BACKGROUND:Neurodevelopmental conditions (NDC), including attention deficit/hyperactivity disorder (ADHD) and autism, are associated with increased rates of neurodegenerative diseases, including Alzheimer's disease and related dementias (ADRD) and Parkinson's disease. Such associations are unstudied in diverse populations and while controlling for a range of important covariates. The purpose of this study was to examine the association of ADRD and Parkinson's disease with NDCs in a diverse sample of adults. METHODS:This case-control study used data from the United States All of Us Research Program 2018-2023 from approximately 600 000 adults in the United States. We matched on ADRD and Parkinson's disease status to examine the association of these conditions with NDCs. RESULTS:NDC was more prevalent in ADRD cases than in non-ADRD controls (7.8% vs 2.4%) and among Parkinson's disease cases than non-Parkinson's disease controls (4.5% vs 1.8%). After adjustment for sex, age, education level, body mass index, cardiometabolic conditions, and psychiatric conditions, individuals with ADRD had significantly higher odds of having an NDC compared with controls (adjusted odds ratio, 2.68; 95% CI, 2.40-2.99). Similarly, Parkinson's disease cases had 2.09 times the odds of having an NDC as non-Parkinson's disease controls (95% CI 1.66, 2.59) in adjusted models. CONCLUSIONS:As the population of individuals with NDCs ages, and more older adults find themselves in the care of clinicians with expertise in ADRD and Parkinson's disease, it is imperative to understand the support needs of this population, and to provide targets for reducing ADRD prevalence in younger or middle adulthood.

Importance:Public concern and speculation have emerged around a possible link between neonatal male circumcision (NMC) and autism spectrum disorder (ASD). Evidence is limited and inconsistent. Objective:To examine associations between NMC and child ASD and autism-related traits and behaviors. Design, Setting, and Participants:This prospective cohort study was conducted among cohort sites participating in the Environmental Influences on Child Health Outcomes (ECHO) Cohort between February 2003 and September 2025. Statistical analyses were conducted from November 2025 to February 2026. The analysis included male, singleton children with data on NMC status and child ASD. Exposure:NMC status within 28 days of birth at a medical facility. Main outcomes and Measures:ASD diagnosis was based on parent report of diagnosis by a medical professional or documentation of criterion standard clinical assessments. Social Responsiveness Scale (SRS-2) T-scores assessed the presence and distribution of autism traits, and Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) Autism Spectrum Problems subscale T-scores from the Child Behavior Checklist (CBCL) 1.5/5 assessed the occurrence of child autism-related behaviors. Results:The sample included 2771 male children from 14 ECHO sites, of whom 1840 (66%) were circumcised before hospital discharge, and 192 (7%) had an autism diagnosis. Among 1840 circumcised males, 108 (6%) had autism, compared with 84 of 931 uncircumcised males (9%). Mean (SD) age at autism diagnosis was 3.8 (2.2) years. Among circumcised males, 31 (4%) were administered acetaminophen during the procedure, and 128 (7%) within the 30 days after birth. After adjusting for confounders, there was no association between NMC and ASD diagnosis (odds ratio [OR], 0.83; 95% CI, 0.59-1.17). After stratification by region, preterm birth, and neonatal intensive care unit admission, an inverse or no association was observed between NMC and ASD diagnosis. Adjusted analyses showed no associations between NMC and SRS-2 continuous (β = -0.62; 95% CI, -1.46 to 0.22) or binary (OR, 0.75; 95% CI, 0.48-1.15) T-scores. Similarly, no associations were observed between NMC and CBCL 1.5/5 continuous (β = 0.01; 95% CI, -0.54 to 0.56) or binary (OR, 1.30; 95% CI, 0.75-2.26) T-scores. Overall, inverse or no associations were observed across all strata for SRS-2 and CBCL 1.5/5 outcomes. Conclusions and Relevance:This cohort study yielded no evidence that NMC was associated with ASD risk, whether assessed by parent report of medical professional diagnosis or validated instruments measuring autism-related traits and behavior. These findings may provide reassurance for families who are considering or have elected NMC for their child.

