwide population-based cohort in Sweden.Methods: We searched PubMed, Embase and PsycINFO during 1975-2018. We used random-effects models to calculate pooled risk ratios (RRs) with 95% confidence interval. In the population-based study, Cox proportional hazard models were used to calculate the unadjusted hazard ratios (HRs) and HRs adjusted for all confounders identified in previous studies. Stratified Cox models were applied to data on full cousins and full siblings to further control for unmeasured familial confounding.Results: Eight cohorts with a total of 784 804 mother-child pairs were included in the meta-analysis. Maternal overweight [RRoverweight = 1.31 (1.25-1.38), I2 = 6.80%] and obesity [RRobesity = 1.92 (1.84-2.00), I2 = 0.00%] were both associated with an increased risk of ADHD in offspring. In the population-based cohort of 971 501 individuals born between 1992 and 2004, unadjusted Cox models revealed similar associations [HRoverweight = 1.30 (1.28-1.34), HRobesity = 1.92 (1.87-1.98)]. These associations gradually attenuated towards the null when adjusted for measured confounders [HRoverweight = 1.21 (1.19-1.25), HRobesity = 1.60 (1.55-1.65)], unmeasured factors shared by cousins [HRoverweight = 1.10 (0.98-1.23), HRobesity = 1.44 (1.22-1.70)] and unmeasured factors shared by siblings [HRoverweight = 1.01 (0.92-1.11), HRobesity = 1.10 (0.94-1.27)].Conclusion: Pre-pregnancy overweight/obesity is associated with an increased risk of ADHD in offspring. The observed association is largely due to unmeasured familial confounding. [ABSTRACT FROM AUTHOR]

Social skills group training (SSGT) is widely used for intellectually able children and adolescents with autism spectrum disorder (ASD). Previous studies indicate small to moderate effects on social communication capacities. The duration of most available programs is relatively short, and extended training might lead to further improvement. This randomized controlled trial compared an extended 24-week version of the SSGT program KONTAKT with standard care. The weekly sessions gradually shifted in content from acquisition of new skills to real-world application of the acquired skills. A total of 50 participants with ASD (15 females; 35 males) aged 8-17 years were included. The study was conducted at two child and adolescent psychiatry outpatient units in Sweden. The primary outcome was the Social Responsiveness Scale-Second Edition (SRS-2) rated by parents and blinded teachers. Secondary outcomes included parent- and teacher-rated adaptive behaviors, trainer-rated global functioning and clinical severity, and self-reported child and caregiver stress. Assessments were made at baseline, posttreatment, and at 3-months follow-up. Parent-rated SRS-2 scores indicated large effects posttreatment [− 19.2; 95% CI − 29.9 to − 8.5; p < .001, effect size (ES) = 0.76], which were maintained at follow-up (− 20.7; 95% CI − 31.7 to − 9.7; p < .0001, ES = 0.82). These estimates indicate substantially larger improvement than previously reported for shorter SSGT. However, the effects on teacher-rated SRS-2 and most secondary outcomes did not reach statistical significance. Our results suggest added benefits of extended SSGT training, implying that service providers might reach better results by optimizing the delivery of SSGT. [ABSTRACT FROM AUTHOR]

