Tourette Syndrome (TS) has previously been associated with deficits in inhibitory control (IC). However, studies on IC in individuals with TS have produced conflicting results. In the present study, we investigated IC, comparing the Stop Signal Reaction Time (SSRT) measure with parent and teacher ratings of daily life IC in 169 children aged 8–12 , and 22 with TS + ADHD). We further investigated associations of IC with TS and ADHD symptom severity. Children with TS showed intact SSRT performance, but impairments in daily life IC, as reported by parents and teachers. For the latter, we observed a staircase distribution of groups, with the healthy controls presenting with the best IC, followed by TS, TS + ADHD, and finally ADHD. Dimensional analyses indicated a strong association between ADHD severity and both measures of IC. Our results indicate that children with TS are not impaired in a laboratory-based measure of IC, although some difficulties were evident from measures of everyday behaviour, which may in part be due to parents and teachers interpreting tics as disinhibited behaviour. Comorbid ADHD or the severity of subthreshold ADHD symptomatology appeared to account for IC deficits. Tourette Syndrome (TS) is a neurodevelopmental disorder, characterized by multiple motor tics and a minimum of one vocal tic, presenting before the age of 18 and lasting for at least one year . Tics arInhibitory control (IC) is an executive function defined as the ability to inhibit cognition and/or behaviour that is irrelevant or inappropriate to the execution of goal-oriented actions and adaptive behaviour ,4. IC isTS has been theoretically conceptualised as a disorder of inhibition due to several clinical features of the disorder . First, Empirical studies on IC in patients with TS have produced mixed results. A recent meta-analysis suggested mild but significant impairments in IC in individuals with TS compared to healthy controls in various performance-based inhibitory tasks, although subgroup analyses suggested an effect of comorbid ADHD . DespiteOnly a few previous studies on TS have included contrast groups of children with comorbid ADHD. One recent study indicated significantly impaired IC in the TS + ADHD group, whereas children with TS only did not differ from the healthy controls in a stop signal task . AnotherThe aim of the present study was to investigate the specific association between TS and IC deficits assessed with an objective laboratory-based measure, as well as a more subjective parent- and teacher-reported questionnaire. The lab-based behavioural task thus measures response inhibition when stopping an ongoing motor response (action cancellation), reflecting latent level IC without the influence of impulsivity components. On the other hand, the rating-based questionnaire measures the ability to control impulses and stop inappropriate behaviour, thus reflecting the everyday presence of IC and related impulsive behaviour, as perceived by parents and teachers. To better understand the role of comorbid ADHD on inhibitory deficits in TS, we included children with TS, ADHD, and TS + ADHD, as well as typically developing controls. Furthermore, we explored associations between IC and the severity of tics, premonitory urges, and ADHD. We expected children with TS without ADHD to perform equally to typically developing controls, followed by children with TS + ADHD, and lastly ADHD. Finally, we expected IC to be associated with ADHD symptoms, but not with TS symptoms. A better understanding of the nature of (dis)inhibition in TS may have clinical implications related to the available therapeutic interventions, which largely depend on the ability of individuals with TS to withhold their tics.The present study is an observational, cross-sectional, between-group, case-control design. n = 60) and typically developing children (n = 60), and two clinical contrast groups consisting of ADHD only (n = 27), and TS + ADHD . We previously reported on different data from the same cohort on topics of emotion regulation and response inhibition ,19. Chil n = 22; . ExclusiWe screened all participants with the Kiddie-Schedule for Affective Disorders and Schizophrenia—Present and Lifetime Version (K-SADS-PL) , which iMoreover, children who obtained a TS diagnosis from the K-SADS-PL underwent the Yale Global Tic Severity Scale (YGTSS) , which iFor all four groups, one parent and one teacher completed the ADHD Rating Scale (ADHD-RS), which measures ADHD symptoms and produces sub-scales for inattention and hyperactivity/impulsivity . In the The stop signal task (SST)  is a popIn the present study, we used hardware and software from The Cambridge Neuropsychological Test Automated Battery (CANTAB) , which oRIEF is a parent- and teacher-rated questionnaire with 86 items, assessing children’s executive functions based on their everyday behaviour in two contexts (home and school) . Each itStatistical analyses were performed with SPSS version 25.0, using two-tailed tests and an alpha level of 0.05. We tested all continuous outcomes for normality with the Shapiro–Wilk test and by visual inspection and used non-parametric tests when specific assumptions were violated. We controlled for the family-wise error rate with the Bonferroni correction where relevant. We aimed to achieve a power of 0.8  for the t test, differences in ADHD-RS scores with the Kruskal–Wallis test and the Mann–Whitney test, and finally, we tested for differences in SES and comorbidity with Fisher’s exact test.We tested for differences in age and IQ with ANOVA and post hoc LSD tests and for differences in sex with the r) were calculated for the significant pairwise comparisons by dividing the test statistic (z) by the squared total sample size.We removed values that differed by more than ± 2 SDs from the mean from the SSRT and BRIEF analysis. For group comparisons of SSRT, SSD, and BRIEF-Inhibit, we used the Kruskal–Wallis and the Mann–Whitney tests. Effect sizes (We assessed associations between inhibition (SSRT and BRIEF-Inhibit) and symptom severity and age of tic onset with Pearson’s product–moment correlation and the point–biserial correlation.p = 0.001) and SES (p < 0.001), with the highest scores in the control group, followed by TS, TS + ADHD, and finally the ADHD group. Furthermore, groups differed regarding ADHD-RS (p < 0.001), with most symptoms in the ADHD group, followed by TS + ADHD, TS, and finally the control group. Pairwise comparisons revealed that group differences in IQ and SES were driven by the ADHD group scoring significantly lower than the control group  and the TS group (p = 0.001). Finally, group differences in ADHD-RS were driven by all groups differing in relation to inattention and hyperactivity (except for TS + ADHD and ADHD) and CD (except for TS versus controls and TS + ADHD versus ADHD).The four groups did not differ significantly in relation to age or sex, nor did the clinical groups differ regarding comorbidity, age of tic onset, or YGTSS . The grop = 0.000; p = 0.002). It is noteworthy that the SSRT distribution was right-skewed, which is often the case for RT data and is in accordance with the horse-race model [One hundred sixty-three participants completed the SST, with three cases being excluded from the analysis due to the SSRT differing more than 2.5 SDs from the mean. SSRT was based on the last half of trials. Lower SSRT signifies a faster inhibition process, reflecting superior IC skills. SSRT and SSD were not normally distributed , and the TS group , with a medium to large effect. None of the other group differences were statistically significant, indicating that TS, TS + ADHD, and the healthy controls did not differ considerably regarding SSRT.There was a significant main group effect on SSRT  and teachers (p < 0.001). For both, the control group had the lowest scores, followed by TS, TS + ADHD, and finally ADHD . The same was the case for teacher reports ; ; ; ; ADHD > control, p < 0.001, r = 0.7).There was a significant main group effect on BRIEF-Inhibit, as reported by parents (lly ADHD . Pairwisp < 0.001) and remained significant with a Bonferroni-corrected threshold (0.05/9 = 0.006). The associations were positive, indicating that children with prolonged SSRT and increased BRIEF-Inhibit scores correspondingly displayed a high amount of ADHD symptoms. This result, however, appeared to be confounded by the presence of an ADHD diagnosis, as the associations between SSRT and inattention/hyperactivity were not significant when looking at the TS group only . Results remained significant in the TS only group for the association between BRIEF and ADHD symptomatology . Finally, the age of tic onset correlated inversely with SSRT; however, this did not remain significant when adjusting for multiple comparisons.We did not find any significant associations between measures of IC and TS symptom severity . ConversThe aim of the present study was to investigate the extent to which TS is associated with two aspects of IC deficits, namely, an objective, performance- and lab-based measure, and a daily life subjective parent- and teacher-reported questionnaire. For all group comparisons, we observed a staircase distribution of daily life IC, with the healthy control group presenting with the highest scores, followed by TS, TS + ADHD, and finally the ADHD group, although children with TS and the healthy controls did not differ significantly regarding the performance-based SSRT, in accordance with previous findings ,34,35,36The inconsistency between IC deficits in everyday life and in relation to the SST adds to the mixed results of previous studies. A possible explanation for this could be test-specific features