The aim of research is to provide greater understanding of ADHD in adult females by exploring first-hand experiences of female university students with ADHD in the UK, and the impact of such experiences on social, academic, and psychological functioning.Semi-structured interviews were conducted with eight adult women attending university in the UK—all clinically diagnosed with ADHD during adulthood.Participants experiences were rich and insightful, identifying that many women with ADHD experience stigmatization and social discrimination, amongst other social, academic, and psychological difficulties.Overall, the research identifies the pressing need for greater understanding and appreciation of ADHD in females, particularly amongst health professionals. Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder characterized by a persistent pattern of inattention and/or hyperactivity-impulsivity which interferes with daily functioning . There aA potential explanation for underdiagnosed ADHD in females is differences in core symptomatic presentation between males and females. Research suggests that females are more disposed to internalized symptoms, such as inattentiveness and disorganization, and present with fewer symptoms of hyperactivity and other disruptive external behaviours . On the Within the UK, clinical research surrounding ADHD lays focus to males, and, as a result, current diagnostic criteria and general understanding of ADHD is biased towards a male presentation of the disorder  with ADHThe presence of co-morbidities in females also appears to cloud ADHD diagnosis. The overall prevalence of a comorbid psychiatric disorder for those with ADHD ranges from 40% to 80% . The mosOverall, ADHD is associated with significant likelihood of developing psychological, social, and emotional difficulties, which can be amplified when left undiagnosed and untreated. In general, ADHD is significantly associated with poor academic functioning across the lifespan, from school readiness to going to university . ProblemThe potential absence of academic difficulties at school age may present greater challenges in recognizing ADHD in young females, providing further explanation for why many females do not receive a diagnosis of ADHD during their childhood. Individuals with ADHD commonly experience impaired social behaviours and interpersonal relationships . UniversOverall, the literature highlights that there is insufficient understanding of ADHD in females, resulting in many females not being diagnosed with ADHD until they reach adulthood, and suffering with many of the consequences of a late diagnosis. Further research studies of females with ADHD are needed to improve understanding of the disorder and draw attention to the subtle differences in symptom presentation between males and females. The aim of this qualitative research is to approach these gaps in the literature by exploring the personal experiences of adult, female university students with ADHD in the UK, and the impact of such experiences on their social, academic, and psychological functioning. This is an exploratory piece of research; therefore, the research does not address any specific research questions or hypotheses.A qualitative approach was use, utilizing semi-structured interviews to gain an in-depth understanding of the personal experiences of adult female students with a clinical diagnosis of ADHD attending university in the UK. Semi-structured, in-depth interviews were identified as the optimal method for collecting qualitative data about participants’ experiences of ADHD . The GenA purposeful sampling method was used, recruiting participants based on a set of pre-determined criteria. The inclusion criteria comprised of being an adult female (18-years +), a student at any university within the UK with a clinical diagnosis of ADHD—no formal confirmation of participant’s diagnosis of ADHD was required. Exclusion criteria included participants who had a co-morbid diagnoses of another serious mental health disorder, such as a depressive disorder or a personality disorder. These exclusion criteria were selected as acknowledgement that diagnosis of another serious mental health disorder may present greater influence on the experiences being investigated in comparison to ADHD autonomously.Participants were recruited via advertisements in several UK-based ADHD support groups for women on Facebook and Instagram. Twenty-five women registered their interest in taking part in the study, eight of which fully completed the consent forms, GHQ-9 questionnaire and attended their allocated interview time. Thirteen individuals did not provide full consent, three individuals did not return the questionnaire and one participant did not attend their interview. Eight interviews were conducted with intention of further interviews if data did not reach saturation. Following analysis of the data, it was agreed between the researchers that no further theoretical insights or themes would emerge from further interviews and that data had reached saturation .The eight participants were adult women, aged between 22 and 53 years old (mean age of 31 years old). All participants were formally diagnosed with ADHD in adulthood, and either part-time or full-time students at a university in the UK. Further participant demographics, such as ethnicity or sexual orientation, were not collected, as this information was not relevant to the outcomes of the research.Following obtainment of informed consent, participants were asked to complete the GHQ 28, which consisted of 28 short questions asking participants how their general health had been over the weeks prior to the study . ParticiTopics of discussion included: reasons for seeking a diagnosis, personal feelings after receiving a diagnosis, and the impact of ADHD on participants’ social, academic, and psychological functioning. Questions asked within the interviews were developed and agreed among the researchers to ensure the primary research question was approached and allow an easier triangulation process. A full outline of the interview questions used can be found in Participants were scored on their responses to the GHQ-28 using a Likert scale scoring system of 0 to 3 . Mean scores and standard deviations were calculated for each of the four subscales of the GHQ-28. The lowest possible total subscale score is 0 and the highest subscale score is 21. Lower scores indicated lower levels of psychological distress, and higher scores indicated higher levels of psychological distress amongst participants. All interviews were transcribed and analysed by one author and checked by the other. A full transcript of the interviews can be found in Both authors independently analysed the raw data and developed initial codes and themes. These codes and themes were then compared between the researchers referring to the raw data to ensure validity. Any discrepancies of themes and codes developed were discussed with agreement that a third researcher would be involved if an agreement could not be made. There were no discrepancies between the codes and themes made.Ethical Approval was obtained from the University of Nottingham Research Ethics Committee (Ref: S1439R). The ethical considerations reviewed for this study centred around confidentiality, and implications of the discussion of personal memories surrounding a problem which had received clinical psychological attention. Informed 10 consent was required from all research participants. Participants were informed that the researcher was not a clinical professional, therefore could not provide any form of diagnosis or psychological care. At the end of the online interviews, participants were fully debriefed and provided links to professional support services, both within the University of Nottingham and outside the University of Nottingham, should participants have felt affected by the nature of the interview and/or discussion of sensitive topics. To maintain confidentiality, all identifiable information was removed from the data following transcription and names were replaced with pseudonyms.Mean scores and standard deviations (SD) for each of the subscales of the General Health Questionnaire-28 (GHQ-28) are outlined in Female adults suffering with ADHD are at a high risk of being confronted with stigmatization due to the lack of disorder-related understanding and male stereotypes surrounding ADHD, amongst other factors . Topics “I felt like I wasn’t taken seriously during my assessment. . .because I arrived really early, which the person assessing me kept bringing up, like, well you arrived on time so obviously that’s not a problem for you. And they were making comments like I wasn’t fidgeting enough, at least in their eyes. And those kind of comments knocked my confidence and I felt like I wasn’t being believed”Similarly, one participant was told that she was depressed during her initial ADHD assessment as she was overwhelmed and visibly emotional. The participant knew that she was not depressed, and so felt that her feelings and experiences were being dismissed by the GP. “People [at work] were making comments and I was getting into trouble for things that I now realise were symptoms [of ADHD] . . .and I felt like it was really unfair, and it was messing with my head a little bit”Furthermore, several participants also described experiencing negative attitudes towards ADHD, from family members and academic staff. Participants expressed shock over the stigma surrounding ADHD that they faced.“I had one tutor at university who didn’t believe in ADHD and dyslexia and that, she just believed it was a lazy excuse for not going to school”“When I told my auntie [about my diagnosis], she was really unsupportive, and I was really shocked. She says she knows a lot of kids with ADHD and autism and says it is brought on by their diet and that makes them go crazy when their parents give them processed food”One participant explained that they did not wish that they had their diagnosis sooner, as they felt that they would have faced even greater public misconception. Overall, participants remarked that the lack of understanding and awareness of ADHD in females is what led to their ADHD being undiagnosed throughout their childhood. However, some participants did acknowledge that awareness of ADHD in females is improving, but there is still a long way to go.As a result of the stigmatization and negative misconceptions surrounding ADHD, some participants avoided telling close friends, family, and colleagues about their diagnosis. Participants described that they felt like they would be judged and perceived differently for having ADHD.“Even now, I don’t tell many people in my personal life about my diagnosis. I am a bit more open about it at university, but I am worried about what some family members and close friends will think of me if I tell them about it” “Now, like I don’t really tell people [about my diagnosis], like I tell my close friends and family, but for work, it’s very much a need to know basis, because I think, if you’re female, most people will just go right well you don’t have ADHD and you can’t be bothered explaining yourself really, so there’s just no point”Prior to receiving a diagnosis, participants described struggling with various aspects of daily life, without realizing that their struggles were consistent with symptoms of ADHD. For many participants, these problems were most prevalent in an academic setting, primarily due to the inability to focus and maintain concentration. It has been widely documented in the literature that inattention, a core symptom of ADHD, is associated with poor academic functioning . Several“I was great in the subjects that I was good at, which was usually the more creative ones like, you know, the more practical subjects like PE, drama, and art, and I did really well in those. And it’s not to say I did really badly in other subjects, I was capable of doing it, but I just couldn’t focus to do it, so I refused to do the work”Furthermore, most participants described having problems with time management and procrastination, and struggling to organize their thoughts, which acted as a barrier to performing well academically. Before receiving a diagnosis, many participants described that they felt that these symptoms were part of their personality and felt that they were “simply just not academic.” Though, not all participants struggled with academic performance; one participant described being a perfectionist and seeking a lot of self-worth and validation from her academic work, which led to overworking herself at school from a young age.