South Africa presents with high preterm birth (PTB) and low birth weight (LBW) rates (14.17%). Numerous conditions characterised by language impairment are associated with LBW and/or PTB. Speech-language therapists may fail to identify older children whose language impairment may have originated from LBW and/or PTB.To describe the frequency of LBW and/or PTB, in comparison with full-term birth, and associated conditions in children at an early communication intervention (ECI) clinic.Retrospective data of 530 children aged 3–74 months were analysed, with 91.9% presenting with language impairment.Almost 40% had LBW and/or PTB, and late PTB was the largest category. Factors associated with LBW and/or PTB were prenatal risks, including small-for-gestational age, perinatal risks, including caesarean section, and primary developmental conditions. Secondary language impairment was prevalent, associated with genetic conditions and global developmental delay.The frequency of LBW and/or PTB was unexpectedly high, drawing attention to the origins of language impairment in almost 40% of the caseload at the ECI clinic. As a low-to-middle-income country, South Africa presents with preterm birth (PTB)  and low birth weight (LBW) (< 2500 g) rates as high as 14.17%, as opposed to 7% in high-income countries , with a gender distribution of 333 (63%) males and 197 (37%) females. The male gender bias in the sample is a known risk factor in children with language impairment  was used to analyse the data. Data were divided into two distinct groups: the LBW and/or PTB group, which included all children who were born preterm, or LBW or were born preterm with LBW; and the NBW and/ or FT group, which included children who were FT or post-term, with normal or high birth weight. For this distinction, the WHO classification system for PTB and LBW was used  was used to identify significant associations between variables. Associations between variables were investigated for the two groups to determine if there were significant differences between children with LBW and/or PTB, and children born FT with NBW. A significance level of p ≤ 0.05 was deemed significant. Owing to the retrospective nature of the study, patient files were not all complete for every variable considered. Results were, therefore, based on the available data for each variable.Descriptive statistics were calculated for all variables, including means, standard deviations and proportions. Student’s Institutional ethical clearance was obtained for the study before data collection was initiated (protocol number 12142078-GW20160314HS).n = 528). The average gestational age for the LBW and/or PTB group was 35 weeks, which is considered late preterm (32–37 weeks), whereas the average for the NBW and/or FT group was 39.3 weeks, which is FT (38–41 weeks). The average birth weight for the LBW and/or PTB group was 2303.3 g, which corresponds with infants born late preterm  had language impairment. This high frequency occurrence is linked to the clinic’s typical service users, that is, young children with communication and language concerns. The majority of the preterm children in the sample, 143 out of 176 (81.25%), were late preterm (35 weeks), with LBW (2303.3 g). It is known that late PTB represents the largest group of children with LBW and/or PTB, occurring five times more than children born before 32 weeks’ gestational age, or 80% of the population , are linked to LBW and/or PTB  than in the NBW and/or FT group (26.8%). Rushe  found thFactors found to be most significantly associated with PTB and LBW in this study were small-for-gestational age, maternal prenatal risks, caesarean section delivery and postnatal risks. Maternal prenatal risks were found to be significantly associated with LBW and/or PTB. Factors such as medical conditions and treatment during pregnancy; mental health conditions; placental problems such as pre-eclampsia; multiple pregnancy; and smoking, alcohol and drug use during pregnancy are known risks for LBW and/or PTB Allen, . It is aThe frequency of LBW and/or PTB was almost 40% in the study sample of children with language impairment. In this predominantly late LBW and/or PTB sample, secondary language impairment was prevalent and found to be associated with genetic conditions and global developmental delay. The finding concurs with some studies suggesting that primary language impairment is not more prevalent among children with LBW and/or PTB than among those born NBW and/or FT, but rather occurs as a secondary impairment. The large sample size of the study strengthens the reliability of the findings. Limitations of the study include the sample size being limited to a single ECI clinic with a predominantly middle-to-high income population within South Africa, thus not offering insight applicable to the wider population of children with language impairment in South Africa. Furthermore, the LBW and/or PTB group were compared to FT children with language impairment, not with typically developing children. Further research in the prevalence of language impairment among preterm infants within the South African population, and the distinction between primary and secondary language impairment within this population, may provide further insight into the impact that PTB and/ or LBW has on language development.Children with LBW and/or PTB can be identified early, as they enter the health care system upon their untimely birth. With a known risk for language impairment and subsequent risk for learning difficulties, timely ECI is essential. The LBW and/or PTB population in South Africa and elsewhere is a growing health concern requiring attention and public awareness. Young children with LBW and/or PTB and their mothers should ultimately benefit from the National Integrated Early Childhood Development System, as ‘many disabilities are preventable or could have their severity limited if pregnant women, infants and young children received access to early quality screening, preventative and rehabilitative care’ (Republic of South Africa [RSA],


The aim of the current paper is to provide the first comparison of computational mechanisms and neurofunctional substrates in adolescents with attention-deficit/hyperactivity disorder (ADHD) and adolescents with obsessive-compulsive disorder (OCD) during decision making under ambiguity.Sixteen boys with ADHD, 20 boys with OCD, and 20 matched control subjects (12–18 years of age) completed a functional magnetic resonance imaging version of the Iowa Gambling Task. Brain activation was compared between groups using three-way analysis of covariance. Hierarchical Bayesian analysis was used to compare computational modeling parameters between groups.Patient groups shared reduced choice consistency and relied less on reinforcement learning during decision making relative to control subjects, while adolescents with ADHD alone demonstrated increased reward sensitivity. During advantageous choices, both disorders shared underactivation in ventral striatum, while OCD patients showed disorder-specific underactivation in the ventromedial orbitofrontal cortex. During outcome evaluation, shared underactivation to losses in patients relative to control subjects was found in the medial prefrontal cortex and shared underactivation to wins was found in the left putamen/caudate. ADHD boys showed disorder-specific dysfunction in the right putamen/caudate, which was activated more to losses in patients with ADHD but more to wins in control subjects.The findings suggest shared deficits in using learned reward expectancies to guide decision making, as well as shared dysfunction in medio-fronto-striato-limbic brain regions. However, findings of unique dysfunction in the ventromedial orbitofrontal cortex in OCD and in the right putamen in ADHD indicate additional, disorder-specific abnormalities and extend similar findings from inhibitory control tasks in the disorders to the domain of decision making under ambiguity. Attention-deficit/hyperactivity disorder (ADHD) is defined by age-inappropriate problems with inattention, impulsivity, and hyperactivity In early models, ADHD and OCD were placed at opposing ends of a hypothesized impulsivity-compulsivity spectrum One of the most commonly used tasks to measure reward-based decision making is the Iowa Gambling Task (IGT), in which participants are instructed to select cards one at a time from one of four possible decks In the brain, performance during decision making on the IGT recruits activation in the ventromedial orbitofrontal cortex (vmOFC) and the ventral striatum (VS), regions that are closely interconnected as part of a dopaminergic mesolimbic circuit The aim of this study was to conduct a comparison of neurofunctional abnormalities during performance of the IGT in adolescent ADHD and OCD patients. In both patient groups we anticipated an impaired ability to align deck choice with expected values Fifty-six  right-handed Control participants had no diagnoses of any psychiatric conditions and were recruited using local advertising. Data for some participants have been published elsewhere The study was conducted in accordance with the Declaration of Helsinki. Ethical approval was obtained from the local Research Ethics Committee (05/Q0706/275). Study details were explained to both child and guardian, and written informed consent was obtained for all participants.Participants were presented with four decks of cards  on a computer screen and asked to select one of the decks by pressing with their right hand one of four buttons. Participants completed 80 trials and were instructed to win as much money as possible and lose as little money as possible. Participants were not informed of how many trials they would perform. There was a 50% probability of winning on each deck. Decks A and B (disadvantageous decks) gave relatively large gains  but even larger losses , whereas decks C and D (advantageous decks) gave small gains  but even smaller losses . A £2,000 “loan” and running total were presented at the bottom of the task display.Each trial of the IGT is divided as follows: 1) the choice phase, 2) a 6-second delay between choosing a deck and being presented with the outcome, and 3) the 3-second outcome evaluation phase. Total trial length was 15 seconds, ending with a blank screen after outcome presentation that served as an implicit baseline in the functional magnetic resonance imaging (fMRI) analysis .Participants were informed that performance on the task determined the amount of money they would receive at the end of the session. In fact, all participants received the full amount (£30). Participants were acclimatized to the scanner environment in a “mock” scanner. This practice session consisted of 12 trials that presented equal payoffs across all decks. Participants were informed of this difference between the practice and experimental sessions. After completing the practice session, the researcher ensured that all participants understood the task through discussion with the participant and accompanying parent..7.5.6; https://jasp-stats.org/). Models were favored if Bayesian