representing different sub-domains of the complex construct of IC. Even within the domain of objective, lab-based measures, discrepancies are evident. In a recent study comprising largely the same group of participants as in the present study, we found IC to be superior in children with TS, although this was based on a different test of IC (a modified Simon task) and was carried out in an MRI scanner . OverallThe present results consistently point to the notion that ADHD symptomatology in paediatric TS is associated with IC deficits. The staircase distribution of the groups on the BRIEF-Inhibit scale and the SSRT  indicates an objective impairment only when comorbid ADHD is present in addition to TS. Interestingly, children with TS + ADHD perform better than children with only ADHD, suggesting that TS somehow appears to be a protective factor with regard to IC deficits, and supporting the hypothesis that children with TS develop compensatory mechanisms to increase their IC. To further examine whether subthreshold symptoms of ADHD could explain IC deficits in the TS group, we repeated the correlation analysis in the TS group isolated from the remaining groups. Interestingly, the association between ADHD symptomatology and SSRT was small and non-significant when exploring only the TS group, while the correlation coefficient with the BRIEF-Inhibit scale was moderate and remained significant. This may indicate that for the objective and direct measure of IC, the presence of TS compensated for the presence of subthreshold ADHD symptoms. This was not the case for everyday behaviour, as perceived by parents and teachers, which could illustrate that the two measures represent distinct aspects of IC and supports the finding that the BRIEF-Inhibit scale is highly sensitive to ADHD .The present SSRT results reflect an ability of children with TS to inhibit actions that are already initiated, possibly translating to the inhibition of tics by cancelling or compensating for the feeling of premonitory urges or the activation of motor behaviour. SSRT, however, reflects volitional inhibition, and thus the current study adds to the body of literature that indicates intact voluntary inhibition in TS, but does not take into account the potential deficits in automatic inhibition, which may play a part in tic generation; namely, tic generation and inhibitory deficits have been suggested to derive from an imbalance among volitional, goal-oriented actions, and automated, habitual action, with the latter appearing to be impaired in TS ,38, althThe major strengths of this study were the inclusion of medicine-naïve children as well as clinical contrast groups of children with ADHD and TS + ADHD, in addition to the large primary groups of TS and typically developing controls. This design makes it possible to control for the effects of psychotropic medication and comorbid ADHD and focuses on the age group in which tics are most frequent. We recruited children in the control group randomly via the Danish Civil Registration System, thus increasing representativeness and reducing selection bias. Furthermore, the combination of performance- and rating-based measures, as well as dimensional measures of TS and ADHD symptomatology, enables a more nuanced investigation of IC across different contexts.Several limitations exist as well. First, due to the modest sample sizes in the clinical contrast groups, the study may have been underpowered to detect between-group differences in these two groups. The small sample sizes were due to the focus on the two primary groups (TS and controls) and difficulty recruiting patients with ADHD from the psychiatric outpatient clinic. Second, the age of tic onset was not assessed systematically during the screening, but collected retrospectively from the K-SADS summary, and the variable was calculated for only a limited portion of the sample (72% of the TS group and 73% of the TS + ADHD group). Additionally, we did not screen systematically for the genetic or immunological causes of tics, but all patients underwent a physical screening. Third, the use of specific samples while controlling for comorbidity could be a limitation as well as a strength, since these samples may not be as representative of the population based on which we aim to draw conclusions. The inclusion of dimensional measures of TS and ADHD symptom severity, however, nuances the findings and allows for analyses of subthreshold symptoms of psychopathology. The ADHD group presented with significantly lower IQ than the control group, which, however, reflects the general presentation of the disorder. We thus chose not to include IQ as a covariate in the analysis, since this would compromise the representativity of the ADHD sample . FurtherIn conclusion, our mixed report results support the hypothesis of intact response inhibition in children with TS and suggest that these children are able to volitionally inhibit motor actions when they act in a goal-directed manner. Simultaneously, children with TS presented with inhibitory deficits in their everyday life, which seemed to relate strongly to ADHD symptomatology and may in part be explained by the difficulty distinguishing tics from other types of disinhibited behaviour. Future studies could advantageously examine this discrepancy further, as well as the subtypes of the broad concept of IC and their relation to treatment outcomes to not only increase the understanding of potential mediators of treatment effectiveness, but also enable a realistic assessment of treatment eligibility before embarking on the highly demanding treatment options of HRT and ERP.


Bartonella spp. are Gram-negative zoonotic bacteria transmitted to humans via various blood-sucking arthropods. Rodents have been identified as reservoir hosts of several zoonotic pathogens, including Bartonella spp. In Thailand, studies of Bartonella spp. in rodents from urban areas are limited; thus, a study in this area is necessary. The objectives of this study were to detect Bartonella spp. in rodents in Thailand and to compare the species’ distribution across different areas. In total, 70 blood samples from rodents in urban and suburban areas were tested for Bartonella spp. using a conventional polymerase chain reaction that targeted the citrate synthase (gltA) gene. All Bartonella-positive sequences were analyzed using polymorphism in order to build a phylogenetic tree. Approximately 38% of the rodents studied contained Bartonella DNA. Both Rattus exulans (Pacific rat) and R. tanezumi (Asian house rat) contained Bartonella spp. Four species of Bartonella were detected in blood samples: B. tribocorum, B. phoceensis, B. grahamii, and B. rattimassiliensis. In addition, eight Pacific rats contained the B. kosoyi–B. tribocorum complex. Bartonella phoceensis and B. tribocorum–B. kosoyi complexes were found in a specific habitat (p < 0.05). Interestingly, only seven haplotypes were identified in the sequences analyzed, and only haplotype A was found in both rodent species. Finally, a monitoring program for zoonotic Bartonella infection, especially the B. kosoyi–B. tribocorum complex, B. phoceensis, B. grahamii, and B. rattimassiliensis should be established, especially in high-risk areas. Bartonella spp. are Gram-negative intraerythrocytic bacteria [Bartonella have been confirmed as zoonotic pathogens, including B. henselae, B. clarridgeiae, B. elizabethae, B. grahamii, B. koehlerae, B. quintana, B. washoensis, and B. vinsonii [Bartonella are being found continuously [Bartonella spp. are zoonotic pathogens [Bartonella spp., including cats [Bartonella spp. have been detected in rodents in several continents, including Asia [bacteria  that havbacteria  and are bacteria . Severalvinsonii . New meminuously , and morathogens  that areathogens . Severaling cats ,8, dogs ing cats ,4, cattling cats ,10, and ing cats ,12. Furting Asia , Africa ing Asia , Europe ing Asia , Americaing Asia , and Ausing Asia .Rickettsia spp., Leptospira spp., Coxiella burnetii, Orientia tsutsugamushi, and Bartonella spp. [Bartonella spp. from outdoor activities [Bartonella spp. that have been associated with specific species of rodent could be the causative agents of Bartonella-related diseases in humans, such as endocarditis, lymphadenopathy, and some neurological abnormalities [Some rodents have been suspected of being a source of zoonotic pathogens transmitted to humans , such aslla spp. . From a tivities  and othetivities ,20. Sevemalities ,21.Bartonella infection in rodents frequently shows persistent and subclinical bacteremia [Bartonella spp. [Bartonella have been found in rodents [Bartonella doshiae [B. elizabethae [B. grahamii [B. rochalimae [B. tamiae [B. tribocorum [B. vinsonii subsp. arupensis [B. washoensis [Bartonella spp. found in rodents that cause human infections. Compared with other mammals, the different level of infection and high genetic diversity of Bartonella spp. in rodents has been noted [cteremia ,18. Appr rodents . Bartone doshiae , B. elizzabethae , B. grahgrahamii , B. rochchalimae , B. tami. tamiae , B. tribibocorum , B. vinsrupensis , and B. shoensis  have beeen noted .Bartonella based on a molecular detection [Bartonella spp. has been mainly conducted in companion animals [Bartonella are also necessary [Bartonella infection in rodents and to compare the species of Bartonella in areas of different characteristics (urban and suburban environments).In 2010, Thai febrile patients showed evidence of zoonotic species of etection ,30. In T animals ,32,33 an animals ; however animals . With reecessary . The curp), taken from a previous study in Thailand [p = 4.38%) was re-calculated from data on settlement and rain-fed