Herein, Bi2S3 is proposed as a promising cathode material for rechargeable aqueous ZIBs. Improved cyclic stability and fast diffusion of Zn2+ is observed. Also, the layered structure of Bi2S3 with the weak van der Waals interaction between layers offers paths for diffusion and occupancy of Zn2+. As a result, the Zn/Bi2S3 battery delivers high capacity of 161 mAh g−1 at 0.2 A g−1 and good cycling stability up to 100 cycles with ca. 100% retention. The battery also demonstrates good cyclic performance of ca. 80.3% over 2000 cycles at 1 A g−1. The storage mechanism in the Bi2S3 cathode is related to the reversible Zn ion intercalation/extraction reactions and the capacitive contribution. This work indicates that Bi2S3 shows great potential as the cathode of ZIBs with good performance and stability.Aqueous Zn ion batteries (ZIBs) are promising in energy storage due to the low cost, high safety, and material abundance. The development of metal oxides as the cathode for ZIBs is limited by the strong electrostatic forces between OThe online version of this article (10.1007/s40820-019-0352-3) contains supplementary material, which is available to authorized users. Poise−1) –16. Desp2− from M–O where M = Mn or V. Such concern is amplified for ZIBs as compared to LIB due to the shuttling of densely positive charged Zn2+ across the material which may lead to strong electrostatic forces between O2− and Zn2+ [2+ onto O2− is to replace oxide in metal oxide with sulfide. Even though metal sulfides are less studied in ZIBs than metal oxide, the anion replacement from O2− to S2− may reduce the tendency of these electrostatic “adhesion” and therefore leading to improved cyclic stability and minimizing the initial irreversible capacity loss [2 [2S3 is a semiconductor material with a narrow band gap of 1.3 eV, and high ionic conductivity which have attracted significant attention in electrochemistry application. In particular, the highly anisotropic Bi4S6 layers that are held together by weak van der Waals interaction provides sufficient pathway for foreign ions to intercalate into. As such, it has been studied as lithium-ion battery, and sodium ion battery cathodes [2+ storage.The most widely studied ZIBs cathode materials remain to be metal oxides such as vanadium-based oxides and manganese-based oxides –21. Despand Zn2+ , 22. Theand Zn2+ , 24. An ity loss , 22. Fur loss [2 , and thicathodes , 27. Suc2S3 is investigated as ZIBs cathode in this work. Bi2S3 nanoparticles were synthesized using a facile chemical method followed by calcining. Bi2S3 with layered structure offers paths for fast diffusion and occupancy of Zn2+, and also shows good cyclic stability. The as-prepared Bi2S3 delivers a high capacity of 161 mAh g−1 at a current density of 0.2 A g−1 and exhibits enhanced cyclic stability (100% retention after 100 cycles at 0.2 A g−1) as the cathode for ZIBs. The energy storage mechanism of the Bi2S3 electrode is revealed by a series of measurements. Results demonstrate that the capacitive process and the intercalation/deintercalation of Zn2+ in the Bi2S3 interlayer occur during discharging/charging processes. Our finding shows that Bi2S3 is a promising cathode material with high capacity and good stability for the development of high-performance aqueous Zn ion battery system.Hence, motivated by this phenomenon, Bi2S, Bi(NO3)3·5H2O, and ZnSO4·7H2O were purchased from Sigma-Aldrich. Acetic acid was purchased from Fluka. Carbon paper  was purchased from Ce-Tech Co. Ltd.Na2S3 nanoparticles were synthesized by a simple chemical reaction followed by a simple calcining method. Typically, 0.97 g of Bi(NO3)3·5H2O was dissolved into 100 mL H2O containing 9 mL acetic acid. Then, 30 mL of Na2S solution (0.003 mol) was added into the above solution and kept for stirring 2 h. The solid were collected by centrifugation, washed with ethanol and distilled water for three times, and then dried at 60 °C. The dried solid was then heat-treated in a vacuum oven at 200 °C for 3 h to yield crystallized Bi2S3 nanoparticles.BiThe powder X-ray diffraction (XRD) pattern was measured by a powder diffractometer (Bruker D8 Advanced Diffractometer System) with a Cu Kα (1.5418 Å) source. Scanning electron microscopy (SEM) images were recorded on a ZEISS SEM Supra 40 (5 kV). Transmission electron microscopy (TEM) was performed on a JEOL-3010 (300 kV acceleration voltage). TEM samples were prepared by dripping the sample solutions onto a copper grid. Surface composition was studied by X-ray photoelectron spectroscopy (XPS) using a Kratos Analytical Axis UltraDLD UHV spectrometer with a monochromatized Al Ka X-ray source (1486.6 eV) scanning a spot size of 700 µm by 300 µm.2S3 nanoparticles were mixed with carbon black and polyvinyl difluoride in a 7:2:1 weight ratio with N-methyl-2-pyrrolidone. The mixture was hand-grinded and then coated onto the carbon paper, and finally dried at 80 °C for further use as cathode. Zn foil was used as the anode and filter paper was applied as the separator. 2 M of ZnSO4 was employed as the electrolyte. For both cyclic voltammetry and charge/discharge tests, the voltage was measured in the range of 0.4–1.2 V. The current densities of 0.2, 0.3, 0.4, 0.5, 0.6, 0.8, 1, 2, 3, 4, 5, 6, 8, and 10 A g−1 were selected for charge/discharge test. Electrochemical impedance spectroscopy was tested in the frequency range from 0.01 to 105 Hz. Specific capacity, energy density, and power density were determined using the mass of the active material from the cathode. The mass of the active material is about 1 mg, pasted onto a 1.2 cm in diameter carbon paper.All electrochemical tests were tested using an electrochemical station (Bio-logic VMP 3) at room temperature. A CR2025-type coin cell was constructed to evaluate the electrochemical performance. The as-prepared Bi2S3 nanoparticles were synthesized via a simple chemical reaction followed by calcination. The XRD pattern of the obtained Bi2S3 nanoparticles displays a high degree of crystallization. All the diffraction peaks of the obtained sample can be indexed to orthorhombic Bi2S3 (JCPDS No. 17-0320)  is obtained with a Brunauer–Emmett–Teller surface area of 16 m2 g−1, and the H1 hysteresis loop demonstrates the presence of mesopores [2S3 is expected to show good electrochemical performance.TEM images show that the Biogy Fig. d, e. Theage Fig. f. The SAesopores . The por2S3 cell using Bi2S3 as cathode and Zn foil as anode in an aqueous solution of 2 M ZnSO4. Figure 2S3 cell at scan rate of 0.5 mV s−1 in the voltage window of 0.4–1.2 V. Obvious redox peaks could be observed, which may be related to the interaction between Bi2S3 and Zn ions. In addition, galvanostatic discharge/charge (GCD) profiles are in accordance with the CV curves, which show one plateau around 0.6 V . The good stability indicates that the Bi2S3 is a promising material for Zn ion battery application.The energy and power densities of the Zn/Bi2S3 battery to study the detailed reaction kinetics. Figure 2S3 shows low resistance of Rs , RCT , and ZW (936.2 OhΩ), illustrating the fast reaction kinetics. The fast reaction kinetics could be attributed to the reduced electrostatic “adhesion” of Zn2+ onto anion S2− which leads to fast diffusion of Zn2+. To reveal the electrochemical kinetics of the Bi2S3 electrode, CV curves at different scan rates from 0.1 to 0.5 mV s−1 are studied in Fig. i) and scan rates (v) is shown as Eq. b is defined as the slope of log(i) versus log(v) curve. Typically, the value of b (0.5–1) is related to the type of electrochemical process. When b value reaches 0.5, it indicates that the electrochemical kinetics process is dominated by ionic diffusion. Surface capacitive effects become dominant as the b value is 1. From Fig. b values for peak 1, 2, and 3 are determined to be 0.81, 0.91, and 0.97, separately. These b values hint that the ionic diffusion along with surface capacitive effects would control the electrochemical kinetics reaction for Zn/Bi2S3 cell. The contribution from capacitor-like and diffusion-controlled processes can further be determined by Eq. i is related to the total current response, k1v represents current from surface capacitive effects, and k2v1/2 means current because of ionic diffusion process. As k1 could be achieved via fitting i/v1/2 versus v1/2 plots, the contribution from capacitive effect is determined to be 86.5% at scan rate of 0.1 mV s−1. As scan rate increases, the percentage of capacitive contribution is up to 90.1%, 91.8%, 92.8%, and 93.5% at 0.2, 0.3, 0.4, and 0.5 mV s−1, respectively  measurements are performed on the Zn/Bi4·3Zn(OH)2·4H2O (JCPDS No. 09-0204) is successively formed during the discharge process. Subsequently, ZnSO4·3Zn(OH)2·4H2O disappears after being fully charged to 1.2 V. These results demonstrate the reversible formation/decomposition of ZnSO4·3Zn(OH)2·4H2O during the discharge/charge process. The storage mechanism was also investigated by the XPS spectra at different charge/discharge states 2 and ZnSO4 from ZnSO4·3Zn(OH)2·4H2O, separately [2+ peaks at 1023.3/1046.3 eV associated with the inserted Zn2+ in Bi2S3 increases, confirming the Zn2+ insertion process.The storage mechanism is investigated by ex situ XRD, XPS spectra, SEM–EDX elemental mappings and TEM. Before charge/discharge process, we performed CV for 30 cycles to get a stable state. From the charge/discharge processes as shown in Fig. parately . Meantim2+ in Zn(OH)2 and ZnSO4 from ZnSO4·3Zn(OH)2·4H2O gradually disappear, further confirming the reversible conversion of ZnSO4·3Zn(OH)2·4H2O, consistent with the XRD result. Simultaneously, the peak intensity gradually decreases for the inserted Zn2+ in Bi2S3. It indicates the continuous and reversible intercalation/extraction of Zn2+ in Bi2S3 during the electrochemical processes. SEM–EDX elemental mappings of the fully discharged Bi2S3 electrode are shown in Fig. S3. Obviously, elemental Zn is uniformly distributed in the Bi2S3 nanoparticles, which confirms the insertion mechanism of Zn ion into Bi2S3 layers.During the charging process, the peaks associated with the Zn2S3 electrode was further investigated by TEM analysis. For the Bi2S3 electrode at the fully discharged state, in Fig. 4·3Zn(OH)2·4H2O, indicating the generation of ZnSO4·3Zn(OH)2·4H2O during the discharge process, consistent with the XRD and XPS analysis. Also, Bi2S3 with nanoparticles structure could be observed. The lattice spacing of 0.61 nm, which was enlarged when compared with that of the fresh Bi2S3 with lattice distance of 0.503 nm, was clearly observed in the HRTEM image 2·4H2O is successively formed which is confirmed by the XRD, XPS (the detected Zn2+ peaks in Zn(OH)2 and ZnSO4 from ZnSO4·3Zn(OH)2·4H2O) and TEM (the observed interplanar distances of ca. 1 nm for ZnSO4·3Zn(OH)2·4H2O) results. Meantime, Zn2+ is inserted into