Development Of Attention Deficit Hyperactivity Disorder Research Articles

Exposure to noise at home, emotional behaviour, and attention deficit hyperactivity disorder in 9-year-old children

The purpose of this study was to assess the relationship between noise disturbance at home, sleep disturbance, and neurodevelopmental problems in 9-year-old children. Noise exposure (frequency) perceived by 430 9-year-old children from the INMA cohort in Valencia, Spain, were reported by their mothers. The risk of developing attention deficit hyperactivity disorder, as well as internalizing and externalizing problems, were assessed using the Child Behaviour Checklist. The risk of internalizing (18%) and externalizing problems (11.7%) was higher compared to the risk of developing attention deficit hyperactivity disorder (1.4%) and were more prevalent in boys than in girls. The most common and bothersome noise exposures were generated at home (50.8-55.3%) and by neighbours (24.5%). The risk of neurodevelopmental problems was associated with sleep disturbances, particularly in relation with attention deficit hyperactivity disorder (16.1 vs 4%; p<0.001), with no differences observed between sex. Sleep disturbances were significantly more common in children exposed to noise from household or neighbours. High levels of noise exposure from street traffic and neighbours were linked to an increased risk of attention deficit hyperactivity disorder, while noise from other children at home was associated with a higher risk of internalizing and externalizing problems. These effects remained consistent even after adjusting for sleep disturbances. High levels of noise annoyance from various sources perceived at home are differently associated with the risks of different neurodevelopmental problems in 9-year-old boys and girls, with sleep disturbances not influencing this relationship.

Long-term Neurobehavioral and Metabolic Outcomes in Offspring of Mothers With Diabetes During Pregnancy: A Large, Population-Based Cohort Study in Ontario, Canada.

Offspring of women with diabetes are at increased risk of developing neurobehavioral and cardiometabolic disorders, but there is scant evidence regarding the association between glycemic level during pregnancy and these long-term offspring outcomes. We conducted a population-based, cohort study of deliveries in Ontario between April 1991 and March 2018. Women had preexisting diabetes, gestational diabetes, or no diabetes. We applied a Cox proportional hazard model to examine the risk of developing attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and cardiometabolic outcomes in offspring and assessed the association between pregnancy HbA1c levels and risk of outcomes, adjusting for confounders. A total of 3,407,961 mother/infant pairs were followed up to 29 years. Using a Cox proportional hazard model, offspring of women with type 1 diabetes had the highest risk of ADHD (adjusted hazard ratio [aHR] 1.43 [95% CI 1.36-1.49]), ASD (aHR 1.94 [1.80-2.09]), diabetes (aHR 4.73 [4.34-5.16]), hypertension (aHR 2.32 [2.07-2.61]), and cardiovascular disease (CVD) (aHR 1.72 [1.56-1.90]), followed by offspring of women with type 2 diabetes and gestational diabetes compared with those unexposed. Among women with preexisting diabetes, there was an association between level of pregnancy HbA1c and offspring diabetes (aHR 1.22 [95% CI 1.12-1.32]), hypertension (aHR 1.42 [1.29-1.57]), and CVD (aHR 1.20 [1.11-1.29]) but no statistically significant association with neurobehavioral outcomes. In utero exposure to maternal diabetes was associated with an increase in ADHD, ASD, and cardiometabolic outcomes in offspring, with differences seen across diabetes subtypes. Pregnancy glycemia was associated with cardiometabolic outcomes, but not neurobehavioral outcomes, and provides a potentially modifiable risk factor to decrease cardiometabolic outcomes in offspring.

Early childhood general anesthesia and risk of Attention Deficit Hyperactivity Disorder.

The relationship between early childhood exposure to general anesthesia (GA) and the risk of developing Attention Deficit Hyperactivity Disorder (ADHD) is still uncertain and previous studies have presented conflicting results. This population-based cohort study aimed to investigate the potential relationship between GA exposure and ADHD risk using propensity score matching (PSM) in a large sample size. The study included 15,072 children aged 0-3 years who received GA and were hospitalized for more than 1 day in Taiwan from 2004 to 2014. The nonexposed group was randomly selected through 1:1 PSM from the Taiwan Maternal and Child Health Database (TMCHD). The primary objectives of this study were to determine the incidence rates (IR) and incidence rate ratios (IRR) of ADHD in the two cohorts, employing Poisson regression models. The GA group and non-GA group each comprised 7,536 patients. The IR of ADHD was higher in the GA group (122.45 per 10,000 person-years) than in the non-GA group (64.15 per 10,000 person-years), and the IRR of ADHD in the GA group was 1.39 (95% CI: 1.26, 1.55). The study found that the number of times of exposure to GA, duration of exposure, male gender, and central nervous system surgery were significant risk factors for ADHD in the future. This study's findings suggest that there is a significant correlation between early childhood exposure to GA and the risk of developing ADHD, and GA may be an important risk factor for ADHD in children undergoing surgery. The study also identified several risk factors for ADHD, including the number of times of exposure to GA, duration of exposure, male gender, and central nervous system surgery.