areas derived from the previous study. For the sample size calculation, the maximum tolerated error (d) and alpha (α) were set at 5%. In total, the calculated sample size was 65 rodents based on the following equation:The sample size was calculated using an equation for the infinite population proportion  and a prThailand . BangkokThe sampling was approved by the Kasetsart University Institutional Animal Care and Use Committee, Bangkok, Thailand, under the Ethical Review Board of the Office of the National Research Council of Thailand . This study was a cross-sectional survey of rodents trapped from fields in two provinces (Bangkok and Nakhon Sawan), as shown in TM Blood DNA Extraction Mini Kit, Favorgen Biotech Corporation, Pingtung, Taiwan). The extraction protocol was performed according to the manufacturer’s instructions, and 100 µL of nuclease-free water was used as the elution solution. The extracted DNA was kept at −20 °C until a polymerase chain reaction (PCR) was performed.Two hundred microliters of whole blood was extracted for genomic DNA testing using a commercial extraction kit  and BhCS.1137n (5′-AATGCAAAAAGAACAGTAAACA-3′) were used to target the citrate synthase (gltA) gene of Bartonella spp. [Bartonella-positive blood sample, and the conditions of amplification were controlled using a thermocycler . In total, 25 µL of PCR mixture  were run for PCR detection and commercial Taq DNA polymerase was used . The running of PCR for BhCS.781p and BhCS.1137n was performed as follows: 5 min at 95 °C for initial denaturation, 35 repeated cycles of denaturation , annealing , and elongation . The last elongation was conducted at 72 °C for 5 min. Bartonella henselae strain Houston-1 DNA and nuclease-free water were used as the positive and negative controls, respectively. The amplified products were kept at 4 °C until gel electrophoresis.TM Nucleic Acid Stain  was used for DNA staining. DNA visualization was performed using an ultraviolet illuminator  and a 100-bp DNA ladder was used as the DNA size marker . The 379 bp band was cut and purified using a DNA purification kit . The running protocol followed the manufacturer’s instructions. Forty microliters of eluted purified DNA fragments were sent to a commercial sequencing unit using Sanger’s sequencing technology .Twenty microliters of the amplified product was run in 1.5% agarose gel under a 0.5X tris-acetate EDTA (TAE) buffer for 45 min at 100 V, and UltraPowerhttp://www.dnabaser.com, accessed on 20 November 2021) under the default low-quality end trimming conditions  of good base). The trimmed DNA chromatograms were edited using the SnapGene® Viewer version 5.3.2 software  and analyzed using BLASTn . A phylogenetic tree was constructed using the neighbor-joining method based on a proper substitution model with 1000 bootstrapping replications in the Molecular Evolutionary Genetics Analysis (MEGA) version X software . Bartonella positive sequences were analyzed for polymorphism based on the number of variable sites (VS), the proportion of G + C content (GC), the number of haplotypes (h), the average number of nucleotide differences (k), haplotype diversity (Hd), and nucleotide diversity (π) using the DNA Sequence Polymorphism (DnaSP) version 6.12.03 software . Then, the sequences were analyzed based on a median-joining network using the Population Analysis with Reticulate Trees (PopART) version 1.7 software  with the default setting (epsilon = 0). All Bartonella-matched sequences were submitted to GenBank with accession numbers: OK381826–OK381850.The obtained DNA sequences were trimmed using the Chromatogram Explorer Lite version 5.0.2 software . Prevalence was calculated, and the Wilson score interval method was used to estimate the 95% confidence interval of prevalence . Associaon 4.0.2 .Rattus exulans in urban (Bangkok) and 40 R. tanezumi in suburban (Nakhon Sawan). Of these, 27  had Bartonella DNA in their blood samples. Overall, no associated factors of Bartonella infection were identified in the rodents  had a gltA fragment of Bartonella spp. The BLAST results revealed a B. kosoyi–B. tribocorum complex  and B. phoceensis . All BLASTn results are presented in Of the Pacific rat blood samples, 13  were positive for R. exulans closely matched the B. kosoyi sequences (% identity = 99.36–100%) isolated from black rats (R. rattus) (CP031843) and B. tribocorum sequences (% identity = 99.36–100%) isolated from humans (HG969192). Surprisingly, the results of BLASTn for both B. kosoyi and B. tribocorum had similarity percentages; however, there were differences in non-compatible positions. Hence, these sequences (n = 8) were called a B. kosoyi–B. tribocorum complex. Interestingly, 14 sequences from R. tanezumi and R. exulans were similar to the B. phoceensis sequence (% identity = 97.94–100%) isolated from brown rats (R. norvegicus) (AY515126). In more minor findings, two other sequences (one from an Asian house rat and the other from a Pacific rat) matched B. rattimassiliensis  and B. grahamii , respectively. Comparing the two species (B. phoceensis and the B. kosoyi–B. tribocorum complex) and areas (Bangkok and Nakhon Sawan), there were significant differences in the proportion of Bartonella spp. Overall, B. phoceensis was found mostly in Nakhon Sawan, while the B. kosoyi–B. tribocorum complex was found only in Bangkok.Eight sequences from gltA fragments identified five species of Bartonella; the phylogenetic tree of the Bartonella positive sequences is presented in B. phoceensis complex (n = 14) and a B. kosoyi–B. tribocorum complex (n = 9). However, two sequences in the B. phoceensis complex were separate from the others. In the same way, in the B. tribocorum–B. kosoyi complex, one sequence was separate from the others. The polymorphism information of the partial gltA sequences that matched the B. kosoyi–B. tribocorum complex and B. phoceensis is presented in gltA sequences (n = 13 for R. exulans and n = 14 for R. tanezumi) showed π = 0.06471 ± 0.00617, Hd = 0.687 ± 0.071, and k = 19.61. Only haplotype A (12 sequences) showed different species of rodent that had B. phoceensis. However, other haplotypes (B-G) revealed specific Bartonella spp. Comparing the with and without reference sequences, those that matched B. kosoyi and B. tribocorum were clearly different from the references (CP031843 and HG969192). In contrast, the diversity difference between the with and without reference groups in B. phoceensis was not different from the previous finding.Sequencing of the R. exulans and R. tanezumi. In Thailand, various species of rodent were identified, including Rattus spp., Bandicota spp., Leopoldamys spp., Mus spp., and Niviventer spp. [Rattus spp. was found in suburban areas in the current study. Of these, R. tanezumi and R. exulans were reported as major species of Rattus in Thailand [R. tanezumi is a synanthropic rodent species mostly found in suburban environments, including residential and agricultural areas [Rattus were also reported such as R. norvegicus and R. rattus [Borrelia spp., Toxoplasma gondii, Yersinia pestis, Bartonella spp., Leptospira spp., and Coxiella burnetii [In this study, the trapped rodents belonged to two species: ter spp. . Rattus Thailand . Interesal areas . In urba. rattus . Due to . rattus . Severalburnetii .Bartonella spp. in their blood samples. Importantly, rodents have been mentioned as a major source of Bartonella infection in humans [Bartonella spp. have been discovered globally, and the rodent-adapted Bartonella spp. have high diversity [gltA gene revealed five species of Bartonella: B. tribocorum, B kosoyi, B. phoceensis, B. grahamii, and B. rattimassiliensis. Of these, three species have been reported as human pathogens [Bartonella spp. in the current study differed from other studies in Malaysia [Bartonella spp. being frequently isolated from R. rattus [Bartonella spp. in R. tanezumi in the current study was similar to that found in a study in Singapore [Bartonella rattimassiliensis and B. phoceensis were positive in R. tanezumi blood samples, which is a result similar to those of studies in Malaysia [Bartonella spp. (B. tribocorum and B. grahamii) were detected in R. exulans blood samples, which was similar to other studies in Thailand [Bartonella spp. in R. exulans differed from other studies [Bartonella infection risk in humans increases from contact among humans, rodents, and ectoparasites [Bartonella spp. and to circulate these pathogens in the rat population [Many rodents in the current study had n humans . Rodent-iversity . Partialathogens ,45. The Malaysia  and ChinMalaysia ; howeverMalaysia  was simi. rattus ,47,48. Tingapore ; howeveringapore ,50,51. BMalaysia , IndonesMalaysia , VietnamMalaysia . In addiThailand ,48,53. N studies ,55. Partarasites . In ThaiBartonella spp. infection in rodents varied from 6% to 100% [Bartonella prevalence rate in rodents, including habitat characteristics, body mass of rodents, age, rodent species, climate, rodent behavior, movement pattern, sampling method, and detection technique [Bartonella diversity were mentioned as common in rodents that had caused the heterogenous distribution of pathogens [Bartonella infection in the studied rodents, the comparison between species of rodent and Bartonella revealed specificity. However, there was a higher infection rate in the urban area (Bangkok). Furthermore, the cool season had a higher rate of Bartonella infection than the warm season. As the preferred habitat of each rodent species differed, the detected Bartonella spp. might have been affected by characteristics of the habitat in the current study. Moreover, the size and structure of the rat population, referred to as “ecological factors”, related to