Methylenetetrahydrofolate reductase is a critical enzyme that has been associated with several complex psychiatric mental health illnesses. The enzyme can be detected by bloodwork or a cheek swab and, once identified as lacking in individuals, can be treated by over-the-counter supplementation with folate. Due to a provider’s limited information and/or the cost to cover the test, the deficiency is not regularly tested for, and, therefore, is missed and not treated. There are very limited studies that demonstrate the benefits of supplements in conjunction with psychotropic medications. This study discusses the case of two biological siblings diagnosed with attention-deficit hyperactivity disorder and autism, who presented with this unique deficiency and had improvement of symptoms once starting the supplement with their traditional psychopharmacological treatment. Recent data from 2019 to 2020 indicate that behaviors with conduct disorders are increasing in children [ASD is a developmental disability consisting of stereotypical behavior, limited communication, and impaired social skills. Subpopulations within the spectrum can present with various other co-occurrences of different severities. Each child with ASD presents differently and responds differently to treatment. As children with ASD grow and become young adults, they have difficulties interacting with their peers, managing themselves on their own, and understanding the behaviors expected of them in school or at work. They usually benefit from early intervention at home and school, which can assist them with activities of daily living, and most often have strategic plans in place to help them succeed .ADHD is a neurobehavioral disorder characterized by symptoms of impulsivity, inattention, and hyperactivity . These sWhile both ADHD and ASD have completely different clinical presentations, it is known that they both have genetic links to their acquisition. Those genetic links are still being explored to this day; however, a common gene mutation has been found in both disorders, and it encourages us to further explore those genes and the treatment options that may be mutually beneficial to treating both conditions. Ultimately, treating psychiatric illnesses in well-rounded ways. The gene of interest that is associated with an increased risk of developing ASD or ADHD is the methylenetetrahydrofolate-reductase (MTHFR) 677C>T polymorphism, which impairs one-carbon (C1) metabolic pathway efficiency .MTHFR is an enzyme that has been associated with several complex psychiatric mental health illnesses. It converts 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate and participates in folate and homocysteine conversion correlated to DNA methylation . MethionTo assess for MTHFR deficiency, providers can order a genetic test by cheek- swab or blood work. The genetic test analyzes how our genes may impact medication outcomes. It assesses genetic variations in DNA and provides information to physicians about how your body metabolizes certain medications that are given to treat psychiatric conditions such as depression, ADHD, and anxiety. Most insurances may not cover the tests unless the patient has a severe condition or has failed multiple treatment regimens .Limited research has been done assessing the role of the MTHFR enzyme in psychiatric illness but from the few studies already performed, it has been found that the reduction of MTHFR activity or folate deficiency has been associated with an onset of several psychiatric diseases, schizophrenia, bipolar disorder, depression, autism, and ADHD -9. The rThe following case series illustrates the journey of two biological siblings, a boy and a girl, with MTHFR deficiencies. They both went through an extensive trial of multiple medications leading up to their diagnosis. The cases below demonstrate the use of L-methylfolate in complex pediatric psychiatric cases with comorbid diagnoses.Case 1The boy was four years old when he first came to the attention of behavioral health specialists. He was diagnosed with in-utero substance exposure, metopic craniosynostosis, global developmental delays, ASD with social-emotional reciprocity requiring substantial support (Level 2), restricted repetitive behavior requiring support (Level 1), with accompanying language impairment, without accompanying cognitive impairment, obstructive sleep apnea, and ADHD. He was placed in the foster care system secondary to neglect, of which the full details were unknown. His biological mother was using substances during the prenatal period, exposing him to cigarettes, methamphetamine, and opioids. As a result, he was born at 39 weeks gestation via emergency cesarean section due to late decelerations and prolonged fetal bradycardia. He had low birthweight and had significant meconium aspiration syndrome, which led to him being placed on high-flow intranasal oxygen, but subsequently needed intubation, and an oscillator. His post-natal care was unknown. He was adopted at 21 months and was observed to have delayed developmental milestones. He learned to walk at 21 months, received occupation and speech therapy through birth-to-three services, and transitioned to the head-start pre-K program at 2.5 years old.His medication trial consisted of the following: clonidine, guanfacine, fluoxetine, long and short-acting methylphenidate, long and short-acting dexmethylphenidate, mirtazapine, prazosin, trazodone, viloxazine, risperidone, and amphetamine. The medications were discontinued after they either showed significant side effects or after they were given a full trial of optimizing the doses over a period of months and deemed ineffective. He completed his genetic test with a cheek swab when he was seven years old due to the delay in insurance approval, and he was found to have a severe MTHFR deficiency. The family started him on over-the-counter L-methylfolate 7.5 mg tablets once a day and noted great improvements in his behaviors two weeks later.Case 2The girl was three years old when she first started treatment for mental health concerns. She was diagnosed with in-utero substance exposure, fetal alcohol spectrum syndrome, global developmental delays, ASD requiring substantial support (Level 2), with accompanying language and cognitive impairment, and ADHD. She was born at 38 weeks gestation via C-section delivery and weighed 4 pounds and 5 ounces. She had aspirated on meconium-stained fluid during birth and had poor effort and tone upon delivery, resulting in her being intubated. She did well after intubation and was initially observed in the holding nursery but began exhibiting significant tachypnea and hypoxemia and was hypoglycemic on an initial heel stick. Thus, she was transferred to the neonatal intensive care unit (NICU) for further monitoring and treatment. She was extubated and weaned to room air the day after her delivery. She was monitored for neonatal abstinence syndrome. She was further monitored for substance withdrawal when she was placed in foster care at three months old and later was adopted at one year old. She had delayed developmental milestones and received speech, occupation, and physical therapy through birth-to-three. She transitioned into the head-start pre-K program at three years old. Her first neuropsychological evaluation was at age three in which she was diagnosed with global developmental delay and oppositional defiant disorder. For this, the family participated in parent-child interactive therapy (PCIT) when she was three to four years old for her behaviors. She only did well with PCIT when the therapist was present but was unsuccessful with it at home. When she was re-tested at age 6 she was diagnosed with ASD, level 2, and intellectual disabilities.Her medication trials included: clonidine, guanfacine, risperidone, Depakote, lamotrigine, amphetamines, dextroamphetamine-amphetamine, methylphenidates, fluoxetine, and sertraline. The medications were stopped when they resulted in side effects or were deemed ineffective. She was five years old when she completed her genetic testing by cheek swab and was also found to have a severe MTHFR deficiency. The family started her on over-the-counter L-methylfolate 7.5 mg tablets once a day and noted great improvements in her behaviors two weeks later as well. The patient went from being defiant and oppositional to being able to be redirected at home and school, following through on instructions, and retaining information better than before.Much research has been dedicated to learning about one of the most important enzymes involved in folate metabolism and pathways involving catecholamine neurotransmitters. The MTHFR C677T mutation is the most common MTHFR mutation . In factDecreased MTHFR activity, which results in decreased folate metabolism, can be seen in multiple psychiatric illnesses such as schizophrenia, bipolar disorder, depression, ASD, and ADHD. As discussed, research indicates the positive effects of l-methylfolate as adjunctive therapy for certain mental health illnesses . NeverthIn summary, this article discusses two cases, that of biological siblings, with behavioral concerns, medication trials, and the discovery of MTHFR deficiency. Further research is needed to expand on this topic. Future steps include studying the long-term benefits of folate supplementation and identifying which psychiatric patients the supplement may or may not be effective with and how patients respond to traditional pharmacological treatment with and without the supplement. If positive effects are shown consistently, future work is needed to try and get Food and Drug Administration (FDA) support for this supplement so it can become a cost-effective treatment option for patients with an MTHFR deficiency and psychiatric comorbidities.


