Neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and intellectual developmental disorder (IDD), are highly prevalent and lack effective treatments, posing significant health challenges. These disorders are frequently comorbid with disruptions in sleep rhythms, and sleep-related indicators are often used to assess disease severity and treatment efficacy. Recent evidence has highlighted the crucial roles of circadian rhythm disturbances and circadian clock gene mutations in the pathogenesis of NDDs. This review focuses on the mechanisms by which circadian rhythm disruptions and circadian clock gene mutations contribute to cognitive, behavioral, and emotional disorders associated with NDDs, particularly through the dysregulation of dopamine system. Additionally, we discussed the potential of targeting the circadian system as novel therapeutic strategies for the treatment of NDDs.
Humans ; Neurodevelopmental Disorders/genetics* ; Attention Deficit Disorder with Hyperactivity/genetics* ; Circadian Rhythm/genetics* ; Autism Spectrum Disorder/genetics* ; Mutation ; Intellectual Disability/genetics* ; Circadian Clocks/physiology* ; Dopamine/metabolism*

This study investigated the effects of Rehmanniae Radix Praeparata on striatal neuronal apoptosis in rats with attention deficit hyperactivity disorder(ADHD) based on the B-cell lymphoma-2(Bcl-2)/Bcl-2-associated X protein(Bax)/caspase-3 signaling pathway. Twenty-four 3-week-old male spontaneously hypertensive rats(SHR) were randomly divided into a model group, a methylphenidate group(2 mg·kg~(-1)·d~(-1)), and a Rehmanniae Radix Praeparata group(2.4 mg·kg~(-1)·d~(-1)). Age-matched male Wistar Kyoto(WKY) rats were used as the normal control group, with 8 rats in each group. The rats were administered by gavage for 28 days. Body weight and food intake were recorded for each group. The open field test and elevated plus maze test were used to assess hyperactivity and impulsive behaviors. Nissl staining was used to detect changes in striatal neurons and Nissl bodies. Terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL) fluorescence staining was used to detect striatal cell apoptosis. Western blot was employed to detect the expression levels of Bcl-2, Bax, and caspase-3 proteins in the striatum. The results showed that compared with the model group, Rehmanniae Radix Praeparata significantly reduced the total movement distance, average movement speed, and central area residence time in the open field test, and significantly reduced the ratio of open arm entries, open arm stay time, and head dipping in the elevated plus maze test. Furthermore, it increased the number of Nissl bodies in striatal neurons, significantly downregulated the apoptosis index, significantly increased Bcl-2 protein expression and the Bcl-2/Bax ratio, and reduced Bax and caspase-3 protein expression. In conclusion, Rehmanniae Radix Praeparata can reduce hyperactivity and impulsive behaviors in ADHD rats. Its mechanism may be related to the regulation of the Bcl-2/Bax/caspase-3 signaling pathway in the striatum, enhancing the anti-apoptotic capacity of striatal neurons.
Animals ; Male ; Apoptosis/drug effects* ; Rats ; Drugs, Chinese Herbal/administration & dosage* ; Caspase 3/genetics* ; Proto-Oncogene Proteins c-bcl-2/genetics* ; bcl-2-Associated X Protein/genetics* ; Rehmannia/chemistry* ; Attention Deficit Disorder with Hyperactivity/physiopathology* ; Signal Transduction/drug effects* ; Neurons/cytology* ; Rats, Inbred SHR ; Rats, Inbred WKY ; Humans ; Corpus Striatum/cytology* ; Plant Extracts

