Search

Abstract Background Behavioural parent training (BPT) is a psychosocial intervention designed for children with attention deficit hyperactivity disorder (ADHD). BPT programs teach parents to use effective commands or rules whilst encouraging them to pay careful attention to their child’s appropriate behaviour. In this study, we will investigate the efficacy of BPT on parental stress, mothers’ sense of emotional closeness to their children, and children’s attachment security to their mothers. We will also examine the effects of BPT on children’s internalising and externalising symptoms, ADHD symptoms, and sensitivity to rewards and punishments compared to usual care alone. The use of bias-prone assessment tools limits the ability of previous studies to assess effectiveness. Therefore, in this study, the child’s attachment security will be assessed in a structured interview conducted by assessors blinded to group allocation, and brain changes will be assessed using magnetic resonance imaging. Methods This randomised controlled clinical trial will aim to compare the efficacy of BPT to routine clinical care for 60 children with ADHD. Participants will be randomised, with stratification by medication status for ADHD (medicated or non-medicated). The BPT intervention group will receive parent training weekly for 10 weeks in a group of six or less. The primary outcome measure will be changes in parental stress. Furthermore, the key secondary outcome measure will be the child’s attachment security, which will be assessed in an interview conducted by assessors blinded to group allocation. We will also evaluate changes in neural connectivity in both children and mothers using magnetic resonance imaging. Other secondary outcomes will include child behavioural problems, ADHD symptoms, emotional regulation, child sensitivity to rewards and punishments, parental behaviour, and the child and parent’s social support network following the completion of 10 sessions. Discussion This study represents the first randomised controlled trial exploring the efficacy of BPT on child attachment security and mothers’ sense of emotional closeness to their children. It aims to provide robust evidence to assist parents of children with ADHD in making appropriate treatment decisions. Trial registration UMIN000038693. Registered on November 9, 2019.

Mathematical algorithms known as “epigenetic clocks” use methylation values at a set of CpG sites to estimate the biological age of an individual in a tissue-specific manner. These clocks have demonstrated both acceleration and delays in epigenetic aging in multiple neuropsychiatric conditions, including schizophrenia and neurodevelopmental disorders such as autism spectrum disorder. However, no study to date has examined epigenetic aging in ADHD despite its status as one of the most prevalent neurodevelopmental conditions, with 1 in 9 children having ever received an ADHD diagnosis in the US. Only a handful of studies have examined epigenetic age in brain tissue from neurodevelopmental conditions, with none focused on ADHD, despite the obvious relevance to pathogenesis. Thus, here we asked if post-mortem brain tissue in those with lifetime histories of ADHD would show accelerated or delayed epigenetic age, as has been found for other neurodevelopmental conditions. We applied four different epigenetic clocks to estimate epigenetic age in individuals with ADHD and unaffected controls from cortical (anterior cingulate cortex, N = 55) and striatal (caudate, N = 56) post-mortem brain tissue, as well as peripheral blood (N = 84) and saliva (N = 112). After determining which epigenetic clock performed best in each tissue, we asked if ADHD was associated with altered biological aging in corticostriatal brain and peripheral tissues. We found that a range of epigenetic clocks accurately predicted chronological age in all tissues. We also found that a diagnosis of ADHD was not significantly associated with differential epigenetic aging, neither for the postmortem ACC or caudate, nor for peripheral tissues. These findings held when accounting for comorbid psychiatric diagnoses, substance use, and stimulant medication. Thus, in this study of epigenetic clocks in ADHD, we find no evidence of altered epigenetic aging in corticostriatal brain regions nor in peripheral tissue. We consider reasons for this unexpected finding, including the limited sampling of brain regions, the age range of individuals studied, and the possibility that processes that accelerate epigenetic age may be counteracted by the developmental delay posited in some models of ADHD.

Abstract While epigenetic modifications have been implicated in ADHD through studies of peripheral tissue, to date there has been no examination of the epigenome of the brain in the disorder. To address this gap, we mapped the methylome of the caudate nucleus and anterior cingulate cortex in post-mortem tissue from fifty-eight individuals with or without ADHD. While no single probe showed adjusted significance in differential methylation, several differentially methylated regions emerged. These regions implicated genes involved in developmental processes including neurogenesis and the differentiation of oligodendrocytes and glial cells. We demonstrate a significant association between differentially methylated genes in the caudate and genes implicated by GWAS not only in ADHD but also in autistic spectrum, obsessive compulsive and bipolar affective disorders through GWAS. Using transcriptomic data available on the same subjects, we found modest correlations between the methylation and expression of genes. In conclusion, this study of the cortico-striatal methylome points to gene and gene pathways involved in neurodevelopment, consistent with studies of common and rare genetic variation, as well as the post-mortem transcriptome in ADHD.