Climate change and increasing demands to reduce the environmental impact of feed production are major challenges for animal nutritionists. Compared to wheat, which is commonly used in high levels in European piglet diets, rye is more efficient in using limited resources, most importantly, water and phosphorus. As a result, its cultivation has a relatively low carbon footprint. The high amounts of non-starch polysaccharides of rye might lead to an increased intestinal fermentation with potential beneficial effects on gut health. However, the high levels of non-starch polysaccharides in rye, which have a major impact on the physico-chemical conditions of the digesta, might affect digestibility and performance especially in young animals. It was therefore of interest to compare the effects of isoenergetic diets with increasing levels of rye as a replacement for wheat fed to young fattening pigs (bodyweight: 16–40 kg). The control diet contained 69% of wheat, while in the other three experimental diets, the amount of wheat was gradually replaced (by a third in each case) with rye. Thus, the experimental diets contained 23, 46, and 69% of rye. A total of 40 young pigs were housed individually in four dietary treatment groups. During a 4 week trial, effects on performance, digestibility, products of intestinal fermentation, and fecal characteristics were evaluated. There were no negative effects on feed intake and gains, even though the feed conversion ratio increased with the highest dietary rye level (69%). Digestibility rates of organic matter and crude protein did not differ significantly. Without affecting the characteristics of the feces, numerically higher amounts of intestinal fermentation products and higher colonic digesta mass were observed. In 2022, the highest annual mean temperature since weather records began was measured in Germany . An incrootprint . Thus, aootprint –15. Geneootprint , moreoveootprint , 16. Nevootprint , 17, 18.ootprint . The sugootprint , 21, 22.ootprint . Furtherootprint , 23. Ryeootprint . Neverthootprint  that salTo use rye as a resource-efficient alternative to wheat, and thus also to be able to use its positive effects on animal health, it is necessary to critically test whether, and to what extent, feed intake, digestibility, performance, including feed conversion ratio (FCR), and intestinal conditions as well as fecal characteristics might be influenced when rye is used instead of wheat. Young fattening pigs were deliberately selected for this study, in which disturbances in the digestive tract are very rapidly accompanied by changes in fecal condition.2.2.1.The experiments were carried out in accordance with German regulations. The studies involving animals were reviewed and approved by the Animal Welfare Officer of the University of Veterinary Medicine Hannover, Hannover, Germany (reference: TiHo-T-2018-24).2.2.ad libitum at any time. Visual and tactile contact between the animals was possible through a hole installed in the partitioning walls between the pens. At the beginning of the feeding trial, the piglets were 46.8 ± 5.28 days old with an average bodyweight of 16.1 ± 4.13 kg.A total of 40 piglets, owned by the Institute for Animal Nutrition, University of Veterinary Medicine Hannover, were housed individually during 5 weeks in the stables of the Institute. The weaned piglets of cross genetics  were allocated to four feeding groups. Pigs were selected on the basis of body weight, sex and sow (siblings distributed between groups) to form four comparable treatment groups. The animals were housed individually in 1 m × 3 m pens with concrete floors, equipped with enrichment materials and nipple drinkers, which provide drinking water 2.3.Each group was fed a pelleted diet consisting of wheat and/or rye, barley, soy, potato protein, and a mineral supplement. The sum of wheat and rye was 69% in all diets, whereby the compound feed of each group was characterized by a different ratio of wheat to rye . Diet I,The chemical composition as well as the particle size distribution of the pelleted diets are described in 2.4.ad libitum. The animals received the pelleted diet every morning at the beginning of an experimental day (08:30). A mass was chosen that also resulted in feed residuals on the following day. Care was taken to ensure that no pellets remained in the trough or pen from the previous day. The mass that was not ingested was weighed in the morning before feeding. The difference between weighing in and weighing out gave the mass of ingested feed in original substance (as fed). To calculate the actual ingested mass, the backweights of each experimental week were collected individually, pooled, and the dry matter content (DM) was determined in an aliquot. The dry matter contents of the diets were known from the previous analyses.In the first week of the study, the piglets were acclimatized to the experimental diets by a gradual changeover from the previously fed diet. After adaptation, the animals were fed 4 weeks with the respective compound feed (CF) variant Body weight (BW) of each animal was determined weekly. The feed conversion ratio (FCR) resulted from the quotient of feed intake (kg as fed) and body mass gain.The apparent total tract digestibility was determined by collection method , 27. In At the end of an experimental day, the feces were homogenized and weighed individually to receive a daily fecal sample for every pig to determine the DM content. The remaining fecal samples were frozen at −18°C. After the end of the collection period, the faecal samples were defrosted and homogenized individually for every piglet. The apparent total tract digestibility (ATTD) was calculated according to the following formula :The samples of feed, digesta, and feces were analyzed by standard procedures in accordance with the official methods of the Agriculture and Testing Research Institutes (VDLUFA) . Feed pa2.5.®  and Stresnil® . After the neuroleptanalgesia had set in, the pigs were euthanized by intracardiac injection of T61® . The dissection started with opening the pigs from the pelvis along the linea alba to the sternum. The stomach was ligated both towards the esophagus and the duodenum with double ligatures. After another double ligature was placed in front of the rectum, the intestinal tract was exenterated in toto. The small intestine, cecum, and colon were then separated by further double ligatures. The organs were separated and weighed. Using the thumb and forefinger, the contents were spread out under continuous well dosed pressure. After this careful emptying, the organs were weighed again to determine the weight of the organs and the mass of the digesta.Anesthesia was conducted using Ketamidor2.6.® 9.4 by means of Enterprise Guide Client Version 7.1 . Descriptive statistics included calculating measures such as mean, standard deviation, and percentages. A test for normal distribution was performed using distribution analysis by means of the Shapiro–Wilk test for analytical evaluation. Depending on this, parametric and non-parametric procedures were then used. Normally distributed model residuals were tested by analysis of variance or using a multiple spanning test (Ryan-Einot-Gabriel-Welsch-Q test). For non-normally distributed data or values in the form of a score, the Kruskal–Wallis test was applied accordingly. The significance level was determined as alpha = 5% (p < 0.05). Significant differences were indicated by appending different superscript letters .The analysis of available data was performed using the computer programs Statistical Analyses System for Windows, SAS3.3.1.The average daily feed intake (ADFI) was recorded daily and is shown in 3.2.During the second week, the apparent total tract digestibility (ATTD) was determined. Significant differences were found in the ATTD of ether extract (EE) only .3.3.There were no significant differences in fecal consistency, dry matter content, and pH values .3.4.No significant differences in organ and digesta mass of cecum and colon, concentrations of SCFA, and lactic acid were found, partly due to high standard deviations of the values.Nevertheless, numerically differences occur. For example, numerically higher masses of the emptied colon and colon digesta were found with highest dietary rye levels. In addition, increasing rye contents in the compound feed resulted in numerically higher (not significant) lactic acid concentrations in the content of the cecum and colon .4.p < 0.05), even though the weight of the animals did not differ. At very high input rates, the addition of enzymes had a positive effect on FCR , a higher feed conversion ratio was determined when wheat and small amounts of barley were replaced by rye in the diet and thus a rye proportion of up to 30% was fed. The control group reached a feed conversion ratio of 1.57 kg/kg, whereas in the experimental group (30% rye), an FCR of 1.64 kg/kg was determined . It was The parameter of fecal characteristics is important, as it determines cleanliness of the stable to a large extent. The fecal characteristics were examined visually and chemically using laboratory analysis . The evaluated score values 1.9–2.2,  correspo5.Even with really high dietary levels of rye (69%), the young fattening pigs achieved an average daily feed intake of more than 1,300 g DM. Digestibility rates (%) of organic matter and crude protein did not differ. With increasing amounts of rye in the diet, digestibility of EE was reduced. Daily weight gains were not significantly affected. When wheat was replaced completely by rye, the FCR increased. Further experiments are needed to determine not only the concentrations but also the production rates of various favorable products of the microbiota. Nevertheless, no negative effects  of feeding even high proportions of hybrid rye in young fattening pigs were found.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The experiments were carried out in accordance with German regulations. The studies involving animals were reviewed and approved by the Animal Welfare Officer of the University of Veterinary Medicine Hannover, Hannover, Germany (reference: TiHo-T-2018-24).VW and JK contributed to the conception, design of the study, and wrote sections of the manuscript. VW organized the database, performed the statistical analysis, and wrote the first draft of the manuscript. All authors contributed to the article and approved the submitted version.The project was supported by funds of the Federal Ministry of Food and Agriculture (BMEL) based on a decision of the Parliament of the Federal Republic of Germany via the Federal Office for Agriculture and Food (BLE) under the innovation support program (FKZ: 281B101016). This Open Access publication was funded by the Deutsche Forschungsgemeinschaft —491094227 “Open Access Publication Funding” and the University of Veterinary Medicine Hannover, Foundation.