Objective: Social skills group training (SSGT) for children and adolescents with autism spectrum disorder (ASD) is widely applied, but effectiveness in real-world practice has not yet been properly evaluated. This study sought to bridge this gap.Method: This 12-week pragmatic randomized controlled trial of SSGT compared to standard care alone was conducted at 13 child and adolescent psychiatry outpatient units in Sweden. Twelve sessions of manualized SSGT ("KONTAKT") were delivered by regular clinical staff. Participants (N = 296; 88 females and 208 males) were children (n = 172) and adolescents (n = 124) aged 8 to 17 years with ASD without intellectual disability. The primary outcome was the Social Responsiveness Scale rating by parents and blinded teachers. Secondary outcomes included parent- and teacher-rated adaptive behaviors, trainer-rated global functioning and clinical severity, and self-reported child and caregiver stress. Assessments were made at baseline, posttreatment, and 3-month follow-up. Moderator analyses were conducted for age and gender.Results: Significant treatment effects on the primary outcome were limited to parent ratings for the adolescent subgroup (posttreatment: -8.3; 95% CI = -14.2 to -1.9; p = .012, effect size [ES] = 0.32; follow-up: -8.6; 95% CI = -15.4 to -1.8; p = .015, ES = 0.33) and females (posttreatment: -8.9; 95% CI = -16.2 to -1.6; p = .019, ES = 0.40). Secondary outcomes indicated moderate effects on adaptive functioning and clinical severity.Conclusion: SSGT for children and adolescents with ASD in regular mental health services is feasible and safe. However, the modest and inconsistent effects underscore the importance of continued efforts to improve SSGT beyond current standards.Clinical Trial Registration Information: Social Skills Group Training ("KONTAKT") for Children and Adolescent With High-functioning Autism Spectrum Disorders; https://clinicaltrials.gov/; NCT01854346. [ABSTRACT FROM AUTHOR]

ADHD is a highly heritable disorder, marked by elevated levels of comorbidity across neurodevelopmental and externalizing conditions. Polygenic risk scores (PRS) for ADHD have previously been shown to predict ADHD clinical case status and ADHD traits in the general population (Martin, Hamshere, Stergiakouli, O'Donovan, & Thapar, 2014; Stergiakouli et al., 2015). However, it is still unknown to what extent these genetic risk variants are disorder specific, and how they may influence neurodevelopmental and externalizing traits associated with ADHD. ADHD PRS were calculated using results from the latest iPSYCH/Psychiatric Genomics Consortium ADHD Genome-Wide Association (GWAS) meta-analysis for 13,471 children from the Child and Adolescent Twin Study in Sweden (CATSS). For replication, ADHD PRS were also calculated from the EAGLE consortia GWAS meta-analyses of ADHD traits. Phenotypes in CATSS were measured via parent-ratings using the Autism-Tics, ADHD, and Other Comorbidities inventory. To estimate the associations between ADHD PRS and neurodevelopmental and externalizing traits, we used confirmatory factor analysis to fit a correlated factors model to the symptoms of trait inattention, impulsivity, autism, learning difficulties, oppositional-defiant and conduct problems. Each latent trait factor was then regressed on ADHD PRS in a structural equation modelling framework. In the second model, we included a latent general psychopathology factor to account for phenotypic associations among the traits. In this model, each item loaded on the latent general factor, in addition to the corresponding latent trait factor described above. Analyses were re-run using the EAGLE ADHD PRS. ADHD PRS were significantly associated with elevated levels of trait inattention, impulsivity, autism, learning difficulties, oppositional-defiant and conduct problems. However, only unique associations with impulsivity and conduct problems remained after accounting for cross-trait covariance via a latent general psychopathology factor, on which all symptoms loaded positively (loadings=.31–.91, S.E.=.004–.028). ADHD PRS explained 1% (β =.10, p < 0.001) of the variance in the latent general factor, 0.5% (β =.073, p < 0.001) in impulsivity and 0.3% (β =.052, p =.035) in conduct problems. Similar results were found for the EAGLE ADHD PRS analyses, although significance and variance explained were attenuated. Our results suggest that common genetic variants associated with clinically diagnosed ADHD have pleiotropic effects on neurodevelopmental and externalizing traits in the general population. These associations appear to be largely non-specific and reflect a general liability towards elevated childhood neurodevelopmental traits. Nonetheless, over and above predicting a general psychopathology factor, the ADHD PRS also seemed to capture genetic risk variants with unique effects on childhood externalizing traits of impulsivity and conduct problems. [ABSTRACT FROM AUTHOR]