Exploring the genetic etiology across the continuum of the general psychopathology factor: a Swedish population-based family and twin study.

Psychiatric comorbidity can be accounted for by a latent general psychopathology factor (p factor), which quantifies the variance that is shared to varying degrees by every dimension of psychopathology. It is unclear whether the entire continuum of the p factor shares the same genetic origin. We investigated whether mild, moderate, and extreme elevations on the p factor shared the same genetic etiology by, first, examining the linearity of the association between p factors across siblings (N = 580,891 pairs). Second, we estimated the group heritability in a twin sample (N = 17,170 pairs), which involves testing whether the same genetic variants influence both extreme and normal variations in the p factor. In both samples, the p factor was based on 10 register-based psychiatric diagnoses. Results showed that the association between siblings' p factors appeared linear, even into the extreme range. Likewise, the twin group heritabilities ranged from 0.42 to 0.45 (95% CI: 0.33-0.57) depending on the thresholds defining the probands (2-3.33 SD beyond the mean; >2 SD beyond the mean; >4.33 SD beyond the mean; and >5.33 SD beyond the mean), and these estimates were highly similar to the estimated individual differences heritability (0.41, 95% CI: 0.39-0.43), indicating that scores above and below these thresholds shared a common genetic origin. Together, these results suggest that the entire continuum of the p factor shares the same genetic origin, with common genetic variants likely playing an important role. This implies, first, genetic risk factors for the aspect that is shared between all forms of psychopathology (i.e., genetic risk factors for the p factor) might be generalizable between population-based cohorts with a higher prevalence of milder cases, and clinical samples with a preponderance of more severe cases. Second, prioritizing low-cost genome-wide association studies capable of identifying common genetic variants, rather than expensive whole genome sequencing that can identify rare variants, may increase the efficiency when studying the genetic architecture of the p factor.

Bidirectional association between autoimmune disease and perinatal depression: a nationwide study with sibling comparison.

Although major depression, characterized by a pro-inflammatory profile, genetically overlap with autoimmune disease (AD) and the perinatal period involve immune system adaptations and AD symptom alterations, the bidirectional link between perinatal depression (PND) and AD is largely unexplored. Hence, the objective of this study was to investigate the bidirectional association between PND and AD. Using nationwide Swedish population and health registers, we conducted a nested case-control study and a matched cohort study. From 1,347,901 pregnancies during 2001-2013, we included 55,299 incident PND, their unaffected full sisters, and 10 unaffected matched women per PND case. We identified 41 subtypes of AD diagnoses recorded in the registers and compared PND with unaffected population-matched women and full sisters, using multivariable regressions. Women with an AD had a 30% higher risk of subsequent PND (95% CI 1.2-1.5) and women exposed to PND had a 30% higher risk of a subsequent AD (95% CI 1.3-1.4). Comparable associations were found when comparing exposed women with their unaffected sisters (nested case-control OR: 1.3, 95% CI 1.2-1.5, matched cohort HR: 1.3, 95% CI 1.1-1.6), and when studying antepartum and postpartum depression. The bidirectional association was more pronounced among women without psychiatric comorbidities (nested case-control OR: 1.5, 95% CI 1.4-1.6, matched cohort HR: 1.4, 95% CI 1.4-1.5) and strongest for multiple sclerosis (nested case-control OR: 2.0, 95% CI 1.6-2.3, matched cohort HR: 1.8, 95% CI 1.0-3.1). These findings demonstrate a bidirectional association between AD and PND independent of psychiatric comorbidities, suggesting possibly shared biological mechanisms. If future translational science confirms the underlying mechanisms, healthcare providers need to be aware of the increased risk of PND among women with ADs and vice versa.

Individualized prediction models in ADHD: a systematic review and meta-regression.