factor (BF)10 > 10 IGT net score was calculated for all 80 trials and separately for each of four blocks of 20 trials. Analysis of performance data was conducted using Bayesian analysis in JASP ; and ω is the reinforcement learning weight The winning value-plus-perseverance model is a hybrid reinforcement learning and perseverance model. In this eight-parameter model, α represents feedback/magnitude sensitivity; λ represents loss-aversion; The fMRI images were acquired at King’s College London on a 3T General Electric Signa Horizon HDx MRI scanner  see .Data were analyzed using the nonparametric XBAM (v4.1) software p < .05; so as to maximize detection power, we used the highest threshold that we have shown empirically to give good type I error control at the cluster level under the null hypothesis using our permutation-based method p value threshold was computed from the data using our permutation-based method such that the final expected number of type I error clusters was < 1  based on regions shown to play a role in IGT performance and/or to differ between ADHD and OCD groups or between patient groups and control subjects p < .004 for the choice phase and p < .0045 for the outcome phase.Follow-up whole-brain comparisons of between-group differences were performed. For the between-group comparisons, <1 false activated cluster was expected at a cluster threshold of t tests (corrected for multiple comparisons for three groups using the least significance difference method). Within-group findings are presented in To interpret the group differences in brain activation from the between-group analysis of covariance, statistical measures of blood oxygen level–dependent response for each participant were extracted from significant clusters, plotted, and subjected to pairwise  post hoc 10 = 3.29, F2,53 = 4.48, p = .02), which was lower in patients with ADHD relative to control subjects (p = .007) and patients with OCD (p = .02), although all groups scored in the normal range for IQ, and no participant had IQ <85. Eight ADHD boys were medication naïve, and 8 were receiving stimulant medication. Sixteen boys with OCD were medication naïve, while 4 were being treated with selective serotonin reuptake inhibitor medication, and 1 patient was receiving risperidone augmentation treatment.There were no group differences in age . Groups 10 = 0.56,F2,53 = 1.18, p = .17), no main effect of block , and no group by block interaction effect . There were no group differences in reaction time or group by choice type interactions on reaction time .A 3 (group) × 4 (block) within-between repeated measures ANOVA showed no credible main effect of group in overall net score (BFion time . Findingc) compared with patients with ADHD  and patients with OCD , as well as higher reinforcement learning weights (ω) than patients with ADHD  and patients with OCD . Patients with ADHD showed increased feedback sensitivity relative to control subjects . There were no credible or significant correlations between symptoms  and model parameters . Complete tables of differential distributions and mean parameter estimates from the value-plus-perseverance model are presented in Control subjects showed greater choice consistency .The ANOVA analysis showed no group differences in mean Euclidean displacement , right putamen (p < .05), precuneus (p = .02), and MPFC (p = .03) remained significant only at relaxed cluster thresholds. An exploratory analysis using a whole-brain cluster threshold of p < .05 is included in the In the outcome phase, within the ROI, left putamen/caudate underactivation to wins was found in ADHD and OCD patients relative to control subjects. In right putamen/caudate, ADHD patients showed disorder-specific dysfunction relative to control subjects and patients with OCD. Patients with ADHD showed greater activation to losses, while control subjects showed greater activation to wins, and OCD patients showed little difference between conditions. In the whole brain, ADHD and OCD patients shared precuneus underactivation during wins relative to control subjects, as well as underactivation during losses in medial PFC (MPFC)  and 2. AThe study investigated shared and disorder-specific neural and computational abnormalities during the IGT in adolescent ADHD and OCD. During decision making, both patient groups shared VS underactivation during advantageous choices, but patients with OCD showed disorder-specific underactivation in vmOFC relative to both control subjects and patients with ADHD. During the outcome phase, shared underactivation in patients to wins was found in the left putamen, and shared underactivation to losses was seen in the MPFC. Disorder-specific dysfunction was found in the right putamen/caudate, which was activated more to wins in control subjects but more to losses in patients with ADHD.There were no significant group differences in net scores, unlike in previous work in both disorders in adolescent samples The computational modeling showed that patient groups made more exploratory choices from decks with lower expected rewards and were more likely to make decisions based on feedback from the most recent trial rather than based on reward expectancies formed over successive trials relative to control subjects .Previous work has reported reduced choice consistency in ADHD In OCD, increased exploration of nonoptimal decks may be related to greater intolerance of uncertainty, reduced confidence in memories and decisions, and increased need for information sampling in the disorder A disorder-specific finding was that ADHD patients alone showed heightened feedback sensitivity. Although sensitivity to the magnitude of deck outcomes is important for IGT performance, increased sensitivity may lead to a tendency to chase large wins on the disadvantageous decks. Heightened feedback sensitivity on the IGT has been associated with impulsivity related behaviors and disorders In the brain, the VS was underactive during advantageous choices in patient groups relative to control subjects. The VS responds to reinforcers including monetary reward In ADHD, the dopamine response in the VS to previously neutral cues or behaviors that are now associated with reward is hypothesized to be disrupted, meaning that the motivational features and underlying VS activation that these cues take on in control subjects may be decreased in ADHD In OCD, findings of VS underactivation are consistent with previous reports of reduced VS response to cues that predict reward As hypothesized, adolescents with OCD showed disorder-specific underactivation in vmOFC during advantageous choices. The vmOFC is closely interconnected with VS and is a key structure for flexible emotional learning and decision making During outcome processing, an unexpected finding was that unlike in some The whole-brain analysis revealed that patient groups shared reduced activation to losses in MPFC. Underactivation to losses in the MPFC is in line with previous findings of reduced MPFC localized feedback–related negativity to monetary loss in ADHD patients Limitations include, first, the fact that 50% of patients with ADHD were receiving stimulant medication, while 20% of patients with OCD were receiving antidepressant medication and one patient with OCD was receiving risperidone. There were too few unmedicated patients to conduct a subgroup analysis. These medication treatments may alter functioning in the dopaminergic mesolimbic pathways responsible for decision making and outcome processing, with stimulant medications increasing striatal dopamine in ADHD, but selective serotonin reuptake inhibitors and risperidone reducing dopaminergic functioning in OCD In summary, this is the first study to compare decision making under ambiguity in adolescent ADHD and OCD using fMRI and computational modeling. Findings of shared choice consistency impairments and smaller reinforcement learning weights, as well as findings of shared VS underactivation during advantageous choices, suggest impairment in both disorders in representing and utilizing learned reward expectancies during decision making. Findings of reduced sensitivity to outcomes in MPFC and left putamen suggest shared alterations in outcome processing when outcomes must be used to guide future behavior. Disorder-specific dysfunction in the vmOFC in OCD and in the right putamen in ADHD parallel previous, similar multimodal meta-analytic findings in voxel-based morphometry studies and fMRI studies of inhibitory control, indicating a possible preservation of disorder-specific markers across tasks and modalities.


Viperin is an interferon-inducible protein that responsible for a variety of antiviral responses to different viruses. Our previous study has shown that the ribonuclease UL41 of herpes simplex virus 1 (HSV-1) can degrade the mRNA of viperin to promote HSV-1 replication. However, it is not clear whether other HSV-1 encoded proteins can regulate the function of viperin. Here, one novel viperin associated protein, glycoprotein D (gD), was identified. To verify the interaction between gD and viperin, gD and viperin expression plasmids were firstly co-transfected into COS-7 cells, and fluorescence microscope showed they co-localized at the perinuclear region, then this potential interaction was confirmed by co-immunoprecipitation (Co-IP) assays. Moreover, confocal microscopy demonstrated that gD and viperin co-localized at the Golgi body and lipid droplets. Furthermore, dual-luciferase reporter and Co-IP assays showed gD and viperin interaction leaded to the increase of IRF7-mediated IFN-β expression through promoting viperin and IRAK1 interaction and facilitating K63-linked IRAK1 polyubiquitination. Nevertheless, gD inhibited TRAF6-induced NF-κB activity by decreasing the interaction of viperin and TRAF6. In addition, gD restrained viperin-mediated interaction between IRAK1 and TRAF6. Eventually, gD and viperin interaction was corroborated to significantly inhibit the proliferation of HSV-1. Taken together, this study would open up new avenues toward delineating the function and physiological significance of gD and viperin during HSV-1 replication cycle. Herpes simplex virus 1 (HSV-1), a widespread human pathogen that can cause lytic infection in mucosal epithelial cells and life-long latent infection in neurons, is a nuclear-replicating DNA virus with a genome encoding ~80 different proteins, among which at least 44 proteins are the structural components of the virions. According to their known or putative localizations in the virions, the proteins can be classified into five groups, namely envelope, tegument, capsid, unclassified, and non-structural proteins .HSV-1 glycoproteins are found in the virion envelope as well as membrane of the infected cell, and gD is a multifunctional protein that can interact with three cellular receptors for entry , includiIt is well-known that innate immune response is the first line for host defense. When viral infection, virus can activate the host innate antiviral response and result in the expression of series cellular protective genes, e.g., proinflammatory cytokines and type I interferon , which then induces a subset of interferon-stimulated genes (ISGs) to reinforce IFN-I signaling and prime cells with enhanced antiviral activity to inhibit viral replication , 12.Viperin is an evolutionarily conserved iron-sulfur (Fe-S) cluster-binding protein –15, whicSince IFN-I and nuclear factor B (NF-κB) play key roles in regulating the antiviral response , HSV-1 hCOS-7 and HEK293T cells were cultured at 37°C in Dulbecco's modified MEM (DMEM. Gibco-BRL) supplemented with 10% heat inactivated fetal bovine serum .Mouse anti-Flag, anti-Myc, anti-hemagglutinin (HA), and anti-β-actin monoclonal antibodies (mAbs) were purchased from ABmart. Rabbit anti-Flag polyclonal antibody (pAb) was purchased from Proteintech. Mouse non-specific control IgG antibody was purchased from eBioscience Inc. Rabbit anti-gD pAb was gifted by Dr. Roselyn J. Eisenberg , and mouse anti-gD mAb was purchased from Santa Cruz Biotechnology.EcoRI and BamHI and then inserted into the corresponding digested pEYFP-N1 (Clontech) to yield plasmid pgD-EYFP, as described previously   as the teviously –43. Repoeviously –43. Ubiqeviously . Other eeviously , pCMV-Fleviously , Flag-taeviously , Flag-taeviously , pcDNA3.eviously , mCherryeviously  and TOM7eviously  were gifCOS-7 cells were grown overnight to 80% confluence on microscopy cover glass (NEST) placed in six well plate (Corning), then plasmid transfection and fluorescence microscopy experiments were carried out as described previously –43, 52. 