Bi2S3 as revealed by the XPS (enhanced Zn2+ peaks intensity of the inserted Zn2+ in Bi2S3), TEM (enlarged lattice distance of 0.61 nm for Bi2S3), and SEM–EDX elemental mappings (uniform distribution of Zn2+ in the discharged Bi2S3) results. During the charging process, ZnSO4·3Zn(OH)2·4H2O gradually disappears. These results demonstrate the reversible formation/decomposition of ZnSO4·3Zn(OH)2·4H2O during the discharge/charge process. At the same time, Zn2+ ions are extracted from Bi2S3 as demonstrated by the decreased XPS intensity of Zn2+ ions. Overall, the designed Bi2S3 electrode shows high zinc ion storage performance with faster reaction kinetics, higher capacity and better long-term cycles, presenting a potentially safe, durable, and low-cost device for large-scale energy storage.Hence, based on the collective results, the electrochemical mechanism of Zn/Bi2S3 nanoparticles as cathodes for aqueous rechargeable ZIBs. The obtained Bi2S3 nanoparticles display high capacity of 161 mAh g−1 at current density of 0.2 A g−1. Good rate behavior is demonstrated, and the Zn/Bi2S3 cells show good cycling stability over 100 cycles. At high current density of 1 A g−1, the cell still keeps 80.3% retention after 2000 cycles. Mechanistic details of the Zn storage based on surface capacitive effects and Zn2+ ions insertion are demonstrated. The high capacity, good stability, and low cost make our battery promising for stationary energy storage applications.In conclusion, we report a simple chemical method followed by calcining to synthesize BiSupplementary material 1 (PDF 299 kb)Below is the link to the electronic supplementary material.


P < 0.05). The Planctomycetes was the most abundant phyla both in native Tibetans and in Hans. Furthermore, the most relatively abundant phyla for native Tibetans were Bacteroidetes (15.66%), Firmicutes (11.10%), Proteobacteria (1.32%), Actinobacteria (1.10%), and Tenericutes (0.35%), while the most relatively abundant phyla for Hans were Bacteroidetes (16.28%), Firmicutes (8.41%), Proteobacteria (2.93%), Actinobacteria (0.49%), and Cyanobacteria (0.21%). The abundance of the majority of genera was significantly higher in Tibetans than in Hans (P < 0.01). The number of microbial genes was 4.9 times higher in Tibetans than in Hans. The metabolic pathways and clusters of orthologous groups differed significantly between the two populations (P < 0.05). The abundance of carbohydrate-active enzyme modules and antibiotic resistance genes was significantly lower in Tibetans compared to Hans (P < 0.05). Our results suggest that different genetic factors (race) and environmental factors (diets and consumption of antibiotics) may play important roles in shaping the composition and function of gut microbiota in populations living at high altitudes.The human gut microbiota is affected by genetic and environmental factors. It remains unclear how host genetic and environmental factors affect the composition and function of gut microbiota in populations living at high altitudes. We used a metagenome-wide analysis to investigate the gut microbiota composition in 15 native Tibetans and 12 Hans living on the Tibetan Plateau. The composition of gut microbiota differed significantly between these two groups ( The gut microbiota plays important roles in maintaining normal physiological and metabolic functions of the human body , 2. It cAbout one-third of the gut microbiota is common to most people , but theAnother factor that affects the gut microbiota is geographic location and its associated natural environment , 12. NatThe native Tibetans have developed unique lifestyles and dietary habits to adapt to the special plateau environment. Colonoscopy exams of more than 6,000 native Tibetans showed that they have much lower rates of intestinal polyps, adenoma, colon cancer, and other intestinal diseases, compared to people who live at lower altitudes, especially in the coastal areas of China or in western countries . TherefoEnterococcaceae, Prevotellaceae, Prevotella, and Enterococcus, in comparison to other populations [Metagenomic analysis, including 16S rRNA sequence analysis, of human gut microbiota has revealed many functional roles of the gut microbiota to human hosts , 16. Usiulations . We alsoulations . In thisThe participants in this study included 15 native Tibetans and 12 Hans. The Han population migrated to and has lived in Lhasa for over 10 years. The Tibetans included 8 men and 7 women between 32 and 44 years old. The Hans included 6 men and 6 women between 33 and 43 years old. Physical examination and medical records in the People's Hospital of Tibet Autonomous Region showed that the participants had no bowel diseases or metabolic diseases and had not taken any antibiotics within 2 months prior to sample collection. The native Tibetans followed the traditional lifestyle and dietary habits of their ethnic group. Meat, Zanba (a roasted barley flour), and dairy products formed their major diet, while few vegetables and fruits were consumed. The Hans followed their traditional dietary habits, which included wheat, rice, and more vegetables/fruits. The study was approved by the Ethics Committee of Guangzhou First People's Hospital of Guangzhou Medical University. Written informed consent was obtained from all individual participants prior to the study.Approximately 20 g fresh fecal samples were collected in sterilized 10 mL centrifuge tubes. All samples were collected by trained doctors from the First People's Hospital of Guangzhou and the People's Hospital of Tibet Autonomous Region. DNA in fecal samples was extracted using the E.Z.N.A. Stool DNA Kit  according to the manufacturer's instructions.DNA libraries were constructed with a mean insert size of 300 bases using the TruSeq™ DNA Sample Prep Kit according to the manufacturer's instruction . The libraries were amplified by polymerase chain reaction (PCR) and sequenced using 100 base paired-end reads on the Illumina HiSeq System (Illumina); the reads were deposited into the NCBI short read archive database (SRP199009). The high quality reads after quality control were used for further analysis, including all abundance analysis.http://blast.ncbi.nlm.nih.gov/Blast.cgi). Microbial species were determined by BLAST analysis of the clean reads against the small subunit rRNA (SSU rRNA) database (https://www.arb-silva.de) [Basic Local Alignment Search Tool (BLAST) analysis was conducted using BLAST Version 2.2.28+ (ilva.de) , 19.Principal component analysis (PCA) was performed based on the composition of the bacterial communities as described previously . Principhttp://soap.genomics.org.cn). Contigs longer than 100 bp were then used to predict open reading frames (ORFs) using MetaGeneAnnotator [http://metagene.cb.k.u-tokyo.ac.jp). The nonredundant ORFs, as well as the clusters of nonredundant ORFs, were predicted using CD-HIT software [http://www.bioinformatics.org/cd-hit). The abundance of nonredundant ORFs was calculated using SOAPaligner software (http://soap.genomics.org.cn/).Contigs were constructed using SOAPdenovo software (version 1.3)  (http://nnotator  (http://software  (http://http://eggnog.embl.de).Clusters of orthologous groups (COGs) were predicted based on ORFs using BLAST analysis against the eggNOG database  pathways and modules were predicted by BLAST analysis of the high quality reads against the KEGG database.http://www.cazy.org) using hmmscan software (http://hmmer.janelia.org/search/hmmscan). The antibiotic resistance genes were predicted using BLAST analysis against the antibiotic resistance gene database [http://ardb.cbcb.umd.edu).The abundance of carbohydrate-active enzymes was analyzed by comparing the clean reads to the carbohydrate-active enzyme database  < 0.01 were considered statistically significant.Wilcoxon rank-sum test was used to compare the statistical differences between the microbiota of the two populations. Both a P < 0.01). In contrast, no significant difference was found for other parameters including age, gender, and BMI (P > 0.05).The baseline and physical characteristics of the study population are listed in After removing low quality reads and host sequences, averages of 22,407,937 and 30,918,028 high quality reads were obtained from the fecal DNA samples of native Tibetans and Hans, respectively , Firmicutes (11.10%), Proteobacteria (1.32%), Actinobacteria (1.10%), and Tenericutes (0.35%), while the most relatively abundant phyla for Hans were Bacteroidetes (16.28%), Firmicutes (8.41%), Proteobacteria (2.93%), Actinobacteria (0.49%), and Cyanobacteria (0.21%). A total of 1,625 genera were identified, among which 1002 genera were shared between Tibetans and Hans, but 217 genera were in Tibetans only and 406 genera were in Hans only (Wilcoxon rank-sum test showed that many of the microbes from the two populations differed significantly at both phylum  and genuP < 0.01) (P < 0.01). Only three genera, including Myroides, Nitrosomonadaceae_uncultured, and SC-I-84_norank, were more abundant in Hans than in Tibetans (P < 0.01) . The top 10 most abundant COGs in each ethnic group are listed in The identified genes were further analyzed according to the COGs, which are classified into different functional categories. As shown in P < 0.05, The abundance of 61 metabolic pathways was identified to be significantly different between the native Tibetans and Hans (P < 0.05). All modules, except module M00178 (bacteria ribosome that is involved in RNA/protein processing), were more abundant in the Han population than in the native Tibetans (P < 0.05) , and the relative abundance of the carbohydrate-active enzyme module was calculated. The abundance of carbohydrate-active enzyme modules is significantly higher in the Hans than in the native Tibetans (P < 0.05). And the most abundant enzyme module for both the native Tibetans and the Hans was glycoside hydrolases, followed by glycosyltransferases , we analyzed the relative abundances of antibiotic resistance genes in the gut microbiota of the native Tibetans and Hans. Among the 373 types of antibiotic resistance genes available in the database, we identified 56 types in the Han samples (P < 0.05). P < 0.05)  . In addiIn this study, the numbers of microbial species (at both phylum and genus levels) and numbers of genes were greater in Tibetans. The difference of average ORF length in the two groups may be the possible reason for this result. Additionally, the gene copy numbers in each phylum were higher in the Hans than in the native Tibetans. This also explains, in part, the higher number of high quality reads in the Han population. It is not clear why the gene length was shorter in the Tibetan samples. It is possible that DNAs from different samples have different sensitivities to PCR amplification and/or the sequencing method . We can