Bartonella prevalence and diversity, particularly in the urban environment [The previously reported prevalence of  to 100% . There aechnique ,46,57,58athogens . Even ifironment ,59,60.Bartonella spp. One R. exulans was carrying B. grahamii, which has been defined as a human pathogen and Ctenophthalamus nobilis has been suspected of being a possible vector [B. tribocorum, a zoonotic species [R. exulans. Interestingly, rodents have adapted to promote Bartonella spp. transmission to humans; in addition, Polyplax spinulosa and Xenopsylla cheopis have been mentioned as vectors of this species [R. tanezumi provided evidence of B. rattimassiliensis, which has also been identified as a zoonotic species carried by P. spinulosa, Haemophysalis longicornis, and Hoplopleura pacifica [Bartonella phoceensis was found in both R. tanezumi and R. exulans. Bartonella phoceensis has not been reported as causing human infection, and P. spinulosa has been suggested as a vector carrying this non-zoonotic species [B. tribocorum-positive R. exulans also matched a sequence of B. kosoyi with the same similarity and query coverage percentage but with differences in nucleotide substitution positions. The finding of B. kosoyi in R. exulans was similar to that in a study in Myanmar [gltA between B. tribocorum and B. kosoyi. However, the genome of B. kosoyi is closely related to B. elizabethae [Bartonella [B. kosoyi infection in humans, even though it has been isolated in rodents elsewhere [Inferring detected species, 11 of the 25 rodents carried zoonotic e vector . Additio species , was als species . In othepacifica . Bartone species . Interes Myanmar . To datezabethae , which hrtonella . In addilsewhere ,62,63.Bartonella detection [Bartonella detection in the current study, and seven haplotypes of partial gltA sequences were revealed. Several genetic events including mutation, demography, and recombination were factors regulating haplotype diversity [gltA sequences (approximately the 327 base pair) have been acclaimed for taxonomic classification in the genus Bartonella [rpoB) gene has been noted to increase identification efficacy, especially for the classification of new species [gltA sequencing was suggested as a common method for Bartonella diversity study in wild animals [gltA sequences of Bartonella spp. have been continuously updated, and this has facilitated more species to be distinguished [gltA was an important gene for critical functions [Bartonella using a reliable gltA marker. All sequences had values of similarity percentage > 96%, indicating a full match for the species, based on the recommendations from the La Scola study [The citrate synthase gene is widely used for etection ,65. The iversity . Trimmedrtonella  and for rtonella ,65,66. H animals ,68. Compnguished ,65. FurtBartonella spp. in the ectoparasites of the captured rodents was not included in the current study. However, there should be further study of infectious ectoparasites and ectoparasites in habitat environments in order to elucidate the dynamics of Bartonella spp. circulation in rodent populations. A complete explanation of the gltA gene and haplotype requires the analysis of the whole sequence of the gltA gene of Bartonella. A higher-level method should be used to fill this gap in knowledge, and full gene cloning and sequencing techniques should be considered for future studies.Unfortunately, the detection of R. exulans and 35% in R. tanezumi). Importantly, three zoonotic species were detected in the rodents’ blood samples . Furthermore, B. phoceensis was identified as the major Bartonella spp. In this rodent population. Remarkably, Bartonella phoceensis and the complex of B. tribocorum–B. kosoyi were significant in the suburban (Nakhon Sawan province) and urban (Bangkok province) areas, respectively. Comparing polymorphism in Bartonella-positive and matched reference sequences found that the complex of B. tribocorum–B. kosoyi had more differences in nucleotide sequences than B. phoceensis. Seven haplotypes of the sequences analyzed were identified; however, only haplotype A showed infection in both R. exulans and R. tanezumi. The authors suggest monitoring zoonotic species of Bartonella infection in humans, particularly in workers in contact with rodents. Furthermore, updating the knowledge on Bartonella-related diseases should be supported in risk areas.In this study, the overall prevalence was 38.57% in rodents inhabiting areas of central Thailand (43.33% in


Patients with attention‐deficit hyperactivity disorder (ADHD) often exhibit basic or paroxysmal wave abnormalities on electroencephalography (EEG). Methylphenidate (MPH), an anti‐ADHD stimulant, has been reported to lower the seizure threshold. However, there have been no reports comparing EEG changes before and after administration of the central nervous system (CNS) stimulant MPH, or atomoxetine (ATX) hydrochloride, a non‐CNS stimulant. In this study, we investigated changes in sleep EEG before and after the administration of ADHD treatment drugs.With the approval of the ethics committee, the medical records of 28 children with ADHD (23 men and 5 women) who gave consent were retrospectively investigated. The appearance of sudden abnormal waves during a 10‐minute sleep EEG recording was measured in 0.1‐second units, and the duration of these waves was calculated as the paroxysmal index (PI).Paroxysmal index did not differ significantly between patients who received MPH and those who received ATX. In addition, there were no exacerbations of clinical seizures.It was concluded that ADHD medications do not have an adverse effect on epileptic seizures or abnormal sleep EEGs. Patients with attention‐deficit hyperactivity disorder (ADHD) often exhibit basic or paroxysmal wave abnormalities on electroencephalography (EEG). We investigated changes in sleep EEG before and after the administration of ADHD treatment drugs. ADHD medications do not have an adverse effect on epileptic seizures or abnormal sleep EEGs. The rate of comorbid epilepsy in patients with ADHD is 2.6%‐27.7%, which is higher than in the general population.Furthermore, patients with ADHD often exhibit basic or paroxysmal electroencephalography (EEG) abnormalities. According to a study by Hughes et al,Attention‐deficit hyperactivity disorder and autism spectrum disorders (ASD) are neurodevelopmental disorders, and both are onset in childhood. ASD and ADHD often co‐occur, with comorbidity rates in the 40%‐70% range.Several studies have been conducted on epileptic discharge in ADHD. According to one study, 5%‐60% of patients with ADHD demonstrate epileptic discharges, of whom 14% show transition to epilepsy.Methylphenidate (MPH), a commercially available CNS stimulant used to treat ADHD in Japan, has been reported to lower seizure threshold. However, there have been no comparative studies on EEG changes before and after the administration of ADHD treatment drugs, including atomoxetine (ATX), a non‐CNS stimulant. Therefore, we examined the changes in sleep EEGs before and after the administration of anti‐ADHD medication.2The medical records of patients who gave consent were retrospectively examined with the approval of the Ethics Committee of NCNP . Paroxysmal abnormalities were obtained from sleep EEGs, assuming that the record of sleep stages 1‐2 occurred for at least 10 minutes. EEG recordings were performed in all patients under sedation with oral medication, pentobarbital, or triclofos sodium. No complications were observed by sedation in all patients.Electroencephalography assessment was performed by measuring spikes, slow waves, and spike‐and‐wave complexes detected in a 10‐minute EEG recording during light sleep in 0.1‐second units, as previously described by Altunel et alt test in each of the MPH and ATX groups. The U test was used with or without epilepsy and the change in PI before and after treatment.Statistical analysis was performed using the Wilcoxon signed‐rank test to detect PI changes before and after treatment. PI changes before and after treatment were evaluated using the Among those who visited our epilepsy/developmental disorder outpatient clinic in the National Center of Neurology and Psychiatry (NCNP) hospital between March 2011 and April 2016, the following patients were included: (a) those diagnosed with ADHD by certified pediatric neurologists using the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM‐4‐TR) or DSM‐5; (b) those who underwent sleep EEG before and after oral MPH or ATX administration; (c) those in whom there had been no changes in antiepileptic drugs (AEDs) due to seizures; and (d) those in whom there had been no changes in MPH and ATX dose. Other clinical characteristics data were collected from medical records: epilepsy, ASD complications, and drug history. Patients with incomplete EEG records what was <10 minutes or without sleep state were excluded.33.1We included 26 patients (21 men and 5 women) but finally performed the analysis in 28 patients (23 men and 5 women) because two patients were taking MPH and ATX at different times, they were included in this study (Table 3.23.2.1P < 0.06). A comparison of changes in the PI values in the MPH and ATX groups showed no significant differences (t(26) = 0.7, P = 0.49) , indicating older patients had longer durations of abnormal wave decreases after administration . There were no significant correlation changes in PI values with patient age at the first and second in patients without epilepsy.Similarly, changes in PI values with epilepsy showed a significant negative correlation with patient age . Patients not administrated AEDs were too small number, so that there was no indication to do statics.Changes in PI values