MicroRNAs as potential biomarkers for diagnosis of attention deficit hyperactivity disorder

Inappropriate levels of hyperactivity,impulsivity,and inattention characterize attention deficit hyperactivity disorder,a common childhood-onset neuropsychiatric disorder.The cognitive function and learning ability of children with attention deficit hyperactivity disorder are affected,and these symptoms may persist to adulthood if they are not treated.The diagnosis of attention deficit hyperactivity disorder is only based on symptoms and objective tests for attention deficit hyperactivity disorder are missing.Treatments for attention deficit hyperactivity disorder in children include medications,behavior therapy,counseling,and education services which can relieve many of the symptoms of attention deficit hyperactivity disorder but cannot cure it.There is a need for a molecular biomarker to distinguish attention deficit hyperactivity disorder from healthy subjects and other neurological conditions,which would allow for an earlier and more accurate diagnosis and appropriate treatment to be initiated.Abnormal expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of attention deficit hyperactivity disorder.The recent studies reviewed had performed microRNA profiling in whole blood,white blood cells,blood plasma,and blood serum of children with attention deficit hyperactivity disorder.A large number of microRNAs were dysregulated when compared to healthy controls and with some overlap between individual studies.From the studies that had included a validation set of patients and controls,potential candidate biomarkers for attention deficit hyperactivity disorder in children could be miR-140-3p,let-7g-5p,-30e-5p,-223-3p,-142-5p,-486-5p,-151a-3p,-151a-5p,and-126-5p in total white blood cells,and miR-4516,-6090,-4763-3p,-4281,-4466,-101-3p,-130a-3p,-138-5p,-195-5p,and-106b-5p in blood serum.Further studies are warranted with children and adults with attention deficit hyperactivity disorder,and consideration should be given to utilizing rat models of attention deficit hyperactivity disorder.Animal studies could be used to confirm microRNA findings in human patients and to test the effects of targeting specific microRNAs on disease progression and behavior.

Main focus of parents of children with attention deficit hyperactivity disorder and the effectiveness of early clinical screening

BACKGROUND Attention deficit hyperactivity disorder(ADHD)is a common mental and behavioral disorder among children.AIM To explore the focus of attention deficit hyperactivity disorder parents and the effectiveness of early clinical screening METHODS This study found that the main directions of parents seeking medical help were short attention time for children under 7 years old(16.6%)and poor academic performance for children over 7 years old(12.1%).We employed a two-stage experiment to diagnose ADHD.Among the 5683 children evaluated from 2018 to 2021,360 met the DSM-5 criteria.Those diagnosed with ADHD underwent assessments for letter,number,and figure attention.Following the exclusion of ADHD-H diagnoses,the detection rate rose to 96.0%,with 310 out of 323 cases identified.RESULTS This study yielded insights into the primary concerns of parents regarding their children's symptoms and validated the efficacy of a straightforward diagnostic test,offering valuable guidance for directing ADHD treatment,facilitating early detection,and enabling timely intervention.Our research delved into the predominant worries of parents across various age groups.Furthermore,we showcased the precision of the simple exclusion experiment in discerning between ADHD-I and ADHD-C in children.CONCLUSION Our study will help diagnose and guide future treatment directions for ADHD.

Early Intervention Facilitates Neuropsychological Development in Children with Autism and Attention Deficit Hyperactivity Disorder

Objective:This study aims to investigate the impact of early intervention on neuropsychological development in children with autism and attention deficit hyperactivity disorder(ADHD),providing effective intervention strategies for clinical practice.Methods:A total of 130 children with autism and ADHD who visited the hospital between June 2023 and June 2024 were selected as study subjects and randomly divided into an intervention group and a control group,with 65 children in each group.The intervention group received a one-year early comprehensive intervention,including behavioral therapy,cognitive training,and family guidance,while the control group only received routine medical care.The neuropsychological development assessment scale was used to evaluate both groups before and after the intervention to compare changes in their neuropsychological development levels.Results:Children in the intervention group showed significant improvements in cognitive function,social skills,language ability,and attention concentration,with an average improvement score of 23.5 points.Children in the control group did not show significant improvements in these areas,with an average improvement score of only 5.8 points.The difference between the two groups was statistically significant(P<0.05).Conclusion:Early comprehensive intervention has a significant promoting effect on the neuropsychological development of children with autism and ADHD.Targeted behavioral therapy,cognitive training,and family guidance can effectively enhance children’s cognitive,social,language,and attention abilities,laying a solid foundation for their future overall development.Therefore,it is recommended to actively promote and apply early intervention strategies in clinical practice.