PURPOSE: Attention-deficit/hyperactivity disorder (ADHD) increases the risk of road traffic injuries through various mechanisms including higher risky driving behaviors. Therefore, drivers with ADHD are shown to be more prone to road traffic injuries. This study was conducted in a community-based sample of drivers to determine how ADHD affects driving behavior components. METHODS: At the cross-sectional phase of a national population-based cohort, a representative sample of 1769 drivers were enrolled. Manchester driving behavior questionnaire and Conners' adult ADHD rating scales were used to assess driving behavior and ADHD symptom scores, respectively. Data were analyzed using Stata version 17. Multiple linear regression was used to investigate the association of driving behavior with ADHD while adjusting for the potential confounding role of age, sex, marital status, educational level, driving history, etc. RESULTS: According to the results, the normalized driving behavior score of drivers with ADHD was 4.64 points higher than drivers without ADHD. Having an academic compared to school education, increased the driving behavior score by 1.73 points. The normalized driving behavior score of drivers under 18 years of age was 6.27 points higher than drivers aged 31-45 years. The score of the aggressive violation subscale of drivers with ADHD was 7.33 points higher than drivers without ADHD compared to an increment of a range of 4.50-4.82 points for other driving subscales. The score of the ordinary violation subscale of female drivers was 2.23 points lower than that of male drivers. No significant relationship was found between sex and other subscales of driving. CONCLUSION Drivers with ADHD who are in adolescence or early adulthood exhibit more dangerous and aggressive driving behaviors than those who are older. Implementing training interventions to increase awareness of drivers with ADHD, their families, and psychologists regarding the effects of ADHD on driving is an essential step in preventing motor vehicle crashes among drivers with ADHD.
Humans ; Attention Deficit Disorder with Hyperactivity/psychology* ; Automobile Driving/psychology* ; Male ; Adult ; Female ; Middle Aged ; Cross-Sectional Studies ; Accidents, Traffic ; Iran ; Adolescent ; Surveys and Questionnaires ; Young Adult ; Cohort Studies ; Risk-Taking

OBJECTIVES: To investigate the disease burden of attention-deficit/hyperactivity disorder (ADHD) among children and adolescents in China and to predict future trends, in order to provide evidence for disease control strategies. METHODS: Based on data from the Global Burden of Disease Study 2021 (GBD 2021), joinpoint regression and prediction models were constructed to analyze and forecast the trends in ADHD burden indicators among Chinese children and adolescents from 1990 to 2021. RESULTS: In 2021, the incidence, prevalence, and disability-adjusted life years (DALYs) rates of ADHD among children and adolescents in China increased by 41.46%, 21.44%, and 21.75%, respectively, compared to 1990. From 1990 to 2021, the disease burden of ADHD showed an overall upward trend across sex and age groups, with a heavier burden among males. The highest incidence was observed in children aged 5-9 years, while the highest prevalence and DALY rates were found in those aged 10-14 years. By 2031, the incidence, prevalence, and DALY rates of ADHD among Chinese children and adolescents are projected to reach 324.88 per 100 000, 3 762.36 per 100 000, and 45.85 per 100 000, respectively. CONCLUSIONS From 1990 to 2021, the incidence, prevalence, and DALY rates of ADHD among children and adolescents in China have all increased, suggesting that more proactive prevention and intervention measures may be needed to alleviate the disease burden of ADHD in this population.
Humans ; Child ; Adolescent ; Attention Deficit Disorder with Hyperactivity/epidemiology* ; Male ; Female ; Child, Preschool ; China/epidemiology* ; Cost of Illness ; Prevalence ; Incidence ; Disability-Adjusted Life Years ; Forecasting ; East Asian People

OBJECTIVES: To investigate the relationship between the polygenic risks for various psychiatric disorders and clinical and neuropsychological characteristics in children with attention-deficit/hyperactivity disorder (ADHD). METHODS: Using a cross-sectional design, 285 children with ADHD and 107 healthy controls were assessed using the Child Behavior Checklist, the Behavior Rating Inventory of Executive Function for parents, the Wechsler Intelligence Scale for Children, Fourth Edition, and the Cambridge Neuropsychological Test Automated Battery. Blood samples were collected for genetic data. Polygenic risk scores (PRSs) for various psychiatric disorders were calculated using the PRSice-2 software. RESULTS: Compared with the healthy controls, the children with ADHD displayed significantly higher PRSs for ADHD, major depressive disorder, anxiety disorder, and obsessive-compulsive disorder (P<0.05). In terms of daily-life executive function, ADHD-related PRS was significantly correlated with the working memory factor; panic disorder-related PRS was significantly correlated with the initiation factor; bipolar disorder-related PRS was significantly correlated with the shift factor; schizophrenia-related PRS was significantly correlated with the inhibition, emotional control, initiation, working memory, planning, organization, and monitoring factors (P<0.05). The PRS related to anxiety disorders was negatively correlated with total IQ and processing speed index (P<0.05). The PRS related to obsessive-compulsive disorder was negatively correlated with the processing speed index and positively correlated with the stop-signal reaction time index of the stop-signal task (P<0.05). CONCLUSIONS PRSs for various psychiatric disorders are closely correlated with the behavioral and cognitive characteristics in children with ADHD, which provides more insights into the heterogeneity of ADHD.
Humans ; Attention Deficit Disorder with Hyperactivity/genetics* ; Child ; Male ; Female ; Cross-Sectional Studies ; Neuropsychological Tests ; Multifactorial Inheritance ; Adolescent ; Mental Disorders/etiology* ; Executive Function ; Genetic Risk Score

