Background: SPOCK2 is a member of the SPOCK family, a 424-amino acid protein that binds to glycosaminoglycans to form proteoglycans. The purpose of this study was to explore expression profile of SPOCK2, and evaluate prognostic potential and its correlation with immune infiltration in high-grade serous ovarian cancer (HGSOC).Methods: Expression of SPOCK2 mRNA and protein between normal and tumor tissues were analyzed using the Cancer Genome Atlas database (TCGA), Gene Expression Omnibus (GEO), Clinical Proteomic Tumor Analysis Consortium (CPTAC), and the Human Protein Atlas (HPA) databases. Receiver operating characteristic (ROC) curve was used to evaluate diagnostic performance of SPOCK2. Kaplan-Meier method and Cox regression analysis were conducted to assess the effect of SPOCK2 on survival. Nomogram was used to predict the impact of SPOCK2 on prognosis. LinkedOmics were used to find correlated genes and perform functional enrichment analyses. The relationships between SPOCK2 and tumor infiltrating lymphocytes (TILs) were determined by tumor-immune system interaction database (TISIDB) and GSVA package (V1.34.0).Results: SPOCK2 was highly expressed in HGSOC tissue compared to normal tissue at both mRNA (p < 0.001) and protein (p = 0.03) levels. The area under the curve (AUC) is 0.894 (CI: 0.865–0.923). Kaplan-Meier analysis showed that HGSOC patients with high-level SPOCK2 mRNA expression had a worse overall survival (OS) than those with a low expression . Univariate logistic regression analysis found that age, primary therapy outcome, tumor status, tumor residual, and SPOCK2 expression level were significantly associated with OS (p < 0.05). The nomogram model indicated an effective predictive performance of SPOCK2. Kyoto encyclopedia of genes and genomes (KEGG) and gene ontology (GO) term analyses showed that SPOCK2 were mainly involved in regulating extracellular matrix. Immune infiltration analysis showed that SPOCK2 may correlate with abundance of TILs.Conclusion: SPOCK2 has potentials to estimate diagnosis and prognosis for HGSOC and is involved in regulating extracellular matrix and immune cell infiltration. High-grade serous ovarian cancer (HGSOC) is of particular interest, as it comprises over 70% of epithelial ovarian cancer (EOC) and accounts for the majority of deaths within the first 3 months of ovarian cancer diagnoses, indicating high morbidity and mortality that caused by late-stage presentation and insufficient therapies . About 7SPARC (osteonectin), cwcv and kazal-like domains proteoglycan 2 (SPOCK2), also known as testican-2, is a member of the SPARC family composing of FSTL1, SMOC1, SMOC2, SPARC, SPARCL1, SPOCK1, SPOCK2, and SPOCK3 . The proTo incorporate extracellular matrix on cancer immunity and prognosis in HGSOC, we could proceed with SPOCK2. In this study, we first evaluated the patient characteristics and expression of SPOCK2 using the Cancer Genome Atlas (TCGA) and Genotype Tissue Expression (GTEx) datasets, and subsequently examined association between clinical features and prognostic significance of SPOCK2 using Cox regression analysis. Furthermore, we explored the positively and negatively correlated genes of SPOCK2 in HGSOC, and conducted kyoto encyclopedia of genes and genomes (KEGG) pathway analysis and gene ontology (GO) term analysis. Finally, the impact of SPOCK2 on tumor infiltrating immune cells were analyzed. Our study is important in improving understandings of SPOCK2 in HGSOC and finds that SPOCK2 might be a potential prognostic and therapeutic biomarker for HGSOC.https://xenabrowser.net/datapages/) to analyze expression level of SPOCK2. The RNA-seq data with workflow type of HTSeq-FPKM (high throughput sequencing-fregments per kilobase per million) were transformed to TPM (transcription per million reads) format which was processed via the Toil procedure . Since all gene expression data and patient information were downloaded using R (V3.6.3), the consent from the Ethics and Committee was waived.RNA-seq transcriptomic data of normal and tumor tissues were respectively downloaded from GTEx and TCGA datasets using UCSC XENA  to present differential mRNA expression of SPOCK2 according to clinical features (https://www.proteinatlas.org) was used to download immunohistochemical images. With the application of proteomic technologies, we used the clinical proteomic tumor analysis consortium (CPTAC)  to quantify SPOCK2 protein and find associations of SPOCK2 protein level with clinical features (The ggplot2 package (V3.3.3) was used to visualize differential expression of SPOCK2. RNA sequencing data of 8,295 normal and 9,807 tumor tissues was preprocessed, and the Wilcoxon rank sum test was applied to analyze pan-cancer expression level of SPOCK2 in non-paired samples. The Weltch t' test was subsequently used to assess the differential mRNA expression of SPOCK2 between 88 normal ovary tissues and 427 HGSOC samples. In addition, we performed UALCAN (features . To idenfeatures . The assProtein samples were prepared from the ovarian cancer cell lines. Protein concentration was determined with Bradford protein assay reagent using BSA as the standard. Protein (20 µg) was separated by 12% SDS-PAGE, transferred to a polyvinylidene fluoride (PVDF), and blocked with 5% fat-free milk in TBST at room temperature for 1 h. The membranes were incubated at 4°C overnight with the monoclonal antibody against SPOCK2  and Actin  from mouse. Membranes were then incubated with horseradish peroxidase (HRP)-conjugated anti-rabbit and anti-mouse antibodies  at room temperature for 1 h. An enhanced chemiluminescence  detection system (Bio-Rad) was used to visualize immunoreactive bands. The densitometry of each protein band was quantified using ImageJ 1.46r software .p-values were less than 0.05.The survminer package (V0.4.9) was used to evaluate prognostic potential of SPOCK2 and the cut-off point of SPOCK2 expression was determined by its median value. To investigate the effect of SPOCK2 expression level along with other clinical factors  on OS in TCGA patients, the Kaplan-Meier method with a two-sided log-rank test was used. Furthermore, the survival package (V3.2-10) and the Cox regression analysis was applied to calculate the effect of SPOCK2 expression level and other clinicopathological features  on survival. The independent prognostic factors derived from multivariate analysis were employed to predict 1-, 3-, and 5-years survival probability, which were visualized using a nomogram. Moreover, the nomogram-predicted probabilities were graphically demonstrated by calibration curves. The concordance index (C-index) was used to assess the discrimination of the nomogram, which was calculated by a bootstrap approach with 1,000 resamples. Notably, nomograms and calibration curves were generated by the rms (V6.2-0) and survival (V3.2-10) packages. All statistical tests were considered as significant if http://www.linkedomics.org/login.php) is a publicly available dataset that contains multi-omics data from all 32 cancer types and a total of 11,158 TCGA patients (LinkedOmics (patients . The webhttp://www.cis.hku.hk/TISIDB/index.php) which is a web portal for tumor-immune system interactions and integrates multiple heterogeneous data types ; by contrast, SPOCK2 was significantly downregulated in adrenocortical carcinoma (ACC), colon adenocarcinoma (COAD), pleomorphic glioma (GBM), renal chromophobe cell carcinoma (KICH), renal clear cell carcinoma (KIRC), renal papillary cell carcinoma (KIRP), lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), rectum adenocarcinoma (READ), testicular germ cell tumors (TGCT) (p < 0.05).We first carried out pan-cancer analyses to evaluate the SPOCK2 mRNA expression profile in the tumor samples of TCGA and the normal samples of GTEx combined with TCGA across different cancer types. The differential expression analyses of SPOCK2 mRNA was finally referred to 33 cancer types by using Wilcoxon rank sum test . Comparep < 0.001, p = 0.03, n = 88) and HGSOC tissues (n = 427)  . The arep < 0.01) and tumor grade , and has no relation with patient’s age, individual cancer stage, and TP53 mutation status (p > 0.05). The univariate analysis with logistic regression showed that upregulated SPOCK2 mRNA expression is positively associated with tumor residual  , patient’s race , and individual cancer stage   . Further< 0.001) . These rp = 0.005). Next, we performed subgroup survival analyses of OS based on clinical characteristics, which exhibited that prognosis of patients with high-level SPOCK2 expression was significantly poor in the White , stage III&IV , and Grade 3&4  subgroups of OS (p = 0.007) and under 60 years  both have comparatively worse OS than those with low-level expression (p = 0.021), primary therapy outcome , tumor status , tumor residual , and SPOCK2 expression level  were significantly associated with OS (p < 0.001) and tumor status  were independent prognostic factors of OS for HGSOC; SPOCK2 expression level, however, was not still an independent factor related to OS  (Kaplan-Meier curves were used to explore the relationships between SPOCK2 mRNA expression and OS in HGSOC patients. As shown in ps of OS . Notablypression . To furt with OS . In addi= 0.114) .To quantitatively verify that SPOCK2 mRNA is an advisable approach predicting the prognosis of HGSOC patients, SPOCK2 and other clinicopathological parameters including age, FIGO stage, histological grade, and primary therapy outcome were used to construct a prediction model for OS. We, therefore, established a nomogram of OS based on multivariate Cox regression analysis to assign points to the abovementioned variables. The points assigned to these variables were accumulated and recorded as the total score. For example, HGSOC patients with high SPOCK2 mRNA expression (25 points), advanced FIGO stages (59 points), and age over 60 years (19 points) received a total score of 103. Then, we draw a vertical line directly down from the total points axis at scale of 103 to the survival probability axis. Therefore, the 1-, 3-, and 5-years survival probabilities were >95%, 68%, and 36%, respectively . Moreovep < 0.05). Following this, we showed top 50 genes that positively and negatively correlated with SPOCk2 in the heat maps, respectively (p = 8.543E-32), ARHGAP23 , TGM1 , AKAP7 , and MERTK   .We used the LinkInterpreter module to explore functional enrichment information of SPOCK2 that contribute to tumorigenesis or tumor progression of HGSOC. KEGG pathway analysis showed that SPOCK2-correlated genes were mainly involved in focal adhesion, leukocyte transendothelial migration, and ECM-receptor interaction . GO_BP . GO_CC . GO_MF . OverallR = 0.310, p < 0.001), T effector memory (Tem) cells , T central memory (Tcm) cells , and Mast cells ; by contrast, SPOCK2 mRNA expression negatively correlated with infiltration of activated dendritic cells (aDC)  and T helper 2 (Th2) cells  (p < 0.001), Tem cells (p < 0.01), and Tcm cells (p < 0.05), and had less aDC (p < 0.01) and Th2 cells (p < 0.01); however, the plot showed no significant difference of Mast cells infiltrating abundance between SPOCK2-high and -low groups (p > 0.05), which is not consistent with the result of scatter plot  . In additer plot . These rIn this study, we found that both mRNA and protein expression of SPOCK2 were upregulated in ovarian serous cystadenocarcinoma along with a high expression of SPOCK2 mRNA in the most TCGA cancers. Further ROC curve analysis confirmed that SPOCK2 could be a promising diagnostic biomarker to distinguish HGSOC from benign tissues. To investigate factors that influence SPOCK expression, subgroup analyses based on clinical variables were done in all patients enrolled in the UALCAN dataset, suggesting that SPOCK2 expression is correlated with patient’s race, tumor grade, and cancer stage. A critical element of this study is the evaluation of the effect of SPOCK2 on OS by using Kaplan-Meier and univariate logistic regression analyses, in which high SPOCK2 mRNA expression is associated with a shorter OS. Additionally, functional enrichment analysis of SPOCK2-correlated genes revealed that SPOCK2 may play a specific role in regulating functions of extracellular matrix. Exploratory analyses of TILs were conducted to examine the role of SPOCK2 in immune infiltration, showing that there were significant associations between SPOCK2 mRNA expression level and TILs abundance. Overall, this study has led to an improved understanding of SPOCK2 in HGSOC and provided potential therapeutic target.SPOCK family comprised of SPOCK1, SPOCK2, and SPOCK3, and was originally identified by cDNA