Several longitudinal studies have cast doubt on the aetiological overlap between child and adult attention-deficit hyperactivity disorder (ADHD). However, a lack of genetically sensitive data following children across adulthood precludes direct evaluation of aetiological overlap between child and adult ADHD.We circumvent the existing gap in longitudinal data by exploring genetic overlap between maternal (adult) and offspring (child) ADHD and comorbid symptoms in an extended family cohort.Data were drawn from the Norwegian Mother, Father and Child Cohort Study, a Norwegian birth registry cohort of 114 500 children and their parents. Medical Birth Registry of Norway data were used to link extended families. Mothers self-reported their own ADHD symptoms when children were aged 3 years; reported children's ADHD symptoms at age 5 years; and children's ADHD, oppositional defiant disorder (ODD), conduct disorder, anxiety and depression symptoms at age 8 years. Genetic correlations were derived from Multiple-Children-of-Twins-and-Siblings and extended bivariate twin models.Gr = 0.55, 95% CI 0.43−0.93; ODD: Gr = 0.80, 95% CI 0.46−1; conduct disorder: Gr = 0.44, 95% CI 0.28−1; anxiety: Gr = 0.72, 95% CI 0.48−1; depression: Gr = 1, 95% CI 0.66−1). These cross-generational adult–child genetic correlations were of a comparable magnitude to equivalent child–child genetic correlations with ADHD symptoms at age 5 years.Phenotypic correlations between adult ADHD symptoms and child ADHD, ODD, conduct disorder, anxiety and depression symptoms at age 8 years were underpinned by medium-to-large genetic correlations (child ADHD: Our findings provide genetically sensitive evidence that ADHD symptoms in adulthood share a common genetic architecture with symptoms of ADHD and four comorbid disorders at age 8 years. These findings suggest that in the majority of cases, ADHD symptoms in adulthood are not aetiologically distinct from in childhood. The past decade has seen a shift toward widespread recognition that ADHD can affect adults as well as children, and a general consensus that most cases of childhood ADHD persist into at least young adulthood.11 However, the evidence base on lifespan trajectories of ADHD remains quite limited. A recent review of longitudinal research by Asherson and Agnew-Blais12 found evidence for a late-onset group who met the diagnostic criteria for ADHD by early adulthood despite not having met the criteria in childhood.12 In many of these cases, symptoms occurred exclusively in the context of other disorders, broadly supporting suggestions that adult-onset ADHD symptoms could be better explained by other disorders or environmental factors, including substance use disorders.13 However, refuting the notion of overall aetiological distinction, Asherson and Agnew-Blais12 noted that many late-onset cases displayed subthreshold symptoms of ADHD as children, or met the criteria for common comorbid disorders, particularly oppositional defiant disorder (ODD). They also suggested that most late-onset cases could more accurately be classified as ‘adolescent-onset’, with symptoms first emerging at ages 12–16 years. Among their conclusions, they posited that there may be variation in age at onset for ADHD similar to that seen in other neurodevelopmental disorders, such as schizophrenia. This would suggest that most putative cases of ADHD in adults actually represent continuations (or otherwise later-onset presentations) of the neurodevelopmental disorder of ADHD seen in childhood.Since the initial studies suggesting the distinctiveness of childhood and adult ADHD first surfaced, various studies have sought to shed light on the topic.12 highlighted several important gaps in extant research, which preclude clear conclusions as to the overall continuity of ADHD symptoms from childhood to adulthood. Key among them was that most longitudinal childhood cohorts extend only to late adolescence or young adulthood, with a marked lack of data extending further into adulthood. Therefore, although it has been shown that most children with ADHD will still meet the diagnostic criteria by early adulthood, it remains unclear whether they will continue to do so across adulthood. Furthermore, the lack of genetically informative cohort data spanning this longer period prevents the direct assessment of aetiological overlap between ADHD symptoms in childhood and across adulthood. This gap in data is a key obstacle to drawing clear conclusions about whether ADHD in adulthood represents the same aetiological entity as childhood ADHD.Asherson and Agnew-Blais14 reported a high correlation (Gr = 0.81) between polygenic scores for ADHD ascertained in children  and adults . They also found significant correlations between child and adult ADHD polygenic scores and related phenotypes, including smoking, early pregnancy, academic performance and intelligence. An important caveat is that genomic findings continue to suffer from the missing heritability problem, explaining only a small portion of ADHD's total heritability compared with quantitative genetic estimates. For example, the genome-wide association study meta-analysis used by Rovira et al14 explained 17–19% of variance in ADHD symptoms in their child-only and combined child and adult samples, compared with estimates of 70–75% found in twin studies.15 Therefore, further research using methods capable of capturing all genetic variance in ADHD is also needed.Recent genomic research has attempted to bridge this gap, providing some evidence for genetic overlap between ADHD in childhood and adulthood. Rovira et alVery few studies currently exist that can directly address the above questions by following people from childhood to adulthood. One way to circumvent this problem is to use intergenerational family data to estimate genetic covariance between adult and child ADHD across generations. In the present article, we use this novel extended family approach to investigate the aetiological overlap between ADHD in childhood and adulthood, by assessing the extent to which adult ADHD symptoms in mothers are genetically related to symptoms of ADHD and several common comorbid disorders in their offspring. In doing so, we provide an indication of overall aetiological overlap between ADHD symptoms in adulthood and a broader pattern of ADHD-related symptoms in childhood. We do this using the Norwegian Mother, Father and Child Cohort Study (MoBa), a large data-set of related parents and their children.16 Data collection covered pregnancies across all of Norway from 1999 to 2008, with 40.6% of eligible pregnant women consenting to participate in the study. The current study is based on version 12 of the quality-assured data files released for research in January 2019. Using pedigree data from the Medical Birth Registry of Norway (MBRN), a national health registry containing information about all births in Norway, we used deterministic linkage via unique birth and parent numbers spanning several generations, to group MoBa participants into extended families of twins, siblings, half-siblings and cousins in both the parent and child generations. This analytic sample consisted of a total of 25 469 mothers who reported their own ADHD symptoms and/or at least one child measure for 30 833 of their children . Mothers were aged 17–45 years when children were born . Supplementary Table 1 available at https://doi.org/10.1192/bjo.2023.554 displays frequencies of mothers and children stratified by maternal relatedness groups and child relatedness groups.MoBa is a prospective, population-based birth registry cohort of 114 500 children, 95 200 birth mothers and 75 200 birth fathers in Norway.The establishment of MoBa and initial data collection was based on a license from the Norwegian Data Protection Agency and approval from The Regional Committees for Medical and Health Research Ethics. The MoBa cohort is currently regulated by the Norwegian Health Registry Act. The current study was approved by The Regional Committees for Medical and Health Research Ethics .17 It includes six items measuring problems with sustained attention, task initiation and completion, organisation and age-appropriate indicators of hyperactivity (e.g. fidgeting when sitting still for prolonged periods). Mothers rated the frequency with which they experienced these problems in the past 6 months, on a five-point Likert scale of ‘never’, ‘rarely’, ‘sometimes’, ‘often’ and ‘very often’. Mothers were 20–48 years of age when reporting their ADHD symptoms .Mothers reported on their own ADHD symptoms by completing the Adult Self-Report Scale, a self-report screening tool for ADHD in adults which has high levels of concordance (area under the curve of 0.90) with clinical diagnoses.18 Mothers rated the extent to which each item described their child's behaviour in the past month, on a four-point Likert scale of ‘not true’, ‘somewhat true’, ‘quite true’ and ‘very true’.Mothers reported children's ADHD symptoms at age 5 years by completing the Conners’ Parent Rating Scale-Revised Short Form, a well-validated measure of parent-reported child ADHD symptoms, including 12 items covering a range of hyperactive, impulsive and inattentive symptoms in children.19 Mothers rated the extent to which each item described their child's behaviour in the past year, on a four-point Likert scale of ‘never’, ‘rarely’, ‘sometimes’ and ‘often’. Mothers reported children's anxiety symptoms by completing the short version of the Screen for Child Anxiety Related Emotional Disorders, a measure covering symptoms of several DSM-IV anxiety disorders. The five-item short version has similar psychometric properties to the full 41-item scale.20 Mothers rated the extent to which each item described their child's recent behaviour, on a three-point Likert scale of ‘not true’, ‘sometimes true’ and ‘very true’. Finally, mothers reported children's depression symptoms by completing the Short Moods and Feelings Questionnaire, a 13-item measure of recent feelings, thoughts and behaviours related to low mood and based on the DSM-III-TR criteria of depression.21 Mothers rated the extent to which each item described their child's behaviour in the past 2 weeks, on a three-point Likert scale of ‘not true’, ‘sometimes true’ and ‘true’.Mothers reported children's ADHD, ODD and conduct disorder symptoms at age 8 years by completing the Parent/Teacher Rating Scale for Disruptive Behavior Disorders. This measure includes 18 items for ADHD symptoms, eight items for ODD symptoms and eight items for conduct disorder symptoms, based on DSM-IV criteria.v. 8 years), reducing the risk of time-specific shared rater bias affecting our results. To contextualise our findings on adult ADHD, we also assessed associations between the above child symptoms at age 8 years and children's own earlier ADHD symptoms at age 5 years. Child ADHD symptoms at ages 5 and 8 years were assessed with distinct measures (see above).We set out to evaluate genetic overlap between adult  ADHD symptoms, and child (offspring) symptoms of ADHD and several comorbid disorders in mid-childhood. Mothers reported on their own ADHD symptoms several years before reporting on their children's symptoms of ADHD, ODD, conduct disorder, anxiety and depression (i.e. when children were aged 3 22 in R Statistics version 4.0.3 for Windows (https://cran.r-project.org/bin/windows/base/old/4.0.3). First, five Multiple-Children-of-Twins-and-Siblings (MCoTS) models assessed genetic relationships between mothers’ adult ADHD symptoms and child ADHD, ODD, conduct disorder, anxiety and depression symptoms at age 8 years. Second, five extended bivariate twin models assessed genetic relationships between children's early ADHD symptoms at age 5 years and their later ADHD, ODD, conduct disorder, anxiety and depression symptoms at age 8 years. We adapted these bivariate twin models to account for the additional degrees of genetic relatedness between siblings (50%), half-siblings (25%) and cousins (12.5%), and to constrain the shared environmental effect in cousins and paternal half-siblings to zero .Two sets of analyses were conducted, each using the OpenMx 2.18.1 package23 Where bivariate twin models can estimate genetic influences on phenotypic covariance between twins, CoT models can estimate genetic influences on phenotypic covariance between parents and children. Using extended families of twin parents and children, these models derive their power from the comparison of