OBJECTIVES: To evaluate and integrate evidence on the management of sleep disorders in children with attention deficit hyperactivity disorder (ADHD). METHODS: Literature was retrieved based on the 6S model, and evidence related to sleep disorder management in children with ADHD was extracted from the included references. RESULTS: A total of 17 studies were included, from which 16 pieces of evidence were extracted. Of these, 6 were classified as Level 1 evidence and 10 as Level 5. The evidence covered screening, assessment, non-pharmacological interventions, pharmacological interventions, follow-up, and multidisciplinary collaboration. CONCLUSIONS This study integrated evidence on the management of sleep disorders in children with ADHD using an evidence-based approach, providing an evidence-based foundation for managing sleep disorders in this population.
Humans ; Attention Deficit Disorder with Hyperactivity/complications* ; Sleep Wake Disorders/etiology* ; Child ; Evidence-Based Medicine

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in children. Growing evidence links ADHD to gut microbiota dysbiosis, positioning the microbiota-gut-brain axis as a new focus of childhood ADHD research. This review systematically elucidates the association between gut dysbiosis and childhood ADHD and analyzes key mechanisms by which the microbiota-gut-brain axis regulates bidirectional gut-brain communication through multiple pathways. It highlights recent findings on microbiota-targeted strategies to improve ADHD symptoms and discusses therapeutic prospects, with the aim of exploring new avenues for early intervention and treatment in children with ADHD.
Humans ; Attention Deficit Disorder with Hyperactivity/microbiology* ; Gastrointestinal Microbiome/physiology* ; Child ; Brain/physiology* ; Dysbiosis

BACKGROUND: High levels of attention-deficit/hyperactivity disorder (ADHD) traits are associated with various outcomes, including depressive symptoms, functional impairment, and low self-esteem. Additionally, individuals with high levels of ADHD traits are reported to be more adversely affected by fear of coronavirus disease 2019 (COVID-19). The current study aimed to examine whether the association between ADHD traits and outcomes was partially mediated by fear of COVID-19 using mediation analysis. METHODS: A cross-sectional study was conducted in a sample of university students in medical-related faculties (n = 1,166). ADHD traits, fear of COVID-19, depressive symptoms, functional impairment, and self-esteem were assessed using the adult ADHD Self-Report Scale, Fear of COVID-19 Scale, K6 Scale, Sheehan Disability Scale, and Rosenberg Self-Esteem Scale, respectively. We used linear regression analysis and the Paramed command in Stata to analyze whether fear of COVID-19 mediated the association between ADHD traits and outcomes. RESULTS: ADHD traits were significantly associated with outcomes. Regarding the impact of fear of COVID-19, the results revealed a significant association between ADHD traits and fear of COVID-19, and between fear of COVID-19 and outcomes. The results of the mediation analyses showed that the association between ADHD traits and outcomes was partially mediated by the fear of COVID-19 (depressive symptoms: direct effect B = 1.029, 95% confidence interval [CI] 0.878, 1.181, indirect effect B = 0.021, 95% CI 0.002, 0.040; functional impairment: direct effect B = 0.786, 95% CI 0.593, 0.979, indirect effect B = 0.033, 95% CI 0.005, 0.060; self-esteem: direct effect B = -1.052, 95% CI -1.226, -0.878, indirect effect B = -0.024, 95% CI -0.046, -0.002). CONCLUSIONS Developing preventive measures against the adverse impacts of pandemics like COVID-19 will be particularly important for individuals with high levels of ADHD traits in future.
Humans ; COVID-19/psychology* ; Attention Deficit Disorder with Hyperactivity/epidemiology* ; Cross-Sectional Studies ; Self Concept ; Male ; Female ; Depression/epidemiology* ; Fear/psychology* ; Young Adult ; Universities ; Students/psychology* ; Adult ; SARS-CoV-2 ; Mediation Analysis ; Adolescent

