Agnieszka Butwicka

• Sirotina, Ulyana; Bjarnadottir, Bryndis Lara; Butwicka, Agnieszka; Ystrom, Eivind; Suvisaari, Jaana & Kiviruusu, Olli [Show all 11 contributors for this article] (2026). Mental health and healthcare use during COVID‐19 among neurodivergent youth and youth with pre‐existing psychiatric disorders: A systematic review. JCPP Advances. doi: 10.1002/jcv2.70176. Full text in Research Archive Show summary

  Abstract Background Neurodivergent youth and youth with pre‐existing psychiatric disorders may have faced additional challenges in navigating the demands and restrictions of the COVID‐19 pandemic. However, less is known about how mental health outcomes and psychiatric healthcare utilization differed across diagnostic groups and other youth‐related factors. This systematic review synthesizes evidence on mental health symptoms and psychiatric healthcare use among youth with pre‐existing conditions during the pandemic. Methods We searched PubMed, Web of Science and additional sources for cross‐sectional and longitudinal studies with data collected between March 2020 and May 2023. Eligible studies included neurodivergent youth and/or youth with psychiatric disorders confirmed through clinician diagnosis or medical records prior to the pandemic. Given the clinical and methodological diversity of studies, findings were synthesized narratively. Results Forty‐eight studies met the inclusion criteria. Mental health outcomes showed mixed patterns both across and within diagnostic groups, with individual studies reporting symptom increase, stability and improvements. Evidence on psychiatric healthcare utilization was more limited and suggested different patterns between service use and psychotropic medication use. Compared to boys, girls were more likely to experience COVID‐related distress and increases in psychiatric service use during the pandemic. Age‐related findings varied across developmental stages and outcome domains. Most studies ( n  = 40; 83.3%) had a moderate overall risk of bias (RoB), while seven (14.6%) had a high overall RoB. Conclusion Mental health outcomes among youth with pre‐existing conditions during the COVID‐19 pandemic varied both within and across diagnostic groups. Outcomes were also associated with individual, developmental, contextual and service‐related factors. These findings suggest the importance of considering such factors alongside diagnosis when identifying clinical needs and planning support during large‐scale societal disruptions. Evidence on psychiatric healthcare utilization remains limited. More methodologically robust research is needed to clarify mental health and healthcare‐use patterns during major public health emergencies.

• Dong, Zihan; Zhou, Yiling; Yao, Honghui; Liu, Shengxin; Astrup, Aske & Engeland, Anders [Show all 31 contributors for this article] (2026). Major adverse cardiac events and mortality associated with ADHD and its treatment in adults with type 2 diabetes: a multi-national cohort study. BMC Medicine. 24. doi: 10.1186/s12916-026-05246-4. Full text in Research Archive Show summary

  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.

• Sun, Jiangwei; Li, Lin; Chang, Zheng; Butwicka, Agnieszka; Bergman, David & Sun, Shihua [Show all 10 contributors for this article] (2026). Psychiatric Disorders Before and After Inflammatory Bowel Disease Diagnosis: A Nationwide Cohort Study in Sweden 2007 to 2023. Clinical Gastroenterology and Hepatology. ISSN 1542-3565. doi: 10.1016/j.cgh.2026.05.034. Full text in Research Archive Show summary

  Background & Aims Evidence suggests that patients with inflammatory bowel disease are at higher risk of psychiatric disorders, yet temporal pattern of risk elevation before/after inflammatory bowel disease diagnosis and role of familial factors remain unclear. Methods Swedish patients with inflammatory bowel disease diagnosed between 2007 and 2023 were compared with reference individuals in a matched population-based cohort and compared with inflammatory bowel disease–free full siblings in a sibling-controlled cohort. Primary outcome was any psychiatric disorder, whereas secondary outcomes included psychotic disorders, mood disorders, anxiety disorders, eating disorders, substance misuse, personality disorders, attention-deficit/hyperactivity disorder, and autism spectrum disorders. We estimated temporal patterns of hazard ratios from 5 years before to 10 years after inflammatory bowel disease diagnosis by using flexible parametric survival models. Results The study included 43,862 patients with inflammatory bowel disease (mean age at diagnosis, 41.6 years; 47.3% female) and 178,821 reference individuals. The hazard ratio of any psychiatric disorder started to increase from 2 to 3 years before inflammatory bowel disease diagnosis (eg, hazard ratio, 1.15; 95% confidence interval, 1.09–1.21 at −2 years), peaked immediately after inflammatory bowel disease diagnosis (hazard ratio, 1.50; 95% confidence interval, 1.41–1.59 at 0.5 year), and decreased rapidly thereafter but remained increased even at 10 years after diagnosis (hazard ratio, 1.19; 95% confidence interval, 1.13–1.24). The increased hazard ratio was mainly driven by major depressive disorder, anxiety disorders, and substance misuse. No increase was observed for psychotic disorders, personality disorders, and attention-deficit/hyperactivity disorder, although patients with inflammatory bowel disease were more likely to have autism spectrum disorders shortly after diagnosis and eating disorders from ≥5 years onwards. Similar temporal hazard ratio patterns were observed across all subtypes of inflammatory bowel disease: Crohn’s disease, ulcerative colitis, and inflammatory bowel disease–unclassified. Similar risk increases for psychiatric disorders were observed in the sibling-controlled cohort. Conclusions Patients with inflammatory bowel disease were at an increased risk of several psychiatric disorders from 2 to 3 years before diagnosis through up to 10 years after, and this risk increase cannot be fully explained by shared familial factors.