parent–offspring correlations and avuncular correlations (those between children and their aunt/uncle). Namely, children of identical twins share the same proportion of genes with their parent as they do with their aunt or uncle, but share a rearing environment only with their own parent. This separation of genetic and environmental influences allows for inferences as to the extent to which covariance between parents and their offspring is explained by shared genetic influences, with any excess parent–offspring similarity suggesting direct phenotypic transmission through exposure to the parent phenotype. The MCoTS design extends CoT analyses to include sibling, half-sibling and cousin parents, and multiple children per parent. This allows for larger data-sets of extended families to be used, increasing statistical power. In previous work, we have demonstrated that MCoTS models are adequately statistically powered in the MoBa sample.23 The full MCoTS model specification is shown in Supplementary Fig. 3, and the extended bivariate twin model specification is shown in Supplementary Fig. 4.MCoTS analyses are an extension of the Children-of-Twins (CoT) design, a quasi-experimental method of determining the extent to which a parent–offspring association is attributable to shared genetic influences.To control for covariates, we regressed all symptom measures on maternal age, parity (mothers’ number of previous births) and children's year of birth, and all child symptom measures on child gender. The residual measures were then used in analyses.Descriptive statistics of all measures are shown in Gr = 1), ODD (Gr = 0.80), anxiety (Gr = 0.72), ADHD (Gr = 0.55) and conduct disorder (Gr = 0.44) symptoms at age 8 years. Similarly, genetic influences on child ADHD symptoms at age 5 years were correlated with genetic influences on child ADHD (Gr = 0.84), ODD (Gr = 0.70), depression (Gr = 0.64), conduct disorder (Gr = 0.43) and anxiety (Gr = 0.41) symptoms at age 8 years. Standardised parameter estimates of all phenotypic and genetic correlations, including 95% confidence intervals, are shown in Supplementary Table 8.Results from adult ADHD (MCoTS) and child ADHD (extended bivariate twin) models are shown in 23 Importantly, none of the lower bounds of genetic correlations were close to zero, suggesting confidence in the genetic associations observed. Overall, confidence intervals of all adult ADHD genetic correlations were overlapping with their equivalent child ADHD correlations.Children's ADHD and comorbid symptoms at age 8 years shared roughly equal genetic overlap with adult ADHD symptoms and child ADHD symptoms at age 5 years . NotablyWe set out to address a gap in research regarding the aetiological overlap between ADHD symptoms in childhood and adulthood. We did this by assessing the extent to which mothers’ adult ADHD symptoms and children's own early ADHD symptoms at age 5 years were genetically correlated with children's mid-childhood symptoms of ADHD and several common comorbid disorders at age 8 years. At the phenotypic level, children's own early ADHD symptoms were, unsurprisingly, more highly correlated with their later ADHD and comorbid symptoms by mid-childhood, as compared with mothers’ adult ADHD symptoms. However, genetic influences on both adult ADHD symptoms and early child ADHD symptoms shared similarly high correlations with genetic influences on children's ADHD and comorbid symptoms in mid-childhood.Our findings provide novel evidence for a shared genetic architecture between ADHD symptoms in childhood and adulthood, insofar as the genetic influences on ADHD symptoms in mothers were highly correlated with genetic influences on ADHD symptoms in their children at age 8 years. Although past twin research has provided evidence for overlap between ADHD symptoms in childhood and late adolescence to early adulthood, no research to date has directly assessed genetic overlap between ADHD symptoms in childhood and across a broader age range in adulthood (i.e. beyond young adulthood).25 we are not aware of any research assessing the extent to which ADHD symptoms in adults share genetic overlap with children's symptoms of comorbid disorders. Our results demonstrate a very similar pattern of genetic overlap between ADHD symptoms measured at a range of ages in adulthood, and symptoms of ADHD and several common comorbid disorders in mid-childhood. This suggests that genetic influences on ADHD symptoms in adulthood substantially overlap with those on symptoms of ADHD and comorbid disorders in mid-childhood. In other words, it is unlikely that adult ADHD symptoms in our sample represent a distinct aetiological entity from child ADHD symptoms. Our results do not directly address nor rule out the possibility of a late-onset form of ADHD. However, if an aetiologically distinct later-onset form of ADHD exists in some adults, our findings suggest that it is quite rare in our sample, since it did not drastically affect our estimates of genetic overlap with children's ADHD and comorbid symptoms.More broadly, although there has been research on genetic overlap between ADHD and comorbid disorders in childhood,26It is also notable that in a large sample of mothers and children not selected for clinically significant ADHD (most of whom would not meet diagnostic cut-offs), genetically driven correlations were found between mothers’ adult ADHD symptoms and children's ADHD and comorbid symptoms. This suggests that even if their symptoms are at subclinical levels, mothers transmit to their children genetic risk factors for the wider array of symptoms that co-occur with ADHD in clinically significant cases. In other words, mothers with, for example, mildly elevated hyperactivity or inattention may pass on genetic risk for mildly elevated impulsivity, oppositionality or anxiety in children. This is in line with growing evidence that psychiatric and neurodevelopmental disorders represent the extreme ends of normally distributed traits in the population, and co-occur as a rule, rather than being discrete and non-overlapping categories of severe disorder only present among those with specific risk factors.Although our study focused on ADHD and common comorbidities, future studies could apply our approach more broadly to investigate aetiological overlap between any pair of adult and child phenotypes, wherever cohorts of large extended families can be linked by twin, sibling and cousin relationships. An advantage of this method is that it controls for intervention effects at the within-person level, where relevant. For example, in conventional bivariate twin studies, if aetiological overlap were observed between children's ADHD symptoms and their later cardiovascular outcomes, this could, in part, be explained by the effects of ADHD medications on cardiovascular health. However, since most parents in established longitudinal cohorts to date have not received pharmacological treatment for ADHD, if our methodology were applied to investigate aetiological overlap between children's ADHD symptoms and their parents’ adult cardiovascular health outcomes, any overlap observed could not be explained by the potential effects of ADHD medications on cardiovascular health.We investigated our hypotheses by using a large representative national birth registry cohort, including longitudinal child and parent data at a range of ages. Linking this data-set by extended family relationships with birth registry data allowed us to estimate genetic correlations between adult and child traits. This novel approach enabled us to bridge the gap in genetically sensitive data on ADHD and comorbid symptoms extending from childhood into adulthood. Another key strength of the study was that mothers reported their ADHD symptoms well into adulthood, with the youngest aged 20 years and the oldest aged 48 years at the time of self-report.27 Nonetheless, future studies incorporating father-rated adult ADHD symptoms would be useful. Another potential limitation of our analyses was that mothers reported both their own and children's symptoms. Although maternal ratings of child symptoms are likely valid , shared method bias could cause mothers’ child and self-ratings to be excessively correlated because of their own attitudes or traits.28 However, this is unlikely to have inflated our estimates of genetic overlap, as these rely on avuncular correlations, i.e. between an aunt's self-rated ADHD symptoms and their niece or nephew's mother-rated symptoms. Additionally, mothers reported their own ADHD symptoms and children's earlier and later symptoms several years apart , reducing the likelihood of time-specific reporting biases. Systematic and/or heritable biases could still inflate estimates of genetic overlap; for instance, if both mothers in an extended family had higher ADHD symptoms, so tended to be less attentive to children's symptoms, and therefore consistently underreported these. However, several studies have reported a lack of evidence that maternal ADHD symptoms bias mothers’ reporting of their children's ADHD symptoms.30One limitation of our study was a lack of available data on ADHD symptoms in fathers, which could differ in their aetiological overlap with children's ADHD and comorbid symptoms. However, despite well-known gender differences in the prevalence and presentation of ADHD symptoms, genetic and environmental influences on ADHD have been shown not to differ significantly by gender.In conclusion, our analyses address a lack of genetically sensitive research assessing the aetiological overlap between ADHD symptoms in childhood and throughout adulthood, as well as broader overlap with childhood comorbid symptoms. Our findings add to the evidence base for the continuity of childhood ADHD symptom into and across adulthood, by demonstrating a genetically driven co-occurrence of adult ADHD symptoms in mothers and a typical pattern of ADHD-related symptom in their children. Although these findings do not rule out the possibility of an aetiologically distinct form of adult ADHD in a minority of cases, they do provide genetically sensitive support for a common genetic architecture underpinning ADHD symptoms in a large, representative sample of children and adults.Future studies could apply our approach to investigate aetiological overlap between a wider range of ADHD-related phenotypes in childhood and adulthood, or indeed, the overlap between any pair of adult and child phenotypes, where population registry data enable parents and children to be linked by extended family relationships into twin, sibling and cousin pairs. This constitutes a useful method of bridging the gap in genetically sensitive data for phenotypes when measures are available in childhood, but do not extend into adulthood.Wechsler et al. supplementary material


Background: Attention deficit hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder in children and adolescents, with an average worldwide prevalence of 5%. Young people with ADHD experience poorer outcomes than their peers across multiple domains, with treatment shown to reduce these risks. Evidence shows that young people with ADHD can experience multiple challenges when seeking access to healthcare. Debates over how to tackle a ‘failure of healthcare’ for ADHD often include reorganisation of services, including better provision of adult ADHD services, and an expanded role for primary care. However, adult services remain patchy and primary care practitioners feel unsure about how to support young people at this vulnerable stage in their lives, reporting needs for more evidence-based guidance. There is also a lack of national level understanding of the different models, and pathways of care for young people with ADHD aged 16 to 25, hindering efforts to improve access to care and optimise outcomes for this underserved group. Research into this area needs to be guided by people with lived experience of ADHD and informed by perspectives from a range of stakeholders.Aim: To use collaborative research methods to provide an evidence-base by mapping current services. Then co-produce guidance to improve and better co-ordinate healthcare for young people aged 16-25 with ADHD.Methods: A national survey about mental health service provision for adults with ADHD (informed by people with lived experience) was developed and distributed. Evidence from this survey stimulated research into primary care service provision, consisting of three interlinked studies guided by research advisory groups of people with lived experience and healthcare professionalsNone Declared


