Isabell Brikell

Background: Post-traumatic stress disorder (PTSD) is associated with various adverse outcomes, but links with subsequent violent victimisation are uncertain. Methods: We linked data from Swedish sociodemographic and medical registers to create a matched cohort of people with diagnosed PTSD and a comparison sample matched on birth year, sex, and county of residence in the year preceding diagnosis (or matching in the case of undiagnosed individuals). We calculated the cumulative incidence of violent victimisation (defined using ICD codes registered at hospitalisation) and conducted stratified Cox regression analyses, adjusted for parental factors, psychiatric comorbidities, and history of violent victimisation. Findings: The cohort contained 29,688 individuals diagnosed with PTSD, who were matched with 296,880 individuals without PTSD (78.6% female), and followed for up to 34 years. Individuals with PTSD had higher cumulative incidences of violent victimisation after their index diagnosis (18.7% compared to 2.7% at 25 years follow-up). Individuals with both a diagnosis of PTSD and history of violent victimisation had the highest cumulative incidence (28.7%). After adjustment for parental characteristics, prior psychiatric comorbidity and prior violent victimisation, PTSD was associated with an adjusted hazard ratio of 4.0 (95% CI 3.7–4.4). Interpretation: Preventing subsequent violent victimisation among individuals diagnosed with PTSD should be considered by clinical services and incorporated into violence prevention strategies. Funding: AP is funded by the Wellcome Trust (grant code 218497/Z/19/Z). SF and AS are supported by the NIHR Oxford Health Biomedical Research Centre (grant BRC-1215-20005). No funder(s) listed had any role in the design or implementation of this study.

Background: Attention-deficit/hyperactivity disorder (ADHD) has been linked to elevated risk of type 2 diabetes (T2D). However, the impact of ADHD and ADHD medication use on prognosis and health outcomes in T2D remains unclear. This study investigates the associations of (1) ADHD and (2) ADHD medication use with rates of major adverse cardiac events (MACE) and all-cause mortality after a T2D diagnosis. Methods: This multinational cohort study used population-based data from Australia, Denmark, the Netherlands, Norway, Sweden, the United Kingdom, and the United States. Using a standardized analytical protocol, we identified adults with a first recorded T2D diagnosis during 2010-2020. Exposures were (1) ADHD, defined by a recorded ADHD diagnosis or ADHD medication dispensation, and (2) among adults with ADHD, the use of ADHD medication, both analysed as time-varying exposures. Main outcomes were MACE (acute myocardial infarction, stroke, or cardiovascular disease-related death) and all-cause mortality after T2D diagnosis. Cause-specific Cox models estimated hazard ratios (HRs) with 95% confidence intervals (CIs); results were pooled using random-effects meta-analyses and stratified by age and sex. Results: The cohort included 1,929,027 adults with T2D (909,176 [47.1%] males). In pooled analyses, adults with T2D and ADHD had a higher rate of all-cause mortality (HR, 2.42; 95% CI, 1.72-3.41), but not MACE (HR, 1.04; 95% CI, 0.81-1.35), after a T2D diagnosis compared with those without ADHD. Among adults with T2D and ADHD, ADHD medication use was associated with higher rate of MACE in those diagnosed with T2D before age 45 years (HR, 1.58; 95% CI, 1.18-2.10). These associations remained consistent, after adjusting for sex, age, calendar year at T2D diagnosis, psychiatric history, other psychotropic medication use, and cardiometabolic medication use. Conclusions: Adults with T2D and co-occurring ADHD were found to have increased risk of all-cause mortality after T2D diagnosis, while ADHD was not consistently associated with MACE across countries. ADHD medication use was linked to higher rate of MACE in adults with early-onset T2D. These findings suggest the potential need for integrated somatic-psychiatric care and careful consideration of ADHD medication use that may help reduce MACE and mortality, particularly in younger-onset T2D.