“If I didn’t do well on a test at school, I would completely have a meltdown, for me it was like the end of the world. . .I remember being at a parents evening when I was 11 years old, and the teacher told my parents that I was on the verge of burnout if I kept working as much as I was, which, you know, should not be happening to an 11 year old”there is something wrong with me.”Consistent with the literature on ADHD, a recurring theme throughout all women’s experiences was suffering with low self-esteem, which had a profound impact on participants’ social, academic, and psychological functioning . Many pa“I really felt myself being inferior to other people, I suppose, and I always had a feeling that I wasn’t good enough. You know, you’re thinking what is wrong with me? Why can’t I do that? Why can’t I be as organised as other people? How do they do it?”people had to put up with me, instead of enjoying my company, and I felt like I had to apologise for the way that I was,” which had a huge impact on their self-perception. Fifteen Linked to low self-esteem, many participants also described issues specifically related to their social functioning, including problems creating and maintaining friendships. For example, one participant described having “lots of acquaintances, but not very many close friends” as they struggled to hold onto close friendship groups, and often found that they would neglect friendships and relationships when they were busy or stressed. Some participants also described having problems with emotional dysregulation, which had a large impact on their social functioning.One participant described believing that “One of the biggest things that affected me was my emotional sensitivity, and like fear of rejection, like if a friend didn’t text me back, I thought they hated me. . .I think I would have benefited when I was younger knowing about that emotional side, as that really had a huge impact on my friendships and relationships which was pretty difficult”“Emotional dysregulation is a very common symptom of ADHD, often more severe amongst females . An aspeMany participants described that they were prompted to seek a diagnosis by a member of their support network, such as a friend, family member, or colleague, who had recognized that they were presenting with some of the symptoms of ADHD. Despite acknowledging that they were struggling with certain aspects of their life, most participants commented that they did not realize that this could have been due to ADHD, as they were not aware of many of the symptoms of ADHD, particularly in females. A couple of participants reported that they had their suspicions that they might have ADHD but chose not to act on it. For 16 several participants, ADHD had been mentioned in their childhood, but, at the time, it was not taken seriously enough to seek professional help.“I’ve got a friend who has ADHD, and she noticed a lot of similarities between us, and said it seemed like something I should follow up with. I sort of had a suspicion [that it might be ADHD], but I didn’t bother following up with it because it seemed like a lot of work, and at the time, I didn’t think it was impacting my life that much”Some participants also disclosed that they had a comorbid condition, including dyslexia, autism spectrum disorder, or anxiety, and a history of issues with self-harm and eating disorders. Comorbidities were highlighted by several participants as a possible reason why they never realized that they also had ADHD. The presence of comorbidities in this sample are consistent with the literature, highlighting that comorbid disorders present possible overlapping symptoms with ADHD which can create challenges for diagnosis . Seven oAll participants received a diagnosis of ADHD in adulthood. For some participants, the diagnosis process was relatively quick and easy and lasted a matter of 3 months, however, for others, it took up to 2 years.a weight had been lifted off their shoulders,” as they felt that there was an explanation for why they had been struggling in many areas of their life.After receiving a diagnosis, participants reported very mixed emotions. Most participants described feelings of relief and recognition. One participant described feeling like ““For me, there was a lot of relief. I mean, I had spent my whole adult life thinking that I just wasn’t good enough, and I kept falling short in a lot of areas of my life, I 17 thought I was lazy, I thought I was useless. . .so hearing that it wasn’t just me and there is something else going on, I guess, yeah, it was a huge relief”didn’t feel anything.”However, not all participants felt a sense of relief following diagnosis. Despite acknowledging that diagnosis was a positive thing which meant that they would be able to get support, one participant commented that they “made sense.” Validated feelings and experiences improved participants’ self-esteem, and many participants reported being kinder and more compassionate to themselves following diagnosis. Furthermore, many participants implemented appropriate management strategies, such as seeking professional support and using good organization. For many participants, stimulant medication had been the most useful management strategy. Likewise, having a better understanding of their strengths and weaknesses meant that participants felt they had better control over their lives.Although there were mixed emotions initially, all participants described feelings of validation once they had time to think about their diagnosis. Participants were able to understand themselves better and noted that looking back, their behaviour ““Having a diagnosis has changed the way I approach lots of things, I plan things differently, I’m aware that I might struggle with certain things, and I don’t beat myself up if I can’t do things”Since diagnosis, many participants returned to full-time education and started university, as they were able to approach things differently this time round. Participants generally reported receiving lots of support from their university, which made the experience of returning to education much easier for them. Some participants reported feeling like they needed to prove to themselves, and others, that they can do it. Participants described a need to fulfil their potential by going to university, and pursuing the career that they always wanted, but felt they were unable to achieve prior to being diagnosed with ADHD.“I’ve spent my whole life thinking that I wasn’t capable [of going to university], and now I’ve finally got the belief and motivation behind me to do it. It’s almost like I’m 18 trying to prove something just to myself and everybody else that’s doubted my ability”All participants benefited from receiving a diagnosis. However, there are still daily challenges that they face with ADHD. Participants explained that they have good and bad days, and with each day, they are constantly learning new things about themselves.The personal experiences of female students with ADHD explored in this qualitative study are rich and insightful, highlighting the profound impact of ADHD on social, academic, and psychological functioning.The themes and sub-themes identified in this study overlap with previous literature surrounding females with ADHD. Many of the symptoms which affected participants academic functioning correspond with the literature review of ADHD in university students presented by Intense feelings of low self-esteem resonated throughout participants’ experiences. Poor self-esteem is very common amongst females with ADHD , triggerIn accordance with the literature, participants also faced problems forming and maintaining friendships, particularly at school . DespiteThe aim of the research was to explore the impact of ADHD on participants’ social, academic, and psychological functioning, as discussed in the themes of “journey to receiving an ADHD diagnosis” and “adulthood diagnosis.” However, following data analysis, the theme of “stigmatization surrounding ADHD in females” emerged from the data and became a highly influential element in participants’ experiences of ADHD. Most participants described at least one personal experience of public misconception, social discrimination, or prejudice. Stigmatizing attitudes towards both children and adults with ADHD are very common . As a diThere is even greater stigmatization towards females with ADHD, in comparison to males, as it is publicly recognized as a disorder that predominantly affects boys. Overall, the women’s experiences discussed in this qualitative study draw attention to the complexity of ADHD. The heterogeneity of symptom presentation presents many challenges in recognizing and diagnosing ADHD in females. However, the overarching theme amongst all participant’s experiences is a clear lack of understanding of ADHD in females. Even amongst health professionals, there is a lack of appreciation of the differences in symptom presentation between males and females with ADHD, and an overwhelming existence of stigmatization. This lack of disorder-related knowledge, 22 alongside the presence of comorbidities, plays a key role in females receiving a late diagnosis of ADHD.This research responds to gaps in the literature by exploring several rich and detailed accounts of first-hand experiences of ADHD in adult female university students in the UK. However, there are number of caveats with the sample used in this study. Firstly, given that females with ADHD are largely underdiagnosed in the general population, the sample of formally diagnosed females used in this study may not be fully representative of females with ADHD in the wider population . It is lAnother caveat of the sample used in this study is the exclusion of participants who have comorbid diagnoses of another serious mental health disorder, such as a depressive disorder or personality disorder. This presents a severe limitation to the research as there is a high incidence of depression, amongst other psychiatric disorders, in females with ADHD . TherefoDespite the addressed limitations, this research provides meaningful insight into the experiences of women with ADHD. Today, many women with ADHD experience stigmatization and social discrimination. Therefore, the clear take-home message of this study is the need for greater public understanding and appreciation of ADHD in females. Twenty-three Improving public knowledge of ADHD is important moving forwards to reduce stigmatization and debunk stereotypes of ADHD as a disorder that predominantly affects males.Furthermore, greater understanding of ADHD is particularly important in allowing for earlier diagnosis of the disorder. Earlier diagnosis allows individuals with ADHD to develop effective management strategies, which in turn improves their social, academic, and psychological functioning. Greater public understanding of ADHD in females can be achieved through education. Moving forwards, particularly amongst health professionals and teachers, ADHD should be treated as a disorder that affects both males and females, and attention should be drawn to potential differences in symptomatic presentation between males and females.However, ADHD in females should not be treated as separate to ADHD in males, as this can feed into further stereotypes. The findings of this study identify the need for larger scale research surrounding ADHD in females, to strengthen the validity of this research. In conclusion, the results of this qualitative study provide significant insight into the complex and challenging nature of ADHD amongst female university students in the UK.