administrated AEDs showed a significant negative correlation with patient age . In patients without ASD, changes in PI values showed a significant negative correlation with patient age .Changes in PI values with ASD showed no significant negative correlation with patient age (age at the first measurement: Spearman’s 3.2.2P = 0.40) , and whom of AEDs administration and without AEDs (P = 0.86). Between the MPH and ATX groups in patients with or without comorbid ASD and those administration or no administration AEDs had also no significant difference in the changes in PI values between the MPH and ATX groups.There was no difference in the changes in PI values between patients with comorbid ASD and those without ASD , but there was no correlation with inattention. In particular, the MPH group showed a significant correlation between the decrease in PI values and hyperactivity , whereas the ATX group did not show any significant correlation. There was no significant correlation between the PI values and each item of the ADHD‐RS in both patients with and without comorbid ASD. Similarly, there was no significant correlation between patients administrated AEDs and those not administrated AEDs.For the ADHD‐RS, the difference in values before and after oral administration was used to signify the change in symptoms Figures  and 9. Oρ = 0.74; P = 0.035; hyperactivity: ρ = 0.71; P = 0.050), and a significant correlation was also observed with the total score . However, patients without epilepsy showed no significant correlation between PI values and any item of the ADHD‐RS.Patients with comorbid epilepsy showed a significant correlation between the PI values and each item of the ADHD‐RS , both MPH and ATX improve inattention and hyperactivity/impulsivity. One study showed that MPH improved hyperactivity, learning disability symptoms, and heat‐induced seizures in epileptic rats,Regarding ATX and changes in ADHD symptoms and EEG basic waves, Chiarenza et alEight patients with ASD were included in present study. There were no significant PI changes between with and without ASD before and after ADHD treatment. There were a significant correlation changes in PI values and patient age with ASD; however, there was no significant correlation that without ASD in our study. This suggests that ASD is more likely to be complicated by EEG abnormalities, but that there is little improvement with age. Nicotera et alThe first limitation of this study was its single institution design and subsequent small sample size, which may have introduced inherent bias. In Japan, MPH, which can be prescribed only by certified doctors under the strict control of the Ministry of Health, Labor, and Welfare, has been carefully administered to patients with ADHD and epilepsy, meaning that relatively few patients could be examined at our institution. In addition, EEG to measure sleep state is not essential when starting ADHD treatment, and it was difficult to collect many cases because some children underwent only awake EEG. Second, there was no consideration of the developmental effects on EEG changes. Previous studies have reported that changes in the basal wave distribution occur during development from children to adults.In this study, we considered that there were no adverse effects on the abnormal sleep EEG in ADHD patients following administration of ADHD treatment, especially MPH. Although there was a concern that MPH administration in patients with ADHD with a history of epilepsy would exacerbate seizures, the results of this study suggest that it can be safely administered to patients with ADHD symptoms. For patients with ADHD, alleviating ADHD symptoms is also involved in quality of lifeAuthor EN has received speaker honoraria from Eisai Co., Ltd. The other authors declare no competing interests.HY, EN, YKita, and MI were involved in study design and data interpretation. HY, Kita, and MI were involved in the data analysis. All authors critically revised the report, commented on drafts of the manuscript, and approved the final report.Reviewer Board: approval of the Ethics Committee of NCNP .


Attention Deficit and Hyperactivity Disorder (ADHD) is a multi-factorial condition, with inheritance playing a major role. Recognizing parents’ ADHD represents a clue not only for an earlier diagnosis of the disease in their children, but also to optimize psycho-educational therapy outcomes, by addressing the impairment of parenting related to untreated ADHD. This study aimed to assess the frequency of features suggestive of ADHD during childhood among parents of affected children, and the presence of school and emotional impairment.We administered the Wender Utah Rating Scale-25, a self-assessment tool for the retrospective identification of symptoms consistent with ADHD during childhood, to a cohort of 120 parents of 60 children with ADHD, and to a consistent number of “controls”.p < 0.0001).The WURS-25 proved positive in 49.1% of fathers and 30.0% of mothers of ADHD patients, compared to 1.7% of fathers and 1.7% of mothers of non-ADHD patients (p < 0.0001).The questions addressing learning and emotional impairment provided significantly higher scores in parents with an overall positive test compared to those with negative test (This study demonstrates a remarkably high rate of symptoms consistent with ADHD during childhood in parents of affected children. Physicians should be aware that this is a relevant anamnestic clue and, given the relevance of parents’ role in the management of children with ADHD, an important issue to address in order to optimize patients’ treatment. Attention Deficit and Hyperactivity Disorder (ADHD) is a condition characterized by marked, persistent, maladaptive levels of inattention, impulsiveness, and hyperactivity, which has a negative impact on social, educational, and professional performances. Its estimated prevalence worldwide is 5% in children and 2.5% in adults , with stAlthough not yet fully understood, ADHD aetiology is probably multi-factorial. Several factors have been demonstrated to be involved, including low birth weight, smoking, drug and alcohol exposure during pregnancy, among biological factors , and matThis study aimed to assess the frequency of features suggestive of ADHD during childhood among parents of affected children, and the presence of school difficulties and emotional lability.A prospective case–control study was performed at the Child Neurology and Psychiatry Unit of the University teaching, tertiary children’s hospital, Institute for Maternal and Child Health “Burlo Garofolo”, in Trieste, Italy, from April 2019 to October 2019. The study was approved by the Institutional Review Board and all participants gave their written consent to take part in it.We considered as “cases” the parents of children who had received a diagnosis of ADHD  between January 2005 and June 2019. The control group consisted of parents of children with various neuropsychiatric conditions, summarized in Fig. The Wender Utah Rating Scale-25 (WURS-25) , 14 in tWe instructed the subjects to recall their behaviour and mood during primary school (age 6 to 10), rating every item from 0 to 4 , mildly (score = 1), moderately (score = 2), quite a bit (score = 3), or very much (score = 4)). The total score ranges from 0 to 100: we considered 46 as the cut-off score suggestive for previous ADHD 13.Four questions (number 22–25) aimed to evaluate scholastic impairment and provided an overall score ranging from 0 to 16 points. Seven questions  investigated the presence of emotional lability, providing an overall score ranging from 0 to 28 points.p-value < 0.05).We used the Chi-Square Test for the dichotomous variables and the Fisher exact test in case of frequencies below 5. For continuous variables, we used the Wilcoxon-Mann Whitney test  were therefore finally considered, along with 120 parents (60 mothers and 60 fathers): the latter were considered as “cases” and were matched to 60 mothers and 60 fathers of non-ADHD children as a control group.Regarding the disease subtypes, 2/60 (3.3%) children had predominant hyperactivity, 14/60 (23.3%) predominant inattention, and 44/60 (74.3%) a combined disorder. Forty-four out of 60 (73%) children had at least one co-morbidity: 35/60 (58%) patients displayed Oppositional Defiant Disorder, 11/60 (23%) Specific Learning Disorder, 10/60 (17%) Mood or Anxiety Disorder, and 7/60 (12%) other disorders, such as mixed learning disorder, language disorder, autism, epilepsy or obsessive–compulsive disorder. Seventeen out of 60 (28%) enrolled patients had more than one co-morbidity. Finally, 46/60 (77%) children with ADHD were on ongoing drug therapy with methylphenidate, in 15/60 (25%) in association with an antipsychotic drug, with 1 patient taking risperidone as a single drug. Thirteen out of 60 (22%) children were not receiving any drug therapy.Among parents of ADHD children, 60/60 (100%) mothers and 57/60 (95%) fathers answered the questionnaire, versus 60/60 (100%) and 60/60 (100%) mothers and fathers of non-ADHD children, respectively.2 = 51.99, p < 0.0001)  in 46/117 39.3%) parents of children with ADHD and 2/120 (1.7%) parents of non-ADHD children , while this difference was not observed among controls .Among parents of ADHD children, we detected a higher rate of positivity in fathers  compared to mothers  . Similar results were observed in fathers, with a slightly higher correlation .As for mothers, 94.7% of the positive tests belonged to”the case group”, which meant that they had a child with ADHD . The median score was 9 (IQR 7–12) among the 19 mothers who tested positive, versus 3 (IQR 1–4) among the 101 testing negative. A statistically significant difference was found between the two groups (p < 0.0001). Besides, 26.3% of mothers with positive test reported having repeated at least one school year. The median score of fathers was 8 (IQR 7–9) among the 29 who tested positive, versus 3 (IQR 2–5) among the 88 testing negative. Even in this case, there was a statistically significant difference between the two groups (p < 0.0001), and again, the 27.6% of fathers with positive test reported having repeated at least one school year.The median score of the questions investigating school impairment was 8 IQR 7–10) among the 48 parents with overall positive WURS test, versus 3 (IQR 1–4) among the 189 parents testing negative (Table 0 among tp < 0.0001) (Table p < 0.0001). Among fathers, the median score was 13 (IQR 10–15) among the 29 who tested positive, versus 5 (IQR 3–7) among the 88, testing negative (p < 0.0001).The median score of the questions assessing emotional lability was 14 (IQR 11.5–15) among the 48 parents with positive WURS test, versus 5 IQR 3–7) among the 189 who tested negative. The difference was statistically significant (1) Table , Fig. 3.