To examine criminal justice system (CJS) interactions and pathways through the justice system for young adults with ADHD compared to young adults without ADHD.Nationwide 3-year birth cohort study using linked health and CJS data. Cox proportional hazards models were employed to examine associations between ADHD and police proceedings, court charges, court convictions, and incarcerations.Young adults with ADHD were significantly more likely to interact with the CJS including police proceedings  court charges , court convictions , and incarceration .Young adults with ADHD are overrepresented at all stages of the CJS. Results highlight the importance of early identification and responsivity to ADHD within the CJS and suggest that the NZ justice system may require changes to both areas to ensure that young individuals with ADHD receive equitable access to, and treatment within, the CJS. Attention-Deficit/Hyperactivity Disorder (ADHD) is clinically defined as a neurodevelopmental condition characterized by the presence of pervasive and developmentally excessive levels of hyperactivity, impulsivity, and difficulties in attention . The exeDespite these more positive understandings of ADHD, research has consistently identified people with ADHD as experiencing high rates of mental health disorders such as substance use disorders (SUDs), emotional dysregulation, and self-harm. ADHD has also been associated with disruptive, defiant, and antisocial behaviors . People While estimates of ADHD prevalence vary due to methodological differences between studies, it is generally accepted that the global prevalence among children and young people is currently around 5-7% . The malA large body of research suggests that ADHD may be a risk factor for interactions with the criminal justice system (CJS). In a meta-analysis of 15,442 children and adolescents (aged 4–15) with ADHD from nine unique samples, ADHD was associated with a two- to threefold increase in the risk of arrests, convictions, and incarcerations in adolescence and adulthood compared to controls without ADHD . SignifiThis increased risk of CJS interactions is also reflected in the disproportionately higher rates of ADHD reported across multiple contact points within the CJS, including police custody/arrests, prison, probation, and forensic mental health settings . CompareRegarding associations between ADHD and offense types, there is a dearth of research available and existing studies have been limited by small convenience samples or cross-sectional designs , and retSeveral theories exist on the association between ADHD and CJS interactions. Some suggest that the symptomatology of ADHD may lead to crime due to its associations with low self-control, a widely known criminogenic risk factor . Others It is therefore important to not only understand how ADHD might lead to interactions with the CJS but also the ways in which ADHD may shape these interactions and affect an individual’s pathway through the justice system. All signatory states to the United Nations Convention on the Rights of Persons with Disabilities (UNCRPD) have a series of legal obligations to protect disabled people . These include ensuring equal recognition before the law and the provision of effective access to justice, protecting the liberty and security of the person .However, individuals with ADHD may be at risk from their moment of first contact with the CJS  for several reasons. Firstly, they may be perceived as uncooperative or less credible as they are more likely to respond to questions with “don’t know” rather than denying suggestions put to them (possibly due to a lack of confidence in their memory) . SecondlSignatory states are also required to collect appropriate data to demonstrate they are complying with the obligations set forth in the UNCRPD . HoweverLinked population-level health and CJS data from NZ provides an opportunity to fill known gaps in the literature regarding ADHD and CJS interactions. In particular, by enabling analysis of the pathway through the CJS and addressing methodological shortcomings in extant research. They also provide essential data specific to the NZ-context. The aims of the current study are therefore to: (1) Investigate the benefits of using linked administrative data to contribute to research regarding CJS interactions among young people with ADHD; (2) Examine CJS interactions and pathways through the justice system for young adults with ADHD compared to young adults without ADHD; and (3) Assess whether associations exist between ADHD and specific offense types in comparison to individuals without ADHD.This was a national 3-year birth cohort study using data from Statistics New Zealand’s Integrated Data Infrastructure (IDI), a large database of linked de-identified administrative and survey data about people and households. The IDI is a world-leading resource containing population-level data across a range of life domains including health, education, the labor market, housing, social welfare, and the CJS . Individuals were identified with ADHD if they obtained at least one code relating to an ADHD diagnosis in any of the four datasets. As ADHD is considered to be a lifetime neurodevelopmental condition, case identification reviewed diagnosis data from birth through to the end of the study period.ADHD status was determined using an established case identification method . This meFour CJS interaction variables of increasing severity were of interest: police proceedings, court charges, court convictions, and incarcerations. Information on police proceedings was obtained from NZ police recorded offender data. Court charges and convictions were drawn from Ministry of Justice courts data. Incarcerations were obtained from the Department of Corrections dataset. For each CJS interaction variable, individuals were coded as 1 if they had any interaction over an 8-year period from their 17th birthday through to their 25th birthday and 0 for no interaction. Dates for when each type of interaction occurred were also available.Supplemental Material (Table S2). Specific divisions were combined to create different offense types: offenses against people (ANZSOC divisions 1–6); offenses against property ; offenses against organizations, government and community ; and violent offenses . Each offense type was treated as a dichotomous variable (convicted/not convicted). First date of conviction for an offense type was also available.Offense types for criminal convictions were defined using the Australian and New Zealand Standard Offense Classification (ANZSOC), a commonly used method of classifying offense types in Australia and NZ . ANZSOC The seriousness of offenses was defined using the categorization in the Sociodemographic variables included sex , age (in years), ethnicity, area of residence, and area-level deprivation. Ethnicity was measured in total response format, allowing individuals to identify with one or more of the following ethnic groups: European; Māori; Pacific; Asian; Middle Eastern, Latin American, African (MELAA); Other. Multiple ethnic identification is a common occurrence in NZ . Area-leThe sociodemographic characteristics of the participant population were described descriptively, stratified by ADHD status. Observed rates of each of the four CJS interaction types and conviction offense types were calculated for those with and without ADHD. Cox proportional hazards models were employed to examine associations between ADHD and each CJS interaction . Unadjusted and adjusted hazard ratios (HRs) for ADHD with 95% confidence intervals (CIs) were estimated using the robust variance estimator . AdjusteData management was undertaken in SAS Enterprise Guide version 7.1  and analn = 3,975) were identified as having ADHD. The sociodemographic characteristics for those with and without ADHD in our sample are presented in Of the 149,076 individuals in our final sample, 2.7% . Such methodology could be periodically replicated and expanded upon both in NZ and abroad for better monitoring of States Parties progress toward meeting their obligations under the UNCPRD in relation to the CJS. In particular, the use of integrated data to enable analysis of the pathway through the CJS at a population level is novel and provides more nuanced insights into the disabling experiences of young adults with ADHD in the CJS.The current study has a number of strengths. Firstly, we were able to establish a large, 3-year national birth cohort, tracking participants until their 25th birthday. The use of linked data allowed us to identify those with and without ADHD and examine their interactions with the CJS at multiple contact points including police, courts, and corrections. We were also able to explore differences in the types of offending for those with compared to those without ADHD, which allowed us to investigate how their pathways might differ from one another. Additionally, the use of linked data meant that we were able to control for various sociodemographic factors and account for early exits during the observation period .There are several limitations to the current study that should be noted. We did not control for the effects of conditions highly comorbid with ADHD such as CD and SUDs, which may be associated with an increased risk of delinquency and crime . While sThe use of administrative data for identifying ADHD likely undercounts, and may falsely identify, cases. For example, the method relies on health service use and will not capture individuals with ADHD who are not accessing treatments . AlternaTo fully elucidate and understand the relationship between ADHD and CJS interactions, there is a need for more research employing large, representative samples with longitudinal rather than cross-sectional designs. The importance of controlling for co-occurring psychiatric conditions such as CD and SUDs has been highlighted by a number of previous studies, due to their independent associations with crime, and the extent to which this impacts CJS interactions among individuals with ADHD in NZ needs to be determined. Future research could also benefit from exploring the role of other risk and protective factors for CJS interactions among those with ADHD in NZ. For example, research has noted that while co-occurring autism may be a protective factor against crime in those with ADHD , adverseFurther research is necessary to understand why the risk of CJS interactions increases so sharply from conviction to sentence for young persons with ADHD. A better understanding of how young persons with ADHD experience that pathway will inform how best to mitigate this disabling experience. This could present a significant opportunity for NZ and other countries to innovate, including by allowing for supports, accommodation, and alternative pathways  in order to ensure obligations under the UNCRPD are met.Our findings revealed that not only were individuals with ADHD overrepresented at all stages of the CJS and offense types examined, there was also a pattern of increasing risk for CJS interactions as these individuals moved through the system. These results highlight the importance of early identification and responsivity to ADHD within the CJS and suggest that the NZ justice system may require changes to both of these areas to ensure that young individuals with ADHD receive equitable access to, and treatment within, the CJS. The current study has also revealed the utility of effective data linkage in better understanding the pathways of individuals with ADHD through the CJS.Click here for additional data file.Supplemental material, sj-docx-1-jad-10.1177_10870547231177469 for Risk of Criminal Justice System Interactions in Young Adults with Attention-Deficit/Hyperactivity Disorder: Findings From a National Birth Cohort by Francesca Anns, Stephanie D�Souza, Conrad MacCormick, Brigit Mirfin-Veitch, Betony Clasby, Nathan Hughes, Warren Forster, Eden Tuisaula and Nicholas Bowden in Journal of Attention Disorders