• Eriksson, Daniel; Kuja-Halkola, Ralf; Holmqvist, Marie E.; Larsson, Henrik; Butwicka, Agnieszka & Gudbjörnsdottir, Soffia [Show all 9 contributors for this article] (2026). Tissue-specific clustering of genetic correlations across autoimmune diseases in a nationwide sibling study. Journal of Clinical Investigation. ISSN 0021-9738. doi: 10.1172/jci205952. Full text in Research Archive Show summary

  Background Autoimmune diseases (ADs) often co-occur within individuals and families, indicating shared genetic risk factors. However, the composition of genetic overlap across autoimmunity is largely unknown. Methods This nationwide study included 6,336,615 individuals born in Sweden between 1932 and 1983, comprising 3,839,400 full-sibling pairs. Based on national heath-registers, 22 ADs were identified from 1969-2013. Aggregation and co-aggregation of ADs among siblings was used to estimate pairwise genetic correlations of ADs under a liability-threshold model. Network analysis and principal component analysis was used to characterize the structure of shared genetic risk across ADs. Results A total of 707,995 individuals (11.2%) were diagnosed with at least one AD. The studied ADs formed a network of significant genetic correlations (mean r g = 0.24, range 0.08-0.84) with clusters of more closely related ADs (r g ≥ 0.3). We found no evidence of a significant universal factor predisposing to autoimmunity. Conclusions This study demonstrates that ADs share substantial cluster-specific genetic overlap that largely aligns with affected tissue types, leading to distinct groupings of connective tissue diseases, gastrointestinal disorders, and endocrinopathies, whereas diseases of the nervous system show limited genetic cohesion. This suggests that shared biological mechanisms may drive coaggregation within disease groups. Clinically, these insights highlight the importance of monitoring patients and their relatives for related autoimmune disorders. Funding The Swedish Society of Medicine, Region Värmland's County Research Council, The Swedish Research Council, the Knut and Alice Wallenberg Foundation, The Regional Agreement on medical training and Clinical research (ALF) between Stockholm County Council and Karolinska Institutet

• Machado, Gisele Magarotto; Nikolic, Milena; Grønnerød, Cato; Pianowski, Giselle; Butwicka, Agnieszka & Stanisławski, Krzysztof [Show all 8 contributors for this article] (2026). Structure and centrality of clinically meaningful psychopathology constructs across age groups in a Brazilian sample. Personality and Individual Differences. ISSN 0191-8869. 264. doi: 10.1016/j.paid.2026.114043. Full text in Research Archive Show summary

  This cross-sectional study examined the network structure and centrality of clinically meaningful psychopathology constructs across adolescence (14–17 years; N = 895), emerging adulthood (18–29 years; N = 717), and established adulthood (30–45 years; N = 381) in a Brazilian sample. Using the clinical scales of the Personality Assessment Inventory (PAI) and PAI-Adolescent (PAI-A), we applied exploratory graph analysis (EGA) and estimated centrality and bridge centrality metrics to identify communities and structurally connected constructs within each age group. Across all three age groups, EGA revealed a three-community structure partially consistent with dimensional models of psychopathology, identifying internalizing, externalizing, and severe dysregulation clusters. Borderline features were the most central across all networks and served as the dominant bridge in emerging and established adulthood groups, whereas somatic complaints played this role in the adolescent group. A notable difference across age groups was observed for mania, which clustered with the severe dysregulation community in adolescents but with the externalizing community in emerging and established adults. These findings highlight both similarities and cross-sectional age-related differences in the organization of broad psychopathology domains across age groups. The use of a large Brazilian sample contributes to addressing geographic inequities in mental health research.

• Liu, Shengxin; Machado, Gisele Magarotto; Hardiansyah, Irzam; Gu, Xinyue; Ludvigsson, Jonas F. & Lichtenstein, Paul [Show all 13 contributors for this article] (2026). Familial Co‐Aggregation of Neurodevelopmental Conditions and Childhood‐Onset Type 1 Diabetes. Acta Paediatrica. ISSN 0803-5253. p. 1–8. doi: 10.1111/apa.70732. Full text in Research Archive Show summary

  ABSTRACT Aim Childhood‐onset Type 1 diabetes (T1D) is associated with neurodevelopmental conditions (NDCs). We examined whether this association extends to relatives and assessed phenotypic, genetic, and environmental correlations between T1D and NDCs. Methods Using Swedish registers, we identified 4 066 634 individuals born 1973–2015 and linked them to siblings and cousins; 23 212 (0.57%) had T1D before 18 years. Logistic regression estimated odds of receiving a diagnosis of any and each of the examined NDCs among individuals with T1D and their relatives. Bivariate quantitative genetic models estimated phenotypic, additive genetic, shared environmental, and non‐shared environmental correlations. Analyses were conducted in April 2025. Results NDCs were more prevalent among individuals with T1D than in those without (10.3% vs. 6.4%). T1D was associated with higher odds of receiving a diagnosis of any NDCs (OR 1.43; 95% CI 1.37–1.49). Full siblings also had higher odds (OR 1.12; 95% CI 1.06–1.18), whereas no significant associations were observed among other relatives. Cross‐trait phenotypic correlations were small (0.06–0.08). Conclusion Individuals with childhood‐onset T1D and their full siblings had higher odds of recorded NDC diagnoses. Shared familial factors appeared to contribute only modestly, while differential ascertainment and family‐level consequences of T1D may also play a role. These findings support access to neurodevelopmental expertise in paediatric diabetes services.

• Martini, Miriam I; Kuja-Halkola, Ralf; Butwicka, Agnieszka; Rietz, Ebba Du; Kanina, Aleksandra & Larsson, Henrik [Show all 11 contributors for this article] (2026). Associations between childhood somatic conditions and psychiatric diagnoses in autistic young adults: a retrospective, population-based cohort study in Sweden. The Lancet Child and Adolescent Health. ISSN 2352-4642. 10(9), p. 647–657. doi: 10.1016/s2352-4642(26)00124-0. Full text in Research Archive Show summary