Abstract The development of treatment biomarkers for psychiatric disorders has been challenging, particularly for heterogeneous neurodevelopmental conditions such as attention-deficit/hyperactivity disorder (ADHD). Promising findings are also rarely translated into clinical practice, especially with regard to treatment decisions and development of novel treatments. Despite this slow progress, the available neuroimaging, electrophysiological (EEG) and genetic literature provides a solid foundation for biomarker discovery. This article gives an updated review of promising treatment biomarkers for ADHD which may enhance personalized medicine and novel treatment development. The available literature points to promising pre-treatment profiles predicting efficacy of various pharmacological and non-pharmacological treatments for ADHD. These candidate predictive biomarkers, particularly those based on low-cost and non-invasive EEG assessments, show promise for the future stratification of patients to specific treatments. Studies with repeated biomarker assessments further show that different treatments produce distinct changes in brain profiles, which track treatment-related clinical improvements. These candidate monitoring/response biomarkers may aid future monitoring of treatment effects and point to mechanistic targets for novel treatments, such as neurotherapies. Nevertheless, existing research does not support any immediate clinical applications of treatment biomarkers for ADHD. Key barriers are the paucity of replications and external validations, the use of small and homogeneous samples of predominantly White children, and practical limitations, including the cost and technical requirements of biomarker assessments and their unknown feasibility and acceptability for people with ADHD. We conclude with a discussion of future directions and methodological changes to promote clinical translation and enhance personalized treatment decisions for diverse groups of individuals with ADHD.

Abstract Background Recent research has shown the mental health consequence of social distancing during the COVID-19 pandemic, but longitudinal data are relatively scarce. It is unclear whether the pattern of isolation and elevated stress seen at the beginning of the pandemic persists over time. This study evaluates change in social interaction over six months and its impact on emotional wellbeing among older adults. Methods We drew data from a panel study with six repeated assessments of social interaction and emotional wellbeing conducted monthly May through October 2020. The sample included a total of 380 White, Black and Hispanic participants aged 50 and over, of whom 33% had low income, who residing in fourteen U.S. states with active stay-at-home orders in May 2020. The analysis examined how change in living arrangement, in-person interaction outside the household, quality of relationship with family and friends, and perceived social support affected trajectories of isolation stress, COVID worry and sadness. Results While their living arrangements (Odds Ratio [OR] = 0.95, 95% Confidence Interval [CI] = 0.87, 1.03) and relationship quality (OR = 0.94, 95% CI = 0.82, 1.01) remained stable, older adults experienced fluctuations in perceived social support (linear Slope b = -1.42, s.e. = 0.16, p

Abstract Attention-deficit/hyperactivity disorder (ADHD) is associated with a wide array of neural and cognitive features, and other psychiatric disorders, identified mainly through cross-sectional associations studies. However, it is unclear if the disorder is causally associated with these neurocognitive features. Here, we applied a two-sample bidirectional Mendelian randomization (MR) study to summary GWAS data to explore the presence and direction of a causal effect between ADHD and a range of neurocognitive features and other psychiatric disorders. The inverse variance weighted method was used in the main analysis, and two MR methods (MR-Egger, weighted median) were used for robustness checks. We found that genetic risk for ADHD was causally associated with a decreased area of lateral orbitofrontal cortex. Conversely, we found that brain volume and some features of intrinsic functional connectivity had causal effects on ADHD risk. Bidirectional causal links were found between ADHD and adult general intelligence, as well as depression and autistic spectrum disorders. Such work highlights the important ties between ADHD and general cognitive ability, and suggest some neural features, previously merely associated with the disorder, may play a causal role in its pathogenesis.

Summary: Background: Attention deficit/hyperactivity disorder (ADHD) is usually conceptualized as a childhood-onset neurodevelopmental disorder, in which symptoms either decrease steadily into adulthood or remain stable. A recent study challenged this view, reporting that for most with ADHD, diagnostic status fluctuates with age. We ask if such a ‘fluctuating’ ADHD symptom trajectory subgroup is present in other population-based and clinic-based cohorts, centered on childhood and adolescence. Methods: Cohorts were the population-based Adolescent Brain Cognitive Development (ABCD: N = 9735), Neurobehavioral Clinical Research (NCR: N = 258), and the Nathan Kline Institute-Rockland (NKI-Rockland: N = 149). All participants had three or more assessments spanning different age windows. Participants were categorized into developmental diagnostic subgroups: fluctuant ADHD (defined by two or more switches between meeting and not meeting ADHD criteria), remitting ADHD, persisting ADHD, emerging ADHD and never affected. Data were collected between 2011 and 2022. Analyses were performed between May 2022 and April 2023. Findings: A subgroup with fluctuant child and adolescent ADHD diagnoses was found in all cohorts (29.3% of participants with ADHD in ABCD, 26.6% in NCR and 17% in NKI-Rockland). While the proportion of those with fluctuant ADHD increased with the number of assessments, it never constituted the dominant subgroup. Interpretation: We provide further evidence in three cohorts for the existence of a fluctuant ADHD diagnostic subgroup during childhood and adolescence, albeit in a minority of cases. Such fluctuant child and adolescent ADHD diagnoses may suggest a natural history more akin to relapsing-remitting mood disorders and/or a marked sensitivity to environmental shifts that occur across development. Funding: Intramural programs of the NHGRI and NIMH.

