Attention deficit hyperactivity disorder (ADHD) is the most prevalent neuropsychiatric disorder in the world. Currently, the diagnosis is based mainly on interviews, resulting in uncertainties in the clinical assessment. While some neuropsychological tests are used, their specificity and selectivity are low, and more reliable biomarkers are desirable. Previous research indicates that ADHD is associated with morphological changes in the cerebellum, which is essential for motor ability and timing. Here, we compared 29 children diagnosed with ADHD to 96 age-matched controls on prism adaptation, eyeblink conditioning, and timed motor performance in a finger tapping task. Prism adaptation and timing precision in the finger tapping task, but not performance on eyeblink conditioning, differed between the ADHD and control groups, as well as between children with and without Deficits in Attention, Motor control, and Perception (DAMP) – a more severe form of ADHD. The results suggest finger tapping can be used as a cheap, objective, and unbiased biomarker to complement current diagnostic procedures. Attention Deficit Hyperactive Disorder (ADHD) is one of the most common neuropsychiatric disorders in children and adolescents, with a prevalence of 2.2–7.2% depending on age group, assessment procedures, and location –4. Boys The diagnosis of ADHD is most commonly based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) issued by the American Psychiatric Association or the International Statistical Classification of Diseases and Related Health Problems  . SeveralThe Deficits in Attention, Motor control, and Perception (DAMP) concept represents symptoms extending those of ADHD with those of Minor Neurological Deficits (MND) . DAMP waMany studies have examined brain morphology and functional activation patterns in children with ADHD and MND. The results are heterogeneous, but some systematic patterns have emerged. Analyses of resting-state connectivity of the primary motor cortex revealed that children with MND and ADHD have unique alterations in the functional connectivity between the primary motor cortex and sensory networks compared to children with MND or ADHD only . HistoriSeveral studies have examined links between ADHD and brain morphology, including cerebellar morphology. Multiple studies show that patients with ADHD have a smaller cerebellum –45, althIf there is a link between ADHD and cerebellar function, tests of cerebellar function could supplement the diagnosis of ADHD, MND, or DAMP. Evidence shows that performance on tasks related to cerebellar function differs between patients and controls. On eyeblink conditioning, children with ADHD exhibit a similar percentage of conditioned responses, but a larger proportion of abnormally timed conditioned responses –52. In tThe present study aims to assess cerebellar function in children with ADHD and DAMP relative to neurotypical developing controls. The test battery consists of five subtests, three of which have been linked to cerebellar function in previous studies: (1) prism adaptation, (2) isochronous serial interval production (ISIP), also known as finger tapping, and (3) eyeblink conditioning. However, individuals who perform well on one of these tasks do not necessarily perform well on the others, suggesting that they rely on partially distinct cerebellar mechanisms . In addiA total of 125 children were tested in this study. The control group consisted of 96 children, 47 boys, and 49 girls, with an average age of 12.0 ± 1.02, recruited from a local elementary school in Lund (Järnåkraskolan). The ADHD group consisted of 29 children diagnosed with ADHD, 20 boys and 9 girls, with an average age of 12.5 ± 2.25. They were recruited from three institutions in southern Sweden: (1) The child and adolescent psychiatry unit in Malmö (BUP), (2) Modigo – a private clinic that assesses and diagnoses children with neurodevelopmental disorders, and (3) Källan Teaching Group – a public teaching group for children and adolescents with special education needs. The children were tested between 2017 and 2020. The study was approved by the Swedish Ethical Review Authority in Lund, Sweden (DNR. 2017/745).Upon arrival, the children and their legal guardians received information about the test battery and were given an opportunity to ask questions. The children were informed that they could end their participation at any time without any consequences. One legal guardian per participant was allowed in the test room if the child or the legal guardian so wished. The five tests were performed in the same order for all participants: (1) prism adaptation, (2) ISIP, (3) eyeblink conditioning, (4) a standard neuromotor status test, and (5) the similarities part of the Wechsler Intelligence Scale for Children (WISC). The whole session took about one hour to complete and took place in a quiet room at the school or the clinic, whichever was most convenient for the participant.Prism adaptation is used to assess the adaptation of motor activity following changes in visual input. Previous research has linked performance on prism adaptation to cerebellar function , 61. In Two types of finger tapping performance were assessed, formally known as sensorimotor synchronization (SMS) and isochronous serial interval production (ISIP), typically combined in the so-called synchronization-continuation paradigm , known tThe SMS and the ISIP data were analyzed separately. Two metrics were used for the SMS data: the mean inter-tap interval and the mean asynchronies relative to the guiding sounds. Three metrics were used for the ISIP data: the mean inter-tap interval and two measures of variability called drift and local . These mEyeblink conditioning is one of the most used tests when studying cerebellar function. Many studies corroborate its cerebellar dependence. In this task, a conditional stimulus (CS) is paired with an unconditional stimulus (US) that provokes an unconditional response (UR). Over time, the CS will produce a conditional response (CR), even when the US is absent –70. PartThe CS consisted of sinusoidal 1,000 Hz auditory tone with a duration of 1 s. Before the training, we ensured the participant could hear the tone clearly. The US was a ~ 100-ms air puff to the cornea with a pressure between 0,5–1,5 bar. The exact pressure was individually adjusted so that the air puff triggered an eyeblink reflex (a UR) while not being perceived as overly unpleasant. Before starting the tests, we made sure that the participant could hear the tone and that the tone itself did not trigger a blink reflex. We used two different interstimulus intervals (the time between the onset of the CS and US) of 300 and 500 ms. We used 500 ms because that is a common interstimulus interval in human studies. We also added a shorter 300 ms interstimulus interval because it is closer to what is typically used in animal studies and because we reasoned that it would reduce the probability of volitional interference .The inter-trial interval (ITI) was set to vary randomly from 4 to 12 s. Training consisted of 100 trials with 20% randomly interspersed probe trials where the CS was presented without the US. Measurements from the magnetic sensor were sampled using a Micro 1401 AD converter (Cambridge Electronics Design) connected to a PC running Spike2 v.9 (Cambridge Electronics Design). The raw signal from the magnetic sensor was exported to Matlab, where custom scripts were used to identify the timing of blink responses relative to the CS onset. Trials were categorized as invalid if an eyelid movement occurred within 100 ms of the CS onset. On valid trials, the script determined if there was a blink response and then, based on the onset of the response, whether that response should be categorized as a CR. A CR was defined as a blink response with an onset before the air puff. For each participant, we visually inspected 10 randomly selected trials to ensure that the algorithm worked for most trials. While a few categorizations errors did occur, we did not correct them so as not to introduce any subjective bias into the evaluation.The fourth test in the battery was a standardized neuromotor test consisting of several short motor tasks , includiTo assess and control for IQ we administered the similarities part of WISC. In this test children should state in what way to concepts are similar. For example, if the experimenter says apples and bananas are both …, then the child should say fruits or provide and explanation that is equivalent of this statement. The performance on this test was used as a proxy for IQ.Since several variables were not normally distributed, non-parametrical statistical tests were used to test statistical significance. The Mann–Whitney U-test was used for comparisons of the ADHD group and the control group, and the Kruskal–Wallis test for comparisons between children with ADHD without MND, children with DAMP (defined as having both ADHD and MND), children with MND without ADHD, and children without ADHD and MND, with the Mann–Whitney U-test for post hoc analyses. A logistic regression analysis was conducted to assess the various tests’ predictive value for detecting DAMP. Spearman correlations were performed to analyze the associations between the different test variables. ROC analyses were performed to investigate the sensitivity and specificity of the tests in predicting DAMP. Cut-off values with the highest simultaneous sensitivity and specificity were made, and the sensitivities and specificities were calculated. Exact p-values are reported in the table.p > 0.18). Since there was no sex difference in this sample, we did not consider sex further in the remaining analysis.First, we consider differences between the ADHD and control groups. Table To assess whether children with ADHD differed from controls on prism adaptation, we examined two variables, the error on the first trial after putting the prisms on (prism first with) and the first trial after taking the prisms off (prism first without). As illustrated in Fig. p-values > 0.3). As illustrated in Figs. No differences or trends were found for any of the variables examined for eyeblink conditioning. We compared the percentage of conditioned responses (Percent CR), the onset of conditioned responses (Eyeblink onset), and the variation in the onset of conditioned responses (Eyeblink onset SD) , which was seamlessly followed by a production phase (ISIP) when the sounds stopped. As mentioned above, the metrics used for SMS were mean inter onset interval (IOI) and asynchronies and for ISIP mean (IOI), local and drift variability. Comparing the ADHD and controls revealed significant differences in IOI and variability in both the SMS and ISIP phases , Prod mean (p = 0.024), Local (p < 0.001), and Drift (0.001). Significant differences were found between the children with DAMP and control children with MND concerning Sync sd (p < 0.001), Prod mean (p = 0.049), Local (p = 0.002), and Drift (p = 0.001). Significant differences were found between the children with DAMP and the control children without MND, concerning Prism first with (p < 0.001), Sync mean (p = 0.001), Sync sd (p < 0.001), Prod mean (p < 0.001), Local (p < 0.001), and Drift (p < 0.001). Finally, significant differences between the children with ADHD without MND and the controls without MND were found on variables Prism first without (p = 0.006) and Sync mean (p = 0.010). No significant differences were found between the children with ADHD without MND and the controls with MND, or between the control children with MND and the control children without MND. The sensitivity and specificity of the different variables concerning DAMP were assessed with Receiver Operating Characteristic (ROC) analyses.Significant differences were found between the children with ADHD without MND and the children with DAMP concerning the variables Sync SD (ROC curves and area under the curve (AUC) values for the variables with high values concerning AUC (above 0.80) can be found in Fig. When only children with ADHD-diagnoses were analyzed with the variable Drift dichotomized at the cut-off value giving the best simultaneous sensitivity and specificity values in predicting DAMP, both the sensitivity and specificity were found to be 0.89. When we analyzed the odds for DAMP using univariable logistic regression Table , we founOur results show that finger tapping and prism adaptation performance can differentiate between children with and without ADHD and even more accurately between children with and without DAMP. As both types of tests are related to cerebellar function, the results reinforce the view that children with ADHD and DAMP have altered cerebellar function leading to deficits in tasks relying on cerebellar function. The high sensitivity and specificity found for these tests point towards their possible clinical utility, especially the finger tapping test, which is easy and quick to administer. Previous research shows that children with DAMP have more learning difficulties and more autistic traits than children with ADHD without MND . Thus, SROC analyses showed high values for AUC for several cerebellar-related performance variables, especially measures of finger-tapping variation. When it came to finding children with DAMP, the variable Drift had an especially good relation between sensitivity and specificity – higher than quantitative tests currently used for ADHD evaluationss, such as the Integrated visual and auditory continuous performance test (IVA) . Our derPerformance on finger tapping and prism adaptation have been linked to cerebellar performance. The fact that performance on both tests correlated with ADHD diagnosis and DAMP reinforces the view that ADHD is linked to abnormal cerebellar function. We were, therefore, surprised to find that performance on eyeblink conditioning, another test linked to cerebellar function, showed no significant association with ADHD. This appears to contradict Frings et. al., , who repOverall, our results support the hypothesis that children with ADHD and DAMP have altered cerebellar functions and that cerebellar performance tests can be helpful in a clinical context. Compared to other potential biomarkers, such as MRI scans, these tests are fast and easy to conduct, making them a more viable option in most settings. The cerebellum has also been linked to autism , and futTaken together, our results suggest that cerebellar tests, generally and finger tapping in particular, may prove to be a robust research and diagnostic tool in the evaluation of children suspected of having ADHD. Finger tapping seems especially useful when distinguishing between children with ADHD of different severity.