5 cells per well-overnight before transfection. Cells were then co-transfected with 100 ng of the indicated expression plasmid, 100 ng of IFN-β or NF-κB promoter reporter and 10 ng of pRL-TK  to normalize transfection efficiency. Twenty-four hours post-transfection, the luciferase activity was detected with a luciferase assay kit (Promega).The DLR assays were performed as described previously –42, 53. 2 incubator and replaced with medium supplemented with 2% FBS to continue culture for the indicated times, then cells were harvested for luciferase reporter assays to determine the replication kinetics of HSV-1  Luc  was offered by Dr. Chunfu Zheng , which wof HSV-1 , 34. HerHEK293T cells cultured in 6 well plate were transfected with indicated amounts of expression plasmid. Twenty-four hours post-transfection, total RNA was extracted with TRIzol reagent (Invitrogen). Samples were then subjected to reverse transcription to cDNA with RT reagent (TSINGKE). The acquired cDNA was taken as a template for qPCR, to detect the expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH)  and IFN-β, using a qPCR instrument . Primers used for GAPDH (forward primer 5′-AGG TCG GTG TGA ACG GAT TTG-3′ and reverse primer 5′-TGT AGA CCA TGT AGT TGA GGT CA-3′) and IFN-β (forward primer 5′-ATGACCAACAAGTGTCTCCTCC-3′ and reverse primer 5′- GGAATCCAAGCAAGTTGTAGCTC-3′) were referred to Bing Tian's report .Co-IP assays were performed as previously described , 56–58. post hoc tests were performed to identify specific effect. Moreover, Student t test (unpaired two-tailed t-test) was used when needed. Data were expressed as means and standard deviations (mean ± SD) from three independent experiments, with significant differences marked on the figures. Significance levels were defined as ns, not significant, P > 0.05; *P < 0.05; **P < 0.01; ***P < 0.001; and ****P < 0.0001.Statistical analyses were performed using Graphpad Prism 6 software. All data were normally distributed, and the homogeneity of variances was examined with Levene's test. As the samples were normally distributed and displayed homogenous variance, statistical analyses were performed using one-way ANOVA. In the event of a difference being present, Bonferroni-adjusted To find out which HSV-1 protein may interact with viperin, some HSV-1 encoded cytoplasmic localization proteins  were firTo further prove the interaction between gD and viperin, Co-IP assays were carried out. HEK293T cells were co-transfected with pcDNA3.1-gD and pViperin-Flag expression plasmids, then cell lysates were immunoprecipitated with anti-Flag mAb or non-specific control mouse IgG. As a result, gD was immunoprecipitated by Viperin-Flag with anti-Flag mAb , whereasTo continue determine the interaction between gD and viperin in the context of viral infection, HEK293T cells were transfected with pViperin-Flag expression plasmid, then infected with HSV-1 at an MOI of 1. Subsequently, cells were collected and Co-IP assays were performed. As shown in It is known that the N-terminal amphipathic a-helix is important for viperin to target to ER  and lipiIt is reported that viperin can enhance TLR7/9-dependent production of IFN-I . To examSaitoh's study shows that viperin can interact with the signal mediators IRAK1 and TRAF6, so as to recruit them to the lipid bodies, which can regulate TLR7- and TLR9-IRAK1 signaling axis to mediate the expression of functionally important immune molecules in plasmacytoid dendritic cell . To deteIt is shown that the viperin-related K63-linked polyubiquitination of IRAK1 is crucial for the TLR7- and TLR9-dependent IFN-β production . To probViperin is proved to be involved in the activation of NF-κB and AP-1 in T cells . To detePolyubiquitination has emerged as an important regulatory mechanism in NF-κB signaling, and TRAF6 acts as a key substrate of K63-linked polyubiquitin chains in TNFR pathway, which serves as a mechanism to recruit TAK1 and IKK kinases and finally stimulate downstream NF-κB activation . To inveTo further elucidate a clear molecular mechanism of how gD and viperin interaction inhibits NF-κB activity, pViperin-Flag, and TRAF6-myc expression plasmids were co-transfected into HEK293T cells, along with gD-EYFP or EYFP control plasmid. Then, Co-IP assays were carried out. In contrast to the EYFP control, gD significantly reduced the interaction between TRAF6 and viperin, suggesting gD could inhibit TRAF6-mediated NF-κB activity through competive binding viperin with TRAF6 . Taken tIt is documented that the signal mediators IRAK1 and TRAF6 can interact with each other at the lipid bodies . To testIn order to investigate the physiological significance of gD and viperin interaction during HSV-1 infection, HEK293T cells were mock-transfected or transfected with plasmid pViperin-Flag or plasmids combination of 3.1-gD and pViperin-Flag. Twelve hours post-transfection, cells were infected with HSV-1 BAC Luc at an MOI of 1 for 6, 12, or 24 h. Then, luciferase activity assays were performed to determine the replication kinetics of HSV-1. As shown in Many viruses can induce the up-regulation of viperin during infection, and viperin is shown to have critical roles in inhibiting viral replication and facilitating TLR7- and TLR9-mediated production of IFN-I , yet itsIn our previous experiment design, we had considered to detect the co-localization of endogenous gD and viperin during HSV-1 infection, but most of the endogenous viperin mRNA will be degraded by UL41 when HSV-1 infection. Western blot analysis showed that viperin was almost degraded, with very low remaining protein amount, hence in our previous experiment the expression of viperin could not be detected by IFA using endogenous viperin antibody (unpublished data), we therefore would not be able to study the interaction mechanism between gD and viperin without viperin overexpression . ActuallAfter screening, our confocal results found that gD could co-localize with viperin at the Golgi body and lipid droplets, and Co-IP results demonstrated that gD interacted with viperin. It is shown that MAVS can interact with viperin to act as a negative regulator of the interferon response . IRAK1 aIt is well-known that toll-like receptors can recognize various pathogens (including viruses and bacteria) when they stimulate the innate immunity defense system , subsequOur DLR assays showed that gD and viperin interaction could up-regulate IRF7 (but not IRF3) mediated IFN-β activity. Further Co-IP assays demonstrated that gD strengthened the interaction of viperin with IRAK1 and improved K63-linked IRAK1 polyubiquitination, suggesting the co-localization of gD with viperin at the Golgi body and lipid droplets can improve the antiviral ability of viperin. However, the presence of gD and viperin significantly inhibited TRAF6-mediated NF-κB activity in a gD dose-dependent manner. Co-IP results further showed gD reduced the interaction of TRAF6 with viperin, but not affected the ubiquitination of TRAF6 . MoreoveAt the level of plasmid transfection, we had elucidated the specific interaction mechanism between gD and viperin, and we also analyzed and verified the effect of gD and viperin co-expression (overexpression) on HSV-1 proliferation. As mentioned above, the mRNA of viperin will be degraded by UL41 when HSV-1 infection, and the specific interaction mechanism between gD and viperin can not be studied after viperin is degraded. Therefore, we considered it was not necessary to carry out the viperin knockdown experiment, since viperin is actually degraded during HSV-1 infection.vice versa. Hence, gD interacts with viperin to inhibit NF-κB activity while stimulates IRF7-mediated IFN-I transcriptional activity is reasonable. This interaction is supposed to occur in HSV-1 lytic cycle rather than latent infection, since most of the HSV-1 proteins are silent when HSV-1 is latent in neurons, and only latency associated transcript (LAT) and a small amount of proteins are expressed (Generally, a modest level of IFN-I expression is driven by the activation of NF-κB , howeverxpressed .When virus invades the cell, it activates a series of signaling pathways and then induces the expression of hundreds of ISGs to perform antiviral effects. Among them, viperin is an IFN-induced protein, which plays an important role in this process , 12. We In conclusion, here we identified HSV-1 gD could interact with antiviral protein viperin, and co-localize with it at the Golgi body and lipid droplets. Our further results proved that gD and viperin interaction improved IRF7-mediated IFN-β activity to strengthen the antiviral ability of viperin, through enhancing the interaction between viperin and IRAK1, and increasing the K63-linked polyubiquitination of IRAK1. However, gD and viperin interaction could not affect the polyubiquitination of TRAF6, but decrease the interactions of TRAF6 with viperin and IRAK1, which finally inhibited the proliferation of HSV-1. It is noteworthy that the gD and viperin interaction may help us to explore and elucidate the roles of viperin and gD during HSV-1 infection.The raw data supporting the conclusions of this manuscript will be made available by the authors, without undue reservation, to any qualified researcher.MC and ML designed the research. ML, ZL, ZX, XZ, YW, HP, YL, XO, YD, YG, and WG performed the research. MC, ML, and ZL analyzed the data. DC and TP consulted and advised on the research. MC, ML, and ZL wrote and review the manuscript. All the authors read and approved the final manuscript.TP was employed by company South China Vaccine Corporation Limited. The remaining 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.