–7 among This study shows a high rate of symptoms consistent with ADHD during childhood in parents of children affected by this disorder.Several aspects are involved in the multi-factorial pathogenesis of ADHD, including genetic, neurobiological and environmental elements. Inheritance likely plays a fundamental role in pathogenesis: the assessment of its weight would allow not only a better understanding of the disease but also an early diagnosis in the children of affected parents, along with timely treatment and prevention of detrimental consequences. Remarkably, a positive family history may be a relevant diagnostic clue, which physicians should specifically address. On the other hand, parent training is a cornerstone of treatment for children with mild-to-moderate ADHD . Since pIn this study we found a significant association between kinship and parents’ WURS test positivity: in particular, 49.1% of fathers and 30.0% of mothers of ADHD patients, compared to 1.7% of fathers and 1.7% of mothers of non-ADHD patients, had a positive test, reporting features consistent with ADHD during their childhood. Remarkably none of the surveyed parents had ever been diagnosed with ADHD, underlying a lack of standardized diagnostic criteria to detect this condition in the past. However, the WURS test does not allow the retrospective diagnosis of ADHD: indeed, its aim is to highlight the presence of emotional and behavioural traits consistent with the disorder.These results are in line with the previous literature. The role of genetic factors has been assessed over time  , and itRegarding school performances, we found an association between reported parents’ school difficulties and WURS test positivity, confirming the pivotal role of undiagnosed and untreated ADHD in learning difficulties. The latter, as underlined by Marzocchi and colleagues , can be Similar results were found about emotional deregulation. Parents with an overall positive WURS test demonstrated higher scores in the questions assessing emotional lability, compared to parents with negative tests.Tabassam and Grainger widely described the emotional dysfunction in ADHD children, characterized by sudden emotional changes, dysphoria, irritability, low tolerance to frustration, emotional hyper-reactivity, and emotions-recognition deficits . The conThis study, not only confirms these data but also highlights a high occurrence of school and emotional impairment in parents of affected children during their childhood, strengthening the suitability of the WURS test for the retrospective assessment of symptoms suggestive of ADHD, considering the crucial role of these two aspects in the diagnosis of the disorder.The main limits of this study consist of the relatively small sample size and the lack of a correlation analysis between patients and parents, due to the choice to collect and investigate the results in a completely anonymous way. For the same reason, we assessed every parent independently; therefore, it was not possible to compare the association with an affected child with a single positive parent and both parents’ positivity. On the other hand, the guarantee of anonymity provided a parental participation rate of almost 100%, which in turn, represents the strength of this study. A further point of strength was the case–control design, which allowed additional comparative results.This study demonstrated a high rate of symptoms consistent with ADHD during childhood in parents of children affected by this disorder. Physicians should actively investigate parents’ history when evaluating children with suspected ADHD. A proper assessment of the parents of these patients would also be crucial to optimize psycho-educational outcomes.


Irritability is especially pertinent to those with Attention Deficit Hyperactivity Disorder (ADHD) as it is highly prevalent and associated with a more severe clinical presentation and poorer longitudinal outcomes. Preliminary evidence suggests that top-down cognitive processes taking place in emotional contexts  as opposed to those evoked in abstract scenarios  may be relevant to the presentation of irritability in ADHD. This study explored the cognitive mechanisms underlying irritability in young people with ADHD, hypothesising that irritability would be associated with hot, but not cool, executive function impairments.Our sample included 219 individuals with ADHD. A composite irritability score was derived extracting items from a parent interview, with scores ranging from 0 to 5. Associations were investigated using linear regression analyses, between irritability and four hot tasks measuring sensitivity to risk, risk-taking behaviour following reward or punishment, acceptance of reward delay and reaction to unfair behaviour from others, and two cool tasks measuring set-shifting and motor inhibition.As hypothesised, there were no significant associations between irritability and cool executive functions in those with ADHD; however, contrary to expectations, there was also no significant evidence that hot executive functions were associated with irritability.These results, in a large well characterised sample and using a comprehensive task battery, suggest that the variation in irritability in those with ADHD may not be associated with differences in hot or cool executive function performance.The online version contains supplementary material available at 10.1186/s12888-022-03818-1. Irritability is defined as a propensity to react with anger under a minor provocation and this reaction is disproportionate compared to peers at the same developmental stage , 2. IrriADHD is heterogeneous in terms of core symptom presentation and clinical and functional outcomes. This heterogeneity is also observed at the cognitive level; individuals with this condition do not show a specific neuropsychological profile, displaying a variety of impairments in Executive Functioning (EF) , 23, 24.Neuropsychological impairments found in previous studies on those with ADHD are also common in children with high level irritability. Research on pathophysiological mechanisms of this phenotype is a new frontier and it is crucial to understand how it mediates risk for future psychiatric conditions , especiaA few studies also suggest impairments in cool EF, such as behavioural inhibition, as markers of irritability , 8, 27, Studies aiming to understand the sources of comorbidity between irritability and ADHD that focus on neuropsychological mechanisms are however scarce and far from conclusive. Previous work focused on bottom-up emotional reactivity and top-down regulatory mechanisms as possible reasons for the overlap between ADHD and severe irritability . These cBased on these knowledge gaps, it appears important to identify cognitive markers specific to irritability in those with ADHD and to understand shared mechanisms explaining their co-occurrence. To our knowledge this is the first study investigating cognitive markers of irritability in a sample of young people with ADHD. Using existing available data, the aim was to see whether irritability had a specific pattern of association with cool and hot EF. Based on previous research , 8, 27, N = 206). The majority of participants were taking medication for ADHD (78.8%) at the time of follow-up assessment, although they were asked to suspend it 24 h prior to testing.The sample composed of 219 young people aged 10–18 years . Participants were a subsample of children who took part in the Study of ADHD, Genes and Environment (SAGE) at Cardiff University   and who Symptoms and research diagnoses of ADHD were assessed at baseline using the parent version of the Child and Adolescent Psychiatric Assessment (CAPA) . PervasiSample collection preceded the publication of DSM-5. Following its publication, ADHD clinical symptoms and research diagnoses at both time points were reassessed and all participants with a DSM-IV diagnosis met DSM-5 criteria for ADHD. Conduct Disorder (CD) diagnosis was formulated at follow-up using the Development and Well Being Assessment (DAWBA) . All intCronbach alpha = .63).Due to available data, and consistently with previous work , 46, 47,The “Wisconsin Card Sorting Test” (WCST) is a measure of set-shifting behaviour where participants need to identify a matching criteria to sort a set of cards [of cards . These sof cards . To deteThe “Go no Go” task (GnG) is a measure of motor inhibition widely validated and extensively used in ADHD research [research , where presearch . We consThe “Card Playing Task” (CPT) is a measure of response perseveration when facing increasing loss