Whole Exome Sequencing: Novel Genetic Polymorphisms in Saudi Arabian Attention Deficit Hyperactivity Disorder (ADHD) Children

Background: Attention-deficit hyperactivity disorder (ADHD) is a widespread and debilitating disorder with relatively high prevalence in Saudi Arabia. Neuropsychological and radiological investigations have revealed that there are some differences in the components of the brain regions in children with and without ADHD. In this study we have performed whole exome sequencing (WES) in four non-familial cases of ADHD from Makkah Region to identify the genetic polymorphisms associated with the disease in our Saudi population. Methods: Exome sequencing was carried out using Ion Proton with AmpliSeq Exome library methods, and the data were analysed by Ion Reporter 5.6 software. Results: A total of 33 variants were identified from 222 genes selected from the GWAS catalogue for ADHD associated genes. However, the SNPs we identified in these genes were not reported to be associated with ADHD in previous studies. We have identified 2 novel missense variants;one in c.3451G > T;p. (Ala1151Ser) in ITGA1 gene and another is c.988G > A;p. (Ala330Thr) in SPATA13 genes. The variants rs928661, rs11150370 and rs386792899 were the only three variants that appeared on all the 4 patients studied. Six missense variants, rs16841277, rs2228209, rs2230283, rs3741883, rs1716 and rs2272606, were found in 3 different patients, respectively. However, the three documented variants are rs13166360 with bipolar disorder, rs920829 with neuropathic pain, and rs6558702 with schizophrenia. Conclusion: We have identified 2 novel variants in ADHD children. SIFT score of all variants indicates that these substitutions have damaging effects on the protein function. Further screening studies are recommended for confirmation.

Risk for emerging bipolar disorder, variants, and symptoms in children with attention deficit hyperactivity disorder, now grown up

AIM: To determine the prevalence of bipolar disorder(BD) and sub-threshold symptoms in children with attention deficit hyperactivity disorder(ADHD) through 14 years' follow-up, when participants were between 21-24 years old.METHODS: First, we examined rates of BD type Ⅰ?and Ⅱ diagnoses in youth participating in the NIMH-funded Multimodal Treatment Study of ADHD(MTA). We used the diagnostic interview schedule for children(DISC), administered to both parents(DISC-P) and youth(DISCY). We compared the MTA study subjects with ADHD(n = 579) to a local normative comparison group(LNCG, n = 289) at 4 different assessment points: 6, 8, 12, and 14 years of follow-ups. To evaluate the bipolar variants, we compared total symptom counts(TSC) of DSM manic and hypomanic symptoms that were generated by DISC in ADHD and LNCG subjects. Then we sub-divided the TSC into pathognomonic manic(PM) and non-specific manic(NSM) symptoms. We compared the PM and NSM in ADHD and LNCG at each assessment point and over time. We also evaluated the irritability as category A2 manic symptom in both groups and over time. Finally, we studied the irritability symptom in correlation with PM and NSM in ADHD and LNCG subjects.RESULTS: DISC-generated BD diagnosis did not differ significantly in rates between ADHD(1.89%) and LNCG 1.38%). Interestingly, no participant met BD diagnosis more than once in the 4 assessment points in 14 years. However, on the symptom level, ADHD subjects reported significantly higher mean TSC scores: ADHD 3.0; LNCG 1.7; P < 0.001. ADHD status was associated with higher mean NSM: ADHD 2.0 vs LNCG 1.1; P < 0.0001. Also, ADHD subjects had higher PM symptoms than LNCG, with PM means over all time points of 1.3 ADHD; 0.9 LNCG; P = 0.0001. Examining both NSM and PM, ADHD status associated with greater NSM than PM. However, Over 14 years, the NSM symptoms declined and changed to PM over time(df 3, 2523; F = 20.1; P < 0.0001). Finally, Irritability(BD DSM criterion-A2) rates were significantly higher in ADHD than LNCG(χ2 = 122.2, P < 0.0001), but irritability was associated more strongly with NSM than PM(df 3, 2538; F = 43.2; P < 0.0001).CONCLUSION: Individuals with ADHD do not appear to be at significantly greater risk for developing BD, but do show higher rates of BD symptoms, especially NSM. The greater linkage of irritability to NSM than to PM suggests caution when making BD diagnoses based on irritability alone as one of 2(A-level) symptoms for BD diagnosis, particularly in view of its frequent presentation with other psychopathologies.