Background: Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental condition that has a significant impact on the lives of children and adolescents. This study conducts a comprehensive 20-year analysis of data from the National Center for Health Statistics (NCHS) to investigate the prevalence of ADHD among American youth, as well as its demographic patterns and socioeconomic determinants.Methods: A retrospective analysis of NCHS data spanning from 1997 to 2018 was carried out. The dataset included information on ADHD diagnoses, demographic characteristics , socioeconomic indicators , and temporal variables. A range of statistical analyses were performed, encompassing temporal trend analysis, demographic assessments, and socioeconomic examinations.Results: It was consistently observed that boys had a higher prevalence of ADHD (12.93% compared to 5.61%), aligning with established trends. Among adolescents aged 10-17, the prevalence was the highest at 11.09%, while for the 5-9 age group, it stood at 6.57%. In terms of racial and ethnic groups, individuals identifying as two or more races exhibited the highest prevalence at 12.36%, followed by white (9.83%), black or African American (10.09%), Hispanic or Latino (5.36%), and non-Hispanic or Latino (10.64%). Socioeconomic disparities were evident, with a prevalence of 11.41% among those living below the poverty line, compared to 10.6% (100%-199% of the poverty line), 8.6% (200%-399%), and 8.39% (400% or more). Medicaid beneficiaries had the highest prevalence at 12.57%, followed by those with private insurance (9.65%), insured (8.11%), and uninsured (5.83%).Conclusion: These findings underscore the intricate relationship between ADHD prevalence and demographic and socioeconomic factors. It is imperative to address these disparities to ensure equitable assessment and intervention for ADHD, taking into account cultural influences, determinants of health tied to socioeconomic status, and access to healthcare for all children. This analysis by the NCHS provides essential insights into ADHD among American youth, emphasizing the necessity for tailored interventions, equitable healthcare access, and further research to comprehensively address this complex neurodevelopmental disorder. Attention-deficit hyperactivity disorder (ADHD) stands as a significant and widely recognized neurodevelopmental condition that affects a substantial number of children and adolescents throughout the United States. Marked by symptoms of inattention, hyperactivity, and impulsivity, ADHD can exert a profound influence on various aspects of a young individual's life, encompassing academic performance, social interactions, and overall quality of life. Gaining insight into the prevalence, trends, and demographic patterns of ADHD among American youth carries great importance for healthcare professionals, educators, policymakers, and parents alike -3.Salari et al.'s meta-analysis provides a global perspective on ADHD prevalence among children and adolescents, indicating rates of approximately 5.6% for teenagers aged 12-18 and 7% for those under 12 . In the Studying the prevalence of attention-deficit hyperactivity disorder (ADHD) among American youth is crucial for understanding its impact on mental health and educational outcomes. It helps in identifying trends, informing interventions, and allocating resources effectively to support affected individuals and improve their well-being, academic success, and overall quality of life. ADHD has a significant impact on academic performance, social relationships, emotional well-being, behavior, and family dynamics and often co-occurs with conditions like anxiety, mood disorders, and learning disabilities. A comprehensive understanding of long-term trends in ADHD among youth holds wide-ranging implications. It informs early intervention strategies, facilitating timely diagnosis and tailored support to address the challenges associated with ADHD. Furthermore, this knowledge guides educational institutions in adapting teaching methods to accommodate students with ADHD, potentially enhancing academic outcomes and reducing dropout rates -9. On a The National Center for Health Statistics (NCHS) provides a valuable, reliable, and accessible source of data on ADHD, enabling a comprehensive 20-year analysis of the condition's evolution in terms of treatment, prevalence, and diagnosis rates. The data's reliability is underscored by its rigorous sourcing, collection, documentation, and validation. The dataset is rigorous due to its meticulous data sourcing, standardized collection methodologies, and stringent validation processes, ensuring high-quality, reliable health-related information for research, policy-making, and public health analysis. Moreover, its comprehensiveness is bolstered by factors such as sample size, diversity, longitudinal data, granularity, domain expertise, and coverage, making NCHS data exceptionally well-suited for this descriptive study .The primary aim of this study was to conduct a thorough analysis of two decades of NCHS data pertaining to ADHD in children under 18. We embarked on a comprehensive examination of this 20-year dataset, delving into the multifaceted factors that influence ADHD prevalence among youth. Changes in diagnostic criteria and increased ADHD awareness over the past 20 years may influence prevalence rates. Unexplored factors, like genetic predisposition and environmental influences, add complexity to understanding ADHD's multifaceted nature. By exploring various temporal and demographic dimensions, including age, gender, race, and socioeconomic variables such as poverty level and insurance status, our objective was to deepen our understanding of this disorder's impact on children and adolescents. Ultimately, our goal is to provide evidence-based insights to inform its assessment and management.Data source and collectionIn this study, we conducted a retrospective analysis of data sourced from the NCHS, covering a substantial two-decade period from 1997 to 2018. The NCHS holds a prominent position as a nationally recognized and authoritative repository for health-related data within the United States. It offers a comprehensive dataset encompassing various facets of public health, including the prevalence of ADHD and associated demographic and socioeconomic factors . The NCHThe data collection process was initiated by retrieving pertinent information from the NCHS database, spanning the years 1997 to 2018. This meticulous compilation of data included records specifically relevant to ADHD diagnoses, demographic characteristics , socioeconomic indicators (including poverty level and insurance status), and temporal variables. Our primary focus was on data related to children aged 3 to 17 years during this extensive study period.Several key variables were extracted from the NHIS dataset to facilitate our analysis: (1) ADHD diagnosis status: This binary variable served as an indicator of whether an individual had received an ADHD diagnosis or not; (2) Demographic information: Essential demographic variables encompassed age, gender, and race/ethnicity, providing a foundation for exploring ADHD patterns across distinct population subgroups; (3) Socioeconomic variables: The variables of poverty level and insurance status were instrumental in shedding light on the socioeconomic determinants and aspects related to healthcare access concerning ADHD; (4) Temporal variables: The inclusion of the year of diagnosis was pivotal for our temporal trend analysis, enabling us to elucidate the evolution of ADHD prevalence over the extensive 20-year timeframe.Data analysisThe datasets sourced from the NCHS underwent a meticulous process of cleaning and preprocessing, such as data inspection, documentation, and identifying and handling missing data to ensure the integrity of the dataset. This essential phase involved the systematic identification and rectification of missing values, outliers, and inconsistencies within the dataset. To maintain data quality and completeness, rigorous validation checks such as consistency checks, duplicate checks, data integrity checks, and cross-field validation were performed, and when necessary, missing values were imputed through appropriate methods such as mean/median imputation. Furthermore, the dataset was thoughtfully aggregated by relevant parameters, including year, age groups, gender, and other pertinent categories. This strategic aggregation was aimed at facilitating a comprehensive and structured statistical examination of the data. This examination delved into the changes in ADHD prevalence over the 20-year duration of the study, with the primary objective of identifying any significant patterns or fluctuations in the prevalence rates over time. Additionally, the study encompassed demographic and socioeconomic analyses designed to explore potential disparities and uncover associations between various variables. These analyses were conducted with the utilization of appropriate statistical software, such as Microsoft Excel and SPSS, to ensure rigorous and methodologically sound investigations.Ethical considerationsThis study utilized de-identified, publicly available data from the NCHS, ensuring the privacy and confidentiality of participants. No additional ethical approval was required for the analysis of secondary data.The comprehensive analysis of 20 years of NCHS data provided valuable insights into the prevalence, demographic patterns, and temporal trends of ADHD among American youth. Over the 20-year study period from 1997 to 2018, the analysis revealed that the prevalence of ADHD among American youth exhibited fluctuations. The results presented below offer a detailed overview of the key findings , followed by the 5-9 years age group (6.57%). The temporal trends further revealed evolving patterns over the study period.For the 5-9 years age group, ADHD prevalence rates increased from 4.8% in 1997 to 7.0% in 2010, stabilizing at 7.4% in 2018. However, a consistent rise was observed in the 10-17 years age group, with the overall prevalence ranging from 7.6% in 1997 to 12.9% in 2018. Understanding these age-related nuances in ADHD diagnoses is crucial for tailoring interventions and healthcare strategies to meet the unique needs of children at different developmental stages. Figure Based on raceIn our analysis focusing on racial disparities in ADHD prevalence among children, we uncovered noteworthy variations among different racial categories. The data elucidated a higher frequency of ADHD diagnoses among individuals identifying as two or more races in comparison to other racial groups. Across all the years under consideration (1997-2018), the category encompassing two or more races accounted for approximately 12.36% of diagnosed cases. In contrast, the white-only category constituted 9.83%, the black or African American category 10.09%, the