Findings from family-based analyses, such as sibling comparisons, are often reported using only odds ratios or hazard ratios. We demonstrate how this can be improved upon by applying the marginalized between-within framework. We provide an overview of sibling comparison methods and the marginalized between-within framework, which enables estimation of absolute risks and clinically relevant metrics while accounting for shared familial confounding. We illustrate the approach using Swedish registry data to examine the association between maternal smoking and infant mortality, estimating absolute quantities (e.g., cumulative risks), average treatment effects, attributable fractions, and numbers needed to harm (or treat). The marginalized between-within model decomposes effects into within- and between-family components while applying a global baseline across all families. Although it typically yields similar relative estimates to conditional logistic or stratified Cox regression, the model’s specification of a baseline enables the estimation of absolute measures. In the applied example, absolute measures provided more interpretable and policy-relevant insights than relative estimates alone. Code for implementation in Stata and R is provided. The marginalized between-within framework may strengthen the interpretability of family-based analysis by enabling absolute and policy-relevant estimates for both binary and time-to-event outcomes, moving beyond the limitations of solely relying on relative effect measures.

Abstract Objective To understand if sociodemographic and neuropsychiatric characteristics of people diagnosed with autism in the United Kingdom (UK) and Sweden have changed since 2010. Design Cross-context population-based cohort studies. Setting UK primary care records from 2010-2023 and Swedish population-wide register linkages from 2010-2021 Participants 24,537,039 individuals age 16 or over, registered with general practices in the UK, including 141,119 with an autism diagnosis. 9,096,874 people age 16 or over in the Swedish Total Population Register, including over 100,817 with an autism diagnosis. Main outcome measures Annual age-standardised incidence and prevalence of adult autism diagnoses within different sociodemographic groups. Annual age-standardised proportion of adults with new autism diagnoses, lifetime autism diagnoses, and no autism diagnoses, with prior records of other neuropsychiatric conditions or medications. Results Incident adult autism diagnoses were consistently higher in Sweden than the UK, however incidence increased rapidly in the UK after 2020. Incident diagnoses increased fastest for 16-20-year-olds and females in both nations, as well as people in White ethnic groups in the UK and people with Swedish-born parents in Sweden. For example, in the UK in 2023 the age-standardised incidence of autism diagnoses among 16-65 years olds was 11 diagnoses per 10,000 person-years (95%CI: 10.7, 11.3) in the White ethnic group and 2.2 diagnoses per 10,000 person-years (95%CI: 1.9, 2.5) in the South Asian ethnic group. Over time there has been a consistent decline in the proportion of autistic adults with a prior diagnosis of epilepsy, psychosis and intellectual disability and an increase in the proportion with a prior diagnosis of ADHD, anxiety, depression and several other mental illnesses. For example, in the UK between 2010 and 2023 the age-standardised proportions of newly diagnosed autistic adults with prior records of epilepsy decreased from 10% (95%CI: 7.6, 13) to 4% (95%CI: 3.6, 4.5), while the proportion with records of anxiety increased from 28.7% (95%CI: 24.4, 33.6) to 58.3% (95%CI: 56.6, 60.1). Mental health conditions were generally more common in females and the reduction over time in intellectual disability was greater in females than males. Conclusions The socio-demographic and neuro-psychiatric characteristics of individuals diagnosed as autistic have changed dramatically since 2010, a phenomenon observed both in the UK and Sweden. The extent to which these changes indicate nuanced recognition of autism or broadening of diagnostic practice needs investigation. Summary box What is already known on this topic? Autism diagnoses have increased internationally, with prevalence in high income countries starting to overtake estimates from population survey-based methods. It is unclear how much this reflects improved understanding of nuanced presentations or broadening of the medical concept of autism beyond coherent boundaries. What this study adds The social and medical backgrounds of people receiving autism diagnoses has changed dramatically over time, particularly for females in the UK. This suggests that: (1) diagnoses are inequitably distributed in society, (2) other mental health conditions are adding complexity to the diagnostic process, and (3) the average health needs of autistic groups are evolving with consequences for public health policy. Further research is required to understand the drivers of these changes and consequences on the provision of support for autistic people.