A Controlled Study of the Effectiveness of EEG Biofeedback Training on Children with Attention Deficit Hyperactivity Disorder

In order to study the treatment of the children with attention deficit hyperactivity disorder (ADHD), the integrated visual and auditory continuous performance test (IVA-CPT) was clinically applied to evaluate the effectiveness of electroencephalogram (EEG) biofeedback training. Of all the 60 children with ADHD aged more than 6 years, the effective rate of EEG biofeedback training was 91.6 % after 40 sessions of EEG biofeedback training. Before and after treatment by EEG biofeedback training, the overall indexes of IVA were significantly improved among predominately inattentive, hyperactive, and combined subtype of children with ADHD (P<0.001). It was suggested that EEG biofeedback training was an effective and vital treatment on children with ADHD.

Visual-Motor Perceptual and Reading Processes of Schoolchildren With Attention Deficit Hyperactivity Disorder

Objectives:Compare and relate the performance of schoolchildren with Attention Deficit Hyperactivity Disorder(ADHD)and with good academic performance in the visual-motor perceptual and reading processes.Method:Twenty schoolchildren,of both genders,aged between nine and 11 years old,participated in this study.They were divided into two groups:Group I(GI):comprising 10 students diagnosed with ADHD;and Group II(GII):10 students with good academic performance paired according to gender,age group,and educational level with GI.All students were submitted to the Developmental Test of Visual Perception(DTVP 3)and Reading Processes Assessment Protocol(PROLEC).Results:There was lower performance of GI compared to GII in the subtests of copying,eye-hand coordination,and figure-ground in the standard score of general visual perception and visual-motor integration.GI presented lower performance in all reading processes except for the punctuation marks test.There was a statistically significant difference in the comparison between GI and GII regarding the classification of reading processes.A relationship was identified between the reading and visual perception subtests in the GI students,demonstrating a relationship between the visual perceptual motor skills and the reading processes in the group of students with ADHD.Conclusion:Schoolchildren with ADHD performed less well than their peers with good academic performance in the visual-motor perceptual and reading skills;such that the worse their performance in the visual-motor perceptual processes,the worse their performance in the reading processes.

Behavioral and Neural Enhancing Effects of a Summer Treatment Program in Children with Attention Deficit Hyperactivity Disorder

Deficiency in executive functioning is a core symptom of attention deficit hyperactivity disorder (ADHD). The brain part responsible for executive functions is the prefrontal cortex (PFC). Although drug-based interventions can improve PFC activity, reports on PFC activity being improved by behavioral treatment are lacking. We evaluated whether a summer treatment program (STP) administering comprehensive behavioral treatment would increase PFC activity in children with ADHD. We examined behavioral and neural changes in 20 children before and after the STP, conducted over a 2-week period. We asked the parents/guardians to complete the Swanson, Nolan, and Pelham IV scale to assess severity of ADHD. The main task evaluating executive control was the reverse Stroop task. To examine changes in physiological indices, we used near-infrared spectroscopy to measure changes in PFC activity. Subjective assessments by parents/guardians indicated that ADHD symptoms improved significantly. There was also significant improvement in the number of correct responses and interference rates in the reverse Stroop task. Furthermore, post-intervention PFC activity was significantly higher. These results suggest that the STP improved inhibitory control in executive function, which is considered as a key symptom of ADHD. The increase in PFC activity further suggests that the STP improves cognition through neural function.