Screen Time and Attention Deficit Hyperactive Symptoms Among Young Adults in Bangladesh: An Online Cross-Sectional Study During The COVID-19 Pandemic

Objective. Mobile or computer device screening time contributes to developing attention deficithyperactivity disorder (ADHD). This study assessed the role of screening time in developing ADHDsymptoms in adults according to the World Health Organization (WHO) Adult ADHD Self-Report Scale(ASRS). Method. This research is an internet-based self-reported study on young adult people aged over 18 yearsamid Covid-19 to collect information on ADHD symptoms and mobile/computer device screening time usinga web-based structured questionnaire. Results. Among the 310 respondents, 124 (40%) had ADHD symptoms. Males with ADHD symptoms(45%) were more than females (35%). Histories of using digital devices with screening time of more than 4hours a day were seven times more likely to develop ADHD symptoms compared to the respondents who hada history of using digital devices with screening time less than 3 hours (aOR 7.5, 95% CI: 3.62-24.92). Conclusion. The occurrence of ADHD symptoms was not uncommon in young adults amid the COVID-19pandemic. More awareness regarding the negative impact of longer screening time in progressing ADHDamong young adults needs to be improved to reduce the risk of developing ADHD.

Are infants born after an episode of suspected preterm labor at risk of attention deficit hyperactivity disorder? A 30-month follow-up study

An episode of suspected preterm labor may be by itself a pathologic event that may alter the normal course of pregnancy and the offspring's neurodevelopment. Certainly, the association between preterm birth and neurodevelopmental disorders can only be partially explained by the immaturity of the nervous system, as evidenced by the increased risk of attention deficit hyperactivity disorder in late-preterm infants without any neurologic alteration. This study aimed to examine whether infants born after suspected preterm labor may be at an increased risk of developing attention deficit hyperactivity disorder. Moreover, potential obstetrical, perinatal, and psychosocial risk factors associated with attention deficit hyperactivity disorder in this population are examined. A prospective cohort study of 120 mother-infant pairs was conducted from the moment the mothers received a diagnosis of suspected preterm labor until the infants' 30 months of life. Infants were divided according to the prematurity status: full-term infants born after a suspected preterm labor (n=28; born at ≥37 weeks of gestation), late-preterm infants (n=56; born between 32 and <37 weeks of gestation), very-preterm infants (n=36; born before <32 weeks of gestation). At-term infants born without obstetric complications served as a control group (n=46). Infants' attention deficit hyperactivity disorder symptoms were assessed at the age of 30 months. Furthermore, obstetrical, perinatal, and psychosocial risk factors were recorded. All groups of infants born after a suspected preterm labor showed more attention deficit hyperactivity disorder symptoms at the age of 30 months than the control group. Concretely, very-preterm infants showed higher restless or impulsive behaviors, whereas full-term infants born after a suspected preterm labor and late-preterm infants showed higher emotional lability behaviors. Among potential risk factors, male sex and maternal experience of posttraumatic stress symptoms predicted the severity of attention deficit hyperactivity disorder symptoms in infants born after a suspected preterm labor. Infants born after a suspected preterm labor had a higher risk of developing attention deficit hyperactivity disorder symptoms, including those born at term. Infants born after a suspected preterm labor showed a distinctive phenotype and shared specific risk factors suggesting that they conform an undescribed population at risk of attention deficit hyperactivity disorder.

Association of Epigenetic Differences Screened in a Few Cases of Monozygotic Twins Discordant for Attention-Deficit Hyperactivity Disorder With Brain Structures.