Attention-deficit/hyperactivity disorder (ADHD) is highly heritable, but little is known about the relative effects of transmitted  and nontransmitted  common variant risks. Using parent-offspring trios, we tested whether polygenic liability for neurodevelopmental and psychiatric disorders and lower cognitive ability is overtransmitted to ADHD probands. We also tested for indirect or genetic nurture effects by examining whether nontransmitted ADHD polygenic liability is elevated. Finally, we examined whether complete trios are representative of the clinical ADHD population.n = 5081), UK probands with ADHD (n = 857), their biological parents (n = 328 trios), and also a replication sample of 844 ADHD trios.Polygenic risk scores (PRSs) for ADHD, anxiety, autism, bipolar disorder, depression, obsessive-compulsive disorder, schizophrenia, Tourette syndrome, and cognitive ability were calculated in UK control subjects (ADHD PRSs were overtransmitted and cognitive ability and obsessive-compulsive disorder PRSs were undertransmitted. These results were independently replicated. Overtransmission of polygenic liability was not observed for other disorders. Nontransmitted alleles were not enriched for ADHD liability compared with control subjects. Probands from incomplete trios had more hyperactive-impulsive and conduct disorder symptoms, lower IQ, and lower socioeconomic status than complete trios. PRS did not vary by trio status.The results support direct transmission of polygenic liability for ADHD and cognitive ability from parents to offspring, but not for other neurodevelopmental/psychiatric disorders. They also suggest that nontransmitted neurodevelopmental/psychiatric parental alleles do not contribute indirectly to ADHD via genetic nurture. Furthermore, ascertainment of complete ADHD trios may be nonrandom, in terms of demographic and clinical factors. PAGE 6SEE COMMENTARY ON Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder, with robustly associated common genetic risk variants . It sharADHD genetic studies frequently use a case-control design , but an The first aim of this study was to test whether polygenic risk scores (PRSs)  for ADHD, other neurodevelopmental/psychiatric disorders, and lower cognitive ability are overtransmitted from parents to children with ADHD . Given the high heritability of ADHD, we expected to observe overtransmission of risk alleles for ADHD and phenotypes with which ADHD shares genetic liability. This can be tested using the polygenic transmission disequilibrium test (pTDT), which compares proband PRS to the mean of their parents’ PRSs  . Under tThe second aim was to investigate whether nontransmitted ADHD risk alleles are elevated in parents of children with ADHD, compared with population control subjects. Genome-wide association studies (GWASs) of trios use pseudo-control alleles, which represent the parental alleles that are not transmitted to offspring. If the parents have ADHD or multiple offspring with ADHD, these nontransmitted alleles could be enriched for ADHD liability compared with the general population, which could reduce genomic discovery power ,12. Of eA final question was whether children with ADHD recruited into a trio design are representative of the wider clinical ADHD population. The need to obtain DNA from all 3 individuals in a parent-offspring trio could result in biased ascertainment. This can be a challenge because missing genetic information is unlikely to be missing at random . Many chIn this study, we tested the following hypotheses using a UK clinical sample of children diagnosed with ADHD and their biological parents: 1) children with ADHD disproportionately inherit liability for neurodevelopmental/psychiatric disorders and lower cognitive ability, 2) nontransmitted ADHD polygenic liability is elevated compared with control subjects , and 3) children from incomplete trios have a more severe clinical profile and higher neurodevelopmental/psychiatric polygenic liability, than those from complete trios.Children and young people with ADHD  were recruited through child and adolescent psychiatry or pediatric outpatient clinics across Wales and England. Exclusion criteria were a clinical diagnosis of schizophrenia, history of epilepsy, brain damage, or known neurologic or genetic disorder. Inclusion criteria were a DSM-III-R/DSM-IV research-based diagnosis for ADHD, confirmed using the Child and Adolescent Psychiatric Assessment , a semisWritten informed consent was obtained from all parents and young people 16 to 18 years of age and assent was gained from probands <16 years of age. Study approval was obtained from the Northwest England and Wales Multicentre Research Ethics Committees.Inattentive and hyperactive-impulsive symptom scores were generated using DSM-IV criteria. Impairment was assessed using 8 items . Impairment occurring “sometimes” or “often” was coded as 1 and “never” or “rarely” coded as 0, and items were summed.The Child and Adolescent Psychiatric Assessment was also used to assess comorbid symptoms in the preceding 3 months, according to DSM-IV, including CD, oppositional defiant disorder, anxiety, and depression. Probands 12 years of age and older also completed the child version of the Child and Adolescent Psychiatric Assessment. A symptom was considered as present if either the parent or proband reported it. Total symptom scores for CD (9 items), oppositional defiant disorder (8 items), anxiety (12 items), and depression (8 items) were generated. Autistic traits were assessed using the parent-rated Social Communication Questionnaire (39 items) . Full-scSocioeconomic variables  and family history of psychiatric disorders were assessed by parental questionnaire. Low income was defined as self-reported gross annual family income <£20,000 . Parental low educational attainment was defined as parents having left school without qualifications  at age 16 years. Socioeconomic status (SES) was classified by the occupation of the main family wage earner using the UK Standard Occupation Classification . Two SESA detailed description of the genetic data can be found in the PRSs were calculated using common autosomal variants based on 9 large discovery GWASs of primarily European ancestry: ADHD , anxietyComparison individuals were 5081 individuals from the Wellcome Trust Case Control Consortium (WTCCC) (a UK control population sample) not screened for ADHD or other psychiatric disorders . The samThe discovery GWAS used to calculate PRS had no overlap with the target ADHD sample. For the merged ADHD-control sample, we obtained GWAS data excluding the control subjects, where possible .p value thresholds and the first principal component was extracted and analyzed for each discovery phenotype following the PRS-principal components analysis method, an approach that reduces overfitting, maintaining good power  from 825 families met inclusion criteria and passed QC. Complete trios (coded as 0) were defined as families in which both parents provided a DNA sample and were confirmed as the biological parents, regardless of whether both parents passed subsequent QC (n = 367). Incomplete trios (coded as 1) were families in which 1 or both parents did not provide a DNA sample (n = 454). In families in which both parents had provided DNA but 1 or both parents could not be genotyped because of low sample quality, the probands were unclassified, because parent-offspring relatedness could not be confirmed (n = 36).A total of 857 probands with ADHD . This resulted in a sample of 328 trios meeting inclusion criteria for the pTDT and the analysis of nontransmitted parental alleles.Additional filters were applied for the analyses of transmitted (pTDT) and nontransmitted alleles, as follows: probands were excluded if parental samples did not pass QC or if the whole trio was not genotyped on the same array. Only the oldest proband was included for families with multiple probands genotyped . When comparing probands and mothers based on trio status, genotyping batch was also included as a covariate and we accounted for the presence of siblings by specifying family clusters and applying a sandwich estimator to estimate cluster-robust standard errors of regression coefficients. All analyses used generalized estimating equations implemented in the drgee package in R. False discovery rate correction for multiple testing was applied for the genetic analyses in the primary sample.n = 111 [13.2%] females). Only 616 complete trios matched the WTCCC control population sample ancestry for the analyses of nontransmitted parental alleles. See the Independent data from the International Multicentre ADHD Genetics (IMAGE) study  were usePRSs for ADHD were overtransmitted (mean [SE] = 0.30 [0.06]) to probands. There was no evidence of overtransmission of risk alleles for other disorders . PolygenThe results were independently replicated for ADHD (0.20 [0.03]), cognitive ability (−0.06 [0.02]), and OCD (−0.08 [0.03]) PRSs . AnalyseAnalyses in the replication sample are shown in n = 367, incomplete trios: n = 454) indicated that those from incomplete trios were older, had more hyperactive-impulsive ADHD and CD symptoms, had lower IQ, and were more likely to meet diagnostic criteria for CD  are of a similar magnitude to those between ADHD and MDD (rg = 0.42), ASD (rg = 0.36), and anxiety (rg = 0.33) (rg [SE] = −0.17 [0.07]) between ADHD and OCD (Previous estimates of genetic correlation between ADHD and cognitive ability rg = −0.4 are of a = 0.33) ,25,27. D = 0.33) . It is a and OCD  and need and OCD .Contrary to the second hypothesis we tested, we found no evidence in either sample of elevated polygenic liability for ADHD in the nontransmitted parental alleles, compared with a control population. Similarly, the results of our exploratory analyses indicated no enrichment of nontransmitted parental alleles for polygenic liability for other neurodevelopmental/psychiatric disorders or for lower cognitive ability. These results are consistent with a recent study and also a preprint, which examined ADHD symptoms in the general population ,42. Our Our results also indicate that common variant discovery GWASs of ADHD may not be adversely affected by the use of pseudo-control subjects from trios relative to case-control samples, as has been previously suggested . It is lComparison of polygenic liability in complete and incomplete trios indicated weak differences; probands from incomplete trios had elevated PRSs for BD and OCD and their mothers had elevated ADHD PRSs but decreased schizophrenia PRSs. However, these results did not withstand multiple testing correction and require follow-up using larger samples. We were not able to replicate these analyses because incomplete trios were screened out of the IMAGE cohort. There were no differences in family history of ADHD and other disorders. These results indicate that there are no substantial genetic differences (in terms of PRSs or family history) in probands and their mothers depending on whether they were recruited to the study as part of a complete trio or not. As such, ADHD trio samples are reasonably representative of clinical ADHD samples in terms of polygenic background and our results examining polygenic overtransmission and nontransmitted parental alleles reflect typical UK clinical populations.We observed several demographic and clinical differences depending on trio status. Building on a previous study using a subset of 241 (28%) probands drawn from the current sample , we obseOur primary target sample was relatively small, which limited our power to detect smaller effects, particularly for indirect genetic effects, which are likely to be smaller for ADHD than the direct genetic effects. However, we can be more confident in the results owing to our use of a comparable replication sample. One limitation of the replication analysis is that we used the same control individuals as in the primary analysis of nontransmitted alleles, which may have influenced the similarity of these results. We were unable to compare fathers’ polygenic profiles given few fathers in incomplete trios. We were also unable to compare nontransmitted parental alleles for MDD and BD with the control population, owing to the inclusion of the control subjects in those discovery GWASs. Although we found only weak evidence of differences in polygenic liability in complete and incomplete trios, this may have affected the analysis of nontransmitted parental alleles, which needs to be studied further.Overall, our results suggest that probands with ADHD overinherit polygenic liability not just for ADHD but also for lower cognitive ability. We found no evidence of enrichment of polygenic liability for neurodevelopmental or psychiatric phenotypes in nontransmitted parental alleles, suggesting that genetically influenced nurture (as captured by the PRSs we tested) does not contribute to ADHD risk. Finally, our results indicate that probands who are recruited to trio-based genetic study designs may not be entirely representative of clinical samples, showing a somewhat less severe clinical profile and higher family SES.