Attention-deficit hyperactivity disorder (ADHD) is highly prevalent amongst prison inmates and the criminal justice system (CJS) likely bears considerable costs for offenders with ADHD. We aimed to examine the relationship between ADHD and health-related quality of life (HRQoL) and quality-adjusted life years (QALY) amongst imprisoned adults; and to estimate the annual expenditure associated with ADHD status in prison.An observational study was performed in 2011–2013, at Porterfield Prison, Inverness, United Kingdom (UK). The all male sample included 390 adult prison inmates with capacity to consent and no history of moderate or severe intellectual disability. Participants were interviewed using the Diagnostic Interview for ADHD in Adults 2.0. The Health Utilities Index Mark 3 (HUI3) was used to measure health status, and to calculate attribute specific HRQoL scores and QALY. Health service utilisation was obtained through inspection of medical prison records. Inmates with ADHD were compared with inmates without ADHD.Inmates with ADHD had significantly lower QALYs, with a clinically significant adjusted difference of 0.13. Psychiatric co-morbidity accounted for the variation of ADHD on the HUI3 emotion domain only. Medical costs for inmates with ADHD were significantly higher; and behaviour-related prison costs were similar to prisoners without ADHD, reflecting a low frequency of recorded critical incidents.ADHD may directly contribute to adverse health and quality of life through cognitive and executive function deficits, and co-morbid disorders. The extrapolation of conservative cost estimates suggests that the financial burden of medical and behavior-related prison care for inmates with ADHD in the UK is approximately £11.7 million annually. The reported cost estimates are conservative as there is great variability in recorded critical incidents in prisons. In turn, for some prison establishments the prison care costs associated with prisoners with ADHD may be considerably greater. Among the general population attention-deficit hyperactivity disorder (ADHD) confers significant financial burden , 2 and gADHD is a childhood onset neurodevelopmental disorder  often peHealth economic evaluations have become an essential part of research and provide evidence supporting health interventions . ADHD isDespite the disproportionate representation of ADHD within the prison population, the health-related quality of life (HRQoL) and related costs remains unknown.In this study we aim to examine the impact of ADHD amongst imprisoned adults. We set out to determine prisoners’: 1) scope and extent of impaired HRQoL utility scores and quality-adjusted life years (QALY) and 2) service use and costs attributable to ADHD.Following approval from the Scottish Prison Service Research Access and Ethics Committee and in accordance with the Declaration of Helsinki written consent was obtained by prisoners who were recruited by opportunity sampling from Porterfield Prison, Inverness, Scotland, UK, over a period of 18 months in 2011–2013. Participants included 390 adult male prisoners who consented to participate. Those with moderate or severe learning difficulties, lack of fluency in the English language, and severe mental illness (as judged by prison officers) were excluded from participating.Participants in the study were indirectly compensated. The study group deposited £20 per participant into a Prison Common Good Fund, which was managed by a group of prisoners. The fund was then used to purchase items for the common good of all prisoners to enhance prison life.Prisoners who indicated interest attended an appointment with the researcher where they were given detailed oral and written information about the study and the consent procedures. After obtaining written consent, researchers administered a comprehensive battery of measures, which took approximately 4 h to complete . The researchers received comprehensive training to administer the measures from the Maudsley Hospital Adult ADHD Service. Further details about the comprehensive battery of measures have been published elsewhere .Data related to medical service use were gathered through inspection of prison medical records and medical costs were calculated based on reference costs reported by the . Data related to behavioural disturbance incidents were gathered through inspection of prison records and related costs were calculated based on similar reference costs and were reported as prison costs (see details below).The HUI3 is a multi-attribute health status classification system that enables researchers to map levels in the following categories: vision, hearing, speech, ambulation, dexterity, emotion, cognition, and pain; using decision tables and coding algorithms, which can be represented in terms of attribute specific HRQoL scores , 27. HRQAll participants underwent a comprehensive evaluation for ADHD and were interviewed using the Diagnostic Interview for ADHD in Adults 2.0 (DIVA-2) . The DIVParticipants were also questioned whether they were previously diagnosed or treated for ADHD or any other psychiatric illness.The Brief Symptom Inventory (BSI) is a brief psychological self-report scale . The BSIDetailed medical service utilization history was obtained through inspection of participants prison medical records. Data from prisoners’ medical charts (covering the 3 months prior to the appointment with the researcher) were abstracted, verified, and entered into a database for analyses. The authors chose to include 3 months of service for practical reasons; and additionally thought this time period fairly represented the medical service use of all prisoners given the variance in prison stays. Data included details from appointments with a general practitioner, physical health nurse, mental health nurse, addiction services nurses, or any other type of nurse, psychiatrist, psychologist, podiatrist, oral health practictioner, or any other type of health related visit such as Well-man clinic or other health clinics, and hospital outpatient visit. Medical costs for these appointments were calculated according to reference costs reported by the NHS Trust . MedicatPrisoners’ behavioural disturbance incidents were obtained from prison records. Reports of non-attendance to prison activities, being under observation, number of adjudications, and critical incidents were collected and used to calculate the related prison costs. Prison costs were calculated based upon reference costs from the UK Ministry of Justice and HM Prison Service , Social All reported costs were in Pounds Sterling (£) for the years 2012–2015, and adjusted using the Consumer Price Index .Frequencies were reported for all categorical variables, and means with their standard deviation for continuous variables. The median and inter-quartile range was used for all cost related values.Tobit models were used in favour of traditional ordered logistic regression models. A Tobit model is designed to estimate linear relationships between variables when there are ceiling or flooring effects on the outcome [Because of the HUI3 utility scores’ interval properties, we used t-tests for unadjusted analyses. To estimate the association between ADHD and HUI3 single attribute and composite utility scores, Type I  outcome . IgnorinConsidering the highly skewed nature of cost variables we used generalised linear models (GLM) with a gamma distribution and log-link function. This way the natural log is modeled and then the predicted margins are calculated in order to obtain the cost differential for those with ADHD . All cosp ≤ 0.05 for all statistical tests. All analyses were performed using Stata version 13 (StataCorp) [We established a significance level at ataCorp) .p < 0.01). 18.8% (18/96) prisoners with ADHD reported a prior diagnosis of ADHD and 15.6% (15/96) reported having ever received pharmacological treatment for ADHD.The all male sample was essentially Caucasian British (99.0%) with an average age of 30.3 years (sd 8.3). Prisoners with ADHD had a significantly lower mean age than those without ADHD (28.2 years (sd 7.5) vs. 31.0 years  2 (df 1) = 10.2, p = 0.001; Odds Ratio = 2.3, Confidence Interval 1.3–3.9).Out of the total sample of 390 participants, 81 (20.8%) required assistance with reading the questionnaires. For those diagnosed with ADHD, 31/96 (32.3%) required assistance in contrast to 50/294 (17.0%) of the other participants. This difference is significant (ChiTable p < 0.05), ambulation (p < 0.01), emotion (p < 0.001), cognition (p < 0.001), pain (p < 0.05), and HRQoL composite (p < 0.001). Figure Independent sample t-tests were estimated for all utility scores and HRQoL Table  comparinn p < 0.0, emotionTobit models were significant in each adjusted model for vision, ambulation, emotion, cognition, and QALY. The inclusion of anxiety and depressive disorders in models 2 and 3, attenuated the associations with emotion, hearing, and pain attributes. Attenuation of the association with hearing and pain should be interpreted with caution, as their unadjusted effect sizes were small. Models 2 and 3 show that prisoners with ADHD have a significant difference in QALY of 0.13 and 0.10, compared to those without ADHD.Table 25% of all participants had missing values by endorsing ‘Don’t Know’ on several questions of the HUI3. Patterns of missing values were analysed and the most plausible values were imputed using a technique developed by Naeim and colleagues specifically for HUI-3 scores .All 41 questions of the HUI-3 instrument allow respondents to answer ‘Don’t Know’. Because there are no instructions in the instrument manual for how to manage or score these answers, the ‘Don’t Know’ category interferes with the scoring leading to substantial amounts of missing data. Common methods for imputing data in this scenario may not be as effective or can even be misleading, given that answers to other questions within the same domain (e.g. vision) often help identify a sole correct answer to those marked as ‘Don’t Know’. The well cited imputation method by Naeim et al.  advises Furthermore, we performed a sensitivity analysis based only on those with complete HUI3 data to examine any differences in estimates before and after using the inspection and deduction method to account for ‘Don’t Know’ answers.Table p < 0.05), physical health nurses (p < 0.05), and mental health nurses (p < 0.01) in the three-month period assessed. No significant associations were observed for any other health services.Table p < 0.05), but prison costs were not. Cost items were assessed based on a 3 month window, then calculated for 1 year assuming similar patterns of health service utilisation and behaviour in prison. Total medical and prison costs for inmates with ADHD were £ 590 more per year than for inmates without ADHD.Table To the best of our knowledge, our study is the first addressing ADHD health status using HUI3 amongst prison inmates. Previous studies documented the relationship between symptom severity and poorer HRQoL, including somatic symptoms , whereasWe analysed the role of ADHD on QALY based on a one-year horizon. Notably, the proportion of inmates with a HRQoL over 0.90  was vastly superior amongst those without ADHD. The final adjusted model that accounted for psychiatric co-morbidity produced a 0.13 difference in QALY, four-fold above the 0.03 clinically relevant threshold estimated by the instrument developers . QALY baThe significantly poorer vision score among the ADHD group may relate to their reading difficulties. In the present study, those diagnosed with ADHD were over two times more likely to require assistance with reading the questionnaires than the other participants. With respect to mobility, the finding that prisoners with ADHD have significantly poorer ambulation problems may reflect that prisoners with ADHD suffer more injuries that hinder their mobility compared with non-ADHD prisoners. Data obtained from the Danish registry