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Abstract Emerging evidence suggests that ADHD is associated with increased risk for metabolic and cardiovascular (cardiometabolic) diseases. However, an understanding of the mechanisms underlying these associations is still limited. In this study we estimated the associations of polygenic scores (PGS) for ADHD with several cardiometabolic diseases and biomarkers. Furthermore, we investigated to what extent the PGS effect was influenced by direct and indirect genetic effects (i.e., shared familial effects). We derived ADHD-PGS in 50,768 individuals aged 18–90 years from the Dutch Lifelines Cohort study. Using generalised estimating equations, we estimated the association of PGS with cardiometabolic diseases, derived from self-report and several biomarkers measured during a physical examination. We additionally ran within-sibling PGS analyses, using fixed effects models, to disentangle direct effects of individuals’ own ADHD genetic risk from confounding due to indirect genetic effects of relatives, as well as population stratification. We found that higher ADHD-PGS were statistically significantly associated with several cardiometabolic diseases (R-squared [R2] range = 0.03–0.50%) and biomarkers (related to inflammation, blood pressure, lipid metabolism, amongst others) (R2 range = 0.01–0.16%) (P

Abstract Peyronie’s disease (PD) has detrimental effects on the quality of life, mental health, sexual functioning and several other aspects that increase the risk of relationship problems. However, no study to date has assessed the risk of relationship separation in med with PD. Herein, we utilized data from Swedish national registers to examine the risk of relationship separation in men with PD. We conducted a matched cohort study on men born 1933–1992, followed from 1997 to 2013. PD was defined as a physician-assigned diagnosis according to the International Classification of Diseases, Tenth version. Each man with PD (n = 8020) was matched with 10 comparison men. We defined relationship separation as (1) ever separated, and (2) separation rate. We used log-linear regression to estimate the risk ratio, and rate ratio of relationship separation. We adjusted for matching variables (birth year and country of birth), and an indicator of each follow-up year. We found that men with PD had a 13% increased risk of relationship separation (risk ratio 1.13, 95% confidence interval [CI] 1.08–1.17). The rate of relationship separation events, measured on a yearly basis, was increased by 18% (rate ratio 1.18, CI 1.12–1.24), and remained similar when adjusting for follow-up year and socio-economic status.

Background A self-harm episode is a major risk factor for repeat self-harm. Existing tools to assess and predict repeat self-harm have major methodological limitations, and few are externally validated.Objective To develop and validate a risk assessment model of repeat self-harm up to 6 months after an episode of non-fatal self-harm that resulted in an emergency visit to hospital or specialised care.Methods Using Swedish national registers, we identified 53 172 people aged≥10 years who self-harmed during 2008–2012. We allocated 37 523 individuals to development (2820 or 7.5% repeat self-harm incidents within 6 months) and 15 649 to geographic validation (1373 repeat episodes) samples, based on region of residence. In a temporal validation of people who self-harmed during 2018–2019, we identified 25 036 individuals (2886 repeat episodes). We fitted a multivariable accelerated failure time model to predict risk of repeat self-harm.Findings In the external validations (n=40 685), rates of repeat self-harm were 8.8%–11.5% over 6 months. The final model retained 17 factors. Calibration and discrimination were similar in both validation samples, with observed-to-expected ratio=1.15 (95% CI=1.09 to 1.21) and c-statistic=0.72 (95% CI=0.70 to 0.73) in the geographical validation. At 6 months and a 10% risk cut-off, sensitivity was 51.5% (95% CI=48.8% to 54.2%) and specificity was 80.7% (95% CI=80.1% to 81.4%) in geographic validation; corresponding values were 56.9% (95% CI=55.1% to 58.7%) and 76.0% (95% CI=75.5% to 76.6%) in temporal validation. Discrimination was slightly worse at the 1-month prediction horizon (c-statistics of 0.66–0.68).Conclusions Using mostly routinely collected data, simple risk assessment models and tools can provide acceptable levels of accuracy for repeat of self-harm.Clinical implications This risk model (OXford SElf-harm repeat tool) may assist clinical decision-making.

Abstract Background Research on genetic and environmental influences on speech and/or language difficulties (SaLD) is sparse, with inconsistent heritability estimates. We aimed to estimate the prevalence of parental reported SaLD and the relative contributions of genetic and environmental factors for the phenotype using a Swedish population‐based twin sample. We hypothesized that there would be a stronger genetic than environmental effect on SaLD. Methods Data were collected from The Child and Adolescent Twin Study in Sweden. The study sample included 16,774 twin pairs (16,946 males, 16,602 females), of which 5141 were monozygotic, 5861 dizygotic (DZ), and 5772 opposite‐sex DZ pairs. The language items in the Autism–Tics, Attention‐Deficit Hyperactivity Disorder, and other Comorbidities inventory were used to categorize individuals as having parental‐reported SaLD. A classical twin design was used to estimate the relative contribution of genetic and environmental factors to the liability of SaLD. Results The prevalence of SaLD was 7.85% (95% confidence interval (CI) [7.57%–8.15%]) and 7.27% (95% CI [6.99%–7.55%]) when excluding individuals with autism and intellectual disability (ID). We also found that SaLD were significantly more prevalent in males than females with a ratio of 2:1. The heritability was estimated to be 75% (95% CI [67%–83%]) for SaLD. Shared environment played a significant role with an estimated contribution of 22% (95% CI [14%–30%]). The heritability estimate was reduced to 70% but with overlapping CI when excluding individuals with autism and ID. Conclusions We provide evidence that SaLD is common in the population and under strong genetic influence. Future studies should focus on mapping the genetic architecture of SaLD and related disorders.

Abstract To increase the number of pre‐registered observational studies, Journal of Child Psychology and Psychiatry (JCPP) Advances is delighted to now invite Registered Reports. Registered Reports are a format of article in which the study protocol is pre‐registered and peer‐reviewed before the research is conducted. If the protocol is of high quality and the proposed research topic is important, JCPP Advances will commit to publishing the study regardless of the results. This article format crucially addresses publication bias, as decisions on publication are entirely independent of the results.

Abstract Background Over the last decades, the prevalence of Attention‐deficit/hyperactivity disorder (ADHD) has increased. However, the underlying explanation for this increase remains unclear. We aimed to assess whether there has been a secular change in how parents perceive the impairment conferred by ADHD symptomatology. Methods Data for this study were obtained from the Child and Adolescent Twin Study in Sweden, involving 27,240 individuals whose parents answered a questionnaire when the children were 9 years old. We assessed the relationship between parentally perceived impairment caused by ADHD symptoms scores over time. The analysis was performed separately for five different birth cohorts, spanning three‐year periods from 1995 to 2009 and for ADHD inattention and hyperactivity/impulsivity dimensions. Results We found a consistent upward trend of parents reporting impairment in relation to ADHD symptomatology across birth cohorts. Over a 12‐year period, comparing those born 2007–2009 (assessed 2016–2018) with those born 1995–1997 (assessed 2004–2006), impairment scores increased by 27% at clinically relevant levels of ADHD symptomatology. Notably, when specifically evaluating the hyperactivity/impulsivity dimension, the disparity was even more striking, with an increase of up to 77%. Conclusions This study revealed a significant secular change in parental perception of impairment attributed to ADHD symptomatology over recent decades, providing new insights into the increased prevalence of ADHD. It underscores the need to better understand the factors that have contributed to the increased perception of impairment related to ADHD symptoms.

Background Little is known about the impact of cumulative attention-deficit/hyperactivity disorder (ADHD) medication use on the risk of type 2 diabetes (T2D).Objective The objective is to examine the association between cumulative use of ADHD medication and risk of incident T2D.Methods A nested case–control study was conducted in a national cohort of individuals aged 18–70 years with incident ADHD (n=138 778) between 2007 and 2020 through Swedish registers. Individuals with incident T2D after ADHD were selected as cases (n=2355) and matched with up to five controls (n=11 681) on age at baseline, sex and birth year. Conditional logistic regression models examined the association between cumulative duration of ADHD medication use and T2D.Findings Compared with no use, a decreased risk of T2D was observed for those on cumulative use of ADHD medications up to 3 years (ORs: 03 years, 0.97 (95% CI, 0.84 to 1.12)). When investigating medication types separately, methylphenidate showed results similar to main analyses, lisdexamfetamine showed no association with T2D, whereas long-term (>3 years) use of atomoxetine was associated with an increased risk of T2D (OR: 1.44 (95% CI, 1.01 to 2.04)).Conclusion Cumulative use of ADHD medication does not increase the risk for T2D, with the exception of long-term use of atomoxetine.Clinical implications Findings suggest that clinicians should be aware of the potential risk of T2D associated with the cumulative use of atomoxetine among patients with ADHD; however, further replication is strongly needed.