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Children who experience mental health issues, such as attention deficit hyperactivity disorder (ADHD), experience significant distress and impairment at home, at school, and in the community. Without adequate care or prevention, this frequently results in adulthood-long distress and impairment at large societal costs. Determining the prevalence of ADHD cases among preschoolers as well as some associated maternal and child risk factors was the aim of this study.An analytical cross-sectional study including 1048 preschool children aged 3–6 years was carried out in Tanta City, Gharbia Governorate. From March to April 2022, a proportionate stratified cluster random sample of them was picked. Data were gathered using a predesigned instrument that included sociodemographic information, family history, maternal and child risk factors, and the Arabic version of the ADHD Rating Scale IV questionnaire.The prevalence of ADHD among preschoolers was 10.5%. The inattention type was the most common (5.3%), followed by the hyperactivity type (3.4%). There were statistically significant associations regarding positive family history of psychological and neurological symptoms (17.9% positive vs. 9.7% negative), family history of ADHD symptoms (24.5% positive vs. 9.4% negative), active smoking by the mother (21.1% positive vs. 5.3% negative), cesarean section delivery (66.4% positive vs. 53.9% negative), elevated blood pressure during pregnancy (19.1% positive vs. 12.4% negative), and history of taking drugs during pregnancy (43.6% positive vs. 31.7% negative). Significant child risk factors were: exposure to any source containing lead that causes slow poisoning (25.5% positive vs. 12.3% negative), children with cardiac health problems (38.2% positive vs. 16.6% negative), and hours spent by a child in front of the TV or mobile phone (any screens) per day (60.0% of those with positive screening spent more than 2 h/day vs. 45.7% negative).In the Gharbia governorate, 10.5% of preschoolers suffer from ADHD. Significant maternal risk factors for ADHD included a positive family history of psychiatric and neurological symptoms, a family history of ADHD symptoms, active maternal smoking, caesarean section delivery, increased blood pressure during pregnancy, and a history of drug use during pregnancy. Youngsters who had cardiac health issues and who spent more time each day watching TV or using a mobile device (screen use) were at substantial risk. In children worldwide, attention deficit hyperactivity disorder (ADHD) is one of the most prevalent psychiatric diseases. There are three different varieties of it: largely inattention, hyperactive, and composite type. It is characterized by a concomitant inattention and impulsivity or hyperactivity . Many, iAlso, it is linked to risky prenatal maternal factors that negatively impact the fetus, such as alcohol consumption, stress on the mother, bleeding during pregnancy, corticosteroids, use of illegal drugs, smoking, and exposure to toxins . ResearcIn a meta-analysis research published in 2015, the prevalence among people under the age of 18 was estimated to be 7.2% globally, which, according to the 2013 Census Bureau, equates to 129 million youngsters [In the United States National Survey of Children's Health (2016), parents stated that 9.4% of children aged 2 to 17 had been diagnosed with ADHD. More precisely, 2.4% of children aged 2 to 5 had the disorder, 9.6% of children aged 6 to 11 had it, and 13.6% of teenagers aged 12 to 17 had it. Also, they stated that a total of 8.4% of kids between the ages of 2 and 5 years, 8.9% of kids between the ages of 6 and 11 years, and 11.9% of teenagers between the ages of 12 and 17 reported having ADHD now [Prevalence among preschoolers was found to be 4.6% in a 2018 study conducted in Germany . AnotherADHD often persists into adulthood if not managed and is considered a risk factor for other mental disorders and undesirable outcomes, including educational underachievement, difficulties with employment and interpersonal relations, and criminality .The estimated costs pended on individual adjustment, the reforming of family and school life, health care services, and social services underscore the importance of earlier identification and treatment. To our knowledge, a few studies have investigated the prevalence of ADHD in the Gharbia governorate and its associated risk factors. So, the aim of this study was to determine the prevalence of ADHD among preschoolers and identify some associated maternal and child risk factors in Gharbia Governorate, Egypt.This is an analytic cross-sectional study that was conducted in Tanta city, Gharbia governorate, Egypt. Gharbia governorate is in the northern part of Egypt. It consists of 8 cities and covers more than 25 thousand square kilometers, making it the tenth largest governorate in Egypt. Gharbia is also quite densely populated, with more than five million people according to the Central Agency for Public Mobilization and Statistics (CAPMAS). Tanta is Gharbia's capital city and is the fifth most populated city in Egypt, with more than 400 thousand residents.The sample size was calculated using the Epi Info (2000) program, depending on a past review of the literature. Elsaid N et al.  estimateA proportionate stratified cluster random sampling technique was used as follows: first stage: simple random by choosing one district (Tanta) out of eight in Gharbia governorate, Egypt. Second stage: stratification of Tanta city into two geographical districts  Third stage: stratification of each educational administration into government and private schools The East Administration involved 16 governmental and 9 private schools. The West Administration involved 15 government and 10 private schools. Fourth stage: systemic random selection of schools by list for both governmental and private schools 15 governmental (8 east and 7 west) and 11 private schools (8 east and 3 west) were chosen. Fifth stage: cluster random selections of classes; two classes from each school were chosen randomly .The number of children selected from governmental schools was 563 (298 from the east and 265 from the west administration), representing 64.7% of the total sample size, while the number of children selected from private schools was 307 (205 from the east and 102 from the west administration), representing 35.3% of the total sample size.Inclusion criteria: Children ages 3–6 years, both males and females.Exclusion criteria: children with a neurological or chronic illness, e.g., epilepsy, cerebral palsy, autism, and movement disorders.Tools of the study: We used two questionnaires.Socio-demographic data include age, sex, residence, birth order, father and mother's education, and family income.Family history: psychological and neurological illness and history of ADHD among relatives.Maternal risk factors include neurological and psychological symptoms , active and passive smoking by the mother during pregnancy, timing and type of delivery, blood pressure during child pregnancy, and a history of taking drugs during child pregnancy.Child risk factors include: child exposure to any source containing lead that causes slow poisoning; significant head injury since birth; cardiac health problems; and the number of hours that the child spends in front of the TV or mobile phone (or any screens) per day.Healthcare professionals utilize the criteria in the Diagnostic and Statistical Manual, Fifth Edition (DSM-5) of the American Psychiatric Association to diagnose ADHD . With a If two or more of the following symptoms are noticed in young children, a referral should be made to a specialist with experience with ADHD in the preschool years . A) TrouADHD Screening Questionnaire: ADHD Rating Scale IV (ADHD-RSIV) Arabic Version is originally based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria and frequently used in epidemiological studies . It contWe used a validated and reliable ADHD screening questionnaire that had been used in previous studies . We tranAuthors tested the risk factors questionnaire reliability in a pilot study by recruiting 20 parents of preschool child not included in the present study. We used data to assess internal consistency using Cronbach’s alpha, which was 0.793 and represented adequate internal consistency.The authors calculated the content validity index (CVI) and content validity ratio (CVR) as measurements of the content validity of the first questionnaire. The individual-CVI ranged from 0.82 to 1.00, with twenty items having an I-CVI of 1.00 and two items having an I-CVI of 0.82. All items were considered relevant. The CVR was generated for each item. Twenty items had a CVR of 1.00, and two had a score of 0.99.The study was conducted on 1048 preschool children aged 3–6 years old. They were chosen randomly from selected schools during the period from March 2022 to April 2022. This study was conducted after its approval by the ethical committee of the faculty of medicine at Tanta University. All parents or legal guardians of children gave valid written informed consent after a clear explanation of the study's aims and techniques.The questionnaires were filled out by parents only or legal guardians in the absence of parents. Parents were asked to fill out a predesigned, self-administered questionnaire and the Arabic form of the ADHD screening sheet. Those who were illiterate were interviewed by the researchers and well-trained third-year medical students during the arrival or departure of their children from school. Children with positive screening results were referred to a psychiatrist specializing in ADHD diagnosis for further assessment and treatment.P value was set to be significant at < 0.05.Data was collected and statistically analyzed using an IBM personal computer with Statistical Package for Social Science (SPSS) version 21. Qualitative data was expressed as a number and percent and tested by the chi-squared test. Quantitative data was expressed as mean and standard deviation and tested by the t-test. The crude and adjusted odds ratios using logistic regression analysis were calculated at 95% confidence intervals. Logistic regression was used to calculate the effects of risk factors as independent variables. The The prevalence of attention deficit hyperactivity disorder among preschool children was 10.5%. The inattention type was the most common, present in 5.3% of cases, followed by the hyperactivity type (3.4%) . More than half of males screened positive (57.3%), compared to 42.7% of females. Also, most rural preschoolers screened positive (68.2%) compared to 31.8% of urban preschoolers. There were statistically significant associations regarding father, mother education (a higher percentage of positive screening was reported in university-educated parents (55.5%) vs. 4.5% for illiterate fathers and 6.4% for illiterate mothers), and also family income (66.4% of those who had enough income were positive screeners compared to 13.6% who had not enough) , family history of ADHD symptoms (24.5% positive compared to 9.4% negative), all degrees of kinship , active smoking of the mother (21.1% positive compared to 5.3% negative), cesarean section delivery (66.4% positive compared to 53.9% negative), elevated blood pressure during pregnancy (19.1% positive compared to12.4% negative), and history of taking drugs during pregnancy (43.6% positive compared to 31.7% negative). Higher frequency of positive screening was detected with antibiotics, hormonal therapy, and anticoagulants taken during pregnancy , while higher frequency of negative screening was detected with calcium and multivitamins 39.4% (Table Exposure to any source containing lead that causes slow poisoning (25.5% positive compared to 12.3% negative), children having cardiac health problems (38.2% positive compared to 16.6% negative), and hours spent by a child in front of the TV or mobile phone (any screens) per day were significant risk factors for ADHD (60.0% of those with positive screening spent more than 2 h/day compared to 45.7% negative)  per day Table .Table 4LADHD is a neurodevelopmental disorder with a common onset in the preschool years of childhood. It is characterized by a persistent pattern of inattention and/or hyperactivity. The present study showed a pooled prevalence of ADHD among preschool children of 10.5%.This is notably larger than other international studies, which showed a lower prevalence of 2 to 7.8% , 16. It The inattention type was the most common type present in our study, affecting 5.3% of cases, followed by the hyperactivity type (3.4%). In agreement with our results, the systematic review in Africa concluded that the inattentive type was the most predominant, followed by hyperactive-impulsive and the combined type, with a prevalence of 2.95%, 2.77%, and 2.44%, respectively . This waVariability in ADHD prevalence may be attributed to different research methodologies, a lack of parents' knowledge about ADHD, and it being a multifactorial disorder . Also, CThe current study revealed a higher prevalence of ADHD in males (57.3%) than females (42.7%). However, the difference was not statistically significant. This finding disagrees with other studies such as Albatti 2017), Hamidzadeh et al. 2020, and Hassaan FM 2020 , Hamidza, 22. GenADHD has also been linked to other socio-demographic factors, like first-born status , and thiStatistically significant associations regarding fathers', mothers', and enough family income were detected in this study. Hassaan FM 2020 showed a low frequency of ADHD in children with highly educated parents and a high frequency of ADHD in patients with low socioeconomic status, despite being non-statistically significant  which isLower socioeconomic status with a higher prevalence of ADHD was also reported by Rowland AS, 2018 . HoweverThe present study reported that a positive family history of psychological and neurological symptoms, a family history of ADHD symptoms, active smoking by the