Bacteroides species are dominant in people who consume more proteins and animal fats, whereas the Prevotella species, which are rich in genes for cellulose and xylan hydrolysis, are predominant in those who eat more carbohydrates and fibers [Prevotella was most abundant in native Tibetans, while Bacteroides was the most abundant genus in the Hans. However, the native Tibetans normally consume more proteins (meat and dairy products), while the Hans consume more carbohydrates (wheat and rice) and vegetables. The abundance of Bacteroides and Prevotella in native Tibetans and Hans was apparently different from previous reports [Prevotella was found to make up more than 50% of the gut bacteria in children from rural Africa but was absent in children living in more industrialized Europe [Prevotella was predominant in native Africans who lived in rural areas and Bacteroides was more abundant in urbanized African Americans [It has been reported that the d fibers . Interes reports . We specd Europe . A similmericans . It is pmericans , 30. TheMyroides was the second most abundant genus in Hans and the third most abundant genus in native Tibetans. Myroides is not a common bacterial genus found in human gut microbiota but rather is commonly found in the environment [Myroides was reported to be associated with chronic obstructive pulmonary disease and pneumonia [In the present study, we also found that ironment . Also, Mneumonia , which mneumonia .In our study, we found that many metabolic pathways differed greatly between the gut microbiota of the two populations. For example, the tropane, piperidine, and pyridine alkaloid biosynthesis pathway, which is required for metabolism and biosynthesis of other secondary metabolites, was significantly different. The abundance of this pathway was significantly higher in the Hans than in the native Tibetans, suggesting that microbes in Hans have a higher capacity for synthesizing secondary metabolites.Studies have shown that antibiotic usage affects the assembly of the microbiota and is associated with increased risks of diseases , 34. A r


The main objective of this study is to investigate the multiple relations and to determine the differences between executive functions (EFs), emotion regulation, and behavioral and emotional problems in children with attention-deficit/hyperactivity disorder (ADHD), borderline intellectual disability (ID), and typical development (TD). The sample included 85 children aged 6 to 11 years, 42 with typical development (TD), 27 with ADHD, and 16 with borderline ID. The results emphasized a positive correlation between adaptive emotion regulation strategies and EFs, and no significant relations between the maladaptive emotion regulation strategies and EFs. In addition, the executive function of planning correlated negatively with anxiety, ADHD symptoms, and conduct problems. The performance of both clinical groups regarding EFs was significantly lower than that of the TD group, and they differed significantly from each other only on visual attention. The presence of oppositional-defiant and conduct problems was higher in both clinical groups than in the TD group, and more anxiety symptoms were reported in children with ADHD. This study supports the idea that emotion regulation, Efs, and clinical symptoms are interconnected. It also profiles the deficits in cognitive functioning and emotion regulation in two clinical groups, thus helping future intervention programs. One of the key concepts in developmental psychopathology is that of executive dysfunction. Several developmental disorders have been associated with deficits in executive functions (EF), including attention deficit and hyperactivity disorder (ADHD)  and inteEmotion dysregulation is also common in individuals with neurodevelopmental disorders, including ADHD and ID. Emotion regulation is a component of the broader concept of self-regulation. Diamond (2013) claims that self-regulation “refers primarily to control and regulation of one’s emotions and overlaps substantially with inhibitory control”, an important component of executive functions (EFs) ,5. Some Theories on ADHD suggest that deficits in EFs are at the core of the ADHD-syndrome and play a key role in explaining the problems that children with ADHD confront in daily life ,10. EvidWhen it comes to intellectual disability (ID), emotion dysregulation has received little attention. Individuals with ID may experience deficiencies in the awareness and understanding of their emotional experience, and possibly an increased predisposition to rigidly adhere to a specific self-regulatory response  . They teOne of the most influential taxonomies of EFs is that proposed by Miyake et al. (2000) ,17,18. TIn ADHD, clinicians and researchers reported poor inhibition ,20 and iResearch also documents a clear EFs impairment in ID. Children with ID display deficits in WM, auditory sustained attention, visual selective attention, visual categorization, inhibition, and planning when compared to the performance of a mentally age-matched group ,23,24. IThe relation between emotion regulation, EFs, and behavioral problems has received little attention. Having deficits in emotion regulation is an important risk factor for conduct problems . Self-reThe main objective of our study is to investigate the multiple relations and to determine the differences between EFs, emotion regulation, and the behavioral/emotional problems in children with ADHD, borderline ID, and typical development (TD). Within this objective, we aim to test a mediation model, considering that the relationship between emotion regulation and conduct problems is mediated by planning, a high-order EF. Most studies on EFs in neurodevelopmental disorders have focused on the core EFs, but we assessed other EFs, such as visual attention, planning, and STM (as a component of WM). Unlike EFs, emotion regulation in ADHD has been the subject of few studies. The research on EFs and emotion regulation in children with borderline ID is scant. Moreover, we used a multi-method approach for assessing emotion regulation , thus making possible a more comprehensive assessment of the concept. We conducted a prospective study on 85 children aged 6 to 11 years , 42 typically developed (TD) children  and 43 diagnosed with attention-deficit/hyperactivity disorder (ADHD) or borderline intellectual disability . The TD children sample included 22 girls and 20 boys, recruited from a public school in Gherla. Twenty children were first-graders and 22 were third graders. The clinical groups included 27 children diagnosed with ADHD and 16 diagnosed with borderline ID, without comorbidities, diagnosed via the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD 10)-based clinical interviews. Twenty-four children were recruited from special education schools, and 19 children were recruited from the Clinic of Pediatric Psychiatry from Cluj-Napoca. Child Behavior Checklist (CBCL) . CBCL isEmotion Regulation Checklist (ERC) . ERC is Child Adjustment Scale . The ChiVisual attention domain measures visual attention speed and accuracy . The chiTower subtest is a task that assesses a series of executive functions such as planning, monitoring, problem-solving, and self-regulation . The chiBlock construction is a visuospatial processing task that requires children to build constructions using a different number of blocks. This task has a medium level of difficulty, and every subset has a time limit of 30 to 60 s.Delayed faces memory assesses children’s memory capacity. Children are shown 16 pictures of boys and girls, and they must memorize them. After 30 minutes, the experimenter shows the children 16 sets of pictures, each containing three pictures, and the children’s task is to recognize the person that they have seen before from every set of pictures. During the delayed memory task, children must hold in mind for several minutes some visual information. We considered the delayed memory task a measure of short-term memory (STM). NEPSY: A developmental neuropsychological assessment . NEPSY aTower construction task  . The chiRaven’s progressive matrices were used to assessed children’s intellectual abilities. A questionnaire was used to collect general information regarding children’s age, educational level, clinical diagnosis, and other demographic data. We used a quasi-experimental design to analyze the associations between children’s characteristics (TD children and children diagnosed with ADHD or borderline ID), adaptive or maladaptive emotional regulation strategies, and executive functions. The study was carried according to the law concerning the conduct of clinical trials, including abidance by international ethical standards foreseen in the updated Helsinki Declaration of Human Rights. We obtained the approval of the local ethics committee to conduct the study. Data were used respecting the regulation regarding the privacy and subject’s identity protection, and informed consent was obtained for each participant. All questionnaires were filled in by the parents. Children that agreed to participate in the study were assessed in a 30–40-minute individual session. The TD children were assessed in a school laboratory and the children diagnosed with ADHD or ID, in a playroom used for psychological assessments. The NEPSY battery tasks were completed first . The anger-eliciting task was applied next. After receiving the instructions, behaviors and the involvement level were coded using the observational scale . Every ct-test was used to compare the studied variables between the clinical groups (ADHD and borderline ID) and the non-clinical group (TD). Data were analyzed using SPSS 20. Pearson correlation was used to test the associations between the studied variables  for the entire sample, and separately for two age groups (7 to 9 and 9 to 11 years). Independent t-test for independent samples was used to investigate the differences between the TD children and those diagnosed with ADHD or borderline ID.Means (M) and standard deviations (SD) were computed for the cognitive functions, emotion regulation, and behavioral and emotional problems in the typical development (TD) and clinical groups see . A t-tesAs seen in TD group scored higher on cognitive functions than both ADHD and borderline ID groups, the difference being significant for visual attention, memory, and planning. The difference was not significant for visuospatial processing see . When cot-test was used to assess the differences in emotion regulation strategies across groups. No significant differences were registered , t(56) = −4.10, p = 0.036. Significant differences were registered also for conduct problems between TD children  and children with ADHD , t(67) = −3.52, p = 0.00, and between TD children and those with borderline ID , t(56) = −1.72, p = 0.00. For the ADHD problems reported by the parents on CBCL, a significant difference t(67) = −2.89, p = 0.00 was registered between TD children  and those with ADHD . The ADHD group reported more anxiety problems  than the TD group , and the difference was significant, t(67) = −1.39, p = 0.02.A ered see . The adaered see . Signifip = 0.002.No significant differences were registered between the ADHD group and borderline ID group for cognitive function visuospatial processing, memory and planning, the adaptative and maladaptive emotion regulation strategies, and emotional and behavioral problems measured by CBCL see . The onlp = 0.034. The correlations were also significant with delayed memory r(69) = 0.298, p = 0.013, planning r(69) = 0.364, p = 0.002 and visuospatial processing r(69) = 0.246, p = 0.042. The correlations were positive, meaning that a frequent use of adaptive emotion regulation strategies is associated with better cognitive function performances. When considering the whole sample, we found significant correlations between the cognitive functions assessed and the emotion regulation strategies measured by the observational scale. The executive functions correlated positively with the adaptive emotion regulation strategies as a unitary concept. The correlation between the adaptive emotion regulation strategies and visual attention was r(69) = 0.256, p = 0.001, planning r(69) = 0.322, p = 0.007, delayed memory r(69) = 0.267, p = 0.026, and visuospatial processing r(69) = 0.306, p = 0.011. Substituting the anger, another adaptive emotion regulation strategy, correlated positively with both visual attention r(69) = 0.279, p = 0.020 and visuospatial processing r(69) = 0.352, p = 0.003. When analyzing the specific adaptive emotion regulation strategies, verbalizing the strategies correlated positively with visual attention r(69) = 0.383, No significant correlations were found between the maladaptive strategies as a unitary concept and the cognitive functions assessed. This may be explained partially by the fact that verbal focusing correlated positively with visual attention r(69) = 0.239, p = 0.047, whereas resignation correlated negatively with all cognitive functions assessed, ranging from −0.359 with delayed memory to −0.238 with planning, meaning that a lesser use of resignation is associated with better performances on visual attention, delayed memory, planning, and visuospatial processing.  = 0.270, p = 0.025, and visuospatial processing r(69) = 0.513, p = 0.000, but no significant correlation between emotion regulation reported by parents and planning r(69) = 0.181, p > 0.05. When analyzing the relation between emotion regulation reported by the parents  and the p = 0.031, ADHD problems r(84) = −0.221, p = 0.043 and conduct problems r(84) = −0.276, p = 0.011. Delayed memory also correlated negatively with conduct problems r(84) = −0.237, p = 0.032. Analyzing the possible relationship between the cognitive functions assessed and emotional/behavioral problems as measured by CBCL, planning correlated negatively with anxiety problems r(84) = −0.235, p = 0.022. Negative correlations were noted between substituting the anger (an adaptive emotion regulation strategy) and visual attention r(20)= −0.462, p = 0.040, and between visual attention and affective problems measured by CBCL r(20) = −0.581, p = 0.007, meaning that, in this age-group, having poor executive function is associated with a higher level of affective problems. For the 9 to 11 years group, delayed memory correlated with the adaptive emotion regulation strategies r(22) = 0.595, p = 0.003. Maladaptive emotion regulation strategies (as a unitary concept) correlated negatively with planning r(22) = −0.473, p = 0.026, meaning that, in this age-group, having poor executive function is associated with the use of maladaptive emotion regulation strategies. Moreover, maladaptive emotion regulation strategies correlated positively with conduct problems measured by CBCL r(22) = 0.482, p = 0.023. We did not find any significant correlation between the reported emotion regulation and other variables. . For the 7 to 9 years group, a positive correlation was found between adaptive emotional regulation strategies (as a unitary concept) and planning r(20) = 0.509, p = 0.04. The executive function of planning, as a mediator, showed a correlation with maladaptive emotion regulation strategies r(69) = 0.099, p = 0.41 that did not reach significance and a significant negative correlation with conduct problems measured by CBCL r(84) = −0.276, p = 0.01. Thus, the preliminary conditions for demonstrating mediation were not met, and the mediation analysis could not be performed.The model tested had the executive function of planning as a mediator in the relation between maladaptive emotion regulation strategies and conduct problems measured by CBCL. Statistical analysis showed a positive correlation between maladaptive emotion regulation strategies and conduct problems r(69) = 0.245, The main objective of our study is to profile the deficits in cognitive functioning  and emotion regulation for two neurodevelopmental disorders: ADHD and borderline ID. Both clinical groups scored significantly lower on EFs than the TD group. The attention impairment reported for the ADHD group is consistent with other study results . For theIn terms of emotion regulation, the comparisons between the three groups did not reveal any significant difference, but the children with ADHD reported higher use of maladaptive strategies than the TD and borderline ID children. Adaptive strategies were more frequently used by TD children, the clinical groups reporting lower, but similar frequencies. The presence of oppositional-defiant and conduct problems was higher in the ADHD and borderline ID groups than in the TD group. Planning correlated negatively with ADHD and conduct problems. These findings suggest that clinical group behavioral problems may be a result of poor executive functioning and not of poor emotion regulation.As expected, the ADHD symptoms were more prevalent in the ADHD group than in the TD group. In addition, children diagnosed with ADHD reported more anxiety and affective symptoms than the TD children. There are studies on ADHD comorbidities suggesting that in cases with comorbidities, there is also a greater involvement of large neural networks. In the Sonuga–Barke dual-pathway model, the individual’s executive functions are divided into the traditional executive functions or cold executive functions, such as attention, working memory, planning, and inhibition, and hot executive functions which are related to neuropsychological processes such as emotion and motivation . The disThe two clinical groups differed from each other only in regard to visual attention; the ADHD group performing better than the borderline ID group. Visual attention is defined as the mechanism by which we select visual information relevant to everyday behavior . EvidencAnother goal of this study is to investigate the relations between EFs, emotion regulation, and emotional and behavioral problems as measured by CBCL. The results on the observational scale emphasized a positive correlation between adaptive emotion regulation strategies (as a unitary concept) and each measured EFs: visual attention, planning, and delayed memory or STM (as a component of WM). Further, we analyzed each adaptive emotion regulation strategy in relation to EFs. Verbalizing the strategies positively correlated with all EFs and substituting the anger positively correlated only with visual attention, reinforcing the common belief that adaptive emotion regulation strategies associate with better EF performances. The unitary concept of maladaptive emotion regulation strategies, measured by the observational scale, did not relate to EFs. This situation is partially explained by the fact that one maladaptive strategy correlated negatively with all EFs, whereas another one correlated positively with visual attention. For the emotional adjustment reported by parents, we found a positive relation between emotion regulation and both visual attention and delayed memory (STM). These findings suggest that children with good executive functions may use both adaptive and maladaptive emotion regulation strategies, but children with poor executive functions are more prone to use maladaptive emotion regulation strategies, such as resignation. The examination of the relation between EFs and emotional/behavioral problems revealed that planning correlated negatively with anxiety, ADHD symptoms, and conduct problems. These findings are consistent with previous studies showing that a deficit in planning can be related to behavioral problems . In addiDifferences regarding the relations between EFs, emotion regulation, and emotional/behavioral problems were observed between the two age groups. The younger group (aged 7 to 9 years) showed a positive correlation between adaptive emotion regulation strategies (as a unitary concept) and planning. The adaptive emotion regulation strategy of substituting the anger correlated negatively with visual attention. In the older group (aged 9 to 11 years), maladaptive emotion regulation strategies (as a unitary concept) correlated negatively with planning and positively with conduct problems. Moreover, we did not find support for our mediation model. The executive function of planning did not mediate the relation between maladaptive emotion regulation strategies and conduct problems. Even though the Diamond’s (2013) model of EFs suggests that emotion regulation influences the higher executive functions, such as planning , we did This study has several limitations. The clinical sample size was relatively small, primarily because we included only patients diagnosed with ADHD or borderline ID without other diagnosed comorbidities. Another important limitation is that our sample had a wide range of ages. As we noticed, there were differences between the two age groups regarding the relationship between emotion regulation and EFs, and this fact might have influenced the findings for the entire sample. Even though our study is a complex one and tries to cover almost all the executive functions mentioned by Diamond (2013)  in her mThe study supports the idea that emotion regulation, EFs, and clinical symptoms are interconnected. Moreover, it suggests that behavioral problems in the clinical groups may be due to poor executive functioning and not a result of poor emotion regulation. Finally, it brings to light new aspects regarding cognitive functioning, emotion regulation, and behavioral and emotional problems in ADHD and borderline ID. A better understanding of each neurodevelopmental disorder can lead to the advancement of more targeted intervention programs.