The undeniable importance of reading in higher education prompted this investigation into the reading skills of a group often overlooked in previous research: master's level students studying in English-medium instruction (EMI) environments. Participants (148 master's-level students of engineering) completed the Nelson-Denny Reading Test (Form G), a test of reading speed and reading comprehension. The results indicate that, at group level, these students attained levels of comprehension and rates of (silent) reading which are broadly comparable to those found for second-language users of English in better researched settings. However, a great deal of individual variation was observed, suggesting that some students may find it challenging to read for study purposes. The implications of these findings for various stakeholder groups in EMI are discussed.

The treatment of a variety of protozoal infections, in particular those causing disabling human diseases, is still hampered by a lack of drugs or increasing resistance to registered drugs. However, in recent years, remarkable progress has been achieved to combat neglected tropical diseases by sequencing the parasites’ genomes or the validation of new targets in the parasites by novel genetic manipulation techniques, leading to loss of function. The novel amino acid hypusine is a posttranslational modification (PTM) that occurs in eukaryotic initiation factor 5A (EIF5A) at a specific lysine residue. This modification occurs by two steps catalyzed by deoxyhypusine synthase (dhs) and deoxyhypusine hydroxylase (DOHH) enzymes. dhs from Plasmodium has been validated as a druggable target by small molecules and reverse genetics. Recently, the synthesis of a series of human dhs inhibitors led to 6-bromo-N-(1H-indol-4yl)-1-benzothiophene-2-carboxamide, a potent allosteric inhibitor with an IC50 value of 0.062 µM. We investigated this allosteric dhs inhibitor in Plasmodium. In vitro P. falciparum growth assays showed weak inhibition activity, with IC50 values of 46.1 µM for the Dd2 strain and 51.5 µM for the 3D7 strain, respectively. The antimalarial activity could not be attributed to the targeting of the Pfdhs gene, as shown by chemogenomic profiling with transgenically modified P. falciparum lines. Moreover, in dose-dependent enzymatic assays with purified recombinant P. falciparum dhs protein, only 45% inhibition was observed at an inhibitor dose of 0.4 µM. These data are in agreement with a homology-modeled Pfdhs, suggesting significant structural differences in the allosteric site between the human and parasite enzymes. Virtual screening of the allosteric database identified candidate ligand binding to novel binding pockets identified in P. falciparum dhs, which might foster the development of parasite-specific inhibitors.

Abstract Categorical diagnoses from the Diagnostic and Statistical Manual of Mental Disorders (DSM) or International Classification of Diseases (ICD) manuals are increasingly found to be incongruent with emerging neuroscientific evidence that points towards shared neurobiological dysfunction underlying attention deficit/hyperactivity disorder and autism spectrum disorder. Using resting-state functional magnetic resonance imaging data, functional connectivity of the default mode network, the dorsal attention and salience network was studied in 1305 typically developing and diagnosed participants. A transdiagnostic hierarchical Bayesian modeling framework combining Indian Buffet Processes and Latent Dirichlet Allocation was proposed to address the urgent need for objective brain-derived measures that can acknowledge shared brain network dysfunction in both disorders. We identified three main variation factors characterized by distinct coupling patterns of the temporoparietal cortices in the default mode network with the dorsal attention and salience network. The brain-derived factors were demonstrated to effectively capture the underlying neural dysfunction shared in both disorders more accurately, and to enable more reliable diagnoses of neurobiological dysfunction. The brain-derived phenotypes alone allowed for a classification accuracy reflecting an underlying neuropathology of 67.33% (+/−3.07) in new individuals, which significantly outperformed the 46.73% (+/−3.97) accuracy of categorical diagnoses. Our results provide initial evidence that shared neural dysfunction in ADHD and ASD can be derived from conventional brain recordings in a data-led fashion. Our work is encouraging to pursue a translational endeavor to find and further study brain-derived phenotypes, which could potentially be used to improve clinical decision-making and optimize treatment in the future.