The present study examined the relationship between DNA methylation differences and variations in brain structures involved in the development of attention-deficit hyperactivity disorder (ADHD). First, we used monozygotic (MZ) twins discordant (2 pairs of 4 individuals, 2 boys, mean age 12.5 years) for ADHD to identify candidate DNA methylation sites involved in the development of ADHD. Next, we tried to replicate these candidates in a case-control study (ADHD: N = 18, 15 boys, mean age 10.0 years; Controls: N = 62, 40 boys, mean age 13.9 years). Finally, we examined how methylation rates at those sites relate to the degree of local structural alterations where significant differences were observed between cases and controls. As a result, we identified 61 candidate DNA methylation sites involved in ADHD development in two pairs of discordant MZ twins, among which elevated methylation at a site in the sortilin-related Vps10p domain containing receptor 2 (SorCS2) gene was replicated in the case-control study. We also observed that the ADHD group had significantly reduced gray matter volume (GMV) in the precentral and posterior orbital gyri compared to the control group and that this volume reduction was positively associated with SorCS2 methylation. Furthermore, the reduced GMV regions in children with ADHD are involved in language processing and emotional control, while SorCS2 methylation is also negatively associated with emotional behavioral problems in children. These results indicate that SorCS2 methylation might mediate a reduced GMV in the precentral and posterior orbital gyri and therefore influence the pathology of children with ADHD.

Relationship between Parenting Stress and Risk of Attention Deficit Hyperactivity Disorder (ADHD) in Elementary School Children

Background: Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorderduring child development with three symptoms which are comprised of inattention, hyperactivity, andimpulsiveness that may persist into adulthood. This condition can be a stressor for parents in performingparenting and may lead into a state of parenting stress. Objective: To analyze the relationship betweenparenting stress and the risk of developing Attention Deficit Hyperactivity Disorder (ADHD) inelementary school children. Methods: This research was conducted in Surabaya from November 2020to January 2021 with respondents consisting of parents of elementary school children who have ADHDrisk and agreed to participate in this study with a total of 55 samples selected using a purposive samplingtechnique. The research design was cross-sectional using demographic questionnaire, AbbreviatedConners Rating Scale (ACRS), and Parenting Stress Index-Short Form (PSI-SF) which were filledout by respondents through an online form. The data were processed and analyzed using One-SampleChi-Square analysis test program with a p-value &lt;0.05, considered statistically significant. Results:The majority of parents experienced moderate parenting stress levels (58.2%). There was a significantrelationship between each level of parenting stress and the risk of ADHD in children (p &lt; 0.001).Conclusions: There is a significant relationship between parenting stress and the risk of ADHD inchildren.

Reward-Related Dysfunctions in Children Developing Attention Deficit Hyperactivity Disorder-Roles of Oppositional and Callous-Unemotional Symptoms.

Objectives: Neurocognitive functions might indicate specific pathways in developing attention deficit hyperactivity disorder (ADHD). We focus on reward-related dysfunctions and analyze whether reward-related inhibitory control (RRIC), approach motivation, and autonomic reactivity to reward-related stimuli are linked to developing ADHD, while accounting for comorbid symptoms of oppositional defiant disorder (ODD), and callous-unemotional (CU) traits.Methods: A sample of 198 preschool children (115 boys; age: m = 58, s = 6 months) was re-assessed at age 8 years (m = 101.4, s = 3.6 months). ADHD diagnosis was made by clinical interviews. We measured ODD symptoms and CU traits using a multi-informant approach, RRIC (Snack-Delay task, Gift-Bag task) and approach tendency using neuropsychological tasks, and autonomic reactivity via indices of electrodermal activity (EDA).Results: Low RRIC and low autonomic reactivity were uniquely associated with ADHD, while longitudinal and cross-sectional links between approach motivation and ADHD were completely explained by comorbid ODD and CU symptoms.Conclusion: High approach motivation indicated developing ADHD with ODD and CU problems, while low RRIC and low reward-related autonomic reactivity were linked to developing pure ADHD. The results are in line with models on neurocognitive subtypes in externalizing disorders.

