Magnetic resonance imaging evaluation and nuclear receptor binding SET domain protein 1 mutation in the Sotos syndrome with attention-deficit/hyperactivity disorder

Sotos syndrome is characterized by overgrowth features and is caused by alterations in the nuclear receptor binding SET domain protein 1 gene.Attentiondeficit/hyperactivity disorder(ADHD)is considered a neurodevelopment and psychiatric disorder in childhood.Genetic characteristics and clinical presentation could play an important role in the diagnosis of Sotos syndrome and ADHD.Magnetic resonance imaging(MRI)has been used to assess medical images in Sotos syndrome and ADHD.The images process is considered to display in MRI while wavelet fusion has been used to integrate distinct images for achieving more complete information in single image in this editorial.In the future,genetic mechanisms and artificial intelligence related to medical images could be used in the clinical diagnosis of Sotos syndrome and ADHD.

Proteomic analysis of effects of Chinese herbs to calm the liver and suppress hyperactive yang in a rat migraine model

BACKGROUND： The expression of ubiquitin and energy-associated protein can provoke migraines. Studies have suggested that expression is closely linked to ＂hyperactivity of liver-yang theory＂ in Traditional Chinese Medicine （TCM）, as well as the function of periphery sympathetic nerve medulla. OBJECTIVE： To observe proteomic changes in a rat migraine model with regard to hyperactivity of liver-yang when treated with Chinese herbs to calm the liver and suppress hyperactive yang compound. DESIGN, TIME AND SETTING： A randomized controlled study. This study was performed at the laboratory of Institute of Integrated Traditional Chinese and Western Medicine, Institute of Human Reproduction and Stem Cell Engineering and Key Laboratory of Cancer Proteomics of Ministry of Health, Xiangya Hospital Affiliated to Central South University between September 2006 and July 2007. MATERIALS： Thirty, male, healthy, Sprague-Dawley rats, aged eight weeks, were included in the final analysis. Aconite, to calm the liver and suppress hyperactive yang compound, was provided by the Dispensary of Traditional Chinese medicine, Xiangya Hospital, Central South University. A physiological electronic stimulator, type SDQ-1, was provided by Bengbu Practical Institute of Technology. The left trigeminal ganglion was localized and stimulated for 10 minutes, and the rats were orally administered an aconite concoction to establish a rat migraine model with hyperactivity of liver-yang. METHODS： Rats were randomly divided into a normal control group, model group, and TCM treatment group, with 10 rats in each group. The TCM treatment group was orally treated to calm the liver and suppress the hyperactive yang compound once a day for 28 days. In contrast, the model group and normal group were orally administered the same amount of distilled water once a day for 28 days. MAIN OUTCOME MEASURES： The total proteins from adrenal glands of the three groups were separated by two-dimensional gel electrophoresis （2-DE）, and 2-DE images were analyzed by PDQuest 7.0 software. Matrix-Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry （MALDI-TOF-MS） was used to obtain peptide mass fingerprints of the differential proteins. Databases were searched to identify the proteins, RESULTS： A total of 30 rats were included in the final analysis. Reproducible 2-DE patterns from rat adrenal gland of the three groups were obtained. Compared with the normal group, nine proteins were down-regulated and five proteins were up-regulated in the model group; however, these expressions returned to normal, or near normal levels, in the TCM treatment group. A total of eight differentially expressed proteins were identified： glycogen phosphorylase, ATP synthase D chain, isovaleryl-CoA dehydrogenase, ubiquitin, Annexin-3, Annexin-A1, Peroxirdoxin-II, and heat shock protein-27. CONCLUSION： Liver calming and suppression of the hyperactive yang compound may up-regulate expression of proteins related to energy metabolism and the ubiquitin system. Compounds that are used to treat migraines may contribute to protein functions in the peripheral sympathetic nervous system.