Promoting access to effective depression treatment represents a crucial opportunity to mitigate increased suicide risk. We examined treatment trajectories for 8- to 29-year-old autistic enrollees of Medicaid, the U.S. safety net insurance program, with a new claim for major depressive disorder (MDD; N = 44,074). Using group-based trajectory modeling, we identified groups with similar probabilities of receiving psychotherapy or antidepressants in the 5 months following their new MDD claim - a period of acute treatment need. We also examined odds of trajectory group membership by demographic factors and co-occurring intellectual disability (ID) using multinomial logistic regression. Trajectory modeling suggested existence of four treatment trajectories: no/limited treatment (39%), gradual treatment decline (21%), late treatment initiation (14%), and continuous treatment (25%). Adjusted odds of continuous treatment, relative to no/limited treatment, were lower for Black enrollees (odds ratio [OR]: 0.63, 95% confidence interval [CI]: [0.59, 0.68]), Hispanic enrollees (OR: 0.58, 95% CI: [0.54, 0.62]), and those with co-occurring ID (OR: 0.84, 95% CI: [0.79, 0.89]), and highest for 8- to 12-year-olds (OR: 1.80, 95% CI: [1.60, 2.03]) and females (OR: 1.15, 95% CI: [1.09, 1.21]). Many Medicaid-enrolled autistic people do not receive depression treatment. Improving treatment in autistic enrollees requires varied and multi-faceted approaches that must consider demographic and clinical factors.Lay AbstractWe wanted to know if autistic people on Medicaid get therapy or antidepressants after being diagnosed with depression. We also looked at whether people who are also diagnosed with intellectual disability, are female, are children, or are Black or Hispanic are more or less likely to get this care. Earlier studies show that just over half of the people on Medicaid get any treatment after being diagnosed with depression. But no one has looked closely at autistic people on Medicaid. Getting treatment can help reduce depression symptoms and may lower the risk of suicide. In our study, we looked at autistic people on Medicaid who were newly diagnosed with depression. We tracked whether they got therapy or antidepressants over the next 5 months. We grouped people based on how much treatment they got. The largest group (39%) got no treatment. The second group (21%) started treatment but did not continue for all 5 months. The third group (14%) started treatment around the third month and kept going for 2 months. The last group (25%) got treatment for all 5 months. Autistic people who were Black, Hispanic, or had intellectual disability were least likely to get enough treatment. Autistic children and females were most likely to get enough treatment. In short, many autistic people are not getting the care they need for depression. Some may not get enough treatment to feel better. This can make depression last longer and raise the risk of suicide. We need to improve access to care, especially for those who are least likely to get it.

BACKGROUND:Although lithium has been used effectively as a medication to treat bipolar and major depressive disorders, there are limited data defining lithium use patterns during pregnancy. AIMS:To investigate trends and patterns of lithium prescribing in the perinatal period (before, during and after pregnancy) among pregnancies in the UK. METHOD:We conducted a population-based study using primary healthcare records from the Clinical Practice Research Datalink GOLD, analysing 752 112 pregnancies during the period 1995-2018. We assessed the prevalence and patterns of lithium prescriptions, including discontinuation, continuation and dosage. Maternal characteristics were defined for lithium non-users and users, and between those who continued and discontinued use. RESULTS:From 1995 to 2018, the prevalence of lithium prescribing per 10 000 pregnancies was 3.02 (95% CI: 2.64, 3.44) before pregnancy, 1.89 (95% CI: 1.59, 2.23) during pregnancy and 2.81 (95% CI: 2.44, 3.21) postpartum. Prescribing during pregnancy was low across the study period, with the most recent prevalence in 2018 of 1.03 (95% CI: 0.26, 4.11) per 10 000 pregnancies. Among 337 pregnancies with perinatal lithium prescribing, 48.4% involved a diagnosis of bipolar disorder. Of 227 pregnancies where lithium was prescribed preconception, 15.4% continued treatment throughout pregnancy; discontinuation occurred before pregnancy in 20.7%, and during second or third trimester in 30.8%; 33.0% followed other prescribing patterns. Women who discontinued lithium were more likely to be younger, have a body mass index ≥30 kg/m2, a diagnosis of bipolar disorder, a history of smoking and >10 primary care consultations in the 12 months preconception, compared with those who continued treatment. CONCLUSIONS:Lithium prescribing during pregnancy in the UK is uncommon and discontinuation is frequent, particularly in the later stages of pregnancy. These findings highlight the need for proactive perinatal mental healthcare strategies and close clinical monitoring, to reduce unintentional first-trimester exposure while ensuring continuity of care for maternal mental health.