  Background: Autistic people are at an increased risk of psychiatric and somatic health conditions in young adulthood, but the influence of childhood somatic conditions on adult psychiatric conditions has not been examined. This study aimed to investigate whether childhood somatic conditions are associated with adult psychiatric conditions in autistic young adults. Methods: This retrospective, longitudinal, population-based cohort study design used data from linking nationwide Swedish registers. From the Medical Birth Register, we identified all individuals born in Sweden between Jan 1, 1985, and Dec 31, 2004 who were residing in Sweden at age 16 years. Between Jan 1, 2001, and Dec 31, 2020, individuals were followed up from age 16 years until a psychiatric diagnosis, their 25th birthday, death, emigration, or the end of follow-up, whichever came first. Autism, psychiatric, and somatic diagnoses were obtained from the National Patient Register and Prescribed Drug Register. We extracted diagnoses of nine childhood somatic conditions (asthma, chronic pain, epilepsy, cardiovascular conditions, migraine, autoimmune conditions, infections, irritable bowel syndrome, and type 1 diabetes) before age 16 years as exposures and ten adult psychiatric conditions (anxiety, obsessive-compulsive, depressive, bipolar, psychotic, sleep, and substance use disorders, anorexia nervosa, other eating disorders, and self-harm) between ages 16 years and 24 years as outcomes. Associations between childhood somatic conditions and adult psychiatric conditions were estimated using Cox regression in autistic and non-autistic people, adjusted for birth year and sex, with additional stratified analyses by sex and co-occurring intellectual disability among autistic people. We involved people with lived experience in the study design and implementation. Findings: From nationwide registers, we identified 1 944 781 individuals born between 1985 and 2004 in Sweden, including 58 410 (3·0%) autistic people (21 758 [37·3%] females and 36 652 [62·7%] males), who were followed up from age 16 years for a mean of 7·1 years (SD 2·8). Of 58 410 autistic people, 32 828 (56·2%) had any childhood somatic condition and 29 793 (51·0%) had any adult psychiatric condition. Of 1 886 371 non-autistic people, 835 810 (44·3%) had any childhood somatic condition and 251 333 (13·3%) had any adult psychiatric condition. Autistic people with any childhood somatic condition had an increased risk of any adult psychiatric condition compared with autistic people without any childhood somatic condition (adjusted HR 1·14 [95% CI 1·11–1·17]). For non-autistic people with versus without any childhood somatic condition, the adjusted HR was 1·41 (1·40–1·43). In people with any childhood somatic condition, autistic people showed an increased risk of any adult psychiatric condition compared with non-autistic people (5·36 [5·27–5·45]). In those without any childhood somatic condition, autistic people also showed an increased risk compared with non-autistic people (6·65 [6·53–6·77]). Interpretation: Although childhood somatic conditions contribute to adult psychiatric conditions, autistic people show elevated psychiatric vulnerability regardless of childhood somatic condition status. The findings highlight the need for integrated somatic–psychiatric health care and suggest that risk in this group is likely shaped by a broader range of factors beyond childhood somatic conditions alone.

• Butwicka, Agnieszka; Konowałek, Łukasz; Martin, Joanna; Rzeszutek, Marcin & Wolańczyk, Tomasz (2026). The exponential increase in the number of prescriptions for ADHD medication between 2012 and 2022 in Poland in patients aged 5–59 years: a pharmacoepidemiological study | European Child & Adolescent Psychiatry | Springer Nature Link. European Child and Adolescent Psychiatry. ISSN 1018-8827. doi: 10.1007/s00787-026-03104-5. Full text in Research Archive Show summary

  There are currently no pharmacoepidemiological data on the use of ADHD medications in Poland. Moreover, evidence from Central and Eastern Europe remains limited, despite a global increase in ADHD diagnosis and pharmacological treatment. This lack of evidence highlights the need for population-based analyses of prescribing trends in this setting. This study aims to analyze data from the Polish prescription register to estimate the increase in the total number of prescriptions for methylphenidate and atomoxetine from 2012 to 2022, as well as identify any factors that may have influenced this trend. A retrospective population-based study utilizing a large electronic database containing all (n = 925 536) prescriptions for ADHD medication in Poland for the period between 2012 and 2022 for patients aged 5–59 years was conducted. We performed regression-based temporal trend analyses, including age- and sex-stratified interaction models. The prevalence of ADHD medications rose from 170.33 prescriptions per 100 000 in 2012 (n = 48,429) to 591.50 per 100 000 in 2022 (n = 155,068), marking a 247% increase. Methylphenidate remained the most prescribed medication, with its prevalence increasing from 168.28 prescriptions per 100,000 in 2012 to 481.45 prescriptions per 100,000 in 2022 (186% increase), while atomoxetine experienced an increase from 2.02 prescriptions per 100,000 in 2012 to 110.05 prescriptions per 100,000 in 2022 (5242% increase). ADHD medication usage increased across all age groups, with the highest prescription rates observed among children aged 7–12 and significant growth seen in adolescents aged 13–17. The use of ADHD medications has increased among all age groups and in males as well as females. The rate of increase was highest among females, particularly in the group of young adults (18–24 year olds). Our study provides data on prescription trends in Poland, contributing to the limited evidence from Central and Eastern Europe.

• Dong, Zihan; Liu, Shengxin; Lundholm, Cecilia; Brikell, Margareta Isabell; Kuja-Halkola, Ralf & D’Onofrio, Brian M [Show all 12 contributors for this article] (2026). ADHD and cardiometabolic risk profile in adults with type 2 diabetes: a longitudinal register-based study. BMJ Open. 16. doi: 10.1136/bmjopen-2025-113372. Full text in Research Archive Show summary

  Objective: To investigate the association between attention-deficit/hyperactivity disorder (ADHD) and cardiometabolic risk profile at the time of type 2 diabetes (T2D) diagnosis and examine longitudinal changes in cardiometabolic measures following T2D diagnosis. Design and setting: A nationwide cohort study using linked Swedish health registers. Participants: Adults aged 18–65 years with a first recorded diagnosis of T2D between 1996 and 2020. ADHD, treated as a lifetime condition, was identified through diagnostic and prescription records. Outcome measures: The cardiometabolic risk profile, comprising nine clinical parameters and two behavioural factors, was assessed at T2D diagnosis and was tracked for up to 5 years post-diagnosis. Linear regression (βADHD) and Poisson regression models with robust variance (risk ratios (RRs)) compared cardiometabolic risk factors at diagnosis between individuals with and without ADHD. Generalised estimating equations (βADHD*t) assessed longitudinal changes in clinical parameters following the diagnosis. Results: Among 80 607 individuals with T2D, 1204 (1.5%) had an ADHD diagnosis. At T2D diagnosis, individuals with ADHD were younger and had statistically significantly higher body mass index (BMI) (βADHD: 1.93 (95% CI 1.54 to 2.32)), triglycerides (βADHD: 0.31 (95% CI 0.17 to 0.45)) and smoking prevalence (RR: 1.58 (95% CI 1.44 to 1.74)) compared with those without ADHD. Other cardiometabolic risk factors did not differ significantly. Over the subsequent 5 years, trajectories in cardiometabolic risk factors were broadly similar, except for a greater reduction in BMI in individuals with ADHD (βADHD*t: −0.26 (95% CI −0.34 to −0.17)), independent of baseline BMI and glucose-lowering medications. After inverse probability of treatment weighting, the BMI reduction was substantially reduced and not significant (βADHD*t: −0.05 (95% CI −0.17 to 0.07)). Conclusions: Among adults with newly diagnosed T2D, those with co-occurring ADHD had broadly similar cardiometabolic profiles to those without ADHD but presented at a younger age with a modestly higher BMI, triglycerides and smoking prevalence. Individuals with ADHD also showed a slightly greater reduction in BMI over time following T2D diagnosis. Despite modest overall cardiometabolic differences, incorporating ADHD status into preventive diabetes care may help identify a younger, more vulnerable subgroup who could benefit from targeted risk factor management.