Inhibitory effects of jujuboside A on EEG and hippocampal glutamate in hyperactive rat

In this study, the inhibitory effect of jujuboside A (JuA) on a penicillin sodium (Na-PCN) induced hyperactivity model was investigated. Cortical EEG (electroencephalogram) and the concentration of hippocampal Glutamate (Glu) were monitored simultaneously in vivo as indicators of rat’s excitatory state. Power spectral density (PSD) and gravity frequency of PSD were calculated. JuA (0.05 g/L and 0.1 g/L) inhibited the EEG excitation effect caused by Na-PCN by increasing the power of δ1 and δ2 bands (P<0.01 vs model) and lowering the gravity frequency of PSD (P<0.01 vs model). JuA also remarkably reduced the Glu elevation induced by Na-PCN (P<0.05 vs model). Diazepam also depressed Glu concentration and lowered the gravity frequency, but it showed a different EEG pattern in increased β2-activity (P<0.01 vs model). EEG excitation caused by Na-PCN correlated with Glu elevation during the first hour. Neurophysiological inhibitory effects of JuA and diazepam were more persistent than their Glu inhibitoty effects.

Clinical and genetic characteristics of a child with Sotos syndrome and attention-deficit/hyperactivity disorder:A case report

BACKGROUND Sotos syndrome is an autosomal dominant disorder,whereas attention-deficit/hyperactivity disorder(ADHD)is a neurodevelopmental condition.This report aimed to summarize the clinical and genetic features of a pediatric case of Soros syndrome and ADHD in a child exhibiting precocious puberty.CASE SUMMARY The patient presented with accelerated growth and advanced skeletal maturation;however,she lacked any distinct facial characteristics related to specific genetic disorders.Genetic analyses revealed a paternally inherited heterozygous synonymous mutation[c.4605C>T(p.Arg1535Arg)].Functional analyses suggested that this mutation may disrupt splicing,and bioinformatics analyses predicted that this mutation was likely pathogenic.After an initial diagnosis of Sotos syndrome,the patient was diagnosed with ADHD during the follow-up period at the age of 8 years and 7 months.CONCLUSION The potential for comorbid ADHD in Sotos syndrome patients should be considered to avoid the risk of a missed diagnosis.

Food intolerance and the few-foods(or oligoantigenic)diet in children with attention-deficit hyperactivity disorder

The hypothesis that some children with attention-deficit hyperactivity disorder(ADHD)may show sensitivity or allergic reactions to various food items has led to the development of the the few-foods(or oligoantigenic)diet.The rationale of the diet is to eliminate certain foods from the diet in order to exclude potential allergens contained either naturally in food or in artificial ingredients with allergenic properties.The oligoantigenic diet attempts to identify individual foods to which a person might be sensitive.First,ADHD symptoms are monitored while multiple foods are excluded from the diet.Subsequently,if symptoms remit,foods are re-introduced,while observing the individual for the return of symptoms.An advantage of the oligoantigenic diet is that it can be tailored to the individual.A growing body of evidence suggests that behavioral symptoms of subgroups of children with ADHD may benefit from the elimination of certain foods.The effect sizes of an oligoantigenic diet regarding improvement of ADHD symptoms have been found to be medium to large.Available evidence suggests that the investigation of the role of food hypersensitivities in ADHD is a promising avenue worthy of further exploration.Further large-scale,randomized controlled studies including assessment of long-term outcome are therefore warranted.

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.

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.

Impact of educational interventions on mothers’ awareness and communication with their attention-deficit hyperactivity disorder children

Objective:The objectives of this study are to evaluate the effects of the educational intervention on mothers’knowledge,awareness,and communication difficulties experienced with their children and mothers’capacity to successfully interact with their affected child before and after the intervention.Materials and Methods:A quasi-experimental research design was used.A total of 30 mothers and their children complaining of attention-deficit hyperactivity disorder from four Dawadmi primary schools were included.Data were collected through a self-developed questionnaire from September 2023 to January 2024 after study acceptance by Shaqra University’s scientific deanship.Intervention prepared according to subjects’needs and current scientific base and demonstrated in 10 sessions in schools.Results:Regarding mothers’age,more than one-fourth of them(26.7%)ranged from 31 to 35 year old,and about a third(36.7%)had secondary education.Regarding mother’s job,about 76.7%do not work,and the majority of affected children(66.6%)were male,there were significant improvements in mothers’knowledge pre-and postintervention also a significant improvement in mothers’awareness about symptoms of poor attention,hyperactivity,and impulsivity pre-and postintervention was found.Significant differences were found before and after the intervention regarding the impact of the intervention in decreasing mothers’challenges.Conclusion:The study hypothesis was accepted,and the intervention improved mothers;knowledge,awareness,and communication challenges.The intervention should be conducted and followed up for a long period of time to manage all mother’s and children’s daily challenges,improve children’s daily activities,and stabilize effective communication patterns between children and their family members.