Subjects with ADHD and high working memory performance (n = 50) do not differ from the controls in their theta/beta ratios at any derivation. Our results suggest that neuropsychological profiling could be useful for patient subgrouping. Further research will allow for the distinction of neuropsychological profiles and their neurophysiological correlates, leading to a better classification of ADHD subtypes, thus improving treatment selection.ADHD is a neurodevelopmental disorder appearing in childhood but remaining in many cases in adults. There are both pharmacological and non-pharmacological approaches to treating ADHD, but they do not have the same efficacy in all subjects. Better knowledge of the neurophysiological basis of this disorder will allow for the design of more effective treatments. Studies performing qEEG analysis in children suggest the existence of subgroups of ADHD patients with different neurophysiological traits. There are fewer studies in adults, who might have undergone plastic changes allowing them to cope with ADHD symptoms along with brain maturation. Herein, we study cognitive performance and the theta/beta ratio in young adults with ADHD symptoms. We found that subjects with ADHD symptoms and low working memory performance ( ADHD is a neurodevelopmental disorder presenting with hyperactivity, impulsivity and inattention symptoms. It is diagnosed mainly in children, although it is also present in adults ,2,3.There are different therapeutic approaches to treating ADHD patients, including both pharmacological and non-pharmacological treatments. The literature supports the efficacy of different drugs ,5,6 in tAs with any other disorder, the development of better therapeutic strategies for ADHD depends on an improved understanding of the underlying physiological changes associated with the presence of its symptoms. In this regard, different studies address the changes in brain structure and function associated with ADHD. A recent large-scale study in non-referred patients, with a high representativeness of the general population, analyzed magnetic resonance imaging in children with and without ADHD. They report reductions in the surface area of the anterior and posterior cingulate cortex, middle an inferior temporal gyri, precentral and postcentral gyri, lingual gyrus, pericalcarine cortex and cuneus .Other studies have addressed, through quantitative electroencephalography (qEEG), the neurophysiological correlates of ADHD, mainly in children and adolescents. Many reports indicate that ADHD patients present an increase in slow-wave and a decrease in fast-wave activity ,24. A frStudies in adults have failed to find the neurophysiological correlates described in children , includiVariations in neurophysiological correlates of the same condition might lead to differences in other parameters, such as cognitive performance, between subjects filling the same diagnostic criteria for a particular condition. For example, a study performed in alcohol-dependent subjects reported two different subgroups, each with different alterations in brain activity and different cognitive performance, albeit with the same diagnosis . Thus, mPatients with ADHD represent a heterogeneous group, where persons filling the same diagnostic criteria might differ greatly in the etiology for this condition, as well as in its neurophysiological correlates . FittingParticipants were first-year health sciences students who were verbally invited to participate in this study during their classes. All procedures and data management were carried out in accordance with the Declaration of Helsinki, and the protocol was approved by the Committee of Evaluation of Research Functions of the Health Sciences Division. All participants signed an informed consent form. Participants reported no current or previous history of neurological illness and were not under any pharmacological treatment that could affect EEG activity.Risk of ADHD was assessed through the Spanish version of the Adult ADHD Self-Report Scale (ASRS-V1.1), which has been previously validated in Spanish and Mexican populations ,36. The Additionally, participants answered the Spanish version of the Alcohol Use Disorders Identification Test (AUDIT) to assess hazardous alcohol consumption and risk of alcohol dependence . As prevParticipants completed a working memory test using the software e-Prime 2.0. In each trial, participants were presented with a series of digits from 1 to 6 appearing on the screen. After the last digit of each series, the computer emitted a bleep sound and the test digit appeared in red, participants had to determine whether the test digit was present in the previously presented series. The working memory test consisted of 48 trials. Accuracy index and reaction time were recorded and extracted through the same software for statistical analysis.EEG recording was performed in a dimly lit room where participants were comfortably seated. Recording was performed in the closed-eyes condition using a 19-channel Medicaid Fenix electroencephalograph . Low- and high-frequency filters were set at 0.5 and 30 Hz, respectively, and a 50/60 Hz notch filter was used. Sampling frequency was 240 Hz, with a 16-bit resolution. Signal was collected through 19 electrodes placed in the international 10/20 system  fitted in an electrode cap . Linked mastoids were used as references, and Fpz was used as the ground electrode. A clinical neurophysiologist (ES-R) performed rigorous visual analysis of all EEG recordings.EEG segments of at least 2.56 s were manually selected until they amounted to at least one minute. The selection process included only segments where the subject was awake and presented alpha activity. We also excluded segments with muscular activity or blinking.We used the Quantitative EEG Analysis software  to obtain Absolute Power (AP) for the theta (3.91–7.42 Hz) and beta (12.89–19.14 Hz) frequency bands  by meansFor comparison between the ADHD and control groups, we used unpaired T tests for theta/beta ratio on all 19 derivations, as well as for the accuracy index and reaction time values of the working memory test, and for the scores of Barrat’s impulsiveness scale. When analyzing ADHD subgroups, we performed ANOVAs and Fisher post hoc tests in all cases. All analyses were performed using Statview software (version 4.57).After excluding subjects with EEG abnormalities, 207 subjects who completed all of the clinimetric tests remained. Data from all of the subjects rating positive for ADHD symptoms were considered for statistical analyses, while only those subjects rating negative for all the applied tests  were included in the control group. Accordingly, 61 subjects rating negative for ADHD but positive for the other tests  were excluded from the analysis. After the exclusion of subjects who did not fit the inclusion criteria, only 146 subjects were included in the analysis, 66 rated negative for all the applied tests and were included in the control group, and 80 subjects rated positive for ADHD in the ASRS-V1.1. The gender and age composition for each group can be found in n = 50) and the second with an AI ≤ 0.9 . Since the controls greatly outnumbered both ADHD groups addressed in the second analysis, we randomized our controls using SPSS software to select only 40 controls. The age and gender composition of the groups for this analysis can be found in Subjects within the ADHD group varied greatly in their performance on the working memory test, highlighting cognitive heterogeneity in these subjects. Given the existence of subgroups of ADHD patients reported in children ,27, and The unpaired T test revealed no difference between the ADHD and control groups, in either reaction time or accuracy index A.p < 0.05). It should be noted that this tendency was also observed at F4 , O2 , Fz  and Cz , where the p value was lower than 0.1, but did not reach significance (p < 0.05)  .p < 0.0001), motor , non-planning  and total impulsiveness   .p < 0.0001). The Fisher post hoc test revealed that ADHD LAI presented lower AI (0.777 ± 0.024) than both the ADHD HAI (0.961 ± 0.004) and control (0.921 ± 0.014) groups (p < 0.0001 in both cases). Additionally, AHDH HAI presented higher AI than the control group (p < 0.05)  See B.We did not find any difference in reaction time.p < 0.05) and T6 . The post hoc tests revealed a higher theta/beta ratio in ADHD LAI than in the controls at both O2  and T6   .p = 0.0501) and Cz . Similarly, post hoc tests indicated a higher theta/beta ratio in the ADHD LAI group when compared with the controls at O1  and Cz   .p < 0.0001). The Fisher post hoc test indicated that both ADHD LAI  and ADHD HAI  presented higher impulsiveness than the controls (10.35 ± 0.517)  .p < 0.0001). In this case, we also observed higher scores in ADHD LAI  and ADHD HAI  when compared to the controls (10.525 ± 0.808)  .p < 0.01). We observed higher scores in both ADHD LAI  and ADHD HAI  than in the controls (12.325 ± 0.589)  .p < 0.0001). In this case, we also observed higher values in the ADHD LAI  and ADHD HAI  than in the controls (33.65 ± 1.447)  .Herein, we performed two different analyses on the same set of participants, assessing theta/beta ratio in subjects with ADHD symptomatology, either as one general group , or subdp = 0.0828), Fz (p = 0.0886), Cz (p = 0.0862) and O2 (p = 0.05)  . The ana = 0.05) .The analysis of their performance in the working memory test revealed no difference between the ADHD and the control groups A; howeveIt should be noted that, in addition to the reported variation in ADHD etiology and brain correlates, there is at least another report revealing both cognitive and neurophysiological heterogeneity in a group of subjects with alcohol addiction. The study reports two subpopulations of alcohol-dependent subjects within the same study population. One of the groups presented increased delta and theta activity, while the other presented decreased delta and theta activity. Furthermore, both groups presented different results when the authors analyzed p300, as well as variations in cognitive performance . Herein,p < 0.0001). Moreover, subjects in the ADHD HAI group performed even better than the controls (p < 0.05). This is to be expected, since we used the accuracy index to subdivide the ADHD group, leaving only those who scored above 0.9 in the ADHD HAI group. Conversely, in the control group we did not make this distinction, and included subjects who rated ≤ 0.9 as well as those with higher scores. The presence of subjects with lower scores in the working memory test in the control group could be due to the diversity commonly found in any population, and not to the presence of some pathological process in these subjects. Moreover, it should be noted that while there was a significant difference between the control and ADHD HAI groups (p < 0.05), the difference between both of these groups and the ADHD LAI group was much larger (p < 0.0001). It could be argued that the ADHD LAI group could also include subjects whose poor performance in the working memory test was not due to this disorder, but rather, is evidence of normal neuropsychological heterogeneity. This could be the case for some of the subjects, and cannot be disregarded with all the tests applied in this work; however, given that ADHD patients often present cognitive deficit [As observed in  deficit ,49, the p = 0.0501) and T6 (p = 0.0724). Post hoc tests also indicated a higher theta/beta ratio in the ADHD LAI group than in controls for these derivations. It is noteworthy that theta/beta ratio for the ADHA HAI group did not differ from either the control or ADHD LAI groups.The analysis of the theta/beta ratio considering the two subgroups of subjects with ADHD symptomatology  revealedRegarding Barrat’s impulsiveness test, both ADHD HAI and ADHA LAI presented higher impulsiveness than the controls in all four subscales . FurtherRegarding the areas where changes in theta/beta ratio were observed, they were mainly in central and occipital regions, with slight differences when analyzing one and two ADHD groups. This is in agreement with previous reports indicating an increase in theta/beta ratio at Cz in children with ADHD ,28, and It is difficult to determine the cause of the difference in brain activity observed in the two ADHD subgroups. An increased theta/beta ratio has been observed in conditions such as cognitive impairment in elder people ,53, and One of