A significant proportion of currently enrolled college students receive support for attention deficit/hyperactivity disorder (ADHD) and these students are often at risk of academic failure. Retrieval practice or self-testing is an effective, accessible, and affordable tool for improving academic performance. Three recent studies found conflicting results with regards to the effectiveness of retrieval practice in this population.The present study compared 36 individuals with ADHD to 36 controls. Participants studied Swahili-English word pairs that varied in difficulty. Half of the pairs were repeatedly studied, and the other half repeatedly tested.On a final test, all participants showed a benefit of retrieval practice relative to restudy and participant status did not moderate the effect. However, unmedicated individuals with ADHD performed worse overall, both during the encoding phase and on the final test, whereas medicated participants were not significantly different from controls.An examination of self-reported encoding strategies found unmedicated participants used fewer deep strategies at encoding, consistent with prior work on ADHD and memory. Although retrieval practice is effective in this group, improved strategy use may be necessary to ensure performance that is fully equivalent to that of students without ADHD. Attention deficit/hyperactivity disorder (ADHD) is characterized by inattentiveness and/or hyperactivity/impulsivity, high levels of distractibility, difficulty maintaining focus and sustaining attention . InitialLong-term memory is important for academic success, and adults with ADHD perform worse on tests of verbal long-term memory . Two soutesting effect (TE) and has been found across different types of materials and different populations , selected from a larger sample of over 300 participants who participated in a previous study on the benefits of retrieval practice. Control participants were selected from this pool to match individuals with ADHD in age, biological sex, GPA, and measures of cognitive performance  and via email, and the remaining 21 students signed up via the participant sign-up pools at the college as well as a state university and self-identified as having a diagnosis. Participants reported the diagnosis was made by a doctoral level therapist in seven cases, by a practitioner holding a master’s degree in two, and by a medical doctor in the remaining cases. Participants were asked to answer yes or no whether they were currently taking medication to treat their ADHD but were not asked to report the type(s) of medication used. Twenty-one participants (58%) reported taking medication at the time of the study and one regularly took medication but did not take it the day of the study. In addition to self-report, all participants, except for two individuals with ADHD, completed a current symptom checklist  that meaWe aimed to recruit as many participants as possible, and, at minimum, a sample size for participants with ADHD comparable to previous studies  were selected from the SD = 0.05), 0.55 (SD = 0.04), 0.72 (SD = 0.04), and 0.84 (SD = 0.07), from most difficult to easiest, respectively. The 24 pairs drawn from the two easiest levels constituted the Easy set of items and the 24 pairs drawn from the two hardest difficulty levels constituted the Difficult set. Half of the pairs from each difficulty set were assigned to the repeated study condition and half to the repeated test condition with the stimulus condition counterbalanced across participants.A set of 48 Swahili-English word pairs  appear for 7 s, during which time participants typed their response using the computer’s keyboard, followed by the intact pair for 1 s . Thus, the repeated test block included feedback. Pair order within blocks was randomized anew on each block. Responses during the encoding and final test phases were coded as correct if participants recalled the correct answer or minor spelling/morphological variations . See Participants first studied all 48 pairs, in random order, for 8 s each. They next completed four additional blocks of repeated study and repeated testing. The re-study block always preceded the repeated test block to avoid contamination from prior retrieval cf.. In the Two days later, participants returned to the lab and completed a final cued recall test. All 48 Swahili cues were presented, one at a time, in random order. Participants had unlimited time to respond and no feedback was given.Participants completed a set of cognitive tasks to measure individual differences in intelligence and working memory. As noted in the Participants section, this task battery was administered to allow us to match participants with ADHD to participants without ADHD on fluid intelligence, working memory and vocabulary.We used a computerized version of this measure of general fluid intelligence. On each trial, participants were presented a matrix of eight shapes/complex patterns and had to select one of four options that best completed the matrix across rows and columns. The task was self-paced and consisted of 48 trials of increasing difficulty .We used the automated version of this measure of verbal working memory as developed by In this computerized measure of visuospatial working memory, participants had to remember the order in which 2–5 locations lit up on a 4 × 4 grid . BetweenA computerized version of never or rarely) to 4 (very often) scale and higher scores (max = 72) reflect greater severity of symptoms.The measure consists of 18 questions asking participants to indicate how often, in the previous 6 months, they experienced specific behaviors, such as interrupting others, not finishing work, or feeling restless . ResponsThis measure consists of 12 questions assessing how students typically study and is a modification of a survey developed by Definitely cannot do it) to 100  to 3  scale with higher scores (max = 81) indicating greater test anxiety . The tasks were administered in such a manner that the two sessions lasted approximately an equal amount of time (90 min). At the conclusion of the second session, participants were thanked, debriefed, and compensated.We begin our results section by first reporting the demographic characteristics of each group. Although we matched participants on fluid intelligence, working memory and vocabulary, we measured other traits, academic self-efficacy and test anxiety, that we expected to differ between groups based on prior ADHD research . We thent values < 1. As expected, there was a significant difference in reported ADHD symptoms, t(68) = −4.47, p < 0.001, d = 1.1. There was also a significant difference in academic self-efficacy, t(70) = 2.94, p < 0.01, d = 0.69, with lower self-efficacy for learning in our ADHD group which is consistent with prior reports (t(70) = −1.26, p = 0.21. Greater test anxiety in ADHD has been reported in prior studies  = 9, p = 0.003. Whereas all of the control participants reported using self-testing, eight (22%) individuals with ADHD indicated they did not. Among those who did use self-testing, the groups did not differ with respect as to why , all ps > 0.23. The two groups did not differ in their responses to any of the other items, all ps > 0.08, suggesting that the groups were well matched in terms of their academic skills and learning habits.An examination of the responses to the study habits measure indicated few differences between participant groups. The two groups did not differ in their use of spacing or cramming, the extent to which they re-read textbooks or notes, or time of day during which they studied. However, consistent with previous research , individM = 0.33, SE = 0.03) performed worse than the cognitively matched control participants  during the encoding phase, F = 5.64, p = 0.020, p2η = 0.08. Performance improved across learning blocks, F = 212.56, p < 0.001, p2η = 0.75. All pairwise comparisons were significant at the 0.001 level following a Bonferroni correction for multiple comparisons. There was also a main effect of difficulty, F = 230.37, p < 0.001, p2η = 0.77. All pairwise comparisons were significant, ps ≤ 0.001. Pair difficulty and block interacted, F = 6.87, p = 0.001, p2η = 0.09. To explore the interaction, we examined the effect of block within each level of difficulty. All effects were significant, all Fs > 46.5, all ps < 0.001, as were all pairwise comparisons . The interaction was driven by a steeper increase in retention from Block 1 to Block 2 for easy items compared to difficult items  × 2 (difficulty) × 2 (participant group) mixed ANOVA, in which block and difficulty were within-subjects factors and group was a between-subjects factor. Overall, participants with ADHD ; intermediate processing ; or deep processing . Coders also noted the use of the keyword method . Proportions of reported strategies are presented in 2χ(1) = 5.10, p = 0.024, although the total number of strategies and use of shallow strategies did not differ across groups.Participants were asked to describe the encoding strategies they used to learn the word pairs. Participants could report multiple strategies. However, we did not ask for any information about the timing of these strategies . These self-reports were independently coded by two coders with an inter-rater reliability measured using the intraclass correlation coefficient (ICC). The ICC was 0.9 indicating excellent agreement between the coders. Responses were coded in terms of the strategies indicated using the following criteria: d method , which iM = 0.52, SE = 0.03) than pairs that were restudied , F = 10.27, p = 0.002, p2η = 0.13, thus demonstrating a TE. Easy pairs were recalled more successfully  than difficult pairs , F = 265.67, p < 0.001, p2η = 0.79 consistent with the norming data  x 2 (pair difficulty) x 2 (participant group) mixed ANOVA, in which condition and pair difficulty were within-subjects factors and group a between-subjects factor see . Pairs ting data . No intetudy cf., 2020.F = 4946.19, p < 0.001, p2η = 0.53, as final recall increased from 0.07 proportion correct for items never recalled during the encoding phase to 0.56 for items recalled once, to 0.78 for items recalled twice, to 0.90 for items recalled three times, and to 0.97 for items recalled four times. There was no main effect of group, F = 1.98, p = 0.16, or of difficulty, F = 3.56, p = 0.06, and no interactions, all Fs < 1.2. In sum, both groups’ final test performance was similarly improved as a function of initial retrieval success.Retrieval success has been shown to moderate the magnitude of the TE with final test performance higher for items correctly retrieved more often during the encoding phase . We condF = 11.6, p < 0.001 2R = 0.25, with deep strategy use significantly predicting performance, t = 4.80, p < 0.001, whereas the use of shallow strategies did not, t = 1.05, p = 0.30. We then reexamined the group difference in memory performance at encoding including deep strategy use as a covariate and found the effect of group was no longer significant at encoding, F = 1.97, p = 0.17, p2η = 0.03. This suggests that the encoding differences found between the students with and without ADHD may be due to differential use of deep strategies.Although our groups were matched on fluid intelligence and working memory capacity, we did see a difference in self-reported encoding strategies with non-ADHD participants reporting significantly greater use of deep encoding strategies. Deeper encoding strategies have long been shown to improve memory performance . We examn = 20) and unmedicated (n = 16) participants with ADHD now as separate groups compared to the control group. Group assignment for participants with ADHD was based on whether they reported taking medication on the days of the study. A comparison of self-reported symptomatology between our medicated and unmedicated groups was not significant, p < 0.99. As in our initial analysis of encoding performance, there were main effects of difficulty, F = 236.37, p < 0.001, p2η = 0.77, block . The main effect of group was also significant, F = 4.54, p = 0.014, p2η = 0.12, and did not interact with any other factors. Post-hoc comparisons using a Bonferroni correction revealed a significant difference in performance between the control group and the unmedicated ADHD group, p = 0.011, whereas the differences between the medicated ADHD group and the control group (p = 0.86) and between the medicated and unmedicated ADHD groups (p = 0.23) were not significant. These data are shown in 2χ(1) = 8.92, p = 0.003 and the medicated ADHD group (9 out of 20), 2χ(1) = 4.43, p = 0.04, whereas the medicated ADHD group did not differ from the control group, 2χ(1) = 0.75, p = 0.39.As we reported in the Participants section, 20 out of 36 participants with ADHD reported taking medication for their ADHD diagnosis at the time of the study. Given