Attention-deficit/hyperactivity disorder (ADHD) is defined as a cognitive or behavioural developmental disorder. Inattentiveness, overactivity and impulsivity are regarded as the main clinical symptoms of ADHD. These symptoms may occur together or separately resulting in three recognised presentations: predominantly inattentive, predominantly hyperactive–impulsive and combined presentations.This study investigated deficiencies in behavioural planning in South African primary school children with and without ADHD.Tzaneen area in Limpopo province, South Africa.A total of 156 children (78 with ADHD and 78 matched controls without ADHD) of both genders, who were medication naïve and aged 6–15 years, participated in the study. The performance of the two groups was compared on a test of planning and problem-solving, the Tower of London (ToL) task. The results were analysed as a function of gender, age and ADHD presentation.p < 0.001). There were no significant differences in the number of moves and time taken by the predominantly hyperactive-impulsive presentations of ADHD when compared to the controls. Gender and age did not influence the performance.Children with ADHD especially ADHD-PI and ADHD-C used significantly more moves and took a longer time to complete the task than the controls (The results showed that children with ADHD showed significantly more deficits mainly the ADHD-PI and ADHD-C presentations, which indicates that inattention is mainly responsible for deficiencies in behaviour planning. The ADHD-HI presentations and the control group were not affected. Neurotransmitter circuits are involved in EFs, with the dopamine system, especially, playing an essential part in planning and cognitive flexibility by supplying the PFC.14 Therefore, a hypofunctioning mesocortical dopamine branch will cause poor behaviour planning.14 In this study the focus was on behaviour planning. Children who are deficient in planning behaviour display insufficient problem-solving strategies, which, in turn, compromise their learning ability at school.Executive dysfunction is generally attributed to structural and functional frontal pathology.16 To plan, one must be able to conceptualise changes from present circumstances . The planner must also be able to conceive of alternatives, weigh and make choices, and entertain both sequential and hierarchical ideas necessary for the development of a conceptual framework or structure that will give direction to the carrying out of a plan. Good impulse control and reasonably intact memory functions are also necessary in planning.17 Moreover, all of this conceptual activity requires a capacity for sustained attention.18 The literature suggests that children with ADHD often show poor performance on tasks that require strategic planning.19Planning can be described as the execution of goal-directed behaviour to predict and evaluate outcomes. Also identifying, organising steps and elements needed to carry out an intention.19 stated that children with ADHD exhibited poor performance where planning or a proper strategy was needed. Pila-Nemutandani and Meyer.20, Schmitz et al.21 and Mokobane et al.22 noticed that children with the combined (ADHD-C) presentation were highly deficient in behavioural planning and faced more difficulties when compared to both the predominantly hyperactive-impulsive (ADHD-HI) and predominantly inattentive (ADHD-PI) presentations and neurotypically children. However, a study by Geurts et al.23 showed no deficiencies in children with ADHD and normal controls with regard to planning.A study by Kofman et al.The purpose of the study was to investigate whether children with ADHD have deficits in behaviour planning as measured by the Tower of London (TOL)The study was conducted in primary schools in the Tzaneen area, Limpopo, during 2017. A quantitative, cross-sectional case–control study, experimental design was used. To establish whether children with ADHD are deficient in behaviour planning, the sample was divided into participants with ADHD and matched controls without symptoms of ADHD.The selected regions were in a rural area in which assessment of this nature is very rare. The areas were selected based on the remoteness of the regions so that the community could benefit from such research.n = 156) was divided equally in terms of gender (76 boys and 80 girls), aged 6–15 years of age, were recruited from a school-based population in the Tzaneen area in the Limpopo province, South Africa. They were Sepedi and Xitsonga speaking, grade 1–grade 7 learners. The participants were divided into two age groups: 6–10 and 11–15 years. The sample was chosen because of its accessibility. To detect symptoms of ADHD, the learners were screened using the disruptive behavioural disorder (DBD) rating scale, based on ratings from parents and teachers.25 A total number of 5480 children were screened for ADHD using the DBD rating scale. Cut-off points were based on the results obtained from a previous study that had been conducted in Limpopo by Meyer et al.5 Learners who met the criteria for ADHD were assigned by the researcher as follows: participants with scores ≥ 17 on the hyperactivity and impulsiveness scale were classified as ADHD-HI presentations and those having a score ≥ 20 on the inattention scale were classified as ADHD-PI presentations, based on the epidemiological study by Meyer et al.5 Participants who met the criteria on both scales, ADHD-HI and ADHD-PI, were categorised as ADHD-C presentations. The cut-off point for the neurotypical control group was set at the 85th percentile or below to decrease the risk for false-positives in the group. Thus, children with scores of less than 15 on the hyperactivity and impulsivity scale and the inattention scale, matched for gender, age and home language, were selected as controls. Children were divided into an ADHD group and a control group, without ADHD symptoms. Seventy-eight children were found positive for ADHD symptoms (ADHD group) and they were matched for gender, age and home language with children without ADHD . Children with an intelligence quotient (IQ) lower than 80 and/or who are suffering from any head injury, epilepsy, cerebral palsy, cerebral malaria, autism spectrum disorder or severe psychiatric disorders, as reported on the demographic questionnaire by parents and confirmed by the teachers, were excluded from this study. At the time of testing, the researcher ensured that none of the children were taking psychostimulant medication.The sample  and the time taken to complete the specific response were recorded. The testing procedure for each child lasted 30 min and was conducted by a clinical psychologist and four research assistants (who held bachelor’s degrees in psychology) and were fluent in the child’s home language.Screening instruments: Disruptive behaviour disorder rating scale. The disruptive behaviour disorder rating scale (DBD), by Pelham et al.25 used to screen for ADHD symptoms, was completed by parents and teachers. The scale was standardised and normed for all language and population groups in Limpopo province, South Africa.5 The DBD assesses the presence and degree of ADHD-related symptoms (inattention and hyperactivity/impulsivity), oppositional defiant disorder (ODD) and conduct disorder (CD) as formulated in the DSM-IV-TR. The DBD has been translated into five South African languages, namely, Sepedi, Tshivenda, Afrikaans, Tsonga and Tswana, which are spoken in the Limpopo province. Internal consistency and norms for each language group have been established.5α for the primary school population in the Limpopo province was calculated at 0.90 for the HI scale and 0.92 for the inattention scale.5 For this study, the sample’s Cronbach’s α for the HI scale was calculated at 0.74, and at 0.79 for the inattention scale.Cronbach’s The Tower of London: The TOL is a widely used instrument for assessing planning ability. Shallice26 developed the instrument to assess higher order problem-solving capacity, specifically executive planning. It can also be used in a neuropsychological battery to assess motor planning and processing information.27 The TOL requires ‘forward thinking’ or planning and measures spatial planning and problem-solving because an early incorrect move can render the problem almost unsolvable.30 The TOL is considered to be a frontal lobe test which is believed to measure EFs involved with strategic planning.32 It has been proven to be sensitive in distinguishing planning behaviour deficits in children with ADHD and in neurotypically children.33r = 0.72, and internal consistency, Cronbach’s α = 0.69.34The apparatus consisting of three wooden beads  had been placed. The researcher presented an example of the problems, on cards, which were to be solved in two to five steps. In a practice problem, the same initial position was used, where two steps were needed to reach a solution. The task consisted of 12 problems, which had been graded in terms of their difficulty. From the start position, the participants were expected to move the beads to the finish position shown on the cards, making use of the least number of steps. The reliability coefficients were split-half reliability, 35 The results for each test were analysed with 4 × 2 (ADHD presentation × gender) ANOVA’s for independent samples. Post hoc tests consisted of multiple comparisons using the Bonferroni method.36Analysis of variance (ANOVA) was used to investigate possible between-group differences using the ToL raw scores. Analysis was done using Statistica 10 StatSoft.We confirm that this manuscript is the original and has not been submitted to any other journal for publication. University of KwaZulu-Natal, is fully aware of this submission. Ethical approval to conduct the study was obtained . In addition, permission was obtained from the Department of Education, Limpopo province, and school principals of the selected schools. Informed consent was obtained from the parents or legal guardians of the learners to participate in the study. The children also assented to their participation in the study. Participation in the study was voluntary, and participants were informed that they could withdraw at any stage.p < 0.001) and the HI scores (p < 0.001) of the DBD rating when the ADHD and control group were compared. The demographics and DBD scores for the sample are presented in The study hypothesised that children with ADHD will have impairments in behaviour planning when compared with neurotypically children. Age did not affect the results; therefore, it was not taken into account for further analysis. Statistically significant differences were found for the inattention scores  = 10.54, p < 0.001, Post hoc analysis (Bonferroni) revealed that there was a statistically significant difference in performance between both the ADHD-PI and ADHD-C presentations and the control group (p < 0.001). The ADHD-PI and ADHD-C subtypes used significantly more moves than the controls. There was no significant difference in the number of moves used by the ADHD-HI subtype when compared to the controls.There was neither main nor interacting effect for gender and age; therefore, the gender and age groups were analysed together. There was, however, a statistically significant difference in performance between the ADHD and control groups: F = 11.52, p < 0.001, Post hoc analysis (Bonferroni) revealed that the differences between the ADHD-PI and ADHD-C and the control group were statistically significant, both at the p < 0.001 level. The children with ADHD-PI and ADHD-C took significantly more time than the controls to move the beads. There was no significant difference in the time taken by the ADHD-HI presentation when compared to the controls. Effect sizes  are related only to ADHD-C not to ADHD-PI and ADHD-HI. Barkley’s findings is supported by several other studies which show that ADHD-C is accompanied by more serious impairment than ADHD-PI.58 Therefore, the ADHD-C and the ADHD-PI presentations seemed to have more difficulty in planning ahead than the ADHD-HI and the non-ADHD comparison group.However, the current study differs from the study by Houghton et al.59 These areas, especially the prefrontal areas, seem to be dysfunctional in children with ADHD, probably because of a hypofunctioning mesocortical dopamine branch, causing deficient attention and poor behavioural organisation.14The posterior parietal cortex is connected with the PFC and has been shown to represent neural correlates of decision-making and planning.58 They have a compromised learning ability at school, which makes it difficult for them to apply new skills. It is essential that teachers and parents recognise children with ADHD early so that they can provide appropriate and effective intervention. Early referrals and necessary follow-up treatment at an early age is essential. In this regard, early pharmacological and/ or behavioural treatment should be provided when applicable.Children with ADHD usually are hasty and disorderly when they plan behaviour.The sample size was small, especially when the ADHD group was subdivided into three presentations. This may have influenced on the statistical outcome. Caution should be exercised when generalising these results to all South African children as the sample was homogeneous, consisting of rural Sepedi and Xitsonga speaking children only from the same geographical area. It is recommended for future studies to include more language groups. The TOL instructions should be standardised in different languages.The goal of the study was to assess the behaviour planning deficits in children with ADHD. The study showed that especially the inattentive and combined ADHD presentations have problems with planning, and problem-solving using the TOL.