In a parallel-language environment students are often required to read in a language different from the one they use in lectures, seminars, and among themselves. Relatively little research has been done on the overall reading success of such groups or on the componential make up of their L2 reading skills. This paper compares the English-language reading skills of Swedish students of biology with that of equivalent British biology students. Many Swedish readers perform within or above the normal British range on the study-reading test, but the overall average score of this sample of Swedish readers was considerably lower than that of the British sample. For the Swedes study-reading success correlates significantly with vocabulary knowledge, inferencing and newspaper reading, and at a lower level for word recognition speed. For the British informants the pattern is similar, but with no significant correlation for word-recognition speed. Multiple regression analyses show that academic vocabulary knowledge test scores can account for nearly half the variance in study-reading scores and newspaper reading test scores for about ten percent more. For the British informants the same pattern emerged, but the contributions of vocabulary knowledge was considerably greater and that of newspaper skimming rather less.

In a parallel-language environment the use of textbooks in English in courses otherwise in the local language is naturalized and not widely discussed or questioned. The aim of this study was to elicit the attitudes and syllabus infrastructure that underlie the practice. A large-scale survey was carried out and answers were obtained from over 20% of teachers at Swedish universities. Results confirmed that a majority regarded English as important during and/or after university studies and showed that they considered the use of English-language textbooks as providing a useful opportunity for incidental language learning. In strong contrast to the situation in a content and language integrated learning environment, only a small minority of courses were reported to have any specified learning outcome related to English. Open answers showed awareness of the benefits and risks of parallel-language practices, but no interest in making aims explicit. In our view, there is no contradiction between incidental learning and explicit aims, and course aims which remain implicit make rational planning and constructive alignment more difficult. They also inhibit discussion of appropriate methodology.

In a parallel language environment it is important that teaching takes account of both the languages students are expected to work in. Lectures in the mother tongue need to offer access to textbooks in English and encouragement to read. This paper describes a preliminary study for an investigation of the extent to which they actually do so. A corpus of lectures in English for mainly L1 English students (from BASE and MICASE) was examined for the types of reference to reading which occur, classified by their potential usefulness for access and encouragement. Such references were called ‘intertextual episodes’. Seven preliminary categories of intertextual episode were identified. In some disciplines the text is the topic of the lecture rather than a medium for information on the topic, and this category was not pursued further. In the remaining six the text was a medium for information about the topic. Three of them involved management, of texts by the lecturer her/himself, of student writing, or of student reading. The remaining three involved reference to the content of the text either introducing it to students, reporting its content, or, really the most interesting category, relativizing it and thus potentially encouraging critical reading. Straightforward reporting that certain content was in the text at a certain point was the most common type, followed by management of student reading. Relativization was relatively infrequent. The exercise has provided us with categories which can be used for an experimental phase where the effect of different types of reference can be tested, and for observation of the references actually used in L1 lectures in a parallel-language environment.

Philip Shaw reviews the current exhibition at the National Library of Medicine in Bethesda, Maryland.

The present quantitative study focuses on witnesses’ speech in Swedish criminal trials, more specifically on potential differences between men’s and women’s language styles. Since the 1970s, research on language and gender has been divided into three main approaches towards the relationship between men’s and women’s language use: the deficit approach, the dominance approach and the cultural approach. The present study uses the more recent dynamic approach to show how gender is acted out in each situation taking into account a number of factors, e.g. context. The aim of our work is first and foremost to study the possible correlation between the witnesses’ gender and language in the courtroom context and then to investigate if income and/or level of education provide better explanations for possible variation by looking at a broad range of linguistic variables. The results show no statistically significant gender or social status differences in the witnesses’ speech. However, when comparing the results of the testifying police officers accidentally included in the study with the rest of the witnesses, the differences turned out to be significant. This shows that, in this case, factors such as previous courtroom experience and familiarity with the context were probably more influential on the speech of the informants than gender, income and education, in conformity with the assumptions of the dynamic approach.

Intertextuality is essential in academic writing but it is governed by quite complex conventions. Different intertextuality practices can be judged evidence of academic com-petence or incompetence, or condemned as plagiarism. Learners can break the conventions with criminal intent, or from ignorance, or because their language proficiency prevents them from doing anything else. This paper reports the results of interviews with academic staff in a British university and their postgraduate students about intertextuality practices. The interviewees ahowed a wide range of – sometimes contradictory – attitudes to quotation, referencing, and copying. Several pointed out the developmental advantages of various types of copying.

No abstract.

This article is concerned with the teaching of pragmatic functions when training stu-dents for a future career in intercultural business communication. Having outlined six important constellations likely to result in success or failure, we focus on strategies for the successful handling of customer complaints seen in comparison with responses to complaints in everyday interactions. It is suggested that transfer of behaviour con-sidered suitable in everyday face-to-face interaction to business interaction may lead to unsuccessful processing of customer complaints.