Hair cortisol concentration and neurocognitive functions in preschool children at risk of developing attention deficit hyperactivity disorder

ObjectiveSex differences have been shown in the relation between hair cortisol concentration (HCC) and ADHD symptoms. As an extension of these findings, we analyze whether a child’s sex modulates the associations between HCC and ADHD-related neurocognitive functions. MethodsA community-based sample of 122 children was tested at age 4–5 (T1) and 8 (T2) years. At T1 and T2, ADHD symptoms were assessed with clinical parent interviews and parent and teacher questionnaires. Neurocognitive functions (i.e. T1: inhibitory control, working memory (WM), T2: verbal and performance intelligence (IQ-p)) were assessed using (neuro-)psychological tests. At T1, HCC was analyzed in the most proximal 3 cm scalp hair segment using luminescence immunoassay. ResultsExclusively in boys, low HCC correlated with low WM and IQ-p. The sex-by-HCC interaction effect on WM was significant. In boys, HCC completely explained the links of ADHD inattention symptoms with WM and IQ-p, respectively. ConclusionResults suggest a specific neurocognitive/endocrine profile in preschool boys at risk of developing ADHD, comprising hypocortisolism combined with memory and attention deficits.

From early risk via cognitive functioning to ADHD phenotype: A longitudinal study of boys at familial risk for ADHD

We examined the interplay between familial risk and the quality of the home environment and the intermediate role of cognitive functioning in the development of attention-deficit hyperactivity disorder (ADHD). Participants were 99 boys and their parents (M age = 7.34 years, SD = 0.23), who have been followed longitudinally since birth; 62 participants were followed until adolescence (M age = 13.5 years, SD = 0.95). We found that differential susceptibility to home environment in early childhood predicted the cognitive functioning (decreased executive function [EF] and increased intrasubject variability [ISV]) at elementary-school age. Specifically, in a lower quality home environment, those at high familial risk showed poor cognitive functioning (i.e., low EF and high ISV) at elementary-school age but under a supportive environment showed high cognitive functioning (i.e., high EF and low ISV), outperforming their peers at low familial risk. Moreover, child EF, but not ISV, was involved in a developmental path leading to an ADHD phenotype; it was found to mediate the relation between the early risk level (i.e., the interaction between familial risk and home environment) and child ADHD symptoms. A preliminary analysis suggests that EF may have a longitudinal effect on ADHD symptoms in adolescence; after controlling for the level of symptoms at elementary-school age, children with low levels of EF showed a significant increase in their symptoms over time. In general, our results propose a plausible mechanism that explains how the familial risk for ADHD could be translated into actual symptoms among children, at least in the case of boys.

New-generation antiepileptic drugs during pregnancy and the risk of attention-deficit hyperactivity disorder: A scoping review.

The use of maternal antiepileptic drug (AED) during pregnancy is associated with an increased risk of cognitive adverse effects among the offspring. As new-generation AEDs continue to enter the market, evidence on their safety during pregnancy is limited yet necessary. To date, there are no published reviews summarizing the evidence of new-generation AED exposure in utero and the development of attention deficit-hyperactivity disorder (ADHD) in the offspring. The objective of this scoping review is to summarize the available evidence on the risk of ADHD after maternal exposure to new-generation AEDs during pregnancy. We searched EMBASE and MEDLINE for articles published from January 1988 to April 2020. New-generation AEDs were considered if marketed after 1988. ADHD was defined as attention-deficit hyperactivity disorder, hyperkinetic disorder, hyperkinesis, or conduct disorder. Of the total articles screened (n = 805), eight publications were finally included (seven cohort studies and one systematic review). Across the studies, the sample size of pregnant women exposed to AEDs ranged from 1 to 1383. Monotherapy was examined in six studies (mostly lamotrigine), while only two studies examined polytherapy. The included studies reported a range of adjusted relative risks, from 0.84 [0.59-1.19] to 1.63 [0.41-6.06]. Lamotrigine monotherapy holds the largest body of evidence, concluding that no significant risk of ADHD exists among the offspring. However, the available evidence is considered scarce and has several methodological limitations. Disentangling the effect of AEDs from epilepsy itself and examining polytherapies are challenges that merit additional investigations. Further comparative safety studies with longer follow-up periods and large sample sizes are needed to accurately quantify the true impact of new-generation AED exposure during pregnancy and ADHD in children.

Gestational Factors throughout Fetal Neurodevelopment: The Serotonin Link.