cloning, with amino acid homologies . SPOCK pBy analyzing the expression level of SPOCK2 in HGSOC, we noted that both mRNA and protein level of SPOCK2 in HGSOC were significantly higher than those in normal ovary tissues, which were influenced by clinical features such as patient’s race, tumor grade, and cancer stage. Few studies have been conducted to explore the underlying reasons of why these clinical characteristics could change genetic performance of SPOCK2. Nevertheless, some studies have focused on mechanisms of up- and down-regulated expression of SPOCK2 and concluded that promoter methylation of SPOCK2 gene may be one of reasons for abnormal expression of SPOCK2. p = 0.016) in patients with pancreatic ductal adenocarcinoma. Similarly, an in vitro experiment revealed that overexpression of SPOCK2 contribute to inhibit cell proliferation and invasion in endometrium-derived cancer cell lines. The researchers also found that inhibitory functions of SPOCK2 on tumor cell progression were achieved partly through suppressing expression or activation of MT1-MMP and MMP2 , a focal adhesion component, was essential to recruit MT1-MMP molecules . Moreovevia MMP-mediated degradation (During cancer progression, tumor cells can establish an overtly immunosuppressive tumor microenvironment that is composed of infiltrating immune cells, endothelial cells, and fibroblasts, often embedded within extracellular matrix . Numerouradation . In thisradation . Coincidradation . On the in vivo/vitro experiments and use of public databases make it difficult to detail the mechanisms of SPOCK2 that contribute HGSOC progression, this article is expected to provide a new direction for predicting prognosis and exploring therapeutic targets. In the future, more fundamental experiments with clinical samples instead of data mining should be well-designed.This study provided evidence for upregulated expression of SPOCK2 and found that SPOCK2 had diagnostic and prognostic potential for HGSOC. In addition to explorations of SPOCK2-related pathways that indicated a critical role in remodeling extracellular matrix, immune cell infiltration analyses provided new understandings for associations between SPOCK2 and TILs. Although a lack of


Patients with severe OUD who have not responded to oral opioid maintenance treatment can be treated with intravenous diamorphine up to three times per day. Here, we investigated the prevalence of ADHD among patients undergoing either daily diamorphine maintenance treatment or daily oral opioid maintenance treatment. (2) Methods: We assessed all participants with the WURS-k and the ADHD-SR. The Diagnostic Interview for ADHD in Adults (DIVA) was performed with all participants who met the cut-off in the WURS-k and/or ADHD-SR. (3) Results: The overall prevalence of ADHD was 17.9%. Prevalence of ADHD among patients undergoing daily diamorphine maintenance treatment was 14.3%. Prevalence of ADHD among patients undergoing daily oral opioid maintenance treatment was 20.3%. The combined presentation of ADHD was the most prevalent condition. In urine samples of participants with comorbid ADHD, heroin was detected the most and cocaine the least frequently. (4) Conclusions: Almost one out of five patients with OUD suffered from comorbid ADHD. In 83.3%, ADHD had not been diagnosed prior to participation in this study. Thus, patients with SUD could benefit from being routinely screened for ADHD. Attention deficit hyperactivity disorder (ADHD) has a prevalence of 2.5% in adults and 3.4% in childhood and is one of the most prevalent neurodevelopmental disorders among children and adolescents ,2. ADHD ADHD has been associated with a more severe course of substance use as well as with social and mental health impairment . MoreoveAn expert group suggests starting the diagnostic process for ADHD among SUD patients as soon as possible, when there are neither serious withdrawal symptoms nor serious intoxication .The prevalence of ADHD in SUD populations has been found to be inconsistent ranging from 5.22%  to 62% . A meta-OUD patients with comorbid ADHD that undergo oral opioid maintenance treatment are characterized by greater addiction severity and higher psychiatric comorbidity rates . Most ofHence, the primary objective of this study was to contribute to closing this knowledge gap by determining, for the first time, the prevalence of ADHD in a population of adult patients with severe opioid use disorder (OUD) undergoing daily intravenous diamorphine maintenance treatment in Germany. In addition, for comparison, we examined a population of adult patients with OUD undergoing daily oral opioid maintenance treatment in the same city.Diamorphinambulanz of the university hospital of Bonn with daily intravenous diamorphine maintenance treatment (DIA) and another population treated at the Medizinische Ambulanz und Substitutionsbehandlung of the Verein für Gefährdetenhilfe (VfG) treated with daily oral opioid maintenance treatment (OOT).We investigated two populations of patients with OUD recruited in two outpatient departments in Bonn, Germany; namely, a population treated at the Patient recruitment started after ethical approval of the local Ethics Committee of the University Clinic of Bonn had been obtained.Every patient of these outpatient departments was addressed and informed about the aims and procedure of this study. Inclusion criteria were minimum age of 18 years and a diagnosis of opioid dependence according to the International Statistical Classification of Diseases and Related Health Problems–10 (ICD-10) [Diagnosis of ADHD followed the guidelines of the National Institute for Health and Care Excellence (NICE) . After wUrine samples are usually analyzed monthly for every patient undergoing opioid maintenance treatment. The urine samples of DIA patients are analyzed for illicit and pharmaceutical diamorphine/heroin use by gas chromatography-mass spectrometry .The WURS-k is a retrospective questionnaire about ADHD symptoms between the ages of 8 and 12 years. ADHD-SR is a questionnaire about ADHD symptoms in adulthood. Cut-off criteria in WURS-k is 30 out of 84 points and cut-off criteria in ADHD-SR is 18 out of 66 points. Combined, these two questionnaires have a sensitivity of 94% and specificity of 56% .DIVA 2.0 is a clinical diagnostic interview for ADHD in childhood and adulthood in line with the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders 4 (DSM-IV) . It cons® was used for statistical analysis.Recruitment and screening at the VFG site took place between 24 May and 11 June 2021, while recruitment and screening at the DIA site took place between 9 and 23 August 2021. DIVA 2.0 Interviews were held by appointment in the following months. IBM SPSS Version 28.0.1.1 (14)The study included 106 participants in total, where 20.8% were female and the mean age was 49.58 ± 7.71 years. In total, 22.6% fulfilled diagnostic criteria for childhood ADHD and 17.9% for persisting adult ADHD using the DIVA 2.0 interview. In 83.3%, ADHD had not been diagnosed before participating in this study.DIA: 43 out of 54 patients agreed to participate. There was one dropout because one participant did not want to conduct the DIVA interview after completing the questionnaires. In total, 21.4% was female and the mean age was 50.48 ± 7.82 years. Moreover, 45.2% were treated with intravenous diamorphine alone and the remaining individuals additionally received methadone once a day. In total, 16.7% met ADHD diagnosis criteria and in 14.3% ADHD persisted in adulthood. In 85.7% of cases, ADHD had not been diagnosed before participating in this study.OOT: 64 out of 134 patients agreed to participate. There were no dropouts. In total, 20.3% were female and the mean age was 48.98 ± 7.65 years. Among them, 84.4% were treated with l-polamidone, 11% with buprenorphine, 1.6% with methadone, and 3.1% with morphine. Moreover, 26.6% met ADHD diagnosis criteria and in 20.3%, ADHD persisted in adulthood. In 82.4% of cases, ADHD had not been diagnosed before participating in this study.In summary, almost every fifth study participant suffering from OUD was diagnosed with comorbid adult ADHD, and most of them (83.3%) had been undiagnosed previous to this study.The two populations show very similar mean age and gender distribution; however, of note, there was a 6% difference in the prevalence of ADHD in adulthood.Overall, 25.5% met the cut-off criteria for ADHD in WURS-k and 28.3% in ADHD-SR, while 18.9% met the cut-off criteria for ADHD in both. Of 37 DIVA 2.0 interviews, 64.9% confirmed the presence of the ADHD diagnosis, with the combined presentation being the most prevalent.For DIVA 2.0 subtype results, see DIA: 19% met the cut-off criteria in WURS-k, 19% in ADHD-SR, and 14.3% met the cut-off criteria in both. Out of 10 DIVA 2.0 interviews, 70% confirmed the presence of ADHD, with the combined presentation being the most prevalent.OOT: 25.5% met cut-off criteria in WURS-k, 29.7% in ADHD-SR, and 20.3% met the cut-off criteria of both inventories. Out of 27 DIVA 2.0 interviews, 63% confirmed the presence of ADHD, with combined presentation being the most prevalent.In detail:With 35.1% of false positive results, WURS-k and ADHD-SR appeared to be a very useful diagnostic tool in this study because of their simple and low-threshold usability. To meet the standards of the international  and GermWe analyzed urine samples of 24 participants. In total, 29.2% of the participants screened negative for all substances. For the prevalence of each substance, see These urine analyses show that patients with ADHD tend to abuse substances with sedative properties, such as heroin or benzodiazepines.OUD patients with adult ADHD might benefit less from treatment with intravenous diamorphine, and therefore, do not make use of it.OUD patients with adult ADHD could have difficulties sustaining the intravenous diamorphine maintenance treatment with up to three treatments per day. Thus, they are underrepresented in this special subgroup of OUD patients.In our sample of adult patients with OUD undergoing daily opioid maintenance treatment, we found an ADHD prevalence of 17.9%. This is consistent with previous studies among patients with OUD in other settings ,28,29 anThe biggest difference to the ADHD population without OUD is the large proportion of the predominantly hyperactive-impulsive presentation. This difference further increased in the DIA subpopulation. In this subpopulation, the combined presentation was the most prevalent (50%) followed by the predominantly hyperactive-impulsive presentation (33.3%) and the predominantly inattentive presentation (16.7%). Peculiar is the fact that the predominantly hyperactive-impulsive presentation was more prevalent among OUD patients, in particular in the DIA patient cohort, than among patients suffering from ADHD without comorbid OUD.Further studies directly comparing subtype prevalence in ADHD populations with and without comorbid OUD, as well as studies with more participants in intravenous diamorphine maintenance treatment clinics would be needed to determine if this observation is statistically significant and reproducible. Clinical significance could then be further assessed, e.g., in order to determine whether OUD patients with comorbid ADHD of the hyperactive-impulsive subtype benefit more from diamorphine maintenance treatment than oral opioid maintenance treatment alone.Our urine analyses suggest that patients with ADHD tend to abuse substances with sedative properties, such as heroin or benzodiazepines. This fits the results of the aforementioned meta-analysis (2012), which demonstrated a higher prevalence of ADHD among patients with OUD and alcohol use disorder than among patients with cocaine use disorder . There wLimitations: We examined a small sample cohort of a special subpopulation of OUD outpatients recruited in one region. Future studies should include larger numbers of participants in order to allow for statistical analysis of results as well as recruitment of more diverse populations in different locations.The higher rate of non-included patients in the OOT than in the DIA populations must be considered in the interpretation.Diagnosis of ADHD relied on interviewing the patients themselves. An interview with the partner or the parents would have provided even more diagnostic certainty. However, this was not possible within the framework of our study design.The diagnostic procedure required two steps: first a screening questionnaire and then a structured interview. Thus, underestimation of ADHD prevalence due to false-negative screenings is possible.Furthermore, additional comorbidities are frequent in OUD and ADHD patients and can complicate diagnostic assessment; the same applies to the frequent abuse of other substances in patients with OUD.In our sample, which is as far as we know the first sample ever looking for ADHD in a population of patients with severe OUD on daily diamorphine maintenance treatment, almost every fifth study participant suffering from severe OUD met the diagnostic criteria of adult ADHD, of which 83.3% had been undiagnosed before. Future approaches should implant a routine screening for ADHD among SUD patients and develop new therapeutical concepts for this group of special patients in order to hopefully improve the physical and mental health of patients with ADHD and comorbid SUD. Additionally, early diagnosis of ADHD could attenuate the severity of SUD or even prevent the occurrence of SUD.In particular, the possible benefit of intravenous diamorphine treatment for patients suffering from severe OUD and comorbid ADHD should be investigated more intensively with larger participant numbers in multicentric study designs.