There have been increasing efforts to develop prediction models supporting personalised detection, prediction, or treatment of ADHD. We overviewed the current status of prediction science in ADHD by: (1) systematically reviewing and appraising available prediction models; (2) quantitatively assessing factors impacting the performance of published models. We did a PRISMA/CHARMS/TRIPOD-compliant systematic review (PROSPERO: CRD42023387502), searching, until 20/12/2023, studies reporting internally and/or externally validated diagnostic/prognostic/treatment-response prediction models in ADHD. Using meta-regressions, we explored the impact of factors affecting the area under the curve (AUC) of the models. We assessed the study risk of bias with the Prediction Model Risk of Bias Assessment Tool (PROBAST). From 7764 identified records, 100 prediction models were included (88% diagnostic, 5% prognostic, and 7% treatment-response). Of these, 96% and 7% were internally and externally validated, respectively. None was implemented in clinical practice. Only 8% of the models were deemed at low risk of bias; 67% were considered at high risk of bias. Clinical, neuroimaging, and cognitive predictors were used in 35%, 31%, and 27% of the studies, respectively. The performance of ADHD prediction models was increased in those models including, compared to those models not including, clinical predictors (ß = 6.54, p = 0.007). Type of validation, age range, type of model, number of predictors, study quality, and other type of predictors did not alter the AUC. Several prediction models have been developed to support the diagnosis of ADHD. However, efforts to predict outcomes or treatment response have been limited, and none of the available models is ready for implementation into clinical practice. The use of clinical predictors, which may be combined with other type of predictors, seems to improve the performance of the models. A new generation of research should address these gaps by conducting high quality, replicable, and externally validated models, followed by implementation research.

Genome-Wide Association Study of Obsessive-Compulsive Symptoms including 33,943 individuals from the general population.

While 1-2% of individuals meet the criteria for a clinical diagnosis of obsessive-compulsive disorder (OCD), many more (~13-38%) experience subclinical obsessive-compulsive symptoms (OCS) during their life. To characterize the genetic underpinnings of OCS and its genetic relationship to OCD, we conducted the largest genome-wide association study (GWAS) meta-analysis of parent- or self-reported OCS to date (N = 33,943 with complete phenotypic and genome-wide data), combining the results from seven large-scale population-based cohorts from Sweden, the Netherlands, England, and Canada (including six twin cohorts and one cohort of unrelated individuals). We found no genome-wide significant associations at the single-nucleotide polymorphism (SNP) or gene-level, but a polygenic risk score (PRS) based on the OCD GWAS previously published by the Psychiatric Genetics Consortium (PGC-OCD) was significantly associated with OCS (Pfixed = 3.06 × 10-5). Also, one curated gene set (Mootha Gluconeogenesis) reached Bonferroni-corrected significance (Ngenes = 28, Beta = 0.79, SE = 0.16, Pbon = 0.008). Expression of genes in this set is high at sites of insulin mediated glucose disposal. Dysregulated insulin signaling in the etiology of OCS has been suggested by a previous study describing a genetic overlap of OCS with insulin signaling-related traits in children and adolescents. We report a SNP heritability of 4.1% (P = 0.0044) in the meta-analyzed GWAS, and heritability estimates based on the twin cohorts of 33-43%. Genetic correlation analysis showed that OCS were most strongly associated with OCD (rG = 0.72, p = 0.0007) among all tested psychiatric disorders (N = 11). Of all 97 tested phenotypes, 24 showed a significant genetic correlation with OCS, and 66 traits showed concordant directions of effect with OCS and OCD. OCS have a significant polygenic contribution and share genetic risk with diagnosed OCD, supporting the hypothesis that OCD represents the extreme end of widely distributed OCS in the population.

Associations between attention-deficit hyperactivity disorder genetic liability and ICD-10 medical conditions in adults: utilizing electronic health records in a Phenome-Wide Association Study.