reported that the morbidity rate is nearly three times higher if you have ADHD, and that 77.7% of unnatural deaths were accounted for by accidental injury . AdditioADHD is frequently reported to be associated with a substantial reduction in the quality of life of children  and withThere is evidence to suggest that poor HRQoL in individuals with ADHD may be driven by the existence of co-morbid conditions . In our Health economic studies on the general population report that ADHD (including symptoms of hyperactivity) is associated with significant economic burden , 2; howeA US study of disability claims reported that patients with ADHD had 2.6 more medical claims than those without ADHD and that ADHD imposed a significant financial burden . A recenHospital inpatient stays are a significant driver of costs attributable to ADHD. A retrospective analysis during a 9 year period reported that median hospital inpatient, hospital outpatient, or ED admission costs for individuals with ADHD were more than double for those without ADHD . PharmacOur total estimated annual cost of £590 per inmate with ADHD demonstrates that the costs attributable to ADHD are relatively high. But because our estimate did not include costs for hospital stays, medication, and/or psychological treatment, the total cost estimate therefore represents a conservative figure.In our study, costs associated with ADHD were driven by increased medical service use and not by behavioural disturbance incidents. This may indicate that costs related to behavioural incidents were more generally distributed across the prison sample and due to many other factors besides having a diagnosis of ADHD. Service utilisation patterns were restricted to general medical and nursing services. Low endorsement of engagement with these and other services may have been a true reflection of the patterns of use in our sample, or of the Scottish prison system at large. As many resources were not used, costs remained lower compared with other studies mentioned.Because the present study found there were significantly greater medical costs but not behaviour-related prison costs, the cost implication seems to be largely for the NHS. While the assignment of prisoner medical costs based on NHS reimbursements may not perfectly represent prisoners medical costs (possibly over- or under-estimated), it helped to estimate and interpret costs using standard more widely used and familiar terms. There may be, however, variability in the recording of critical incident data, which will be a fundamental driver of prison costs, leading to increased number of seclusions, adjudications, injury costs and potentially staff sickness. In a previous study conducted in a large prison in Aberdeen there were highly significant differences found in aggressive critical incidents between an ADHD and a non-ADHD group . Hence fA key strength of the study is its large sample size and a methodology in which every participant was clinically diagnosed using the DIVA-2. Nonetheless, there are several limitations.Because of missing data, some bias may be present in our analyses of HUI3 specific attribute scores. However, our models accounted for missing data using a well established and oft cited method and the sensitivity analysis on adjusted models allowed us to have confidence in our methods.Ethnic minority groups and females did not have representation in this sample, therefore, it remains unclear whether these findings may be fully applicable and generalized to the entire prison population.ADHD diagnosis was based on self-reported information and we did not include informant  reports. Recall bias is unaccounted for and may have been a factor in symptom measures and service use. Nevertheless, any bias related to under-reporting was presumed to have similar effects on estimates for both the ADHD and non-ADHD groups. Other studies have reported considerably higher rates of critical incidents , 54, andOur extrapolation method (using 3 months of data to estimate 1 year) may be limited in its accuracy. We used a one-year horizon for our HRQoL and service use estimates, and more time than this would have conferred too much uncertainty. Future research should address measuring utilities over more time, thereby providing a better foundation of QALY estimates beyond 1 year. Finally, the opportunity sampling method used may have introduced selection bias into the results, limiting their generalizability both within the prison and across other prisons.Research on HRQoL and costs related to adult ADHD is limited in the general population and is virtually non-existent in the prison population. We addressed this paucity of data on HRQoL, QALY, service utilization, and costs attributable to ADHD based on 1 year in prison. We performed HRQoL and cost analyses for adult prison inmates with ADHD based on a cross-section of the Scottish prison system in the UK.Our study provides evidence that HRQoL of life is considerably poorer in adult male prison inmates with ADHD, with an adjusted reduction of 0.13 QALY. Affected health attributes extend beyond emotional and cognitive deficits, suggesting chronic effects of ADHD on health over the lifespan. ADHD may contribute to adverse health and quality of life directly through executive function and cognitive deficits; and co-morbid disorders. Combined costs within prison were significantly higher for those with ADHD and were driven by medical expenses. Service utilisation was for the most part limited to general practitioner services and nursing staff visits.Approximately 80% of inmates considered to have ADHD did not receive a prior diagnosis — indicating that a significant proportion of adult prison inmates are inadequately identified and treated. This has policy implications for both the National Health and the prison service. There is a need for the prison service to develop improved awareness about ADHD in adult prisoners, including the clinical and behavoural presentation of ADHD. There is also a need to introduce a brief and reliable screen on admission, such as the 6-item B-BAARS, which has high sensitivity and specificity . FurtherIn 2015 the Ministry of Justice reported a population of 77,472 adult male inmates in the UK. Given the prevalence rate of 25.5% of ADHD among prisoners  and our ADHD is a prevalent mental health disorder, and a known risk factor for a series of adverse health and social outcomes. Population studies report the community (and society at large) bears considerable medical costs associated with ADHD , 23. AltOur results provide evidence that adult prisoners with ADHD represent a unique population with unmet needs and high costs. Given the Swedish study of patients showing a 32% reduction in criminality for men and 41% for women during periods when they were receiving ADHD medication , effectiWe recommend directing efforts to increase access to effective interventions for adult inmates with ADHD. Setting up provisions for better access to early diagnosis and treatment is likely to improve inmates’ HRQoL and decrease impairment related to ADHD symptoms and associated co-morbidities.


This review summarizes the recent progress of Grubbs–Hoveyda (GH) type olefin metathesis catalysts incorporated into the robust fold of β-barrel proteins. Anchoring strategies are discussed and challenges and opportunities in this emerging field are shown from simple small-molecule transformations over ring-opening metathesis polymerizations to in vivo olefin metathesis. Olefin metathesis constitutes the rearrangement of C=C double bonds in the presence of transition metal catalysts based on V, Mo, W, Re, Ru, and Os together with alkylating co-catalysts. This transformation is widely used in organic synthesis as well as in polymerization of various unsaturated monomers . AccordiN-heterocyclic carbene (NHC) ligand and a chelating styrene to the so-called Grubbs 1st generation catalyst, the relatively air- and moisture-stable Grubbs–Hoveyda type (GH-type) catalysts were obtained ..7  was incorporated  was most effective among the catalysts, and up to 78% conversion , suggesting the living nature of the ROMP even within the protein scaffold. Neither regioselectivity (cis/trans) nor tacticity were affected ..NB4exp) NB4exp was subjected to conjugation of catalysts Ru-4/5/6. Indeed, all catalysts underwent covalent anchoring with high conjugational yield (confirmed via ICP–OES and ESIMS) [Ru-5@NB4exp as well as Ru-6@NB4exp showed high activity in the ROMP of norbornene 7 with TONs up to 10,000. For the catalyst Ru-4 with the short linker, the activity of Ru-4@NB4exp dropped to TON = 3,000, even though the conjugation was almost quantitative [NB4exp were capable of catalyzing both CM and RCM. This makes NB4exp based biohybrid catalysts the first artificial metatheases to catalyze all basic metathesis reactions [d ESIMS) . Upon catitative . Howevereactions .For the artificial metathease based on Sav, additional structural motifs – α-helices – were introduced into the loops. These loops are supposed to embed the active site. However, in first ring-closing metathesis reactions, the influence of the newly introduced α-helices was negligible .In this review, we discussed the combination of GH-type catalysts and β-barrel proteins to construct artificial metatheases. The β-barrel motif offers a robust, well-defined but easily modifiable second coordination sphere. This makes the artificial metatheases applicable in all basic metathesis reactions. The channel provided by β-barrel proteins is a potentially useful feature to immobilize the GH-type complex within the protein. So far, no advantage has been drawn out of this feature. Strategies to enlarge small cavities of small β-barrel proteins likely will lead to more selective artificial metatheases. Directed evolution may open new opportunities for catalyst optimization .


Attention-deficit hyperactivity disorder (ADHD) is the most common psychiatric disorder in children – affecting 2% to 16% of the school-age population . However, in South Africa, data on prevalence rates, access to care and treatment for ADHD are limited and research is lacking. Many children- especially those in underprivileged communities- suffering from ADHD remain undiagnosed, or if diagnosed, do not receive optimal treatment. The Goldilocks and The Bear Foundation provides screening for ADHD and other mental health disorders to learners at school level. We will be presenting the statistics compiled for the first year of operation (July 2017 – June 2018).In the schools visited, children are referred to the Foundation by the School Based Support. Collateral information is obtained from educators and parents, and parental consent secured before any child is evaluated. Trained nurses do the basic physical screening and behavioural observations for each child. All information is collated and controlled by a trained psychiatrist or psychologist, who determine the possible diagnosis and refer accordingly . A detailed database was built capturing all the aforementioned information.We have visited 18 schools (N = 12 447), of which 13 schools participated (N = 8780). A total of 543 children (6.2%) from the school population were screened. The ratio of boys to girls was 2:1, with an age range of 5–14 years. Of the children included in the current analysis (to be updated at the end of the study period), 2.7% were diagnosed with ADHD and 0.67% with depression and/or anxiety. Further detail will be provided with regard to risk factors and comorbid conditions and problem areas.Although mental health clinics exist in the public sector, children with ADHD often never reach this point of diagnosis and treatment because of a lack of awareness and knowledge in their communities. Improved outcomes are possible to achieve if patients suffering from ADHD are diagnosed as such and receive multi-modal intervention – which would include psychopharmacological interventions, behavioural interventions and support.