OBJECTIVES: To investigate the effects of early life intervention with Bifidobacterium bifidum BD-1 (B. bifidum BD-1) on hyperactivity in a female mouse model of attention deficit hyperactivity disorder (ADHD) and explore the underlying mechanisms. METHODS: Eight newborn female Wistar-Kyoto (WKY) rats and 6 spontaneous hypertensive rats (SHRs) were gavaged with saline and another 6 SHRs were gavaged with B. bifidum BD-1 (10⁹ CFU) daily for 3 weeks. Open field test of the rats was conducted at 7 weeks, and fecal samples were collected at weaning (3 weeks) and at 7 weeks for 16S rRNA sequencing. Immunofluorescent staining was used to detect dopamine transporter (DAT) and tyrosine hydroxylase (Th) levels in the striatum and activated microglia in the prefrontal cortex. Treg cells in the mesenteric lymph nodes, spleen and blood were analyzed using flow cytometry. RESULTS: The SHRs traveled a significantly greater distance in open fields test than WKY rats, and this behavior was significantly attenuated by B. bifidum BD-1 intervention. The expression of DAT and Th in the striatum was significantly lower in the SHRs than in WKY rats, while B. bifidum BD-1 treatment obviously increased Th levels in the SHRs. B. bifidum BD-1 intervention significantly deceased the number of activated microglia and increased Treg cell counts in the spleen of SHRs. The treatment also enhanced α diversity in gut microbiota of the SHRs and resulted in a decreased Firmicutes/Bacteroidota ratio, more active Muribaculaceae growth, and suppression of Clostridia_UCG-014 proliferation. CONCLUSIONS Early life intervention with B. bifidum BD-1 alleviates hyperactivity in female SHRs by modulating the gut microbiota and peripheral immune response, suppressing neuroinflammation and improving dopaminergic system function. These findings provide evidence for early prevention strategies and support the development and application of psychobiotics for ADHD.
Animals ; Female ; Rats ; Rats, Inbred WKY ; Rats, Inbred SHR ; Attention Deficit Disorder with Hyperactivity/therapy* ; Bifidobacterium bifidum ; Probiotics/therapeutic use* ; Dopamine Plasma Membrane Transport Proteins/metabolism* ; Tyrosine 3-Monooxygenase/metabolism* ; Gastrointestinal Microbiome ; Disease Models, Animal

Attention deficit hyperactivity disorder (ADHD), a prevalent neurodevelopmental disorder influenced by both genetic and environmental factors, remains poorly understood regarding how its polygenic risk score (PRS) impacts functional networks and symptomology. This study capitalized on data from 11,430 children in the Adolescent Brain Cognitive Development study to explore the interplay between PRS_ADHD, brain function, and behavioral problems, along with their interactive effects. The results showed that children with a higher PRS_ADHD exhibited more severe attention deficits and rule-breaking problems, and experienced sleep disturbances, particularly in initiating and maintaining sleep. We also identified the central executive network, default mode network, and sensory-motor network as the functional networks most associated with PRS and symptoms in ADHD cases, with potential mediating roles. Particularly, the impact of PRS_ADHD was enhanced in children experiencing heightened sleep disturbances, emphasizing the need for early intervention in sleep issues to potentially mitigate subsequent ADHD symptoms.
Humans ; Attention Deficit Disorder with Hyperactivity/physiopathology* ; Male ; Female ; Sleep Wake Disorders/physiopathology* ; Adolescent ; Child ; Brain/diagnostic imaging* ; Multifactorial Inheritance ; Genetic Predisposition to Disease