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is often comorbid with other medical conditions in adult patients. However, ADHD is extremely underdiagnosed in adults and little is known about the medical comorbidities in undiagnosed adult individuals with high ADHD liability. In this study we investigated associations between ADHD genetic liability and electronic health record (EHR)-based ICD-10 diagnoses across all diagnostic categories, in individuals without ADHD diagnosis history. METHODS: We used data from the Estonian Biobank cohort (N = 111 261) and generated polygenic risk scores (PRS) for ADHD (PRSADHD) based on the ADHD genome-wide association study. We performed a phenome-wide association study (PheWAS) to test for associations between standardized PRSADHD and 1515 EHR-based ICD-10 diagnoses in the full and sex-stratified sample. We compared the observed significant ICD-10 associations to associations with (1) ADHD diagnosis and (2) questionnaire-based high ADHD risk analyses. RESULTS: After Bonferroni correction (p = 3.3 × 10-5) we identified 80 medical conditions associated with PRSADHD. The strongest evidence was seen with chronic obstructive pulmonary disease (OR 1.15, CI 1.11-1.18), obesity (OR 1.13, CI 1.11-1.15), and type 2 diabetes (OR 1.11, CI 1.09-1.14). Sex-stratified analysis generally showed similar associations in males and females. Out of all identified associations, 40% and 78% were also observed using ADHD diagnosis or questionnaire-based ADHD, respectively, as the predictor. CONCLUSIONS: Overall our findings indicate that ADHD genetic liability is associated with an increased risk of a substantial number of medical conditions in undiagnosed individuals. These results highlight the need for timely detection and improved management of ADHD symptoms in adults.

Childhood and adolescence outcomes in offspring to parents with bipolar disorder: the impact of lifetime parental comorbidity, parental sex, and bipolar subtype.

BACKGROUND: Offspring of parents with bipolar disorder have increased risks of their own psychopathology. However, a large-scale survey of psychiatric, somatic, and adverse social outcomes up to adulthood, which could aid in prioritizing and tailoring prevention, is lacking. It also remains to clarify how risks are modified by other parental factors. METHODS: Swedish population registers were linked to compare offspring having (N = 24,788) and not having (N = 247,880) a parent with bipolar disorder with respect to psychiatric diagnoses and psychotropic medication, birth-related and somatic conditions, social outcomes, accidents, suicide attempts, and mortality. Individuals were followed until age 18. We estimated the influence of lifetime parental psychiatric comorbidity, bipolar disorder subtype, and sex on outcomes. RESULTS: Children of parents with bipolar disorder had 2-3 times higher risks of all psychiatric diagnoses, except for bipolar disorder, for which the risk was 11-fold. Significantly increased risks were also found for several somatic conditions, low school grades, criminal behavior, victimization, accidents, and suicidal behavior. Adjusting for lifetime parental psychiatric comorbidity attenuated most associations. Offspring of a parent with bipolar disorder type 2 had statistically significantly higher risks of attention deficit hyperactivity disorder, respiratory tract conditions, and accidents compared with offspring of a parent with bipolar disorder type 1. Offspring of mothers with bipolar disorder had higher risks of several psychiatric diagnoses, respiratory tract conditions, low school grades, and accidents compared with offspring of fathers with bipolar disorder. Having two parents with bipolar disorder entailed the highest risks of psychiatric outcomes in offspring. CONCLUSIONS: Early intervention and family support are particularly warranted for the offspring of a parent with bipolar disorder in the presence of lifetime parental psychiatric comorbidity, when the parent has bipolar disorder type 2, or when the mother or both parents have bipolar disorder.

Age effects on autism heritability and etiological stability of autistic traits.