mother, cesarean section delivery, elevated blood pressure during pregnancy, and a history of taking drugs during pregnancy were significant maternal risk factors for ADHD.These findings are similar to those reported by Hamidzadeh et al. (2021), who found a significant relationship between a family history of psychological problems and ADHD . ResearcThis study reported that children with cardiac health problems are a significant risk factor for ADHD. This finding is in line with the results of Hamidzadeh et al. (2021) , 34. ConIncreased screen hours spent in front of a TV or mobile phone per day were significant child risk factors for ADHD. Research has widely discussed the relationship between ADHD and screen time. Children and adolescents diagnosed with ADHD or rated as having attention problems or impulsiveness were found to have a greater rate of screen time . Screen This relationship may have become more evident in COVID-19 times, when parents had to be parents and teachers at the same time. It’s expected that they may sometimes allow their children more screen time .Logistic regression in this study showed that active smoking by the mother, history of taking drugs during child pregnancy, and screen time are the most relevant risk factors for ADHD among the studied group.Pregnant women should be encouraged to quit smoking and avoid exposure to tobacco smoke, as maternal active smoking during pregnancy contributes to the increased risk of ADHD at preschool age .A meta-analysis of 27 articles showed that prenatal exposure to maternal smoking during pregnancy was significantly associated with childhood ADHD after adjusting for parental psychiatric history and socioeconomic status .Drugs during pregnancy can affect the baby's growing brain, leading to intellectual and social problems in childhood. Even mothers who took the pain reliever acetaminophen during pregnancy were at higher risk for ADHD and behavior problems . AnotherIn the Gharbia Governorate, attention deficit hyperactivity disorder was relatively common among preschoolers. There were certain maternal risk factors found, such as the mother's active smoking, a caesarean delivery, high blood pressure during pregnancy, and a history of drug use while pregnant. Youngsters who had cardiac health issues and who spent more time each day watching TV or using a mobile device (screen use) were at substantial risk. Also, risk variables included a positive family history of psychiatric and neurological symptoms as well as a family history of ADHD symptoms.ADHD screening should be a prerequisite for school entry in all Egyptian schools for the early management of these cases to help them lead a good quality of life.This study recruited a large sample size of both sexes and residence areas in one of the most densely populated parts of the mid-Delta region of Egypt and targeted young children to allow for early detection and proper management of this important disorder.However, parent reported ADHD diagnosis may include false-positive results, especially for mild, untreated cases. Also, a false diagnosis may be due to a more strict assessment of children’s behavior and a free atmosphere for children at home.Alcohol intake is low, as the Egyptian population is mostly Muslim. The Holy Book of the Quran strictly prohibits alcohol use.Viral infections, as the Egyptian females usually can't differentiate between bacterial and viral infections, and most of them don't prefer to go to physicians, especially for simple infections.Also, breast feeding Egyptian females can't remember the duration of breast feeding, and most of them resort to early weaning practices.The authors could not investigate some other risk factors in this study, such as:


Karuthakar, Poovan samba, Mattaikar, Edakkal, Manvilayan, and Varappu kudainchan were identified as genotypes tolerant to early water submergence. The shoot and root length of susceptible landraces were significantly lower than the tolerant landraces under hypoxia condition, implying that landraces with longer shoots and roots had a higher survival rate. The response index substantiated this. The results clearly show that tolerant and moderately tolerant landraces possessed higher mean values for root and shoot lengths than susceptible landraces. The landraces grouped under the long–bold category had superior AGP and AVI scores to other grain type groups. This raises the possibility that differences in kernel breadth, which is linked to grain type, could affect anaerobic germination potential. Molecular confirmation using gene-specific markers, viz., DFR, TTP_G4, RM478, RM208, and RM24161, for which the polymorphic information content (PIC) value ranged from 0.36 (RM478) to 0.68 (RM206) suggests that this diverse panel of landraces must be assessed further using advanced molecular tools to precisely clarify the genetic mechanism behind this phenomenon. The tolerant landraces thus identified may become donors in breeding programs. The introduction of these traits would contribute to the development of rice varieties tolerant to anaerobic stress, resulting in sustainable yields. This solution could promote the DSR system across the world.Direct-seeded rice (DSR) is a promising alternative to the traditional puddled rice system. It has become more popular among rice growers as a result of socioeconomic shifts and global climate change. Although DSR offers advantages, rice plants experience greater anaerobic stress at sowing from unpredicted rainfall. Rice is unique among cereals in its ability to germinate under anaerobiosis. The coleoptile of rice rapidly elongates above the water surface to obtain more oxygen and enhance vigorous seedling growth. A panel of 115 landraces and four check varieties were subjected to anaerobic stress with a water level of 10 cm for up to 15 days. The present study observed significant variation in anaerobic germination percentage (AGP) (10%–100%) and anaerobic vigor index (AVI) . Landraces  Direct-seeded rice (DSR) is a cultivation method that has gained popularity across rice-growing regions in recent years. Contributing factors to this trend the include reduced costs of production, reduced water demand, reduced labor requirements, and early maturity. Particularly in Asia, vast areas once covered by puddled transplant systems have adopted DSR systems . HoweverOryza sativa L.) is a semiaquatic plant , with its potential to germinate under hypoxic conditions due to its α-amylase genes  mapping studies have identified numerous QTLs that govern major and minor effects of AGT . QTL qAGmosome 9  and was   is a special landrace widely cultivated in the northern districts of Tamil Nadu, India. It can germinate in flood conditions and grow up to 3 feet in height , Aduthurai, Tamil Nadu, India (10°99'85"N and 79°48'01"E). These uniform healthy seeds were screened for AGT. Morphological traits such as kernel length (KL), kernel breadth (KB), length-to-breadth ratio (LBR), and 100-seed weight (HSW) were recorded for the selected genotypes. Grains of the selected genotypes were classified into different grain types as per the literature  in a plastic tray (sized 60 × 30 × 40 cm) with three replicates. Cups were then immediately submerged in water 10 cm above the soil surface, where they were held for 15 days  was calculated using the formula proposed by Total genomic DNA was isolated for all the genotypes using the CTAB (cetyltrimethylammonium bromide) method . The quaThe allelic status of the AGT genotypes was examined using inserations and deletions (InDels) and simple sequence repeats (SSR) markers linked to AGT. The details of the markers used in this genotypic analysis are given in per se performance, promising genotypes for AGT were identified.An analysis of variance (ANOVA) for traits associated with AG potential was conducted with R studio software  using thp< 0.01) was found for AGP, ranging from 10% (Samba mosanam) to 100% (Karuthakar), and AVI ranged from 150 (Samba massanam) to 4,433 (Poovan samba) (Samba mosanam) to 35.76 cm (Poovan samba), whereas the root length varied from 1.69 cm  to 11.63 cm (Iravai pandi). The response index ranged from –1.92 (Thillainayagam) to 17.42 . The traits SRR (1.09–12.29), NOL (0.67–2.56) and NOR (2.40–11.41) showed considerable variation. Significant variations were found in morphological characteristics  and test seed weight (p< 0.01) among the landraces studied. The KL, KB, LBR, and grain weight ranged from 4.00  to 9.70 mm (Chinnar), 1.60 (Jai Sri Ram) to 3.80 mm (Thondi), 1.67  to 3.95 (Chinna punchai), and 0.78 (Thulasi vasanai) to 3.65 g (Thondi), respectively, among the studied landraces.This study investigated variations in the physical characteristics and anaerobic germination potential of native south Indian landraces under normal and hypoxic conditions to assess the tolerance of these landraces to flooding at the time of germination. The variance analyses conducted on the anaerobic germination-associated traits of the 119 genotypes revealed highly significant genotypic variance within each individual year and in the pooled data over the years, except in the case of the fresh and dry weights of the seedlings Table 2.The phenotypic coefficient of variation (PCV), genotypic coefficient of variation (GCV), heritability, and genetic advance (GA) were evaluated for the 119 rice genotypes. The PCV values ranged from 15.38% (LBR) to 88.15% (DW), whereas GCV ranged from 15.14% (LBR) to 71.06% (AVI). The PCV value was higher than the GCV value for all studied traits. This finding demonstrates the predominance of environmental interaction in determining the expression of these traits. AGT-associated traits, such as AGP, AVI, SL, and RL, had a high PCV coupled with strong GCV values. Broad-sense heritability varied widely from 18.23% to 98.85%. Traits associated with AG potential, such as AGP, AVI, RI, SL, and RL, along with seed morphological traits such as KL, KB, LBR, and HSW, had high heritability. Genetic advance as a percentage of means ranged from 12.87% (SRR) to 540.89% (RI). Traits such as AGP, AVI, SL, RL, RI, and grain weight displayed a high genetic advance as a percentage of mean (GAM) and high heritability.viz., KL, KB, LBR, and HSW, varied widely , followed by Salem samba, Maranellu, and ‘IR 42’ (13.33%). Karuthakar displayed the maximum AGP (100%) after 15 days of hypoxia. On the basis of AGP, the landraces were divided into four categories, as proposed by Anaerobic germination percentage is a key trait to identify the genotypes that are tolerant to hypoxia under the DSR cultivation system. Thillainayagam) to 17.42 . Thirty-six landraces scored as susceptible or moderately susceptible had RI values less than zero. This finding implies a reduction of shoot length under hypoxia. In addition, AVI was calculated based on a seedling’s growth characteristics and AGP. Landraces Poovan samba , Karuthakar , Mattaikar , and Edakkal  had higher AVI values than the susceptible landraces Samba massanam (150), Salem samba (250), Maranellu (260), and ‘IR 42’ (279).Shoot elongation under anaerobic stress is another important adaptive mechanism that helps emerging seedlings tolerate early-stage submergence. The response index (RI) is generally used to identify the genotypes with shoot elongation under stress compared with the control environment. RI values ranged from –11.92  values were found to be significantly and positively associated with RI, shoot and root length, number of leaves and roots, grain breadth, and HSW. However, a positive and non-significant association was observed with grain length  under hypoxic conditions. A significant negative correlation was observed between grain length–breadth ratio and AGP  and AVI . Furthermore, LBR exhibited a strong negative association with kernel breadth  and grain weight, and a positive significant correlation with grain length. A highly significant association under anaerobic treatment was found between RI and the following traits: SRR, shoot length, and number of leaves. The association among shoot length, root length, SRR, and number of roots was significant and positive. Similarly, both grain length and breadth were positively correlated with grain weight.In this study, a simple correlation analysis was conducted between the seedlings’ morphological traits and the early-stage submergence tolerance traits, such as AGP and AVI, among the genotypes under study. The AGP and AVI  with an eigenvalue of > 1 accounted