the current challenges in ADHD treatment is precisely the different effects that a given treatment might have on different subjects, which is probably due to the heterogeneity in the etiology and neurophysiological correlates of this disorder in different patients . This maGiven the high heterogeneity of ADHD patients, there is increasing interest in personalizing treatment, either pharmacological or non-pharmacological, for each patient in order to attain the best possible therapeutic response with minimal adverse effects. Several approaches have been used to attain this goal through a better understanding of the mechanisms through which pharmacological treatments produce a reduction in ADHD symptoms. For example, a recent randomized control trial evaluated the effect of lisdexamfetamine on ADHD symptoms and brain structure through magnetic resonance imaging. Their results suggests that stimulant medication (such as amphetamines) produce an improvement in ADHD symptoms through a decrease in striatal and thalamic dynamic functional connectivity, thus increasing connection stability . A complOther studies aim to identify specific neurophysiological features that could predict a good response to pharmacological treatment. For example, in children and adolescents, increased basal theta activity , and a hAll the aforementioned studies provide important insights into both the neurophysiological mechanisms through which pharmacological treatments produce an improvement in ADHD symptoms, and possible strategies through which to improve treatment selection, through analysis of their effect on brain activity. However, these approaches need specific tests and equipment that are not always available. Our results suggest that cognitive performance could help us distinguish between different subgroups of ADHD patients, by means of an easy and affordable approach.Among the strategies explored until now, neuropsychological profiling presents two important advantages as a tool for patient’s classification: (1) The distinction of different cognitive profiles provides information on brain processes affected differentially in persons with the same ADHD diagnosis, probably reflecting more accurately the main changes in brain function in each subgroup. (2) Neuropsychological profiling could allow for the inexpensive screening of patients to determine the specific subgroup to which they belong. Further research is needed to fully understand the scope of the cognitive profiling of ADHD patients as a strategy to classify them, in order to select the most suitable therapeutic approach for each group of patients. It would be necessary to know both the cognitive performance and neurophysiological correlates of each sub-group. However, given the low cost of this procedure, this knowledge could provide an accessible option to guide treatment selection.Many of the subjects with ADHD symptoms in our study also rated positive for other conditions, such as alcohol use disorders, depression and suicide risk. While comorbidities make it harder to define specific subgroups of subjects with ADHD symptoms, it is worth noting that it is quite frequent for ADHD patients to present comorbidities ,47, whicThe prevalence of ADHD symptoms among the participants in this study is higher than the reported community prevalence of ADHD, which is around 5% for children and even lower for adolescents . SeveralA limitation of this study is that we categorized our subjects with ADHD symptoms based on a single test (working memory), probably disregarding other cognitive features that might prove useful to distinguish subpopulations among subjects with ADHD symptoms. Our selection of working memory performance to classify subjects with ADHD symptoms was due to the large variety of conditions in which working memory is affected, including ADHD , multiplHowever, even though we used only one test to classify the subjects, we already found that our population with ADHD symptoms was not homogeneous, differing at least in their performance in the working memory test and in their theta/beta ratios. It is probable that a wider neuropsychological assessment would lead to a better classification of ADHD subjects. For this purpose, the inclusion of other tests for attention and impulse control, such as CPT or the Iowa gambling test, could prove useful in future studies. In order to achieve this goal, further research should be conducted on three topics: (1) the neuropsychological profiling of ADHD patient subgroups; (2) determination of the neurophysiological correlates of each ADHD subgroup; and (3) a close follow-up of the effects of selected treatments on ADHD symptoms in each subgroup.Subjects with ADHD symptoms present high variation in brain activity, as well as in their response to treatment. Previous studies suggest the existence of different subgroups of ADHD patients with different etiologies for the disorder and different responses to treatments. In order to achieve more optimal treatment selection, strategies designed to identify these subgroups will allow for the development of therapeutic strategies designed for each specific subgroup of patients.There are articles reporting the classification of ADHD patients based on their qEEG ,26,27. O


Objective: Associations between measures of executive functioning (EF) and cardiorespiratory fitness (CRF) were examined for adults with and without ADHD. Method: Measures of executive functioning including the Stroop task, Wisconsin Card Sorting task, and Operation Span Task were completed virtually . Participants completed the Six-Minute Walk Test to estimate CRF. Results: Mean performance measures of executive function did not differ by group. However, higher estimated CRF was associated with better Stroop task performance, and the association was strongest for individuals with ADHD. Conclusion: In adults with ADHD, higher estimated CRF was associated with better inhibitory control, but not with other measures of executive functioning. Attention deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders affecting approximately six percent of children and three percent of adults worldwide . A core Executive dysfunction associated with ADHD can arise from an impairment in one of three executive functions: inhibitory control, cognitive flexibility, or working memory. Inhibitory control refers to one’s ability to override an automatic or prepotent response to a stimulus , and hasThe most common intervention for ADHD symptoms is pharmacotherapy . ApproxiPhysical activity has been identified as one of the best non-pharmacological interventions for managing ADHD symptoms ,35. PhysThe beneficial effects of an acute bout of physical activity for executive dysfunction in children are noteworthy. An acute bout of physical activity in children with ADHD has been documented to elicit significant improvements in inhibitory control, cognitive flexibility, and working memory ,47,48,49With respect to the chronic effects of regular engagement in physical activity on executive functions, even less is known about the effects in adults with ADHD. Engaging in chronic physical activity can improve cardiorespiratory fitness (CRF), defined as the circulatory and respiratory systems’ ability to supply oxygen to the skeletal muscles for energy production . PreviouIn adults with ADHD, we are only aware of two prior studies that have examined the relationship between CRF and executive functions specifically. In one study, Jeoung (2014) explored the association between CRF and measures of self-reported executive dysfunction including inattention/memory, hyperactivity/restlessness, and impulsivity/emotional lability in men with ADHD. They found that those with higher CRF had fewer self-reported symptoms of executive dysfunction. However, this research is limited because it did not include women with ADHD, nor did it include objective assessments of executive functioning . In the The present study was designed to fill these gaps by investigating the relationship between CRF and three domains of executive functioning in adults with ADHD. We examined cross-sectional differences between adults with and without ADHD on performance measures of inhibitory control, cognitive flexibility, and working memory. We used an objective estimate of CRF and assessed whether it predicted performance on each measure of executive function. We also explored whether the association between CRF and executive functions differed by group (ADHD vs. Control). It was hypothesized that adults with ADHD would have poorer performance across all three domains of executive functioning. It was also expected that participants with higher CRF would have better executive functioning across all three domains, but the associations would be stronger for adults with ADHD. Previous research reveals stronger relationships between fitness and cognition in individuals with greater executive dysfunction  compared to those with less executive dysfunction  . Therefo2 deviation from zero, Cohen’s f = 0.23, β = 0.95 and α = 0.05) using G*Power version 3.1.9.2 [Previous research using this data set, including an overview of the participants, is provided in Ogrodnik et al. (2023) . This pr 3.1.9.2 . Eighty- 3.1.9.2 .The CAARS is a reliable and validated 30-item self-report questionnaire, which was used to evaluate ADHD symptoms in all participants ,68. Item2 max, which reflects an estimated maximum rate of oxygen consumption [2 max was calculated through Equation (1) as this has been shown to be a valid and reliable measure “and accounts for approximately 72% of the variance associated with the gold-standard measure for cardiorespiratory fitness” [The six-minute walk test (6MWT) is a tool used to measure the distance an individual can walk on a straight path in six-minutes ,70. The sumption . Estimatfitness” ,74,75.EAll cognitive tasks were administered virtually using Inquisit Web (Version 6.3.5). Participants were provided the web-license link by a research assistant and completed all tasks on their personal computer. All tasks used were from the Millisecond library .The Stroop task, version “Colour Word Stroop with Keyboard Responding” , was useThe Wisconsin Card Sorting Task  was usedThe Operation Span Task  was usedFactors of sex, sleep, and mental health were characterized and included as covariates because they are known to impact both CRF ,81,82 anMental health was characterized using the Depression, Anxiety, and Stress Scale 42 . The DASThis study was completed via a virtual visit on Zoom (Version 5.11.10) that lasted approximately 2.5 h. Participants completed the DASS and CAARS questionnaires along with a demographic questionnaire that included questions about biological sex and sleep the night before. Then, participants completed the cognitive tasks via Inquisit Web, in the following order: (1) Stroop, (2) WCST, and (3) OSPAN. The researcher provided instructions prior to each task and remained on the Zoom call while participants completed each task independently. Finally, participants completed the estimated CRF protocol. As the first step, each participant rested for five minutes and took three measurements of their resting heart rate monitored by the researcher. Then, the researcher provided instructions on how to complete the 6MWT, including how to use the 6WT mobile application. Participants temporarily left the Zoom call to complete the 6WT outside, unsupervised. After finding an appropriate location to complete the test , participants started the application, which automatically timed the six minutes and recorded the distance walked. The session ended after participants returned to the Zoom call to report their 6MWT distance and debriefed with the researcher.IBM SPSS (V28) was used for all data analyses, with an alpha level set to less than 0.05. Descriptive statistics were calculated, and normality was assessed for all measures outlined above. Normality was assessed using visual inspection alongside values of skewness and kurtosis, and the Shapiro–Wilk test. Outliers were considered if a data point exceeded three standard deviations beyond the mean . Only onThree domains of executive functioning  were evaluated. Inhibitory control was evaluated using the Stroop task performance scores of overall accuracy, accuracy on incongruent trials, and interference scores. Cognitive flexibility was evaluated using the WCST percent perseverative errors and percent of correct