Review of barriers and interventions to promote treatment engagement for pediatric attention deficit hyperactivity disorder care

Attention deficit hyperactivity disorder(ADHD)is a common and impairing behavioral health disorder,impacting over 5%of children worldwide.There are multiple evidence-based pharmacological and psychosocial treatments for ADHD,and greater service utilization is associated with improved acute and long-term outcomes.However,long-term outcomes are suboptimal as multimodal treatments are often not accessed and most care ends prematurely.This narrative review discusses barriers to engagement for children and adolescents with ADHD and their families as well as interventions to overcome these barriers.Families face a variety of structural and attitudinal barriers,ranging from cost and access to stigma and low self-efficacy to successfully implement change.There are multiple interventions that may enhance engagement with ADHD care including psychoeducation,integration of behavioral services in general medical settings,telehealth as well as specific adaptations to existing ADHD treatments,such as the use of motivational interviewing or shared decision making.Integration of behavioral health into general medical settings and telehealth have been found in controlled studies to increase access by reducing both structural and attitudinal barriers.Adding motivational interviewing,shared decision making and other engagement interventions to evidence-based ADHD treatments has been found to reduce attitudinal barriers that translates into improved participation and satisfaction while enhancing outcomes.However,little is known about how to promote extended engagement with ADHD services even though a chronic care model for ADHD is recommended.

Attention-Deficit/Hyperactivity Disorder in Adults with High-Functioning Pervasive Developmental Disorders in Japan

Aims: This study was designed to verify the proportion of Japanese adults with pervasive developmental disorder (PDD) who met the diagnostic criteria (other than E) for attention-deficit/hyperactivity disorder (ADHD) in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR). Furthermore, we examined to what extent adults with PDD think that they exhibit ADHD symptoms. Methods: We developed an original Japanese self-report questionnaire to determine the presence or absence of 18 symptoms from the diagnostic criteria for ADHD in the DSM-IV-TR. We administered the questionnaire to 64 adults with high-functioning PDD (45 men and 19 women) and 21 adults with ADHD (10 men and 11 women), aged 18 to 59 years, with a full-scale intelligence quotient ≥75. Target patients were evaluated for ADHD by their psychiatrists. Results: Twenty-nine (45.3%) adults with PDD also had ADHD. The percentage of these adults who had over six perceived inattention symptoms from the DSM-IV-TR was 96.6%. The percentage of these adults who had over six perceived hyperactivity-impulsivity symptoms was 65.5%. Thirty-five (55.6%) adults with PDD responded that they were aware of having ADHD symptoms at the level of the relevant diagnostic criteria. Conclusions: The present study is the first to examine the frequency of objective and perceived ADHD symptoms in adults with PDD in Japan. Our results show that both objective and perceived ADHD symptoms frequently appear in a large number of adults with PDD. This suggests that it is necessary to attend to concomitant ADHD symptoms in the medical care of adults with PDD.

ADHD in Children and Adolescents: Barriers to Ethical and Successful Treatment

This review provides a comprehensive analysis of attention deficit hyperactivity disorder (ADHD), a neurodevelopmental disorder characterized by inattention, hyperactivity, or impulsivity. The global prevalence of the disorder ranges from 2% to 7%, with an average of around 5%. ADHD affects individuals of all ages, with symptoms typically becoming visible as early as 3 years. The symptoms range from mild to severe and may persist into adulthood. The disorder affects a variety of demographic groups, including differences in age, gender, race, and ethnicity, with varying effects, prevalence, and treatment options among these groups. Treatment options for ADHD range from behavioral interventions to prescription medication, with a number of medications available on the market for treating ADHD. The review also highlights the issues of relapse and safety concerns associated with the use of medication, as well as the challenges associated with diversity and socioeconomic barriers in the diagnosis and treatment of the disorder.