for 79.15% of the total variation Table 6.Karuthakar, Edakkal, and Varappu kudainchan, were clustered within the first quadrant (top left), whereas Poovan samba, Mattaikar, Mandamaranellu, and Manvilayan were grouped within the fourth quadrant (bottom left). Furthermore, cultivars ‘IR42’, ‘FR13 A’, ‘CO 43’, and ‘CO 43 Sub1’ were placed in the second quadrant (top right). The first and the fourth quadrants together comprised all of the tolerant and moderately tolerant landraces, except Karnel (second quadrant) and Chittimutiyalu (third quadrant), with high AGP, AVI, RI, and shoot and root length values along with an LBR ratio of > 2.5. The second and third quadrants encompassed the majority of the susceptible landraces, including ‘IR 42’. Landraces such as Samba Massanam (10%), Maranellu (13.33%), and Salem samba (13.33%) were highly susceptible and belonged to the most divergent cluster in the second quadrant, which distinguishes them from the rest of the landraces.Biplot analysis between PC1 and PC2 explains the distribution and nature of the diversity based on the variables as well as genotypes , AVI , SL (33.36 cm), RL (9.53 cm), RI (12.82), NOL (2.20), and NOR (6.95) compared with other clusters. Cluster VI, included 19 moderately tolerant landraces and seven tolerant landraces (≥ 90% AGP), such as Manvilayan, Mandamaranellu, Varappu kudainchan, Varisuriyan, Mohini samba, Katta samba, and Kaan, possessed a high mean value for SRR (4.29). The majority of landraces with high values for AGP-associated traits were in clusters IV and VI. These landraces possessed high values for AGP (> 73.33%), AVI , shoot length (25.11–35.76 cm), and RI. Cluster V had 26 landraces, 17 of which were identified as moderately tolerant (> 71% of AGP) and nine as moderately susceptible. Cluster III had 35 genotypes, forming the largest cluster, with an AGP of 16.67%–56.67%, and including ‘FR13 A’, ‘CO 43’, and ‘CO 43 Sub1’. Cluster II included 24 landraces, whereas susceptible control variety ‘IR 42’ clustered with other susceptible landraces Maranellu, Salem samba, and Samba masanam in cluster I. The mean values of each cluster significantly differed for all traits, except kernel length, kernel breadth, and grain weight. On average, the phenotypic within-cluster distance was found to be highest in cluster IV, followed by clusters I and II; cluster V had the lowest mean distance . SRR showed a significant association (p< 0.05) with RM478 (R2 = 6.28%). Similarly, KB and LBR showed a highly significant association (p< 0.01) with RM206. HSW had a significant genetic association with two polymorphic markers (RM478 and RM206).We conducted a single-factor ANOVA-based single-marker analysis to validate genetic associations among four polymorphic markers and the traits associated with AG potential. Statistically, five significant genetic associations were observed for four traits  Table 9.Karuthakar and Poovan samba, in cluster III, formed a distinct sub-cluster. Cluster IV displayed a higher mean distance (3.73). Inter-cluster distance was highest between clusters I and IV, followed by the clusters I and III (The 119 genotypes considered for the investigation were grouped into four clusters ranging from 16 landraces (cluster II) to 49 landraces (cluster IV)  coupled with high heritability. High heritability plus high genetic advance would be the best genotype selection indicators , suggesting that selection would be effective based on these traits. Furthermore, dicators . Thus, tKaruthakar, Poovan samba, Mattaikar, Edakkal, Manvilayan, Mandamaranellu, Varappu kudainchan, Varisurian, Katta samba, Kaan, and Mohini samba were found to have > 90% AGP, and are regarded as AGT landraces. Karuthakar, Poovan samba, Mattaikar, and Edakkal were found to possess high AGP and AVI values.It is crucial to select rice genotypes with high seedling vigor for germination under anaerobic conditions in a DSR system. Among the 119 genotypes studied, the landraces Edakkal, Karuthakar, and Varappu kudainchan minimized root length reduction and expressed higher shoot length. AGP and AVI when compared among the other tolerant genotypes which were expressing root elongation under hypoxia. Genotypes ‘FR13 A’ and ‘CO 43’ with the Sub1 locus recorded lower shoot length and RI than the AGT landraces. This finding infers that the Sub1 gene introgressed genotypes that were unable to cope with submergence during the germination process, despite being tolerant to vegetative-stage submergence. Sub1 locus-conferring genotypes undergo a quiescent strategy  and 44 (cluster V) landraces each. Of the 47 tolerant landraces (> 70% AGP) identified, 30 (63.8%) were grouped in clusters I and VI. The landraces in clusters I and VI all exhibit long–bold grain types, except otential . Hybridip< 0.05) associations for HSW with RM478 and RM206. Conversely, only the single marker RM206 could be significantly associated with KB and LBR. Higher phenotypic variance values of significant markers indicate that they control a considerable amount of genetic variation in grain dimensions and could be reliable genetic markers for the further improvement of rice grain shape. For AGT-associated traits, only SRR had a significant association with RM478 when compared with other traits. In marker-assisted breeding programs, a strong MTA is preferred over a weak MTA to effectively exploit that particular marker for trait improvement. Hence, further analysis using a diverse set of polymorphic markers dispersed over the entire genome or next-generation sequencing would help to identify strong MTAs for AGT-associated traits that could be exploited in future breeding programs to develop an AGT varieties.The two InDel and three SSR markers used in this study were selected based on earlier reports that investigated AGT . ClusterKaruthakar, Poovan samba, Mattaikar, Manvilayan, Edakkal, and Varappu kudainchan are promising candidates for traits associated with anaerobic germination potential. Salient agronomic features of these AGT landraces are reported in Karuthakar, Poovan samba, and Mattaikar possess significant sheath and seedling elongation characteristics (In this study, promising trait-specific landraces were identified for traits associated with anaerobic germination potential and were compared with grain type. The genotypes that were identified as having anaerobic germination potential registered significantly higher values for the corresponding traits than the overall mean. Among the studied landraces, eristics . These aKaruthakar, Poovan samba, Mattaikkar, Edakkal, and Manvilayan, which can be used as donors in future breeding programs. This may in turn pave the way for understanding the genetic mechanisms that underlie anaerobic germination tolerance.The development and use of AG-tolerant rice varieties has drawn considerable interest recently; such varieties will promote food supply and rice production stability during climate change and global warming. The outcomes of this study provide the possibility of improving rice cultivars with AGT, as these germplasms provide wider genetic variations for traits associated with anaerobic germination potential. Modern breeding tools based on sequencing approaches and genomic selection will enable crop breeders to target desirable traits in chromosomes, and identify and elucidate the genetic mechanisms at play. Genome-wide association studies would be the ideal way to study such a diverse panel of landraces. They also provide the possibility of discovering superior AG-tolerant alleles or novel genes, which may offer tolerance to early submergence during germination. This trait can reduce crop loss occurring after persistent flooding in flood-prone areas during monsoons. The current study identified novel sources of AGT in landraces The original contributions presented in the study are included in the article/All authors listed have made a substantial, direct, and intellectual contribution to the work, and approved it for publication.


The serum levels of DEFA1 showed an inverse correlation with the inattention scores in the SNAP-IV parent form (p = 0.042) and teacher form (p = 0.010), and the hyperactivity/impulsivity scores in the SNAP-IV teacher form (p = 0.014). The serum levels of occludin showed a positive correlation with the subtest of detectability in the CPT (p = 0.020). Our study provides new reference into the relation between gut leakage markers and cognition, which may advance research of the pathophysiology of ADHD.Attention-deficit/hyperactivity disorder (ADHD) is a commonly seen mental disorder in children. Intestinal permeability may be associated with the pathogenesis of ADHD. The study herein investigated the role of gut leakage biomarkers in the susceptibility of ADHD. A total of 130 children with ADHD and 73 healthy controls (HC) individuals were recruited. Serum concentrations of zonulin, occludin, and defensin (DEFA1) were determined. Visual attention was assessed with Conners’ continuous performance test (CPT). In order to rate participants’ ADHD core symptoms at home and school, their parents and teachers completed the Swanson, Nolan, and Pelham—Version IV Scale (SNAP-IV), respectively. We found significantly lower DEFA1 levels in the ADHD group compared to that in the HC group ( Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder commonly seen in children and may persist into adulthood . InterveMultiple factors are involved in the etiology of ADHD, including genetic, environmental and psychosocial factors. Recently, the link between intestinal function, gut microbiota and the central nervous system, referred to as dysfunctionality of the “gut–brain axis”, has also been of interest contributing to the underlying pathophysiology of ADHD ,9,10. ThThe intestinal microbiota may affect the growth and development of the overall body and multiple organs including the brain ,28. WithWe hypothesized that intestinal permeability may have a role in the pathogenesis of ADHD. Therefore, we plan to explore the serum levels of zonulin, occludin, and DEFA1 in patients with ADHD and controls. In addition, we suggested that increased intestinal permeability is involved in the cognitive dysfunction and clinical symptoms of ADHD. Therefore, our study aimed to investigate the association between the peripheral levels of zonulin, occludin, and DEFA1 and the cognitive function and clinical features of ADHD.All subjects gave their informed consent for inclusion before they participated in the study. The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee of Kaohsiung Chang Gung Memorial Hospital (IRB No. 201702019A3) on 20 February 2020. Children with ADHD were recruited from the Kaohsiung Chang Gung Children’s Hospital and HCs from the local community. Before taking part in this study, all participants and their parents or guardians fully understood all the terms of the study protocols and wholeheartedly agreed to sign forms to participate in this study.The inclusion criteria for patients with ADHD were as follows: (i) A confirmed diagnosis made by a senior child psychiatrist through structural interviews implementing the Kiddie-Schedule for Affective Disorder and Schizophrenia-Epidemiological Version (K-SADS-E) ,37; (ii)The HC group included children between 6 and 16 years old having no diagnosis of ADHD in the same catchment area. HCs were also interviewed under the structural interview of K-SADS-E to confirm that they had none of the aforementioned major neuropsychiatric diseases . Individuals with any major physical illnesses during recruitment who had ever received any antibiotics, anti-inflammatory drugs, or probiotics one month prior to the recruitment, or who were vegetarians, were also excluded.It was necessary to store the serum samples, which were obtained between 08:00 and 10:00, under the condition of −80 °C until the laboratory assessment started. Concentrations of zonulin in the serum were measured using commercial ELISA assays according to the manufacturer’s protocols from Immundiagnostik AG . All study samples and standards were checked in duplicate. The serum occludin levels were measured with the Human Occludin ELISA kit , using the sandwich-enzyme-linked immunosorbent assay method. Serum DEFA1 levels were assessed with the Human DEFA1 PicoKine ELISA Kit.The psychologist adopted Conners’ CPT  and Connp = 0.05, and allocation ratio ADHD/control = 2/1. The sample sizes were estimated to be 39/19 to detect a large effect size (Cohen’s d = 0.8); 96/48 to detect a medium effect size (Cohen’s d = 0.5); and 591/295 to detect a small effect size (Cohen’s d = 0.2). In the current study, we planned to detect at least a medium effect size. Data analyses were performed utilizing the Statistical Package for the Social Sciences Version 16.0 . The average ± standard deviation or frequency was presented in the form of variables. The analysis for the dichotomous variables such as the sex distribution of children with ADHD and HCs was carried out using a chi-square test. As for repeated variables, the differences in demographics, clinical symptoms, and neuropsychological function between patients and controls were decided using an independent t-test. Two-tailed p < 0.05 was the significance for statistics.The sample size was measured with the software package G-Power 3.1, based on the settings of 80% power, Finally, we performed a sensitivity test in which we excluded four healthy control subjects with particularly high levels of DEFA1. A linear regression model was performed to examine the effect of ADHD status on DEFA1 levels (outcome variable), and sex (m/f) and BMI were the explanatory variables.We recruited a total of 130 children with ADHD  and 73 HC individuals . As shown in p = 0.008) (r = −0.146 p = 0.042) and that in the SNAP-IV teacher form (r = −0.187 p = 0.010) (r = −0.179 p = 0.014) (r = 0.166 p = 0.020) (The serum levels of the gut leakage markers are shown in = 0.008) C. The se= 0.008) A,B. We f= 0.008) . We foun= 0.010) . In addi= 0.014) . However= 0.020) . We did p = 0.034), controlling for the potential confounding effects of sex and BMI.Finally, we excluded four healthy control subjects with particularly high levels of DEFA1 (≥77.5 ng/mL). A linear regression model  revealedIn this study, we found significant differences in the gut leakage marker, DEFA1, between the ADHD group and the HC group. This significant difference remained even after we excluded four healthy control subjects with particularly high levels of DEFA1 and controlling for the potential confounding effects of sex and BMI. The sensitivity test in 3.4 further verified that ADHD status did influence the serum DEFA1 levels. However, we found no significant differences in the other two gut leakage markers, zonulin and occludin, between the ADHD and HC groups. In addition, the serum level of DEFA1 showed an inverse correlation with both the inattention and hyperactivity/impulsivity scores in the SNAP-IV teacher form, demonstrating its inverse correlation with symptoms of ADHD. To our knowledge, our study is the first study to evaluate the association between gut leakage markers and vulnerability, clinical symptoms, and cognitive functions of ADHD.DEFA1 gene encodes the human neutrophil peptides. Increased copy numbers of the DEFA1 gene were correlated with increased levels of the DEFA1 protein [DEFA1 gene was associated with recurrent urinary tract infections in children [DEFA1 gene contribute to a higher risk for hospital-acquired infections [Our results were different from our initial hypothesis, for we presumed that higher gut leakage markers were associated with the vulnerability of ADHD, and gut leakage markers may positively correlate with clinical symptoms. Our finding of lower DEFA1 levels in the ADHD group compared to controls may not be unsupported. Previous studies found that decreased levels of DEFA1 were associated with several infectious diseases, while increased levels of DEFA1 may protect against the progression of infection ,47. DEFA protein . Previouchildren . It was fections . Anotherfections . Therefofections . AlthougMoreover, we did not find an association between ADHD and other gut leakage markers of zonulin and occludin. Our study agrees with  which foAlthough we found a correlation between the CPT and occludin, we did not find any correlation between the gut leakage markers with the other subtest of the CPT besides detectability or any of the subtests in CATA. CPT3 generally detects visual attention while CATA examines auditory attention. A developmental lag in the maturation of the brain may lead to deficits in visual and auditory attention in ADHD ,55. The Our study has the following limitations. First, we may not establish a causal relationship with the current study design. This is a cross-sectional design study analyzing correlations rather than a longitudinal study which may follow temporal changes. In this way, our study was unable to control for many early-life factors that may influence the initial colonization and development of microbiota in the gut system. We did not control for types of birth delivery, breastfeeding or not, dietary patterns, the use of probiotics, and previous antibiotic treatment ,62 for tIn conclusion, we report significant differences in the gut leakage marker DEFA1 between the children with ADHD and the HC group in the current study. In addition, the serum level of DEFA1 showed an inverse correlation with both the inattention and hyperactivity/impulsivity scores reported by parents and teachers, reflecting its association with the clinical symptoms of ADHD. We also found a positive correlation between occludin levels and detectability in the CPT, indicating that gut leakage markers may not only be associated with vulnerability to ADHD, but also associated with its cognitive deficit, inattentiveness. Our results suggest that the gut leakage mechanism may play a significant role in the clinical presentation, cognitive deficits, and pathophysiology of ADHD.


Attention-Deficit / Hyperactivity Disorder is a developmental neurological disorder that has three basic characteristics: Attention Deficit, Hyperactivity, and impulsivity. This study aimed to investigate the prevalence of ADHD in children and adolescents.2 test was used to analyze study heterogeneity, and the Egger test was used to assess publication bias.This investigation was carried out using the meta-analysis method under PRISMA guidelines. Until October 2020, the articles were gathered by scanning PubMed, Scopus, WOS, and Science Direct databases. The second version of Comprehensive Meta-Analysis software was used to run analyses after extracting data from chosen papers. At a significance level of 0.05, the IThis analysis includes 61 cross-sectional research, with 53 research used to determine the prevalence of ADHD in children, 7.6% of 96,907 children aged 3 to 12 years had ADHD , and 5.6% of teenagers aged 12 to 18 years have ADHD . The prevalence of ADHD in children and adolescents according to the DSM-V criterion is also higher than previous diagnostic criteria, according to studies.The findings of this study based on meta-analysis show the high prevalence of attention deficit hyperactivity disorder (ADHD). The findings of this study demonstrate the importance of management and policy in the treatment and control of ADHD in children and adolescents.The online version contains supplementary material available at 10.1186/s13052-023-01456-1. Attention Deficit Hyperactivity Disorder (ADHD) is one of the most frequent neurodevelopmental disorders in childhood and adolescence, which is typically first, diagnosed in childhood and often persists into adulthood. It is one of the most prevalent causes of children being sent to psychology and psychiatric clinics , 2. ChilAttention deficit disorder affects children differently depending on their age and gender, and it is more common in boys than in girls . The iniSymptoms of ADHD are frequent in school-aged children and can last far into adulthood. In general, ADHD is usually characterized by impulsivity, attention deficit, and hyperactivity. A person with inattention may have trouble remaining on task, maintaining focus, and maintaining organization. A hyperactive person may appear to move around frequently or fidget excessively. An impulsive person may behave without thinking or struggle with self-control. –6. PatieAs previously mentioned, boys are more likely to manifest ADHD symptoms  with thrGuardiola et al. carried out a study in which they assessed the prevalence of ADHD in 484 pupils using two criteria: DSM-IV and neuropsychological criteria. The results showed that the incidence of ADHD using the DSM-IV criterion and the neuropsychological criterion were 18% and 3.5%, respectively . ShabaniAccording to a survey conducted by Adonna et al., 8.7% of Nigerian students aged 7 to 12 had ADHD. In addition, the prevalence of attention-deficit subtypes was determined to be 4.9%, hyperactivity/impulsivity subtype 1.2%, and hyperactivity and attention deficit subtype 2.6% in this study . ADHD waAnother study on the prevalence of ADHD was undertaken by Maulov et al. A total of 210 Lebanese teenagers between the ages of 11 and 17 were studied. 10.2% of persons have ADHD, according to the findings of this study .There are several inconsistencies across research on the prevalence of ADHD in children and adolescents, which are influenced by a variety of factors including diagnostic criteria variances. As a result, this study was conducted to determine the prevalence of ADHD in children and adolescents based on various diagnostic criteria and age groups.This research looked at the prevalence of ADHD in children and adolescents by a systematic review and meta-analysis of cross-sectional data. The technique for carrying out the various stages of this study following the criteria of Guideline  was creaIn general, the criteria for selecting documents in systematic review and meta-analysis are within the framework of PICOS  . In thisThe authors reviewed four electronic bibliographic databases, including PubMed, Scopus, WOS, and science direct, as well as any electronic publications printed before October 2020. Mesh terms and keywords used in review studies and previously published studies were utilized to choose the relevant keywords, which were chosen by one of the authors (MSH) and confirmed by the first and second authors. All keywords were selected in English. The search strategy in this study was designed using the terms “prevalence OR outbreak OR Global prevalence AND ADHD OR ADDH OR “Attention Deficit Hyperactivity Disorder”.After using Endnote software to remove duplicate articles, an author (MSH) examined the study’s title and abstract. Excluded studies were those that did not meet the entry and exit criteria. The whole text of the paper was then examined by two writers (MSH and HGH) based on inclusion and exclusion criteria. These experiments were carried out independently and by blinding. Any comments given to affirm or reject the research were re-examined after the reviews were completed at this step. In the case of a disagreement, the study was confirmed using the third author’s (MM) reviews. If the full text of the study was not available, an email or research gate request was submitted to the paper’s lead author.In this study, the STROBE checklist  was usedInformation gathering was performed by two authors (MSH and HGH). This data was gathered using the methodology and findings of preliminary research. A form was created to extract information such as the first author’s name, year of publication, country, population examined by gender, diagnostic criteria, and diagnostic instruments. Data were extracted by (MSH) and reviewed by (MM).2 test. The Egger test and its accompanying Funnel plot were used to analyze the publication bias due to the large number of samples included in the study. Comprehensive Meta-Analysis software (Version 2) was used to examine the data.The heterogeneity of the studies was assessed using the IA systematic review and meta-analysis of information on research on the prevalence of ADHD in children and adolescents around the world was conducted in this study, with no time constraint until 2020 and following PRISMA principles. 1837 potentially related articles were found and transferred to the information management software based on an initial database search (EndNote). A total of 1837 studies were found, with 170 duplicate studies being eliminated. Out of 1667 papers, 1442 were eliminated during the screening phase after titles and abstracts were examined for inclusion and exclusion criteria. 