Positive Effect of Transcranial Direct Current Stimulation on Visual Verbal Working Memory in Patients with Attention-Deficit/Hyperactivity Disorder

Background: Working memory is an executive function that plays an important role in many aspects of daily life, and its impairment in patients with attention-deficit/hyperactivity disorder (ADHD) affects quality of life. The dorsolateral prefrontal cortex (DLPFC) has been a good target site for transcranial direct current stimulation (tDCS) due to its intense involvement in working memory. In our 2018 study, tDCS improved visual-verbal working memory in healthy subjects. Objective: This study examines the effects of tDCS on ADHD patients, particularly on verbal working memory. Methods: We conducted an experiment involving verbal working memory of two modalities, visual and auditory, and a sustained attention task that could affect working memory in 9 ADHD patients. Active or sham tDCS was applied to the left DLPFC in a single-blind crossover design. Results: tDCS significantly improved the accuracy of visual-verbal working memory. In contrast, tDCS did not affect auditory-verbal working memory and sustained attention. Conclusion: tDCS to the left DLPFC improved visual-verbal working memory in ADHD patients, with important implications for potential ADHD treatments.

Clarifying the relationship and analyzing the influential factors of bronchial asthma in children with attention-deficit hyperactivity disorder

BACKGROUND Bronchial asthma is closely related to the occurrence of attention-deficit hyperactivity disorder(ADHD)in children,which can easily have adverse effects on children’s learning and social interactions.Studies have shown that childhood asthma can increase the risk of ADHD and the core symptoms of ADHD.Compared with children with ADHD alone,children with asthma and ADHD are more likely to show high levels of hyperactivity,hyperactive-impulsive and other externalizing behaviors and anxiety in clinical practice and have more symptoms of somatization and emotional internalization.AIM To explore the relationship between ADHD in children and bronchial asthma and to analyze its influencing factors.METHODS This retrospective cohort study was conducted at Dongying People's Hospital from September 2018 to August 2023.Children diagnosed with ADHD at this hospital were selected as the ADHD group,while healthy children without ADHD who underwent physical examinations during the same period served as the control group.Clinical and parental data were collected for all participating children,and multivariate logistic regression analysis was employed to identify risk factors for comorbid asthma in children with ADHD.RESULTSSignificant differences were detected between the ADHD group and the control group in terms of family history ofasthma and allergic diseases, maternal complications during pregnancy, maternal use of asthma and allergymedications during pregnancy, maternal anxiety and depression during pregnancy, and parental relationshipstatus (P < 0.05). Out of the 183 children in the ADHD group, 25 had comorbid asthma, resulting in a comorbidityrate of 13.66% (25/183), compared to the comorbidity rate of 2.91% (16/549) among the 549 children in the controlgroup. The difference in the asthma comorbidity rate between the two groups was statistically significant (P <0.05). The results of the multivariate logistic regression analysis indicated that family history of asthma and allergicdiseases, maternal complications during pregnancy, maternal use of asthma and allergy medications duringpregnancy, maternal anxiety and depression during pregnancy, and parental relationship status are independentrisk factors increasing the risk of comorbid asthma in children with ADHD (P < 0.05).CONCLUSIONChildren with ADHD were more likely to have comorbid asthma than healthy control children were. A familyhistory of asthma, adverse maternal factors during pregnancy, and parental relationship status were identified asrisk factors influencing the comorbidity of asthma in children with ADHD. Clinically, targeted interventions basedon these factors can be implemented to reduce the risk of comorbid asthma. This information is relevant for resultssections of abstracts in scientific articles.