Hispanic or Latino category 5.36%, and the non-Hispanic or Latino category 10.64%. These findings not only highlight the diversity in ADHD prevalence but also suggest that nuanced approaches are warranted when addressing this neurodevelopmental condition in various racial subgroups.An examination of temporal trends within specific racial categories revealed intriguing insights. Among the Hispanic or Latino and non-Hispanic or Latino groups, ADHD prevalence exhibited an upward trajectory, with rates increasing to 5.76% and 10.64%, respectively, by the year 2018. Conversely, the black or African American population displayed a non-uniform pattern, initially experiencing a decline from 10.5% to 9.4% between 2012 and 2013, followed by a subsequent increase to 13.2% by 2018. Particularly noteworthy was the two or more races category, which witnessed a substantial 5.3% increase in prevalence from 2000 to 2008, ultimately reaching 14.5% by 2018, up from 12.7% in 2008.For a visual representation of these disparities, refer to Figure Based on poverty levelWithin our comprehensive 20-year analysis, noteworthy trends in ADHD prevalence emerged based on the percentage of poverty level among children under the age of 18. Notably, children hailing from families residing below the poverty line consistently displayed elevated rates of ADHD diagnoses when juxtaposed with their counterparts from higher-income households. The data underscored a recurring pattern where ADHD diagnoses were more frequently ascribed to individuals below the 100% poverty level, corroborating prior research findings. Over the entirety of the study period, the segment falling below the 100% poverty threshold accounted for approximately 11.41% of diagnosed cases. In comparison, the categories spanning 100%-199%, 200%-399%, and 400% or more of the poverty level represented 9.73%, 8.6%, and 8.39% of diagnoses, respectively.An upward trajectory in prevalence was notably evident within three of the four poverty level categories: below 100%, 200%-399%, and 400% or more. The below 100% category consistently exhibited a pronounced increase throughout the study duration. In contrast, the 100%-199% category initially witnessed an ascent, climbing from 6.7% to 10.6% between 1997 and 2009. This was followed by a decline to 9.4% in 2013, only to subsequently rise to 11.7% by 2018.These findings highlight the paramount influence of socioeconomic factors on the prevalence of ADHD. They underscore the significance of addressing the social determinants of health to ensure equitable access to both the assessment and interventions related to ADHD for all children, irrespective of their economic backgrounds. To provide a visual representation of these disparities, please refer to Figure Based on health insurance statusOur extensive 20-year analysis has unveiled compelling associations between the health insurance status at the time of the interview and the prevalence of ADHD among children under the age of 18. Striking disparities in ADHD diagnosis rates were observed among children with different insurance statuses. Most notably, individuals lacking health insurance consistently exhibited markedly higher rates of ADHD diagnoses in comparison to their insured counterparts. The data firmly established that ADHD diagnoses were more frequently conferred upon those covered by Medicaid as opposed to those possessing private insurance or those who were uninsured, thus aligning seamlessly with earlier research findings. Across all the years under examination, Medicaid accounted for a substantial 12.57% of diagnosed cases, while insured individuals constituted 9.65%, those with private insurance comprised 8.11%, and the uninsured exhibited the lowest percentage at 5.83%.For a visual representation of these disparities, Figure The 20-year analysis of NCHS data on ADHD in American youth has provided invaluable insights into the prevalence, demographic patterns, and socioeconomic determinants of this complex neurodevelopmental disorder. Our discussion aims to illuminate the key findings derived from this extensive analysis. The prevalence rates revealed notable trends over the past two decades, shedding light on the evolving landscape of ADHD among American youth. We explore the implications of these findings, considering their potential impact on public health interventions, resource allocation, and targeted support for affected individuals and communities.One of the most noteworthy findings of this study pertains to the variation in ADHD prevalence across diverse demographic groups. Gender disparities were unmistakable, with boys consistently displaying higher prevalence rates than girls, aligning seamlessly with established research trends. This gender gap has been persistently observed in prior research conducted by Vuori et al. and London et al., thus underscoring the imperative for a more comprehensive exploration of the underlying factors contributing to this disparity -13.Age-specific patterns revealed that ADHD diagnoses were more prevalent among adolescents aged 10 to 17 years, implying the unique challenges associated with this developmental phase. These age-specific patterns are in concordance with earlier studies, which consistently reported higher ADHD prevalence rates among adolescents aged 10 to 17 years ,14-15. TMoreover, our analysis revealed disparities based on race/ethnicity, with higher prevalence rates among children identifying as belonging to two or more races. Previous research has also probed racial disparities in ADHD diagnoses, consistently revealing fluctuations in ADHD prevalence among various racial and ethnic groups. Some studies have indicated elevated prevalence rates among non-Hispanic white children, while others have demonstrated higher rates among non-Hispanic black children ,16-18. TSocioeconomic factors emerged as another pivotal aspect, as children from families situated below the poverty line exhibited higher rates of ADHD diagnoses. The influence of socioeconomic status on ADHD prevalence is a crucial discovery with far-reaching implications. Children hailing from economically disadvantaged backgrounds demonstrated an increased likelihood of receiving an ADHD diagnosis -21. ThisAnother substantial revelation was the connection between health insurance status and ADHD prevalence. Children lacking health insurance consistently exhibited elevated rates of ADHD diagnoses. Our findings align with previous research, emphasizing the role of healthcare access and coverage in addressing this neurodevelopmental disorder -23. ThisThe strength of the study lies in its meticulous examination of ADHD trends among American youth through a comprehensive 20-year analysis of NCHS data. The extended temporal scope provides a unique opportunity to discern patterns and changes in ADHD prevalence over time, offering a valuable longitudinal perspective. The inclusion of a large and diverse dataset ensures the robustness of the findings, allowing for meaningful statistical analyses and reliable prevalence estimates. By exploring sociodemographic factors such as gender, race, and socioeconomic status, the study adds depth to our understanding of ADHD disparities within different population groups. Additionally, the study's alignment with the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) criteria for ADHD diagnosis ensures methodological rigor and enhances the credibility of its conclusions. The authors' acknowledgment of limitations, including the absence of information on genetic and environmental factors, demonstrates transparency and provides a foundation for future research directions. The study's reliance on available NCHS data may introduce potential biases or variations stemming from reporting practices. Changes in diagnostic criteria and heightened awareness of ADHD over the 20-year duration may have exerted an influence on prevalence rates. Moreover, unexplored factors, such as genetic predisposition and environmental influences, could contribute to the complexity of ADHD. Grasping the intricacies of ADHD prevalence and its interplay with demographic and socioeconomic factors is essential for tailoring interventions and support mechanisms. Early intervention programs, educational accommodations, and targeted policies must take these variations into account to provide effective assistance to children and adolescents grappling with ADHD.Longitudinal research holds promise as a necessary avenue for tracking individuals with ADHD as they traverse from childhood into adolescence and adulthood. Such studies can offer invaluable insights into the persistence of ADHD symptoms and the efficacy of interventions spanning the entire lifespan. The study does not investigate the longitudinal trajectory of individuals with ADHD from childhood into adolescence and adulthood, nor does it delve into the persistence of ADHD symptoms or the effectiveness of interventions throughout the lifespan. Longitudinal studies are most appropriate for these inquiries as they allow for tracking individuals over time, capturing the evolving nature of ADHD, potential variations in symptoms, and the long-term impact of interventions. This approach provides a comprehensive understanding of ADHD's trajectory, offering insights crucial for tailored interventions and informed healthcare policies.Overall, this study contributes significantly to the literature by offering a comprehensive and nuanced exploration of ADHD prevalence and its sociodemographic determinants among American youth.In conclusion, our comprehensive 20-year analysis of ADHD prevalence among children under 18, based on various demographic and socioeconomic factors, reveals noteworthy patterns. Gender, race/ethnicity, poverty level, and health insurance status all exhibit significant associations with ADHD diagnoses. Boys consistently had a higher prevalence than girls, and certain racial groups, notably those identifying as two or more races, displayed elevated rates. Children below the poverty line experienced higher ADHD rates, and those without health insurance were at a disadvantage compared to their insured counterparts. These findings underscore the complex interplay of demographic and socioeconomic factors in ADHD prevalence, highlighting the importance of tailored assessment and intervention strategies. Recognizing and addressing these disparities are essential steps toward developing equitable approaches to ADHD assessment and intervention, considering cultural and racial influences, and ensuring healthcare accessibility for all children. Additionally, our research calls for further exploration into the multifaceted factors contributing to ADHD disparities and the development of equitable healthcare policies and interventions to address the unique needs of children with ADHD, with a focus on longitudinal studies that track individuals with ADHD across the lifespan.