Serotonin (5-HT) is a critical player in brain development and neuropsychiatric disorders. Fetal 5-HT levels can be influenced by several gestational factors, such as maternal genotype, diet, stress, medication, and immune activation. In this review, addressing both human and animal studies, we discuss how these gestational factors affect placental and fetal brain 5-HT levels, leading to changes in brain structure and function and behavior. We conclude that gestational factors are able to interact and thereby amplify or counteract each other’s impact on the fetal 5-HT-ergic system. We, therefore, argue that beyond the understanding of how single gestational factors affect 5-HT-ergic brain development and behavior in offspring, it is critical to elucidate the consequences of interacting factors. Moreover, we describe how each gestational factor is able to alter the 5-HT-ergic influence on the thalamocortical- and prefrontal-limbic circuitry and the hypothalamo-pituitary-adrenocortical-axis. These alterations have been associated with risks to develop attention deficit hyperactivity disorder, autism spectrum disorders, depression, and/or anxiety. Consequently, the manipulation of gestational factors may be used to combat pregnancy-related risks for neuropsychiatric disorders.

The affective temperament traits and pregnancy-related depression in mothers may constitute risk factors for their children with attention deficit and hyperactivity disorder

We investigated whether the affective temperaments of mothers and maternal depression before and during the index pregnancy are related to the development of Attention-Deficit Hyperactivity Disorder (ADHD) in their children. One hundred and twenty children were screened for the diagnosis of ADHD. After exclusion and inclusion criteria were applied for children and their mothers, we compared the mothers of children with (n = 63) and without ADHD (n = 60) in terms of affective temperament traits, depression before and during the index pregnancy, and some environmental risk factors. The rate of boys were significantly higher among children with ADHD compared to healthy controls. The mothers of children with ADHD had significantly lower education levels, more cigarette consumption during pregnancy, and more depression rates before the pregnancy than those of healthy children. Male gender (p = .002), Hamilton Depression Rating Scale (HDRS) (p = .002), cyclothymic (p = .022), irritable (p = .035) and anxious temperament scores (p = .016) significantly predicted the association between the mothers and their children with ADHD. Our findings might suggest that male child gender, the severity of depression at index pregnancy, higher cyclothymic, irritable, and anxious temperament scores in mothers may constitute as important risk factors for the development of ADHD in their children.Impact statementWhat is already known on this subject? Although the effects of maternal depression on ADHD were extensively investigated, the relationship between affective temperament traits of mothers and ADHD in their children has not been sufficiently examined. To investigate the roles of maternal affective temperament traits and pregnancy-related depression on offspring ADHD would help us to understand the etiopathogenic bases of ADHD.What do the results of this study add? Cyclothymic, irritable and anxious temperaments of mothers were significantly associated with the offspring ADHD after adjusting for the gender, maternal smoking, prepartum and antenatal depression.What are the implications of these findings for clinical practice and/or further research? These findings might demonstrate that some maternal affective temperaments and depression during pregnancy are suggestive of an inherited predisposition to ADHD in offsprings. Longitudinal studies are required to demonstrate the relationship between maternal affective temperament features and the development of affective illness in children with ADHD.

Low-moderate prenatal alcohol exposure and offspring attention-deficit hyperactivity disorder (ADHD): systematic review and meta-analysis.

To evaluate the available evidence on the association between low-to-moderate prenatal alcohol exposure (PAE) and the development of attention-deficit hyperactivity disorder (ADHD) symptoms in the offspring. We systematically reviewed and meta-analysed studies reporting an association between low and/or moderate PAE and offspring ADHD symptoms (attention and/or hyperactivity). Systematic searches were performed in EMBASE, Pubmed, Medline, and PsycINFO and reviewed from selected references. Random effects modelling was conducted to pool adjusted odds ratios (OR) in different alcohol consumption levels (≤ 20g/week, ≤ 50g/week, and ≤ 70g/week). Stratified analysis by sex per alcohol level was conducted to investigate the difference on OR and the magnitude between-study heterogeneity. Ten studies were included in the systematic review and six in the meta-analysis. Eight studies found no association and two studies suggested an apparent protective effect of low PAE in hyperactivity/inattention symptoms in boys. These results were confirmed by the meta-analysis showing no association between ≤ 20g/week [OR 1.01 (0.68-1.49)], ≤ 50g/week [OR 0.94 (0.85-1.03)] and ≤ 70g/week [OR 0.94 (0.86-1.02)] and ADHD symptoms, with no evidence of publication bias. Stratified analysis by sex for a PAE ≤ 50g/week exposed less risk of ADHD symptoms in boys compared to girls [OR 0.89 (0.83-0.96)]. We found no increased risk of ADHD symptoms in offspring born to mothers who drank alcohol up to 70g/week.