Abstract Background BIPCOM aims to (1) identify medical comorbidities in people with bipolar disorder (BD); (2) examine risk factors and clinical profiles of Medical Comorbidities (MC) in this clinical group, with a special focus on Metabolic Syndrome (MetS); (3) develop a Clinical Support Tool (CST) for the personalized management of BD and medical comorbidities. Methods The BIPCOM project aims to investigate MC, specifically MetS, in individuals with BD using various approaches. Initially, prevalence rates, characteristics, genetic and non-genetic risk factors, and the natural progression of MetS among individuals with BD will be assessed by analysing Nordic registers, biobanks, and existing patient datasets from 11 European recruiting centres across 5 countries. Subsequently, a clinical study involving 400 participants from these sites will be conducted to examine the clinical profiles and incidence of specific MetS risk factors over 1 year. Baseline assessments, 1-year follow-ups, biomarker analyses, and physical activity measurements with wearable biosensors, and focus groups will be performed. Using this comprehensive data, a CST will be developed to enhance the prevention, early detection, and personalized treatment of MC in BD, by incorporating clinical, biological, sex and genetic information. This protocol will highlight the study's methodology. Discussion BIPCOM's data collection will pave the way for tailored treatment and prevention approaches for individuals with BD. This approach has the potential to generate significant healthcare savings by preventing complications, hospitalizations, and emergency visits related to comorbidities and cardiovascular risks in BD. BIPCOM's data collection will enhance BD patient care through personalized strategies, resulting in improved quality of life and reduced costly interventions. The findings of the study will contribute to a better understanding of the relationship between medical comorbidities and BD, enabling accurate prediction and effective management of MetS and cardiovascular diseases. Trial registration: ISRCTN68010602 at https://www.isrctn.com/ISRCTN68010602 . Registration date: 18/04/2023.

Abstract Darier disease (DD) is a rare monogenetic skin disorder with limited data on its potential association with neurological disorders. This study aimed to investigate the association between DD and neurological disorders, specifically Parkinson's disease, dementias, and epilepsy. Using Swedish national registers in a period spanning between 1977 and 2013, 935 individuals with DD were compared with up to 100 comparison individuals each, randomly selected from the general population based on birth year, sex, and county of residence at the time of the first diagnosis of DD. Individuals with DD had increased risks of being diagnosed with Parkinson's disease (RR 2.1, CI 1.1; 4.4), vascular dementia (RR 2.1, CI 1.0; 4.2), and epilepsy, (RR 2.5, CI 1.8; 3.5). No association of DD with other dementias were detected. This study demonstrates a new association between DD and neurodegenerative disorders and epilepsy, underlining the need for increased awareness, interdisciplinary collaboration, and further research to understand the underlying mechanisms. Early identification and management of neurological complications in DD patients could improve treatment strategies and patient outcomes. The findings also highlight the role of SERCA2 in the pathophysiology of neurological disorders, offering new targets for future research and potentials for novel treatments.

Abstract Background Evidence for substance use‐related problems in individuals with mild intellectual disability is sparse and mainly limited to selected psychiatric populations. We evaluated the risk of substance use‐related problems in individuals with mild intellectual disability compared to the general population. Additionally, we have performed secondary sibling comparison analyses to account for familial confounding. Methods We conducted a population‐based cohort study of individuals born in Sweden between 1973 and 2003. A total of 18,307 individuals with mild intellectual disability were compared to 915,350 reference individuals from the general population and 18,996 full siblings of individuals with mild intellectual disability. Information on mild intellectual disability and substance use‐related problems was obtained from several Swedish national and regional school and healthcare registers. Substance use‐related problems were measured via corresponding diagnostic and legal codes and included alcohol use disorder, drug use disorder, alcohol‐related somatic disease, conviction for a substance‐related crime, and substance‐related death. Results Individuals with mild intellectual disability had a higher risk of any substance use‐related problem compared to the general population (HR, 1.81; 95% CI, 1.72–1.91), both in males (HR, 1.76; 95% CI, 1.65–1.89) and females (HR, 1.89; 95% CI, 1.74–2.05). The risks of substance use‐related problems were particularly elevated among individuals with mild intellectual disability and psychiatric comorbidities (HR, 2.21–8.24). The associations were attenuated in the sibling comparison models. Conclusions Individuals with mild intellectual disability, especially those with psychiatric comorbidity, are at an elevated risk of substance use‐related problems. Familial factors shared by full siblings contribute considerably to the association between mild intellectual disability and substance use‐related problems.

Abstract Background Individuals with Attention‐Deficit/Hyperactivity Disorder (ADHD) face an elevated risk of criminal convictions compared to those without ADHD. However, understanding this link involves considering sex differences, coexisting psychiatric conditions, and unmeasured familial factors. This study aimed to explore the connection between ADHD and criminal convictions (both violent and non‐violent) in males and females, while also assessing the impact of comorbid psychiatric disorders and familial factors. Methods Using Swedish national registers, we identified individuals born between 1986 and 1997 (635,391 males and 600,548 females). ADHD was defined through clinical diagnosis and prescribed medications, while criminal convictions were determined based on Swedish lower court records. Unmeasured familial factors were accounted for using a sibling design approach. Results Findings revealed that individuals with ADHD had a notably higher absolute and relative risk of both violent and non‐violent criminal convictions compared to those without ADHD. While criminal convictions were more frequent among males with ADHD, females with ADHD exhibited higher relative risks (HR violent 10.50, non‐violent 4.04) than their male counterparts (HR violent 6.03, non‐violent 3.57). Additionally, lower socioeconomic status (SES) in individuals with ADHD was associated with increased relative risks for criminal convictions compared to individuals with ADHD who had higher SES. Adjusting for childhood and internalizing psychiatric disorders partially attenuated these associations, while substance use disorders (SUD) substantially attenuated them. SUD also contributed to an elevated absolute risk of criminal convictions in both male and female individuals with ADHD. Accounting for unmeasured shared familial factors slightly reduced the estimates, but the association between ADHD and criminal convictions persisted. Conclusion In conclusion, ADHD remains a potent independent risk factor for criminal convictions, with varying effects based on gender. This underscores the importance of tailored crime prevention strategies and early interventions for individuals with ADHD, especially when comorbid SUD is present.

Abstract Background Leveraging a large nationwide study of Icelandic women, we aimed to narrow the evidence gap around female attention-deficit/hyperactivity disorder (ADHD) and cardiometabolic comorbidities by determining the prevalence of obesity, hypertension, type 2 diabetes, and cardiovascular diseases among women with ADHD and examine the association between cardiometabolic conditions and co-occurring ADHD with anxiety and mood disorders, alcoholism/substance use disorder (SUD), self-harm, and suicide attempts. Methods We conducted a cross-sectional analysis of the nationwide, all-female, population-based SAGA Cohort Study (n = 26,668). To ascertain diagnoses and symptoms, we used self-reported history of ADHD diagnoses, selected cardiometabolic conditions and psychiatric disorders, and measured current depressive, anxiety, and PTSD symptoms through appropriate questionnaires (PHQ-9, GAD-7, and PCL-5). We calculated age-adjusted prevalences of cardiometabolic conditions by women’s ADHD status and estimated adjusted prevalence ratios (PR) and 95% confidence intervals (CI), using modified Poisson regression models. Similarly, we assessed the association of cardiometabolic conditions and co-occurring ADHD with current psychiatric symptoms and psychiatric disorders, using adjusted PRs and 95% CIs. Results We identified 2299 (8.6%) women with a history of ADHD diagnosis. The age-adjusted prevalence of having at least one cardiometabolic condition was higher among women with ADHD (49.5%) than those without (41.7%), (PR = 1.19, 95% CI 1.14–1.25), with higher prevalence of all measured cardiometabolic conditions (myocardial infarctions (PR = 2.53, 95% CI 1.83-–3.49), type 2 diabetes (PR = 2.08, 95% CI 1.66–2.61), hypertension (PR = 1.23, 95% CI 1.12–1.34), and obesity (PR = 1.18, 95% CI 1.11–1.25)). Women with cardiometabolic conditions and co-occurring ADHD had, compared with those without ADHD, substantially increased prevalence of (a) all measured mood and anxiety disorders, e.g., depression (PR = 2.38, 95% CI 2.19–2.58), bipolar disorder (PR = 4.81, 95% CI 3.65–6.35), posttraumatic stress disorder (PR = 2.78, 95% CI 2.52–3.07), social phobia (PR = 2.96, 95% CI 2.64–3.32); (b) moderate/severe depressive, anxiety, and PTSD symptoms with PR = 1.76 (95% CI 1.67–1.85), PR = 1.97 (95% CI 1.82–2.12), and PR = 2.01 (95% CI 1.88–2.15), respectively; (c) alcoholism/SUD, PR = 4.79 (95% CI 3.90–5.89); and (d) self-harm, PR = 1.47 (95% CI 1.29–1.67) and suicide attempts, PR = 2.37 (95% CI 2.05–2.73). Conclusions ADHD is overrepresented among women with cardiometabolic conditions and contributes substantially to other psychiatric comorbidities among women with cardiometabolic conditions.