• Taylor, Mark J.; Martini, Miriam I.; Kuja-Halkola, Ralf; Cassidy, Sarah; Ronald, Angelica & Tideman, Magnus [Show all 13 contributors for this article] (2026). Association between co-occurring psychiatric conditions and premature mortality in autistic people: population-based cohort study. British Journal of Psychiatry. ISSN 0007-1250. p. 1–9. doi: 10.1192/bjp.2026.10696. Full text in Research Archive Show summary

  Background Autistic people are at an elevated risk of premature mortality; however, few studies have identified factors that explain this association. Co-occurring psychiatric conditions are a strong candidate, given that autistic people are at a high risk of such conditions and these conditions are broadly associated with premature mortality. Aims We aimed to investigate the degree to which co-occurring psychiatric conditions are associated with premature mortality in autistic people. We explored these associations across sex and co-occurring other neurodevelopmental conditions. Method We conducted a cohort study based on registry linkage. We identified 2 958 317 individuals born in Sweden from 1974 to 2004, including 70 546 (2.38%) individuals with an autism diagnosis. We identified diagnoses of 13 psychiatric conditions. The cohort was followed up from age 16 to age 46 at the oldest. We compared the risk of mortality (from all-causes, suicide, other external causes and natural causes) across autistic people with psychiatric conditions and (a) non-autistic people without psychiatric diagnoses; (b) autistic people without psychiatric diagnoses; and (c) non-autistic people with psychiatric diagnoses. We conducted separate analyses by sex and co-occurring neurodevelopmental conditions. Results The mortality rate in autistic people with psychiatric conditions was 3.2 deaths per 1000 person-years, which was higher than that observed in non-autistic (0.27 deaths per 1000 person-years) and autistic people without psychiatric conditions (0.96 deaths per 1000 person-years). The relative risk of premature mortality was higher in autistic people with psychiatric conditions compared with both non-autistic (hazard ratio 13.85, 12.86–14.91) and autistic people (hazard ratio 3.44, 2.94–4.02) without psychiatric conditions and also exceeded the risk of premature mortality in individuals with psychiatric conditions alone (hazard ratio 1.47, 1.37–1.58). Similar patterns emerged across sex, intellectual disability and attention-deficit hyperactivity disorder. Conclusions Co-occurring psychiatric conditions are a risk factor for premature mortality in autistic people. Timely detection and treatment of such conditions in autistic people may facilitate healthier, lengthier lives for autistic people.

• Nguyen, Thuy-Dung; Gong, Tong; Hu, Kejia; Kuja-Halkola, Ralf; Borges, Karen & Butwicka, Agnieszka [Show all 17 contributors for this article] (2026). Sex differences in familial risk and genetic components of suicide attempts: a register-based cohort study in Sweden. BMJ Mental Health. 29(1), p. 302082–302082. doi: 10.1136/bmjment-2025-302082. Full text in Research Archive Show summary

  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.

• Kanina, Aleksandra; Li, Zhou; Rosenqvist, Mina; Butwicka, Agnieszka; Larsson, Henrik & Johansson, Stefan [Show all 9 contributors for this article] (2025). The Association Between Clinically Diagnosed Neonatal Jaundice and Autism: A Swedish Register-Based Cohort Study. Acta Paediatrica. ISSN 0803-5253. 114(11), p. 2925–2934. doi: 10.1111/apa.70191. Full text in Research Archive Show summary

  Aim Neonatal jaundice may increase the likelihood of autism through its influence on neurodevelopment. We assessed whether neonatal jaundice increases the risk for autism while accounting for confounding of perinatal risk factors. Method We used a population-based cohort of 1 669 830 individuals born in Sweden between 1992 and 2010. Information on jaundice and autism was retrieved from Swedish registers. Participants were followed from the age of 3, with available follow-up until 2013. We used Cox regression to estimate the hazard ratios (HRs) relating autism to neonatal jaundice. Results Prior to accounting for covariates such as prenatal and perinatal factors, we observed an association between neonatal jaundice and autism (HR = 1.48, 95% CI: 1.37–1.60). This association significantly weakened after adjusting for potential confounders, particularly gestational age and birth weight. After adjusting for all covariates, the association nullified (HR = 1.02, 95% CI: 0.93–1.12). Conclusion The association between neonatal jaundice and autism is confounded, in particular by preterm birth. Our results highlight the importance of accounting for perinatal confounders when investigating the link between early life factors and autism, which may not always be genetic or familial.

• Kanina, Aleksandra; Stener-Victorin, Elisabet; Butwicka, Agnieszka; Öberg, Anna Sara; Rosenqvist, Mina A & Cesta, Carolyn E (2025). Adverse Cardiometabolic Outcomes in Men With Sisters With Polycystic Ovary Syndrome. Journal of Clinical Endocrinology and Metabolism (JCEM). ISSN 0021-972X. 110(11), p. e3810–e3817. doi: 10.1210/clinem/dgaf121. Full text in Research Archive Show summary

  Aims Smaller clinical studies report risks of cardiometabolic dysfunction in brothers of women with polycystic ovary syndrome (PCOS). We aim to investigate the risk of adverse cardiometabolic outcomes in men with a sister with PCOS in a large longitudinal population-based cohort. Methods Men born in Sweden (1973-2013) with ≥1 sister were followed from age 5 until 31 December 2018 (n = 1 098 203) and potential PCOS diagnoses in sisters identified. Risk of a clinical diagnosis of obesity, type 2 diabetes, or hypertension was estimated using Cox regression. In a subcohort, the association between categories of body mass index and blood pressure measured at age 18 to 20 years were estimated using logistic regression. Analyses were adjusted for birth year and parental education. Results Men with a sister with PCOS had an increased risk of obesity [adjusted hazard ratio (aHR): 2.02; 95% confidence interval (CI) 1.85-2.21], type 2 diabetes (aHR: 1.62; 95% CI: 1.34-1.96), and hypertension (aHR: 1.24; 95% CI: 1.08-1.43), compared to men with unaffected sisters. In the subcohort evaluated at age 18 to 20 (n = 147 802), having a sister with PCOS (n = 2970) was associated with being overweight [adjusted odds ratio (aOR): 1.33; 95% CI: 1.19-1.49] and obese (aOR: 1.78; 95% CI: 1.47-2.15) but not elevated blood pressure. Conclusion Having a sister with PCOS is associated with adverse cardiometabolic outcomes in men, already in early adulthood. Results contribute further knowledge on the familial impact of PCOS and highlight a patient group who may benefit from early screening and prevention.