Background: Links between eating disorders (EDs)  and the major neurodevelopmental disorders of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) have been repeatedly highlighted. In both ASD and ADHD, these links range from an elevated risk for EDs to common symptomatic overlaps and etiological commonalities with EDs.Methods: We performed a systematic literature search (through July 2019) with Medline via Ovid for epidemiological data on EDs  in combination with both ASD and ADHD.Results: The reviewed studies showed that, on average, 4.7% of patients with certain ED diagnoses  received an ASD diagnosis. Reliable data on the prevalence of EDs in ASD samples are still scarce. Comorbid ASD is most commonly diagnosed in patients with AN. The prevalence of ADHD in EDs ranged between 1.6% and 18%. Comorbid ADHD was more often reported in the AN-binge eating/purging subtype and BN than in the AN restrictive subtype. The prevalence of EDs in ADHD ranged between no association and a lifetime prevalence of 21.8% of developing an ED in women with ADHD.Conclusions: Studies on the prevalence rates of EDs in ADHD and ASD and vice versa are heterogeneous, but they indicate frequent association. While there is growing evidence of clinical overlaps between the three disorders, it remains difficult to determine whether overlapping characteristics  are due to common comorbidities  or are instead primarily associated with EDs and neurodevelopmental disorders. Furthermore, prospective studies are required to better understand how these disorders are related and whether ADHD and ASD could be either specific or nonspecific predisposing factors for the development of EDs. The exact relationship and overlap between eating disorders (EDs)  and neurodevelopmental disorders (NDDs), such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), as defined in DSM-5, remain unclear. The core pathological features of AN are a persistent restriction of energy intake and/or purging behavior, an intense fear of weight gain, as well as a disturbance in the self-perception of one’s body shape. BN is characterized by binge eating episodes and inappropriate compensatory behaviors . BED, whASD is a pervasive NDD with an onset in early childhood that is characterized by deficits in social communication and interaction combined with restrictive, repetitive patterns of behavior and/or interests. The presence of symptoms in an early developmental period is mandatory for diagnosis. ADHD, another common NDD, also manifests during infancy. The core symptoms of ADHD include attention deficits, hyperactivity, and impulsiveness . Many pavice versa or have analyzed the symptomatic overlap between these disorders. Overlapping features between EDs (predominantly AN) and ASD comprise repetitive and restricted behavior, social withdrawal, and difficulties in understanding another’s mental state  in ASD and ADHD samples or al state . ADHD shal state .Some studies have shown associations between ARFID, pica, and ASD , 11, butWhile the association between ADHD and ASD is not the focus of this review, the relationship between these two diseases and EDs is systematically reviewed.vice versa. In this review, we did not focus on ARFID, pica, and rumination disorder.To answer the research question, we performed a systematic literature review by focusing on prevalence rates of ASD and ADHD in AN, BN, and BED and vice versa?Based on studies that addressed either symptomatic, developmental, or genetic differences and commonalities between NDDs and EDs, our specific objective was to clarify the following question: How common are AN, BN, and BED in ASD and ADHD samples and ® Daily, and Ovid MEDLINE® (1946 to 07/13/2019)] and searched for epidemiological data on specific EDs  in ASD and ADHD. The exact search strategy is presented in We conducted a Medline search via Ovid  oOn average, 4.7% of the ED  patients received an ASD diagnosis per either the DSM-III-R, DSM-IV, DSM-5, or ADOS-2  in combiLiterature focusing on EDs in ASD samples is scarce. Karjalainen et al.  investigA total of 252 studies  were initially identified, of which 16 met the inclusion criteria , 51–64. The prevalence of ADHD in EDs ranged between 1.6%  and 18.0Available studies that have focused on the prevalence of EDs in ADHD are heterogeneous, and their results have varied from no association between EDs and ADHD , 58, 68,A previous systematic review  reportedThe different diagnostic tools , study samples, and methodologies that were used make it difficult to compare the studies and determine the exact prevalence rate of ASD in EDs. Furthermore, diagnostic criteria have changed over the years due to the different versions of the ICD and the DSM. For example, in the DSM-5, autistic disorder, disintegrative disorder in childhood, and Asperger’s syndrome were dimensionally subsumed to ASD. Additionally, the DSM-5 criteria revised AN  and BN , and BED was officially recognized as a formal diagnosis and as the third ED entity .Studies suggest an overrepresentation of ASD in EDs, especially in AN. However, the overlap of EDs with ASD that was found in our study was less than it was with other mental disorders [e.g., 31–89% of patients with AN suffer from depression , and 15–https://www.cdc.gov/ncbddd/autism/data.html; retrieval date July 14, 2019). We calculated the prevalence rate as 4.7% of patients with an ED being diagnosed with ASD, which exceeds the prevalence rate for ASD in the general population.Per the Centers for Disease Control and Prevention, 1 in 59 children (∼1.7%) has been identified with ASD in the general population , impaired set shifting (the ability to shift from one approach to another fluently and with little difficulty), and difficulties in theory of mind tasks  , 98, 99.Poor theory of mind in AN, however, seems to be limited to the acute state of AN, which could be a consequence of starvation . Both diEating disturbances, such as avoidance of certain food types, sensitivity to food textures, and unusual behaviors at mealtimes, are another overlapping representation in ASD and AN . AccordiIt is difficult to identify the complex relationships between ASD and EDs. It is possible that the overlap of symptoms makes AN and ASD share common underlying cognitive patterns and neuronal pathophysiology. Possible ways in which these traits might be interrelated between ASD and AN are described later. 1) Some of the shared clinical symptoms, such as social anxiety, might be secondary to both. 2) A fearful avoidant and obsessive personality structure –114 as wTo date, several studies have focused on the relationship between ADHD and EDs. In the reviewed studies, the prevalence rates for ADHD in EDs ranged between 1.6%  and 18.0Studies that have focused on the prevalence of EDs in ADHD are heterogeneous, and they vary between no relationship between EDs and ADHD and 21.8% of females with ADHD and a lifetime ED history .A previous systematic review found evidence of an association between childhood ADHD and the later development of either an ED or disordered eating. Support for this association was strongest for BN, multiple types of EDs clustered together, and disordered eating . Surman It is difficult to compare previous studies because of the mixed composition of ED samples , the different age groups, and the various study designs . For the analysis of EDs in ADHD samples, it is especially important to compare studies with participants of the same age group to avoid confounding effects when an ED is diagnosed later in development than is ADHD.The core symptoms of ADHD, inattention, hyperactivity, and impulsivity are often present in EDs . AttentiWhen analyzing shared traits between EDs, ASD, and ADHD, it should be considered that additional shared common comorbidities might result in clinical and symptomatic overlap. Comorbidities are the rule rather the exception in patients with EDs , ASD 12, 128, anThe comorbidity of EDs  and ASD Because of the number of shared comorbidities, it might be difficult to completely determine their influence on symptom overlap between EDs, ASD, and ADHD and the prevalence rates of comorbidity. For future studies, it is therefore essential to carefully measure the rate of major overlapping comorbidities between EDs, ASD, and ADHD.In addition, it is important to recognize that several symptoms in AN may be a consequence of malnutrition . StarvatPer the DSM-5, NDDs are characterized by a manifestation of a set of stable perceptive, cognitive, emotional, and behavioral features early in development. NDDs frequently co-occur . A requiRegarding the overrepresentation of ASD and ADHD in EDs, it could be discussed whether ASD and ADHD themselves might be predisposing factors for the development of EDs, which mainly occur during adolescence . DevelopTherefore, it appears that NDDs may constitute a vulnerability factor for EDs. As such, EDs might be regarded one of many possible progressive (comorbid) “sequelae” of NDDs. An NDD is not a prerequisite for EDs, and EDs can also occur later in life; therefore, in our view, EDs, in general, should not be considered NDDs, but they could be regarded as a possible later aggravator of an NDD when symptoms evolve from the disease. EDs with a combined NDD may be considered special subgroups of EDs.The literature points to considerable comorbidity rates and a symptomatic overlap between certain EDs, ASD, and ADHD. Nevertheless, the question of how much of the overlap is due to shared traits of the disorders per se and how much is due to either shared comorbid conditions or resembling traits has not been fully determined. There is a need for longitudinal studies to answer this question. Clinically, it is important to carefully conduct diagnostic procedures while considering the comorbidity rates and the overlap of symptoms. A thorough diagnostic workup should be conducted to develop individualized treatment strategies. In our view, EDs in general should not be regarded as NDDs. However, in a relevant subgroup of patients, they might be understood as a second-decade sequel of possibly subsyndromal NDDs, when EDs evolve from symptoms and/or psychodynamic problems that are linked to NDDs. EDs with combined NDDs may be considered special subgroups of EDs. To date, studies that have focused on the overlap between all three disorders are scarce. In the future, the risk of developing an ED in individuals who have been diagnosed with either ASD or ADHD should be systematically investigated, preferably in prospective studies. Case studies might add useful information to help derive hypotheses about factors that promote the development of a comorbid ED in adolescence. Prospective imaging studies in individuals at high risk for EDs (both with and without NDDs) could elicit more information about underlying common neurobiological structures. In addition, genetic studies could provide more information about possible overlapping genetic risk factors.KN, SM, AZ, and LT wrote the manuscript. KN, VM, and DE performed literature search. KN, SM, AZ, LT, AJ, VM and DE were crucial involved in the theoretical discussion and the preparation of the manuscript. All authors read and approved the final version of the manuscript.The article processing charge was funded by the German Research Foundation (DFG) and the University of Freiburg in the funding program Open Access Publishing.LT: advisory boards, lectures, or travel grants within the last 4 years: Eli Lilly, Janssen-Cilag, Novartis, Shire, UCB, GSK, Servier, Janssen, and Cyberonics. DE was supported by the Berta-Ottenstein-Programme for Advanced Clinician Scientists, Faculty of Medicine, University of Freiburg.The remaining 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.