Nutritional epigenetics education improves diet and attitude of parents of children with autism or attention deficit/hyperactivity disorder

BACKGROUND Unhealthy maternal diet leads to heavy metal exposures from the consumption of ultra-processed foods that may impact gene behavior across generations,creating conditions for the neurodevelopmental disorders known as autism and attention deficit/hyperactivity disorder(ADHD).Children with these disorders have difficulty metabolizing and excreting heavy metals from their bloodstream,and the severity of their symptoms correlates with the heavy metal levels measured in their blood.Psychiatrists may play a key role in helping parents reduce their ultra-processed food and dietary heavy metal intake by providing access to effective nutritional epigenetics education.AIM To test the efficacy of nutritional epigenetics instruction in reducing parental ultra-processed food intake.METHODS The study utilized a semi-randomized test and control group pretest-posttest pilot study design with participants recruited from parents having a learning-disabled child with autism or ADHD.Twenty-two parents who met the inclusion criteria were randomly selected to serve in the test(n=11)or control(n=11)group.The test group participated in the six-week online nutritional epigenetics tutorial,while the control group did not.The efficacy of the nutritional epigenetics instruction was determined by measuring changes in parent diet and attitude using data derived from an online diet survey administered to the participants during the pre and post intervention periods.Diet intake scores were derived for both ultra-processed and whole/organic foods.Paired sample t-tests were conducted to determine any differences in mean diet scores within each group.RESULTS There was a significant difference in the diet scores of the test group between the pre-and post-intervention periods.The parents in the test group significantly reduced their intake of ultra-processed foods with a preintervention diet score of 70(mean=5.385,SD=2.534)and a post-intervention diet score of 113(mean=8.692,SD=1.750)and the paired t-test analysis showing a significance of P<0.001.The test group also significantly increased their consumption of whole and/or organic foods with a pre-intervention diet score of 100(mean=5.882,SD=2.472)and post-intervention diet score of 121(mean=7.118,SD=2.390)and the paired t-test analysis showing a significance of P<0.05.CONCLUSION Here we show nutritional epigenetics education can be used to reduce ultra-processed food intake and improve attitude among parents having learning-disabled children with autism or 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.

Acute and chronic excitotoxicity in ischemic stroke and late-onset Alzheimer's disease

Stroke and Alzheimer's disease are common neurological disorders and often occur in the same individuals.The comorbidity of the two neurological disorders represents a grave health threat to older populations.This review presents a brief background of the development of novel concepts and their clinical potentials.The activity of glutamatergic N-methyl-D-aspartate receptors and N-methyl-D-aspartate receptor-mediated Ca^(2+)influx is critical for neuronal function.An ischemic insult induces prompt and excessive glutamate release and drastic increases of intracellular Ca^(2+)mainly via N-methyl-D-aspartate receptors,particularly of those at the extrasynaptic site.This Ca^(2+)-evoked neuronal cell death in the ischemic core is dominated by necrosis within a few hours and days known as acute excitotoxicity.Furthermore,mild but sustained Ca^(2+)increases under neurodegenerative conditions such as in the distant penumbra of the ischemic brain and early stages of Alzheimer's disease are not immediately toxic,but gradually set off deteriorating Ca^(2+)-dependent signals and neuronal cell loss mostly because of activation of programmed cell death pathways.Based on the Ca^(2+)hypothesis of Alzheimer's disease and recent advances,this Ca^(2+)-activated“silent”degenerative excitotoxicity evolves from years to decades and is recognized as a unique slow and chronic neuropathogenesis.The N-methyl-D-aspartate receptor subunit GluN3A,primarily at the extrasynaptic site,serves as a gatekeeper for the N-methyl-D-aspartate receptor activity and is neuroprotective against both acute and chronic excitotoxicity.Ischemic stroke and Alzheimer's disease,therefore,share an N-methyl-D-aspartate receptor-and Ca^(2+)-mediated mechanism,although with much different time courses.It is thus proposed that early interventions to control Ca^(2+)homeostasis at the preclinical stage are pivotal for individuals who are susceptible to sporadic late-onset Alzheimer's disease and Alzheimer's disease-related dementia.This early treatment simultaneously serves as a preconditioning therapy against ischemic stroke that often attacks the same individuals during abnormal aging.