• Hu, Kejia; Nguyen, Thuy- Dung; Borges, Karen; Kuja-Halkola, Ralf; Butwicka, Agnieszka & Brikell, Margareta Isabell [Show all 16 contributors for this article] (2025). Risk factors, impact, and healthcare use related to initial suicide attempts: comprehensive analysis of Swedish population. BMJ Medicine. 4(1). doi: 10.1136/bmjmed-2024-001129. Full text in Research Archive Show summary

  Objective To provide a comprehensive analysis of initial suicide attempts, covering incidence, risk factors, outcomes, and healthcare use in the month before and the month after the attempts. Design Comprehensive analysis of the Swedish population that included three designs: a retrospective cohort study to investigate incidence and healthcare use, a nested case-control study to investigate risk factors, and a matched cohort study to examine subsequent suicide attempts and mortality. Setting Comprehensive Swedish national registers that include patient diagnoses from hospitals and specialist outpatient care, and cause of death information updated to the end of 2019. Participants 3.7 million people born in Sweden in 1963-98 and followed from age 10 to 57 years. Main outcome measure First lifetime suicide attempt identified in patient and death registers using ICD (international classification of diseases) codes for intentional self-harm, any self-harm with lethal methods or requiring hospital admission, or any self-harm resulting in death. Results The lifetime risk of an initial suicide attempt in the study population was 4.6%, with greater risk in females and highest risk between ages 18 and 24. One in 10 families in Sweden had at least one family member who attempted suicide. Overdose and poisoning were the most common methods. Previous psychiatric disorders, general medical diseases, and adverse life events were associated with increased risk of initial suicide attempt, while higher socioeconomic status was associated with decreased risk. People with an initial suicide attempt were at substantially increased risk of subsequent attempts (hazard ratio 23.4), death by suicide (16.4), and all cause mortality (7.3). At least 60% of those who made an initial suicide attempt had a healthcare contact in the month before the attempt. Conclusions This study provides comprehensive data on the incidence, risk factors, outcomes, and healthcare use of initial suicide attempts in the Swedish population, highlighting the need for systematic prevention efforts for people who have attempted suicide for the first time.

• Haskell, Erin; Sigmarsdottir, Berglind; Thorisdottir, Ingibjorg Eva; Valborgarson, Audun; Aparicio, Elena Bonilla & Kiviruusu, Olli [Show all 15 contributors for this article] (2025). Adolescent mental health before, during, and after the COVID-19 pandemic in Iceland: a repeated, cross-sectional, population-based study. The Lancet Regional Health - Europe. 53. doi: 10.1016/j.lanepe.2025.101301. Full text in Research Archive Show summary

  Background Adolescents' mental health declined during the COVID-19 pandemic, yet little is known about the long-term outcomes after the pandemic's declassification as a global health emergency (5 May 2023). This study examined changes in adolescent mental health in Iceland from 2016 to 2023, using a bioecological framework to identify risk and protective factors. Methods Youth in Iceland surveys were administered nationwide to 13-15-year-olds in 2016, 2018, 2020, 2021, 2022 and 2023, with an average 75% response rate across the years. The surveys included measures on depressive symptoms, anxiety and hostility (Symptom Checklist-90), parental social support (Perceived Parental Support Scale), screen time, and stress/trauma exposure (Negative Life Events Scale). Stepwise-reduced mixed-effects models assessed the association of age, gender, time and risk/protective factors and their effect on mental health. Multiple imputation addressed missing data, and Bonferroni corrections adjusted for multiple testing. Findings 62,011 adolescents participated: 48.2% female (n = 29,890), 50.0% male (n = 31,002), 1.8% non-binary (n = 1119). Depressive symptoms showed signs of improvement post-pandemic (2023) compared to 2021 (β 0.19, 95% CI 0.13–0.24), yet remained higher than pre-pandemic levels (2016: β −0.38, 95% CI −0.44 to −0.33; 2018: β −0.26, 95% CI −0.31 to −0.20). Anxiety and hostility also increased and remained higher than pre-pandemic levels in 2023 (anxiety: 2016 β −0.29, 95% CI −0.35 to −0.24, 2018 β −0.20, 95% CI −0.26 to −0.15; hostility: 2016 β −0.26, 95% CI −0.31 to −0.20, 2018 β −0.12, 95% CI −0.18 to −0.07). Across all the models examining the predictors from diverse bioecological spheres, low parental social support, high social media use, and bad grades were consistently associated with poor mental health, regardless of mental health outcome and gender. Interpretation The COVID-19 pandemic has had a serious and continuing negative effect on adolescents’ mental health. Targeted interventions are needed to address the increase in mental health problems during the COVID-19 pandemic, with a focus on enhancing parental support and managing screen use.

• Kanina, Aleksandra; Sjölander, Arvid; Martini, Miriam I.; Butwicka, Agnieszka; Larsson, Henrik & Hughes, Amanda M. [Show all 11 contributors for this article] (2025). Prenatal exposure to adverse life events and autism and autistic-like traits in children in the Norwegian Mother, Father and Child Cohort Study (MoBa). JCPP Advances. 5(4). doi: 10.1002/jcv2.70002. Full text in Research Archive Show summary