Objective: This study investigates excessive mind wandering (MW) in adult ADHD using a new scale: the Mind Excessively Wandering Scale (MEWS). Method: Data from two studies of adult ADHD was used in assessing the psychometric properties of the MEWS. Case-control differences in MW, the association with ADHD symptoms, and the contribution to functional impairment were investigated. Results: The MEWS functioned well as a brief measure of excessive MW in adult ADHD, showing good internal consistency (α > .9), and high sensitivity (.9) and specificity (.9) for the ADHD diagnosis, comparable with that of existing ADHD symptom rating scales. Elevated levels of MW were found in adults with ADHD, which contributed to impairment independently of core ADHD symptom dimensions. Conclusion: Findings suggest excessive MW is a common co-occurring feature of adult ADHD that has specific implications for the functional impairments experienced. The MEWS has potential utility as a screening tool in clinical practice to assist diagnostic assessment. The diagnosis of ADHD is based mainly on descriptions of behaviors that reflect inattention, hyperactivity, and impulsivity. Yet older children, adolescents, and adults frequently report phenomenological descriptions of internal subjective experiences that may underlie the behavioral changes seen in ADHD. Characteristic descriptions of the mental state in ADHD include reports of ceaseless mental activity, thoughts that are constantly on the go, or a mind constantly full of thoughts. Thoughts are experienced as uncontrolled, with multiple occurring at the same time. Another common description is of short-lived thoughts that flit from one thing to another, jumping between different ideas . Here, wMW is conceptualized as periods in time when attention and the contents of thoughts shift away from external sources and/or ongoing tasks to unrelated internal thoughts or feelings . It is aExcessive spontaneous MW has been associated with functional impairment and implicated in psychopathologies such as ADHD . Mental Using an experience sampling technique to measure on- and off-task thoughts during an attention task, ADHD symptomatology has also been shown to positively correlate with both the frequency of MW and the lack of awareness of engaging in MW . A sub-cCollectively, these findings suggest that adults with ADHD are highly susceptible to excessive spontaneous MW and may have a core difficulty controlling spontaneous thoughts unrelated to the current context. Excessive MW could therefore underlie many of the symptoms and impairments that characterize the disorder. To explore the role that MW may play in the pathogenesis of ADHD, as well as its potential role in diagnosis, our research group developed the Mind Excessively Wandering Scale  participated in the MIRIAD project. There were no significant differences between groups for age or IQ  project, a longitudinal case-control study of emotional lability (EL) and neuropsychological functioning in adult men with ADHD with no co-occurring comorbidities . Forty-or IQ see . ADHD par IQ see .As the MEWS was developed after the MIRIAD project began, only a subset of the ADHD cases and controls provided MEWS data. At study entry (baseline), 25 cases and 24 controls completed the MEWS. Follow-up assessments completed approximately 9 months after baseline provided data on 18 cases and 18 controls at both time points. In addition, six cases and 18 controls provided MEWS data at follow-up assessment alone. Of the 18 ADHD cases with data at both time points, 16 were treated with methylphenidate and one with atomoxetine at follow-up, initiated by local services and not following a specific protocol. Ethical approval for this study was obtained from the Joint Research Ethics Committee of the Institute of Psychiatry and SLaM.M age = 33.52 years, SD = 10.26 years) and 30 healthy controls . Groups did not significantly differ on age, sex, or IQ (see Participants were from the OCEAN (Oils and Cognitive Effects in Adult ADHD Neurodevelopment) project, a study investigating the relationship of omega-3 dietary supplementation  to cognitive and electrophysiological measures in adults with ADHD. Participants were aged between 18 and 65 years. The sample consisted of 81 adults with ADHD , 79 cases and 29 controls provided MEWS data. Two separate follow-up assessments of the ADHD cases took place, 3 months (Time 2) and 6 months (Time 3) after baseline. At Time 2 and Time 3, 79 and 55 ADHD cases provided MEWS data, respectively. Ethical approval for the study was granted by the National Research Ethics Service (NRES) Committee London.Diagnostic and Statistical Manual of Mental Disorders  was measured using the Affective Lability Scale–Short Form ALS-SF; , which mFunctional impairment across major life domains  was measured using the Weiss Functional Impairment Rating Scale–Self-Report WFIRS-S; .MW was measured using the newly created MEWS see . This puMean values for each rating scale and subscale were used as summary measures. The raw data and square-root transformations were used in analysis, and parametric and non-parametric tests were used as appropriate.t tests and Mann–Whitney U tests to investigate case-control differences. Receiver operating characteristic (ROC) analysis was used to examine diagnostic accuracy and the optimal cut-off point of the measure.Principal components analysis (PCA) with varimax rotation was conducted to examine the factor structure of the MEWS. Cronbach’s alpha was used as a measure of reliability to assess internal consistency and Pearson’s correlation coefficient was used to analyze test–retest reliability of the scale. Construct validity was assessed with independent z value threshold for affection status corresponding to 3.4% prevalence of ADHD in adults . Factor loadings were greater than .7, with the exception of Item 14 (.51). SD = 3.3 months) for cases and 9.5 months (SD = 4.0 months) for controls between baseline and follow-up. Test–retest reliability was significant for the whole sample , and for both cases  and controls .There was a mean interval of 9.7 months (t(47) = −7.83, p < .0001, comparable with that found for the other rating scales of ADHD symptom domains: inattention, t(73.07) = −14.58, p < .0001; hyperactivity/impulsivity, t(85) = −11.40, p < .0001; emotional lability, U = 168.5, z = −6.53, p < .0001 (t(86) = −13.08, p < .0001, as well as for each domain of impairment, t range = −5.78-11.40, p < .0001, for impairment in family life, work, school, life-skills, self-concept, social problems, and risk taking. Similar results were found at follow-up .Case-control comparisons at baseline revealed significantly elevated ratings of MW in individuals with ADHD,  < .0001 . Particip < .0001) which, being close to 1, indicates excellent discriminant capacity of the MEWS. This was comparable with the AUC value of existing rating scales of ADHD symptom domains . A score of 15 or above provides the optimal balance of sensitivity (.88) and specificity (.88), suggesting a cut-off for disorder threshold .ROC analysis was used to examine the capacity of the scale to discriminate between cases and controls. Area under the curve (AUC) was .92 , hyperactivity/impulsivity , emotional lability , and impairment , as well as ADHD affection status . The strongest correlation was between MW and impairment , hyperactivity/impulsivity , emotional lability , and impairment  = 2.28, p = .04, between the baseline medication-free period  and follow-up .For the sub-sample with both baseline and follow-up data, the correlation of baseline to follow-up change scores for MW with change scores for the rating scale measures of ADHD symptoms and impairments revealed temporal covariance between the measures: positive correlations were found between change in MW and change in inattention (R2 = .824). The addition of MW as a predictor led to a significant increase in predictive power of the model (R2Δ = .024), with the variability accounted for by the model increasing to 84.9%, FΔ = 7.17, p = .01. This indicates that MW is having a small but significant effect beyond that accounted for by inattention and hyperactivity/impulsivity. Inattention carried the most importance in the model (β = .45), followed by MW (β = .31) and hyperactivity/impulsivity (β = .21). Only inattention and MW significantly contributed to the model .Data from 49 participants were used in regression analyses with the WFIRS-S total impairment score. Inattention and hyperactivity/impulsivity accounted for 82.4% of the variability in functional impairment  = 6.57, p < .02, and social problems, R2Δ = .137, FΔ = 4.50, p < .05. For the social problems domain, MW carried more importance in the model (β = .44) than inattention (β = −.42), but not hyperactivity/impulsivity (β = .50). Only MW and hyperactivity/impulsivity significantly contributed to the model . Interpretation of work and life-skills dimensions was not possible due to heteroskedasticity in the data.Within the ADHD group, MW had an independent effect on impairment in the domains of self-concept, The scree plot and eigenvalues suggested a one-factor solution with an eigenvalue of 9.44, accounting for 62.92% of the variance . All items loaded highly onto this factor . Internal consistency was high for all scales for both cases and controls , and MEWS scores showed satisfactory retest reliability across this time period .The mean interval between Time 1 and Time 3 was 6.4 months . This difference was comparable with that found for the other rating scales of ADHD symptom domains , as well as for each domain of impairment .Case-control comparisons revealed significantly elevated ratings of MW in individuals with ADHD (p < .0001). This was comparable with the AUC value of existing rating scales of ADHD symptom domains . A score of 15 on the MEWS provides the optimal balance of sensitivity (.90) and specificity .ROC curve analysis indicated that the MEWS successfully discriminated between cases and controls , hyperactivity/impulsivity , emotional lability , impairment , and ADHD affection status . The strongest correlation was between MW and impairment , hyperactivity/impulsivity , emotional lability , and impairment . MW and impairment showed the strongest relationship . The addition of MW as a predictor led to a significant increase in predictive power of the model (R2Δ = .076), with the variability accounted for by the model increasing to 78.9%, FΔ = 37.17, p < .0001. MW carried the most importance in the model (β = .49), followed by inattention (β = .29) and hyperactivity/impulsivity (β = .17). Only MW (p < .0001) and inattention (p = .002) significantly contributed to the model.Data from 108 participants were used in regression analysis with the WFIRS-S total impairment score. Inattention and hyperactivity/impulsivity accounted for 71.3% of the variability in functional impairment  = 24.79, p < .0001; self-concept, R2Δ = .10, FΔ = 9.72, p = .003; social problems, R2Δ = .10, FΔ = 9.92, p = .002; and risk taking, R2Δ = .09, FΔ = 9.37, p = .003. MW carried the most importance in the model for life-skills (β = .52), self-concept (β = .39), and social problems (β = .39), and was the only significant contributor to the model for the self-concept (p = .003) and social problems (p = .002) domains. Interpretation of the family and work domains was not possible due to heteroskedasticity in the data.Within the ADHD group, MW had an independent effect on impairment in life-skills, We report the psychometric