that informs of an individual’s reward and punishment sensitivity [sitivity . The tasThe “Temporal Discounting Task” (TDT) is the degree to which a reward is devaluated in relation to its temporal delay, an index of impulsivity [ulsivity , 52. In ulsivity . The depulsivity .The “Ultimatum Game” (UG) is an economic-decision making game, often used as a measure of emotion regulation by assessing decision-making performance [formance , 55. In formance , 55, as formance . The depThe “Choice per Risk Task” (CxR) is a measure of risk-taking behaviour and how it is affected by reward and punishment sensitivity [sitivity . The aimsitivity –58. The Demographic information related to child age, sex and Social Economical Status (SES) were collected at baseline. SES was assessed based on parental occupation, according to the criteria of the Standard Occupational Classification . This mep < .006). Parametric methods were used as the variables were all normally distributed and met all the relevant assumptions for analyses. None of the variables were skewed or kurtotic  according to recommendations by George and Mallery (2010) [n = 18; 8.2%) did not stop their ADHD medication 24 h prior testing, sensitivity analyses were performed to see if there was a change in the results by excluding these participants  . As some0 . As soAround half of this sample came from a low socioeconomic background (45.6%), as may be expected in a UK clinical ADHD sample who met ADHD diagnostic criteria at baseline to enter the study. Mean ADHD symptom scores  and ADHD diagnostic rates (80.6%) were high at follow-up. CD diagnosis was also common with a prevalence of 35%. Prevalence of irritability symptoms is shown in Table The presence of any irritability symptoms was common in this clinical ADHD sample, 95% of parents endorsed at least one irritability symptom Table . Consider = .78, p < .001) and with CxR propensity to gamble ; TDT RT was significantly associated with TDT AUC . UG Moderately Unfair offers accepted significantly correlated with CPT total cards played . ADHD symptoms at follow-up also did not show any significant associations with EF measures whereas it was significantly associated with irritability .The cool EFs were significantly associated with demographic characteristics as shown in Table As shown in Table Sensitivity analyses excluding adolescents who had not withdrawn their medication, those with CD diagnosis at follow-up, and exploring within time associations between irritability and EF in adolescence did not alter the findings . As suggested by previous reviews , 8, 27, This study has several strengths. It is innovative as it is the first study looking at cognitive markers of irritability in ADHD, exploring potential pathological mechanisms leading to impairment in this population. It benefits from a clear and circumscribed operationalisation of irritability, as opposed to looking at facets of this construct . A wide range of well validated cognitive tasks was also used, ultimately enhancing the opportunity to directly compare these two cognitive aspects. Nonetheless, the results of this study should be considered in light of several limitations. Firstly, this is a post hoc study and the measures available were originally chosen to address a different aim. Thus, a comprehensive scale specifically designed to tap irritability could not be used. Additionally, the EF tasks were initially selected as well validated in identifying variance in those with ADHD population and not as direct measures of cognitive markers of irritability. Secondly, this study lacks both a comparison and a control group which would complement the study of the cognitive markers of irritability by looking at its impact on hot cognitive functioning both in the general population and in other clinical samples. The lack of typically developing controls also limits the possibility to compare EF performances, ultimately being unable to refine these analyses to those actually showing EF impairments. Thirdly, despite the large number of families with ADHD in this study at baseline, participant drop-out, protocol changes and quality control checks negatively impacted the availability of cognitive data at follow-up. Thus, investigating the same research questions in a larger sample might enable more definitive conclusion. Fourthly, irritability tends to decrease with age , thus exIn conclusion this is the first study investigating an association between reward-related impairments in the form of hot EF and a dimensional measure of irritability in a clinical sample of young people with ADHD, as suggested by previous work and theoretical rationale. Despite the broad range of well validated hot and cool EF measures used, our results failed to support our initial hypothesis; irritability does not seem to be associated with impairments in reward processing, in youths with ADHD. Other neuropsychological processes  may be more relevant to the associations between ADHD and irritability than hot and cool EF and should be investigated. Irritability is a cross-diagnostic symptom, thus investigating its cognitive markers in both externalising and internalising conditions could give better insight about pathophysiological mechanisms of this phenotype across different cohorts. Addressing these aspects in future research could improve the theoretical models of ADHD and provide a better understanding of the importance of irritability across conditions, being ultimately useful in clinical practice.Additional file 1: Table S1. Pattern of associations between irritability and hot and cool EF measures. Table S2. Pattern of associations between irritability and hot and cool EF measures. Table S3. Correlations between irritability measured in adolescence and executive functions. Table S4. Correlation matrix between EF measures, IQ and Irritability.


The current study investigates the possibility that athletes have more parallel ADHD symptoms than non-athletes. High-level youth sport athletes were compared with non-athletes in leisure time  and in the school in ADHD symptoms. Athletes and students were evaluated by a trained psychotherapist using Adult ADHD Self-Report Scale (ASRS) on activities at school and during activities in leisure/sports time. They also filled in the Autism Spectrum Questionnaire (AQ) as a self-report assessment. Results showed significant differences in ASRS-scores for athletes in school and in their sport, with high scores in school and low scores in sport. No differences were found in AQ between the groups. The findings indicate that many athletes might display a cognitive profile of parallel of ADHD criteria. Future research needs to further investigate potential benefits of the cognitive profile in athletes and how they handle different contexts including sport and school settings. Attention deficit hyperactivity disorder (ADHD) is considered a disorder that can cause behavioral and emotional problems for the individual . StudiesAttention deficit hyperactivity disorder involves distractibility, and difficulty with attention, impulse control, and activity control, in reference to what the situation requires . For an An interesting theory is Hartmans anthropological/sociological theory where ADHD is described as hunter in a farmer society. In this model, it is stated that ADHD traits of hunter–gatherers would have been environmentally advantageous. This includes hyperactivity, thus being energetic and tireless behaviour, and having high impulsivity, and the ability to change the strategy quickly. Accordingly, the very attributes that render ADHD individuals good “hunters” , are less compatible with modern, daily demands of the “farmer society.” The potentially advantageous traits from hunters are easily translated into sports where being energetic, monitoring the field of play and being ready to take action are effective in many situations and types of sports.Difficulties in focusing and keeping attention have been well studied in ADHD. Another area that has been researched is selective attention although few studies have considered how selective attention can be an advantage, i.e., in terms of hyper focusing, which has been reported as a phenomenon of ADHD ,18. HypeFurthermore, studies have shown that reward, in neurofeedback, has a positive influence on ADHD and, furthermore, a positive effect on endurance, which is a difficulty for ADHD children . In sporResearch in ADHD in athletes has mainly focused on the negative effects of ADHD. This includes studies reporting an increased risk of injury , and higInterestingly, it has been suggested that ADHD may be more common in competitive athletes than in the general population ,38. In aIn conclusion, some common symptoms of ADHD may enhance athletic performance. Many children with ADHD report to ‘hyperfocus’ on their enjoyable sporting activities without being distracted . It has The aim of the current study was to compare athletes to non-athletes, both of school-going age, in terms of Adult ADHD Self-Report Scale (ASRS) criteria , i.e., AMage 16.94 years, age range 16–19 years), were recruited from two high schools in Sweden, one group being athletes  and another, non-athletes . The athlete group were enrolled in the Swedish national sports talent program  and intensively involved in their sport and are considered among the most talented in the country and are not having any diagnosis nor do they have disability service at the sport academies. They competed at club/local (11.2%), regional (23.4%), national (52.3%), and international (13.1%) level and represented a variety of sports including team sports  and individual sports . The athletes invested 12.20 (standard deviation (SD) 