Gut–brain axis (GBA) is a system widely studied nowadays, especially in the neuropsychiatry field. It is postulated to correlate with many psychiatric conditions, one of them being attention-deficit hyperactivity disorder (ADHD). ADHD is a disorder that affects many aspects of life, including but not limited to financial, psychosocial, and cultural aspects. Multiple studies have made a comparison of the gut microbiota between ADHD and healthy controls. Our aims were to review the existing studies analyzing the gut microbiota between human samples in ADHD and healthy individuals.The literature was obtained using Google Scholar, Pubmed, and Science Direct search engine. The keywords used were “ADHD”, “gut microbiota”, “stool”, “gut”, and “microbiota”. The selected studies were all case–control studies, which identify the gut microbiota between ADHD and healthy individuals.Bifidobacterium was found in higher amount in ADHD patients, but other study stated that the abundance of this genus was lower in ADHD with post-micronutrient treatment. This may suggest that micronutrient can modulate the population of Bifidobacterium and improve the behavior of ADHD patients. Other notable findings include a significantly lower population of Dialister in unmedicated ADHD, which rose after patients were medicated. A smaller amount of Faecalibacterium were also found in ADHD patients. This may explain the pathogenesis of ADHD, as Faecalibacterium is known for its anti-inflammatory products. It is possible the scarcity of this genera could induce overproduction of pro-inflammatory cytokines, which is in accordance with the high level of pro-inflammatory cytokines found in children with ADHD.We found six studies which were eligible for review. The model and methods of each study is different. Forty-nine bacterial taxa were found, yet none of them can explain the precise relationship between ADHD and the gut microbiota. There were no studies that examined which bacterial taxa correlated most to ADHD. This might occur due to the different model and methods in each study. Further study is needed to identify the correlation between gut microbiota and ADHD. Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder affecting 7.2% children below 18 years old globally . In addiGut–brain axis (GBA) is a system widely studied right now because of the novel understanding that the gut microbiota environment can affect brain activity and vice versa. The bidirectional communication involves the central nervous system, brain and spinal cord, autonomic nervous system, enteric nervous system, and hypothalamic pituitary adrenal (HPA) axis . UnbalanA study conducted in animal models has found that several taxa differed significantly between mice that were colonized by ADHD microbiota and healthy control mice. Fourteen genera increased, while 17 genera were found to be more abundant in control. Mice with transplanted microbiota displayed abnormalities in their brain such as decreased integrity in both white and gray matter regions. Other than that, the MRI result showed a decreased resting-state connectivity between right motor and visual cortices [Finally, several studies have compared the gut microbiota in ADHD with healthy individuals. We systematically reviewed the scientific literature of case–control studies focusing on gut microbiota composition in ADHD.The population of this systematic review is ADHD patient, the intervention is the profiles of gut microbiota, the comparator is healthy control, and the outcome of this study is to find any differences in gut microbiota profiles between ADHD and healthy controls. The literature search was conducted using Google Scholar, PubMed, and Science Direct with keywords “ADHD”, “gut microbiota”, “stool”, “gut”, and “microbiota”. The studies were then selected based on the inclusion and exclusion criterias. The inclusion criteria include: (1) all studies must be in English and discuss gut microbiota in ADHD; (2) the samples in the studies were diagnosed based on Diagnostic and Statistical Manual of Mental Disorders (DSM) 4th or 5th edition or ICD-10 with the code F90.9; (3) the studies conducted in human and the gut microbiota were identified using fecal samples. We excluded studies with samples below ten person(s) and studies that focus on other condition besides ADHD, such as interventional study.The studies selection was conducted using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Three out of six studies were conducted in Asia Two studies Out of all studies, only two studies 2.Two studies , 11 exclThe diagnostic tools included K-SADS (Kiddie Schedule for Affective Disorders and Schizophrenia) based on DSM-IV, DSM-IV-TR, and DSM-5. Three studies –13 used Four out of six studies used 16s rRNA sequencing, but in different regions. Three studies , 10, 12 Five studies –12, 14 iTwo studies , 12 did p < 0.05) different between ADHD and healthy controls. The result of each study varied that it was difficult to point out which bacteria taxa differed the most in ADHD. Study from Aarts et al. stated that Clostridiales order, Rikenellaceae and Porphyromonadaceae families, and Bifidobacterium and Eggerthella genera might be the potential markers for ADHD. The change in Bifidobacterium abundance is related to phenylalanine pathway for carbohydrate-deficient transferrin. Genus Dialister decreased in the study by Jiang et al. [Faecalibacterium decreased in the study by Jiang et al. [The total of 49 bacterium taxa were found to be significantly  score . Vegetarammation . In ADHDammation . By exclFirmicutes:Bacteroides in obese children. In addition, the concentration of B. vulgatus decreased while Lactobacillus spp. concentration increased. S. staphylococcus was also known to correlate with energy intake [BMI can affect the composition of gut microbiota, especially those who are overweight or obese. There was an increased ratio of y intake . BMI shoDialister genus in ADHD-medicated samples, while Jiang et al. [Dialister is known for its potential in modulating gamma-aminobutyric acid (GABA) neurotransmitter, which may play a role in the pathogenesis of ADHD [There was a decreased α-diversity in ADHD-medicated samples in study by Prehn-Kristensen et al. . In otheg et al.  found de of ADHD . We suggBifidobacterium infantis can decrease pro-inflammatory cytokine in animal model study with irritable bowel syndrome (IBS). Moreover, it is known for its anti-inflammatory effect when consumed with α-linoleic [Consumption of prebiotic/probiotic/antibiotic will affect the gut microbiota composition. For example, linoleic . Other elinoleic .Lactobacilli and Actinobacteria. This change indicates that antibiotics consumption can alter normal gut microbiota composition.Antibiotics such as penicillins, quinolones, macrolides, sulfonamides, and anti-tuberculosis agents are claimed to induce psychotic behavior. These antibiotics may disrupt the microbiota’s metabolism, therefore affecting the neurotransmitter and SCFA (short-chain fatty acids) which will lead to brain disturbance through GBA . In addiActinobacteria phylum and Coriobacteria class were found more abundant compared to healthy individuals [Lactobacillus (P = 0.067) and Bifidobacterium (p = 0.012) has been found to be lower [Proteobacteria was increased. Six genera were found increased , while three other genera were found decreased  Escherichia/Shigella was found in Alzheimer’s disease and increased Lactobacillaceae was found in Parkinson’s disease [Prevotella genus [Ruminococcaceae is associated with irritable bowel syndrome [Firmicutes and Clostridia [Other neuropsychiatric disorders such as depression, schizophrenia, bipolar, Alzheimer’s and Parkinson’s diseases are extensively studied about their correlation with gut microbiota. Several genera are known to induce depression through HPA axis, GABA, SCFAs, immune system and gut barrier . In patiividuals . In MDD,be lower ; whereas disease . Therefola genus . A studysyndrome . Other tostridia .Bifidobacterium [Peptostreptococcaceae [Bacteroides spp. were found increased, while one species was found decreased [Bifidobacterium. This genus is known to be the most efficient GABA producer [The role of GABA in the pathogenesis of ADHD is still unknown. A study in 2012 found decreased GABA level in ADHD . On the occaceae  family wecreased , 11. Thoproducer . Thus, wEscherichia coli [. Unfortunately, from all the studies we reviewed, we cannot find a specific gut microbiota that has the ability to modulate or produce dopamine nor norepinephrine. It is still unknown how methylphenidate can affect the composition of gut microbiota of ADHD patients. As stated before, we suggest that the Dialister genus may be the biomarker for those with ADHD medication, but further research is needed to identify the mechanism between methylphenidate and gut microbiota.Though the exact pathogenesis of ADHD is still unclear, if we deduce the mechanism of action of methylphenidate, we can assume that norepinephrine and dopamine play a big role in ADHD. Methylphenidate works by inhibiting the reuptake of dopamine and norepinephrine. D1 dopamine receptor activation (DRD1) regulates NOD-like receptor protein 3 (NLRP3) through cyclic adenosine monophosphate (cAMP), thus destroying NLRP3 in all sites helped by E3 ubiquitin MARCH7. Dopamine and DRD1 may reduce neurotoxin-induced neuroinflammation, lipopolysaccharide (LPS)-induced systemic inflammation, and monosodium urate crystal (MSU)-induced peritoneal inflammation . Norepinhia coli . UnfortuBifidobacterium genus is decreased in children who were given the micronutrient treatment. The decreased level of Bifidobacterium was in line with a decreased in ADHD-IV-RS score [Bifidobacterium in ADHD patients. This could hint that micronutrients may restore the balance of Bifidobacterium, also that this genus may play a big role in the pathogenesis of ADHD. As explained before, Bifidobacterium is one of the many bacteria that can produce GABA. The role of GABA in ADHD still needs to be explored and further study regarding the connection between Bifidobacterium and its effect on ADHD symptoms still needs to be analyzed.A study in 2019 tried to compare the gut microbiota composition between ADHD children who were given micronutrient treatment and those with placebo. It was found that RS score . A studyFaecalibacterium genus [Two studies found a decreased amount of um genus , 11. Thium genus . Microglum genus . Moreoveum genus . FurtherStudies comparing the gut microbiota condition between ADHD and healthy individual are still limited. So far there is no common agreement on which bacterial taxa is most relevant to the incidence of ADHD, thus the link between gut microbiota and ADHD remains unclear. Numerous criteria, such as sample size, gender, BMI, dietary pattern, use of prebiotic/probiotic/antibiotic, and history of ADHD medication, should be taken into consideration in conducting this study in the future. In addition, further studies regarding neurotransmitter-modulated gut microbiota are needed, as there are many bacteria whose function remains undiscovered.