Adults with attention-deficit/hyperactivity disorder (ADHD) have more maladaptive cognitions, emotional problems and a poorer quality of life (QoL). A verification of the psychological model in clinical samples is needed for a better understanding of the mechanisms of ADHD diagnosis on QoL via maladaptive cognitions, emotional symptoms, and their interactions.299 ADHD participants and 122 healthy controls were recruited. ADHD core symptoms, maladaptive cognitions, emotional symptoms and psychological QoL were rated. Pearson’s correlation and structural equation modeling were analyzed to explore the relationship and influence of ADHD diagnosis on QoL.p = 0.368). Moderate to strong correlations were found between emotional symptoms, maladaptive cognitions and QoL, and ADHD core symptoms presented correlations among the above scores  in ADHD participants. The influence of ADHD diagnosis on QoL was mediated through maladaptive cognitions, emotional symptoms, and their bidirectional interactions (p < 0.05), especially those with stable medication.More maladaptive cognitions, emotional symptoms, and poorer QoL were found in the ADHD group, and the dysfunctional attitudes were on par between ADHD with or without medication (Our study is the first to verify the psychological model in adults with ADHD in China. The findings determined the direct influence of ADHD diagnosis on QoL and the indirect influence through maladaptive cognitions, emotional symptoms, and their interactions, emphasizing the importance of interventions for emotional symptoms and maladaptive cognitions for ADHD patients both with or without medication for a better QoL outcome. Limited studies discussed the bidirectional relationships between maladaptive cognitions and emotional symptoms in adults of ADHD and their influences on QoL. One of the few published studies  indicateIn our study, we aimed to explore  the rela2.2.1.The participants were outpatients of Peking University Sixth Hospital and individuals recruited from the internet from March 2019 to September 2022. The key inclusion criteria were as follows:being an outpatient of Peking University Sixth Hospital, aged between 18–45 years, and having received a diagnosis of adult ADHD through Conners’ Adult ADHD Diagnostic Interview  based onADHD medication-naïve or have stable use of ADHD medication (drug fluctuations <10% for at least 1 month) , either The key exclusion criteria included the following:had a history of schizophrenia or pervasive developmental disorder;had a history of severe external brain injuries or neurological diseases with a loss of consciousness, and other serious somatic diseases;exhibiting high suicide risk;having a full-scale intelligence quotient (FIQ) < 80;The healthy controls (HCs) were age– and sex-matched with those in the ADHD group. Additionally, they did not meet the criteria for a diagnosis of ADHD based on an evaluation by trained psychiatrists. Those with a history or current diagnosis of neurological or mental illness, family history of mental illness, or serious somatic disease and FIQ < 80 were excluded.All participants were assessed for mental disorders according to the Structured Clinical Interview for DSM-IV Axis-I  and Axis2.2.The ADHD Rating Scale (ADHD-RS)  was usedAll participants underwent diagnostic interviews and FIQ evaluations by assessors who had received unified training on all the measurement tools, and the consistency was rated. The ethics committee protected the interests of the subjects, such as safety and confidentiality.2.3.post hoc test. Pearson’s correlation was used to assess the correlation among clinical variables, including ADHD core symptoms (ADHD-RS), emotional symptoms (SAS and SDS), maladaptive cognitions (ATQ and DAS) and QoL , in the whole, medicated and non-medicated ADHD groups. Irrelevant, weak, moderate, and strong correlations (r) were defined as r values of 0 ~ 0.09, 0.10 ~ 0.30, 0.30 ~ 0.50, and 0.50 ~ 1.00, respectively.Independent two-sample t tests and chi-square (χ2) tests were used to compare the baseline variables between the ADHD and HC groups. We divided the ADHD participants into a group with ADHD medication (the medicated ADHD group) and a group without medication (the non-medicated ADHD group) according to the stable use of ADHD medication. One-factor analysis of variance (one-way ANOVA) and χ2 tests were used to compare the differences among the medicated, non-medicated and HC groups. The Bonferroni method or χ2 tests were used for the Structural equation mediation model analyses (SEM) were performed using the R package lavaan  with the3.3.1.A total of 299 ADHD participants were recruited, with 170 (56.86%) diagnosed with the predominantly inattentive subtype (ADHD-I), and the others diagnosed with the combined subtype (ADHD-C). 177 (59.20%) participants were diagnosed with comorbidities, including bipolar disorder (BD) , affective disorders , anxiety disorders , eating disorders , and substance use disorders (SUD) . All ADHD participants with comorbidities, especially those with SUD or BD, persisted in complete remission, and the use of ADHD medications was prescribed based on the clinical demand to confirm the efficacy and safety of medication treatment. 189 patients reported stable use of ADHD medication, including methylphenidate , atomoxetine , or both . Among the 189 medicated patients, 34 (11.37%) were co-administered with other psychiatric medications, including antidepressants, mood stabilizers, and antipsychotics.3.2.p = 0.000). The ADHD-RS total, SAS and SDS scores were significantly higher in the ADHD group than in the HC group (p = 0.000). The ATQ and DAS total scores in the ADHD group were significantly higher than those of the HC group, and the WHOQOL-psychological domain score was significantly lower in the ADHD group than in the HC group (p < 0.001) (No significant differences were found between the ADHD group and the HC group in sex and age. The FIQ and years of education in the ADHD group were significantly lower than that in the HC group (< 0.001) .Post hoc pairwise comparisons within each group indicated that the non-medicated ADHD group had significantly higher SAS, SDS, ATQ scores, and significantly lower WHOQOL-psychological domain score than the medicated ADHD group. No difference was found in DAS total score between the medicated and the non-medicated ADHD groups (p = 0.368)  .3.3.r = 0.157 ~ 0.416, p < 0.001) and a negative correlation with WHOQOL-BREF-psychological domain  were found, and the correlations were small to moderate. Emotional symptoms (SAS and SDS) were positively correlated with maladaptive cognitions (ATQ and DAS)  and negatively correlated with the WHOQOL-BREF-psychological domain , and the correlations were moderate to strong. When controlling for the use of medication, the correlation still existed . The mediation effect model showed that the direct  and total effect  of ADHD diagnosis on the WHOQOL-psychological domain score were significant. The indirect effect through maladaptive cognitions  and emotional symptoms  were also significant. The indirect effect of ADHD diagnosis on QoL was statistically significant both through maladaptive cognitions and then emotional symptoms , and also through emotional symptoms and then maladaptive cognitions . When controlling for the use of medication, all the mediation paths existed (p = 0.000) except the mediation role through maladaptive cognitions and then emotional symptoms did not exist .The structural model for ADHD diagnosis on QoL in the whole ADHD group compared with the HC group showed good fit (χ2 (df = 8.000) =15.076, 3.4.2.p = 0.176, CFI = 0.997, RMSEA =0.036, SRMR = 0.014, the non-medicated ADHD group: χ2 (df = 8.000) = 12.731, p = 0.121, CFI = 0.997, RMSEA = 0.051, SRMR = 0.011). The significant direct effect, total effect, and indirect effect through maladaptive cognitions, or through emotional symptoms and then maladaptive cognitions were found in both groups (p < 0.05). The indirect effect through emotional symptoms were significant only in the medicated ADHD group  but not in non-medicated ADHD group (p = 0.369). A trend of significant indirect effect through maladaptive cognitions and then emotional symptoms could be found in the medicated ADHD group . The indirect effect of ADHD through emotional symptoms did not exist dependently , but existed through emotional symptoms and then the maladaptive cognitions  in the non-medicated ADHD group  = 13.945, HD group .4.Our research yielded the following findings. First, more emotional symptoms, maladaptive cognitions, and poorer QoL were found in the ADHD group, both with and without medication. Second, ADHD patients without medication presented more ADHD core symptoms, emotional symptoms, automatic thinking and poor psychological QoL compared with those with medication, and the dysfunctional attitudes remained no differences. In addition, the ADHD core symptoms, emotional symptoms, maladaptive cognitions and psychological QoL were correlated whether controlling for the use of medication or not. Then, the influence of ADHD diagnosis on QoL was mediated through maladaptive cognitions and emotional symptoms, and the bidirectional associations between maladaptive cognitions and emotional symptoms. The use of ADHD medication may reduce the influence on QoL via maladaptive cognitions associated with ADHD since we found the mediation role through maladaptive cognitions and then emotional symptoms was not significant when controlling for the use of medication. A trend of influence of ADHD diagnosis on QoL through maladaptive cognitions and then emotional symptoms still existed in medicated ADHD group, again verified that the use of medication does not fully decrease the dysfunctional attitudes, and the existence of maladaptive cognitions may still increase the risk of emotional distress and then QoL impairments.This study was the first to explore the maladaptive cognitions of adult ADHD in the Chinese population, and the results are consistent with previous findings , 58. TheCompared with those without medication, ADHD patients with stable medication were found to have less ADHD core symptoms, emotional symptoms, and more life satisfaction. Efficacy of medication has been proven in ADHD core symptoms , the comIn our study, the ADHD core symptoms, maladaptive cognitions, and emotional symptoms are all correlated with impairments of