Difficulties with executive function have often been identified in individuals with various neurodevelopmental disorders such as Autism Spectrum Disorder (ASD), Attention-Deficit Hyperactivity Disorder (ADHD), and Developmental Co-ordination Disorder (DCD). Additionally, in childhood and adolescence, executive functioning is an important predictor of academic achievement. However, less research has explored these relationships in adult students, and those with a high level of neurodevelopmental disorder traits but no clinical diagnosis. Therefore, the current study aimed to assess whether ASD, ADHD, and DCD traits can predict academic achievement in university students, and whether traits of these neurodevelopmental conditions moderate the relationship between executive function and academic achievement. Both neurotypical students and those with a clinical diagnosis of a neurodevelopmental disorder were able to participate, with the majority being neurotypical. Participants completed four self-report questionnaires and provided a measure of academic achievement based on their university assignment results. Traits of ASD, ADHD, and DCD alone did not predict achievement, however, traits of ADHD and DCD significantly moderated the relationship between executive function and academic achievement. ASD traits did not significantly moderate this relationship. Implications and suggestions for future research are also discussed. Executive functions are cognitive abilities that are responsible for co-ordinating problem solving and achieving goals , and areThere is a consensus among the literature that better executive functioning is associated with higher academic achievement in childhood and adolescence . WorkingFurthermore, previous research has found evidence that executive function may be impaired in individuals with neurodevelopmental disorders , includiIf executive functioning can predict reading, writing, and mathematics ability , and intAutism spectrum disorder is a neurodevelopmental disorder which is associated with impairments in social interaction and communication . IndividWorking memory has been found to consistently predict academic achievement in autistic individuals , with exAttention-deficit hyperactivity disorder is characterized by hyperactivity, impulsive behaviors, and being easily distracted , and chiThere is evidence that academic performance in individuals with ADHD can be predicted by executive functions; verbal working memory ability can predict academic achievement consistently across various academic subjects in those with ADHD  and visuThese relationships can be seen in adults as well as children; executive function impairments are also associated with academic achievement in university students with ADHD , althougAutism spectrum disorder and attention-deficit hyperactivity disorder can also co-occur with Developmental Co-ordination Disorder DCD; . DCD is Furthermore, motor difficulties in children just 6 months old may predict an ASD diagnosis later on , and MilSimilarly to ASD and ADHD, DCD has often been associated with executive function impairments  and poorFurthermore, motor skills can contribute to academic achievement in both the typically developing population  and indiThe motor difficulties seen in DCD have been associated with executive function impairments ; childreDespite numerous papers highlighting the contribution of executive function to academic achievement in those with neurodevelopmental disorders, less is known about this area in adults, as the vast majority of this research has been conducted with children. Some research has begun to address the contribution of executive function to academic achievement in adults with neurodevelopmental disorders; DCD and dyslexia have been related to lower academic confidence in university students with these conditions , and theIt may be possible for individuals to have high levels of traits of a neurodevelopmental condition despite lacking a clinical diagnosis . For exaIf neurodevelopmental disorder traits are found to have a significant role in the relationship between executive function and academic achievement in university students, this could result in potential changes to intervention strategies for individuals with these conditions or those with high levels of neurodevelopmental disorder traits. It could also perhaps improve access to better quality support for students with such conditions or traits, especially for those with a high level of ASD, ADHD, or DCD traits who may otherwise be missed due to the lack of a diagnosis. Additionally, identifying high levels of neurodevelopmental disorder traits in students may provide prognostic value; it may indicate that a student could potentially be at risk of academic underachievement.Thus, if these traits are identified early, any necessary interventions such as those that seek to improve executive functioning can be put in place for the student earlier on, giving them a higher chance of academic success , 10.8% were male (N = 17). 1.9% of participants preferred not to state their gender (N = 3). The age range was 18–47 . Twenty-one participants had a diagnosis of at least one neurodevelopmental condition; nine had a diagnosis of autism, nine had ADHD, two had attention-deficit disorder (ADD), seven had dyslexia, and one had dyspraxia. Of these, six participants had co-occurring neurodevelopmental disorders; three had co-occurring ASD and ADHD, one had ASD and ADD, one had ADHD and dyslexia, and one had ADHD, DCD, and dyslexia. The remaining participants (N = 137) were neurotypical, therefore, this was a majority non-clinical sample. To be eligible to participate in this study, participants had to be university students aged 18 and above. This included both undergraduates and postgraduates, full time or part time. However, they had to be on taught programs to be able to participate, therefore, PhD students were not included.One hundred and seventy-five university students took part in this study, however, there were only one hundred and fifty-eight completed responses that were used for the analysis. Of these 158 participants, 87.3% were female , partly true (2), or true (3). This scale was chosen over laboratory methods due to the convenience of it being able to be completed by a large sample, and it may also provide a better insight into executive functions in everyday life rather than laboratory-based methods which may lack ecological validity somewhat , slightly agree (2), slightly disagree (3), or definitely disagree (4). Definitely agree and slightly agree responses were scored 1 point on autism-typical items such as “I prefer to do things the same way over and over again.” There were 26 reverse scored items, such as “I prefer to do things with others rather than on my own,” where slightly disagree and definitely disagree were scored 1 point.ASD traits were measured using the Autism Quotient AQ; , which cnever (1) to very often (5). DCD traits were measured using the Adult DCD Checklist  to always (4). Responses on all measures were scored summed to provide a total score.ADHD traits were measured using the Adult ADHD Self-Report Scale ASRS; , which hist ADC; , which hAcademic achievement was measured using students’ results from the first assignment and most recent assignment they submitted during the academic year in which they participated. These scores were used to calculate a mean to provide a measure of academic achievement. In the event that a participant had only completed one assignment during the academic year at the time of participating, they were asked to provide the same number as they did for the previous question. Items across all measures were scored such that higher scores meant better executive functioning, higher levels of ASD, ADHD, and DCD traits, and higher academic achievement.Participants were asked for demographic data (age and gender), and whether or not they have a neurodevelopmental disorder. If so, they were asked to specify which. Participants were then asked for the result of their first university assessment and most recent assessment of the academic year in numerical form out of 100, as a measure for academic achievement. Participants then completed the AQ , ASRS K, the ACDThe means, standard deviations, and range of scores for each measure are shown in R2 = 0.02, F = 1.06, p = 0.367, but this was non-significant. Individually, traits of ASD β = –0.14, t(154) = –1.52, p = 0.13; ADHD β = 0.14, t(154) = –1.27, p = 0.205, and DCD β = –0.03, t(154) = –3.12, p = 0.75, did not significantly predict academic achievement.A multiple regression revealed that ASD, ADHD, and DCD traits accounted for 2% of variance in academic achievement, R2 = 0.05, F = 2.82, p = 0.04. However, the interaction was non-significant .Three moderated regression analyses were performed using the PROCESS macro model 1, with executive function as the predictor, academic achievement as the outcome, and traits of ASD, ADHD, and DCD as the moderator in each regression, respectively. All variables were centered, and the conditioning values were set to –1 SD, mean, +1 SD. With ASD traits as the moderator, 5% of the variance in academic achievement was explained, R2 = 0.05, F = 2.94, p = 0.03. The interaction between executive function and ADHD traits was significant , suggesting that ADHD traits significantly moderated the relationship between EF and academic achievement. The association between EF and achievement was negative, but simple slopes analysis revealed that this was only significant at a low level of ADHD traits (p < 0.006). At average and high levels of ADHD traits, the interaction was non-significant. At a high level of ADHD traits, the relationship between EF and achievement was positive, but as this was non-significant it cannot be reliably interpreted.With ADHD traits as the moderator, 5% of the variance in academic achievement was explained, R2 = 0.05, F = 2.87, p = 0.038. The interaction between executive function and DCD traits was significant , suggesting that DCD traits significantly moderated the relationship between EF and academic achievement. The association between EF and achievement was negative, but simple slopes analysis revealed that this was only significant at a low level of DCD traits (p < 0.005). At average and high levels of DCD traits, the interaction was non-significant. At a high level of DCD traits, the relationship between EF and achievement was positive, but as this was non-significant it cannot be reliably interpreted.With DCD traits as the moderator, 5% of the variance in academic achievement was explained, The first aim of the current study was to assess whether traits of ASD, ADHD, and DCD could significantly predict academic achievement in university students, with the hypothesis that higher levels of traits would significantly predict lower academic achievement. ASD, ADHD, and DCD traits did not significantly predict achievement, suggesting that having a high level of traits of these conditions does not significantly predict that a student will have lower achievement. Thus, the hypothesis was not supported. Although the direction of this relationship was in line with the findings of previous studies such as Furthermore, the relationship between these variables was weak, which suggests that having a high level of autistic traits may have less of an influence on academic achievement than having a clinical diagnosis of ASD and/or DCD does. Further to this, the relationship between ADHD traits and achievement was not only