Neurosteroid replacement therapy using the allopregnanolone-analogue ganaxolone following preterm birth in male guinea pigs.

Children born preterm, especially boys, are at increased risk of developing attention deficit hyperactivity disorder (ADHD) and learning difficulties. We propose that neurosteroid-replacement therapy with ganaxolone (GNX) following preterm birth may mitigate preterm-associated neurodevelopmental impairment. Time-mated sows were delivered preterm (d62) or at term (d69). Male preterm pups were randomized to ganaxolone (Prem-GNX; 2.5 mg/kg subcutaneously twice daily until term equivalence), or preterm control (Prem-CON). Surviving male juvenile pups underwent behavioural testing at d25-corrected postnatal age (CPNA). Brain tissue was collected at CPNA28 and mature myelinating oligodendrocytes of the hippocampus and subcortical white matter were quantified by immunostaining of myelin basic protein (MBP). Ganaxolone treatment returned the hyperactive behavioural phenotype of preterm-born juvenile males to a term-born phenotype. Deficits in MBP immunostaining of the preterm hippocampus and subcortical white matter were also ameliorated in animals receiving ganaxolone. However, during the treatment period weight gain was poor, and pups were sedated, ultimately increasing the neonatal mortality rate. Ganaxolone improved neurobehavioural outcomes in males suggesting that neonatal treatment may be an option for reducing preterm-associated neurodevelopmental impairment. However, dosing studies are required to reduce the burden of unwanted side effects.

Maternal alcohol use during pregnancy and offspring attention-deficit hyperactivity disorder (ADHD): a prospective sibling control study.

Maternal alcohol use during pregnancy has repeatedly been associated with development of attention-deficit hyperactivity disorder (ADHD) in the offspring. It is, however not known whether this reflects a direct casual intra-uterine effect or a non-causal relationship due to confounding. We used three different approaches to control for measured and unmeasured confounding: statistical adjustment for covariates, negative control comparison against maternal pre-pregnancy alcohol use, and comparison among differentially exposed siblings. The sample comprised 114 247 children (34 283 siblings) from 94 907 mothers, recruited to the Norwegian Mother and Child Birth Cohort Study between 1999 and 2008. Self-reported measurements of alcohol use were obtained in week 30 during the pregnancy. Mothers rated offspring ADHD symptoms at 5 years on two measures. Clinical ADHD diagnoses were obtained from the Norwegian Patient Registry. We found an overall positive association between maternal alcohol use during pregnancy and offspring ADHD symptoms, which was only marginally attenuated after inclusion of measured covariates. Both the negative control and the sibling comparison analysis further attenuated the estimated association, but it remained greater than zero [β = 0.017, 95% confidence interval (CI) = 0.005-0.030). No association was found between maternal alcohol use during pregnancy and offspring ADHD diagnosis. For offspring ADHD symptoms we found a weak, but possibly causal association with maternal alcohol use during pregnancy, but no such effect was observed for clinical ADHD diagnosis.

What's new in atopic eczema? An analysis of systematic reviews published in 2014. Part 1. Epidemiology, risk factors and outcomes.

This review summarizes key findings from nine systematic reviews on atopic eczema (AE) published or first indexed in 2014. It focuses on epidemiology, disease processes and methodological issues. There is reasonable evidence to conclude that high birth weight (>4000g) is a risk factor for the development of AE. A lower socioeconomic position is associated with lower prevalence of AE. The effect of exposure to traffic-related air pollution in childhood on the development of AE is uncertain. CD14 polymorphisms do not appear to have an effect in AE. There may be a role for interleukin-18 in AE development. Patients with AE are at decreased risk of brain tumours, but at increased risk of developing attention deficit hyperactivity disorder. Evidence supports the view that normal-appearing skin in AE is in fact structurally abnormal. Lower success rates at inducing remission in AE are associated with increased risk of relapse during long-term follow-up. The Eczema Area Severity Index (EASI) has been agreed as the preferred core instrument to measure clinical signs in future research. There remains a lack of consensus on the definition of an AE flare.

Dopamine D4 receptor ubiquitination.