research suggesting that ADHD medication can improve memory performance , we examFs < 1. However, now the main effect of group was significant, F = 3.26, p = 0.04, p2η = 0.09. Post hoc comparisons revealed that the difference between the unmedicated ADHD group and the control group was significant (p = 0.04), whereas the difference between the two ADHD groups (p = 0.27) and between the medicated ADHD group and the control group (p > 0.99) were not. These data are shown in ps > 0.10.Turning to performance at final test, we reanalyzed the data using a 2 (condition: repeated study vs. repeated test) × 2 (pair difficulty) × 3 (participant group) mixed ANOVA. There were significant main effects of condition and difficulty with no interactions, Overall, our results are consistent with the prior literature both in terms of the benefits of retrieval practice for college students with ADHD , 2020 anHowever, our examination of the effects of medication status found unmedicated students performed significantly worse than the control group at both encoding and final test, while medicated students performed similarly to the controls. The unmedicated group also reported significantly less use of deep encoding strategies than both the medicated group and the controls. Although these results are preliminary, they are consistent with work conducted with unmedicated children and adolescents with ADHD that reports poorer memory performance due to less effortful encoding strategies  and a meRelating our study to the prior studies of the testing effect in ADHD, our results are consistent with Another important takeaway from our results is that although retrieval practice is equally effective, it does not make up for the deficits at encoding seen in the unmedicated participants with ADHD. Consistent with prior work showing that the performance deficits in ADHD are largely due to poor encoding, this suggests that, once encoding is successful, retrieval can and does occur. However, although retrieval practice appears to promote better encoding than re-study, it does not compensate for poor encoding strategies. Thus, an emphasis on the remediation of deficits at encoding may be needed for some students with ADHD to perform optimally. Participants using deeper encoding strategies have been shown to outperform those benefiting from retrieval practice . HoweverOur results suggest that the significant difference seen during encoding between the ADHD group and control group in our initial analysis may have been due to having a mixture of medicated participants with ADHD who performed similarly to controls and un-medicated participants with ADHD who performed significantly worse than the control group. This is consistent with a number of studies demonstrating improved memory performance with use of stimulant medication . Howeverhttps://doi.org/10.15786/20520690.v1, University of Wyoming libraries data repository.The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found at: The studies involving human participants were reviewed and approved by Colby College Institutional Review Board and University of Wyoming Institutional Review Board. The patients/participants provided their written informed consent to participate in this study.JC and MM contributed to the concept, stimulus development, data collection, and analyses. LC and SB collected, scored, and coded data. MM, JC, LC, SB, and JS contributed to the writing. All authors contributed to the article and approved the submitted version.The research was supported by a Social Sciences Division Grant from Colby College awarded to JC. At the time of the analyses and writing, JC was supported by a James S. McDonnell Foundation Understanding Human Cognition award # 220020426 and MM was supported by National Science Foundation Grant # 1660996.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Environmental exposure to endocrine-disrupting chemicals (EDCs) is linked to the development of uterine fibroids (UFs) in women. UFs, non-cancerous tumors, are thought to originate from abnormal myometrial stem cells (MMSCs). Defective DNA repair capacity may contribute to the emergence of mutations that promote tumor growth. The multifunctional cytokine TGFβ1 is associated with UF progression and DNA damage repair pathways. To investigate the impact of EDC exposure on TGFβ1 and nucleotide excision repair (NER) pathways, we isolated MMSCs from 5-months old Eker rats exposed neonatally to Diethylstilbestrol (DES), an EDC, or to vehicle (VEH). EDC-MMSCs exhibited overactivated TGFβ1 signaling and reduced mRNA and protein levels of NER pathway components compared to VEH-MMSCs. EDC-MMSCs also demonstrated impaired NER capacity. Exposing VEH-MMSCs to TGFβ1 decreased NER capacity while inhibiting TGFβ signaling in EDC-MMSCs restored it. RNA-seq analysis and further validation revealed decreased expression of Uvrag, a tumor suppressor gene involved in DNA damage recognition, in VEH-MMSCs treated with TGFβ1, but increased expression in EDC-MMSCs after TGFβ signaling inhibition. Overall, we demonstrated that the overactivation of the TGFβ pathway links early-life exposure to EDCs with impaired NER capacity, which would lead to increased genetic instability, arise of mutations, and fibroid tumorigenesis. We demonstrated that the overactivation of the TGFβ pathway links early-life exposure to EDCs with impaired NER capacity, which would lead to increased fibroid incidence. The incidence of uterine fibroids (UFs) is extremely common among women of reproductive age. Although non-cancerous, these tumors are associated with significant morbidity, including prolonged or heavy menstrual bleeding, pelvic pain, and in some cases, they can be related to pregnancy loss and infertility . DespiteTsc2 tumor suppressor gene and female Eker rats develop UFs spontaneously with a high frequency during their adulthood . The chemiluminescence was detected with a Carestream Imaging Station . For examining repair kinetics, the percentage (%) of CPD repair was calculated by comparing the optical density at the indicated time to that of the corresponding absorbance at time zero when there was no opportunity for repair, and 100% of CPDs were present post-UVB. The 10 mJ/cm2 UVB dose was chosen as there was little acute, UV-induced cell death (observed under light bright microscopy) induced under these conditions, while there were sufficient levels of DNA damage to reproducibly measure its repair .VEH- and EDC-MMSCs pellets were collected as described above at different time points  post-UVB light exposure , precision weights were applied to gene counts based on within-group sample-level variance and gene-level mean-variance trends using VOOM from Limma 3.52.4. The count data was fitted to a gene-wise linear model with group status as a coefficient, and an empirical Bayes method was used to estimate the posterior odds of differential expression after adjusting for gene-level posterior residual standard deviations. Significant differential genes were decided with a minimum absolute fold change of 1.5 and a false-discovery rate of 0.05. GSEA was tested using the Hallmark MSigDB collection.RNA quality and quantity were assessed using the Agilent bio-analyzer. Strand-specific RNA-SEQ libraries were prepared using a TruSEQ mRNA-SEQ library protocol (Illumina provided). Library quality and quantity were assessed using the Agilent bio-analyzer, and libraries were sequenced using an Illumina NovaSEQ6000 (Illumina provided reagents and protocols). A variety of R packages were used for this analysis. All packages used are available from the Comprehensive R Archive Network (CRAN), Comparisons between groups were made by two-tailed unpaired Student’s t-test using GraphPad Prism 9 . The assumption of normality was assessed by Shapiro–Wilks test. All data are presented as mean ± standard error of mean (S.E.M.). A difference between groups with *p < 0.05, **p < 0.005, ***p < 0.0005, or ****p < 0.0001 was considered statistically significant.Tgfb1 gene expression in the hypothalamus of Fischer rats [Smad3 , an EDC that mimic estrogen action . We founher rats . Moreoveher rats , linkingher rats , were inher rats  . Moreover, 6 genes involved in nucleotide excision repair (NER) pathway showed changes in their mRNA expression levels between EDC-MMSCs and VEH-MMSC . NER is the main pathway involved in repairing bulky DNA adducts formed by environmental carcinogenic sources such as UV light exposure or chemical agents . DES, thage site , were siage site . In thisage site . We obseMMSCs present self-renewal and differentiation capacities which are critical for myometrial tissue homeostasis. To evaluate whether the observed changes in NER pathway members take place also at the tissue level, we performed XPA and XPC IHC in myometrial tissues collected from adult rats (pre-fibroid) exposed neonatally to VEH or EDC . We foun2 UVB light and the cellular morphology were monitored by phase contrast light microscopy before and 9,12 and 24 h after the exposure. To determine whether early life exposure to EDCs affects NER repair capability in MMSCs, we assessed the repair kinetic of cyclobutane pyrimidine dimers (CPD) after UVB exposure in VEH- and EDC-MMSCs. Cells were irradiated with 10 mJ/cmTGFβ1 signaling has been implicated in regulating NER in human immortalized keratinocytes (HaCaT) cells , but the link between these two pathways has not been evaluated in MMSC. We hypothesized that TGFβ1 pathway activation will compromise NER-dependent DNA repair in the healthy MMSC while TGFβ1 signaling inhibition will revert NER impairment in EDC-MMSC. To verify this hypothesis, we treated VEH-MMSCs with exogenous TGFβ1 and we observed that this activation suppressed CPD repair at 6 h  and at 12 h  after UVB light exposure . In thisXpa and Xpc, two NER members that were downregulated in EDC- compared to VEH-MMSCs  showed the opposite result, since its levels were decreased in EDC- compared to VEH-MMSCs  expression was downregulated in VEH-MMSCs after the treatment with exogenous TGFβ1 and upregulated after TGFβ Receptor I inhibition in EDC-MMSCs. Uvrag specifically interacts with DDB1, which together with DDB2, checks the whole genome for damage independently of transcriptional status [Uvrag mRNA levels were decreased in EDC compared to VEH-MMSCS. Next, we analyzed the top enriched Hallmark gene sets in VEH-MMSCs treated with TGFβ1versus vehicle  is a multipotent cytokine that is involved in several pathological processes in many cell types. Misregulation of TGFβ activity has been related to tumorigenesis , includiin uterus or during early life is associated with the progression of diseases later in life [Besides the capacity of the EDCs to mimic the action of endogenous hormones, they have also been reported to exert genotoxic and mutagenic effects , 52. The in life , 54. Dev in life –58. In a in life , 60. It TSC-2 in the Eker rat or MED12 in women. In particular, the Eker rat (TSC-2Ek/+), inactivation of the wild-type TSC-2 allele commonly occurs by loss of heterozygosity . However, other mechanisms such as point mutation have also been reported [TSC-2 allele in EDC-MMSCs, which would trigger the development of uterine tumors at a higher frequency in EDC-exposed Eker rats than unexposed. We found that the observed decreased NER capacity could be related to lower mRNA and protein levels of several members of this pathway, such as XPC, an indispensable factor for the initial recognition of bulky DNA damage [Several studies have demonstrated the presence of MMSCs , 62, whireported . Here wereported . TherefoA damage . There iA damage  describeA damage , and impA damage  in rat MUVRAG, which is essential in the NER pathway.Furthermore, we showed that increased levels of TGFβ1 affected the repair of bulky DNA damage, through modulation of nucleotide excision repair (NER). Although contradictory, several works showed a connection between TGFβ1 and DNA damage. While some authors showed that the inhibition of TGFβ pathway tends to mitigate DNA damage responses and increase genomic instability –74, otheEDC exposure may be one factor driving the observed disparities in UF burden between Black and White women , as studIn summary, our findings pinpoint a link between the overactivation of TGFβ and the impaired ability of rat MMSCs to repair DNA damage through the NER pathway, and both provoked by the developmental exposition to EDC, which have implications for uterine tumor development .