non-significant, but also positive. This was the opposite direction to what was hypothesized based on previous literature such as It should be noted, however, that the current study did not specifically recruit participants with a clinical diagnosis of ASD, ADHD, or DCD; rather, the majority were neurotypical university students, although 21 of the 158 participants did have a diagnosis of at least one neurodevelopmental condition. As the study was looking at traits in a majority neurotypical sample, this may be the reason that levels of ASD, ADHD, and DCD traits did not significantly predict academic achievement as hypothesized.Additionally, many of the studies that have identified poorer academic performance in individuals with neurodevelopmental disorders studied children, such as The non-significant relationship between ASD, ADHD, and DCD traits and achievement could also perhaps be explained by the possibility that some of the students who participated in this study may have received additional academic support, which could positively affect their academic performance. In addition, those with higher levels of traits but not high enough for a clinical diagnosis may not experience significant academic difficulty. This may be why these individuals do not reach the threshold for a clinical diagnosis; the level of traits they report may not have enough of a significant impact on their daily life that their academic performance is affected, which can be the reason why many individuals with ADHD, for example, are brought to the attention of clinicians to begin with . HoweverThe second aim was to determine whether traits of ASD, ADHD, and DCD moderate the relationship between executive function and academic achievement, with the hypothesis that higher levels of ASD, ADHD, and DCD traits would significantly moderate a positive relationship between executive function and academic achievement. ASD traits did not significantly moderate the relationship between EF and academic achievement, but ADHD and DCD traits did significantly moderate this relationship. However, the interaction was only significant at lower levels of ADHD and DCD traits, and the relationship between executive function and achievement was negative. This suggests that lower levels of ADHD and DCD traits, respectively, significantly moderated a negative relationship between executive function and achievement therefore the second hypothesis is not fully supported despite the statistical significance.These findings do not provide adequate support for the findings of It is also worth noting that the relationship between executive function and achievement was only negative at lower and average levels of both ADHD and DCD traits. At higher levels of ADHD and DCD traits, this relationship was positive, which, although statistically non-significant, supports the direction of the second hypothesis. Despite the statistical non-significance, this does not suggest that there is no relationship between these variables. Rather, this may suggest that for some neurotypical individuals, having a high level of ADHD and/or DCD traits and poorer executive function could potentially be a risk factor for lower academic performance. However, additional research would be needed to explore this possibility further, and investigate whether or not this result is repeated and significant in a larger number of students from a wider variety of higher education institutions. Such findings may be of prognostic value; academic support could be put in place earlier for students with poorer executive functioning and higher levels of ADHD and/or DCD traits to promote academic success. It should also be noted that the percentage of variance in academic achievement accounted for by EF and traits of ASD, ADHD, and DCD, respectively, is fairly low, which could suggest that there is another factor that could account for variance in achievement that was not measured in the present study.The current study can offer a contribution to the gap in the literature concerning the role of neurodevelopmental disorder traits in the relationship between executive function and achievement in the adult student population, and the nature of the relationship between these variables in neurotypical students. This study also contributes evidence of a moderating role of ADHD and DCD traits in the relationship between EF and achievement in neurotypical university students, suggesting that the relationship between EF and neurodevelopmental disorder traits in relation to academic performance may not only be limited to individuals with a clinical diagnosis of a neurodevelopmental condition. However, further research is needed to support this suggestion, as research into this understudied area is limited and therefore reduces the extent to which the findings can be reliably interpreted and compared with findings of previous research.The current study also offers evidence to suggest that students with a high level of neurodevelopmental disorder traits but no clinical diagnosis may not potentially be as at risk of academic underachievement compared with individuals who have a clinical diagnosis of ASD, ADHD, or DCD. However, this does not necessarily mean that no neurotypical university students with a high level of ASD, ADHD, or DCD traits will ever be at risk of academic underachievement. ASD and DCD traits displayed a negative relationship with academic achievement, and, although non-significant, there could be a possibility that individual students with a high level of ASD or DCD traits, who do not reach the threshold for a clinical diagnosis, could face academic difficulty. With no clinical diagnosis, they may not come to the attention of university academic support services, potentially placing them at risk of academic underachievement.Despite the contributions of this study, it has some noteworthy limitations. Firstly, executive function and DCD traits were measured using a self-report questionnaire rather than lab-based assessments. The Amsterdam Executive Function Inventory AEFI;  and the More recently, the Free Research Executive Function Evaluation FREE;  test batFor the DCD checklist, the first section contains items regarding childhood, which gathers retrospective data. This could mean that these answers may no longer be relevant to the participants’ current motor skills, potentially affecting the accuracy of the results. To address this limitation, a lab-based task could be used to measure motor skills in addition to the self-report measure of DCD traits, such as the Test of Motor Competence (TMC), an assessment battery that assesses both gross and fine motor skills, as described by Another limitation of the present study was that the majority of participants were female. Research has suggested that a higher number of males have ASD compared to females , and thaA further notable limitation is that the study did not require participants to disclose which institution they were studying at, or which course they were on. The majority of the participants were studying at the researcher’s affiliated institution, which means that these results mainly reflect the responses of university students studying in the United Kingdom in one institution. The study was also available to students studying at universities in other countries, therefore, the study has not taken into account any potential influences of cultural factors or socioeconomic status. It may have also been useful to know which courses the participants were studying, in order to account for the possibility that some students may not be studying “academic” subjects, and may not be graded using the percentage format.The current study also did not consider whether participants had accessed any assistance from university academic support services or if they were in receipt of additional examination requirements such as extra time. Accessing such support may positively affect students’ academic performance which may render any relationship between neurodevelopmental disorder traits and academic achievement non-significant. To address this limitation, future research should note whether participants have accessed academic skills support and whether they receive any additional examination requirements, and if so, which. This could also provide data on the role of academic support as a possible protective factor in the relationship between neurodevelopmental disorder traits and academic achievement. Future research could explore whether such interventions can improve academic achievement outcomes in university students with a high level of neurodevelopmental disorder traits, as well as those with a clinical diagnosis.As it is consistent among the literature that executive function can be impaired and academic achievement can be lower in individuals with ASD, there may be a possibility that while the interaction between executive function and ASD traits was non-significant in a sample of majority neurotypical students, this relationship may be significant in individuals with a clinical diagnosis of ASD. This may be especially relevant as the result was very close to the significance threshold, thus, future research with a clinical sample may find a significant result. Therefore, future research could explore the potential moderating role of ASD traits on the relationship between executive function and achievement in university students with a clinical diagnosis of ASD, and perhaps other conditions known to affect academic performance in university students, such as dyslexia .It may also be worth investigating the possibility of a different relationship between executive function, neurodevelopmental disorder traits and academic achievement; for example, the potential mediating role of executive function in the relationship between neurodevelopmental disorder traits and academic achievement in university students. There is evidence for this potential relationship coming from similar studies by A further possible direction for future research could be to consider the roles of traits that overlap between neurodevelopmental disorders, and of co-occurrence of such conditions, in academic achievement. It is possible for neurodevelopmental disorders such as ASD, ADHD, and DCD to co-occur , and theThe results of this study appear to suggest that neurodevelopmental disorder traits alone do not significantly predict achievement. This may provide evidence that also relates to clinical samples; the poorer academic achievement associated with neurodevelopmental disorders may be influenced by factors other than the traits of the neurodevelopmental conditions themselves. However, when ADHD and DCD traits, respectively, interact with executive functioning, they do significantly predict achievement. Thus, the relationship between neurodevelopmental disorder traits and academic achievement may only be significant in neurotypical individuals when executive function is taken into account.However, it may still be possible for individual students with a high level of traits to be at risk of academic underachievement—students with a high level of ADHD or DCD traits and poor executive function may be at risk of lower achievement, although further research is needed to determine whether this result would be replicated and significant in a larger sample of students from a wider range of higher education institutions. Furthermore, as executive function displayed a negative relationship with achievement, this could suggest that executive function may be more of a significant contributor to academic achievement in children than in adult students, however, this area still remains understudied in adults. Given that the percentage of variance in academic achievement accounted for by executive function and traits of ASD, ADHD, and DCD, respectively, was low, this may suggest that there is a possibility of another factor influencing achievement. Future studies that seek to explore this topic further should incorporate laboratory-based methods when assessing executive function in addition to self-report measures relating to everyday tasks, to provide a thorough and reliable insight into the nature of the relationship between executive function, neurodevelopmental disorder traits, and academic achievement.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Psychology and Counselling Departmental Ethics Committee, University of Greenwich, London, United Kingdom. The patients/participants provided their written informed consent to participate in this study.CS contributed to the planning, design, data collection and analysis, and write-up of this research.