Background: Early discontinuation of attention-deficit/hyperactivity disorder (ADHD) medication is common and linked to worse outcomes. Identifying clinical predictors could aid personalised treatment yet evidence is inconsistent across ages and countries/regions. Objective: Investigate psychiatric and neurological comorbidity as predictors of early ADHD medication discontinuation in new ADHD medication users across age groups, sex and countries/regions. Methods: Using health records from eight countries/regions, we identified 1 000 411 (44% female) new ADHD medication users (2011–2020). Discontinuation was defined as a ≥180 day gap between dispensations. We examined 23 indicators of psychiatric or neurological comorbidity, severity and psychotropic medication use. Associations were estimated using Cox regression, pooled with random-effects meta-analyses and stratified by age-at-initiation and sex. Findings: Discontinuation rates varied widely (children 19%–61%, adolescents 37%–68%, young adults 52–67%, adults 38%–68%). In pooled analyses, earlier discontinuation in children was predicted by intellectual disability, autism and use of psychotropic medications (HR range 1.32–1.51), while conduct/oppositional defiant disorder (CD/ODD) was protective (HR 0.83, 95% CI 0.73 to 0.94). In adolescents, no indicators remained statistically significant after multiple-testing control. In young adults, CD/ODD (HR 1.42, 95% CI 1.30 to 1.55), and in adults, schizophrenia (HR 1.25, 95% CI 1.09 to 1.44) and tic disorders (HR 1.27, 95% CI 1.11 to 1.46) predicted earlier discontinuation. Statistical heterogeneity was substantial, largely driven by US estimates. In meta-analyses excluding the USA, additional associations emerged. For example, in children, OCD and anxiety disorders predicted earlier discontinuation, while eating disorders and antidepressants/anxiolytics were protective in adults. Associations with schizophrenia, tic disorders and CD/ODD were no longer significant. Country-specific analyses showed similar association patterns, except in the USA, Hong Kong and the UK. Sex differences were limited. Conclusions: Children with neuropsychiatric comorbidity and related comedication are more likely to discontinue ADHD medication early, whereas few consistent predictors were seen from adolescence onwards. Marked cross-country variation, particularly in the USA, points to system-level influences on treatment patterns. Clinical implications: Improving ADHD medication persistence will require consideration of healthcare context and age-specific strategies, including close monitoring for children with complex neuropsychiatric profiles, and consideration of broader factors in adolescents and adults, where clinical predictors were limited.

Background: Self-harm in young people is associated with elevated risks for subsequent self-harm, suicide attempts and suicide, particularly during the first year. Yet the trajectory across sex, age and self-harm methods remains poorly understood. Objective: To estimate risk for subsequent self-harm, suicide attempts and suicide following a first hospital-treated self-harm event in young people. Methods: This study included 77 647 individuals (57.0% female) whose first hospital-treated (ie, within inpatient or outpatient specialised healthcare) self-harm episode occurred between ages 10–24 years during 1973–2019. We estimated cumulative incidence and incidence rate for subsequent self-harm, suicide attempts and suicide at 1 month, 3 months and 1 year following the initial episode. Findings: Within 1 year, the cumulative incidence was 17.3% (95% CI 17.0 to17.5) for subsequent self-harm, 8.3% (8.1 to 8.5) for suicide attempt and 0.3% (0.2 to 0.3) for suicide. The highest risks occurred in the first month: 8.4% (8.2 to 8.6) for self-harm, 2.9% (2.8 to 3.0) for suicide attempt and 0.04% (0.03 to 0.05) for suicide. In the first month, the incidence rate of self-harm was 2.97 per 1000 person-days (2.90 to 3.05), falling to 0.55 (0.54 to 0.56) over the year. The suicide attempt rate declined from 0.98 (0.94 to 1.02) to 0.24 (0.24 to 0.25) and the suicide rate from 0.013 (0.009 to 0.019) to 0.007 (0.006 to 0.008). Males exhibited the highest suicide risk and females the highest attempts risk. First-month self-harm risk was greatest among males and children aged 10–12. Conclusions: The month following a self-harm episode is marked by an elevated risk of subsequent self-harm, suicide attempts and suicide, yet risk remains elevated over the full year. Clinical implications: These findings underscore the need for both acute and sustained prevention efforts. Special attention should be given to males and children aged 10–12 presenting with self-harm of ambiguous intent, as their risk of repetition may otherwise go unrecognised.