Cognitive Function of Children and Adolescents with Attention Deficit Hyperactivity Disorder and Learning Difficulties： A Developmental Perspective

Background： The cognitive function of children with either attention deficit hyperactivity disorder （ADHD） or learning disabilities （LDs） is known to be impaired. However, little is known about the cognitive function of children with comorbid ADHD and LD. The present study aimed to explore the cognitive function of children and adolescents with ADH D and learning difficulties in comparison with children with ADHD and healthy controls in different age groups in a large Chinese sample. Methods： Totally, 1043 participants with ADHD and learning difficulties （the ADHD ＋ learning difficulties group）, 870 with pure ADHD （the pure ADHD group）, and 496 healthy controls were recruited. To investigate the difference in cognitive impairment using a developmental approach, all participants were divided into three age groups （6-8, 9-11, and 12-14 years old）. Measurements were the Chinese-Wechsler Intelligence Scale for Children, the Stroop Color-Word Test, the Trail-Making Test, and the Behavior Rating Inventory of Executive Function-Parents （BRIEF）. Multivariate analysis of variance was used. Results： The results showed that after controlling for the effect of ADHD symptoms, the A DHD ＋ learning difficulties group was still significantly worse than the pureADHD group, which was, in turn, worse than the control group on full intelligence quotient （98.66 ± 13.87 vs. 105.17 ± 14.36 vs. 112.93 ± 13.87, P 〈 0.001 ）. The same relationship was also evident for shift function （shifting time of the Trail-Making Test, 122.50 [62.00, 194.25] s vs. 122.00 [73.00, 201.50] s vs. 66.00 [45.00, 108.00] s, P 〈 0.001） and everyday life executive function （BRIEF total score, 145.71 ± 19.35 vs. 138.96± 18.00 vs. 122.71 ± 20.45, P 〈 0.001 ） after controlling for the effect of the severity of ADHD symptoms, intelligence quotient, age, and gender. As for the age groups, the differences among groups became nonsignificant in the 12-14 years old group for inhibition （meaning interference of the Stroop Color-Word Test, 18.00 [13.00, 25.00] s vs. 17.00 [15.00, 26.00] s vs. 17.00 [10.50, 20.00] s, P =0.704） and shift function （shifting time of the Trail-Making Test, 62.00 [43.00, 97.00] s vs. 53.00 [38.00, 81.00] s vs. 101.00 [88.00, 114.00] s, P = 0.778）. Conclusions： Children and adolescents with ADHD and learning difficulties have more severe cognitive impairment than pure ADHD patients even after controlling for the effect of ADHD symptoms. However, the differences in impairment in inhibition and shift function are no longer significant when these individuals were 12-14 years old.

Frequency-specific abnormalities in regional homogeneity among children with attention deficit hyperactivity disorder: a resting-state f MRI study

Although many functional magnetic resonance imaging(f MRI) studies have investigated the neurophysiology of attention deficit hyperactivity disorder(ADHD),the existing studies have not yielded consistent findings.This may be related to the different properties of different frequency bands. To investigate the frequency-specific regional homogeneity(Re Ho) of spontaneous neural activities in ADHD, the current study used resting-state f MRI to explore the Re Ho properties of five frequency bands, slow-5(0.01–0.027 Hz), slow-4(0.027–0.073 Hz),slow-3(0.073–0.198 Hz), slow-2(0.198–0.25 Hz) and the extra-low frequency(0–0.01 Hz), in 30 drug-naive boys with ADHD and 30 healthy controls. Compared with controls, the ADHD group showed decreased Re Ho in the default mode network(DMN) including the medial prefrontal cortex and precuneus, middle frontal gyrus and angular gyrus. ADHD patients also showed increased Re Ho in the posterior cerebellum. Significant interactions between frequency band and group were observed predominantly in the dorsolateral prefrontal and parietal cortices, orbital frontal cortex, supplementary motor area,inferior occipital gyrus, thalamus and anterior cerebellum.In particular, we found that the between-group difference in the extra-low frequency band(0–0.01 Hz) seemed to be greater than that in the other frequency bands for most brain regions. The findings suggest that ADHD children display widespread abnormalities in regional brain activity,particularly in the DMN and attention network, and these abnormalities show frequency specificity.