164 articles were removed from the remaining 225 studies during the competency evaluation phase due to irrelevance after analyzing the full text of the article based on inclusion and exclusion criteria. All 61 articles were approved in the qualitative evaluation stage after reading the complete text of the article and calculating the STROBE score (Table 2 test results (98.6) and the heterogeneity of the chosen research, a stochastic effects model was utilized to combine studies and estimate overall prevalence. Study heterogeneity can be caused by differences in sample size, sampling error, research year, and study location. The funnel diagram and Egger test at a significance level of 0.05 revealed that there was no publication bias in the distribution of data in the current investigation (P = 0.107).  in 53 studies with a total sample size of 96,904 participants who looked at children under the age of 12. The shape of the Forrest plot depicts the overall prevalence in the studies under consideration, with the midpoint of each line segment representing the prevalence in each study and the shape of a rhombus indicating population prevalence for the entire research ; 10.1% ; 11.3% ; and 4.4% , respectively  and the heterogeneity of the selected research. Differences in sample size, sampling error, year, or study location can all contribute to the study heterogeneity The possibility of bias in the dissemination of data was determined using a funnel diagram and the Egger test at a significance level of 0.05 in the current study (P = 0.774). . Fig. .In 25 studies involving teenagers aged 12 to 18, the prevalence of ADHD was determined to be 5.6% . The total prevalence in the studies examined is depicted in the Forrest plot, with the midpoint of each segment showing the prevalence in each study and the rhombus shape indicating the general population prevalence  and symptomatic (not include childhood ADHD) ADHD was investigated in this study. Around 140 million persons were evaluated for persistent ADHD in this study, with only 2.58% having the disease. The study also looked at symptomatic ADHD in a population of 370 million individuals, with 6.76% of people over the age of 18 having the disorder. On the other hand, the findings of this study demonstrated that when participants’ ages increase in both groups, the prevalence of ADHD decreases, which is consistent with our findings . AnotherOne of the limitations of this study is the high heterogeneity of studies in terms of age group. Since the purpose of this study was to measure the prevalence of children and adolescents separately, studies that report the prevalence of ADHD in children and adolescents combined were removed. Furthermore, because this study only looked at cross-sectional papers, it was impossible to track the participants and measure their symptoms over time.The findings of this study based on meta-analysis demonstrate the significant prevalence of attention deficit hyperactivity disorder (ADHD)The results of this investigation corroborate prior research and highlight the importance of planning and policy-making in the treatment and control of ADHD in children and adolescents. Future research should look into the prevalence of ADHD in different age groups and how it affects their personal and social lives.Below is the link to the electronic supplementary material.Supplementary Material 1


Adolescents with attention-deficit/hyperactivity disorder (ADHD) experience aspects of their lives in diverse ways. They often have more energy and creativity which are positive traits of ADHD, while their inability to control their actions in academic or social spheres may cause feelings of inadequacy.To explore illness-perception, including emotional experiences, in adolescent ADHD.Using convenience sampling, 12 adolescent participants, eight boys and four girls, diagnosed with ADHD, were included. Participants followed up at Weskoppies Tertiary Psychiatric Hospital’s child-and-adolescent outpatient clinic.This qualitative study used semi-structured question guides to conduct interviews that allowed participants to actively construct their knowledge of their disorder. Maintaining a phenomenological perspective, thematical analysis of data was done.Adolescents’ perceptions of their ADHD could be placed into three categories. ‘Negative self-perception in ADHD’ represented adolescents’ descriptions of ‘inability’ and ‘lack of control’ over their cognitive processes, behaviour, emotions, and restlessness. Adolescents perceived ‘feeling judged by others’, amplified self-stigmatisation and discrimination. This antagonistic environment caused conflict between their self-perception and others’ perception of them, further intensifying feelings of ‘not being normal’. The theme ‘self-empowerment strategies’, included controlling external stimuli, accepting support from others, and personalised learning strategies.Adolescents with ADHD struggle with cognitive, behavioural, and emotional control, and frequently experience stigmatisation and discrimination. They often learn to rely on self-taught coping strategies.This research grants perspective to educators and clinicians on experiences of adolescents with ADHD, and identifies the need to address stigmatisation. It recognises the value of personalisation of coping methods. Certain symptoms of ADHD can present similarly to symptoms seen in other externalising disorders, wherein children may exhibit inappropriate behaviours towards their environment. These inappropriate behaviours include impulsivity, hostility, and irritability, and are frequently the parental reason for reaching out to mental health services.5 Adolescents with and without ADHD, go through similar processes of identity development. These processes include striving for independence, developing and establishing identity, forming work habits, planning for the future, and developing decision-making skills.6 The perception adolescents have of their ADHD is anticipated to influence how they perceive these developmental aspects and affect their functioning.7 Understanding their ADHD will help adolescents to develop an awareness of the effects it has on their lives, and to independently develop coping mechanisms. Illness-perception studies of ADHD in adolescents have largely been conducted in developed countries. Understanding the subjective experiences of adolescents who live with ADHD in South Africa, would help healthcare workers to understand and co-construct treatment modalities.Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent neurodevelopmental disorders in childhood. Symptoms of inattention, hyperactivity, and impulsivity can present in a variety of ways.8 These representations generally comprise of five key aspects, namely, identity, cause, timeline, consequences, and cure control.9 The illness-perception questionnaire has predominantly been used in medical illnesses but has become more popular in mental health research.10 In a systematic review, Wong et al. use the CSM to explore illness perceptions in children diagnosed with ADHD and their parents.9 Wong et al. further reflect on prior use of the CSM in Schizophrenia and Anorexia, and how there is benefit in including another key aspect of ‘emotional representations’ in assessments.9According to the Common-Sense Model (CSM) of illness perception and the associated illness-perception-questionnaire IPQ-R, people actively develop representations of their illnesses.9 Discrepancies in perceptions of illness and achievements, may result in conflict between adolescents and parents.11 Perceptions of ADHD are likely to be influenced by external factors such as where children go to school and whether they have access to private mental health care. Limitations faced in South Africa’s public sector include a lack of resources like medication and specialised schools and programmes, in addition to a large, underdiagnosed population. Multidisciplinary involvement in the private sector is often limited, and may result in isolated pharmacological intervention.Adolescents who accept their ADHD are more compliant with pharmacological and non-pharmacological interventions, yet, perceptions of illness may change over time, and some patients may become hopeless and give up.In this illness-perception study, we qualitatively investigated illness-perception in adolescents with ADHD in South Africa. We asked adolescents how they perceive their symptoms and environment. We asked them whether they thought their emotions were affected by ADHD and what they found to be relieving factors and coping mechanisms.13 We conducted in-person semi-structured interviews to explore illness-perception and emotional representations in adolescents diagnosed with ADHD.This qualitative study was conducted from a constructivist worldview with a phenomenological approach. This approach forestalled to provide an in-depth understanding of the participants’ actual lived experiences as their environment presented itself.This study took place at Weskoppies tertiary psychiatric hospital, which receives referrals from the private and public health sectors. Weskoppies Hospital’s Child and Adolescent Clinic (WHCAC) provides care to approximately 250 children and adolescents monthly. Multidisciplinary psychiatric services are provided for various severities of mental illness, including, ADHD, mood-, psychotic-, anxiety-, behavioural-, and other neurodevelopmental disorders. Most of the patients have moderate or severe mental illness and are of both lower-and middle-class socioeconomic status. In this study, the participants’ severity of ADHD varied in complexity and outcome.2 Participants had to be stabilised on treatment for ADHD and comorbidities, and compliant with follow-up. We excluded participants with comorbidities such as autism spectrum disorder, moderate to severe intellectual disability, and language disorders. Due to the frequency of comorbidity, mood disorders were not excluded. The typical episodic nature of mood disorders and the longstanding course of ADHD were considered, and both conditions needed to be stabilised on treatment. We also excluded patients presenting for first evaluations. Lastly, participants had to be able to converse in English or Afrikaans, as understandable to the researcher.We included adolescents who were 15 to 17 years old and diagnosed with ADHD by a psychiatrist and multi-disciplinary team using the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) or the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) diagnostic criteria, and those with DSM-IV diagnostic criteria were subsequently confirmed with DSM-5 criteria.13To limit selection bias, we used convenience sampling, and approached 17 parent-adolescent pairs, at WHCAC. Thirteen parent-adolescent pairs showed interest and agreed to participate. The study was verbally explained while referring to an information brochure as a visual aid. Provisions were made for questions or clarifications, and consent, assent, and withdrawal processes were discussed. To limit observation bias, participants were interviewed without their parents. Question-guided interviews, led by the principal researcher, were based on the IPQ-R, and where needed, a simplified version of the IPQ-R . We exclDuring planning and peer debriefing, we recognised a need to simplify the CSM IPQ-R. The integrity of the concepts of identity, cause, timeline, consequences, cure control, emotional representations, and coherence, was maintained; however, some participants required questioning by using simplified terminology .The IPQ-R and interview question framework guided the principal researcher to assist participants in exploring perceptions and understanding of their ADHD, while remaining on topic, and expanding with follow-up questions. Where participants did not understand, the interviewer simplified or clarified questions. We enhanced participants’ comfort and openness by employing interview methods such as paraphrasing, clarification, and gesturing continuance. All the interviews were audio-recorded and the interviewer made field notes, to track her thoughts, and note participants’ non-verbal cues. Peer debriefing resulted in questions being added to the interview framework as more codes arose and clarifications were required.Data were collected from November 2020 to March 2021. Audio recordings lasted from 13 min to 36 min, with a median duration of 26 min. Verbatim transcriptions and required translations were done by W.B., with line numbers assigned to questions and participant responses. Each participant was assigned a pseudonym, correlating with their gender and ethnicity, to provide a ‘real-life’ experience for the reader.14 Initial data revisions drew on manual