Antidepressant prescribing and autism diagnoses have increased in recent years. We aimed to describe and compare trends in antidepressant prescribing, indications, doses and durations in autistic and non-autistic males and females in the United Kingdom (UK) from 1997 to 2023. Using population-representative UK primary care records, we defined three autistic groups-autistic adults with intellectual disability (ID), autistic adults without ID and all autistic adults-and four non-autistic groups. In each calendar year we calculated: annual, lifetime and new antidepressant prescribing; indications for serotonin-selective reuptake inhibitor initiation; average doses prescribed for citalopram, fluoxetine, and sertraline; and the proportion of courses that lasted over 1, 2, and 3 years. We also repeated analyses with sex-stratification. In all, 34,173,295 non-autistic adults and 172,242 autistic adults were included (47,011 with ID and 125,231 without ID). 30% of autistic adults and 14.7% of non-autistic adults were prescribed an antidepressant in 2023. Prescriptions, doses and course durations increased over time for all groups. Prescriptions were highest in autistic adults without ID and females, whereas course durations were highest in autistic adults with ID. Recording of depression and anxiety as indications was lower for those with ID. Antidepressant prescribing has increased more for autistic adults than non-autistic adults since 1997, with more new starters, higher doses and longer course durations. This potentially increases the risk of adverse medication effects for autistic adults and emphasizes the need for stronger evidence around the effectiveness and tolerability of mental health interventions and the reasons for systematic differences in prescribing.

Background: Sibling-matched designs control for shared familial confounding but remain vulnerable to non-shared confounders. Bi-directional sensitivity analyses, which stratify families by whether the older or younger sibling was exposed, are commonly used to assess carryover effects. We aimed to demonstrate how this methodological approach can introduce severe confounding by parity. Methods: We conducted simulations motivated by a recent epidemiological study. The true causal effect of a hypothetical exposure (prenatal acetaminophen) on neurodevelopmental outcomes was set to strictly null. To introduce parity-related confounding, baseline exposure and outcome probabilities were varied slightly by birth order. We compared conditional logistic regression effect estimates from total sibling models against bi-directional stratified models. Results: In the total simulated sibling cohort, models yielded the true null effect (odds ratio = 1.00) when adjusting for parity. However, the bi-directional analyses exhibited divergent artifactual signals. Because parity is perfectly collinear with exposure in these stratified subsets, it cannot be adjusted for. For example, when the older sibling was exposed, the odds ratio for autism spectrum disorder was 1.68; when the younger was exposed, the odds ratio was 0.60. Conclusions: Divergent estimates in bi-directional sibling analyses can be a predictable artifact of parity confounding rather than evidence of carryover effects or invalidating unmeasured bias. Overall sibling models adjusting for parity may remain robust despite divergent stratified sensitivity results. ### Competing Interest Statement Disclosures BKL reports speaking fees from Gerson Lehrman Group; consulting fees from AlphaSights; ser-vice as an academic council member for Cura AI; and work as an expert reviewer for SciPinion, all outside the submitted work. VHA reports speaking fees from Angelini Pharma, outside the submitted work. ### Funding Statement Funding VHA is funded by Swedish Society for Medical Research (PG-24-0427) BKL is funded by NIH 1OT2OD040415. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present work are contained in the Supplement.