psychological life quality. The correlation between emotional symptoms and QoL in the ADHD group was moderate to strong, consistent with the findings of bidirectional associations of emotional symptoms and QoL . MeanwhiWe first explored the possible mechanism connecting adult ADHD diagnosis and QoL through the mediators of maladaptive cognitions and emotional symptoms. The mediation analysis found the direct and indirect influences of ADHD diagnosis on QoL via bidirectional associations between maladaptive cognitions and emotional symptoms, consistent with the theoretical psychological model in adult ADHD , 31, 32,Studies found that unwanted intrusive and worrisome thoughts may trouble patients’ anxiety symptoms , and negAccumulated studies supported the proposed association between adult ADHD and maladaptive cognitions of failure, combatting stigma, being different from others, and their influences on self-efficacy and self-esteem . ResearcWhen controlling for the use of medication, we found the mediation role through maladaptive cognitions and then emotional symptoms was not significant, indicating that the use of medication reduces the influence on QoL via maladaptive cognitions associated with ADHD. Whereas, the existence of emotional symptoms still influences QoL through maladaptive cognitions, since patients with stable medication still had more emotional symptoms compared with the healthy controls. We then compared the medicated and non-medicated ADHD groups, and found the different mediation roles of maladaptive cognitions and emotional symptoms in the two subgroups. Compared with ADHD patients with medication, those without medication got a higher mediation ratio on QoL via maladaptive emotions related to ADHD. ADHD with stable medication got higher mediation ratio on QoL through emotional symptoms as well as through emotional symptoms and then maladaptive cognitions, suggesting that the existence of emotional symptoms in patients after stable medication will affect quality of life directly or indirectly through maladaptive cognitions. Besides, a trend of mediation effect through maladaptive cognitions and then emotional symptoms can also be found in those with stable medication, since the use of medication does not fully decrease maladaptive cognitions, especially the dysfunctional attitudes directly, and the existence of maladaptive cognitions may still increase the risk of emotional distress. Thus, a further work in individuals’ maladaptive cognitions and emotional distress is important for a better functional outcome in adults with ADHD.Our study further confirmed the psychological model of ADHD in clinical samples, and emphasized the importance of emotional symptoms and maladaptive cognitions on the influence of QoL. Similar results could be found in other clinical researches , suggestCBT has been found to be effective for emotional symptoms, maladaptive cognitions and QoL based on our researches . PreviouOur study also had some limitations. The evaluation of patients’ maladaptive cognitions focuses on negative automatic thinking (ATQ) and dysfunctional beliefs (DAS), which are common scales for evaluating patients’ negative thinking and dysfunctional attitudes and have been applied many times in ADHD patients , 23 but 5.This study was the first to investigate the maladaptive cognitions of adults with ADHD in China, and found defects in maladaptive cognitions, emotional symptoms, and reduced psychological QoL both with or without stable medication. Our study further validated the psychological model of ADHD in a Chinese population with the use of clinical samples and determined the direct influence of ADHD diagnosis on QoL and the indirect influence through maladaptive cognitions, emotional symptoms, and their bidirectional interactions. Results further emphasized the importance of interventions for emotional symptoms and maladaptive cognitions in patients with ADHD both with or without medication for a better QoL outcome, and provided a theoretical basis for the subsequent development of precision treatment strategies based on the individual and psychological characteristics of patients with ADHD.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.The studies involving human participants were reviewed and approved by This trial has been approved by the Ethics and Clinical Research Committees of Peking University Sixth Hospital [(2018) Ethics review number ] and wilM-RP and Q-JQ: conceptualization. M-RP, S-YZ, and Q-JQ: design and methodology. M-RP, S-YZ, C-LC, S-WQ: conduction of the study. M-RP, S-WQ, M-JZ, MD, and F-FS: statistical analysis and interpretation. M-RP: writing—original draft preparation. LL, H-ML, Y-FW, and Q-JQ: writing—review and editing. Q-JQ: resources. Y-FW and Q-JQ: supervision. All authors contributed to the article and approved the submitted version.This work was supported by the Capital’s funds for Health Improvement and Research (CFH: 2020–2-4112) and the Beijing Nova Program (20220484061).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.


Attention-deficit/hyperactivity disorder (ADHD) is one of the most widespread and highly heritable neurodevelopmental disorders affecting children worldwide. Although synaptosomal-associated protein 25 (SNAP-25) is a possible gene hypothesized to be associated with working memory deficits in ADHD, little is known about its specific impact on the hippocampus. The goal of the current study was to determine how variations in ADHD’s SNAP-25 Mnll polymorphism (rs3746544) affect hippocampal functional connectivity (FC).A total of 88 boys between the ages of 7 and 10 years were recruited for the study, including 60 patients with ADHD and 28 healthy controls (HCs). Data from resting-state functional magnetic resonance imaging (rs-fMRI) and clinical information were acquired and assessed. Two single nucleotide polymorphisms (SNP) in the SNAP-25 gene were genotyped, according to which the study’s findings separated ADHD patients into two groups: TT homozygotes (TT = 35) and G-allele carriers (TG = 25).Based on the rs-fMRI data, the FC of the right hippocampus and left frontal gyrus was evaluated using group-based comparisons. The corresponding sensitivities and specificities were assessed. Following comparisons between the patient groups, different hippocampal FCs were identified. When compared to TT patients, children with TG had a lower FC between the right precuneus and the right hippocampus, and a higher FC between the right hippocampus and the left middle frontal gyrus.The fundamental neurological pathways connecting the SNAP-25 Mnll polymorphism with ADHD via the FC of the hippocampus were newly revealed in this study. As a result, the hippocampal FC may further serve as an imaging biomarker for ADHD. One of the most common mental conditions, attention-deficit/hyperactivity disorder (ADHD), affects almost one in 20 children and adolescents globally and is characterized by fundamental symptoms of hyperactivity, impulsivity, and inattention . ADHD isThe hippocampus plays a crucial role in spatial navigation and consolidation of information from short-term to long-term memory . StudiesAs research progresses, increasing attention has been placed on the relevance of genetic factors and their relationship to ADHD, particularly through the application of neuroimaging techniques, such as resting-state functional magnetic resonance imaging (rs-fMRI), structural MRI, and diffusion tensor imaging (DTI). These studies have investigated various gene polymorphisms that could influence brain function, connectivity, and structure related to ADHD. For instance, certain dopaminergic genes, like DAT1 (SLC6A3) and DRD4, have shown significant associations with ADHD . rs-fMRIAnother gene of interest in ADHD neuroimaging is the brain-derived neurotrophic factor (BDNF) gene. Reductions in gray matter volume in prefrontal and limbic structures were associated with the BDNF Val66Met polymorphism, which plays a role in neuronal survival, growth, and differentiation . MoreoveAdditionally, the catechol-O-methyltransferase (COMT) gene has been investigated in the context of ADHD. The COMT Val158Met polymorphism is associated with altered fronto-striatal connectivity , and it Similarly, serotonin-related genes, such as the serotonin transporter (5-HTT) gene and the serotonin 2A receptor (HTR2A) gene, have also been examined, as imbalances in the serotonergic system are thought to contribute to ADHD . A studyFurthermore, the SNAP-25 gene, encoding the SNAP-25 protein, has been shown to play a significant role in the process of synaptic vesicle fusion. This process is crucial for communication between neurons, which in turn is critical for memory and learning . The proWhile there have been some studies investigating hippocampus-related functional connectivity (FC) alterations in ADHD , the relConsequently, the SNAP-25 gene has been shown to play a role in ADHD. In this study, we further investigate its impact by categorizing ADHD patients into subtypes based on their SNAP-25 genotypes. We hypothesize that these genotypic subtypes might exhibit different patterns of functional connectivity, thus providing a more nuanced understanding of ADHD.We expect our findings to provide additional insights into the underlying neurobiological mechanisms linking SNAP-25 gene variations with ADHD symptomatology and working memory deficits. This deeper understanding may not only enhance the accuracy of ADHD diagnosis but also contribute to the development of personalized intervention strategies. For instance, if the effects of the SNAP-25 Mnll variant on hippocampal FC are found to be significant, targeted therapies could be designed to address these changes and improve working memory in children with ADHD.This study recruited 60 children with ADHD aged between 7 and 10 years from Shenzhen Children’s Hospital through a carefully planned collaboration with local schools and pediatric clinics. Our primary goal was to investigate the relationship between hippocampal functional connectivity (FC) alterations and ADHD symptomatology, as well as assess the impact of these alterations on working memory performance in children with ADHD. Prior to enrollment, clinicians at the Shenzhen Children’s Hospital identified potential participants and informed their parents about the research study. All participants and their parents were interviewed by experienced clinicians