Abstract Background Emerging research suggests that attention-deficit/hyperactivity disorder (ADHD) increases the risk for cardiovascular (CVDs) and metabolic disorders (i.e., cardiometabolic disorders) in adulthood. Yet, available studies are scarce and have mainly been focused on individuals receiving clinical ADHD diagnoses. We aimed to investigate the prospective associations of ADHD symptoms in young and mid-adulthood with subsequent cardiometabolic disorders and the underlying mechanisms. Methods We studied 10,394 twins from the Swedish Twin Registry (STR), born between 1958 and 1985 without previous medical history of cardiometabolic disorders. They provided self-assessment of ADHD symptoms (score range 0–36) via a validated, DSM-IV-based scale in a web-based questionnaire/telephone interview within the Study of Twin Adults: Genes and Environment (STAGE), in 2005–2006 (aged 19–47 years), and were followed until the end of 2018 (33–59 years) to identify incident clinical diagnoses/medication prescriptions for cardiometabolic disorders acquired from Swedish national registers. We used Cox regression models to investigate the associations between ADHD symptoms score and cardiometabolic outcomes, with and without adjustment for relevant covariates, and a co-twin control design to study familial confounding. Results A one-unit increase in the level of ADHD symptoms was associated with a 2% increase in the rate of CVDs (hazard ratio [HR] = 1.02, 95% confidence interval 1.01–1.04) and a 3% increase in the rate of metabolic disorders (HR = 1.03, 1.02–1.05), after adjusting for birth year and sex. The associations were no longer significant after adjusting for educational attainment, lifestyle factors, and comorbid psychiatric disorders. The associations remained significant after adjusting for familial factors shared by dizygotic twin pairs but became nonsignificant after adjusting for factors shared by monozygotic twin pairs. However, the strength of the associations attenuated significantly in monozygotic twins compared to dizygotic twins for CVDs only, suggesting genetic confounding. Conclusions ADHD symptom score is associated with a higher risk for cardiometabolic disorders, which may be explained by lower educational attainment, adverse lifestyle factors, and psychiatric comorbidities. Moreover, the associations appear to be partly confounded by shared genetic factors, especially for CVDs. Further research is needed to investigate the identified associations at the level of individual cardiometabolic disorders and to follow-up participants until a more advanced older age.

Abstract Cumulative exposure to psychosocial adversity at an early age has been shown to be a risk factor for attention-deficit hyperactivity disorder (ADHD) and autism that often co-occur. However, it is not clear if this association reflects a causal effect or familial confounding. We aimed to assess whether cumulative psychosocial adversity in the family increases the risk for ADHD and autism in offspring while accounting for unmeasured familial confounding. We used a population-based cohort of 1,877,901 individuals born in Sweden between 1990 and 2009. Participants were followed from the age of 3 until 2013, with a median follow up time of 13.8 years. We created a cumulative index based on 7 psychosocial adversity factors. We used Cox regression to estimate the hazard ratios (HRs) relating neurodevelopmental conditions to cumulative psychosocial adversity. To address familial confounding, the analyses were repeated in groups of relatives of different kinship: siblings and half-siblings and cousins. A dose-response relationship was observed between cumulative exposure to psychosocial adversity and ADHD at a general population level (covariate adjusted HRs (aHRs) with 95% confidence intervals ranged from 1.55 [one adversity; 1.53–1.58] to 2.65 [ ≥ 4 adversities; 1.98–3.54]). No clear dose-response relation was seen for autism (aHRs ranged from 1.04 [.59–1.84] to 1.37 [1.30–1.45]). HRs of ADHD and autism decreased with increasing level of kinship in the analysis of relatives. Cumulative exposure to psychosocial adversity was associated with both ADHD and autism in the general population, these associations were partly explained by unmeasured familial confounding between relatives. This highlights the need for using family-based designs in studies of psychosocial adversity and ADHD and autism.

IntroductionTraumatic brain injury (TBI) is associated with health problems across multiple domains and TBI patients are reported to have high rates of medication use. However, prior evidence is thin due to methodological limitations. Our aim was thus to examine the use of a wide spectrum of medications prescribed to address pain and somatic conditions in a population-based cohort of TBI patients, and to compare this to a sex- and age-matched cohort. We also examined how patient factors such as sex, age, and TBI severity were associated with medication use.MethodsWe assessed Swedish nationwide registers to include all individuals treated for TBI in hospitals or specialist outpatient care between 2006 and 2012. We examined dispensed prescriptions for eight different non-psychotropic medication classes for the 12 months before, and 12 months after, the TBI. We applied a fixed-effects model to compare TBI patients with the matched population cohort. We also stratified TBI patients by sex, age, TBI severity and carried out comparisons using a generalized linear model.ResultsWe identified 239,425 individuals with an incident TBI and 239,425 matched individuals. TBI patients were more likely to use any medication [Odds ratio (OR) = 2.03, 95% Confidence Interval (CI) = 2.00–2.05], to present with polypharmacy (OR = 1.96, 95% CI = 1.90–2.02), and to use each of the eight medication classes before their TBI, as compared to the matched population cohort. Following the TBI, TBI patients were more likely to use any medication (OR = 1.83, 95% CI = 1.80–1.86), to present with polypharmacy (OR = 1.74, 95% CI = 1.67–1.80), and to use all medication classes, although differences were attenuated. However, differences increased for antibiotics/antivirals (OR = 2.02, 95% CI = 1.99–2.05) and NSAIDs/antirheumatics (OR = 1.62, 95% CI = 1.59–1.65) post-TBI. We also found that females and older patients were more likely to use medications after their TBI than males and younger patients, respectively. Patients with more severe TBIs demonstrated increased use of antibiotics/ antivirals and NSAIDs/antirheumatics than those with less severe TBIs.DiscussionTaken together, our results point to poor overall health in TBI patients, suggesting that medical follow-up should be routine, particularly in females with TBI, and include a review of medication use to address potential polypharmacy.

BackgroundHailey-Hailey disease (HHD) is a rare autosomal dominant skin disease caused by mutations in the ATP2C1 gene, which encodes the secretory Ca2+/Mn2+-ATPase (SPCA1) pump in the Golgi apparatus. Although ATP2C1 is ubiquitously expressed in the body, possible extracutaneous manifestations of HHD are unknown. However, dysfunction of the Golgi apparatus not specifically coupled to ATP2C1 has been associated with heart disease.ObjectiveTo investigate the association between HHD and common heart disease in a Swedish, population-based cohort.MethodsWe conducted a population-based cohort study based on a linkage of Swedish nationwide registers to investigate the relationship between HHD and heart disease. We have been granted ethical approval from the Swedish Ethical Review Authority to conduct this study. The patients in this manuscript have given written informed consent to the publication of their case details. A total of 342 individuals with an ICD-10 diagnosis of HHD (Q82.8E) were identified and matched with randomly selected comparison individuals without HHD on a 1:100 ratio. Furthermore, in a separate clinical cohort we matched 23 HHD patients for age, sex, and BMI with control subjects to examine electrocardiogram parameters, electrolytes, and cardiovascular biomarkers.ResultsCompared with individuals without HHD, individuals with HHD had an excess risk of arrhythmia (RR 1.4, CI 1.0-2.0), whereas no increased risks of myocardial infarction (RR 1.1, CI 0.6-1.7) or heart failure (RR 1.0, CI 0.6-1.6; Table 1) were found. We found no difference in ECG parameters, cardiovascular biomarkers, and electrolytes in the clinical subset.ConclusionThis study reveals that HHD is associated with an increased risk of arrhythmia and represents the first data of any extracutaneous comorbidity in HHD. Thus, HHD may be a systemic disease. Our findings also shed light on the importance of the Golgi apparatus' Ca2+/Mn2+ homeostasis in common heart disease.