This JAMA Guide to Statistics and Methods explains how sibling analysis can be used to account for confounding in observational studies, using the example of a study on acid suppressants during pregnancy and risk of neuropsychiatric disorders in offspring.

The transition to adult healthcare is a vulnerable time for individuals with autism spectrum disorder (ASD). Prior research using Medicaid data (2001–2005) found this group had declining utilization rates into adulthood for some types of care (e.g., psychiatric outpatient). Substantial changes to Medicaid and the ASD population have occurred since this time. We reassessed healthcare resource utilization (HCRU) across the transition to adulthood Medicaid claims data from 2015 to 2019. We selected enrollees with at least one fee for service claim, aged 16–19 years in 2015, who were also enrolled in 2019 using diagnostic groupings: ASD/no ID (n = 23,460), ID/no ASD (n = 21,256) and ASD + ID (n = 10,115). HCRU indicators included utilization rates and per capita expenditures for outpatient, inpatient, long-term, and medication care, with each type further divided into psychiatric and non-psychiatric (i.e., medical). The ID groups had overall higher HCRU than the ASD only group. ASD + ID adults had especially high HCRU for psychiatric outpatient care. HCRU increased into adulthood for psychiatric outpatient and long-term care, driven by higher expenditures among those with >0 expenditures. HCRU declined into adulthood for inpatient care and medication use. In contrast to 2001–2005, having an ID diagnosis resulted in greater HRCU across transition to adulthood, potentially reflecting changes in the Medicaid ASD population over time. Consistent with 2001–2005, utilization rates generally declined for all three groups across the transition to adulthood. Greater expenditure among those using psychiatric outpatient and long-term care in adulthood resulted in greater overall resource utilization than adolescence.

IMPORTANCE:Individuals with psychiatric disorders have increased risk of cardiometabolic diseases (CMDs). Evaluating how psychiatric genetic liability relates to CMD may clarify mechanisms. OBJECTIVE:Identify genetic overlap between psychiatric disorders and CMDs independent of cross-disorder pleiotropy, BMI, and smoking. DESIGN SETTING AND PARTICIPANTS:Three Northern European cohorts (the Swedish Twin Registry, the Estonian Biobank, and the Norwegian Mother, Father and Child Cohort Study [MoBa]) totaling 355,159 individuals. Associations with CMDs were estimated as adjusted odds ratios (AORs) from logistic models mutually adjusted for all psychiatric PRSs and in models additionally adjusting for body mass index (BMI) and smoking. Cohort-specific AORs were pooled by inverse-variance weighting. MAIN OUTCOMES AND MEASURES:Exposures were PRSs for attention-deficit/hyperactivity disorder (ADHD), major depressive disorder (MDD), anxiety disorder, posttraumatic stress disorder (PTSD), bipolar disorder, and schizophrenia. Outcomes were diagnoses of CMDs (hyperlipidemia, obesity, type 2 diabetes, hypertensive diseases, arteriosclerosis, ischemic heart disease, heart failure, thromboembolic disease, cerebrovascular disease, and arrhythmias), ascertained from electronic health records. RESULTS:The MDD PRS was associated with increased risk of all CMDs across analyses (AORs ranged from 1.13 [95% CI, 1.10-1.15] for heart failure to 1.02 [95% CI, 1.00-1.05] for arrhythmias). The ADHD PRS was associated with increased risk of all CMDs (AOR ranged from 1.11 [95% CI, 1.09-1.12] for obesity to 1.02 [95% CI, 1.01-1.03] for hyperlipidemia), however associations where attenuated when adjusting for BMI and smoking (lifestyle adjusted AOR for obesity: 1.03 [95% CI, 1.02-1.05]). When not mutually adjusting for all psychiatric PRSs, anxiety disorder and PTSD PRSs were associated with all CMDs; these associations diminished after adjustment. The bipolar and schizophrenia PRSs were inversely associated with most CMDs (AOR for schizophrenia PRS and obesity, 0.93 [95% CI, 0.92-0.94]). CONCLUSIONS AND RELEVANCE:Associations between psychiatric PRSs and CMDs diverged: ADHD, MDD, anxiety disorder, and PTSD PRSs were positively associated with CMDs, whereas bipolar and schizophrenia PRSs were inversely associated. Genetic liability to MDD showed robust associations with CMDs independent of cross-disorder pleiotropy, BMI, and smoking status, whereas associations between the ADHD PRS and CMDs were largely attenuated after adjustment for BMI and smoking.