to confirm or exclude a diagnosis of ADHD or any other psychiatric disorder using a clinical interview and the Schedule for Affective Disorders and Schizophrenia for School-Age Children–present and lifetime version (K-SADS-PL) , based oChildren with ADHD were required to meet the following inclusion criteria: (1) 7–10 years old, (2) educated in private or public schools, and (3) diagnosed with ADHD. Healthy control subjects had the same age and education requirements as ADHD subjects. The exclusion criteria for both groups included a history of head injury with loss of consciousness, severe physical disease or neurological abnormalities, drug or substance misuse, full-scale IQ measured by Wechsler Intelligence Scale for Chinese Children-IV (WISC-IV-Chinese) below 70, prescription medications for ADHD or other medical conditions used over the long term, and comorbid conduct disorder or Oppositional Defiant Disorder (ODD).To better understand the relationship between ADHD symptoms and participant characteristics, we assessed ADHD symptomatology using the Conners’ Parent Rating Scale , which eThe MRI scans were only performed on participants who were right-handed dominant, had no visible abnormalities on their MRI images, and did not have a history of claustrophobia. ADHD participants presented with six or more inattentive symptoms as well as six or more hyperactive/impulsive symptoms, and in subsequent statistical analysis, the summing severity scores of each symptom were used as indicators of symptom severity.As discussed in section “2.3. Genotyping for the detection of SNAP-25 MnII variants” below, we subdivided these ADHD subjects into two subgroups based on their SNAP-25 rs3746544 genotypes, to study the potential correlation between certain genotypes and FC alterations in ADHD symptomatology. The breakdown was as follows:1.TT homozygotes: 35 participants2.G-allele carriers (TG): 25 participantsThe healthy control group did not undergo genotyping, as our study was focused exclusively around ADHD symptomatology and the potential connection to specific genotypes.All children and their parents were informed about the purpose and procedures of the study. Children gave their assent to participate, and their parents provided written informed consent on their behalf. The Shenzhen Children’s Hospital Medical Ethics Committee approved this study. All methods were performed in accordance with relevant guidelines and regulations.Attention-deficit/hyperactivity disorder patients, along with TT homozygotes, G-allele carriers, and HCs, underwent an exhaustive set of cognitive and behavioral evaluations. Parents of the participating children completed the Conners’ Parent Rating Scale . This coCognitive function was evaluated using the Wechsler Intelligence Scale for Children, Fourth Edition- Chinese version (WISC-IV-Chinese) , a globaThese evaluations are crucial to understanding the cognitive and behavioral profiles of our participants. In this study, we employed the original summary scores for each index from the WISC-IV-Chinese and each factor from the Conners’ Parent Rating Scale. Our comprehensive assessments of ADHD symptoms and cognitive functions provide us with a rich dataset that can be correlated with the observed FC alterations in our study. Such correlations may elucidate the clinical implications of the FC alterations we identified and may provide further insights into the symptomatology and cognitive profile associated with ADHD.Following the manufacturer’s guidelines, peripheral venous blood samples were collected from the participants, and SNAP-25 rs3746544 genotyping was carried out using the Flexi Gene DNA Kit . Rs3746544 had a forward primer of 5′ TTCTCCTCCAAATGCTGTCG 3′ and reverse primer of 5′ CCACCGAGGAGAAAATG 3′. EX-Taq polymerase and GC buffer  were used in a thermocycler to perform the polymerase chain reaction (PCR) amplification . A denaturing cycle at 94°C for 2 min was followed by 30 cycles of 94°C for 30 s, 52°C for 30 s, 72°C for 45 s, and finally an extension step at 72°C for 8 min, in the PCR technique. The TT homozygote group had 35 members (TT group = 35), whereas the TG group had 25 G-allele carriers (TG group = 25).We decided to concentrate on the TT homozygotes and the TG G-allele carriers. The distribution of these genotypes in our sample is approximately balanced . This distribution was not designed to reflect population prevalence or vulnerability to ADHD. Instead, it aimed to provide a balanced dataset for comparing functional connectivity patterns.2; slice thickness = 3 mm; no gap. Structure 3D-MPRAGE: T1 Repetition Time  = 2300 ms, Echo Time  = 2.26; Number of Averages = 1.0, Slice Thickness = 1.0 mm, Field of View (FOV) = 256 mm.The Radiology Department of Shenzhen Children’s Hospital in Shenzhen, China, used a 3.0-T system scanner (Siemens Magnetom Skyra) to collect rs-fMRI data from each participant. The following parameters were used in the echo-planar imaging (EPI) process to acquire the rs-fMRI data: repetition time (TR) = 2000∼ms; echo time = 30∼ms; flip angle = 90°; matrix size = 64 \times 64; 32 axial slices; field of view = 24 \times 24 cm1 The image preprocessing in the analysis as follow: the first 10 volumes were dropped because of the instability of the initial magnetic resonance imaging data and the participants’ adaptation to the experimental apparatus. First, the slice time corrected, remaining 230 volumes were realigned to account for the head movement. The head motion criterion of translation <3 mm or rotation <3° in any direction was used to retain all patients with ADHD. Subsequently, the data were normalized and resampled into 3 mm× 3 mm × 3 mm voxels. The time course of each voxel was regressed to remove unwanted factors such as the global signal, white matter signal, cerebrospinal fluid signal, and Friston-24 parameters of head motion. To lessen the impact of low-frequency drift and high-frequency physiological noise, the data were linearly detrended, filtered at 0.01–0.08 Hz, and smoothed with a 6 mm full-width-at-half-maximum Gaussian kernel. The calculation of frame-wise displacement (FD) across the time point for each participant was then performed to evaluate head motion. The bad time point and its 1-back and 2-forward volumes were finally estimated by cubic spline interpolation using scrubbing methods (The DPARSF (v5.1) toolkit  was used methods  at an FDP < 0.6).p < 0.001, cluster-level p < 0.05, and GRF-adjusted. Then, by averaging the Z-scores of each peak coordinate, we identified the functional connectivity signals that revealed distinct variations across the three groups. Brain regions that had undergone numerous compression corrections were subjected to post hoc analysis of two-tailed ANOVA tests to ascertain the direction of FC change between the three. Statistical significance was defined as p < 0.05/4 (Bonferroni’s corrected). Using the Montreal Neurological Institute (MNI) atlas, a standardized and internationally recognized spatial framework, we identified the exact location and boundaries of the hippocampus. We aligned our subjects’ brain images to this atlas, effectively superimposing the predefined hippocampal region onto each subject’s brain image. We then visually confirmed the alignment and made necessary adjustments to ensure an accurate fit. This rigorous process ensured the consistency of our hippocampal ROI across all subjects. To compare the FC maps between the three groups , one-way ANOVA was performed. Age and FD were regressed as covariates. The basic threshold used for the data provided here was voxel-wise p < 0.05 threshold was used as the statistical significance criterion.The FC values that significantly deviated from the baseline were extracted, and partial correlation analysis was used to examine the relationship between the altered FC  and ADHD symptom severity, working memory scores, and Conners’ scale scores. This was done while controlling for nuisance covariates such as age, grade, and mean FD. An uncorrected It is important to note that IQ was not included as a covariate in this analysis. While IQ is often used as a covariate in many neurodevelopmental studies, there are compelling reasons to avoid such an approach. As argued by The feasibility of employing z-variance as a diagnostic biomarker for differentiating patients with ADHD from HCs was evaluated using a support vector machine (SVM) built into the LIBSVM library [LIbrary for Support Vector Machines ]. Based n = 30) and another for testing (n = 30). These groups were randomly selected from our total pool of 60 ADHD patients and were statistically comparable in terms of demographic information and clinical characteristics. As detailed in p > 0.05 for all variables), confirming the comparability of these groups for SVM classification.Our ADHD patient groups utilized in the ROC analysis comprised two genotypes: 35 TT homozygotes and 25 G-allele carriers (TG). For the SVM classification, these ADHD patient groups were split into two: one for training the classifier . This normalization process ensured that features had equal weighting and did not introduce bias to the classification performance.To train the classifier, the normalized averaged ROI values were used. In order to distinguish patients with ADHD from HCs in the independent sample, the averaged z-variance values of the same ROIs were obtained for each participant, normalized, and then input into the classifier as features.p-value.The statistical significance of the classification performance [area under the curve (AUC) of the receiver operating characteristic curves (ROC)] was determined using a non-parametric permutation test. The actual group labels (ADHD and HC) were randomly shuffled in each permutation test trial, and the same classification process was used to determine the classification accuracy score based on the shuffled dataset. This process was repeated 5,000 times to assess the level of statistical significance and obtain the Three TT homozygotes patients were excluded from further analyses due to excessive head motion. The final cohort contained 35 TT homozygotes, 25 G-allele carriers, and 28 HC . No signP < 0.001, cluster P < 0.05/2, controlling for age, grade level, and the mean FD). Significant differences were observed between the three groups in both the left and right hippocampus seeds. Notably, significant differences in FC were found between the