Abstract Background Gaming is a popular past‐time activity among children and adolescents, but it there is also a possible link to negative consequences such as psychological distress and lowered academic achievement. However, there are fundamental knowledge gaps remaining regarding central characteristics of gaming such as heritability, stability over time, and sex differences. We examined the genetic and environmental contribution to gaming behavior, including sex differences, continuity and change, in a longitudinal cohort of twins. Methods This is the first longitudinal twin study on gaming, involving 32,006 twins in Sweden. Parents were asked about the twins' gaming at ages 9, 15 and 18. We used univariate and multivariate twin analyses to estimate the relative contribution of genetic and environmental influences at each time‐point as well as across time. Sex‐differences were also explored. Results The results showed large sex differences, where genetics explained more of the variance for boys (31.3%–62.5% depending on age) than for girls (19.4%–23.4%). Genetic factors explained an increasing amount of the variance for boys (31.3% at age 9, 62.5% at age 15 and 53.9% at age 18). Shared environmental factors explained a larger proportion of the variance among girls, which remained relatively stable over time (70.5% at age 9, 61.8% at age 15 and 60.5% at age 18). The results also indicated that most of the variance came from genetic and environmental sources specific to each age. Conclusions Compared to many other behavioral phenotypes, such as gambling, gaming was relatively unstable with a large degree of genetic innovation. There were large sex differences in the contribution of genetic and environmental factors. This suggests that excessive gaming could be the result of age‐ and sex‐specific genetic and environmental factors, and should be taken into account when mapping gaming behaviors, since these behaviors might be under continual etiological transformation.

Abstract Three papers in the December issue (2023) of JCPP Advances focus on children of parents with depression or anxiety. They highlight the value of using prospective longitudinal data to improve the understanding about the development of children of parents with depression or anxiety from early childhood to young adulthood. They contribute to an advanced understanding of long‐term outcomes, causality and resilience for children of parents with depression or anxiety.

A new category of Al-doped cobalt-based dual phase entropic alloys with high corrosion resistance properties was designed in the present work. CALPHAD (CALculation of PHAse Diagram) aided prediction was performed to facilitate the alloy design. Two groups of alloys have been extensively investigated by various techniques. One group was quenched in water from the homogenization temperature (i.e. 1200 °C) to room temperature. The other group was subsequently quenched in liquid nitrogen from room temperature. The microstructure of the proposed alloys was characterized by X-ray diffraction (XRD). Several kinds of electrochemical tests were performed to study the corrosion behaviors of the designed alloys in NaCl solution, including open circuit potential (OCP), polarization and cyclic polarization curves, electrochemical impedance spectroscopy (EIS), electrochemical noise (ECN), linear voltammetry curves and staircase voltammetry scan, and Mott–Schottky method. The obtained results show that Al has a minor influence on the corrosion property of this series alloy with a 0 to 2 at.% Al addition. All the designed alloys hold quite acceptable corrosion resistance. In addition, a mechanical property, i.e. micro-hardness, is also provided as a supplement information. This work sheds light on the correlation between computational thermodynamics and corrosion behaviors in cobalt-based dual-phase entropic alloys, as well as to provide a feasibility study on the important role of CALPHAD method for a rapid development of a new category of high performance alloys.

Abstract Background Autism spectrum condition and attention-deficit/hyperactivity disorder (ADHD) are associated with a range of physical health conditions. The aim of this study was to examine the etiological components contributing to co-occurring physical health conditions in autism and ADHD. Methods In this nationwide Child and Adolescent Twin Study in Sweden, we analyzed data from 10,347 twin pairs aged 9 and 12. Clinical diagnoses of autism, ADHD, and physical health conditions were identified through the Swedish National Patient Register. Subclinical phenotypes of autism and ADHD were defined by symptom thresholds on a standardized parent-interview, the Autism–Tics, ADHD, and Other Comorbidities inventory. Associations between physical health conditions and autism/ADHD phenotypes were examined using generalized estimating equations. Bivariate twin models were applied to estimate the extent to which genetic and environmental risk factors accounted for physical health comorbidities. Results Similar patterns of association with physical health conditions were found in clinical and subclinical autism/ADHD, with odds ratios ranging from 1.31 for asthma in subclinical ADHD to 8.03 for epilepsy in clinical autism. The estimated genetic correlation (r a ) with epilepsy was 0.50 for clinical autism and 0.35 for subclinical autism. In addition, a modest genetic correlation was estimated between clinical autism and constipation (r a = 0.31), functional diarrhea (r a = 0.27) as well as mixed gastrointestinal disorders (r a = 0.30). Genetic effects contributed 0.86 for mixed gastrointestinal disorders in clinical ADHD (r a = 0.21). Finally, subclinical ADHD shared genetic risk factors with epilepsy, constipation, and mixed gastrointestinal disorders (r a = 0.30, 0.17, and 0.17, respectively). Limitations Importantly, since medical records from primary care were not included in the registry data used, we probably identified only more severe rather than the full range of physical health conditions. Furthermore, it needs to be considered that the higher prevalence of physical health conditions among autistic children and children with ADHD could be associated with the increased number of medical visits. Conclusions Shared genetic effects contribute significantly to autism and ADHD phenotypes with the co-occurring physical health conditions across different organ systems, including epilepsy and gastrointestinal disorders. The shared genetic liability with co-occurring physical health conditions was present across different levels of autism and ADHD symptom severity.

Hailey-Hailey disease is a rare hereditary skin disease caused by mutations in the ATP2C1 gene encoding the secretory pathway Ca2+/Mn2+-ATPase 1 (SPCA1) protein. Extracutaneous manifestations of Hailey-Hailey disease are plausible but still largely unknown. The aim of this study was to explore the association between Hailey-Hailey disease and diabetes. A population-based cohort study of 347 individuals with Hailey-Hailey disease was performed to assess the risks of type 1 diabetes and type 2 diabetes, using Swedish nationwide registries. Pedigrees from 2 Swedish families with Hailey-Hailey disease were also investigated: 1 with concurrent type 1 diabetes and HLA-DQ3, the other with type 2 diabetes. Lastly, a clinical cohort with 23 individuals with Hailey-Hailey disease and matched healthy controls was evaluated regarding diabetes. In the register data males with Hailey-Hailey disease had a 70% elevated risk of type 2 diabetes, whereas no excess risk among women could be confirmed. In both pedigrees an unusually high inheritance for diabetes was observed. In the clinical cohort, individuals with Hailey-Hailey disease displayed a metabolic phenotype indicative of type 2 diabetes. Hailey-Hailey disease seems to act as a synergistic risk factor for diabetes. This study indicates, for the first time, an association between Hailey-Hailey disease and diabetes and represents human evidence that SPCA1 and the Golgi apparatus may be implicated in diabetes pathophysiology.