Background The first generation of individuals diagnosed with neurodevelopmental conditions such as autism spectrum disorder and attention-deficit/hyperactivity disorder are now entering late adulthood. Emerging evidence suggests phenotypic correlations between early-life neurodevelopmental conditions and late-life neurodegenerative diseases, including Parkinson’s disease, Alzheimer’s disease, and amyotrophic lateral sclerosis. While clinical and biological links between these groups of disorders have been proposed, it remains unclear whether they share a common genetic architecture. Familial co-aggregation indicates possible genetic overlap, but genotype-based investigations have thus far been limited—focusing largely on genome-wide correlation estimates or candidate gene studies. Methods We leveraged the latest summary statistics from large-scale genome-wide association studies of autism spectrum disorder, attention-deficit/hyperactivity disorder, Parkinson’s disease, Alzheimer’s disease, and amyotrophic lateral sclerosis to investigate shared genetic architecture at multiple levels. We applied three complementary approaches: genome-wide correlation using linkage disequilibrium score regression, local genetic correlation using LAVA, and polygenic overlap estimation using MiXeR. We also conducted Mendelian randomization to explore potential causal pathways. Results Consistent with prior studies, we observed marginal genome-wide genetic correlations between neurodevelopmental and neurodegenerative conditions (all global Rg between –0.11 and 0.16; p > 0.5), and little evidence of causal links using Mendelian randomization. However, local genetic correlation analyses identified 17 loci with statistically significant correlations—both positive and negative—after correction for multiple testing. These included 9 loci for Alzheimer’s disease, 6 for Parkinson’s disease, and 2 for amyotrophic lateral sclerosis, each associated with either autism spectrum disorder or attention-deficit/hyperactivity disorder, suggesting region-specific pleiotropy. MiXeR revealed a key asymmetry: neurodevelopmental conditions, particularly autism spectrum disorder, were highly polygenic, with thousands of independent variants contributing to heritability, whereas neurodegenerative diseases showed substantially lower polygenicity. This imbalance likely obscures genome-wide genetic overlap. However, when viewed from the perspective of neurodegenerative conditions, a substantial proportion of their heritability—up to approximately 50% in the case of Alzheimer’s disease—was attributable to variants also associated with autism spectrum disorder or attention-deficit/hyperactivity disorder. Discussion Despite low global genetic correlations, substantial polygenic overlap exists between neurodevelopmental and neurodegenerative diseases, particularly when analyses are anchored on the genetic architecture of neurodegenerative conditions. These findings suggest that standard genome-wide correlation metrics may underestimate shared genetic risk due to opposing effect directions and marked differences in polygenicity. Methods that directly model causal variant overlap offer a clearer view of the convergent genetic basis that may underlie observed epidemiological associations and familial co-aggregation patterns.