right hippocampus seed and right precuneus  for the hippocampus seed regions   (As shown in  = 0.04) . It also = 0.02) . No signReceiver operating characteristic analysis confirmed that HCs and patients with ADHD can be distinguished based on FC between the right hippocampus, right precuneus, and left middle frontal gyrus. As shown in In this study, we built upon our previous research  to invesMemory and spatial navigation are both attributed to the hippocampus. The left and right hippocampi have often been regarded as functionally equal in rats, and this bilateral brain region has been widely researched. Recently, the molecular and morphological properties of the neural connections in the brain hemisphere have been found to exhibit unanticipated asymmetries . SimilarWe found altered FC between the right hippocampus and the (right) precuneus in both the TT and TG patient groups compared to the healthy control group (HCs). Disrupted FC between the left hippocampus and the (left) middle frontal gyrus was observed in patient groups. The precuneus, involved in a wide range of complex tasks such as memory, information integration, mental imagery, and affective reactions to pain, has been extensively reported in correlation with hippocampal FC, especially regarding mild cognitive impairment and Alzheimer’s disease .r = −0.40, p = 0.04). In addition to the previously mentioned findings, our study has further identified a significant negative correlation between altered FC in the left hippocampus and the left middle frontal gyrus in the TT group . This adds another dimension to our understanding of how ADHD may impact brain connectivity and cognitive abilities. It is becoming increasingly clear that genetic variations in ADHD patients play a pivotal role in their brain function, contributing to the symptomatic heterogeneity observed in this disorder. The results underscore the importance of considering the interplay of genetic factors and functional connectivity when examining the complex manifestations of ADHD and its associated cognitive deficits.The left middle frontal gyrus is crucial for literacy development. In Chinese reading, the left middle frontal gyrus serves as a specialized hub region that connects ventral and dorsal pathways . In dyslRegarding the cognitive implications of these FC alterations, the co-occurrence of lower IQ scores and academic achievement deficits and learning problems in ADHD children is well-established. We observed decreased FC values between the left hippocampus and the left middle frontal gyrus in the TT group compared to the TG group, although not statistically significant. Similar findings were reported by These altered hippocampus-precuneus-middle frontal gyrus connections may clarify the compromised attention-related encoding and retrieval processes leading to cognitive deficits in ADHD . A thesiOur first main finding was that FC alterations within the hippocampal FC in Chinese children with ADHD are genetically driven through observations of SNAP-25 variants. If replicated, this result indicates that SNAP-25 is a sensitive marker of disrupted connectivity patterns in ADHD. Although the relationship between SNAP-25 and altered structure or connectivity patterns has been repeatedly reported in patients with bipolar disorder , autism On the other hand, The presynaptic plasma membrane protein SNAP-25 is abundantly and selectively expressed in nerve cells . ConsideHowever, consistent with our findings, SNAP-25 was found to encode a protein that is crucial for synaptic vesicle fusion and neurotransmitter release. Furthermore, recent studies have indicated that SNAP-25 is involved in learning and memory, two processes essential for human cognition and intelligence . Single Although our study does not provide direct clinical applications of SNAP-25 genotyping in ADHD, it suggests the possibility of subtype-specific FC patterns. This might mean that TT homozygotes and G-allele carriers could have differences in ADHD presentation, which could potentially inform future diagnostic and treatment strategies. Further research is necessary to verify these findings and explore their clinical implications in more detail.We acknowledge that our study has several limitations despite providing evidence from many levels. First, the sample size of the fMRI study was rather small; therefore, caution should be exercised when interpreting data. Whole-brain structural and connectivity analyses could potentially be performed using independent samples with a larger sample size. Second, replication of our findings is problematic because of the small number of accessible brain samples. The investigation of SNAP-25 expression levels in various regions depending on the genotype would be of significant interest because of the critical role of the hippocampus in ADHD and the regions that have been demonstrated to be functionally connected. However, changes in the SNAP-25 level and its SNARE complex binding partners have frequently been observed in mouse models and humans with psychiatric illnesses, highlighting the significance of this complex’s control. Moreover, replication from multiple polymorphisms in subjects among genetically different ethnic groups can also reveal significant findings. Even though the analyses took age into account, further evaluations of individuals who had reached adulthood could provide more light on developmental features. Another limitation is that although we examined the relationship between the hippocampus and cognitive deficits, our study did not take into account a more comprehensive psychological assessment of the cognitive parameters associated with ADHD. Therefore, future research can include more features, particularly those related to children’s performance at school or at home. Other patient-specific factors were also reported to limit our study, such as male preponderance, existence of comorbidities, and heterogeneity in clinical presentation, which are typically prevalent in ADHD studies. Therefore, to obtain more accurate results, further research should use more complex patient groups, in which both genetic and symptomatology-based subtypes are considered.MnlI marker of SNAP-25 with ADHD. Based on genotyping for the detection of SNAP-25 MnII variants, we were able to obtain a new subtyping of patient groups (TT and TG) for further application in functional imaging analysis. In other words, instead of adopting the typical symptomatology-based ADHD subtypes, we use genetics-based subtypes, which we believe provides more accurate findings, especially for heritable and genetic disorders such as ADHD. For our FC analysis, we investigated the role of the hippocampal FC in childhood ADHD and its possible association with cognitive impairment. In view of the influence of SNAP-25 on disease processes, an additional thorough integration of genetics-based investigations with neuroimaging is essential to pave the way for larger, more varied, and in-depth genome-wide association studies.A major obstacle in understanding neuropsychiatric illnesses is the functional characterization of disease-associated variants, which will open an avenue for the creation of personalized therapies. According to a growing body of research, the SNARE complex, and more specifically, the SNAP-25 protein, may play a role in mental diseases. Here, as a first step, we were able to corroborate the association of one of the SNAP-25 variants with ADHD by providing modest evidence for the fwen62@126.com) on reasonable request.The datasets generated and/or analyzed during the current study are not publicly available because of Chinese Ethics Committee regulations but are available from the corresponding author (FW, The studies involving human participants were reviewed and approved by the Medical Ethics Committee of the Shenzhen Children’s Hospital. Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin.FW, HZ, BY, and AF designed the study. WH, YZ, DF, and LZ collected the data and organized the clinical information. FW, AF, BY, and HZ reviewed the methods. AF, WH, and DF analyzed the data. WH and AF wrote the manuscript. All authors discussed, approved, and proofread the results and the final manuscript.


Many metabolic diseases influence brain function and are associated with psychiatric symptoms and neuropsychiatric disorders . Attention-deficit-/hyperactivity disorder (ADHD) is among the most common neurodevelopmental disorders in children, with a worldwide prevalence of about 5% in childhood. Tyrosinemia is caused by a genetic mutation in the fumarylacetoacetase gene that leads to a deficiency in the encoded enzyme, which catalyzes the cleavage of tyrosine metabolites to acetoacetic acid and fumaric acid. In recent studies of children with tyrosinemia type 1, a strong correlation was observed between symptoms of ADHD and blood levels of tyrosine, supporting a direct role of this amino acid in the pathogenesis.we report this case of tyrosinemia type 1 associated to ADHD symptoms to contribute in literature to provide more insights into possible shared pathophysiological mechanisms and how these affect their treatment.We report the case of an 8-year-old child, followed since the age of 3 months for a tyrosinemia type 1 who presented symptoms of ADHD.SNAP IV - Swanson, Nolan and Pelham Teacher and Parent Rating Scale was used with the mother, the items concerning inattention (items 1 to 10) and Hyperactivity-Impulsivity (items 11 to 20) were revealing; The Conners Evaluation Questionnaire was delivered, confirming the same result, a neuropsychological evaluation of the child with IQ evaluation by WISC-IV - Wechsler Intelligence Scale for Children and Adolescents revealed limited intellectual performance with an IQ of 65.scales and questionnaires were used to detect ADHD symptoms, the NMDs, such as HT-1, constitute a large group of conditions that are often containable with early clinical intervention, but still present lifelong difficulties and high societal costs. many studies suggest that there may be similar biological mechanisms behind the cognitive difficulties seen in ADHD and HT-1. In clinical settings, the impaired dopamine synthesis due to substrate inhibition in treated HT-1 may be compensated for by standard ADHD medication, such as methylphenidate or amphetamine. Similarly, the reduced serotonin synthesis may be counteracted by tryptophan supplementation.None Declared