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The Association Between EPHA5 Gene Polymorphism and Attention-Deficit/Hyperactivity Disorder Based on the "Gene-Brain-Cognition" Model
Medical Journal of Peking Union Medical College Hospital 2026, 17(4): 1033-1041
Published: 27 November 2025
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Objective

Based on the "gene-brain-cognition" model, this study aimed to investigate the association between the rs4860671 polymorphism of the EPHA5 gene and attention-deficit/hyperactivity disorder (ADHD), and to analyze its impact on executive function and resting-state brain activity in affected children.

Methods

This was a case-control study. Children with ADHD attending the outpatient clinic of Peking University Sixth Hospital from 2015 to 2020 and typically developing children from general primary and secondary schools in Beijing during the same period were enrolled as subjects. Genotypes of the EPHA5 rs4860671 polymorphism were determined in both groups. Resting-state functional magnetic resonance imaging was used to assess spontaneous brain activity. In addition, the ADHD Rating Scale and the Behavior Rating Inventory of Executive Function were administered to evaluate ADHD core symptoms and executive function, respectively. Genetic association analysis, analysis of covariance, and mediation analysis were systematically performed to explore the associations of the rs4860671 polymorphism with ADHD clinical symptoms, executive function, and brain functional activity.

Results

A total of 244 children with ADHD and 83 healthy controls were included. Among them, 188 children with ADHD and 70 healthy controls completed MRI scanning. Allelic analysis revealed that the frequency of the G allele of rs4860671 was significantly higher in children with ADHD than in healthy controls (77.5% vs. 69.9%, P=0.049). Genotype distribution analysis also demonstrated a significant difference between the two groups under the dominant model (P=0.031). Regarding executive function, children carrying the GG genotype of rs4860671 had higher scores in emotion control compared with those carrying the A allele (AA+AG) (15.99±4.62 vs. 14.53±4.03, P=0.017), indicating poorer emotion regulation ability. Further mediation analysis showed that emotion control fully mediated the relationship between rs4860671 genotype and core symptoms of ADHD. Neuroimaging analysis revealed that among children with ADHD, carriers of the GG genotype exhibited decreased spontaneous brain activity in the right inferior occipital gyrus and left middle occipital gyrus compared with A allele carriers.

Conclusions

The rs4860671 polymorphism of the EPHA5 gene may be involved in the pathogenesis of ADHD by influencing emotion regulation ability and visual network functional activity. This finding provides new scientific evidence for a deeper understanding of the neurobiological mechanisms underlying ADHD.

Issue
A Survey on the Mental Health Status of Social Workers Under Long-term Stress of COVID-19 and the Exploration of Associated Factors: A Case Study of Chaoyang District, Beijing
Medical Journal of Peking Union Medical College Hospital 2024, 15(4): 845-854
Published: 30 July 2024
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Objective

To study the prevalence of depression, anxiety, and insomnia among social workers during the prolonged battle against the COVID-19 pandemic and explore the associated risk factors.

Methods

Using a stratified cluster sampling method, we selected all social workers in the five streets of Chaoyang District, Beijing(Jiuxianqiao, Wangjing, Taiyanggong, Shibalidian, Sunhe) from November 2021 to March 2022 as the study population(social worker group), and the frontline medical staffs(medical professional group) of the same age range of the corresponding community hospitals of the same five streets, and the community residents(resident group) as the control population. The ratio of the social worker group, medical professional group, and resident group was 1∶1∶1. The Sojump platform was used to send electronic questionnaires to the wechat groups of social workers, healthcare workers, and community residents to carry out the survey. The screen positive rates for anxiety, depression, and sleep disorders were compared among the 3 groups. Multifactorial Logistic regression and decision tree were used to analyze the influencing factors of anxiety, depression, and sleep disorders among social workers.

Results

A total of 954 questionnaires were collected, of which 62 were disqualified and excluded. Finally, 892 valid questionnaires(93.5%) were included for data analysis. Among them, there were 372 questionnaires(41.7%) from the social worker group, 262(29.4%) from the medical professional group, and 258(28.9%) from the resident group. The prevalences of anxiety, depression, and sleep disorders among social workers group were found to be 15.3%, 22.0%, and 48.1%, respectively, which were significantly higher than those in the medical professional group(7.6%, 10.3%, and 30.5%) and the resident group(7.0%, 8.5%, and 29.5%), all P < 0.001. Multiple Logistic regression showed that family burden(OR=1.80, 95% CI: 1.09-2.96) and Chinese perceived stress scale(CPSS) score(OR=1.34, 95% CI: 1.24-1.45) were independent influencing factors for anxiety among social workers; CPSS score(OR=1.29, 95% CI: 1.20-1.39) and social support rating scale(SSRS) score(OR=0.96, 95% CI: 0.92-1.00) were independent influencing factors for depression among social workers; family history of mental illness(OR=4.91, 95% CI: 1.27-18.94), CPSS score(OR=1.20, 95% CI: 1.14-1.27), and SSRS score(OR=0.95, 95% CI: 0.91-0.98) were independent influencing factors for sleep disorders among social workers. The results of decision tree analysis were consistent with those of multiple Logistic regression analysis. Family burden, CPSS score, and SSRS score were important variables affecting the mental health of social workers, among which CPSS score was strongly associated with anxiety, depression, and sleep disorders among social workers.

Conclusions

Social workers exhibited significant levels of anxiety, depression, and sleep disorders during the long-term pandemic prevention, with CPSS being the most significant influencing factor.

Issue
Cerebral Blood Flow Characteristics of Boys with Different Subtypes of Attention Deficit Hyperactivity Disorder and Their Relationship with Executive Function
Medical Journal of Peking Union Medical College Hospital 2025, 16(2): 314-320
Published: 12 December 2024
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Objective

To analyze the differences in cerebral blood flow (CBF) characteristics among children with different subtypes of attention deficit and hyperactivity disorder (ADHD) and their relationship with executive function using arterial spin labeling (ASL) technology.

Methods

A case-control study was conducted, including children diagnosed with ADHD at the outpatient clinic of Peking University Sixth Hospital from July 2015 to December 2019 as the ADHD group, and typically developing schoolchildren from January to December 2021 as the healthy control group. Both groups underwent pseudo-continuous ASL (pCASL) scanning to measure CBF, and executive function was assessed using the parent version of the Behavior Rating Inventory of Executive Function (BRIEF). Differences in CBF between ADHD children and healthy controls were compared. For brain regions showing significant group differences, CBF values were extracted and linear regression models were constructed with BRIEF scores to further explore the relationship between regional CBF and executive function.

Results

A total of 134 boys with ADHD were included[83 with ADHD predominantly inattentive subtype (ADHD-I) and 51 with ADHD combined subtype (ADHD-C)], along with 25 healthy control boys. Intergroup comparisons revealed that the CBF in the left middle temporal gyrus was significantly lower in ADHD-C children compared to both ADHD-I children (P=0.010) and healthy controls (P < 0.001), while no significant difference was observed between ADHD-I children and healthy controls (P=0.280). After adjusting for age and total IQ scores, the linear regression model showed that the CBF in the left middle temporal gyrus of ADHD-C children was negatively correlated with the planning/organization score on the BRIEF (β=-0.062, P=0.030).

Conclusions

The CBF in the left middle temporal gyrus of boys with ADHD-C is significantly lower than that of boys with ADHD-I and healthy controls. This reduced regional CBF may be associated with executive function deficits in organization and planning abilities in ADHD-C, providing new insights into the neurobiological mechanisms underlying ADHD subtypes.

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