Background Assessment of suicide risk in individuals who have self-harmed is common in emergency departments, but is often based on tools developed for other purposes.Objective We developed and validated a predictive model for suicide following self-harm.Methods We used data from Swedish population-based registers. A cohort of 53 172 individuals aged 10+ years, with healthcare episodes of self-harm, was split into development (37 523 individuals, of whom 391 died from suicide within 12 months) and validation (15 649 individuals, 178 suicides within 12 months) samples. We fitted a multivariable accelerated failure time model for the association between risk factors and time to suicide. The final model contains 11 factors: age, sex, and variables related to substance misuse, mental health and treatment, and history of self-harm. Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis guidelines were followed for the design and reporting of this work.Findings An 11-item risk model to predict suicide was developed using sociodemographic and clinical risk factors, and showed good discrimination (c-index 0.77, 95% CI 0.75 to 0.78) and calibration in external validation. For risk of suicide within 12 months, using a 1% cut-off, sensitivity was 82% (75% to 87%) and specificity was 54% (53% to 55%). A web-based risk calculator is available (Oxford Suicide Assessment Tool for Self-harm or OxSATS).Conclusions OxSATS accurately predicts 12-month risk of suicide. Further validations and linkage to effective interventions are required to examine clinical utility.Clinical implications Using a clinical prediction score may assist clinical decision-making and resource allocation.

Climate change is expected to alter global temperature and precipitation patterns resulting in complex environmental impacts. The proposed higher precipitation in northern Scandinavia would increase runoff from land, hence increase the inflow of terrestrial dissolved organic matter (tDOM) in coastal regions. This could promote heterotrophic bacterial production and shift the food web structure, by favoring the microbial food web. The altered climate is also expected to affect transport and availability of organic micropollutants (MPs), with downstream effects on exposure and accumulation in biota. This study aimed to assess climate-induced changes in a Bothnian Sea food web structure as well as bioaccumulation patterns of MPs. We performed a mesocosms-study, focusing on aquatic food webs with fish as top predator. Alongside increased temperature, mesocosm treatments included tDOM and MP addition. The tDOM addition affected nutrient availability and boosted both phytoplankton and heterotrophic bacteria in our fairly shallow mesocosms. The increased tDOM further benefitted flagellates, ciliates and mesozooplankton, while the temperature increase and MP addition had minor effect on those organism groups. Temperature, on the other hand, had a negative impact on fish growth and survival, whereas tDOM and MP addition only had minor impact on fish. Moreover, there were indications that bioaccumulation of MPs in fish either increased with tDOM addition or decreased at higher temperatures. If there was an impact on bioaccumulation, moderately lipophilic MPs (log Kow 3.6 – 4.6) were generally affected by tDOM addition and more lipophilic MPs (log Kow 3.8 to 6.4) were generally affected by increased temperature. This study suggest that both increased temperatures and addition of tDOM likely will affect bioaccumulation patterns of MPs in shallow coastal regions, albeit with counteracting effects.

Background Although there is robust evidence for several factors which may precipitate self-harm, the contributions of different physical injuries are largely unknown.Objective To examine whether specific physical injuries are associated with risks of self-harm in people with psychiatric disorders.Methods By using population and secondary care registers, we identified all people born in Finland (1955–2000) and Sweden (1948–1993) with schizophrenia-spectrum disorder (n=136 182), bipolar disorder (n=68 437) or depression (n=461 071). Falls, transport-related injury, traumatic brain injury and injury from interpersonal assault were identified within these subsamples. We used conditional logistic regression models adjusted for age and calendar month to compare self-harm risk in the week after each injury to earlier weekly control periods, which allowed us to account for unmeasured confounders, including genetics and early environments.Findings A total of 249 210 individuals had been diagnosed with a psychiatric disorder and a physical injury during the follow-up. The absolute risk of self-harm after a physical injury ranged between transport-related injury and injury from interpersonal assault (averaging 17.4–37.0 events per 10 000 person-weeks). Risk of self-harm increased by a factor of two to three (adjusted OR: 2.0–2.9) in the week following a physical injury, as compared with earlier, unexposed periods for the same individuals.Conclusions Physical injuries are important proximal risk factors for self-harm in people with psychiatric disorders.Clinical implications Mechanisms underlying the associations could provide treatment targets. When treating patients with psychiatric illnesses, emergency and trauma medical services should actively work in liaison with psychiatric services to implement self-harm prevention strategies.

Abstract Attention‐deficit/hyperactivity disorder (ADHD) often co‐occurs with other psychiatric and physical diseases. However, available evidence on associations between ADHD and cardiovascular diseases (CVDs) is mixed. To systematically review, quantitatively synthesize, and appraise available evidence on the link between ADHD with CVDs, we searched relevant articles in PubMed, Embase, PsycINFO, and Web of Science from inception to May 1, 2022. Study quality was assessed by using the Newcastle‐Ottawa Scale, and random‐effects model meta‐analyses were performed. A total of 18,391,169 (ADHD: n = 421,224) individuals from 11 studies were included in our systematic review and 8,196,648 (ADHD = 332,619) individuals from five studies were included in the main meta‐analysis of adjusted estimates. Pooled estimates showed that ADHD was significantly associated with an increased risk of CVDs in analyses based on adjusted effect size (odds ratio (OR) = 1.96; 95% confidence interval (CI) = 1.19–2.23, Q = 140.74, PQ

Summary: Background: Intellectual disability (ID) is a disorder with unknown aetiology in many cases. Maternal alcohol use is a known risk factor for ID, but less is known about the importance of maternal and paternal substance use disorder (SUD) and risk of ID in offspring. Methods: Data from multiple nationwide registers were used to create a cohort of children born from January 01, 1978 to December 31, 2002. All participants were born in Sweden, had available parental identification information and did not emigrate or die before age 12 (n = 1,940,820). Logistic regression modelling was performed with exposure defined as having a parent who received any SUD diagnosis, including alcohol use disorder (AUD) and drug use disorder (DUD). The outcome was registration of diagnosis of any form of ID. First, we analysed the risk of ID if parental SUD was registered prior to childbirth with stepwise adjustment of multiple covariates. Second, the effect of timing of SUD diagnosis in relation to childbirth was analysed. Findings: Of 37,410 offspring with parental SUD registered prior to birth, 3.0% (n = 1110) had any form of ID compared to 1.2% (n = 23,168) of those 1,903,410 individuals without parental SUD prior birth. Parental SUD prior birth was associated with an increased risk of any form of ID (Odds Ratio [OR]: 2.3 [2.2–2.5]), with ORs similar for maternal (OR: 2.3 [2.1–2.5]) and paternal SUD (OR: 2.3 [2.1–2.5]). These ORs were reduced but remained statistically significant after adjusting for parental education, migration, psychiatric comorbidity, and co-parent SUD (OR parental SUD: 1.6 [1.5–1.8]; OR maternal SUD: 1.4 [1.2–1.5]; OR paternal SUD: 1.6 [1.5–1.7]). Parental SUD was associated with increased risk of ID in offspring irrespective of timing of diagnosis, but if mothers or fathers were diagnosed with AUD during pregnancy (OR maternal AUD: 5.0 [3.1–8.2]; OR paternal AUD: 2.8 [2.2–3.6]), the risk was significantly greater than if the AUD diagnosis was first registered after childbirth (OR maternal AUD: 1.9 [1.8–2.0]; OR paternal AUD: 1.6 [1.6–1.7]). Interpretation: Both paternal and maternal SUD were associated with an increased risk of ID in offspring, with greatest risk observed when AUD was diagnosed during pregnancy. Possible mechanisms may involve shared genetic and environmental factors, including toxic effects from alcohol intake. These findings have clinical implications in suggesting that parental SUD in either parent represents a possibly modifiable risk factor to consider when developing prevention, diagnostics and treatment programs for children with ID. Funding: Stockholm County Council, the Research Council of the Swedish Alcohol Retailing Monopoly, Fredrik and Ingrid Thurings stiftelse, Academy of Finland, the Swedish Research Council and the Swedish Research Council for Health, Working Life and Welfare, Nordforsk by the Nordic Council of Ministers and the Polish Medical Research Agency.