Could human exposure to magnetic field nonionizing radiation be associated with increased risk of attention-deficit/hyperactivity disorder in children?This birth cohort study found a statistically significant association between a high level of maternal exposure to magnetic field nonionizing radiation, as captured with a monitoring meter, during pregnancy and an increased risk of attention-deficit/hyperactivity disorder in offspring. The association was stronger for children who received a diagnosis of attention-deficit/hyperactivity disorder in adolescence (≥12 years of age) than for those without such a diagnosis in adolescence, and primarily for children with attention-deficit/hyperactivity disorder with immune-related comorbidities.The findings should spur more research to examine the biological association of in utero magnetic field exposure with risk of attention-deficit/hyperactivity disorder in offspring. An association between maternal exposure to magnetic field (MF) nonionizing radiation during pregnancy and the risk of attention-deficit/hyperactivity disorder (ADHD) has been reported in both animal and human studies.To determine whether maternal exposure to high levels of MF nonionizing radiation is associated with an increased risk of ADHD in offspring by using more accurate measurements of MF nonionizing radiation levels and physician-diagnosed ADHD, rather than self-reports, and to determine whether the association differs for the subtypes of ADHD with or without immune-related comorbidities.A longitudinal birth cohort study was conducted at Kaiser Permanente Northern California among 1482 mother-child pairs whose mothers were participants of an existing birth cohort and whose level of exposure to MF nonionizing radiation was captured during pregnancy in 2 studies conducted from October 1, 1996, to October 31, 1998, and from May 1, 2006, to February 29, 2012. The offspring were followed up from May 1, 1997, to December 31, 2017.All participating women wore a monitoring meter for 24 hours during pregnancy to capture the level of exposure to MF nonionizing radiation from any sources.Physician-diagnosed ADHD and immune-related comorbidities of asthma or atopic dermatitis up to 20 years of age in offspring captured in the Kaiser Permanente Northern California electronic medical record from May 1, 1997, to December 31, 2017. Confounders were ascertained during in-person interviews during pregnancy.Among the 1454 mother-child pairs , 61 children (4.2%) had physician-diagnosed ADHD. Using Cox proportional hazards regression to account for follow-up time and confounders, compared with children whose mothers had a low level of exposure to MF nonionizing radiation during pregnancy, children whose mothers were exposed to higher levels of MF nonionizing radiation had more than twice the risk of ADHD . The association was stronger for ADHD that persisted into adolescence (≥12 years of age), with an aHR of 3.38 . When the subtypes of ADHD were examined, the association existed primarily for ADHD with immune-related comorbidities (asthma or atopic dermatitis), with an aHR of 4.57  for all ADHD cases and an aHR of 8.27  for persistent cases of ADHD.Consistent with the emerging literature, this study suggests that in utero exposure to high levels of MF nonionizing radiation was associated with an increased risk of ADHD, especially ADHD with immune-related comorbidity. The findings should spur more research to examine the biological association of in utero MF exposure with risk of ADHD in offspring, given that almost everyone is exposed to it. This cohort study examines whether maternal exposure to high levels of magnetic field nonionizing radiation is associated with an increased risk of attention-deficit/hyperactivity disorder (ADHD) in offspring. Emerging human studies have begun to report that maternal exposure to MF nonionizing radiation during pregnancy is associated with an increased risk of several childhood illnesses, including immune-related conditions (such as asthma),9 obesity,10 and neurologic conditions (such as ADHD).12 An experimental study13 provided further evidence of (1) the direct link between in utero exposure to MF nonionizing radiation and ADHD in offspring and (2) a potential mechanism linking in utero exposure of MF nonionizing radiation with ADHD through altered neuronal developmental programming. Additional evidence from experimental animal studies has also recently been reported.14 Finally, a JAMA report showed that MF nonionizing radiation could affect human brain cell functions.16 The emerging evidence indicates that (1) there is a potentially adverse biological association between in utero exposure to MF nonionizing radiation and the health of offspring and (2) fetal brain development and programming is likely one of the vulnerable targets associated with in utero exposure to MF nonionizing radiation.One of the most relevant time windows for environmental risk factors to be associated with brain development is during pregnancy, when fetal brain development is susceptible to external insults that could have a long-lasting effect on brain function and neurobehavior. Among the limited research into the causes of ADHD associated with in utero environmental exposures, to our knowledge, the focus has thus far been on chemicals.If research evidence shows that in utero MF nonionizing radiation exposure is a risk factor for ADHD, then this exposure would be a modifiable risk factor. Although almost everyone today is exposed to MF nonionizing radiation to some degree, prevention measures can be implemented to reduce the level of maternal MF nonionizing radiation exposure during pregnancy. Thus, understanding the association between in utero exposure to MF nonionizing radiation and the risk of ADHD would be an important first step. To further examine the association and improve on weaknesses in previous studies, we conducted a prospective birth cohort study with focuses on (1) an objective measurement of maternal exposure to MF nonionizing radiation during pregnancy and (2) a more accurate determination of ADHD cases through a physician’s diagnosis as opposed to maternal self-reporting.18 The mothers were pregnant women who participated in 2 previous studies  that followed the same study protocol. The level of MF nonionizing radiation exposure was measured by asking participants to wear a monitoring meter throughout a 24-hour monitoring period during pregnancy. Their offspring were followed up from May 1, 1997, to December 31, 2017. The study was approved by the KPNC Institutional Review Board, and all participants provided written informed consent. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines.This study was based on the participants of an existing birth cohort of the Kaiser Permanente Northern California (KPNC) health care delivery system whose members have repeatedly been shown to be representative of the underlying community population.All pregnant KPNC members aged 18 years or older who resided in the San Francisco Bay Area counties were identified through KPNC electronic medical record data. Those who intended to carry the pregnancy to term at the time of recruitment were eligible for participation in the study. All participants were asked to wear a meter that captured the level of MF nonionizing radiation exposure during a 24-hour monitoring period. An in-person interview was also conducted to ascertain risk factors and potential confounders at the same time. Of 2060 participating pregnant women who had valid measurements for MF nonionizing radiation levels during pregnancy, 1568 delivered live-born offspring, while the rest of the pregnancies ended mostly owing to miscarriage. After excluding those whose offspring did not receive pediatric care at KPNC after delivery, 1482 mother-child dyads were eligible for the present study  captured levels of 40 to 800 Hz of MF nonionizing radiation encountered by the participating woman throughout her daily life. The MF nonionizing radiation level was measured in milligauss. To avoid potential measurement biases, the meters were calibrated before each use and programmed to show only the time of day, without displaying any MF nonionizing radiation exposure level, so that participants were not aware of their MF nonionizing radiation levels during the measurement period. This design was implemented to avoid changes in any routine daily activities owing to the MF nonionizing radiation level being displayed.Once a pregnant woman had given consent to participate in the study, she was asked to wear an EMDEX meter (Enertech Inc)21 In our study, we also conducted repeated measurements among a subset of 94 participants, and the correlation coefficient was 0.6 between 2 repeated measurements of MF nonionizing radiation, indicating a relatively stable exposure level during pregnancy.The level of MF exposure has been reported to be relatively stable when measured repeatedly over 12 to 26 months, and the study concluded that the measurement of the MF nonionizing radiation level on a single visit is a good indicator of personal exposure levels during a period of up to 26 months.19 we used a cutoff based on the 25th percentile of the MF index’s distribution, which corresponded to 1.3 mG. The participants whose MF nonionizing radiation level was lower than 1.3 mG were classified as having a low level of MF nonionizing radiation exposure during pregnancy, while the participants whose MF nonionizing radiation level was 1.3 mG or higher were classified as having a relatively higher daily level of MF nonionizing radiation exposure.To examine the association of high levels of MF nonionizing radiation with risk of ADHD, we used the 90th percentile of the 24-hour measurements as the MF index, which reflects the MF nonionizing radiation level at or above which a participant was exposed to for 10% of the time during the day. Given that everyone is exposed to MF nonionizing radiation at some levels, to classify participating women into low or high MF nonionizing radiation exposure groups, based on the experience of previous studies,International Classification of Diseases, Ninth Revision (ICD-9) code 314.x or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) code F90.x. To avoid ambiguous cases that might have had temporary symptoms similar to ADHD, a child was considered to have had ADHD if there were 2 or more ADHD diagnoses that were at least 1 year apart. We excluded 28 children who had only 1 