trials. Working memory was evaluated using the OSPAN score.t-tests. Exploratory moderation analyses were carried out using Model 1 in Hayes PROCESS Macro, Version 4.1 SPSS plug-in, to test the associations between CRF (IV) and measures of executive function (DVs), and to explore whether the associations were moderated by group. Covariates in all models included sex, sleep, and mental health.Continuous variables (domains of executive functioning and estimated CRF) were compared between groups using independent samples Most participants were white (49%) and female (75%) and had an average age of 21 years old (SD = 3.0) see .p < 0.001). Mental health, as measured by the DASS, was significantly worse for the ADHD group  than for controls   [p = 0.43) or in their performance on any task of executive functioning   than the controls  . The gro ≥ 0.17) .all trials of the Stroop task (p < 0.05), and this relationship was observed for those with and without ADHD . Furthermore, there was an association between higher estimated CRF and greater accuracy on incongruent trials of the Stroop task, but this was moderated by group   A,B. No o −0.001) .The current project examined the association between estimated CRF and executive functioning in adults with ADHD compared to neurotypical controls. To our knowledge, this was the first study to examine this association in an adult group across all three domains of executive functioning. Surprisingly, both groups were well-matched in terms of their estimated CRF and executive functioning. Importantly, higher estimated CRF was associated with better inhibitory control for adults with ADHD.A strength of our study is that we used three validated computerized tests of executive functions that are commonly used to assess deficits in inhibitory control , cognitiIndividual differences among adults with ADHD may further minimize group-wise differences. A key difference between our study and prior studies is that our participants were highly educated. Most of our participants were in pursuit of or held a university degree and may have already developed effective strategies for managing their executive dysfunction ,94,95. IThat said, individual differences in inhibitory control performance were observed among adults with ADHD when CRF was accounted for. This observation further supports the importance of acknowledging the heterogeneity in executive dysfunction among adults with ADHD. In the present study, we found that CRF was associated with accuracy on incongruent trials in adults with ADHD. Importantly, this was not observed for neurotypical participants, though higher CRF was associated with better overall accuracy on the Stroop task for all participants. Our results align with previous research which suggests that fitness-related benefits may be most useful for those with executive dysfunction, whereas healthy controls may not show notable benefits given the ceiling effects ,55,98. FWhile not seen in our data, adults with ADHD tend to be less physically active than their neurotypical peers ,107, andsubjective ratings of ADHD symptoms, as indicated by higher CAARS scores for the ADHD group than controls. This demonstrates a divergence between subjective and objective assessments of cognition, which further complicates the assessment of executive dysfunction in adults with ADHD. Although some studies in children with ADHD have found that subjective and objective measures of executive function are moderately correlated [In contrast to the objective measures of executive dysfunction, we observed the expected significant group differences in rrelated ,114,115,rrelated . Our worrrelated ,118.The lack of concordance between subjective and objective measures of executive dysfunction may reflect differences in the nature of the dysfunction being captured by the assessments. Self-reported assessments ask participants to reflect on their daily life, which tends to be more ambiguous and complex than performance-based measures using highly controlled tasks with a unitary predefined goal. Like our results, a prior study found that adults with ADHD self-report worse executive dysfunction than their performance on objective measures would indicate . SimilarThe current data provide insight on executive dysfunction in adult ADHD and its association with CRF. While this study fills an important gap in the literature, it is not without limitations. Most importantly, our data are cross-sectional, and therefore, causality cannot be determined. While previous research in children with ADHD has established that higher fitness is associated with better executive functioning  and thatAll data were collected during the COVID-19 pandemic and, therefore, it is important to acknowledge the potential for measurement errors within our virtual protocol. For example, CRF was estimated using the Six-Minute Walk Test. Although this standardized test shows good validity , it was Taken together, our results provide important insights into the executive dysfunction of adults with ADHD and its association with CRF. Although at the group level adults with ADHD performed similarly to the controls on the tasks of executive function, we observed interesting individual differences, such that higher fitness in adults with ADHD was associated with better inhibitory control. The same individual differences were not observed for cognitive flexibility or working memory. Given that inhibitory control is the hallmark of executive dysfunction for ADHD , using p


The present study aimed to evaluate the characteristics of functional brain connectivity in the resting state in children with attention deficit hyperactivity disorder (ADHD) and to assess the association between the connectivity and inhibition function using near-infrared spectroscopy (NIRS).In total, 34 children aged 6–13 diagnosed with ADHD were recruited from Hangzhou Seventh People’s Hospital. In comparison, 37 healthy children were recruited from a local primary school as controls matched by age and sex. We used NIRS to collect information on brain images. The Stroop test assessed inhibition function. We compared the differences in functional brain connectivity in two groups by analyzing the resting-state brain network. Pearson partial correlation analysis was applied to evaluate the correlation between functional brain connectivity and inhibition in all the children.p = 0.006). Inhibition function of children with ADHD was negatively correlated with functional brain connectivity (p = 0.009), while such correlation was not found in the control group.Compared with the control group, results of NIRS images analysis showed that children with ADHD had significantly low functional brain connectivity in regions of the orbitofrontal cortex, left dorsolateral prefrontal cortex, left pre-motor and supplementary motor cortex, inferior prefrontal gyrus, and right middle temporal gyrus (The present study demonstrated that children with ADHD had relatively low connectivity in several brain regions measured at the resting state. Our results supported the evidence that lack of functional brain connectivity was associated with impaired inhibition function in children with ADHD. Attention-deficit/hyperactivity disorder (ADHD) is among childhood’s most common mental health disorders. A recent meta-analysis of more than 100 studies estimated that the global prevalence rates of ADHD are around 3.4–5.3% . The typDespite abnormal behaviors, structural and functional changes of the brain are commonly observed among individuals with ADHD, such as a decrease in the volume of the white matter, smaller gray matter volume, focal thinning in bilateral frontal regions, and the right cingulate cortex, as well as the decreased functional connectivity , 6. In rResting-state functional near-infrared spectroscopy (rs-fNIRS) imaging is a natural imaging paradigm with many advantages over task-state fNIRS –14. The In the present study, we applied the rs-NIRS among children with ADHD to (1) investigate the altered functional brain connectivity by comparing the children with ADHD and healthy controls and (2) assess the association between functional brain connectivity and inhibition in children with ADHD.This study was a cross-sectional study by enrolling children with ADHD who visited the Hangzhou Seventh People’s Hospital outpatient clinic from July 2019 to July 2020. The inclusion criteria were children (1) with a diagnosis of ADHD made by a psychiatrist according to the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition-Text Revision (DSM-IV) using a semi-structured interview of the Clinical Diagnostic Interview Scale , 18; (2)The control group were students selected from a local primary school between July 2019 to July 2020 according to the Clinical Diagnostic Interview Scale (CDIS) for children , 18. A pThe study was approved by the medical ethics committee of the Hangzhou Seventh People’s Hospital, and the guardians of all the participants in the study signed written consent.This scale is a semi-deterministic diagnostic interview scale developed by the Childhood Disorders Group in the United States. It was translated in Chinese and revised by Li Yang and Yufeng Wang with good reliability and validity . The senThis scale assesses the total intelligence quotient (IQ), verbal IQ, and operational IQ of children aged 6–16. The reliability of each sub-test score is high (around 0.80), and the reliability of the IQ score is above 0.90 . The tesWe used the classical version of the Stroop Color-Word Test to assess the inhibition function , 23. TheWe used the 33-guide Near-Infrared Spectroscopy (NIRS) system  to determine the hemodynamic changes in the prefrontal and temporal lobes of the brain during the resting state of the subjects. Subjects’ performance and changes in signal recordings during the experiment were observed in real time by the researcher, and artificial interference signals were flagged. Data or segments with significant artificial interference were excluded during fNIRS data preprocessing. fNIRS signals were acquired at a frequency of 10 Hz.2) tests to compare the differences in the numbers and percentages between the two groups in terms of the categorical variables. Thirdly, because the data was not normally distributed, we used Tukey method to transfer data into rank and made it conform to the normal distribution. Then, we included the normal-distributed variable in the multivariate ANOVA model by using sex, age, and IQ as covariates.Analysis was performed using the IBM SPSS Statistics for Windows, Version 22.0 . Firstly, we conducted a descriptive analysis. Means and standard deviations (SDs) were calculated for continuous variables. The categorical variables were expressed as numbers and percentages. Secondly, we applied an independent two sample t-tests and one-way Analysis for Variance (ANOVA) to compare the differences across groups; and we conducted the Chi-square , an appropriate approach to compare the differences in the functional connectivity networks between the study group and the control group. First, a functional connectivity matrix was generated for each subject, and then a two-sample p-value is less than 0.05.We conducted Pearson’s partial correlation analysis to assess the association between functional brain connectivity and ADHD inhibition in the two groups separately, adjusted by age, sex, and IQ. The statistical significance is indicated when the p-values > 0.05).In total, 34 children with ADHD were enrolled in the study group, and 37 children were included in the control group. The mean age of children with ADHD was 8.90 (SD:0.40) years; 33 (97%) were males; the mean IQ was 106.6 (SD: 2.5), and 28 (82.3%) children had inattentive subtype (ADHD-I), 2 (5.9%) children with hyperactive/impulsive subtype (ADHD-H), and 4 (11.8%) combined subtype (ADHD-C). The mean age of children in the control group was 8.60 (SD:0.40) years; 35 (94.6%) were males; the mean IQ was 115.9 (SD: 2.5). There were no statistically significant differences in age, sex, and IQ between the ADHD group and the control group (p = 0.03).p = 0.007).We used a network-based statistical (NBS) approach to analyze the brain connectivity function at the resting state in children with and without ADHD. The results are presented in p = 0.01).r = −0.45, p = 0.006) and time of test 4  were negatively correlated with the whole-brain resting-state functional connectivity (RSFC) in the Stroop