Background Consistent evidence suggests a strong association between attention-deficit/hyperactivity disorder (ADHD) and subjectively reported sleep problems. However, the prevalence of clinically ascertained sleep disorder diagnoses and sleep medication prescriptions in individuals with ADHD remains unclear.Objective To determine the rates of sleep disorder diagnoses and sleep medication prescriptions in children, adolescents and adults with ADHD.Methods We linked Swedish national registers to create a cohort of individuals born 1945–2008. We estimated the absolute and relative risks (using logistic regression models) of different sleep disorder diagnoses and medication prescriptions in individuals with and without ADHD. The analyses were performed across five different age groups: children (5–11 years), adolescents (12–17 years), young adults (18–30 years), middle-aged adults (31–45 years) and older adults (46–60 years).Findings Among individuals with ADHD (N=145 490, 2.25% of the cohort), 7.5% had a sleep disorder diagnosis and 47.5% had been prescribed sleep medication. Individuals with ADHD, across all age groups, had a statistically significantly increased risk of having any sleep disorder diagnosis (ORrange=6.4–16.1) and any sleep medication prescription (ORrange=12.0–129.4) compared with individuals without ADHD. While rates of sleep disorders were highest in older adults, the relative risks were highest in youth.Conclusions Individuals with ADHD have a substantially increased risk of sleep disorder diagnoses and sleep medication prescriptions, from childhood into older adulthood.Clinical implications More clinical efforts are needed to tackle impairing sleep problems in individuals with ADHD via systematic sleep assessment, appropriate diagnosis, and pharmacological and non-pharmacological interventions. Sleep medication use should be informed by sleep disorder diagnosis.

Abstract Criminal behaviour has previously been associated with an increased risk for several mental health problems, but little is known about the association between criminal behaviour and dementia. We aimed to examine how the criminal background (type of crime, number of convictions, length of the sentence) is associated with dementia and mild cognitive impairment (MCI), and how mental and physical health disorders and educational attainment influenced these associations. A nationwide cohort of 3,617,028 individuals born between 1932 and 1962 were linked with criminal and medical records using Swedish national registers. We used Cox regression models to examine the associations. Increased risks for dementia (Hazard ratios (HRs) 1.54, 95% confidence interval (CI) 1.50–1.57) and MCI (1.55, 1.50–1.61) were found in individuals with criminal background, particularly among those who committed violent or several crimes, or with long sentences. After full adjustment of covariates, the associations attenuated but remained statistically significant for dementia (1.25, 1.22–1.28) and MCI (1.27, 1.22–1.32). The attenuation was mostly explained by mental health problems -depression, anxiety, schizophrenia spectrum disorders, substance use disorder (SUD), and bipolar disorder- (dementia: 1.34, 1.31–1.37; MCI: 1.35, 1.30–1.40). SUD contributed the most to attenuate the associations. Our results may provide important insights to health and penal systems by showing the importance of considering the severity of the criminal background and life-course mental health when assessing the risk of neurodegenerative disorders.

Abstract Background Emerging evidence points at substantial comorbidity between adult attention deficit hyperactivity disorder (ADHD) and cardiometabolic diseases, but our understanding of the comorbidity and how to manage cardiometabolic disease in adults with ADHD is limited. The ADHD Remote Technology study of cardiometabolic risk factors and medication adherence (ART-CARMA) project uses remote measurement technology to obtain real-world data from daily life to assess the extent to which ADHD medication treatment and physical activity, individually and jointly, may influence cardiometabolic risks in adults with ADHD. Our second main aim is to obtain valuable real-world data on adherence to pharmacological treatment and its predictors and correlates during daily life from adults with ADHD. Methods ART-CARMA is a multi-site prospective cohort study within the EU-funded collaboration ‘TIMESPAN’ (Management of chronic cardiometabolic disease and treatment discontinuity in adult ADHD patients) that will recruit 300 adults from adult ADHD waiting lists. The participants will be monitored remotely over a period of 12 months that starts from pre-treatment initiation. Passive monitoring, which involves the participants wearing a wrist-worn device (EmbracePlus) and downloading the RADAR-base Passive App and the Empatica Care App on their smartphone, provides ongoing data collection on a wide range of variables, such as physical activity, sleep, pulse rate (PR) and pulse rate variability (PRV), systolic peaks, electrodermal activity (EDA), oxygen saturation (SpO2), peripheral temperature, smartphone usage including social connectivity, and the environment (e.g. ambient noise, light levels, relative location). By combining data across these variables measured, processes such as physical activity, sleep, autonomic arousal, and indicators of cardiovascular health can be captured. Active remote monitoring involves the participant completing tasks using a smartphone app (such as completing clinical questionnaires or speech tasks), measuring their blood pressure and weight, or using a PC/laptop (cognitive tasks). The ART system is built on the RADAR-base mobile-health platform. Discussion The long-term goal is to use these data to improve the management of cardiometabolic disease in adults with ADHD, and to improve ADHD medication treatment adherence and the personalisation of treatment.

Abstract Suicidal and aggressive behaviours cause significant personal and societal burden. As risk factors associated with these behaviours frequently overlap, combined approaches in predicting the behaviours may be useful in identifying those at risk for either. The current study aimed to create a model that predicted if individuals will exhibit suicidal behaviour, aggressive behaviour, both, or neither in late adolescence. A sample of 5,974 twins from the Child and Adolescent Twin Study in Sweden (CATSS) was broken down into a training (80%), tune (10%) and test (10%) set. The Netherlands Twin Register (NTR; N = 2702) was used for external validation. Our longitudinal data featured genetic, environmental, and psychosocial predictors derived from parental and self-report data. A stacked ensemble model was created which contained a gradient boosted machine, random forest, elastic net, and neural network. Model performance was transferable between CATSS and NTR (macro area under the receiver operating characteristic curve (AUC) [95% CI] AUCCATSS(test set) = 0.709 (0.671–0.747); AUCNTR = 0.685 (0.656–0.715), suggesting model generalisability across Northern Europe. The notable exception is suicidal behaviours in the NTR, which was no better than chance. The 25 highest scoring variable importance scores for the gradient boosted machines and random forest models included self-reported psychiatric symptoms in mid-adolescence, sex, and polygenic scores for psychiatric traits. The model’s performance is comparable to current prediction models that use clinical interviews and is not yet suitable for clinical use. Moreover, genetic variables may have a role to play in predictive models of adolescent psychopathology.

Abstract Hoarding Disorder (HD) is a mental disorder characterized by persistent difficulties discarding or parting with possessions, often resulting in cluttered living spaces, distress, and impairment. Its etiology is largely unknown, but twin studies suggest that it is moderately heritable. In this study, we pooled phenotypic and genomic data from seven international cohorts (N = 27,537 individuals) and conducted a genome wide association study (GWAS) meta-analysis of parent- or self-reported hoarding symptoms (HS). We followed up the results with gene-based and gene-set analyses, as well as leave-one-out HS polygenic risk score (PRS) analyses. To examine a possible genetic association between hoarding symptoms and other phenotypes we conducted cross-trait PRS analyses. Though we did not report any genome-wide significant SNPs, we report heritability estimates for the twin-cohorts between 26–48%, and a SNP-heritability of 11% for an unrelated sub-cohort. Cross-trait PRS analyses showed that the genetic risk for schizophrenia and autism spectrum disorder were significantly associated with hoarding symptoms. We also found suggestive evidence for an association with educational attainment. There were no significant associations with other phenotypes previously linked to HD, such as obsessive-compulsive disorder, depression, anxiety, or attention-deficit hyperactivity disorder. To conclude, we found that HS are heritable, confirming and extending previous twin studies but we had limited power to detect any genome-wide significant loci. Much larger samples will be needed to further extend these findings and reach a “gene discovery zone”. To move the field forward, future research should not only include genetic analyses of quantitative hoarding traits in larger samples, but also in samples of individuals meeting strict diagnostic criteria for HD, and more ethnically diverse samples.

Abstract Background The knowledge of how the separate Attention-Deficit/Hyperactivity Disorder (ADHD) subdimensions (impulsivity, hyperactivity, and inattention) are associated with nonsuicidal self-injury (NSSI) and suicidal behavior (SB) is limited. The objective of this study was to investigate the associations of childhood ADHD subdimensions with NSSI and SB in children at risk of neurodevelopmental disorders (NDDs; including ADHD). Methods The sample (N = 391) included twin pairs where at least one twin screened positive for at least one NDD or common comorbidity at age 9 or 12. Data on ADHD subdimensions was collected through a telephone interview with a caregiver/legal guardian at age 9 or 12, and data on NSSI and SB was collected through an in-person clinical assessment at age 15. The associations between the ADHD subdimensions and NSSI or SB were tested in three different models: (1) univariable, (2) together with the other ADHD subdimensions, and (3) in a confounder-adjusted model including other NDD symptoms in addition to ADHD subdimensions, for NSSI and SB separately. Results A total of 32 (8.2%) adolescents reported life-time engagement of NSSI, and 18 (4.6%) SB. Childhood impulsivity was associated with SB and childhood inattention with NSSI, in all models. Hyperactivity was not meaningfully associated with any of the outcomes. Conclusion Impulsivity and inattention, but not hyperactivity, may be of particular importance in understanding SB and NSSI. Brief screening for impulsivity and inattention in childhood could facilitate detection of children vulnerable to NSSI and SB and indicate valuable information for preventive and intervention strategies.