As numerous studies have shown, executive dysfunction is the main impairment in attention‐deficit/hyperactivity disorder. According to recent neuroimaging studies, the frontoparietal coherence plays a key role in overall cognitive functions. Therefore, the aim of this study was to compare executive functions during resting‐state EEG by monitoring brain connectivity (coherence) patterns in children with attention deficit hyperactivity disorder (ADHD) with or without reading disability (RD).The statistical sample of the study consisted of 32 children with ADHD aged between 8 and 12 years old with or without specific RD. Each group consisted of 11 boys and 5 girls that were matched on chronological age and gender. EEG was recorded during eyes‐opened condition and brain connectivity within and between frontal and parietal regions was analyzed within theta, alpha, and beta bands.The results revealed that across the frontal regions, the comorbid group showed a significant reduction in the left intrahemispheric coherence in the alpha and beta bands. The ADHD‐alone group exhibited increased theta and decreased alpha and beta coherence in frontal regions. In the frontoparietal regions, children in the comorbid group showed lower coherence between frontal and parietal networks compared to children without comorbid RD.The findings indicate that brain connectivity (coherence) patterns of children with ADHD with comorbid RD were more abnormal and lend support to more disrupted cortical connectivity in the comorbid group. Thus, these findings can be a useful marker for better recognizing ADHD and comorbid disabilities.  AccordiIt seems that individuals with ADHD experience comorbid disorders. Among these conditions, specific reading disability (RD) is one of the most frequent comorbid ones, occurring approximately in 25%–40% of individuals with ADHD , and connective  characters. With this explanation, the recording of electrical waves in the resting state (RS) provides the possibility to obtain information about how neural connections work without performing any cognitive tasks. Most importantly, according to Lord and Opaka‐Jeffrey , examiniIn general, EEG coherence alludes to the functional connection between brain areas , alpha (8–12 Hz), and beta (12–30 Hz) bands that are tightly linked to executive functions.2Thirty‐two native Iranian children aged between 8 and 12 years old participated in this study. A group of 16 children with ADHD with comorbid RD  and a group of 16 ADHD children without RD  were selected. In both groups, the children were matched on chronological age and gender. Both groups were recruited for participation through rehabilitation centers. The diagnoses for ADHD children in both groups were based on Persian version of the Wechsler Intelligence Scale for Children (WISC‐IV), the revised Canners’ parent rating scale, and clinical interviews check list. To observe ethical consideration, the parents were informed in writing about the goals and importance of the research and signed the informed consent form to enter the research. In addition, the participants could opt out of the study at any time. Parents were informed that all information about the subjects would remain confidential, and the names of the individuals would be avoided in the results.2.1To perform this study, the participant sat in front of the laptop monitor and after cleaning the skin of the ears and forehead with medical alcohol, the special cap of the device was placed on his/her head. Based on the international 10–20 system, 19 electrodes for standard electroencephalography recording  were placed on the participant's skull. Electrodes A1 and A2 were placed on the ears as potential references. Electroencephalography recording was done by eWave amplifier. EEG recording was done during eyes opened resting state for 5 min, and during this time, the participants did not perform any tasks. Therefore, EEG recording was conducted in anterior , central , and posterior  areas. According to the prior arrangements, the children were requested not to take any medicine before the electroencephalography recording. All EEG recordings were done between certain hours of the day, that is, around 10–12 in the morning and after a normal night's sleep and breakfast, to make the recordings conditions the same and to avoid the influence of time. During recording, participants were asked to keep looking at the screen and minimize their movements and even not blink. The impedances for all electrodes were maintained below 5 k Ω.2.2p < .05.After artifact correction and preprocessing, 30 epochs of 2 s with minimal artifacts were selected; totally for the final segments of EEG, we had 60 s to analyze. To extract quantitative data for each participant, the recorded EEG was analyzed offline using NeuroGuide software. Fast Fourier transform analysis was used to assess EEG coherence activity in all frequency bands. Therefore, a comparison was made between children with ADHD with comorbid RD and ADHD children without comorbid RD concerning the resting‐state EEG coherence in the theta, alpha, and beta bands for the following analysis: the means of coherence in left  and right  frontal intrahemispheric regions, means of coherence in frontal interhemispheric  regions and left (F3‐P3) and right (F4‐P4) frontoparietal regions. Statistical analyses were performed by SPSS software (version 23.0), and the significance level for all analyses was set at t‐test was undertaken.The analysis was considered according to two fixed‐effects factors; group (ADHD + RD children vs. ADHD children), and EEG coherence of theta, alpha and, beta bands. Before using the parametric analysis of variance test, Levene's test was used to meet its assumptions. As can be seen in Tables 3F (6.44); df (4); p < .001), alpha (F (8.51); df (4); p < .001), and beta (F (4.45); df (4); p < .002) frequency bands. Similarly, children in the ADHD‐alone group showed significantly different coherences across all frontal interhemispheric and intrahemispheric regions and frontoparietal regions in theta (F (13.68); df (4); p < .001), alpha (F (17.90); df (4); p < .001), and beta (F (12.26); df (4); p < .001) bands. The results for the analysis of the frontal regions revealed that children in the ADHD‐alone group had significantly lower interhemispheric coherence in beta compared with left  and right  frontal intrahemispheric regions. In addition, the ADHD group without comorbid RD exhibited elevated coherence in the left frontal intrahemispheric in theta band  when this was compared to frontal interhemispheric region.The ANOVA results for the EEG coherence analysis in frontal regions revealed significant group differences in three frontal regions in all three  bands. As the results showed, the comorbid group exhibited significant EEG coherence changes across left and right frontal intrahemispheric, frontal interhemispheric, and frontoparietal regions in theta  and alpha  EEG coherence in the left frontoparietal region when this was compared to left intrahemispheric frontal region. The ADHD group without comorbid RD exhibited lower alpha coherence in the left frontoparietal region  compared to the left frontoparietal region.The results for EEG coherence in frontoparietal regions revealed that children with ADHD with comorbid RD had significantly lower theta , alpha , and beta bands  when this was compared to left frontal intrahemispheric regions in the ADHD‐alone group.Totally, the results for EEG coherence across frontal regions revealed that the comorbid group had decreased coherence in the left frontal intrahemispheric of theta  and beta  coherence in the left frontoparietal regions. The ADHD‐alone group had lower theta  and beta  coherence in the frontal interhemispheric region compared to the comorbid group. As seen in the example of Figures Moreover, children with ADHD with comorbid RD showed significantly lower alpha (5The aim of the present study was to compare executive functions during resting‐state EEG by monitoring brain connectivity (coherence) patterns in children with ADHD with or without reading disability. Rs‐EEG coherence was examined across theta, alpha, and beta bands in children with ADHD with comorbid RD and compared with ADHD without RD. Consistent with previous findings in brain functional connectivity  in children (Perone & Garstein, The aforementioned research findings can add to the knowledge on the association between EEG resting state coherence abnormalities and cognitive dysfunctions in children with ADHD and comorbid disabilities. In addition, the results suggest that weakness of interaction within and between frontal and posterior networks can be one factor in the executive and attentional deficits in children with ADHD and comorbid reading disabilities.This study had several limitations. First, it had been conducted in the absence of control group. Second, executive functions were assessed in resting‐state condition. Therefore, another brain studies in addition to cognitive tasks are needed to better clarify the main reason underlying executive dysfunction in individual with ADHD and comorbid disorders. Third, the sample size for girls was small. Due to the limited access to the group of girls with ADHD, the research was conducted with a small sample size of this group.6In conclusion, the results of the present study showed that lower EEG coherence in the comorbid group and increased theta or decreased alpha and beta coherence in the ADHD‐alone group within and between frontal regions were associated with executive dysfunction in ADHD groups. Collectively, these findings converge with findings from other studies (Barry et al., The results confirm the idea that frontal and parietal region abnormality may contribute to executive dysfunction in individuals with ADHD. We believe that EEG resting state can be useful marker for better recognize ADHD and comorbid disabilities. Therefore, by employing different cognitive tasks during EEG records we hope to better understand the relationship between EEG features and executive function in an individual with ADHD and comorbid condition.Maryam Tabiee: Conceptualization; data collection; methodology; writing original draft. Ahmad Azhdarloo: Methodology; investigation; QEEG interpretation. Mohammad Azhdarloo: Data collection; investigationThe authors declare that this study was conducted in the absence of any financial support.https://publons.com/publon/10.1002/brb3.2951.The peer review history for this article is available at