BACKGROUND: Autism and autistic traits onset in childhood but persist into adulthood. Little is known about how genetic and environmental factors influence autism and autistic traits into adulthood. We aimed to determine age effects on the heritability of clinically diagnosed autism and the etiological stability of autistic traits from childhood to adulthood using twin methods. METHODS: From 23,849 twin pairs in the Swedish Twin Register born between 1959 and 2010, we identified 485 individuals (1.01%, 31.5% female) with a clinical autism diagnosis. We estimated and compared the relative contribution of genetic, shared, and nonshared environmental influences to autism in childhood and adulthood. We further used multivariate twin analysis with four measurement points among 1,348 twin pairs in the longitudinal Twin Study of Child and Adolescent Development to assess the phenotypic and etiological stability of autistic traits - measured with three scales from the Child Behavior Checklist - from childhood to adulthood. RESULTS: Autism heritability was comparable from childhood, (96% [95% CI, 76-99%]) to adulthood (87% [67-96%]). Autistic traits were moderately stable (phenotypic correlation = 0.35-0.61) from childhood to adulthood, and their heritability varied between 52 and 71%. We observed stable as well as newly emerging genetic influences on autistic traits from ages 8-9 to 19-20, and unique nonshared environmental influences at each age. CONCLUSIONS: Genetic factors are important for autism and autistic traits in adulthood and separate genetic studies in adults are warranted.

Maternal mental health disorders and offspring asthma and allergic diseases: The role of child mental health.

BACKGROUND: Maternal psychological stress during pregnancy and postnatally has been shown to be associated with offspring atopic diseases (asthma, atopic dermatitis and allergic rhinitis). The aim of this study was to assess whether this association may be attributable to the child's own mental health disorders. METHOD: The study population included 15,092 twin children born 2002-2010 in Sweden. Questionnaire data at age 9 years was linked to national patient- and prescription registers. Maternal mental health during pregnancy and 3 years postnatally were identified from diagnosis and medication data (depression, anxiety and stress disorders). Atopic diseases in children were identified from questionnaires, diagnosis and medication data. Child mental health status (depression and anxiety) was identified from questionnaires. Three-way decomposition methods tested for mediation or interaction by child mental health disorders. RESULTS: Maternal mental health disorders were associated with most child atopic diseases including asthma aRR1.36 (95% CI 1.12, 1.60), and child mental health disorders, aRR1.73 (95% CI 1.56, 1.92). Children with mental health disorders were comorbid for atopic diseases with only asthma reaching statistical significance, aRR1.29 (95% CI 1.14, 1.47). Three-way decomposition found that mediation or interaction by child mental health disorders did not account for the mother mental health and child atopy associations except in parent-report asthma, where child mental health disorders mediated 13.4% (95% CI 2.1, 24.7) of the effect, but not for objectively defined (diagnosis and medication) asthma. CONCLUSION: The associations between maternal mental health and child asthma and allergic diseases do not appear to be attributable to child mental health disorders.

ADHD Pharmacotherapy and Mortality in Individuals With ADHD.