diagnosis. Thus, the final analyses included 1454 mother-child dyads. To enhance the accuracy of our ADHD case definition, we further identified children who had an ADHD diagnosis that persisted into adolescence . The persistent cases were more likely to be true and more severe cases of ADHD. If the exposure of MF nonionizing radiation during pregnancy was associated with ADHD and not with other factors , one would expect to observe a stronger association with persistent (true) ADHD cases. Thus, confirmation of a stronger association with persistent cases of ADHD than with cases of children with ADHD who did not receive the diagnosis in adolescence could strengthen the observed association.All eligible participating children included in the study were followed up to 20 years of age until (1) they received a diagnosis of ADHD, (2) they left the KPNC system, or (3) the study period ended (at the end of 2017). Unlike many previous studies based on self-report, the determination of ADHD in this study was based on a physician’s diagnosis recorded in the KPNC electronic medical records. A diagnosis of ADHD was identified through 28 At the same time, MF nonionizing radiation exposure has been reported to have an association with the immune system.33 Thus, it is conceivable that in utero exposure to MF nonionizing radiation may specifically increase the risk of ADHD with an underlying immune cause. To examine this potential causal pathway, we divided children with ADHD into those with immune-related comorbidities (asthma or AD), as reported in the literature,27 and those without these comorbidities. Both asthma and AD were identified based on physicians’ diagnoses: ICD-9 codes of 493.x or ICD-10 codes of J45.x for asthma and ICD-9 codes of 691.8x or ICD-10 codes of L20.x for AD (excluding diaper or skin rash). A stronger association with ADHD cases with immune-related comorbidity, combined with a lack of association with ADHD cases without immune-related comorbidity, would strengthen the biological basis for the association between in utero exposure to MF nonionizing radiation and risk of ADHD because it would be consistent with the underlying mechanistic pathway.In addition, emerging literature has shown that some individuals with ADHD have a higher concurrence of immune-related comorbidities, such as asthma and atopic dermatitis (AD); thus, an immune-related cause for ADHD has been proposed.In-person interviews were conducted with all participants during their pregnancy to ascertain information on many potential confounders. We evaluated several risk factors for ADHD as potential confounders, including maternal age, race/ethnicity, educational level, prenatal smoking and alcohol use, prepregnancy body mass index, sex of offspring, and sociodemographic characteristics.The Cox proportional hazards regression model was used to control for potential confounders. The Cox survival analysis also has the advantage of accounting for differing durations of follow-up for offspring. All children were followed up starting from birth until (1) they received a diagnosis of ADHD or (2) they were censored . We first examined the association between the level of maternal MF nonionizing radiation exposure (high vs low) and the risk of ADHD including all children. We then examined the association for persistent ADHD cases to assess the robustness of the association. Finally, we examined the association separately for ADHD cases with or without the immune-related comorbidities of asthma or AD.34 we did not identify any factors that met the definition for being a confounder using the change-in-estimate criterion. Nevertheless, we included in the model common sociodemographic characteristics, such as maternal age, educational level, and race/ethnicity, as well as some known risk factors for ADHD, such as maternal smoking and alcohol use during pregnancy, prepregnancy body mass index, and sex of offspring. All P values were from 2-sided tests and results were deemed statistically significant at P < .05.We used the change-in-estimate criterion to identify confounders based on whether the ADHD hazard ratio for MF nonionizing radiation changed by 10% or more when the potential confounder was introduced into the model. A Kaplan-Meier survival curve was used to present the ADHD survival pattern separately for offspring with high or low levels of in utero exposure to MF nonionizing radiation. Consistent with previous studies examining the effect of MF nonionizing radiation,34 the level of MF nonionizing radiation exposure was not associated with commonly known ADHD risk factors or socioeconomic characteristics, including maternal smoking and alcohol use during pregnancy, maternal history of ADHD, educational level, marital status, household income, sex of offspring, and breastfeeding history. Among all the factors examined in The mean (SD) maternal age of the study population was 31.4 (5.4) years; the racial/ethnic distribution was 548 white (37.7%), 110 African American (7.6%), 325 Hispanic (22.4%), 376 Asian or Pacific Islander (25.9%), and 95 other or unknown (6.5%); 137 (9.4%) reported smoking during pregnancy, and 620 (42.6%) reported alcohol use during pregnancy. A total of 61 children (4.2%) had physician-diagnosed ADHD. After adjustment for known risk factors for ADHD, including maternal age, educational level, race/ethnicity, maternal smoking and alcohol use during pregnancy, prepregnancy body mass index, and sex of offspring, Given the previously reported associations of MF nonionizing radiation exposure with immune-related diseases and the existence of potential ADHD immune-related causes, we further examined the association of in utero exposure to MF nonionizing radiation with the risk of ADHD separately for children with ADHD and immune-related comorbidities (asthma or AD diagnosis) and children with ADHD without such comorbidities. The 32 Thus, in addition to the overall association, the additional observations of a stronger association with persistent ADHD and ADHD with current immune-related comorbidities are consistent with the underlying biological plausibility and strengthen the observed association.In this large birth cohort study of 1454 mother-child dyads with rarely available data on maternal MF nonionizing radiation exposure during pregnancy captured with a monitoring meter, we followed up the offspring of participating women for physician-diagnosed ADHD and immune-related comorbidities (asthma and AD) up to 20 years of age. We observed that in utero exposure to higher levels of MF nonionizing radiation was associated with more than 2 times the risk of ADHD. The association became stronger for children with persistent ADHD whose condition remained present into adolescence . The obsGiven the limited understanding of the causes of ADHD, these findings could lead to a new research direction to elucidate environmental risk factors for ADHD during fetal development. These new findings would need to be replicated in future studies. If confirmed, the increasingly ubiquitous exposure to MF nonionizing radiation in human populations, including pregnant women, could be an important, nonetheless modifiable, risk factor for ADHD. Currently, the causes and the secular increase in incidence of ADHD remain poorly understood.13 especially in the prefrontal cortex, including impaired glutamatergic synaptic transmission onto layer V pyramidal neurons of the prefrontal cortex. Thus, there is biological plausibility for in utero exposure to MF nonionizing radiation to increase the risk of ADHD in offspring through fetal development of both the brain and the immune system.Although understanding its pathologic pathways remains limited at this point, in utero exposure to MF nonionizing radiation has been associated with neuropathologic changes in the brain,Given that the exposure of interest was maternal MF nonionizing radiation exposure during pregnancy, the factors that existed after birth, by definition, cannot act as confounders because they occurred after the exposure; thus, they are likely on the causal pathway. Other factors  did not meet the criteria of being a confounder to be associated with both the MF nonionizing radiation exposure and ADHD, as already described. Nevertheless, we included them in the regression models, and adjustment for those variables did not change the results.This study has some limitations. Despite the significantly improved accuracy of our MF nonionizing radiation exposure measurements compared with previous studies, we were not able to ask women to carry the meter throughout pregnancy because it was not feasible. Thus, there may still be some inaccuracy in maternal MF nonionizing radiation exposure level. Given that this was a prospective study design, maternal MF nonionizing radiation exposure was ascertained during pregnancy before ADHD diagnosis in offspring. Any measurement inaccuracy, if it existed, would have been nondifferential . In principle, nondifferential measurement error would have attenuated the observed association. In other words, without the measurement error, the observed association would have been even stronger. In addition, the study measured MF nonionizing radiation at a low frequency (≤800 Hz); thus, the findings may not apply to MF nonionizing radiation at higher frequencies.This study also has some strengths, including (1) a prospective design, thus reducing the likelihood of participation bias; (2) physician-diagnosed, rather than self-reported, ADHD, thus increasing the accuracy of outcome measurement; and (3) an objective measure of maternal MF nonionizing radiation level ascertained by a meter to reduce measurement error for the exposure.Using a longitudinal birth cohort study design, we examined the association between maternal exposure to MF nonionizing radiation during pregnancy and risk of ADHD in offspring throughout childhood up to age 20 years. The study improved over previous studies by enhancing the accuracy of measuring MF nonionizing radiation exposure and of ADHD diagnosis. The findings provide new evidence that in utero exposure to a high level of MF nonionizing radiation is associated with an increased risk of ADHD in offspring. The association is primarily between MF nonionizing radiation exposure and ADHD with immune-related comorbidities and persistent cases of ADHD. The findings reveal a possible new risk factor that is ubiquitous in our modern day lives and should spur more research to examine this potential association.