exploration, and ATLAS.ti software was used for further full scale coding and clarifications. Data familiarisation comprised of revising the raw data while simultaneously listening to recordings, reading verbatim transcriptions, and reviewing field notes. ATLAS.ti was used to review participants’ first-person, subjective perceptions of the different aspects of ADHD. With open coding of transcribed data, concepts that expressed similar feelings, experiences, and ideas, were highlighted and organised as a condensed whole. Axial coding was used to group codes into themes and sub-themes, with comparisons between interviews. Irrelevant or unclear themes were discarded. Themes were organised by analysing and identifying re-emerging patterns, then either merging, separating, or improving themes across participants’ transcriptions. Themes and sub-themes were refined to ensure a precise understanding of the message relayed by the data and to ensure accurate expression of the participants’ experiences of specifically their ADHD. Concise and logical naming of themes was done, and an audit trail was kept. The Standards for Reporting Qualitative Research guided the reporting of results.15Data analysis and management comprised of typical thematical analysis.Approval for this research was obtained by the Faculty of Health Sciences MMed Committee and from the University of Pretoria Ethics Committee (Ethics Reference No: 652/2020).As minors with mental illness represent a vulnerable population, written consent and assent were obtained from parents and adolescent participants after explaining the study. Participants were assigned an alphanumerical code to ensure anonymity. Safeguarding precautions were implemented to prevent unjustifiable risk or harm to participants, and secure storage of data was done according to the university’s policies.Seven of the 12 participants had comorbidities, mainly comprising of mood disorders .Field notes reflected that even though the participants denied feeling restless, they fidgeted with their hands, rocked on chairs, or tapped their feet. Participants struggled to maintain attention with long explanations and often came across as childlike.Three themes with subthemes emerged from patient interviews. The three themes included ‘negative self-perception in ADHD’, ‘feeling judged by others’ and ‘self-empowerment strategies’.We identified four subthemes under this theme: (1) lack of control of cognitive processes, (2) lack of behavioural control, (3) emotional dysregulation, and (4) somatic discomfort with activity restriction.Participants described a discrepancy between the control they desired to have over their cognitive processes and actions, in contrast to their perceived focus and expressed behaviour. They described cognitive processes as ‘their brain switching-off’, ‘thoughts jump’, or ‘zoning-out’:‘In class, I would concentrate for 5 or 10 minutes, and then my brain switches off and I start to think about other things. Then it takes me a while to concentrate on schoolwork again.’ ‘Uhm, my thoughts jump around, and I can think of the most random things… I don’t know, and I will go too deep into conversations, or, and when someone will be talking to me about something I will zone out and not even know what they are saying, and I’ll just agree to everything… I won’t really… I’ll hear what is happening, but I won’t really listen to it.’ External stimuli frequently resulted in unwanted distractions:‘And then when the answer is in my head and then the teacher talks to me, then it will just disappear.’ I]f you are distractible, and you can’t concentrate in class, and you can’t sit still, something pulls your attention away.’ ‘… eachers helped me because I have ADHD and struggle to concentrate… they gave me only a little bit of work to study every day and then the next day a little bit because if I had to study everything at once my brain would switch off and I would struggle to concentrate. The teachers decided they will break the work down into little pieces so I can do the work.’ ‘… [‘Anatomy, the one that I am doing now. It is easier to color in the muscle, and then to study it according to that color. So, coloring-in is one of them. And, like in my room, I pack certain things in certain places and it has to stay there.’ In this qualitative study, we explored the various ways in which adolescents with ADHD from Pretoria, South Africa perceived the impact of ADHD on their lives, how it affected their emotions, and what they experienced as coping strategies. The participants’ perceptions regarding their ADHD were explored in a setting where adolescents are required to self-adapt to a resource-deprived system. This system often struggles to accommodate children with different learning strategies or concentration levels.16 In our study, adolescents felt that their environment expected them to sit still, be quiet and concentrate. Cognitively, concentration difficulties were expressed as attention being drawn away or ‘zoning out’, which often caused them to fall behind. Behaviourally, adolescents struggled to control their psychomotor activity, felt restless, and were unable to ignore external stimuli. The restricting activity of these adolescents resulted in intense physiological and mental discomfort. Adolescents with ADHD are known to experience feelings of irritability and aggression and have somatic complaints.17 We also found that emotional dysregulation correlated with previously described ‘unpredictable shifts’ to ‘unusually intense’ reactions, that were ‘disproportionate’ to developmental age and the situational trigger.18 Emotional dysregulation may make it harder for adolescents to recognise, describe or think about their emotions. In our study, some adolescents showed improved emotional regulation and less aggression on stimulant medication, specifically long-acting methylphenidate.20Adolescents with ADHD’s feelings of loneliness often get amplified by not being in control of the cognitive, behavioural, and emotional aspects of their lives.23 These adolescents are generally aware of their shortcomings and are concerned about their futures.22 They compare themselves to their peers and find the classroom to be consistently challenging. Our findings corroborated with findings by Schoeman et al., where participants felt different, labelled, or misunderstood, and thus felt stigmatised and were treated differently by a discriminating environment.24 This misunderstanding has been expressed in previous research, where teachers often associated behaviour problems with an impaired family structure or the ‘problem child’.25 In the same study, learners with ADHD often misbehaved when they perceived the absence of valuable subject content, or experienced peer pressure, emotional turmoil, or stress caused by lessons.25 Teachers may not always understand ADHD and may use harsher discipline measures including name-calling, cursing, and degrading the upbringing of adolescents with ADHD.26 Mitzi et al. describe how adolescents with ADHD with improved self-awareness, had positive cognitive and social experiences.27 Adolescents with ADHD have to learn to control their symptoms, overcome struggles, build resilience, and develop coping strategies to enhance performance.22 In our study, adolescents with ADHD had to learn to cope with external environmental distractions. They found that controlled external stimuli such as listening to music via headphones would ameliorate multiple distractions such as teachers or peers talking or something passing by. Other beneficial external stimuli included eating and movement and practical methods like physical subjects, colour-coding, shapes, and breaking tasks into steps. Adolescents with ADHD typically lose motivation when tasks are lengthy and boring, but are motivated by variability in tasks.28 These adolescents are also motivated by adult support and positive reinforcement through social or monetary means.28 Our research correlated with the benefit of developing routines and problem-solving strategies in adolescents with ADHD.18 Adolescents with ADHD experience rules, regulations, routines, and an organised environment, conducive to both cognitive performance and emotional regulation. Adolescents who participated in the formulation of their routine felt an enhanced sense of responsibility and self-awareness. Parents and teachers who create an organised environment and establish a routine, rather than relying on punitive discipline, also have favourable outcomes for the education of adolescents with ADHD.25Adolescents with ADHD often perceive themselves as ‘not normal’ and as in other studies, this often resulted in them feeling excluded, which leads some of them to conceal their diagnosis.30 In our study, adolescents reported that exercise improved their mood, but not their concentration.Physical exercise is a known coping strategy for adolescents with ADHD; it improves impulsivity and behaviour, and in some cases improves attention, in both reading comprehension and mathematics.25Although ADHD is often perceived to be an externalising illness, adolescents in this study communicated internal struggles. They perceived a lack of control over- and unpredictable cognitive processes, behaviour, and emotions. In this study, adolescents perceived their environment to be distracting and negatively expectant. These adolescents were exhausted by having to maintain attention and keep up with the rest of the class. Remaining still while feeling restless often led to physiological discomfort. These internal experiences may result in unpredictable and often misunderstood behaviour, which others then classify as externalising symptoms. As externalising symptoms manifest, adolescents with ADHD may be discriminated against. Adolescents without good support structures or coping mechanisms may find themselves in negative, symptom-provoking discrimination cycles which will amplify their feelings of abnormality. We recommend that caregivers should consider how the environment can distract a child with ADHD rather than labelling a child with ADHD as the distraction.31 Yet, patients with private medical insurance may have different experiences of their ADHD. Due to the nature of qualitative research, the limitations to statistical validity and objectivity should be considered when reading this study. More than half of the adolescent participants in our study had comorbidities, most frequently mood disorders. Even though these comorbidities can be expected in ADHD, and both ADHD and comorbidities were required to be stabilised as inclusion criteria, this needs to be taken into consideration when interoperating the study.This study explores the benefits of assessing illness-perception of adolescents with ADHD, in a South African context. It considers how the exploration of illness-perception might provide a platform for understanding and individualising adherence and coping strategies. This study corroborates previous global research on illness burden and discrimination and adds to the limited data available in the South African context. Several limitations are acknowledged in this study, including small sample size and short duration of some interviews; however, interviews continued until data saturation was reached. Generalisability is limited due to the participants in this study representing patients attending a single tertiary psychiatric hospital in the resource-limited public sector in South Africa, who are typically of lower socioeconomic status. However, overlapping experiences have been found in resource-rich developed countries.Our findings reveal that adolescents with ADHD in South Africa struggle to control their cognitive, behavioural, and emotional spheres. Our findings corroborate previous research which describes mood aspects, emotional dysregulation, stigmatisation, and discrimination – the latter enhancing the feelings of being ‘not normal’. Adolescents with ADHD can identify coping strategies and relieving factors, including controlling external stimuli, accepting support from others, and personalised learning strategies This qualitative study supports the premise that the external environment is distracting for adolescents with ADHD. Future research should focus on how the individualised illness-perceptions of ADHD, might assist healthcare workers and parents, to co-construct modalities to enhance adherence, coping, and address stigmatisation in resource-deprived settings.