Importance: Attention-deficit/hyperactivity disorder (ADHD) is associated with increased risks of adverse health outcomes including premature death, but it is unclear whether ADHD pharmacotherapy influences the mortality risk. Objective: To investigate whether initiation of ADHD pharmacotherapy was associated with reduced mortality risk in individuals with ADHD. Design, Setting, and Participants: In an observational nationwide cohort study in Sweden applying the target trial emulation framework, we identified individuals aged 6 through 64 years with an incident diagnosis of ADHD from 2007 through 2018 and no ADHD medication dispensation prior to diagnosis. Follow-up started from ADHD diagnosis until death, emigration, 2 years after ADHD diagnosis, or December 31, 2020, whichever came first. Exposures: ADHD medication initiation was defined as dispensing of medication within 3 months of diagnosis. Main Outcomes and Measures: We assessed all-cause mortality within 2 years of ADHD diagnosis, as well as natural-cause (eg, physical conditions) and unnatural-cause mortality (eg, unintentional injuries, suicide, and accidental poisonings). Results: Of 148 578 individuals with ADHD (61 356 females [41.3%]), 84 204 (56.7%) initiated ADHD medication. The median age at diagnosis was 17.4 years (IQR, 11.6-29.1 years). The 2-year mortality risk was lower in the initiation treatment strategy group (39.1 per 10 000 individuals) than in the noninitiation treatment strategy group (48.1 per 10 000 individuals), with a risk difference of -8.9 per 10 000 individuals (95% CI, -17.3 to -0.6). ADHD medication initiation was associated with significantly lower rate of all-cause mortality (hazard ratio [HR], 0.79; 95% CI, 0.70 to 0.88) and unnatural-cause mortality (2-year mortality risk, 25.9 per 10 000 individuals vs 33.3 per 10 000 individuals; risk difference, -7.4 per 10 000 individuals; 95% CI, -14.2 to -0.5; HR, 0.75; 95% CI, 0.66 to 0.86), but not natural-cause mortality (2-year mortality risk, 13.1 per 10 000 individuals vs 14.7 per 10 000 individuals; risk difference, -1.6 per 10 000 individuals; 95% CI, -6.4 to 3.2; HR, 0.86; 95% CI, 0.71 to 1.05). Conclusions and Relevance: Among individuals diagnosed with ADHD, medication initiation was associated with significantly lower all-cause mortality, particularly for death due to unnatural causes.

Block2: A comprehensive open source framework to develop and apply state-of-the-art DMRG algorithms in electronic structure and beyond.

block2 is an open source framework to implement and perform density matrix renormalization group and matrix product state algorithms. Out-of-the-box it supports the eigenstate, time-dependent, response, and finite-temperature algorithms. In addition, it carries special optimizations for ab initio electronic structure Hamiltonians and implements many quantum chemistry extensions to the density matrix renormalization group, such as dynamical correlation theories. The code is designed with an emphasis on flexibility, extensibility, and efficiency and to support integration with external numerical packages. Here, we explain the design principles and currently supported features and present numerical examples in a range of applications.

Darier disease is associated with neurodegenerative disorders and epilepsy.

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.

Adolescent Psychedelic Use and Psychotic or Manic Symptoms.

Importance: While psychedelic-assisted therapy has shown promise in the treatment of certain psychiatric disorders, little is known about the potential risk of psychotic or manic symptoms following naturalistic psychedelic use, especially among adolescents. Objective: To investigate associations between naturalistic psychedelic use and self-reported psychotic or manic symptoms in adolescents using a genetically informative design. Design, Setting, and Participants: This study included a large sample of adolescent twins (assessed at age 15, 18, and 24 years) born between July 1992 and December 2005 from the Swedish Twin Registry and cross-sectionally evaluated the associations between past psychedelic use and psychotic or manic symptoms at age 15 years. Individuals were included if they answered questions related to past use of psychedelics. Data were analyzed from October 2022 to November 2023. Main Outcomes and Measures: Primary outcome measures were self-reported psychotic and manic symptoms at age 15 years. Lifetime use of psychedelics and other drugs was also assessed at the same time point. Results: Among the 16 255 participants included in the analyses, 8889 were female and 7366 were male. Among them, 541 participants reported past use of psychedelics, most of whom (535 of 541 [99%]) also reported past use of other drugs (ie, cannabis, stimulants, sedatives, opioids, inhalants, or performance enhancers). When adjusting for substance-specific and substance-aggregated drug use, psychedelic use was associated with reduced psychotic symptoms in both linear regression analyses (ß, -0.79; 95% CI, -1.18 to -0.41 and ß, -0.39; 95% CI, -0.50 to -0.27, respectively) and co-twin control analyses (ß, -0.89; 95% CI, -1.61 to -0.16 and ß, -0.24; 95% CI, -0.48 to -0.01, respectively). In relation to manic symptoms, likewise adjusting for substance-specific and substance-aggregated drug use, statistically significant interactions were found between psychedelic use and genetic vulnerability to schizophrenia (ß, 0.17; 95% CI, 0.01 to 0.32 and ß, 0.17; 95% CI, 0.02 to 0.32, respectively) or bipolar I disorder (ß, 0.20; 95% CI, 0.04 to 0.36 and ß, 0.17; 95% CI, 0.01 to 0.33, respectively). Conclusions and Relevance: The findings in this study suggest that, after adjusting for other drug use, naturalistic use of psychedelic may be associated with lower rates of psychotic symptoms among adolescents. At the same time, the association between psychedelic use and manic symptoms seems to be associated with genetic vulnerability to schizophrenia or bipolar I disorder. These findings should be considered in light of the study's limitations and should therefore be interpreted with caution.