test, respectively. In the control group, we did not find a statistically significant correlation between the inhibition test scores and the whole-brain RSFC.In the present study, we found that functional brain connectivity was diminished in specific brain regions in children within the ADHD group compared to the control group using the resting-state functional near-infrared spectroscopy (rs-fNIRS) and brain network statistics (NBS). The function of brain connectivity was weaker in children with ADHD than those in the control group. More specifically, the areas with weaker signals are mainly located in the prefrontal cortex, premotor areas, and supplementary motor areas, primarily related to the executive control networks and sensorimotor networks. Studies on imaging the ADHD brain have primarily focused on functional magnetic resonance imaging (MRI) techniques. A recent meta-analysis of 96 relevant studies demonstrated reduced activity in the left inferior frontal gyrus in children with ADHD at both task and resting states . We alsoWe found a negative correlation between the inhibition and whole-brain RSFC in the ADHD group; that is, the poorer the inhibition function, the weaker the functional connectivity. We did not observe such a correlation in the control group. Inhibition is mainly related to the prefrontal cortex (PFC), and the function of the PFC in children with ADHD varies with age . PsycholThe core defect of ADHD is inhibition dysfunction . PatientThe present study is one of the few that applied rs-NIRS to verify the correlation between a lack of functional brain connectivity in the whole brain and impaired inhibition function in children with ADHD. However, several limitations warrant attention. First, fNIRS has less spatial resolution than fMRI and can only detect hemodynamic changes on the brain’s surface (about 2–3 cm below the skull). Second, due to the relatively small sample size, this study did not further explore the influence of sex and disease-specific factors on brain connectivity and inhibition. We recommended further studies to extend the sample and assess the association between functional connectivity and inhibition by adjusting a comprehensive set of covariates and confounders. Third, the cross-sectional design of the present study does not allow, the conclusion of causation to be reliably drawn. Prospective cohort studies are needed to illustrate the causal effects.Our study demonstrated that children with ADHD had significantly decreased functional brain connectivity in several specific brain regions under the resting state compared with the control group. A lack of functional connectivity was significantly associated with poor inhibition function among children with ADHD.The original data supporting the conclusion of this article will be made available from the first author, WL, upon reasonable request.The studies involving human participants were reviewed and approved by the Medical Ethics Committee of Hangzhou Seventh People’s Hospital. Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin.WL, RY, and GB involved in the study conceptualization and study design. WL and LC collected the data and carried out the statistical analyses. WL and GB wrote the first draft of the manuscript. RY and GB supervised the project. All authors provided the critical revisions of the manuscript for important intellectual content and contributed to the interpretation of the data and approved the final version of the article.


To investigate the CBCT findings of the apical anatomy of immature maxillary central incisors.CBCT images of 100 immature maxillary central incisors in Nolla 8 and 100 immature maxillary central incisors in Nolla 9 were collected. The mesiodistal and carniocaudal diameters of the apical foramen of immature maxillary central incisors were measured by software included with CBCT, as well as the mesiodistal, carniocaudal and facioligual diameters of the apical shadow. The apical shadow and apical foramen diameters were compared between Nolla 8 and Nolla 9. Data were analyzed using the MedCalc software package.For immature maxillary central incisors, the mesiodistal and facioligual diameters of the apical foramen were 2.75±0.68 mm and 3.28±0.74 mm in Nolla 8 and 1.50±0.51 mm and 1.92±0.79 mm in Nolla 9. The mesiodistal, facioligual and carniocaudal diameters of the apical shadow were 3.84±0.73 mm, 4.49±0.68 mm and 3.41±1.27 mm in Nolla 8 and 2.76±0.60 mm, 3.41±0.80 mm and 2.06±0.65 mm in Nolla 9, respectively.The immature maxillary central incisors in Nolla 8 have a larger apical shadow and apical foramen than those in Nolla 9. The apical region of the maxillary central incisors in Nolla 8 was more likely to have a broad, blurred lamina dura. With the development of the apical foramen, the lamina dura in the apical region tended to be clear and sharp.To our knowledge, this is the first study to radiologically analyse the in vivo anatomy of the apical foramen and apical shadow of immature maxillary central incisors. The results of this study provide a more detailed understanding of the apical anatomy of the immature maxillary central incisor for the diagnosis and treatment of apical lesions. In 1960, Nolla , and theCBCT has been widely used in oral clinics since the 1990s. It has isotropic characteristics and can image the anatomical structure 1:1. Haridas  noted thd=1), Nolla 8 and Nolla 9 standard deviations (σ=1.2 and 0.8 respectively), and sample rate (= 1). In total, 46 should be recruited. However, the sample size was increased to 100 to be adequate for achieving objectives of the study. Stratified sampling method was used to acquire the final study group. Finally, 100 immature maxillary central incisors in Nolla 8 and 100 in Nolla 9 from 509 patients were evaluated in this study. Written informed consent was obtained from all guardians of the participants.The trial protocol was approved by the institutional review board of the hospital . Children who underwent CBCT in our imaging department between January 2020 and December 2020 were selected. The CBCT images were mainly taken for the purposes of orthodontic treatment, dental caries, maxillofacial tumour and cyst. Inclusion criteria were healthy immature maxillary central incisors, an undeveloped apical foramen, aged from 6 to 9 years, good image quality without artifacts. After statistics, 778 cases were included. Exclusion criteria were supernumerary teeth in maxillary anterior region, crowded dentition in maxillary anterior region, maxillofacial tumour and cyst in maxillary anterior region. After evaluation, 269 cases were excluded from 778. Two paediatric dental specialists who were blinded to the clinical and CBCT information, classified immature maxillary central incisors into Nolla 8 and Nolla 9 according to the Nolla staging system. Furthermore, We measured the unilateral immature maxillary central incisors in random order to avoid selection bias. The sample size was calculated by the MedCalc software package. In order to accurately determine the sample size, we conducted a pre-experiment because we could not find a similar previous study. In this pre-experiment, we measured the mesiodistal diameters of the apical shadows of 10 immature maxillary central incisors in Nolla 8 and 10 in Nolla 9. Considering the mean and standard deviation of the obtained in the pre-experiment, the following parameters were used in the design: Alpha (α=5%), Beta (β=10%), average difference . Images were reformatted to a horizontal line parallel to the incisal edge and a sagittal line parallel to the long axis of the maxillary central incisor by software MPR included with CBCT. While maintaining this interface, the mouse was then moved until a maximum cross-section of the apical shadow of the immature maxillary central incisor was obtained in the coronal planes. Measurements were then taken in the coronal plane, including the mesiodistal diameters of the apical foramen and the apical shadow Fig. . The maxTen teeth (5 each in Nolla 8 and Nolla 9) were randomly selected for measurement by the same investigator, and 10 sets of data were obtained. Two weeks later, the second measurements were taken on the 10 teeth, and another 10 sets of data were obtained. Interclass correlation coefficients and Bland‒Altman plots were used to assess the reliability of the first and second measurements.t test for normally distributed data and the χ2 test for categorical data. Similarly, the Pearson correlation test was used to analyze the correlation between the diameters of the apical shadow and the apical foramen. Regression equations for the carniocaudal diameter of the apical shadow and the mesiodistal diameter of the apical foramen were established. P values < 0.05 were considered significant.All analyses were performed with the MedCalc software package. The Shapiro‒Wilk test was conducted to test data distribution. Normally distributed data of continuous variables are presented as the mean±SD, and categorical data are presented as n (%). Data were compared using the parametric The institutional review board of the hospital. Imaging data of 200 immature maxillary central incisors were included in the PACS system of our imaging department. Baseline characteristics are shown in Table Bland‒Altman plots of 10 paired data points for the first and second measurements are shown in Fig. In the apical region of maxillary central incisors in Nolla 8, the lamina dura was more likely to be broad and blurred, and with the development of the apical foramen, the lamina dura in the apical region tended to be clear and sharp, as shown in Figs. P < 0.05), as shown in Table P > 0.05), each diameter of the apical shadow and apical foramen of immature maxillary central incisors was significantly larger in males than in females (P < 0.05). The results are presented in Table The results showed that the diameters of the apical shadow and apical foramen of immature maxillary central incisors conformed to a normal distribution. The results of the diameters of apical shadow and apical foramen of immature maxillary central incisors in Nolla 8 and Nolla 9 are shown in Table P < 0.001), and the regression equation is shown in Table According to the correlation analysis, the mesiodistal, facioligual and carniocaudal diameters of the apical shadow were positively correlated with the mesiodistal and facioligual diameters of the apical foramen (Periapical disease is one of the most frequent oral diseases. It may induce pathological changes in dental-pulp tissue, thereby affecting the prognosis and long-term preservation of the affected teeth. In particular, immature permanent teeth have the unique anatomical and physiological characteristics of incomplete root development, a large apical foramen and inadequate blood supply. Once immature permanent teeth become affected by periapical disease, treatment of the affected teeth becomes very challenging. When periapical disease occurs in immature permanent teeth, root development is arrested, the apical foramen is widened, and the lamina dura may be partially or completely destroyed . The diaTo our knowledge, the immature maxillary central incisor is the earliest eruption of permanent teeth but is also the most prone to dental trauma of the permanent teeth . When luIn clinical practice, digital periapical radiogram continues to be one of the most commonly used methods for periapical diseases . It is rThe apical foramen of immature permanent teeth was not completely formed, and the apical foramen tended to close with age. In the current study, we demonstrated that the age in Nolla 8 was lower than that in Nolla 9. Our results support previous conclusions in children that the apical foramen is larger in Nolla 8 than in Nolla 9. Jiang  et al. uThe periodontal development of immature permanent teeth was incomplete, and there were residual dental papilla and dental sacs in the apical region. Kim  et al. mOur study had several limitations. First, due to the retrospective single-center design, sampling bias cannot be discounted. .A multicenter approach with a larger sample size is required to re-evaluate the results of our study. Second, the lack of a uniform standard for the morphology of the lamina dura could be underestimated its potential value in predicting periapical disease.In conclusion, the clinical diagnosis and treatment of periapical periodontitis and lesions could be improved with a better understanding of apical anatomy.