Tourette syndrome associated with attention deficit hyperactivity disorder: The impact of tics and psychopharmacological treatment options

Tourette syndrome(TS) is a neurodevelopmental disorder characterized by multiple chronic motor and vocal tics beginning in childhood. Several studies describe the association between TS and attention deficit hyperactivity disorder(ADHD). Fifty percent of children diagnosed with ADHD have comorbid tic disorder. ADHD related symptoms have been reported in 35% to 90% of children with TS. Since ADHD is the most prevalent comorbid condition with TS and those with concomitant TS and ADHD present with considerable psychosocial and behavioral impairments, it is essential for clinicians to be familiar with these diagnoses and their management. This paper highlights the association between treating ADHD with stimulants and the development of tic disorders. The two cases discussed underscore the fact that children with TS may present with ADHD symptomatology prior to the appearance of any TS related symptoms. Appropriate management of TS in a patient diagnosed with ADHD can lead to quality of life improvements and a reduction in psychosocial impairments.

Association of Serotonin Receptors with Attention Deficit Hyperactivity Disorder： A Systematic Review and Meta-analysis

Attention deficit hyperactivity disorder （ADHD） is one of the most common mental disorders in childhood, with a high heritability about 60% to 90%. Serotonin is a monoamine neurotransmitter. Numerous studies have reported the association between the serotonin receptor family （5-HTR） gene polymorphisms and ADHD, but the results are still controversial. In this study, we conducted a meta-analysis of the association between 5-HTRIB, 5-HTR2A, and 5-HTR2C genetic variants and ADHD. The results showed that the 861G allele of 5-HTRIB SNP rs6296 could significantly increase the risk of ADHD （OR= 1.09, 95% CI： 1.01-1.18）; the 5-HTR2C gene rs518147 （OR=1.69, 95% CI： 1.38-2.07） and rs3813929 （OR = 1.57, 95% CI： 1.25-1.97） were all associated with the risk of ADHD. In addition, we also carried on a case- control study to explore the relevance between potential candidate genes 5-HTR1A, 5-HTRIE, 5-HTR3A and ADHD. The results indicated that 5-HTRIA rs6295 genotype （CC＋CG vs. GG OR=Z00, 95% CI： 1.23-3.27） and allele （OR=1.77, 95% CI： 1.16-2.72） models were statistically significantly different between case group and control group. This study is the first comprehensive exploration and summary of the association between serotonin receptor family genetic variations and ADHD, and it also provides more evidence for the etiology of ADHD.

Attention deficit hyperactivity disorder and comorbidity: A review of literature

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder with onset in early childhood.It is a clinically heterogenous condition with comorbidity posing a distinct challenge to diagnosing and managing these children and adolescents.This review aims to provide an overview of comorbidity with ADHD including other neurodevelopmental disorders,learning disorders,externalising and internalising disorders.Challenges in screening for,diagnosing and managing comorbidity with ADHD are summarised.Also,methodological challenges and future directions in research in this interesting field are highlighted.

Does mindfulness meditation improve attention in attention deficit hyperactivity disorder?

Attention deficit hyperactivity disorder(ADHD) manifests by high levels of inattention, impulsiveness and hyperactivity. ADHD starts in childhood and results in impairments that continue into adulthood. While hyperactivity declines over time, inattention and executive function difficulties persist, leading to functional deficits. Adolescents and adults with ADHD have pervasive impairment in interpersonal and family relationships. They may develop addiction, delinquent behavior and comorbid psychiatric disorders. Despite advances in diagnosis and treatment, persistent residual symptoms are common, highlighting the need for novel treatment strategies. Mindfulness training, derived from Eastern meditation practices, may improve self-regulation of attention. It may also be a useful strategy to augment standard ADHD treatments and may be used as a potential tool to reduce impairments in patients with residual symptoms of ADHD. Clinically, this would manifest by an increased ability to suppress task-unrelated thoughts and distractions resulting in improved attention, completion of tasks and potential improvement in occupational and social function.