Background: Patients in forensic psychiatric care (FPC) are often treated with various psychotropic medications. However, evidence regarding their effectiveness in this setting is lacking. Objective: The study aimed to estimate how different psychotropic medications are associated with the use of coercive measures and recidivism during FPC. Methods: In this observational national register-based study, we included all patients newly registered as admitted to FPC in Sweden between January 2009 and August 2024. Exposures included major classes of psychotropic medication (typical antipsychotics, atypical antipsychotics, antidepressants, hypnotics and sedatives, antiepileptic medications, opioids, medications for addictive disorders and mood stabilisers), antipsychotic treatment strategies (no use, monotherapy, polypharmacy, long-acting injectables or clozapine) and specific antipsychotic agents. Outcomes were the use of coercive measures and recidivism into criminal behaviour. We performed a within-individual analysis using conditional generalised estimating equation models, where the risk of outcomes was compared between exposed and non-exposed time periods. Findings: In total, 2690 patients were included, of which 25.1% experienced at least one occasion of coercion and 27.1% at least one event of recidivism during FPC. Atypical antipsychotics were associated with a reduced risk of subsequent use of coercive measures (OR 0.70, 95% CI 0.55 to 0.89) and recidivism (OR 0.79, 95% CI 0.63 to 0.99). Medication for addictive disorders was associated with a reduced risk of coercive measures by 34% (OR 0.66, 95% CI 0.47 to 0.93). Among antipsychotic agents, clozapine was associated with the largest risk reduction in the use of coercive measures (OR 0.48, 95% CI 0.33 to 0.69) and recidivism (OR 0.49, 95% CI 0.33 to 0.74). There was no significant difference between long-acting injectable, oral monotherapy or polypharmacy. Conclusions: We observed that atypical antipsychotics, especially clozapine, were associated with a risk reduction for coercive measures and recidivism during FPC. Additionally, medications for addictive disorders were associated with a reduced risk of coercive measures. Clinical implications: Our results can help inform decision-making processes in this clinical setting regarding pharmacotherapy but should be interpreted as one of many aspects influencing treatment success in FPC.

Borderline personality disorder (BPD) often co-occurs with other health conditions, but the role of genetics vs. environment is unclear. In this multigenerational cohort study using Swedish national registers, the authors quantified the co-aggregation of BPD with other phenotypes in families and estimated the genetic vs. environmental contributions. In a birth cohort of individuals born 1973–2001 and their twins, siblings, cousins, parents, and aunts/uncles, the exposure was BPD in the proband. Odds ratios were estimated for 19 psychiatric, 18 somatic, and seven behavioral/injury outcome phenotypes within individuals and relative pairs. Structural equation modeling was used to estimate genetic, common environmental, and unique environmental contributions to phenotypic associations and genetic correlations ( r _g ). Of the 2.7 million individuals in the birth cohort (mean age at follow-up end = 31.7 years, SD = 9.8, 48.5% female), 24,547 (86% female) were diagnosed with BPD by follow-up end. Relatives of individuals with BPD had increased risk for various psychiatric, somatic, and behavioral phenotypes, except cystic fibrosis. Psychiatric phenotypes showed the strongest phenotypic and genetic correlations, with equal contributions from genetic and unique environmental factors. The pattern varied for somatic phenotypes, which also had weaker correlations. Sleep disorders showed the strongest genetic overlap with BPD ( r _g = 0.74, 95%CI = 0.39–1.08). Behavioral phenotypes related to BPD symptoms showed strong associations and genetic overlap ( e.g ., self-harm r _g = 0.80, 95%CI = 0.55–1.04), whereas accident-related phenotypes had weaker associations and varied genetic/environmental contributions. BPD co-aggregates with many phenotypes, with psychiatric conditions showing the strongest genetic overlap. These findings guide further research on BPD comorbidity causes and interventions.