ABSTRACT The goal of this article is to summarize common methods of antibiotic measurement used in clinical research and demonstrate analytic methods for selection of exposure variables. Variable selection was demonstrated using three methods for modeling exposure, using data from a case-control study on Clostridioides difficile infection in hospitalized patients: 1) factor analysis of mixed data, 2) multiple logistic regression models, and 3) Least Absolute Shrinkage and Selection Operator (LASSO) regression. The factor analysis identified 9 variables contributing the most variation in the dataset: any antibiotic treatment ; number of classes ; number of treatments ; dose ; and classes monobactam , β -lactam β -lactamase inhibitors , rifamycin , carbapenem , and cephalosporin . The regression models resulting in the best model fit used predictors any antibiotic exposure and proportion of hospitalization on antibiotics . The LASSO model selected 22 variables for inclusion in the predictive model, exposure variables including: any antibiotic treatment ; classes β -lactam β -lactamase inhibitors , carbapenem , cephalosporin , fluoroquinolone , monobactam , rifamycin , sulfonamides , and miscellaneous ; and proportion of hospitalization on antibiotics . Investigators studying antibiotic exposure should consider multiple aspects of treatment informed by their research question and the theory on how antibiotics may impact the distribution of the outcome in their target population.

Background: Antidepressant prescribing and autism diagnoses have both increased in recent years, however antidepressant prescribing patterns for autistic adults are not well understood. Aims: (1) To describe antidepressant trends in autistic and non-autistic adults in the UK from 1997 to 2023. (2) To compare trends between autistic adults and age- and sex-matched non-autistic adults. (3) To investigate how trends vary by intellectual disability (ID) status, age-group and sex. Methods: Using population-representative primary care records from the Clinical Practice Research Datalink Aurum, we defined three autistic groups - autistic adults with ID, autistic adults without ID and all autistic adults - and four non-autistic groups - all non-autistic adults and an age- and sex-matched comparator group for each autistic group. In each calendar year we calculated: annual, lifetime and new antidepressant prescribing; indications for serotonin-selective reuptake inhibitor initiation; average doses prescribed for citalopram, fluoxetine, and sertraline; and the proportion of courses that lasted over 1, 2 and 3 years. We performed primary analyses in 16-64 year olds and repeated them with stratification by sex and age-group. Results: In all, 34,173,295 non-autistic adults and 172,242 autistic adults were included (47,011 with ID and 125,231 without ID). 30% of autistic adults and 14.7% of non-autistic adults were prescribed an antidepressant in 2023. Annual prescribing, average doses and course durations increased for all groups during the study period, and were higher for autistic adults than non-autistic adults. Annual, new and lifetime prescribing were highest in autistic adults without ID, whereas course durations were highest in autistic adults with ID. Recording of depression and anxiety as indications was lower for those with ID. Trends were largely similar across sex and age strata, with higher prescribing among females. Conclusions: Antidepressant prescribing for autistic adults has increased since 1997 and patterns of use vary by intellectual disability status. ### Competing Interest Statement BL reports receiving consulting fees for literature reviews performed for Beasley Allen Law Firm, Patterson Belknap Webb & Tyler LLP, and AlphaSights. ### Funding Statement AS is supported by a GW4-Clinical Academic Training PhD Programme for Health Professionals Fellowship, funded by the Wellcome Trust (317441/Z/24/Z), and received additional funding for this work through a Royal College of Psychiatrists Academic Trainee Small Grant. This work was also supported by the National Institute for Health and Care Research (NIHR) Bristol Biomedical Research Centre (GMK, PMD, DR; grant no: NIHR 203315). GMK, DR & PMD also acknowledge funding support from the UK Medical Research Council (MRC) which forms part of the Integrative Epidemiology Unit at the University of Bristol (MC\_UU\_00032/2 and MC\_UU\_00032/6). GMK acknowledges additional funding from the Wellcome Trust (201486/Z/16/Z and 201486/B/16/Z), the MRC (MR/W014416/1; MR/S037675/1; MR/Z50354X/1, and MR/Z503745/1). The views expressed are those of the authors and not necessarily those of the UK NIHR or the Department of Health and Social Care. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: All procedures involving human subjects/patients were approved by the Independent Scientific Advisory Committee of Clinical Practice Research Datalink (CPRD; protocol number 23_002605). CPRD has obtained ethical approval from a National Research Ethics Service Committee (NRES) for all purely observational research using anonymised CPRD data. Individual patient consent for this study was not required as all data sent to CPRD by GP practices is pseudonymised at source, with patients able to opt-out of data sharing for research purposes. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes This study is based in part on data from the Clinical Practice Research Datalink obtained under licence from the UK Medicines and Healthcare products Regulatory Agency. The data is provided by patients and collected by the NHS as part of their care and support. The interpretation and conclusions contained in this study are those of the author/s alone. Instructions for how to access the data are available at https://www.cprd.com/access-data. Analytic code are available at https://github.com/awssadik/antidepressants-autism-uk.