Attention deficit hyperactivity disorder (ADHD) has been associated with difficulties in regulating aversion states, high functional impairment, and a high risk of psychopathology across the lifespan. ADHD is clinically heterogeneous, with a wide spectrum of severity and associated symptoms. Clinical characteristics need to be carefully defined in different periods of life as ADHD course, symptoms, and comorbidities may fluctuate and change over time. Adolescence usually represents the transition from primary to secondary education, with a qualitative and quantitative change in environmental and functional demands, thus driving symptoms’ change.In order to characterize age-related clinical features of children (<11 years) and adolescents (≥11 years) with ADHD, we conducted a naturalistic study on 750 children and adolescents assessed for ADHD at our Neuropsychiatry Unit over the course of 3 years (2018–2020).We found that ADHD symptoms were significantly higher in children than adolescents. More importantly, we found worse global functioning, lower adaptive skills, higher levels of anxiety and depressive symptoms, somatic complaints, emotional dysregulation, social problems, and aggression in adolescents, despite a lower severity of ADHD-specific symptoms.These results should be confirmed in longitudinal observational studies of adequate sample size in order to reliably describe a potential course characterized by worsening of functioning, reduction in ADHD-specific symptoms and increase in general psychopathology during the transition from childhood to adolescence. Attention deficit and hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders diagnosed in early childhood and adolescence. According to DSM-5, it is characterized by altered and unusual levels of inattention and hyperactivity compared to those observed in typical child development . ADHD syAttention deficit hyperactivity disorder worldwide prevalence in school-age children is 5.3% , with a In two recent papers we have described clinical characteristics of children and adolescents with ADHD on the base of their selection for first MPH prescription and gender , 10. TheHere we propose a cross-sectional study defining clinical characteristics of children and adolescents with ADHD according to their age. Specifically, we carried out a comparison of psychopathological variables, clinical severity, and functioning measures on a large sample of children and adolescents referred for assessment at our child and adolescent Neuropsychiatry Unit, after a dichotomization into two age groups: patients aged < 11 (ADHD/primary school) and patients with ADHD aged ≥ 11 (ADHD/secondary school).Our main hypothesis was that older patients would display a higher severity of mood-related symptoms and other non-ADHD-specific symptoms, along with higher levels of global functional impairment. Such descriptive characterization could significantly help clinicians personalize treatment strategies after diagnostic assessment.In this observational cross-sectional study, 750 children and adolescents with ADHD who attended the Child and Adolescents Neuropsychiatry Unit of the Bambino Gesù Children’s Hospital  were recruited over the course of 3 years, from 2018 to 2020. We included only children and adolescents with 1) an ADHD diagnosis accordingly to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition—DSM-5  received their diagnosis of ADHD from experienced developmental psychiatrists and neuropsychologists according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria  and 237 adolescents with ADHD aged ≥ 11 (ADHD/secondary school). The division of its groups at age 11 was established considering that in Italy the elementary school cycle ends at about age 10 and the first cycle of secondary school is started at age 11.Considering our sample, 7.87% were Inattentive, 0.93% Hyperactive/Impulsive, 87.33% Combined, and 3.87% ADHD-Not Otherwise Specified (NOS).Psychiatrists and neuropsychologists collaborated in the diagnosis of each case. Psychiatric diagnoses were based on developmental history, extensive clinical examination, and The Kiddie Schedule for Affective Disorders and Schizophrenia for School Aged Children Present and Lifetime Version DSM-5 , a semi-All participants and parents were informed about assessment instruments and treatment options. The study conformed to the Declaration of Helsinki.The data used for the purpose of analysis were obtained retrospectively from the patients’ medical records. The diagnostic evaluation performed at our facility follows a standard procedure: children/adolescents are evaluated on three consecutive days. On the first day, the medical history is collected, and the children/adolescents are tested for cognitive functioning to rule out comorbidity with intellectual disability. Parents fill out several questionnaires to investigate adaptive functioning and emotional and behavioral symptoms. On the second day, a semi-structured interview is administered to children and their parents in order to assess psychopathological aspects and, the clinician completes the impairment scale of functioning. On the third day, children/adolescents undergo a learning/language assessment to rule out other comorbid disorders .To evaluate the global functioning the Children’s Global Assessment Scale (C-GAS)  was admiM = 100, SD = 15).To evaluate IQ, the Perceptual Reasoning Index of the Wechsler Intelligence Scale for Children-IV  or ColorTo assess adaptive skills the questionnaire was administered to parents, namely the Adaptive Behavior Assessment System (ABAS-II) . The staFor the purpose of investigating ADHD symptoms, parents completed the questionnaire Conners’ Parent Rating Scales Long Version Revised–CPRS-R:L . The CPRTo assess behavioral and emotional symptoms the Achenbach System of Empirically Based Assessment (ASEBA) questionnaire was filled out by parents. The CBCL parent questionnaire  is a welThe dysregulation profile (DP) of CBCL, characterized by simultaneous high values (greater than two standard deviations) in three syndromic scales , was calculated using the sum of the T-scores of the three syndromic scales. Scores ≥ 210 are considered clinically significant, those between 180 and 209 are in the borderline range, and those ≤ 179 are non-clinical scores.U Test was used to compare the two groups on age, IQ, ABAS, C-GAS, and DP because the assumption of normality was not fulfilled. Kruskal–Wallis ANOVA was conducted to compare the two groups on CPRS-R:L Scales and CBCL Scales. Bonferroni’s correction for multiple comparisons was applied. For categorical variables, non-parametric analyses were conducted. Specifically, Chi-square analyses were run to test differences between the two groups on gender, ADHD presentation, and drug use. Post-hoc comparison procedures for interpreting Chi-square contingency-table test results were conducted in line with Beasley and Schumacker . Specifically, for continuous variables Mann-Whitney humacker .p < 0.0001, Cohen’s d = 2.70; respectively, M = 7.99, SD = 1.57; M = 13.35, SD = 1.27) but did not differ for gender  and IQ . The two groups differed for ADHD presentation . Post-hoc comparison documented that ADHD/primary school group showed a higher number of children with Hyperactive/Impulsive (p < 0.0001) and NOS (p < 0.0001) than ADHD/secondary school group. Moreover, the two groups did not differ for psychiatric comorbidities . Out of 750 patients, 2% (15 patients) were already in treatment with MPH while 40.7% (305 patients) had a first prescription of MPH after diagnostic assessment. ADHD/primary school and ADHD/secondary school differed for ongoing MPH  and for first MPH prescription   and for adaptive skills derived from ABAS-II scores   see .H(718) = 17.16, p < 0.0001, η2 = 0.004], with mean scores of ADHD/primary school group higher  than those of ADHD/secondary school group . Results on the DSM-IV Hyperactive/Impulsive subscale revealed a significant difference  with mean scores of ADHD/primary school group higher  than those of ADHD/secondary school group  . Results on the DSM-IV Inattentive subscale revealed a significant difference , Somatic Complaints , Social Problems , Aggressive Behavior , but not Attention Problems . DP scores also differed between groups   as within factor and Group (ADHD/primary school vs. ADHD/secondary school) as between factors. Results documented significant differences between the two group in several CBCL subscales, as Anxious/Depressed [.23] see .This observational cross-sectional study investigated age-related clinical characteristics on a group of 750 children and adolescents at their first diagnostic assessment for ADHD at our center.On the epidemiological level, our results were in line with international literature , with a The two groups did not differ for gender and IQ but differed for ADHD presentation as the ADHD/primary school group showed a higher number of children with Hyperactive/Impulsive presentation and ADHD NOS than the ADHD/secondary school group. This is consistent with the observation that younger patients at their first assessment may present more frequently with less specific clinical pictures. Furthermore, at younger ages, functional and academic demands may be less challenging thus keeping some compensated symptoms below the diagnostic threshold. Finally, it is rather typical that hyperactive/impulsive symptoms are significantly more pronounced before pre-pubertal age, with a progressive decline from adolescence to adulthood .Our first main finding is that the two groups differ for functional impairment, and adaptive skills. This is in line with previous evidence that, despite the presence of comorbidity, early ADHD symptoms are among the most important risk factors for impaired daily functioning in adolescence . In partIt should also be noted that additional conditions related to neurodevelopment can significantly impact on functioning. Developmental language delay is one of these conditions, and it is frequently comorbid with ADHD. However, in our sample, developmental delays  have a composite prevalence of 17.35% in subjects < 11 years and 12.26% in subjects > 11 years, and they do not significantly differ between the two groups. Indeed, this prevalence is lower than usually reported (around 30–40%) , 26, altThe second main finding is that ADHD symptoms’ scores  were found to be significantly higher in the ADHD/primary school group as compared to the ADHD/secondary school group. Our results are thus consistent with the typical trajectory of ADHD-specific symptoms, usually showing a gradual decline in the total number of symptoms and/or a severity reduction for certain symptoms’ domains , 23, 28.per se” may exacerbate or even create downstream neural anomalies during the developmental trajectory, so that the presence of pre-existent ADHD symptoms engenders neural dysfunction