Background: Attention-deficit/hyperactivity disorder (ADHD) and substance use disorder (SUD) often coexist. ADHD complicates the course of disease in SUD. While recommended in guidelines, ADHD medication for those with comorbid SUD remains controversial. Objective: This study aims to explore how comorbid SUD affects ADHD medication discontinuation and reinitiation in individuals with ADHD. Methods: Using a matched cohort design, we identified 9283 individuals with ADHD and SUD in Sweden between 2006 and 2020, who had ongoing ADHD medication at the time of their first SUD-related event. Controls with ADHD medication but no SUD (n=46 401) were matched 5:1 on sex and birth year. HRs for treatment discontinuation within 1 year from first SUD, and for treatment reinitiation within 1 year from the first discontinuation, were estimated using stratified Cox models. Findings: Individuals with ADHD and SUD were nearly two times as likely to discontinue ADHD treatment within 1 year (HR: 1.99, 95% CI 1.92 to 2.07) and less likely to re-initiate ADHD treatment (HR: 0.82, 95% CI 0.76 to 0.89) compared with controls. Several factors, including male sex, adolescent to young adult age and lower stimulant medication dose, were associated with increased risk for treatment discontinuation, but only adolescent to young adult age was significantly associated with treatment reinitiation in those with ADHD and SUD. Conclusions: The results suggest less treatment continuity and access for those with ADHD and comorbid SUD. Clinical implications: Treatment providers need to consider the specific needs of individuals with ADHD and comorbid SUD, especially in young males, to improve treatment outcomes for vulnerable groups.

Background: Suicidal behaviour shows notable sex differences, and understanding whether genetic factors contribute to these differences is critical for identifying at-risk individuals and prevention. Objective: We aim to investigate the genetic contribution to suicide attempts and examine whether genetics account for sex differences in incidence. Methods: This population-based cohort study includes 3.1 million individuals born 1963–1998 and followed through Swedish National Registers, including hospitals and specialist outpatient diagnoses and cause of death data. Suicide attempts were identified using ICD codes, indicating intentional self-harm, self-harm using lethal methods or leading to hospitalisation, or resulting in death. Familial aggregation, coaggregation, pedigree heritability and genetic correlations were estimated using genealogical data. For sex-specific analyses, we examined mother–daughter, female sibling, father–son and male sibling pairs, separately. Findings: Suicide attempts were more common among females than males (3.3% vs 2.6%). In both sexes, risk aggregated within families (ORs ranged 1.6–3.4 across relative types) and was higher in first-degree than second-degree relatives. Familial aggregation was stronger in females than in males, and in same-sex first degree relatives compared with cross-sex pairs. Pedigree heritability was 41.9% (95% CI 36.0 to 48.4%) and did not differ significantly by sex (female 51.4% (95% CI 40.1% to 58.6%), male 45.1% (95% CI 32.3% to 52.5%), Bootstrap p value 0.40). Suicide attempt showed moderate to high pedigree genetic correlations with psychiatric disorders, strongest with substance use disorders (SUD, r _g =0.85 (95% CI 0.83 to 0.96)), with no significant sex differences. The genetic correlation between female and male suicide attempts was high (0.85 (95% CI 0.80 to 0.99)), suggesting a substantial genetic overlap. Conclusions: Suicide attempt has a moderate heritable component that largely overlaps between females and males and with other psychiatric disorders, particularly SUD. Stronger familial aggregation in females and in same-sex pairs highlights the potential role of sex-specific environmental or social factors. Future research should focus on non-genetic contributors and their potential interaction with genetic factors to better understand and address sex disparities in suicidal behaviour Clinical implications: Genetic risk for suicide attempt is substantial but does not fully explain sex differences in incidence. Clinicians should, therefore, consider non-genetic, including sex-specific environmental and social factors, alongside family history and psychiatric comorbidity when assessing suicidal risk.