脑电反馈治疗对共患ADHD和学习障碍患儿注意、智力影响

【目的】探讨脑电生物反馈治疗对共患注意缺陷多动性障碍（attention deficit hyperactivity disorder，ADHD）和学习障碍患儿注意、智力的改善作用。【方法】应用Sprit-8脑电生物反馈治疗仪，对48例（6～12岁）共患ADHD和学习障碍患儿进行40次增强16～20Hzp波，抑制4--8Hz0波脑电反馈治疗，治疗前后采用脑电反馈仪检测患儿脑电波θ／β、θ／SMR功率比值的变化，采用听视觉持续注意测验软件检测注意稳定性变化，采用瑞文推理测验（SPM）评价智力水平变化。【结果】脑电反馈治疗后患儿θ／β、θ／SMR值较前明显下降（P〈0．01），注意指标中的漏报数、错误数、反应时间较前降低（P〈0．01），智商较前改善（P〈0．01）。【结论】脑电反馈治疗能够明显改善共患ADHD和学习障碍患儿的脑电异常、智力、注意力，且对脑电异常改善作用无左右脑半球特异性。

盐酸哌甲酯控释剂治疗儿童ADHD临床疗效影响因素分析

目的观察中枢神经兴奋剂盐酸哌甲酯控释剂治疗注意缺陷多动障碍(ADHD)患儿临床疗效的影响因素。方法采取自身对照研究方法,选取2014年1月至2015年12月在上海市儿童医院儿保门诊就诊被诊断为ADHD并需要进行治疗的患儿711例;经过盐酸哌甲酯控释剂治疗后,分别于6周、6个月后采用斯诺佩评估量表(SNAP-Ⅳ)的家长使用量表、联合型瑞文测验(CRT)等相关测试,进行治疗前后疗效评估。结果盐酸哌甲酯控释剂对注意力缺陷型和混合型的ADHD患儿治疗效果明显优于多动型/冲动型(χ~2=73.109,P<0.01);对认知功能好的ADHD患儿疗效优于合并认知障碍者(χ~2=100.225,P<0.01)。结论盐酸哌甲酯控释剂治疗儿童不同类型ADHD疗效肯定;疗效受到ADHD类型、患儿智力、药物剂量等的影响。

ADHD儿童在钟表绘画测验中的执行功能特征

目的研究ADHD儿童在钟表绘画(CDT)测试中体现出的执行功能特征。方法对60例ADHD儿童和60例正常对照儿童进行CDT测试,综合分析两组儿童的大脑额叶执行功能的差异。结果ADHD儿童在CDT测试中的时间总分和构造总分低于对照组(3.23±1.40/4.15±0.78,11.2±1.48/11.90±0.76,t=7.742、5.073,P<0.01)。在给定十字位相标定点(3、6、9、12点)后ADHD儿童的钟面构造得分高于给定标定点之前(11.93±0.95/11.19±1.48,t=5.645,P<0.001),但时间设置评分却没有明显的提高(P>0.05)。结论ADHD儿童CDT测试得分偏低体现了其存在计划性、注意调控功能和工作记忆的缺陷,这些缺陷的核心问题是执行功能的缺陷。

伴与不伴抑郁情绪的ADHD儿童的临床症状初步研究

目的 了解注意缺陷多动障碍（ADHD）儿童抑郁情绪检出率,比较伴与不伴抑郁情绪的ADHD儿童的临床症状.方法 取儿童精神科门诊9～14岁ADHD儿童66名（男57、女9）,用儿童抑郁障碍自评量表（DSRSC）、儿童焦虑性情绪障碍筛查表（SCARED）和儿童行为量表（CBCL）进行评定,并按照DSRSC评分是否达到或高于划界分把ADHD儿童分为伴与不伴抑郁情绪两组.结果 ADHD儿童中18人DSRSC评分达到或高于划界分,抑郁情绪检出率为27.3%,CBCL评定显示退缩、焦虑/抑郁、社交问题、注意问题、攻击性行为、内化性行为问题和行为问题总分伴抑郁情绪组显著高于不伴抑郁情绪组,SCARED评定显示躯体/惊恐、广泛性焦虑、学校恐怖3个因子分和焦虑总分伴抑郁组显著高于不伴抑郁组.结论 ADHD儿童抑郁情绪检出率较高,伴抑郁的ADHD比单纯ADHD儿童有更多的行为问题,情绪问题更严重.