that in turn exacerbates future symptoms, including general psychopathology, and functioning problems  could be explained in terms of a particular developmental model called “cascading anomalies.” On the base of this model early symptoms of ADHD “problems . In thisproblems , 30 coulproblems .per se.” However, this aspects can mask underlying ADHD-specific symptoms, thus making them more difficult to detect and inducing clinicians to underestimate them  are not available in our sample. For this reason, it is not possible to make reliable considerations on psychopathological evolution after age 11 as assessment after that age can be prone to confounding factors due to puberty. However, it should be also noted that clinical measures used in this study are all based on scores that are standardized on the typically developing general population.Fifth, there is growing evidence supporting a significant association between SARS-CoV-2 related restrictions and contextual-familiar aspects impacting on ADHD symptoms’ severity, along with a significant increase in general psychopathology, especially in adolescence –49. Our Finally, we acknowledge that our paper reports on a much-studied topic in ADHD; for this reason, its originality for readers may be considered limited.Despite these limitations, we reckon that our study has the strength to provide significant and rich clinical information on a very large sample of children and adolescents with ADHD. Taken together, our results confirm a higher level of general psychopathology in adolescents with ADHD as compared to children, along with a higher severity of overall ADHD-specific symptoms in children. More importantly, older patients displayed lower levels of global functioning and poorer adaptive skills despite lower ADHD-specific symptoms’ levels. Functioning could thus remain at a low level despite less symptoms, and functional compromise could worsen due to age-related increased demands. In coping with this condition, general psychopathology phenomena might be triggered or worsened.Indeed, our results should be interpreted cautiously as they lack longitudinal structure and data from healthy controls. Further studies with longitudinal designs and including data from age-matched typically developing subjects are needed in order to clarify whether the developmental trajectory of ADHD between childhood and adolescence is characterized by functional worsening, paralleled by an increase in general psychopathology, and a reduction of ADHD-specific symptoms.Although these results need further confirmation, they preliminarily suggest something that should not be overlooked by clinicians in order to properly tailor multimodal treatment strategies to patients. Specifically, pharmacological treatment and/or more intensive multimodal rehabilitation treatments may be needed in older patients even in presence of a less severe ADHD-specific symptomatology, in order to tackle significant functional impairment and co-existing psychopathology.The data presented in this study are available on request from the corresponding author. The data are not publicly available due to privacy and ethical restrictions.The studies involving human participants were reviewed and approved by Ethics Committee of the Bambino Gesù Children’s Hospital (2541_OPBG_2021). Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin. All procedures were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the Ethics Committee of the Bambino Gesù Children’s Hospital (2541_OPBG_2021). Data were retrospectively selected and completely de-identified at the time of the study. The privacy rights of human subjects were always observed.PD, DM, and SV: conceptualization. PD, BD’A, DM, and SV: methodology. SV and DM: supervision. PD, BD’A, IP, DM, SD, and SV: writing—original draft. PD, BD’A, and DM: writing—review and editing. All authors writing—review and editing, read, and agreed to the published version of the manuscript.


The results revealed that mothers’, fathers’, and teachers’ responses to the Conners 3 rating scale distinguished well between the gifted group and the other two groups, but not between the gifted/ADHD and ADHD groups. The learning difficulties observed by teachers was the most significant element that distinguished gifted/ADHD students from non-gifted ADHD students. Other results indicated that mothers and fathers reported more inattention problems in their gifted/ADHD children than teachers. Additionally, mothers tended to observe more learning and executive function problems in their gifted/ADHD children than teachers did. These findings highlight the importance of multiple informants complementing each other in the assessment process for ADHD in a gifted context to counteract the masking effect between giftedness and ADHD.The potential for the misdiagnosis of giftedness as attention deficit/hyperactivity disorder (ADHD) has been well documented, as has the clinical diagnostic profile of individuals with both giftedness and ADHD. This study aimed to examine parents’ and teachers’ responses to the Conners 3 behavioral rating scale of gifted students with ADHD compared to gifted students without ADHD and non-gifted students with ADHD. Ninety-two children aged 6 to 16 years were included in the study. On the basis of clinical assessments utilizing the K-SADS, the WISC-V, and other neurocognitive tests, the students were split into three groups: gifted/ADHD ( Attention deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders in school-aged children and is characterized by symptoms of inattention and hyperactivity–impulsivity that are present before age 12 and interfere with daily functioning in at least two settings  ,4,5. AddGiftedness and ADHD can co-exist in children. This is known as “twice exceptionality” and is characterized by a potential for high performance in skills or creativity in one or more areas of activity coupled with the presence of a mental health or neurodevelopmental disorder such as ADHD . The preHowever, the accurate diagnosis of ADHD in the gifted population has proven to be very difficult . One of In addition, gifted children may exhibit behaviors that look similar to the characteristics of ADHD, contributing to misdiagnosis. For example, a gifted child who is bored in class because they are not stimulated enough may become agitated, which may resemble some of the symptoms of ADHD. To this end, two studies have shown that pre-service teachers were more likely to assign a diagnosis of ADHD even when the alternative of giftedness was suggested to them ,29. AddiIn the assessment of ADHD in school-aged children, the use of observations provided by multiple informants, especially parents and teachers, is a particularly necessary practice considering that the diagnostic criteria for ADHD require impairment in at least two settings such as at home and at school . In addiNevertheless, two studies have explored the symptoms of ADHD in gifted children using behavioral rating scales. First of all, in their study, Gomez and colleagues  observedn = 21), the lack of comparison groups, and the fact that the children did not have a formal diagnosis of ADHD limit the generalization of the results. Nevertheless, the author states the need for a study to compare between parent and teacher ratings of gifted children—with and without ADHD—as well as non-gifted children—with and without ADHD—to highlight differences in how ADHD symptoms are expressed by gifted children and in how these symptoms are perceived by parents and teachers. The author also claims that there is a need for further understanding of the use of behavioral rating scales, particularly the Conners 3, among gifted/ADHD students.Furthermore, Wood  conducteThe primary objective is to examine parents and teachers’ responses to the Conners 3 behavioral rating scale for gifted/ADHD children compared to gifted students without ADHD (gifted children) and non-gifted ADHD children (ADHD children). Our first hypothesis was that parents and teachers would report more ADHD symptoms in ADHD children than in gifted children or in gifted/ADHD children (H1). Our second hypothesis was that symptoms of inattention, hyperactivity–impulsivity, and learning problems perceived by the parents and the teacher would significantly distinguish gifted children from gifted/ADHD and ADHD children (H2). The secondary goal is to explore the differences between mothers’, fathers’, and teachers’ responses of gifted children, gifted/ADHD children, and ADHD children to the Conners 3 rating scale. We hypothesized that mothers would rate all children more highly on the Conners 3 scale than fathers and teachers (H3). This study will provide us with a deeper understanding of the expression of ADHD in gifted children on the basis of the perceptions of several informants using one of the most widely used behavioral rating scales.ageM = 9.85; SD = 2.51; 73.91% male), along with their parents  and teachers (n = 92). While the gifted/ADHD group  and the ADHD group  were composed of 35 children, the gifted group was composed of 22 children . All were French-speaking participants. Data for all participants were collected from the Child and Adolescent Assessment and Intervention Clinic of the University of Sherbrooke in Longueuil  and from one private clinic in Montreal  from 2015 to 2021. The research project was approved by the Research Ethics Board of the Humanities and Social Sciences Department of the University of Sherbrooke. For the collection of the archival data, only data from records that included a signed consent form for data collection to be used in future research that met the study’s inclusion and exclusion criteria were extracted anonymously and entered into the database.Our clinical sample consisted of 92 drug-naïve children aged six to 16 years  or the General Aptitude Index (GAI) of the Wechsler Intelligence Scale for Children Fifth Edition (WISC-V) ,37. ThesStudents with a mental health disorder  were included in the study to increase the representativeness of the results, thus addressing a limitation raised in previous studies of youth with ADHD  or gifteThe measures  included in the current study were the Wechsler Intelligence Scale for Children   and the The Wechsler Intelligence Scale for Children—fifth edition (WISC-V)  is the mThe Conners Rating Scales—3rd Edition  is widelp-values because of the increased risk of a type I error when making multiples comparisons. For significant MANOVAs, Bonferroni post hoc tests and discriminant analyses were conducted. Conducting of these two types of analyses followed a recommendation by Field (2013) [Analyses were conducted using IBM SPSS (Version 27). The data were screened for normality. The method used in handling data is the listwise detection . Thus, td (2013)  that a dp2; 0.14 = large, 0.06 = medium, 0.01 = small) [Repeated-measures ANOVAs were conducted