properties and initial validation findings for a new self-report scale of excessive MW in adults with ADHD. Using two independent samples, we found that MEWS scores functioned extremely well as a measure of the mental phenomenon of MW in ADHD, with good reliability and high sensitivity and specificity for ADHD case-control differences. We found that elevated levels of MW (as indexed by the MEWS) in participants with ADHD were related to self-report measures of functional impairment. Furthermore, the contribution of MW to impairment was independent of the core ADHD symptoms of inattention and hyperactivity/impulsivity. These findings suggest that excessive MW is a characteristic feature of adult ADHD that has specific effects on impairment.Principal components analysis indicated a unidimensional structure to the scale and other psychometric properties of the MEWS were comparable with existing rating scales of ADHD core symptoms, including good internal consistency and test–retest reliability. The MEWS was able to differentiate between those with and without ADHD with high sensitivity and specificity of the scale, using a threshold score of 15. This is remarkable given that patients were selected for high ADHD symptoms and not specifically for subjective reports of internal thought processes as measured by the MEWS.In both studies, item total correlations with the full 15-item scale and factor loadings were high apart from Items 6 , 10 (I try to distract myself from my thoughts by doing something else or listening to music), and 14 . This is likely explained by the nature of these items, which refer to how individuals cope with MW or how it directly affects their functioning, as opposed to a description of the mental phenomenon. To investigate whether the scale could be shortened by dropping Items 6, 10, and 14 without reducing its sensitivity and specificity, we repeated the ROC analysis, finding the shorter 12-item scale had a sensitivity of .89 and specificity of .90 . Further analyses in larger data sets could be used to further refine the scale, but based on these data we recommend that future studies use the reduced 12-item scale.Our findings are in line with previous studies which report elevated levels of MW in ADHD compared with controls, whether measured using clinical rating scales  or experChange scores for MW also covaried with ADHD symptoms and impairments over time, indicating a close temporal relationship consistent with a potential causal role of MW in ADHD. The finding of significant pre–post treatment effects of methylphenidate in a subset of Study 1 participants raises the possibility that treatment effects on ADHD might be mediated by reductions in MW. However, we were unable to test specifically for treatment effects of methylphenidate because we did not randomize to treatment or include a placebo control arm.The link between MW and impairment was particularly strong, indicating the clinical importance of MW in adults with ADHD. Of specific interest was the finding that MW showed a main effect on impairment beyond the influence of inattention and hyperactivity/impulsivity and was overall the strongest predictor of impairment in Study 2. Investigating specific domains of impairment, MW was found to be an independent predictor of self-concept and social problems in both studies, and additionally life-skills and risk taking in Study 2. The reasons the MEWS is a particularly good predictor of impairment in ADHD are not well understood, but could be explained by both clinical and theoretical considerations. One possible explanation is that the scale items are rooted in qualitative accounts from adult ADHD patients of experiences of their mental state. When asked to describe the subjective experience of the flow of their thoughts, adults with ADHD repeatedly give descriptions of ceaseless, short-lived, and unfocused thoughts that flit from one topic to another . Such a not listen or lack awareness of social cues. MW may make it difficult to follow a single line of thought and interrupting others during conversations could be a strategy to avoid losing their train of thought. Behaviors such as these are likely to have negative effects on an individual’s social interactions.First, excessive MW may have a specific effect on functional outcomes due to the failure to deal with distraction and deficient mental processing of “task”relevant events. In social situations, an individual with excessive MW may miss verbal and non-verbal information and effectively Second, lack of attention paid to events due to one’s mind constantly being “on the go” in a non-focused way can also create difficulties with thinking through and planning activities, linked to forgetfulness and disorganization and leading to impairments in basic life-skills. Impaired self-concept may then arise as a bi-product of the effect of excessive MW on other domains of functioning, but could also be due to distress from the constant effort to focus or the experience of having a mind constantly full of unfocused distractible thoughts. Many patients report a sense of calm and relief when the flow of their thoughts becomes more focused and regulated following stimulants or other treatments for ADHD.Third, the connection between MW and risk-taking behavior is less obvious, but could be due to the impact of highly salient activities, which engage the attention of individuals, leading to a reduction of spontaneous MW and a sense of relief. For the same reasons, some patients with even severe levels of ADHD may excel at activities such as exciting/stimulating sports. Although there is as yet no direct evidence for this hypothesis, studies investigating default mode deactivation  and reacThese accounts of MW leading to impairment in ADHD remain speculative because of the lack of research on MW in ADHD. However, an increase in understanding of MW states in control participants provides a strong theoretical basis for the hypothesis that excessive MW may underlie many of the behavioral symptoms and impairments seen in ADHD. In healthy control samples, MW is associated with performance deficits that overlap with impairments seen in ADHD, including educational performance, driving accidents, and performance on cognitive tasks including errors of commission and RTV during sustained attention and inhibition tasks . Understd = .85 on ADHD symptoms compared with a treatment as usual group  was found to mediate the relationship between ADHD symptoms and detrimental forms of MW, suggesting that psychological treatments aimed at enhancing meta-awareness of MW, such as mindfulness-based interventions (MBIs), might ameliorate the negative consequences of MW in ADHD . Recent al group . Future Current screening tools for adult ADHD consist of rating scales for inattention and hyperactivity/impulsivity. Our findings suggest potential utility of the MEWS as an additional screening tool for adult ADHD in clinical practice, particularly as the MEWS is a strong predictor of impairment. Furthermore, as discussed above MW may also be measured more objectively using experience sampling methods in daily life or during experimental paradigms. Measures of MW may therefore assist in the accurate diagnosis of individuals based on their mental state rather than descriptions of behavior, which may be more subject to bias or influenced by an individual’s ability to develop compensatory behavioral strategies.However, currently we do not know the role that excessive MW, as measured by the MEWS, plays in other clinical disorders. For example, in depression depressive rumination represents another form of MW. Thus, the specificity of the MEWS across common mental health disorders needs to be explored. Therefore, we do not currently recommend the routine use of the MEWS to identify patients with ADHD until the scale has been comprehensively evaluated in other psychiatric disorders with overlapping clinical features, although high MEWS scores could be used to support the diagnosis. Investigation of the role of excessive MW in childhood and early adolescent ADHD is also recommended, including use of the scale in this population. Whether children and young adolescents would be able to conceptualize MW and reliably report on their mental state requires investigation.Some participants in Study 2 presented with co-occurring anxiety and depression, raising the possibility that MW might be linked to comorbid conditions. However, in Study 1 participants were free from co-occurring disorders , yet simIn relation to ADHD, a key question is whether MW differs conceptually from the inattentive symptoms currently used to define the disorder or whether the mental phenomenon of MW underlies the behavioral expression of inattention. As discussed above, it is feasible that measures of MW in ADHD are a more direct reflection of the neurobiology, leading to the inattentive symptoms of ADHD. Further work is required to evaluate the plausible hypothesis that aberrant regulation of DMN activity linked to excessive MW leads to ADHD symptoms and impairments. The study of MW has several potential advantages over behavioral inattention for research, because it may be measured using rating scales, as reported here, as well as experience sampling during daily life , or duriA fruitful next step in this research will be to take the MEWS into experimental paradigms. For example, an experimental trial of methylphenidate could be used to formally evaluate whether improvements in MW mediate improvements in ADHD symptoms and impairments, and to investigate the underlying neural mechanisms. Yet, currently, there are very little data that link rating scale measures of MW to experimentally derived measures in ADHD. Validation of MW in ADHD is therefore required across the various levels of measurement . We hypothesize that MW is a phenomenon that can be reliably measured, and it will be highly informative to see to what extent MEWS scores reflect TUTs measured during cognitive task performance in ADHD. It will also be advantageous to see how it relates to various cognitive measures such as omission and commission errors , and RTVThis research provides further insight into the mental phenomenon of MW in ADHD. We investigate a questionnaire-based measure of excessive MW recently developed in our research group. The MEWS was found to be a valid and reliable measure, with comparable sensitivity and specificity for case-control differences as existing rating scale measures of core ADHD symptoms currently used in clinical practice. The MEWS functioned extremely well for a brief 15-item measure and is potentially a useful measure to incorporate in future clinical and etiological research. MEWS scores were found to be a particularly good predictor of impairment, highlighting the clinical utility of the tool for diagnosis and treatment. Based on these findings, there is strong premise to view MW as a common co-occurring feature of adult ADHD with a specific effect on impairment, potentially explaining a variety of deficits not easily accounted for by the core symptom dimensions.Click here for additional data file.Supplemental material, Mindwandering_and_ADHD_SupplementaryMaterial_JAD for Validation of the Mind Excessively Wandering Scale and the Relationship of Mind Wandering to Impairment in Adult ADHD by Florence D. Mowlem, Caroline Skirrow, Peter Reid, Stefanos Maltezos, Simrit K. Nijjar, Andrew Merwood, Edward Barker, Ruth Cooper, Jonna Kuntsi and Philip Asherson in Journal of Attention Disorders