With climate change predicted to alter water column stability and mixing across the world’s oceans, a mesocosm experiment was designed to ascertain how a natural phytoplankton community would respond to these changes. As a departure from other mesocosm experiments, we used heating and cooling to produce four different climate-inspired mixing scenarios ranging from well-mixed water columns representative of typical open turbulence (ϵ = 3 x 10-8 m2/s3) through to a quiescent water column with stable stratification (ϵ = 5 x 10-10 m2/s3). This method of turbulence generation is an improvement on previous techniques (e.g., grid, shaker, and aeration) which tend to produce excessive dissipation rates inconsistent with oceanic turbulence observations. Profiles of classical physical parameters used to describe turbulence and mixing (turbulent dissipation rate, buoyancy frequency, turbulent eddy diffusivity, Ozmidov scale) were representative of the profiles found in natural waters under similar mixing conditions. Chlorophyll-a profiles and cell enumeration showed a clear biological response to the different turbulence scenarios. However, the responses of specific phytoplankton groups (diatoms and dinoflagellates) did not conform to the usual expectations: diatoms are generally expected to thrive under convective, turbulent regimes, while dinoflagellates are expected to thrive in converse conditions, i.e., in stable, stratified conditions. Our results suggest that responses to mixing regimes are taxon-specific, with no overwhelming physical effect of the turbulence regime. Rather, each taxon seemed to very quickly reach a given vertical distribution that it managed to hold, whether actively or passively, with a high degree of success. Future studies on the effects of climate change on phytoplankton vertical distribution should thus focus on the factors and mechanisms that combine to determine the specific distribution of species within taxa. Our convection-based mesocosm approach, because it uses a primary physical force that generates turbulence in open waters, should prove a valuable tool in this endeavor.

Abstract Growing evidence suggests that ADHD, an early onset neurodevelopmental disorder, is associated with poor somatic health in adulthood. However, the mechanisms underlying these associations are poorly understood. Here, we tested whether ADHD polygenic risk scores (PRS) are associated with mid-to-late life somatic health in a general population sample. Furthermore, we explored whether potential associations were moderated and mediated by life-course risk factors. We derived ADHD-PRS in 10,645 Swedish twins born between 1911 and 1958. Sixteen cardiometabolic, autoimmune/inflammatory, and neurological health conditions were evaluated using self-report (age range at measure 42–88 years) and clinical diagnoses defined by International Classification of Diseases codes in national registers. We estimated associations of ADHD-PRS with somatic outcomes using generalized estimating equations, and tested moderation and mediation of these associations by four life-course risk factors (education level, body mass index [BMI], tobacco use, alcohol misuse). Results showed that higher ADHD-PRS were associated with increased risk of seven somatic outcomes (heart failure, cerebro- and peripheral vascular disease, obesity, type 1 diabetes, rheumatoid arthritis, and migraine) with odds ratios ranging 1.07 to 1.20. We observed significant mediation effects by education, BMI, tobacco use, and alcohol misuse, primarily for associations of ADHD-PRS with cardiometabolic outcomes. No moderation effects survived multiple testing correction. Our findings suggests that higher ADHD genetic liability confers a modest risk increase for several somatic health problems in mid-to-late life, particularly in the cardiometabolic domain. These associations were observable in the general population, even in the absence of medical treatment for ADHD, and appear to be in part mediated by life-course risk factors.

Abstract Background Internalizing disorders, such as anxiety and depressive disorders, are common mental disorders in young people, but a detailed understanding of the symptom continuity from childhood to adolescence that additionally includes a variety of neurodevelopmental disorder (NDD) symptoms is lacking. We therefore aimed to assess the extent to which parent-reported anxiety, depression, and NDD symptoms in childhood predict parent-reported internalizing symptoms in adolescence. Methods We used the nation-wide population-based Child and Adolescent Twin Study in Sweden, comprising 4492 twins born in Sweden between 1998 and 2003 that were assessed at age 9, and then again at age 15. Linear regression in a structural equation modelling framework was used to analyze the data. Results Overall, our results indicate that 15.9% of the variance in internalizing symptoms at age 15 can be predicted by anxiety, depression, and NDD symptoms at age 9. Anxiety and NDD symptoms in childhood predicted the largest amount of internalizing symptoms in adolescence. Conclusions Adolescent internalizing symptoms are modestly affected by childhood symptoms of anxiety, depression, and NDDs, suggesting that they may represent different constructs across age. Future studies should further empirically investigate differences in etiology and trajectories of childhood versus adolescent internalizing symptoms.

In metallurgical converter processes, numerical modeling is a useful tool for understanding the complexity of the systems. In this paper, we present a practical model that couples fluid dynamics and chemical reactions to explore the impact of mixing time on decarburization. Using computational fluid dynamics (CFD), in this study, we investigate an arbitrary metallurgical reactor with continuous oxygen supply, focusing on the Fe–C–O system. The model employs local equilibrium, a turbulence limiter, and finite volume method for mass, momentum, and energy transfer. Tracer injection points in the gas plume’s rising region exhibit faster mixing, and a comparison of reaction cases reveals distinct decarburization rates based on oxygen injection distribution and the influence of turbulence on reactions. Overall, while mixing time matters, the results show that this system is primarily governed by thermodynamics and oxygen supply, and a 270% increase in mixing time increase had a small impact on the end carbon content.

Abstract Although highly heritable, environment also contributes to the etiology of autism spectrum disorder (ASD), with several specific environmental factors previously suggested. A registry-linked population-based twin cohort of 15,701 pairs (586 individuals with an ASD diagnosis), was established within the Child and Adolescent Twin Study in Sweden. Participants were evaluated for autistic symptoms at age 9 using the Autism-Tics, ADHD and other Comorbidities parental interview. A series of binary cut-offs indicated whether participants scored over various ASD symptom percentiles. Three early medical factors previously associated with ASD, beyond familial confounding (low birth weight, congenital malformations and perinatal hypoxia), were summed up creating an individual cumulative exposure load. A series of unconditional logistic regressions between all individuals and conditional regressions within twin pairs were performed for each outcome and exposure level. Between all individuals increasing cumulative early exposure loads were associated with increasing risk of ASD diagnosis (OR 3.33 (95%CI 1.79–6.20) for three exposures) and autistic symptoms (ranging from OR 2.12 (1.57–2.86) for three exposures at the 55th symptom percentile cut-off to OR 3.39 (2.2–5.24) at the 95th). Within twin pairs, the association between three exposures and an ASD diagnosis remained similar, but not statistically significant (OR 2.39 (0.62–9.24)). Having a higher load of early cumulative exposure was consistently associated with autistic symptoms after adjusting for familial confounding and sex (OR 3.45 (1.66–7.15) to OR 7.36 (1.99–27.18)). This study gives support to the cumulative stress hypothesis of ASD, and the dimensional model regarding environmental exposures, after adjustment for familial confounding.