to explore the differences between mothers’, fathers’, and teacher’s responses to the Conners 3 scale. Each scale was a three-level, within-subject factor that considered all three respondents , and group membership was the between-subject factor. Following Field’s  recommen= small) .ps < 0.03–0.001). Additionally, no significant differences were found in terms of age.p < 0.001, ηp2 = 0.70, and the symptoms scale , λ = 0.24, F = 5.75, p < 0.001, ηp2 = 0.51. As is shown in The MANOVA model addressing the first hypothesis compared the responses to the six content scales and the four DSM-5 symptom scales of the Conners 3 rating scale of the parents and teachers of ADHD children, gifted children, and gifted/ADHD children. Using Wilk’s lambda, there were significant differences in ADHD symptoms at the content scale , λ = 0.12, F = 4.67, The Bonferroni post hoc tests following the significant MANOVAs showed that compared to gifted students, the parents and teachers of ADHD and gifted/ADHD students rated them significantly higher on the “inattention”, “ADHD inattentive type”, “hyperactivity-impulsivity", “ADHD hyperactive type”, “learning problems”, and “executive functions” scales see . Moreove2 = 0.82, whereas the second explained only 9.10%, canonical R2 = 0.31. In combination, these discriminant functions significantly differentiated the groups of children, λ = 0.12, χ2(36) = 139.41, p < 0.001, but removing the first function indicated that the second function did not significantly differentiate the groups, λ = 0.69, χ2(17) = 25.08, p = 0.093. The discriminant function plot showed that the first function discriminated gifted children from gifted/ADHD children and ADHD children, and the second function differentiated gifted/ADHD children from gifted children and ADHD children , and the second function, explaining 10.40% of the variance , significantly differentiated between the groups of children, λ = 0.24, χ2(24) = 102.34, p < 0.001. However, when removing the first function, the second one did not significantly differentiate between the groups, λ = 0.79, χ2(11) = 16.94, p = 0.110. The discriminant function plot showed that the first function discriminated gifted children from gifted/ADHD children and ADHD children, and the second function discriminated gifted/ADHD children from gifted children and ADHD children , the “learning problems” scale  = 5.97, p = 0.003), the “executive functioning” scale  = 4.20, p = 0.017), and the “peer relations” scale  = 3.84, p = 0.023). These analyses also showed that there was a significant difference in the rating of the respondents that was specific to the ADHD group on the “learning problems” scale  = 4.69, p = 0.010), the “executive functioning” scale  = 6.71, p = 0.002), and the “conduct disorder” scale  = 7.24, p = 0.001). Furthermore, for scales with no respondent × group interaction effects, the results revealed the main effects of respondents for all groups combined.The repeated-measures ANOVA design addressing the third hypothesis compared mothers’, fathers’, and teachers’ responses to the Conners 3 content and symptom scales across the three study groups. p < 0.001, ηp2 = 0.34) and fathers  = 14.97, p < 0.001, ηp2 = 0.32). They also tended to rate these students lower than mothers on the “learning problems”  = 8.23, p = 0.007, ηp2 = 0.22) and the “executive functioning” scales  = 7.84, p = 0.009, ηp2 = 0.20). Additionally, fathers were likely to rate ADHD students less highly on the “executive functioning” scale than mothers  = 6.68, p = 0.015 ηp2 = 0.193) and teachers  = 9.16, p = 0.005, ηp2 = 0.25). As for the mothers of ADHD children, they were more likely to rate them higher on the “conduct disorder” scale than fathers  = 7.25, p = 0.012, ηp2 = 0.21) and teachers  = 7.10, p = 0.013, ηp2 = 0.20).A contrast analysis was performed by applying the Bonferroni correction (α/3 = 0.017) to establish between which respondents the differences were significant. These analyses showed that teachers tended to rate students in the gifted/ADHD group lower on the “inattention” scale than mothers  = 15.69, p2 < 0.60), executive function problems (0.27 < ηp2 < 0.53), and learning problems (0.30 < ηp2 < 0.47).The main objective of this study was to examine parents’ and teachers’ responses to the Conners 3 behavioral rating scale regarding gifted/ADHD children compared to gifted children without ADHD and non-gifted ADHD children. The research findings suggested that there were differences between the three groups for all symptoms assessed by the Conners 3 scale, except for those of aggression, conduct disorder, and oppositional disorder according to the teacher, as well as for those of peer relations according to the mother and the father. Specifically, on the basis of responses from mothers, fathers, and teachers, significant differences between the three groups, supported by large effect sizes, were observed for inattention problems (0.53 < ηOur first hypothesis of research (H1) stating that parents and teachers would report more ADHD symptoms in ADHD children than in gifted children or in gifted/ADHD children was partially confirmed. On the one hand, parents and teachers of ADHD children reported more problems with inattention, learning, and hyperactivity–impulsivity than those of gifted children. On the other hand, although teachers reported more inattention and learning problems in ADHD students than in gifted/ADHD students, they reported more hyperactivity–impulsivity problems  in gifted/ADHD children than in ADHD children. As for the second hypothesis (H2) stating that symptoms of inattention, hyperactivity–impulsivity, and learning problems perceived by the parents and the teacher would significantly distinguish gifted students from gifted/ADHD and ADHD students, it was also partially confirmed. As a matter of fact, results from the first discriminant analysis showed that the distinction between the gifted group and the two other groups was mainly explained by the fact that they had fewer attention problems as perceived by the mothers, as well as fewer learning problems as perceived by the teachers. Thus, symptoms of hyperactivity–impulsivity contributed little to this distinction. However, it should be noted that one the clearest distinction between the gifted/ADHD group and the other two groups from this analysis was that the gifted/ADHD group was perceived by teachers as having more hyperactivity–impulsivity symptoms than the others.These findings are consistent with those of Gomez and colleagues , who fouIn terms of symptoms of hyperactivity–impulsivity, the fact that parents and teachers reported more hyperactive–impulsive behaviors in gifted/ADHD and ADHD children than in gifted children is consistent with the study by Gomez and colleagues . MoreoveThe results revealed that the mothers and fathers of gifted/ADHD and ADHD children observed more aggression and oppositional behavior than those of gifted children. Moreover, while mothers and fathers reported more conduct disorder behavior in gifted/ADHD children than in gifted children, only the mothers of ADHD children reported more of this behavior in their children than in gifted children. This is consistent with the study by Antshel and colleagues , which iA secondary objective of this study was to explore the differences between mothers’, fathers’, and teachers’ responses to the Conners 3 rating scale. The results showed that in general, mothers reported more ADHD behaviors than fathers and teachers, supporting our third hypothesis (H3). On the one hand, this finding is consistent with many studies that have shown that mothers are more likely to rate their children as having more behavioral problems than fathers ,66,67,68For the gifted/ADHD group, the results revealed that both mothers and fathers tended to report more inattentive behavior in their child than teachers. Specifically, attention difficulties were found to be clinically significant, according to both parents (T-score ≥ 70), while they were found to be high or average according to the teacher. This finding is consistent with that of Wood , who obsFor the group of children with ADHD, the results raised differences among respondents in the way they rated the executive function and conduct disorder behaviors. First, fathers tended to report less executive function problems than teachers and mothers in children with ADHD, which is consistent with the results of previous studies ,78,79. HFirst, one of the strengths of the study is that it draws on the perceptions of multiple informants , as is suggested in the clinical assessment of ADHD . A seconThis study is innovative in that it explored parents’ and teachers’ responses to the Conners 3 behavioral rating scale to better understand the clinical profile of gifted/ADHD youth. The findings suggested that while the use of the Conners 3 scale clearly distinguishes the gifted group from the other two, it does not clearly distinguish the gifted/ADHD group from the ADHD group. The learning difficulties observed by teachers was the most significant element that distinguished gifted/ADHD students from ADHD students. Additionally, the fact that the parents of gifted/ADHD children rated inattentive behaviors more highly than teachers and that mothers rated behaviors related to learning problems and executive functions more highly than teachers highlights the issue of the masking effect surrounding the identification of a dual neurodevelopmental condition. Thus, the results raised the importance of the complementarity of the different informants in the process of the evaluation of ADHD in a context of giftedness to counter the masking effect. Moreover, in a context where the scientific literature raises the risk of misdiagnosis between ADHD and giftedness , it woul