  Background Mothers' experience of adverse life events (ALEs, e.g., divorce, bereavement, injury) during pregnancy has been linked with neurodevelopmental conditions like autism, and related traits like social communication difficulties and repetitive behavior in children. However, both the cumulative association and the underlying mechanism are unclear, and these associations might be confounded by unmeasured genetic or other early environmental factors shared within families. Method This longitudinal population-based cohort study included 114,247 children, born in Norway between 1999 and 2009, who participated in the Norwegian Mother, Father and Child Cohort Study. During week 30 of pregnancy, mothers of 51,940 children (of whom 12,597 were siblings) reported whether they had experienced ALEs. We estimated associations between mothers’ cumulative exposure to and perception of ALE and their children’s clinical diagnosis of autism, and maternal reports on their children's autistic traits at ages 3 and 8 years through the Social Communication Questionnaire (SCQ). Sibling comparisons were conducted to account for unmeasured familial confounding. Results Each additional prenatal ALE was associated with increased adjusted hazard ratios [HR: 1.23, 95% CI: 1.16–1.30] of autism diagnosis, compared to unexposed children. Adjusting for unmeasured familial confounding in sibling comparisons, the association attenuated: HR = 0.53, 95% CI [0.31–0.90]. ALEs perceived as more painful were associated with a 12% elevated likelihood of autism diagnosis [95% CI: 7%–16%], but this association attenuated after sibling comparisons. SCQ scores in children exposed to cumulative prenatal ALE compared to unexposed children were higher at age 3 (β-coefficient: 0.24 (95%CI [0.21–0.27])), but only slightly at age 8 (β-coefficient: 0.07 [95% CI: 0.04–0.10]) with differences nullified in the sibling comparison analysis. Conclusion The association between maternal prenatal exposure to cumulative ALEs and diagnosis of autism and autism-associated traits is likely due to unmeasured familial confounding rather than a direct causal relationship.

• Martini, Miriam I.; Kuja-Halkola, Ralf; Butwicka, Agnieszka; Rietz, Ebba Du; Kanina, Aleksandra & Brikell, Margareta Isabell [Show all 12 contributors for this article] (2025). Sex differences in psychiatric diagnoses preceding autism diagnosis and their stability post autism diagnosis. Journal of Child Psychology and Psychiatry. ISSN 0021-9630. 66(8), p. 1170–1181. doi: 10.1111/jcpp.14130. Full text in Research Archive Show summary

  Background: Autistic individuals often receive psychiatric diagnoses prior to their autism diagnosis. It remains unclear to what extent autistic females and males differ in their likelihood of receiving psychiatric diagnoses prior to their autism diagnosis and continue seeking care for them after an autism diagnosis. Methods: In a nationwide cohort of all individuals born in Sweden 1990-2015 with a clinical autism diagnosis (N = 72,331, nfemales = 24,110), we used linear and logistic regression to estimate the association between sex and (a) psychiatric diagnoses before autism diagnosis, including time trends by autism diagnosis year (2010-2020), (b) autism diagnosis age in those with preceding diagnoses, (c) stability of preceding diagnoses (defined as continued care utilization indicated through diagnosis or medication in the 5 years following autism diagnosis). Results: In total 54.2% of autistic females and 40.9% of autistic males received at least one preceding psychiatric diagnosis (most common: ADHD, anxiety, depression). Autistic females showed higher odds than males for most preceding psychiatric diagnoses (ORrange = 1.29 [1.18, 1.41]-10.69 [8.06, 14.17]), except psychotic disorders (OR = 0.91 [0.78, 1.06]) and ADHD (OR = 0.69 [0.66, 0.71]). Sex differences in preceding diagnoses were persistent across different autism diagnosis years (2010-2020). For most conditions, females with a preceding diagnosis were diagnosed with autism later than males with the same condition. For both sexes, the stability of preceding diagnoses varied considerably (23.1%-88.9%) and was less than 50% for most diagnoses. Females showed a higher stability for anxiety, sleep disorders and self-harm (ORrange = 1.45 [1.30, 1.62]-2.37 [1.93, 2.90]), and males for psychotic disorders (OR = 0.60 [0.44, 0.81]). Conclusions: Autistic females are more likely to be diagnosed with psychiatric conditions prior to an autism diagnosis and receive care for them post autism diagnosis. Our findings emphasize the variability of clinical presentation and importance of disentangling persistent support needs from overlapping diagnostic presentations, particularly in autistic females, to provide appropriate and timely care.

• Bergman, David; Roelstraete, Bjorn; Sun, Jiangwei; Ebrahimi, Fahim; Butwicka, Agnieszka & Pardi, Darrell S. [Show all 7 contributors for this article] (2024). Psychiatric disorders among 5800 patients with microscopic colitis: A nationwide population-based matched cohort study. American Journal of Gastroenterology. ISSN 0002-9270. 119(12), p. 2516–2525. doi: 10.14309/ajg.0000000000002955. Full text in Research Archive Show summary

  INTRODUCTION: Microscopic colitis (MC) is an inflammatory condition of the large intestine. Primarily diagnosed in middle-aged and older adults, the incidence of the disease has increased markedly during the past few decades. While MC is associated with a reduced quality of life, large-scale studies on the association with future psychiatric disorders are lacking. METHODS: We conducted a nationwide matched cohort study in Sweden from 2006 to 2021. Through a nationwide histopathology database (the Epidemiology Strengthened by histoPathology Reports in Sweden study), we identified 5,816 patients with a colorectal biopsy consistent with MC. These patients were matched with 21,509 reference individuals from the general population all of whom with no previous record of psychiatric disorders. RESULTS: From 2006 to 2021, 519 patients with MC (median age 64.4 years [interquartile range = 49.5–73.3]) and 1,313 reference individuals were diagnosed with psychiatric disorders (9.9 vs 6.5 events per 1,000 person-years), corresponding to 1 extra case of psychiatric disorder in 29 patients with MC over 10 years. After adjustments, the hazard ratio for psychiatric disorders was 1.57 (95% confidence interval = 1.42–1.74). We found significantly elevated estimates up to 10 years after MC diagnosis and a trend toward higher risk with increasing age. Specifically, we observed increased risks for unipolar depression, anxiety disorders, stress-related disorders, substance abuse, and suicide attempts. In sibling-controlled analysis, the adjusted hazard ratio was 1.76 (95% confidence interval = 1.44–2.15). DISCUSSION: Patients with MC are at increased risk of incident psychiatric disorders compared with the general population.

• Dong, Zihan; Zhang, Le; Li, Lin; Liu, Shengxin; Brikell, Margareta Isabell & Kuja-Halkola, Ralf [Show all 12 contributors for this article] (2024). Cumulative ADHD medication use and risk of type 2 diabetes in adults: a Swedish Register study. BMJ Mental Health. 27(1), p. 1–8. doi: 10.1136/bmjment-2024-301195. Full text in Research Archive Show summary

  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: 0<duration≤1 year, 0.79 (95% CI, 0.69 to 0.91); 1<duration≤3 years, 0.80 (95% CI, 0.69 to 0.92); duration>3 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.