Who says this is a modern disorder? The early history of attention deficit hyperactivity disorder

Attention-deficit hyperactivity disorder(ADHD) is a complex, heterogeneous and multifactorial neurodevelopmental disorder characterized by persistent symptoms of inattention, hyperactivity and impulsivity. Although the first clinical description of a constellation of symptoms highly resembling to what currently could be diagnosed as ADHD is generally attributed to George F Still in 1902, there are scattered but significant published historical medical, scientific and non-scientific reports, much prior to Still's lectures, of what is currently conceptualized as ADHD. The present report aimed at exploring the early history of ADHD, prior to the 20^(th) century in the medical literature and in other historical sources, to provide clinicians, researchers and other professionals with a better understanding of the roots and current conceptualization of this disorder. It is possible to find clues and highly suggestive descriptions of individuals presenting symptoms resembling what is currently defined as ADHD in the literature, in paintings or in the Bible. However, the earliest medical reports of individuals with abnormal degrees of inattention, distractibility and overactivity date from the last quarter of the 18^(th) century, included in two of the first textbooks specifically on the subject of mental diseases, published by the German Melchior Adam Weikard and the Scottish Sir Alexander Crichton. During the 19^(th) century some eminent physicians from Germany, France or Great Britain, such as Charles West, Thomas C Albutt, Thomas S Clouston, William W, Ireland, John Haslam, Heinrich Neumann, or Désiré-Magloire Bourneville, among others provided clinical depictions of patients that most likely presently would be diagnosed as having ADHD. Whilst some of the children described by Still and his predecessors may have suffered from a variety of neurological and psychiatric disorders, many of these patients showed clear symptoms of ADHD and may present with comorbid disorders, as it is commonly the case in clinical practice.

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.

How does a real-world child psychiatric clinic diagnose and treat attention deficit hyperactivity disorder?

AIM: To investigate child and adolescent psychiatrists'(CAPs) attention deficit hyperactivity disorder(ADHD) and oppositional defiant disorder(ODD) diagnoses and treatments in real-world clinical practice. METHODS: The medical records of 69 ADHD children(mean age = 9.5 years), newly referred to the ADHD clinic, were reviewed for their scores of parent- and teacher-reported Vanderbilt ADHD Diagnostic Rating Scales(VADRSs), CAPs' diagnoses of ADHD and ODD, and CAPs' treatment recommendations. Among 63 ADHD subjects who completed both parent and teacher VADRSs, we examined the agreement of the parent and teacher VADRSs. We also examined the concurrent validity of CAPs' ODD diagnoses against the results from the VADRSs. In addition, we compared CAPs' treatment recommendations against established ADHD and ODD guidelines.RESULTS: Among 63 ADHD subjects, the majority of the subjects(92%) met full ADHD diagnostic criteria at least in one setting(parent or teacher) on the VADRSs. Nearly half of the patients met full ADHD diagnostic criteria in two settings(parent and teacher). Relatively low agreement between the parent and teacher VADRSs were found(95%CI:-0.33 to 0.14). For 29 children who scored positive for ODD on the rating scales, CAPs confirmed the ODD diagnosis in only 12 of these casepositives, which is considered as a fair agreement between CAPs and VADRSs(95%CI: 0.10-0.53). For 27 children with no ODD diagnosis made by either CAP or VADRS, more than half of them were recommended for medication only. In contrast, where CAPs made the diagnosis of ODD, or where the parent or teacher VADRS was positive for ODD, almost all of the patients received recommendations for medication and behavior therapy.CONCLUSION: CAPs' ADHD diagnoses have strong concurrent validity against valid rating scales, but ADHD's most common comorbid condition- ODD- may be underrecognized.