Backgroundβ-blockers are widely used for treating cardiac conditions and are suggested for the treatment of anxiety and aggression, although research is conflicting and limited by methodological problems. In addition, β-blockers have been associated with precipitating other psychiatric disorders and suicidal behaviour, but findings are mixed. We aimed to examine associations between β-blockers and psychiatric and behavioural outcomes in a large population-based cohort in Sweden.Methods and findingsWe conducted a population-based longitudinal cohort study using Swedish nationwide high-quality healthcare, mortality, and crime registers. We included 1,400,766 individuals aged 15 years or older who had collected β-blocker prescriptions and followed them for 8 years between 2006 and 2013. We linked register data on dispensed β-blocker prescriptions with main outcomes, hospitalisations for psychiatric disorders (not including self-injurious behaviour or suicide attempts), suicidal behaviour (including deaths from suicide), and charges of violent crime. We applied within-individual Cox proportional hazards regression to compare periods on treatment with periods off treatment within each individual in order to reduce possible confounding by indication, as this model inherently adjusts for all stable confounders (e.g., genetics and health history). We also adjusted for age as a time-varying covariate. In further analyses, we adjusted by stated indications, prevalent users, cardiac severity, psychiatric and crime history, individual β-blockers, β-blocker selectivity and solubility, and use of other medications. In the cohort, 86.8% (n = 1,215,247) were 50 years and over, and 52.2% (n = 731,322) were women. During the study period, 6.9% (n = 96,801) of the β-blocker users were hospitalised for a psychiatric disorder, 0.7% (n = 9,960) presented with suicidal behaviour, and 0.7% (n = 9,405) were charged with a violent crime. There was heterogeneity in the direction of results; within-individual analyses showed that periods of β-blocker treatment were associated with reduced hazards of psychiatric hospitalisations (hazard ratio [HR]: 0.92, 95% confidence interval [CI]: 0.91 to 0.93, p < 0.001), charges of violent crime (HR: 0.87, 95% CI: 0.81 to 0.93, p < 0.001), and increased hazards of suicidal behaviour (HR: 1.08, 95% CI: 1.02 to 1.15, p = 0.012). After stratifying by diagnosis, reduced associations with psychiatric hospitalisations during β-blocker treatment were mainly driven by lower hospitalisation rates due to depressive (HR: 0.92, 95% CI: 0.89 to 0.96, p < 0.001) and psychotic disorders (HR: 0.89, 95% CI: 0.85 to 0.93, p < 0.001). Reduced associations with violent charges remained in most sensitivity analyses, while associations with psychiatric hospitalisations and suicidal behaviour were inconsistent. Limitations include that the within-individual model does not account for confounders that could change during treatment, unless measured and adjusted for in the model.ConclusionsIn this population-wide study, we found no consistent links between β-blockers and psychiatric outcomes. However, β-blockers were associated with reductions in violence, which remained in sensitivity analyses. The use of β-blockers to manage aggression and violence could be investigated further.

Abstract Readers of JCPP Advances known that the dominant classification system (Diagnostic and Statistical Manual of Mental Disorders) in psychiatry and psychology conceptualizes psychopathology as discrete diagnostic categories. This measurement model builds on a strong assumption of a clear discontinuity between individuals who meet criteria for a diagnosis and those who don't fulfill diagnostic criteria. During the past decades we have seen huge efforts to test this assumption and explore alternative models, such as research from the hierarchical taxonomy of psychopathology consortia. Key findings of these efforts are reviewed and discussed in the December issue of JCPP Advances.

Abstract Objective (1) investigate the associations of attention‐deficit/hyperactivity disorder (ADHD) with systolic and diastolic blood pressure, resting heart rate, pulse pressure (PP), physical fitness, and BMI; (2) explore whether cardiovascular risk factors and ADHD share genetic and environmental influences; (3) assess if pharmacological treatment for ADHD influences these associations. Methods We identified 395,978 individuals born between 1973 and 1991 who had military conscription examinations at a mean age of 18.3 years (SD = 0.57) and their full‐siblings within the same cohort (N = 208,060) by linking population‐based registers in Sweden. Results Significantly increased risk of ADHD was observed in individuals with low systolic blood pressure (SBP) and PP, low physical fitness, and in those who had overweight or obesity after adjustments (adjusted Odds Ratio [OR] ranging from 1.10 to 1.45). Full siblings of individuals with low SBP, low physical fitness, and obesity were more likely to receive an ADHD diagnosis compared to full siblings without those risk factors (OR ranging from 1.17 to 1.31). Additionally, analyses showed robust associations between ADHD and low SBP, low physical fitness, and obesity, even in ADHD medication‐naïve individuals. Conclusions Individuals with several cardiovascular risk factors are more often diagnosed with ADHD, regardless of psychiatric comorbidity. These association are not explained by ADHD pharmacotherapy, rather, they are in part due to shared familial risk factors.

A series of duplex fcc + hcp Co-based entropic alloys are being discovered as a new category of entropic alloys with outstanding mechanical properties, especially to overcome a typical mechanical trade-off between strength and ductility. In this work, CALPHAD-based (CALculation of PHAse Diagram) thermodynamic calculations were performed to facilitate alloy design and to understand corrosion behaviors. The kinetics of the electrochemical corrosion for designed alloys in typical aggressive anion Cl- was investigated by electrochemical tests, including open circuit potential (OCP), polarization and cyclic polarization curves, and electrochemical impedance spectroscopy (EIS). The valence state and the surface morphologies of the passive films were investigated by X-ray photoelectron spectroscopy (XPS) and atomic force microscope (AFM). High corrosion resistance materials with high strength and ductility performances were discovered in the present work. Except for Ni-oxides, various spinel compounds and many other oxides including Co2O3, Cr2O3, Fe2O3, MnO, MoO3, CoCr2O4, FeCr2O4, CoFe2O4, and CoMoO4 were observed in the passive films. The adsorbed and penetrated corrosive anion Cl- will be prone to breakdown the passive films with less Cr2O3, CoCr2O4 and MoO3 to form pitting corrosion (also include other localized corrosion, such as intergranular corrosion and crevice corrosion). The microstructure of the hcp martensite with the fcc matrix has played an important role in the propagation of the localized anodic dissolution in the form of cleavage and quasi-cleavage. The theoretical calculations are in good agreement with the experimental observations. This paper paves a way for the future development of high-performance Co-based entropic alloys served in some harsh environments.

BackgroundOffenders with intellectual disability (ID) constitute a distinct subgroup of offenders with mental disorders. Regarding criminal recidivism, it is unclear whether or not offenders with ID in forensic psychiatric settings differ from offenders without ID. Factors associated with criminal recidivism among offenders with ID have been scarcely investigated.AimTo investigate the association between ID and criminal recidivism among offenders sentenced to forensic psychiatric care and to explore the impact of clinical, sociodemographic and offense variables.Materials and methodsWe conducted a retrospective cohort study based on Swedish nationwide registers. A total of 3,365 individuals being sentenced to forensic psychiatric care in Sweden in 1997–2013 were followed from the forensic psychiatric assessment until first reconviction, death, emigration, or 31 December 2013, whichever occurred first. Cox regression models compared rates of recidivism in individuals with and without ID. Impact of clinical, sociodemographic, and offense variables on risk of criminal recidivism was presented as hazard ratios (HRs) with 95% confidence intervals (CIs).ResultsOut of 3,365 offenders sentenced to forensic psychiatric care, 259 (7.7%) were diagnosed with ID. During follow-up (0–17 years, median 6 years), one third (n = 1,099) of the study population relapsed into criminality, giving a recidivism rate of 50.5 per 1,000 person-years. We observed an association between ID and a decreased risk of recidivism (HR 0.8, 95% CI 0.6–1.0, p = 0.063), although this reached statistical significance only for the subgroup of male offenders (HR 0.8, 95% CI 0.6–1.0, p = 0.040) and not females (HR 1.0, 95% CI 0.6–1.8). ID offenders with concurrent ADHD tended to have a higher rate of recidivism (73.9 per 1,000 person-years, HR 1.2, 95% CI 0.6–2.4) than ID offenders without ADHD (42.5 per 1,000 person-years, HR 0.8, 95% CI 0.6–1.1). Amongst ID offenders, concurrent autism spectrum disorder, young age or male sex were not associated with recidivism, while previous criminal convictions were strongly associated with recidivism.ConclusionA diagnosis of ID was associated with a lower risk of criminal recidivism among male offenders sentenced to forensic psychiatric care. The association between ADHD and recidivism among ID offenders highlights eligible focus areas in the management of offenders with ID.

The densification of cemented carbides during sintering was studied using an existing constitutive model based on powder particle size and material composition. In the present analysis, we study how well the constitutive model can capture the experimental results of a dilatometer test. Three experiments were performed, where the only difference was the transition between the debinding and sintering process. From magnetic measurements, it is concluded that the carbon level in the specimen is affected by changes to the experimental setup. It is shown, using parameter adjustments, that the constitutive model is more suited for a certain experimental setup and carbon level, which is a limitation of the model. In order to capture the mechanical behaviour under different experimental conditions, further constitutive modelling relevant to the carbon level is recommended.