Most research on early outcomes in infants with a family history (FH) of autism has focussed on categorically defined autism, although some have language and developmental delays. Less is known about outcomes in infants with a FH of attention deficit hyperactivity disorder (ADHD).n = 131). We additionally ran an LPA using only autism and ADHD measures, and the broader LPA in an independent cohort (n = 139) and in both cohorts combined (n = 270).Infants with and without a FH of autism and/or ADHD, due to a first‐degree relative with either or both conditions, were recruited at 5 or 10 months. Three year outcomes were characterised using latent profile analysis (LPA) across measures of cognitive ability, adaptive functioning and autism, ADHD and anxiety traits (A Low Developmental Level + High Behavioural Concerns class had elevated autism, ADHD and anxiety scores, low cognitive and adaptive function, and included all but one child with autism. A Low Developmental Level + Typical Behaviour class had average cognitive ability and typical behaviour but low adaptive function. A Typical Developmental Level + Some Behavioural Concerns class had average cognitive and adaptive function but slightly elevated behaviour scores. A High Developmental Level + Typical Behaviour class had above average cognitive ability and typical behaviour. All four LPAs identified classes characterised by combinations of either, or both, Low Development Level and elevated behaviour scores, as well as a typically developing class. No classes had elevated autism or ADHD traits in isolation.Some infants with a FH of autism or ADHD have atypical developmental and behavioural outcomes, but do not show strong autism or ADHD traits in isolation. The field needs to recalibrate aims and methods to embrace the broader transdiagnostic pattern of outcomes seen in these infants. We used a broad range of outcome measures to identify the ‘natural categories’ of early atypical outcome in infants with family history of autism or ADHD. Some infants with a family history of autism or ADHD have neurodevelopmental profiles characterised by combinations of either, or both, low developmental level and atypical behaviour but not elevated autism or ADHD traits in isolation. The field needs to adopt a transdiagnostic approach in the study of early development in autism and ADHD in order to develop fit‐for‐purpose developmental models and translational opportunities. We used a broad range of outcome measures to identify the ‘natural categories’ of early atypical outcome in infants with FH of autism and/or ADHD.Some infants with a FH of autism and/or ADHD have neurodevelopmental profiles characterised by combinations of either, or both, low developmental level and atypical behaviour but not elevated autism or ADHD traits in isolation.The field needs to adopt a transdiagnostic approach in the study of early development in autism and ADHD in order to develop fit‐for‐purpose developmental models and translational opportunities.Autism is a strongly heritable condition  comprised 80 infants with a first‐degree relative (family history (FH)) with autism only (FH‐Autism), 31 infants with a first‐degree relative with ADHD only (FH‐ADHD), 21 infants with first‐degree relatives with both autism and ADHD (FH‐Autism + ADHD), and 29 infants with no first degree relative with either condition )  was the most common route. Some parents reported that they themselves had a diagnosis of either condition or they or their older child had suspected ADHD following which screening with a short version of one the Conners suite of measures was employed ) Table . Of thesThe Mullen Early Learning Composite (ELC) Mullen,  – deriveThe Autism Diagnostic Observation Schedule‐2 . An obsgsem command in Stata 16 . Models were estimated using maximum likelihood to account for data missing at random. To select the “best fitting” solution we examined conventional likelihood‐based (Bayesian information criterion (BIC)) and classification‐based (Integrated Classification Likelihood (ICL); entropy) fit statistics  and behaviour  – namely the indicator variables from which they were derived. We compared the scores of the outcome classes using ANOVA with post‐hoc Tukey‐Kramer corrections to account for unequal cell sizes and tested sex differences in class assignment using chi‐square tests followed by post‐hoc residuals adjusted for the sample size of each group Kirk, . The hign = 20) of the sample and average MAP values for each class all ≥0.83. Table Three‐ and four‐class solutions had similar entropy values  and the best fit statistics , Low Developmental Level + Typical Behaviour , Typical Developmental Level + Some Behavioural Concerns , and High Developmental Level + Typical Behaviour .Scores of the four‐classes on the outcome measures used to derive the classes are shown in Table ANOVAs and Tukey‐Kramer post‐hocs for class differences are in line with class identification. The LDL + HBC class had elevated autism, ADHD and anxiety scores, low cognitive ability and adaptive function. The LDL + TB class had low autism, ADHD and anxiety scores, average cognitive ability but below average adaptive function. The TDL + SBC class had average cognitive ability and adaptive function but slightly elevated scores on the SCQ and the CBCL ADHD and anxiety subscales. The HDL + TB class had low autism, ADHD and anxiety scores, above average cognitive ability and average adaptive function. When considered in terms of the proportion of each class falling above or below clinical thresholds .Table n = 20) of the sample and average MAP values for each class all ≥0.84 , Slight Behavioural Concerns , and Typical Behaviour . These 3 classes are similar to those identified by the LPA with a broader set of indicator variables except that the class with LDL + TB was not identified, reflecting the fact that Mullen and Vineland were not indicators. The HBC class had elevated autism and ADHD scores on the measures used to derive the classes and included all 12 childrenWe ran a second LPA using only measures of autism and ADHD . The three‐class solution provided the most robust and clinically meaningful distribution of classes, with a minimum class size comprising 17.0%  of the sample and average MAP values for each class all ≥0.91 , Typical Developmental Level + High Behavioural Concerns , Low Developmental Level + Typical Behaviour , and High Developmental Level + Typical Behaviour  (See Appendix p < 0.01) and boys in the LDL + HBC (p < 0.01) and LDL + TB (p < 0.05) classes . Similar LDL + HBC and HDL + TB classes to those described above emerged. A second atypical Low Developmental Level + Typical Behaviour (LDL + TB) class had slightly low cognitive ability and adaptive function but did not have elevated scores on autism, ADHD or anxiety measures. A Typical Developmental Level + Some Behavioural Concerns (TDL + SBC) class had slightly elevated scores on ADHD and anxiety measures and on the SCQ but not the ADOS, high average cognitive ability and average adaptive function. These patterns were reflected both in terms of group means (Table p < 0.01) and boys in the LDL + HBC (p < 0.05) and LDL + TB (p < 0.05) classes  class that had elevated autism and ADHD behaviours but also elevated anxiety and below average cognitive ability and adaptive function on measures that were not used to derive the LPA classes. Even when considering this class only in terms of the autism and ADHD indicator variables used in the LPA they had both elevated autism and ADHD scores. One other class had very slightly elevated scores on the parent‐report SCQ and CBCL‐ADHD subscale and another class typical behaviour. This pattern differs from Miller et al.  who usedAlthough we found moderately high recurrence rates of autism in our samples , autism in isolation is not the primary atypical outcome in early childhood of infants with an autism FH (with or without an ADHD FH). This is neither a new nor a surprising finding. In clinical samples both autism and ADHD commonly co‐occur with other neurodevelopmental and neuropsychiatric conditions. Studies of older siblings and family members show not only that autism and ADHD commonly co‐occur , and also elevated rates of emotional and behavioural problems  and behaviour  – namely the indicator variables from which they were derived. Since our focus was on broader transdiagnostic characterisation of developmental and behavioural outcomes in the cohorts at 3 years and not categorical diagnosis we have described the developmental outcomes as ‘low’, ‘typical’ and ‘high’ developmental level and the behavioural outcomes as ‘typical behaviour’ and ‘some’ or ‘high’ ‘behavioural concerns’. These do not equate to clinical classifications and we did not apply a strict threshold for their application – in part because across the LPAs we ran classes often had slightly different profiles of scores across the individual measures. We have used terminology and concepts from the developmental psychopathology/child psychiatry field to describe the outcome classes since ‘developmental level’ and ‘behavioural concerns’ map directly onto the indicator measures used to form LPA classes  and align with both previous literature and conventional clinical usage. However, we acknowledge the changing conceptual and linguistic landscape in the field and the outcome groups could alternatively be labelled as showing moderate or high ‘neurodivergent’ development Dwyer, .However, inspection of both the mean scores and the proportions of each identified class falling above or below the clinical cut‐points on screening and diagnostic measures, or −/+ 1SD on standardised measures, indicate that the atypical classes identified have partially distinct but also partially overlapping profiles. This approach is similar to that adopted in previous studies  and the Research Ethics Committee, Department of Psychological Sciences, Birkbeck, University of London.Supplementary MaterialClick here for additional data file.Figure S1Click here for additional data file.Figure S2Click here for additional data file.