4.46; range 2–24) hours per week in training and competition and had participated in sport for a median of 9.29  years. Both groups were matched in age and school programs, thus studying at the same theoretical educational program.A total of 200 students, 112 female and 88 male  was selected because several studies have shown that Autism Spectrum Disorder (ASD) symptoms coexist in individuals with ADHD , especiaThe AQ is one of the most widely used measures of ASD and has been found to be predictive of diagnosis of ASD in a clinical setting . QuestioThe Regional Ethics Review Board in Uppsala (Dnr. 2016/451) approved the study and after informed consent participants were interviewed by a trained psychotherapist with long experience and good knowledge of ADHD and autism spectrum disorder (ASD). In the interview, they were estimated on ASRS regarding school activity and leisure time/their sport activity time. The athlete themselves also filled in the AQ. The instruments were collected by the interviewer at the end of the interview. All text on the instruments about diagnoses was excluded and all questions were answered without mentioning of ADHD and ASD. The purpose of the evaluations was to identify parallel criteria between the two instruments, and not to identify a diagnosis. The instruments were named 1 and 2, in order for the students to be less influenced by their own preconceived opinion about diagnoses.Data analysis was carried out to compare the two groups in terms of ASRS criteria, in leisure time and in the school environment. The processing of data was conducted using IBM SPSS Statistics for Windows, Version 24.0.  A two-way analysis of variance (ANOVA) F-test was used to analyse differences between the groups (athletes vs. non-athletes) and pair-wise post-hoc comparisons with Tukey’s HSD test was used to compare the sport athletes during sports activities and school. Data were screened for normality and homogeneity of variances was tested using the Levene statistic.p > 0.05) differences between club/local, regional, national, or international levels, in terms of hours invested in training and competitions.Means and standard deviation are shown in p < 0.001), as well as within-group differences in school- and leisure activities  = 335.7, p < 0.001). Also, the interaction term for ADHD criteria vs. school- and leisure/sport activities was significant  = 365.9, p < 0.001).Two-way ANOVA (split-plot design) showed statistically significant between-group differences in ADHD criteria  = 157.3, p < 0.001) difference between the groups during school activities, but not during leisure/sport activities (p > 0.05), with higher scores for the athlete group (see p < 0.001) differences between the activities, i.e., leisure/sports activities and school activities [Cohen’s d = 2.19].Pair-wise post-hoc comparisons with Tukey’s HSD test showed the significant  was large . For theIn Hartmann’s sociological/anthropological theory, the ADHD cognitive profile is described as a hunter in a farming society  and baseSeveral studies indicate that physical activity and environmental factors have a positive effect on inattention and hyperactivity, which are considered core symptoms of ADHD , and alsChildren/adolescents involved in sport often demonstrate discipline and commitment , and eviBased on the discussion above, a question for future research would be whether we can learn from these studies and, instead of over diagnosing and overtreating children/adults ,60, lookThis study has focused on investigating a cognitive profile of ADHD in young athletes and how it differs in different contexts . There is an evident need for more studies concerning young individuals with the cognitive profile of ADHD and how they best develop a functional daily life in school and in leisure time. There is a need to learn more about how sport, with its physical exercise and stimulation, structure, consistent patterns of behavior and the positive reinforcement, can be useful in other areas such as school ,64.Looking at the strength of this study, although more comprehensive evaluation has been suggested for athletes seeking help , researcIn conclusion, in this study, we report that ADHD criteria are highly presented in the athlete group in the school environment and very low during leisure time compared to the non-athlete group. This supports the suggestion that ADHD symptoms might be more prevalent in an athlete population , but impThe ADHD criteria might turn into an advantage rather than a disadvantage for the athletes in their sport achievement . Based o


Similarly, the number of pharmacotherapy cases of ADHD significantly increased from 3886 in 2015 to 12,502 in 2018 (p = 0.01), which is 0.01% to 0.03% of total population. The most commonly used medication at the initiation of pharmacotherapy shifted from Penid in 2015 to Concerta in 2018. Furthermore, combination therapy with two or more drugs was the preferred method in 2016–2018. In conclusion, the identified diagnoses and pharmacotherapy incidences were very low, highlighting the need to improve the public’s awareness of adult ADHD.There is a paucity of published literature on the epidemiology of adult attention-deficit/hyperactivity disorder (ADHD). We investigated the time trends of the diagnostic and pharmacotherapy incidence of ADHD, including the first used medication, in the adult population based on a Korean population-based database from 2015 to 2018. The number of diagnosed cases of ADHD significantly increased from 7782 in 2015 to 17,264 in 2018 ( Attention-deficit/hyperactivity disorder (ADHD) is a common psychiatric disorder with a chronic course that can lead to negative outcomes without optimal treatment ,2. It waThe global prevalence of ADHD in children and adolescents is approximately 2–7% ,5, and aHowever, the epidemiological data of adult ADHD diagnosis and medication are limited compared to those of children and adolescents. In this study, we aimed to investigate the diagnostic and pharmacotherapeutic incidence of ADHD and conducted a trend analysis in the entire adult population (18 and above) using the National Health Insurance Services (NHIS) database.This retrospective analysis used data from the NHIS claims database from 1 January 2014 to 31 December 2018. The inclusion criteria were as follows: (1) aged 18 and above and (2) the presence of an inpatient or outpatient medical claim containing a code for the diagnosis of ADHD  between 1 January 2014 and 31 December 2018, with no medication use during the 1 year preceding the claim. This study was approved by the institutional review board of Myongji Hospital (MJH 2019-05-014).https://kosis.kr/statisticsList/statisticsListIndex.do?menuId=M_01_01&vwcd=MT_ZTITLE&parmTabId=M_01_01&outLink=Y&entrType=#content-group, accessed on 10 May 2021).Subjects diagnosed with ADHD (F90.0x) during a given year, but not the previous year, were defined as incident cases. The annual incidence was calculated from 2015 to 2018 by dividing the number of newly diagnosed cases of ADHD during each year by the number of person-years at risk in the NHIS dataset for the same year. The incidence of ADHD was calculated using the same method. The data on the total population aged 18 and above were obtained from the National Statistical Office  were used to characterize the medication use and the clinical and demographic variables. To assess the trends in adult ADHD diagnosis and medication use, we examined temporal changes from 2015 to 2018 using a time series linear model. SAS 9.3  was used to link and analyze the data. The significance level was set at p = 0.036). The annual diagnostic incidence during the study period also increased from 0.02% in 2015 to 0.04% in 2018. The diagnostic incidence showed an overall male predominance, though this trend gradually decreased. All the age groups, except the 31–40 year and 61 years and over groups, showed significant linear trends. New diagnoses by psychiatrists showed a statistically significant increase during the four-year period (p = 0.0466). The numbers and trends of annual incident cases are shown in p = 0.0196). The annual treatment incidence during the study period also increased from 0.01% in 2015 to 0.03% in 2018. The treatment incidence showed an overall male predominance, though this trend gradually decreased. All the age groups, except the 61 years and over group, showed significant linear trends.The number and trends of the annual pharmacotherapy cases are shown in p = 0.02). The commonly used drugs were Penid, followed by Concerta, atomoxetine, and bupropion.Most patients who initiated pharmacotherapy used two or more drugs, and the trends increased significantly  and treatment population . This finding is consistent with the published results .Although the current study was outstanding in its analysis of the trend of adult ADHD using nationwide population data, several limitations need to be acknowledged. First, the ADHD diagnoses used in the study were derived from administrative claims data based on the International Classification of Disease 10th edition codes by physicians, rather than from structured clinical interviews. Second, the identified incidence rate in this study may be an underestimation of the actual incidence, as the study included only those who visited a clinic or hospital, that is, they had healthcare-seeking behavior. Third, caution is warranted when generalizing the results to other countries where no mandatory NHI system has been adopted.Despite the above-mentioned limitations, the current study is among the few to date that have investigated the trends in the diagnostic and pharmacotherapy incidence of ADHD in the adult population.