Ubiquitination is a post-translational modification that targets proteins for degradation but can also regulate other cellular processes such as endocytosis, trafficking and DNA repair. We investigate ubiquitination of the dopamine D4receptor (D4R) which belongs to the superfamily of G protein-coupled receptors (GPCR). Several polymorphic variants of the D4R exist, which differ in the number of 16-amino acid repeats in the third intracellular loop (IC3) of the receptor. The functional role of this polymorphic region is not known but persons with the seven-repeat allele show a predisposition to develop attention deficit hyperactivity disorder (ADHD). We identified a protein, KLHL12, which specifically interacts with this polymorphic region and enhances ubiquitination of the D4R. We have tested the influence of KLHL12 on the ubiquitination of the most common D4R polymorphic variants and found that KLHL12 strongly promotes ubiquitination of the two- and four-repeat variant but has hardly any effect on ubiquitination of the seven-repeat D4R. This suggests that differential ubiquitination of the D4R may have functional implications. Moreover, we were able to demonstrate that KLHL12-mediated D4R ubiquitination does not lead to receptor degradation. Next, we aimed to identify specific residues in the sequence of D4R which undergo ubiquitination and observed that the lysine-less receptor mutant is still ubiquitinated. Subsequently, we have tested the hypothesis whether KLHL12 could promote ubiquitination on non-lysine residues of the D4R. The importance of the cysteine and serine/threonine residues in the ubiquitination process of the receptor was examined and the obtained results confirmed that D4R can be ubiquitinated on non-lysine residues. In this review we summarize our data on D4R ubiquitination and put this in the light of other GPCR ubiquitination studies.

Adult Behavior in Male Mice Exposed to E-Cigarette Nicotine Vapors during Late Prenatal and Early Postnatal Life.

Nicotine exposure has been associated with an increased likelihood of developing attention deficit hyperactivity disorder (ADHD) in offspring of mothers who smoked during pregnancy. The goal of this study was to determine if exposure to E-cigarette nicotine vapors during late prenatal and early postnatal life altered behavior in adult mice.MethodsTimed-pregnant C57BL/6J mice were exposed to 2.4% nicotine in propylene glycol (PG) or 0% nicotine /PG once a day from gestational day 15 until delivery. After delivery, offspring and mothers were exposed to E-cigarette vapors for an additional 14 days from postnatal day 2 through 16. Following their last exposure serum cotinine levels were measured in female juvenile mice. Male mice underwent behavioral testing at 14 weeks of age to assess sensorimotor, affective, and cognitive functional domains.ResultsAdult male mice exposed to 2.4% nicotine/PG E-cigarette vapors had significantly more head dips in the zero maze test and higher levels of rearing activity in the open field test compared to 0% nicotine/PG exposed mice and untreated controls. In the water maze test after reversal training, the 2.4% nicotine/PG mice spent more than 25% of time in the new location whereas the other groups did not.ConclusionAdult male mice exhibited increased levels of activity in the zero maze and open field tests when exposed to E-cigarette vapor containing nicotine during late prenatal and early postnatal life. These findings indicate that nicotine exposure from E-cigarettes may cause persistent behavioral changes when exposure occurs during a period of rapid brain growth.

Multiple epigenetic factors predict the attention deficit/hyperactivity disorder among the Chinese Han children

Attention deficit/hyperactivity disorder (ADHD) is one of the most common psychiatric disorders of childhood. Despite its prevalence, the critical factors involved in its development remain to be identified. It was recently suggested that epigenetic mechanisms probably contribute to the etiology of ADHD. The present study was designed to examine the associations of epigenetic markers with ADHD among Chinese Han children, aiming to establish the prediction model for this syndrome from the epigenetic perspective. We conducted a pair-matching case–control study, and the ADHD children were systematically evaluated via structured diagnostic interviews, including caregiver interviews, based on the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, revised criteria (DSM-IV-R). The expression levels of risk genes DAT1, DRD4, DRD5, as well as their promoter methylation, were determined respectively, followed by the expression profiles of histone-modifying genes p300, MYST4, HDAC1, MeCP2. The multivariate logistic regressions were performed to establish ADHD prediction models. All of the seven genes tested were identified as risk factors for ADHD. The methylation of one critical CpG site located upstream of DRD4 was shown to affect its transcription, suggesting a role in ADHD's development. Aberrant DNA methylation and histone acetylation were indicated in ADHD patients. In addition, a prediction model was established using the combination of p300, MYST4 and HDAC1, with the accuracy of 0.9338. This is, to our knowledge, the first study to clearly demonstrate the associations between epigenetic markers and ADHD, shedding light on the preliminary diagnosis and etiological studies of this widespread disorder.