Critical Micelle Concentration (CMC) was determined to demonstrate the capacity to reduce surface tension and the toxicity of the surfactants and mixtures. Zeta potential  and micelle diameter (MD) were also determined to confirm the formation of mixed surfactant micelles. The Model of Toxic Units (MTUs) was used to quantify the interactions of surfactants in binary mixtures and to predict if the concentration addition or response addition principle can be assumed for each mixture. The results showed a higher sensitivity of microalgae P. tricornutum to the surfactants tested and their mixtures than bacteria P. putida. Antagonism toxic effects have been detected in the mixture of EC + AO and in one binary mixture of different AOs; this is to say, the mixtures showed lower toxicity than expected.Surfactants can be found in an ever-widening variety of products and applications, in which the combination of several types of surfactants is used to reinforce their properties, looking for synergistic effects between them. After use, they tend to be discarded into wastewater, ending up in aquatic bodies with concerning harmful and toxic effects. The aim of this study is the toxicological assessment of three anionic surfactants  and three amphoteric surfactants , individually and in binary mixtures of them (1:1  Surfactants are commonly used in a wide range of products, including soaps, detergents, shampoos, and cleaning agents, or in agricultural, industrial, or other commercial applications. The global demand for surfactants has increased by around 300%, exceeding the current world production of 3 million tons. per year . After uMixtures of different surfactants  are commonly used in formulations because of their better performance compared with individual surfactants. Suitable mixtures of surfactants are mostly used to increase efficiency and stability or to reduce costs and the potential of the products to cause skin and eye irritation ,8. ConseVibrio fisheri, microalgae, Pseudokirchneriella subcapitata, or microcrustaceans, Daphnia magna, especially for the traditional and more common surfactants , nB is the turbidity of the biomass measured after the test time for the umpteenth concentration in the test flask, cB is the turbidity of the biomass measured after the test time in the control flask, and B0 is the value of the turbidity of the biomass measured at time 0 in the control flask. The values of I were plotted against the surfactant concentrations. The toxicity values were measured as EC50, which is the surfactant concentration that inhibits 50% after 16 h of exposure. The growth inhibition was evaluated as the change in the absorbance of the bacterial culture before and after exposure. The percentage of the inhibition of cell multiplication   and its half maximal effective concentration (ECi50), (Equation (5)) being the toxic unit of the mixture (mixTU), the sum of iTU of the single components (Equation (6)).The model of toxic units (MTU) ,21,22 wamixTU < 1.2, while mixTU ≤ 0.8 indicates synergism (more than additive) and mixTU ≥ 1.2 represents antagonism (less than additive) . In. InEC50,sruption ,52. The P. tricornutum than bacteria P. putida  shows an intermediate value of EC50 compared to the EC50 of the individual surfactants for both species tested. Considering the model of toxic units and the calculated parameter mixTU, the type of action can be assumed to be the concentration addition (0.8 ≤ mixTU ≤ 1.2); this is to say, both surfactants act with the same MoA. As anionic surfactants, it is assumed that they likely act as polar narcosis class 2 [mixTU for the mixture with both species are not below 0.8.Firstly, the mixture of the two anionic surfactants  or response addition (rTU ≠ 1), being more likely less than additive. When testing this mixture with marine microalgae P. tricornutum, the concentration addition is supposed to be the type of action (mixTU = 0.98). The toxicity MoA of amine-oxide-based surfactants has been barely studied, so conclusions are difficult to draw without a deeper and more specific study [In the case of the mixture of EC-Ric study . The CMC12 + AO-Cocoamido, similar conclusions be drawn for bacteria P. putida and marine microalgae P. tricornutum, and an antagonism effect is appreciated, wherein the EC50 for the mixture is higher than the value expected. In the case of P. putida, a type of action that is less than additive and close to the response addition can be suggested . Although both surfactants in the mixture belong to the same surfactant family, AO-R12 is around three times more toxic than AO-Cocoamido, and the toxicity effects appear to be mainly conducted by the AO-R12. In the case of P. tricornutum, a less than additive type of action could also be suggested (mixTU = 1.66), and response addition is not expected. The antagonistic effect of this mixture is also reflected in the CMC of the mixture, showing a CMCU value higher than 1; the CMC for the mixture is higher than the CMC of the individual surfactants. This means that from an environmental point of view, the mixtures of AO-R12 + AO-Cocoamido are more eco-friendly, but from an efficacy point of view, for the decreasing surface and interfacial tension, the mixture of them is not recommended. The ζ-potential measurements of this mixture of surfactants showed an intermediate value between the ζ-potential of the individual surfactants; therefore, the theory stated by Martins et al. [From the toxicity results for the binary mixtures of AO-Rs et al.  proposin14 + AO-Cocoamido and rTU values, response addition can be suggested as the type of action of the mixture for both species, bacteria P. putida and marine microalgae P. tricornutum . That means that each surfactant acts with a different MoA. Although the evidence is not completely clear, AO-Cocoamido could be acting in a similar way to the anionic surfactant, EC-R8E8 (polar narcosis class 2) , whereas MoA for AO-R14 could be assumed to be non-polar narcosis class 1 [14, the one with the stronger hydrophobic character, is 11 times more toxic than AO-Cocoamido for bacteria P. putida and 13 times more toxic for marine microalgae P. tricornutum, so the higher contribution to the growth inhibition can be attributed to the amine-oxide-based surfactant AO-R14.Finally, looking at the results for the binary mixture of AO-R class 1 . It is ww/w) to bacteria P. putida and marine microalgae P. tricornutum. ζ-potential and MD measurements confirmed the formation of mixed surfactant micelles and the shielding effect of the marine medium in the micelles. The toxicity results showed the higher sensitivity of microalgae P. tricornutum to the surfactants tested and the mixtures of them than bacteria P. putida, which is related to the higher capacity to decrease the surface tension of the surfactants in a marine medium [This study assessed and compared the toxic effects of ether carboxylic derivative anionic surfactants and amine-oxide-based amphoteric surfactants individually and in binary mixtures (1:1 e medium . The res8E8 + EC-R12–14E10 with both tested species and for the mixture of EC-R8E8 + AO-Cocoamido to marine microalgae, whereas response addition could be expected as the type of action to the binary mixture of AO-R14 + AO-Cocoamido with P. putida and P. tricornutum. Antagonism toxic effects have also been identified for some mixtures: EC-R8E8 + AO-Cocoamido to bacteria P. putida and AO-R12 + AO-Cocoamido to P. putida and P. tricornutum. This is to say that these mixtures showed lower toxicity than expected when looking at the EC50 values of the individual surfactants.Considering the MTU, concentration addition has been assumed as the type of action for the binary mixture of EC-R14 + AO-Cocoamido, whereas mixture EC-R8E8 + AO-Cocoamido was the least lethal for both species tested. The use of AO-R12 in formulations, and its subsequent presence in aquatic environments, is preferable rather than AO-R14 if an amine-oxide-based surfactant with these characteristics needs to be used since it has antagonistic toxic effects with AO-Cocoamido, albeit the use of the combination of EC-R8E8 + AO-Cocoamido is the best option. The most toxic mixture was AO-R


Although vaccination rates in children exceed 90% in the United States, adults are vaccinated at far lower rates. In order to address this issue, additional community immunizers are needed, and pharmacists are in an ideal position to fill this void.To explore issues and barriers related to implementation of a pharmacy-based adult vaccine benefit and develop recommendations supporting a pathway for benefit expansion.A literature review on the current environment surrounding pharmacy-based adult vaccinations and structured interviews were conducted to inform an expert panel meeting using a modified Delphi process (pre/post survey). The goal was to develop recommendations on how to improve access to adult vaccines.Findings suggest employers play a key role in requesting changes in benefit design to include pharmacy-based vaccinations. However, the lack of consistent communication between pharmacists and primary care providers remains a significant barrier.Pharmacy-based access to vaccinations improves patient access and benefits individuals and employers. In order to take advantage of this opportunity, pharmacists must be viewed within the broader context of preventative care, including pharmacy-based vaccinations.