Medication utilization in traumatic brain injury patients-insights from a population-based matched cohort study.

Introduction: Traumatic 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. Methods: We 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. Results: We 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. Discussion: Taken 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.

Criminal convictions in males and females diagnosed with attention deficit hyperactivity disorder: A Swedish national registry study.

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.

Lower autonomic arousal as a risk factor for criminal offending and unintentional injuries among female conscripts.

BACKGROUND: Lower autonomic arousal is a well-known correlate of criminal offending and other risk-taking behaviors in men, but few studies have investigated this association in women. AIM: To test associations between autonomic arousal and criminal offending as well as unintentional injuries among female conscripts. METHODS: All women born 1958-1994 in Sweden who participated in voluntary military conscription (n = 12,499) were identified by linking Swedish population-based registers. Predictors were resting heart rate (RHR) and systolic blood pressure (SBP). Covariates were height, weight, and physical energy capacity. Main outcomes were criminal convictions (any, violent, and non-violent) from the National Crime Register. Secondary outcome was unintentional injuries requiring medical treatment or causing death. We used survival analyses to test for associations between predictors and outcomes. RESULTS: Low RHR, relative to high RHR, was associated with an increased risk of any criminal conviction, non-violent criminal convictions, and unintentional injuries. Low SBP, relative to high SBP, was associated with an increased risk of violent criminal convictions. CONCLUSIONS: Results support lower autonomic arousal, particularly lower RHR, as a correlate of criminal offending among women that warrants further examination, as the reported findings have potential implications for the prediction of future female crime.

Methylphenidate and Short-Term Cardiovascular Risk.

Importance: There are concerns about the safety of medications for treatment of attention-deficit/hyperactivity disorder (ADHD), with mixed evidence on possible cardiovascular risk. Objective: To assess whether short-term methylphenidate use is associated with risk of cardiovascular events. Design, Setting, and Participants: This retrospective, population-based cohort study was based on national Swedish registry data. Participants were individuals with ADHD aged 12 to 60 years with dispensed prescriptions of methylphenidate between January 1, 2007, and June 30, 2012. Each person receiving methylphenidate (n = 26 710) was matched on birth date, sex, and county to up to 10 nonusers without ADHD (n = 225 672). Statistical analyses were performed from September 13, 2022, to May 16, 2023. Main Outcomes and Measures: Rates of cardiovascular events, including ischemic heart disease, venous thromboembolism, heart failure, or tachyarrhythmias, 1 year before methylphenidate treatment and 6 months after treatment initiation were compared between individuals receiving methylphenidate and matched controls using a bayesian within-individual design. Analyses were stratified by history of cardiovascular events. Results: The cohort included 252 382 individuals (15 442 [57.8% men]; median age, 20 (IQR, 15-31) years). The overall incidence of cardiovascular events was 1.51 per 10 000 person-weeks (95% highest density interval [HDI], 1.35-1.69) for individuals receiving methylphenidate and 0.77 (95% HDI, 0.73-0.82) for the matched controls. Individuals treated with methylphenidate had an 87% posterior probability of having a higher rate of cardiovascular events after treatment initiation (incidence rate ratio [IRR], 1.41; 95% HDI, 1.09-1.88) compared with matched controls (IRR, 1.18; 95% HDI, 1.02-1.37). The posterior probabilities were 70% for at least a 10% increased risk of cardiovascular events in individuals receiving methylphenidate vs 49% in matched controls. No difference was found in this risk between individuals with and without a history of cardiovascular disease (IRR, 1.11; 95% HDI, 0.58-2.13). Conclusions and Relevance: In this cohort study, individuals receiving methylphenidate had a small increased cardiovascular risk vs matched controls in the 6 months after treatment initiation. However, there was little evidence for an increased risk of 20% or higher and for differences in risk increase between people with and without a history of cardiovascular disease. Therefore, before treatment initiation, careful consideration of the risk-benefit trade-off of methylphenidate would be useful, regardless of cardiovascular history.