BACKGROUND:Depression and anxiety during pregnancy is on the rise, thus more pregnant women are being offered antidepressants; however, uncertainties remain surrounding safety. AIM:To investigate the association between first trimester antidepressant use and miscarriage. DESIGN AND SETTING:Population-based cohort study using the UK Clinical Practice Research Datalink (CPRD) GOLD. METHOD:Pregnancies included in the CPRD GOLD Pregnancy Register between 1996 and 2018 were identified. Pregnancies in those with prescriptions for antidepressants overlapping with the first trimester were defined as 'exposed' and compared with pregnancies in those who were unexposed. Cox models, adjusted hazard ratios (aHRs), and absolute risk of miscarriage were calculated adjusted for confounders including depression, anxiety, smoking, and other health, lifestyle, and obstetric factors. RESULTS:Among the 1 021 384 eligible pregnancies, 73 540 patients were prescribed antidepressants in the first trimester (7.2%); 10 693/73 540 (14.5%) pregnancies ended in miscarriage among those prescribed antidepressants versus 116 641/947 844 (12.3%) in those not prescribed antidepressants. Antidepressant prescription during the first trimester was only modestly associated with miscarriage following adjustment (aHR 1.04, 95% confidence interval [CI] = 1.02 to 1.06). These findings translated to an absolute risk adjusted for confounders of 13.1% (95% CI = 13.0 to 13.2) for those not prescribed and 13.6% (95% CI = 13.3 to 13.8) for those prescribed antidepressants. Among those prescribed antidepressants in the 3 months before pregnancy and during the first trimester, the risk of miscarriage was the same as among those unexposed (aHR 1.00, 95% CI = 0.98 to 1.03). CONCLUSION:First trimester antidepressant use was associated with a small, clinically insignificant increased risk of miscarriage, with no evidence suggesting taking antidepressants before pregnancy and into the first trimester increases the risk of miscarriage.

( JAMA . 2024;331(14):1205–1214. doi:10.1001/jama.2024.3172) The potential link between acetaminophen (paracetamol) use during pregnancy and increased risks of neurodevelopmental disorders in children, such as autism, attention-deficit/hyperactivity disorder (ADHD), and intellectual disability, has been a major subject of concern. Confounding bias may play a role in existing findings. If such a link were found, it could significantly impact how fever and pain are managed during pregnancy.

AbstractThe teratogenic potential of valproate in pregnancy is well established; however, evidence regarding the long-term safety of other antiseizure medications (ASMs) during pregnancy remains limited. Using routinely collected primary care data from the UK and nationwide Swedish registries to create a cohort of 3,182,773 children, of which 17,495 were exposed to ASMs in pregnancy, we show that those exposed to valproate were more likely to receive a diagnosis of autism, intellectual disability, and ADHD, when compared to children not exposed to ASMs. Additionally, children exposed to topiramate were 2.5 times more likely to be diagnosed with intellectual disability (95% CI: 1.23–4.98), and those exposed to carbamazepine were 1.25 times more likely to be diagnosed with autism (95% CI: 1.05–1.48) and 1.30 times more likely to be diagnosed with intellectual disability (95% CI: 1.01–1.69). There was little evidence that children exposed to lamotrigine in pregnancy were more likely to receive neurodevelopmental diagnoses. While further research is needed, these findings may support considering safer treatment alternatives well before conception when clinically appropriate.