• Martini, Miriam I.; Butwicka, Agnieszka; Rietz, Ebba Du; Kanina, Aleksandra; Rosenqvist, Mina A. & Larsson, Henrik Bo W. [Show all 8 contributors for this article] (2024). Age effects on autism heritability and etiological stability of autistic traits. Journal of Child Psychology and Psychiatry. ISSN 0021-9630. 65(9), p. 1135–1144. doi: 10.1111/jcpp.13949. Full text in Research Archive Show summary

  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.

• Påhlsson-Notini, Andreas; Liu, Shengxin; Tideman, Magnus; Latvala, Antti; Serlachius, Eva & Larsson, Henrik Bo W. [Show all 11 contributors for this article] (2024). Substance use-related problems in mild intellectual disability: A Swedish nationwide population-based cohort study with sibling comparison. JCPP Advances. 4(2). doi: 10.1002/jcv2.12225. Full text in Research Archive Show summary

  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.

• Ahlberg, Rickard; Garcia-Argibay, Miguel; Rietz, Ebba Du; Butwicka, Agnieszka; Cortese, Samuele & D’Onofrio, Brian M. [Show all 8 contributors for this article] (2023). Associations Between Attention-Deficit/Hyperactivity Disorder (ADHD), ADHD Medication, and Shorter Height: A Quasi-Experimental and Family-Based Study. Journal of the American Academy of Child and Adolescent Psychiatry. ISSN 0890-8567. 62(12), p. 1325–1325. doi: 10.1016/j.jaac.2023.03.015. Full text in Research Archive
• Liu, Shengxin; Larsson, Henrik; Kuja-Halkola, Ralf; Lichtenstein, Paul; Butwicka, Agnieszka & Taylor, Mark J (2023). Age-related physical health of older autistic adults in Sweden: a longitudinal, retrospective, population-based cohort study. The Lancet Healthy Longevity. 4(7). doi: 10.1016/s2666-7568(23)00067-3. Full text in Research Archive
• Taylor, Mark J.; Martin, Joanna; Butwicka, Agnieszka; Lichtenstein, Paul; D'Onofrio, Brian & Lundström, Sebastian [Show all 8 contributors for this article] (2023). A twin study of genetic and environmental contributions to attention‐deficit/hyperactivity disorder over time. Journal of Child Psychology and Psychiatry. ISSN 0021-9630. 64(11), p. 1608–1616. doi: 10.1111/jcpp.13854. Full text in Research Archive Show summary

  Background Attention-deficit/hyperactivity disorder (ADHD) is an increasingly commonly diagnosed neurodevelopmental condition. One possibility is that this reflects a genuine increase in the prevalence of ADHD due to secular environmental changes, yet this hypothesis remains untested. We therefore investigated whether the genetic and environmental variance underlying ADHD, and traits of ADHD, has changed over time. Methods We identified twins born from 1982 to 2008 from the Swedish Twin Registry (STR). We linked the STR with the Swedish National Patient Register and Prescribed Drug Register to identify diagnoses of ADHD and prescriptions of ADHD medication for these twins. We also utilized data collected from participants in the Child and Adolescent Twin Study in Sweden (CATSS), born from 1992 to 2008. Their parents completed a structured ADHD screening tool, which was used to measure traits of ADHD and assign broad screening diagnoses of ADHD. We used the classical twin design to test whether the degree to which variation in these measures was influenced by genetic and environmental variation changed over time. Results We included 22,678 twin pairs from the STR and 15,036 pairs from CATSS. The heritability of ADHD in the STR ranged from 66% to 86% over time, although these fluctuations were not statistically significant. We observed a modest increase in variance in ADHD traits, from 0.98 to 1.09. This was driven by small increases in the underlying genetic and environmental variance, with heritability estimated as 64%–65%. No statistically significant changes in variance in screening diagnoses were observed. Conclusions The relative contribution of genetic and environmental factors to ADHD has remained stable over time, despite its increasing prevalence. Thus, changes in the underlying etiology of ADHD over time are unlikely to explain the increase in ADHD diagnoses.

• Ahlberg, Rickard; Garcia-Argibay, Miguel; Taylor, Marc; Lichtenstein, Paul; D'Onofrio, Brian M & Butwicka, Agnieszka [Show all 10 contributors for this article] (2023). Prevalence of sleep disorder diagnoses and sleep medication prescriptions in individuals with ADHD across the lifespan: a Swedish nationwide register-based study. BMJ Mental Health. 26(1). doi: 10.1136/bmjment-2023-300809. Full text in Research Archive Show summary

  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.

• Kanina, Aleksandra; Larsson, Henrik Bo W.; Sjölander, Arvid; Butwicka, Agnieszka; Taylor, Mark J. & Martini, Miriam I. [Show all 10 contributors for this article] (2023). Association between cumulative psychosocial adversity in the family and ADHD and autism: a family-based cohort study. Translational Psychiatry. 13(1). doi: 10.1038/s41398-023-02571-7. Full text in Research Archive Show summary

  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.

• Khemiri, Lotfi; Kuja-Halkola, Ralf; Larsson, Henrik Bo W.; Butwicka, Agnieszka; Tideman, Magnus & D'Onofrio, Brian M. [Show all 8 contributors for this article] (2023). Parental substance use disorder and risk of intellectual disability in offspring in Sweden: a national register study. EClinicalMedicine. 63. doi: 10.1016/j.eclinm.2023.102170. Full text in Research Archive Show 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.

• Liu, Shengxin; Lagerberg, Tyra; Ludvigsson, Jonas F.; Taylor, Mark J.; Chang, Zheng & D'Onofrio, Brian M. [Show all 11 contributors for this article] (2023). Psychotropic Medication Use in Children and Adolescents With Type 1 Diabetes. JAMA Network Open. 6(10). doi: 10.1001/jamanetworkopen.2023.36621. Full text in Research Archive Show summary