Psychotic-like experiences (PLEs) are increasingly being recognized as subclinical phenomena that might predict the development of various mental disorders that are not limited to the psychosis spectrum. Accumulating evidence suggests that attention-deficit/hyperactivity disorder (ADHD) and post-traumatic stress disorder (PTSD) are highly comorbid mental disorders. However, their interactive effect on the occurrence of PLEs has not been investigated so far. Therefore, in the present study we aimed to investigate the effect of interaction between ADHD and PTSD symptoms on the level of psychotic-like experiences (PLEs) in the non-clinical sample.The study included 3,000 individuals aged 18–35 years with a negative history of psychiatric treatment. The symptoms of ADHD and PTSD were assessed using self-reports.There was a significant association of the interaction between ADHD and PTSD with the level of reporting PLEs. This association remained significant after adjustment for age, gender, the level of education, the current vocational situation, lifetime history of problematic substance use, and depressive symptoms. Post-hoc tests demonstrated significantly higher levels of reporting PLEs in participants with positive screening for both ADHD and PTSD compared to other subgroups of participants. Also, individuals with positive screening for one vulnerability (either ADHD or PTSD) reported significantly higher levels of reporting PLEs compared to those with a negative screening for ADHD and PTSD. In turn, no significant differences between individuals reporting one vulnerability, i.e., between those with positive screening for ADHD and those with positive screening for PTSD, were observed.Findings from the present study imply that both PTSD and ADHD symptoms the interaction effect on the level of reporting PLEs that might be of importance for early intervention strategies. However, observed associations require replication in clinical samples. Most coOne of the most crucial mechanisms that might account for the appearance of psychosis spectrum symptoms are alterations in the process of neurodevelopment , 8. It hExposure to traumatic events is a well-known trigger of various psychiatric disorders, including post-traumatic stress disorder (PTSD) with prevalence rates estimated at 5.6% of trauma-exposed individuals . The assAccumulating evidence indicates that ADHD and PTSD tend to co-occur and might be causally associated . Indeed,To date, none of previous studies have investigated the interactive effects of PTSD and ADHD symptoms on the occurrence of PLEs. In the present study, we hypothesized that PTSD and ADHD symptoms exert interaction effects on the level of reporting PLEs. Our aim was to explore the interaction between PTSD and ADHD symptoms in a non-clinical population of young adults.2.2.1.The total sample included 3,000 individuals recruited through social media and the survey website. Recruitment was conducted via an online survey, with the advertisement targeted at individuals aged 18–35 years, without a history of psychiatric treatment. The findings reported in the present article represent a part of a bigger project investigating epigenetic mechanisms of psychosis proneness. At the screening level, the survey included only email addresses and telephone numbers for participants willing to participate in further stages of the project. Additional personal data were not collected at this stage of the project. Some findings from this study were published previously –34. The 2.2.2.2.1.The occurrence of PLEs was assessed using a 16-item self-report referring to the preceding month. Participants were asked to assess the frequency of PLEs on a 4-point scale , taking into consideration the experiences that had not been related to substance use. Specific items were selected from three questionnaires, including: (1) the Revised Hallucination Scale –37: “I h2.3.The Adult ADHD Self-Report Scale (ASRS) was administered to screen for ADHD. It includes 9 items measuring inattention and 9 items measuring impulsivity/hyperactivity over the period of the preceding 6 months . Each it2.4.Participants were screened for a diagnosis of PTSD using three questions from the Mini-International Neuropsychiatric (M.I.N.I.) : 1) “Hav2.5.Depressive symptoms were measured using the Patient Health Questionnaire-9 (PHQ-9) . It is a2.6.Participants were also asked about age, gender, the level of education, as well a family history of schizophrenia and mood disorders. The level of education was categorized as follows: (1) primary (graduation from primary school only), (2) vocational ; (3) secondary , (4) incomplete higher , and (5) higher . Current vocational situation . The lifetime problematic substance use was assessed using the screening question from the M.I.N.I.  . Positiv2.7.p < 0.05. All analyses were carried out using the SPSS software (version 28).The analysis of variance (ANOVA) was used to test the association of positive screening for PTSD and ADHD (the independent variables) with the level of reporting PLEs (the dependent variable). In the first ANOVA model, results of screening for PTSD and ADHD together with the interaction term (PTSD × ADHD screening results) were included as the only independent variables. The interaction term (PTSD × ADHD screening results) resulted in creating four groups: (1) individuals who screened positive for ADHD, but not for PTSD (the ADHD(+), PTSD(−) group), (2) individuals who screened positive for PTSD, but not for ADHD (the ADHD(−), PTSD(+) group), (3) individuals who screened positive for both ADHD and PTSD (the ADHD(+), PTSD(+) group), and (4) individuals who screened negative for ADHD and PTSD (the ADHD(−), PTSD(−) group). Next, sociodemographic characteristics, including age, gender, the level of education (higher or incomplete higher vs. other) and the current vocational situation (employed or student vs. other) were added as covariates. Finally, the lifetime history of problematic substance use and the PHQ-9 score were added to the ANOVA model as covariates. Post-hoc comparisons were performed using the Games-Howell test. The results of data analysis were interpreted as significant in case of 3.The majority of participants were females (58.3%), individuals with a higher level of education (40.7%), students (51.9%) and people reporting being married or informal relationship (66.6%) (see 2). Post-hoc tests demonstrated that the ADHD(+), PTSD(+) individuals had significantly higher levels of reporting PLEs, DLEs and HLEs compared to the ADHD(+), PTSD(−) individuals as well as the ADHD(−), PTSD(+) individuals  and hallucination-like experiences (HLEs), even after adding potential covariates to the model . The modividuals , Table 34.The current study examined the effect of the interaction between PTSD and ADHD symptoms on the level of reporting PLEs in a non-clinical sample. We found that both groups of symptoms show an interaction effect on the level of reporting PLEs in this population. Hence, our results add to the literature showing that PTSD  as well When interpreting our results, it should be noted that our sample can be described as a well-functioning social group. We assessed both PTSD and ADHD symptoms as a continuum in a non-clinical sample. Hence, more severe states within narrow clinical criteria for respective disorders were not represented in the study. At the same time, several studies indicate the role of exposure to trauma in shaping the risk of psychosis, both in clinical  and non-Referring to the literature, previous studies that have examined the interaction between the occurrence of PTSD and/or ADHD and substance abuse have noted that certain risk factors for the onset of psychotic symptoms secondary to a diagnosis of PTSD and ADHD are present, including problematic substance use . In addiThere are important limitations of the present study that need to be discussed. First, the study was based on a snowball sampling method that might be characterized by certain shortcomings related to the accuracy of assessments . Second,To conclude, the current study investigated the effect of the interaction between PTSD and ADHD symptoms on the risk of PLEs in a non-clinical sample. The results from our study show that both PTSD and ADHD symptoms might have an interaction effect on the level of reporting PLEs. Our results also suggest that individuals who have both PTSD and ADHD symptoms have higher levels of PLEs compared to individuals without these symptoms. This observation highlights the importance of investigating the interaction between PTSD and ADHD on the occurrence of PLEs. Future studies need to investigate our findings in longitudinal cohorts and clinical populations in order to provide specific recommendations for clinical practice. In case of replication within clinical cohorts, findings from the present study would raise awareness about the importance of PTSD and ADHD comorbidity in clinical practice. Also, the findings might provide grounds for investigating the most effective therapeutic interventions in this clinical population.https://osf.io/8ju6b.The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found at: The studies involving humans were approved by the study was approved by the Ethics Committees at the Institute of Psychology , Wroclaw Medical University  and Pomeranian Medical University . The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.HG and JK: writing – original draft. ŁG and JS: writing – review and editing and conceptualization. BM: conceptualization, funding acquisition, formal analysis, writing – original draft, and writing – review and editing. All authors contributed to the article and approved the submitted version.


Attention Deficit Hyperactivity Disorder (ADHD) is characterized by a persistent pattern of inattention, hyperactivity, and impulsivity, which begins in childhood and often persists into adulthood. ADHD has a heterogeneous expression with diversity in behavioral symptoms, cognitive deficits, and comorbidities. So, it is possible to consider it a spectrum with different losses.To describe clusters of multiple neuropsychological, attentional, and behavioral measures in adults with symptoms of ADHD. It could help to seek new directions to examine heterogeneity from a dimensional approach to ADHD.120 adults between 18 and 52 years old (m= 29.5) with ADHD symptoms participated in this study. Performance indices on computerized neuropsychological tests of attention , behavioral self-report scales for ADHD (ASRS-18), impulsivity (BIS-11) executive dysfunction (BDEFS), and functionality, emotional and behavioral problems (Adult Self-Report - ASR of ASEBA) were analyzed. Cluster analysis processed the data to find subgroups based on the scores of instruments. The NbClust tested the best number of clusters that converge to a solution.The 3 clusters solution was obtained by comparing Z scores for each indicator. In cluster 1, the ADHD symptoms were equivalent but expressed more hyperactivity than in other clusters. Also, higher levels of functional impairments and executive dysfunctions  were identified. In the attentional neuropsychological tasks, the indices express a lower level. Cluster 2 expressed a higher level of inattention and attentional, motor, and non-planning impulsivity, and functional impairments in the academic, professional, and legal risk areas. Cluster 3 was the subgroup with the lowest level of symptoms of ADHD.This study identified differences in performances that contribute to understanding the cognitive, behavioral, and emotional expressions of ADHD. Three groups of different prejudices levels should be considered in the development of evaluative models in new studies to consider the spectrum of ADHD.Financial support: FAPESP ; CAPES Proex ; Mackpesquisa; CNPq [grant 307443/2019-1]None Declared