The COVID pandemic that first gripped the world in 2020 caused social and economic dislocations; including healthcare in general, and clinical transplantation in particular . Many trin vitro T-cell inhibitory activity and demonstrated superior protection from allograft rejection in pre-clinical models but were limited to the i.v. formulation of Belatacept. Extensive clinical trials and follow-ups have confirmed the efficacy of Belatacept for kidney transplantation [Belatacept, a fusion protein of the Fc fragment of a human IgG1 linked to the extracellular domain of CTLA-4  was engiantation –8, and tantation . Subcutaantation , 10. Oveantation , due to antation  or the lantation . While rDespite all the problems and the enormous burden on the global health system, which persists to this day, the pandemic also brought forward some innovative ideas. Similar to the fruitful lessons learned from remote patient monitoring and telemedicine during the COVID pandemic, the unique experience of conversion to Abatacept during the early COVID outbreak (4) may have rekindled the interest in this agent for kidney transplantation. While the encouraging observations reported herein from a relatively large number of kidney recipients have piqued the interest for further study, the relatively short treatment interval of 3 months and lack of controls necessitates caution and the need for more evidence of safety and efficacy.ClinicalTrials.gov NCT04955366). Such trials should be encouraged and perhaps multi-center collaboration can be envisioned in the near future to seek a proper role for Abatacept in the transplant immunosuppressive drug armamentarium. At a minimum, the availability of Abatacept as a backup would also be a welcomed addition during periods of Belatacept production shortages.With this in mind, one center has embarked on a randomized controlled phase 2b conversion trial from Belatacept to Abatacept, entering kidney transplant recipients stable for at least 2 years on Belatacept and off all CNI drugs for at least 6 months (


Bartonella henselae is a species of intracellular bacteria transmitted to humans through animal bites and scratches contaminated with the feces of arthropod vectors, and are most commonly associated with cat exposure although transmission from other mammals has been reported. Bartonella henselae infection has a spectrum of clinical manifestations and has rarely been reported as cause of hemophagocytic lymphohistiocytosis (HLH) in immunocompromised hosts.Bartonella henselae infection progressing to HLH in an immunocompetent patient. The patient initially presented with regional lymphadenopathy but the diagnosis was not suspected as the patient reported no exposure to cats. On further history, he did report a scratch from a dog prior to development of symptoms. The patient was treated with methylprednisolone, intravenous immunoglobulin and anakinra for the HLH and three months of Doxycycline for Bartonella infection, with complete resolution of symptoms.We present a report of Bartonella henselae transmission can occur after exposure to other animals and vectors including dogs and clinicians need to maintain an index of suspicion for timely diagnosis. Bartonella henselae is associated with a spectrum of clinical manifestations which can include disseminated infection with severe complications such as hemophagocytic lymphohistiocytosis. Prompt initiation of Bartonella treatment is essential when thought to be the trigger for hemophagocytic lymphohistiocytosis although the optimal treatment regimen is unclear.Although commonly associated with cat exposure,  Bartonella henselae is a species of vector-borne bacteria that has been most commonly associated with direct inoculation through bites and scratches from a cat contaminated with arthropod feces [Bartonella henselae has a broad spectrum of manifestations, with treatment dependent on the specific presenting syndrome [Bartonella henselae has rarely been reported as a cause of HLH, however case reports have occurred in significantly immunocompromised hosts [Bartonella henselae infection in an immunocompetent patient which was initially not suspected in the absence of cat exposure, that subsequently progressed to HLH requiring emergent treatment.od feces , 2. The od feces . Bartoneed hosts –9. We reA 25-year-old man presented to hospital with one week of left neck swelling. Four months previously he had recently returned from an eight-month stay in South Africa and his country of birth, Namibia. While in Africa he had stayed with relatives in an urban apartment; he had no animal exposures, health care contact or participation in rural or freshwater activities. His prior medical history included systemic lupus erythematosus (SLE) previously on prednisone and hydroxychloroquine, however he had stopped all immunosuppression over six months prior to presentation out of personal convictions. He also had been incompletely treated for extensively drug-resistant tuberculous meningitis ten years prior.Physical examination revealed soft tissue swelling and warmth of the left neck and earlobe, without fever or other systemic symptoms. A computerized tomography (CT) scan showed necrotic cervical lymphadenopathy with overlying myositis and cellulitis Fig. . He was Mycobacterium tuberculosis DNA was not amplified by polymerase chain reaction (PCR) on fine needle aspirate of the lymph nodes, but there was insufficient tissue for mycobacterial culture or pathology. Excisional biopsy was not possible due to the overlying cellulitis. Blood, urine, and stool samples were smear negative for acid fast bacilli. Serology was not consistent with an SLE flare. Investigations for travel related infections were also sent including negative blood parasite smears and negative serologies for Hepatitis B, Hepatitis C, and Schistosoma. He did have positive strongyloidiasis serology with negative stool ova and parasite examination and was treated with two doses of ivermectin. He was discharged after nine days with a plan to complete fourteen days of piperacillin-tazobactam for the cellulitis followed by an excisional biopsy. Fungal cultures as well as Bartonella henselae and Brucella serology were pending at the time of discharge.He returned five days later with worsening pain. Laboratory investigations revealed mild anemia and leukocytosis with normal platelet count and liver enzymes Table . HIV serBrucella and histoplasma serologies from his first admission. However, Bartonella henselae Immunoglobulin G was noted to be strongly positive at 1:1024. Based on the strongly positive serology and hallmark clinical syndrome of painful regional lymphadenopathy, a presumptive diagnosis of Bartonella henselae infection was made. Unfortunately, the lymph node aspirate did not have sufficient sample for PCR or culture.The patient returned to hospital six days later with fever, sore throat, malaise, and fatigue. The cellulitis had improved. Investigations revealed new pancytopenia, elevated liver enzymes, hypertriglyceridemia, hyperferritinemia, hypofibrinogenemia, and elevated C-reactive protein Table  and a boOn further history, the patient reported being scratched on the left arm by a family member’s new pet dog approximately 10–14 days prior to the first emergency department visit; the dog was not known to be unwell, but the patient did not know if it was up to date on vaccinations. The patient had no exposure to cats, rodents or other animals, and had no lice, mites or other known arthropod bites, and had participated in no activities high risk for arthropod bites.Bartonella henselae infection, which was presumed to have precipitated HLH. There was initial hesitation to add immunosuppression concern for tuberculous lymphadenitis, however after the negative biopsy and given the progression of HLH, he was ultimately started on high dose methylprednisolone, intravenous immunoglobulin and anakinra. After three days, he began to show clinical improvement and was transitioned to oral prednisone 60 mg daily and other immunosuppressants were stopped. An echocardiogram showed no signs of endocarditis and repeat imagining at six weeks from initial presentation showed resolution of cervical lymphadenopathy. He completed a three-month course of doxycycline and three-month prednisone taper with complete resolution of symptoms.Under multidisciplinary care, he was started on oral doxycycline 100 mg twice daily for Bartonella are a genus of intracellular bacteria that infect mammalian reservoir hosts and are typically transmitted through arthropod vectors [Bartonella henselae is the most well described; cats are considered the reservoir host and transmission occurs through the vector Ctenocephalides felis or cat flea [Bartonella henselae may also be transmitted to humans and other incidental hosts through arthropod bites or via direct inoculation through cat bites and scratches contaminated with arthropod feces [Bartonella henselae has been referred to as Cat-Scratch disease, and has a spectrum of clinical including fever, regional lymphadenopathy, ocular and neurologic involvement, culture-negative endocarditis, hepatosplenic lesions, and angio-proliferative lesions [ vectors , 2. Bartcat flea , 4. Bartod feces , 2. For  lesions , 2, 10.Bartonella has been rapidly expanding in the past decades. Multiple Bartonella species have been identified in a wide variety of mammalian hosts including humans, cats, dogs, rabbits, rodents, horses and other wild animals [Bartonella henselae specifically has been identified both in other animals such as dogs, as well as in a variety of vectors including ticks, however their capacity to transmit infection to humans has been theorized but not confirmed [Bartonella henselae infection occurring in the absence of any cat or cat flea exposure, suggesting that alternative methods of transmission do occur, and dogs have specifically been implicated in a number of cases [However, understanding of  animals –4, 11. A animals –4, 11. Bonfirmed , 3. NoneBartonella species [Bartonella henselae was based on the combination of typical presenting syndrome , compatible exposure, strongly positive serology and response to appropriate treatment. Nonetheless we cannot rule out the possibility that the infection was caused by another cross-reactive Bartonella species [Diagnosis is another area of uncertainty because Bartonella are fastidious organisms that do not grow in typical bacterial cultures , 10. Dia species . In our Treatment of human bartonellosis depends on the specific presenting syndrome. Lymphadenitis can be treated supportively or with a short course of azithromycin , 10. NeuHLH is a life-threatening inflammatory condition where unregulated activation of macrophages results in cytokine storm, tissue damage and organ failure . A diagnMycobacterium tuberculosis, Rickettsia species, Staphylococcus species, and Escherichia coli. [HLH is classified as genetic (primary) or acquired (secondary) , 14. AcqBartonella species have been uncommonly reported as a precipitant of HLH; however, the spectrum of clinical presentations of Bartonella is still being elucidated. It is hypothesized that intracellular bacteria may trigger HLH because they reside in host immune cells and may continuously activate immune receptors [Bartonella infection, all with Bartonella henselae [eceptors . There ahenselae –9. All bhenselae –9. The mhenselae , 7−9. Thhenselae , 7, 8.Bartonella was treated with prolonged courses of either doxycycline or combination therapy regardless of clinical syndrome suggesting that the development of HLH was considered sufficient evidence of disseminated infection by the treating clinicians even in the absence of other findings [In each of the four cases that described management, findings , 7−9. HoBartonella henselae leading to HLH in an immunocompetent patient has been reported, in which the patient had two genetic variants associated with susceptibility to HLH [Bartonella has been underdiagnosed given evolving knowledge of risk factors and diagnostic testing discussed here. Given that Bartonella frequently present alongside other co-infections, it may also be missed if other serologies are incidentally positive. This may be especially relevant since Bartonella has effective treatments while many viral triggers do not.The case we present here is unusual in that the patient did not have profound immunosuppression. Although he had a diagnosis of SLE, he had been off immunosuppression for nearly six months at the time of diagnosis. Only one prior case of y to HLH . HoweverAlthough management of HLH requires prompt initiation of treatment for infection, it is unclear how the development of HLH affects the treatment when other clinical manifestations would typically require only short courses of antibiotics. Despite lymphadenitis being the main presenting symptom in our patient, we elected to consider the infection disseminated as had been done in other reported cases. There is minimal evidence to guide treatment for disseminated bartonellosis and only case reports were available regarding treatment in the setting of HLH.Bartonella henselae transmission and should keep a high index of suspicion in the setting of a compatible syndrome even in the absence of cat exposure. They should also be aware of the possibility of dissemination and severe complications such as HLH in untreated cat scratch disease. When Bartonella is the suspected trigger of HLH, prompt initiation of treatment is essential however there remains a great deal of uncertainty around what the optimal treatment regimen is in this setting.Clinicians should be aware of alternative modes of


Accumulating studies have pointed out that gut-blood and blood-brain barrier dysfunctions due to the alterations in permeability may play a role in the pathophysiology of neurodevelopmental disorders. Tight junctions are crucial components of these barriers and some peptides including claudin-5, occludin, zonulin and tricellulin are important components of these structures.This study aimed to investigate the relationship between these molecules and attention deficit hyperactivity disorder (ADHD) in children and adolescents.A total of 57 children with ADHD and 60 controls aged between 6 and 12 years were included in the study. The severity of ADHD symptoms was assessed through a parent-rated questionnaire and Conner’s Continuous Performance Test. Serum levels of biochemical variables were measured using enzyme-linked immunosorbent assay kits.Serum claudin-5 and tricellulin levels were significantly lower in the ADHD group compared to the control group. The difference between the groups in terms of serum claudin-5 and tricellulin levels remained significant after controlling for confounding factors such as age, gender and autistic characteristics. There was no significant difference between the groups in terms of serum zonulin and occludin levels. (Table 1)These results suggest that claudin-5 and tricellulin may be involved in the etiopathogenesis of ADHD. Alterations in these peptides may affect the brain by leading a dysregulation in intestinal or blood-brain barrier permeability that eventually affects the gut-brain axis. The causal relationship between these peptides and ADHD requires further investigation.None Declared