  Importance Children and adolescents with type 1 diabetes (T1D) face elevated risks of psychiatric disorders. Despite their nonnegligible adverse effects, psychotropic medications are a common cost-effective approach to alleviating psychiatric symptoms, but evidence regarding their dispensation to children and adolescents with T1D remains lacking. Objective To examine the trends and patterns of psychotropic medication dispensation among children and adolescents with T1D in Sweden between 2006 and 2019. Design, Setting, and Participants This cohort study used data from multiple Swedish registers. The main study cohort included children and adolescents residing in Sweden from 2006 to 2019 and was followed up until the earliest of December 31, 2019, 18th birthday, emigration, or death. Data analyses were conducted from November 1, 2022, to April 30, 2023. Exposures Type 1 diabetes. Main Outcomes and Measures The primary outcomes were trends and patterns of psychotropic medication dispensation (including antipsychotics, antidepressants, anxiolytics, hypnotics, mood stabilizers, and medications for attention-deficit/hyperactivity disorder [ADHD]), psychotropic medication initiation, and history of neurodevelopmental and psychiatric diagnosis. Cumulative incidence curves and Cox proportional hazard models were used to estimate the aggregated incidence and hazard ratios of medication initiation after diabetes onset. Results Of 3 723 745 children and adolescents (1 896 199 boys [50.9%]), 13 200 (0.4%; 7242 boys [54.9%]) had T1D (median [IQR] age at diagnosis, 11.1 [7.6-14.7] years). Between 2006 and 2019, psychotropic medication dispensation increased from 0.85% (95% CI, 0.65%-1.10%) to 3.84% (3.11%-4.69%) among children and from 2.72% (95% CI, 2.15%-3.39%) to 13.54% (95% CI, 12.88%-14.23%) among adolescents with T1D, consistently higher than their peers without T1D. The most commonly dispensed medications included hypnotics, ADHD medications, anxiolytics, and selective serotonin reuptake inhibitors, and all exhibited increasing trends. For those with T1D, psychiatric care was the primary prescription source, and up to 50.1% of treatments lasted more than 12 months. In addition, children and adolescents with T1D showed higher cumulative incidence and hazard ratios of medication initiation after diabetes onset than their same-age and same-sex counterparts. Conclusions and Relevance This cohort study found an increasing trend in psychotropic medication dispensation among children and adolescents with T1D from 2006 to 2019, persistently higher than those without T1D. These findings call for further in-depth investigations into the benefits and risks of psychotropic medications within this population and highlight the importance of integrating pediatric diabetes care and mental health care for early detection of psychological needs and careful monitoring of medication use.

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• Kuśmierczyk-Kozieł, Hanna; Michalak, Arkadiusz; Chrzanowski, Jędrzej; Błaziak, Katarzyna; Mianowska, Beata & Szadkowska, Agnieszka [Show all 24 contributors for this article] (2025). Multicenter screening for ADHD among school-age pediatric patients with type 1 diabetes–study protocol. doi: 10.1080/08039488.2025.2455555. Full text in Research Archive Show summary

  Purpose Attention-deficit hyperactivity disorder (ADHD) is a common neurodevelopmental condition that affects approximately 5% of the pediatric population, with increased prevalence among those with type 1 diabetes (T1D). Reports suggest that unrecognized and untreated ADHD impairs T1D control and that ADHD may be underdiagnosed in the Polish population. The International Society for Pediatric and Adolescent Diabetes recommends neurodevelopmental assessments in children with T1D, but specific guidelines on procedures and implementation are lacking. Therefore, we designed a systemic screening protocol aimed at assessing the prevalence of ADHD among Polish children with T1D that could be utilized in clinical practice. Materials and methods The protocol for the study was approved by the Bioethical Committee at the Medical University of Lodz (RNN/280/21/KE). Participation is offered to all children aged 8–16 y.o. with T1D duration ≥1 year and without significant comorbidities (epilepsy, intellectual disability). The protocol includes a first-line procedure using the short version of the Conners 3 questionnaire and on-site structured consultation with a psychologist for those with increased risk of ADHD (utilizing detailed Conners 3 and MINI-Kid questionnaires), followed by a video consultation with a psychiatrist. Results The screening was initiated between January and May 2023 and is ongoing in four Polish reference pediatric centers. These centers provide diabetes care to approximately 2,500 youth with T1D. Over 36 months, our goal is to assist in diagnosing ADHD in approximately 190 children. Conclusions Comorbidity of ADHD and T1D remains an unrecognized challenge for pediatric psychiatric and diabetes care, and there is a need for effective diagnostic protocols.

• Michalak, Arkadiusz; Chrzanowski, Jȩdrzej; Kuśmierczyk-Kozieł, Hanna; Klejman, Ewa; Błaziak, Katarzyna & Mianowska, Beata [Show all 16 contributors for this article] (2023). Lisdexamphetamine versus methylphenidate for paediatric patients with attention-deficit hyperactivity disorder and type 1 diabetes (LAMAinDiab): Protocol for a multicentre, randomised cross-over clinical trial in an outpatient telemedicine-supported setting. BMJ Open. 13(12). doi: 10.1136/bmjopen-2023-078112. Full text in Research Archive Show summary

  Introduction Attention deficit hyperactivity disorder (ADHD) affects 5%–10% of paediatric population and is reportedly more common in children with type 1 diabetes (T1D), exacerbating its clinical course. Proper treatment of ADHD in such patients may thus provide neurological and metabolic benefits. To test this, we designed a non-commercial second phase clinical trial comparing the impact of different pharmacological interventions for ADHD in children with T1D. Methods and analysis This is a multicentre, randomised, open-label, cross-over clinical trial in children and adolescents with ADHD and T1D. The trial will be conducted in four reference paediatric diabetes centres in Poland. Over 36 months, eligible patients with both T1D and ADHD (aged 8–16.5 years, T1D duration >1 year) will be offered participation. Patients’ guardians will undergo online once-weekly training sessions behaviour management for 10 weeks. Afterward, children will be randomised to methylphenidate (long-release capsule, doses 18-36-54 mg) versus lisdexamphetamine (LDX, 30-50-70 mg). Pharmacotherapy will continue for 6 months before switching to alternative medication. Throughout the trial, the participants will be evaluated every 3 months by their diabetologist and online psychological assessments. The primary endpoint (ADHD symptom severity, Conners 3.0 questionnaire) will be assessed by a blinded investigator. Secondary endpoints will include HbA1c, continuous glucose monitoring indices and quality-of-life (PedsQL).

• Kanina, Aleksandra; Larsson, Henrik Bo W.; Sjölander, Arvid; Butwicka, Agnieszka; Taylor, Mark J. & Martini, Miriam I. [Show all 10 contributors for this article] (2023). Correction: Association between cumulative psychosocial adversity in the family and ADHD and autism: a family-based cohort study (Translational Psychiatry, (2023), 13, 1, (282), 10.1038/s41398-023-02571-7). Translational Psychiatry. 13(1). doi: 10.1038/s41398-023-02595-z. Full text in Research Archive

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