Incidence Trajectories of Psychiatric Disorders After Assault, Injury, and Bereavement.

Importance: Traumatic events have been associated with elevated risks of psychiatric disorders, while the contributions of familial factors to these associations remain less clear. Objective: To determine the contribution of familial factors to long-term incidence trajectories of psychiatric disorders following potentially traumatic events. Design, Setting, and Participants: This cohort study evaluated 3 separate cohorts of individuals residing in Sweden who were free of previous diagnosed psychiatric disorders when first exposed to assault (n = 49 957), injury (n = 555 314), or bereavement (n = 321 263) from January 1987 to December 2013, together with their unexposed full siblings, and 10 age-, sex-, and birthplace-matched unexposed individuals (per exposed individual). Cohorts were created from the Swedish Total Population Register linked to health and population registers. Data were analyzed from March 2022 to April 2023. Exposures: Potentially traumatic events, including various types of assault, injuries, and bereavement (death of a child or of a spouse or partner), were ascertained from the Swedish national registers. Main Outcomes and Measures: Incident psychiatric disorders were ascertained from the Swedish Patient Register. Flexible parametric and Cox models were used to estimate associations of potentially traumatic events with incident psychiatric disorders after multivariable adjustment. Results: The median (IQR) age at exposure to assault, injury, and bereavement was 22 (18-31), 19 (8-40), and 60 (51-68) years, respectively. During a median (IQR) follow-up of 4.9 (2.2-8.2), 9.1 (4.1-15.6), and 8.1 (3.4-14.8) years, the incidence rates of any psychiatric disorder were 38.1, 13.9, and 9.0 per 1000 person-years for the exposed groups of the 3 cohorts, respectively. Elevated risk of any psychiatric disorder was observed during the first year after exposure to any assault (hazard ratio [HR], 4.55; 95% CI, 4.34-4.77), injury (HR, 3.31; 95% CI,3.23-3.38), or bereavement (HR, 2.81; 95% CI, 2.72-2.91) and thereafter (assault HR, 2.50; 95% CI, 2.43-2.56; injury HR, 1.69; 95% CI, 1.68-1.70; bereavement HR, 1.42; 95% CI, 1.40-1.44). Comparable associations were obtained in sibling comparison (first year: assault HR, 3.70; 95% CI, 3.37-4.05; injury HR, 2.98; 95% CI, 2.85-3.12; bereavement HR, 2.72; 95% CI, 2.54-2.91; thereafter: assault HR, 1.93; 95% CI, 1.84-2.02; injury HR, 1.51; 95% CI, 1.48-1.53; bereavement HR, 1.35; 95% CI, 1.31-1.38). The risk elevation varied somewhat by type of traumatic events and psychiatric disorders, with the greatest HR noted for posttraumatic stress disorder after sexual assault (sibling comparison HR, 4.52; 95% CI, 3.56-5.73 during entire follow-up period). Conclusions and Relevance: In this study, the long-term risk elevation of psychiatric disorders after potentially traumatic events was largely independent of familial factors. The risk elevation observed immediately after these events motivates early clinical surveillance and mental health services for these vulnerable populations.