Neurofeedback training (NFT) has been shown to be effective in treating several disorders ; however, little is currently known regarding the effectiveness of remote NFT systems.This retrospective study provides real-world data (N=593) to assess the efficacy of app-based remote NFT in improving brain health and cognitive performance.Improvement was measured from pre- to postintervention of in-app assessments that included validated symptom questionnaires , a cognitive test of attention and executive functioning , and resting electroencephalography (EEG) markers. Clinically significant improvement was evaluated using standard approaches.The greatest improvement was reported for the anxiety questionnaire, for which 69% (68/99) of participants moved from abnormal to healthy score ranges. Overall, adult and child participants who engaged in neurofeedback to improve attention and executive functions demonstrated improved ADHD scores and enhanced performance on a cognitive  task. Adults with ADHD additionally demonstrated elevated delta/alpha and theta/alpha ratios at baseline and a reduction in the delta/alpha ratio indicator following neurofeedback.Preliminary findings suggest the efficacy of app-based remote neurofeedback in improving mental health, given the reduced symptom severity from pre- to postassessment for general psychological health, ADHD, anxiety, and depression, as well as adjusted resting EEG neural markers for individuals with symptoms of ADHD. Collectively, this supports the utility of the in-app assessment in monitoring behavioral and neural indices of mental health. Neurofeedback training (NFT) is considered a primary or supplementary treatment for a number of disorders, including attention-deficit/hyperactivity disorder (ADHD) -5, anxieUnlike standard EEG systems, Myndlift is an easy-to-use tool for patients and clinicians . While wReal-world studies provide external validity and accurately represent the heterogeneity of a patient population . From threlative high-frequency power  [Given the success of neurofeedback for child ADHD, more adults with ADHD are turning to NFT for treatment. Currently, 6.76% of adults worldwide—translating to 366.3 million people—are affected . ADHD isnd beta) ,26-28, ond beta) ,30; howend beta) ,32 may nnd beta) . This mand beta) ,35. For nd beta) ,36, a rend beta)  suggestend beta) -43, whilnd beta) ,45. GiveParticipants, 13 years of age or older, signed up through their clinician or a clinician suggested by Myndlift and completed NFT at home or in clinic in a clinical care context. Informed consent was provided through the app, allowing participants’ anonymized data to be used for research. Data were included for analysis if baseline  assessment was conducted after 7 or fewer NFT sessions . For analyses of improvement, postintervention sessions occurred 30 to 180 days after baseline with 20 or more NFT sessions completed . An averProcedures were reviewed by an independent Institutional Review Board (IRB)—Pearl IRB—who permitted IRB exemption for analyses of data previously collected and deidentified, following the guidelines of the Declaration of Helsinki.Participants performed neurofeedback protocols  that werThe in-app assessment includes 14 brief standardized questionnaires commonly used to screen for mental health conditions. In this study, data were reported for the following five questionnaires completed at baseline and follow-up by at least 25 participants: the 12-item General Health Questionnaire (GHQ-12) , the ADHThe assessment contained an 8-minute CPT, a behavioral test of response inhibition, in which participants are instructed to tap the screen when the target object  is shown, but not when other stimuli appear. The interstimulus interval and presence of audiovisual distracter stimuli were varied throughout the task. Outcomes included average response time (RT) and response time variability , as well as omission and commission errors related to inattention and impulsivity, respectively . This tyResting EEG was recorded from 9 electrodes . The EEG assessment was divided into five sequential  phases; in each phase, the auxiliary electrode was placed at a different scalp location: central (Cz), frontal (Fz), left (F3), right (F4), and back or posterior (O1). Each phase was split into eyes-closed and eyes-open blocks. A block continued until 30 seconds of clean EEG—sampled at 256 Hz—had been recorded, which typically took up to 45 seconds.d), and percent of users with clinically significant improvement, defined as 20% improvement [t tests (2-tailed) evaluated statistically significant improvement for each clinical measure (P<.05). By convention, small, medium, and large effects correspond to d=0.2, d=0.5, and d=0.8, respectively. For symptom questionnaires, CPT, and resting EEG analyses, multiple comparisons were corrected using the Benjamini-Hochberg (BH) method [P=.05, reported as BH-adjusted P values (PBH). The Levene test assessed assumptions of equality of variance and corrected for inhomogeneities.Questionnaire results were analyzed in terms of improvement in total score from pre- to postintervention, including mean change in points, effect size  method  to maintz scale—indicates a significant reliable change, similar to others [CPT results were analyzed for participants who completed child  or adult  ADHD questionnaires. Results are given in terms of improvement in RT and SDRT for correct responses , commission errors, and omission errors. This includes mean change, in milliseconds or errors, and effect size. RT and SDRT scores were standardized by age to minimize age effects on performance . Percento others .t tests were conducted for each power ratio across groups . Frequency bands were defined as follows: delta (1-4 Hz), theta (4-8 Hz), alpha (8-13 Hz), and beta (13-30 Hz). These were averaged across frontal electrodes  were separated into groups with abnormal and healthy scores (d=0.99 to 2.41), while the effect sizes for groups with healthy results were large only for child and adult ADHD questionnaires. Improvement in the groups with abnormal results was statistically significant for all questionnaires, with the majority  of users demonstrating clinically significant change  [Results for participants who completed symptom questionnaires  ,66. The =99) for average RT, SDRT, omission errors, and commission errors were divided by abnormal versus healthy scores for child and adult ADHD combined , where nearly half of the participants  demonstrated clinically significant improvement, as indicated by the RCI. Although average RTs improved comparably , differences between pre- and postintervention were significant only for the healthy results group (d=0.56). At least one-third of users improved in their commission errors  and omission errors  from pre- to postintervention. Results from a group (n=104) with unknown ADHD assignment were comparable to those of groups with abnormal and healthy results  and enhanced high beta  protocols. Most adults also performed enhanced alpha , whereas most children also performed enhanced low beta  and enhanced SMR . Results (ncombined . The gre results .=271) in frontal regions  with eyes closed from participants scoring in abnormal (n=125) or healthy ranges (n=146) on the adult ADHD questionnaire.The DAR, TAR, and TBR were calculated from baseline resting EEG data  had significantly greater frontal DAR than healthy participants . The Levene test indicated unequal variances , so degrees of freedom were adjusted from 269 to 235. Post hoc independent-samples t tests confirmed that results were driven by participants in the abnormal results group having significantly greater frontal delta power  and less frontal alpha power  than healthy participants.Regarding the DAR, an independent-samples t test reported a significant difference for the frontal TAR , as participants with abnormal scores  had significantly greater ratios than those with healthy scores . Post hoc t tests confirmed that results were driven by less frontal alpha, as opposed to differences in theta .Regarding the TAR, a comparable t test reported no significant difference between participants with abnormal scores  and those with healthy scores .Regarding the TBR, a final Changes in the DAR, TAR, and TBR in the frontal regions with eyes closed were reported for participants (n=41) scoring in the abnormal (n=20) or healthy ranges (n=21) of the adult ADHD questionnaire . Most paThis retrospective study offers initial evidence of therapist-guided remote neurofeedback as an effective tool for reducing subjective symptoms, improving objective cognitive performance, and adaptively modifying EEG markers. Improvements in attention were evident in children and adults with ADHD, as well as healthy participants. Findings suggest that the TBR is not a reliable marker for adult ADHD, instead demonstrating alternative elevated slow/fast power ratios . MoreoveBased on real-world data, significant improvement was reported across standardized questionnaires. The greatest improvement was observed in participants with abnormal anxiety scores, where most received reduced theta, enhanced high beta, and enhanced alpha protocols. As anticipated, greater effect sizes were observed for participants with scores in the abnormal versus healthy ranges. Interestingly, healthy participants and those with ADHD, both children and adults, demonstrated significant improvement with large effect sizes after completing primarily reduced theta and enhanced high beta protocols, as well as adults who completed enhanced alpha protocols or children who completed reduced low beta and reduced SMR protocols. Consistent with the literature -35, our Apart from the child ADHD assessment, questionnaire analyses included large total sample numbers , and after an average of 53 NFT sessions, 57% to 78% of the participants demonstrated significant improvement, depending on the questionnaire. Results were particularly impressive compared to other in-app mental health therapeutics -76, suchNFT led to greater consistency in response times on a response inhibition task for subjects scoring in healthy or abnormal ADHD ranges, agreeing with similar reports of subjects with ADHD ,80. In aResting EEG findings demonstrated that elevated DAR and TAR were indicative of adult ADHD at baseline. This translated to significantly higher levels of delta and lower levels of alpha, as previously reported in adults with ADHD -42,81,82In contrast to our work and that of others, several groups reported high alpha power at baseline during eyes-closed conditions in adult ADHD populations ,86, or r, resulting in influence over varied frequency bands. Moreover, as this population reflects real-world use, the likelihood of these two forms of treatment to have commenced simultaneously, for treating symptoms of depression, anxiety, and ADHD, would arguably be low. Those seeking treatment with remote neurofeedback most often do so to avoid taking pharmaceuticals [Study results are encouraging, but conclusions should be tempered by limitations, including small subgroup sample sizes and lack of control groups. Moreover, subjects may have received alternative treatment in parallel  that could influence symptom improvement as well as alter neuromarkers. For example, two studies administering stimulants  to treat symptoms of ADHD in adults demonstrated altered delta ,91 and teuticals ,93 or, reuticals . Frank Heuticals , a HarvaPreliminary findings from this retrospective pilot study demonstrate efficacy of remote NFT in improving mental health, particularly for individuals with symptoms of ADHD and anxiety, mainly through reduced theta, enhanced high beta, and enhanced alpha NFT protocols. Moreover, adult ADHD was distinguished from healthy individuals by elevated frontal DARs, where ratios were significantly reduced following NFT. The effectiveness of the system in a real-world population via remote use positions it as an affordable and accessible alternative to clinic-based systems.