Attention‐deficit/hyperactivity disorder (ADHD) is characterized by attention deficit, hyperactivity, impulsivity, and learning and memory impairment. Although the pathogenesis of learning and ...memory impairment is still unknown, some studies have suggested an association with hippocampus dysfunction. We aimed to explore the role of miRNAs in the learning and memory impairments observed in ADHD. Differentially expressed hippocampal micro‐ribonucleic acids (miRNAs) in spontaneously hypertensive rats (SHRs) and Wistar‐Kyoto rats (WKYs) were detected on an Illumina HiSeq. 2000 genome analyzer. A total of 25 differentially expressed miRNAs (fold‐change ≥ 2 and
P‐value < 0.05) were identified. The target genes of these differentially expressed miRNAs were predicted using online tools (TargetScan and miRDB). Gene ontology and pathway analysis of the predicted target genes were carried out to assess their putative biological functions. Meanwhile, quantitative real‐time PCR was used to validate the HiSeq results, revealing that three miRNAs (miR‐1‐b, miR‐741‐3p, and miR‐206‐3p) were upregulated and four (miR‐182, miR‐471‐5p, miR‐183‐5p, and miR‐211‐5p) were downregulated in the SHR group compared with the WKY group. In addition, we confirmed that Dyrk1a is regulated by miR‐211‐5p. These results help us understand the contribution of miRNAs in the hippocampus to ADHD and provide new insights into the pathogenesis of this condition.
1.
The differentially microRNAs (miRNAs) in hippocampus between attention‐deficit/hyperactivity disorder (ADHD) animal model and the control were screened out.
2.
We confirm that Dyrk1A, a predicted target gene, is regulated by miR‐211‐5p.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
This review focuses on the cognitive neuroscience of Attention Deficit Hyperactivity Disorder (ADHD) based on functional magnetic resonance imaging (fMRI) studies and on recent clinically relevant ...applications such as fMRI-based diagnostic classification or neuromodulation therapies targeting fMRI deficits with neurofeedback (NF) or brain stimulation. Meta-analyses of fMRI studies of executive functions (EFs) show that ADHD patients have cognitive-domain dissociated complex multisystem impairments in several right and left hemispheric dorsal, ventral and medial fronto-cingulo-striato-thalamic and fronto-parieto-cerebellar networks that mediate cognitive control, attention, timing and working memory (WM). There is furthermore emerging evidence for abnormalities in orbital and ventromedial prefrontal and limbic areas that mediate motivation and emotion control. In addition, poor deactivation of the default mode network (DMN) suggests an abnormal interrelationship between hypo-engaged task-positive and poorly "switched off" hyper-engaged task-negative networks, both of which are related to impaired cognition. Translational cognitive neuroscience in ADHD is still in its infancy. Pattern recognition analyses have attempted to provide diagnostic classification of ADHD using fMRI data with respectable classification accuracies of over 80%. Necessary replication studies, however, are still outstanding. Brain stimulation has been tested in heterogeneously designed, small numbered proof of concept studies targeting key frontal functional impairments in ADHD. Transcranial direct current stimulation (tDCS) appears to be promising to improve ADHD symptoms and cognitive functions based on some studies, but larger clinical trials of repeated stimulation with and without cognitive training are needed to test clinical efficacy and potential costs on non-targeted functions. Only three studies have piloted NF of fMRI-based frontal dysfunctions in ADHD using fMRI or near-infrared spectroscopy, with the two larger ones finding some improvements in cognition and symptoms, which, however, were not superior to the active control conditions, suggesting potential placebo effects. Neurotherapeutics seems attractive for ADHD due to their safety and potential longer-term neuroplastic effects, which drugs cannot offer. However, they need to be thoroughly tested for short- and longer-term clinical and cognitive efficacy and their potential for individualized treatment.
Background Children exposed to early-life psychosocial deprivation associated with institutional rearing are at markedly elevated risk of developing attention-deficit/hyperactivity disorder (ADHD). ...Neurodevelopmental mechanisms that explain the high prevalence of ADHD in children exposed to institutionalization are unknown. We examined whether abnormalities in cortical thickness and subcortical volume were mechanisms explaining elevations in ADHD among children raised in institutional settings. Methods Data were drawn from the Bucharest Early Intervention Project, a cohort of children raised from early infancy in institutions in Romania ( n = 58) and age-matched community control subjects ( n = 22). Magnetic resonance imaging data were acquired when children were aged 8 to 10 years, and ADHD symptoms were assessed using the Health and Behavior Questionnaire. Results Children reared in institutions exhibited widespread reductions in cortical thickness across prefrontal, parietal, and temporal regions relative to community control subjects. No group differences were found in the volume of subcortical structures. Reduced thickness across numerous cortical areas was associated with higher levels of ADHD symptoms. Cortical thickness in lateral orbitofrontal cortex, insula, inferior parietal cortex, precuneus, superior temporal cortex, and lingual gyrus mediated the association of institutionalization with inattention and impulsivity; additionally, supramarginal gyrus thickness mediated the association with inattention and fusiform gyrus thickness mediated the association with impulsivity. Conclusions Severe early-life deprivation disrupts cortical development resulting in reduced thickness in regions with atypical function during attention tasks in children with ADHD, including the inferior parietal cortex, precuneus, and superior temporal cortex. These reductions in thickness are a neurodevelopmental mechanism explaining elevated ADHD symptoms in children exposed to institutional rearing.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Attention‐deficit hyperactivity disorder (ADHD) is a common childhood neurobehavioural disorder defined by symptoms of developmentally inappropriate inattention, impulsivity and hyperactivity. As is ...the norm for most psychiatric phenotypes, traditional aetiological studies have focused primarily on the interplay between genetic and environmental factors. It is likely that epigenetic factors, i.e., heritable, but reversible changes to genomic function that are independent of DNA sequence, are also important. It is known that epigenetic processes can be induced following exposure to a range of external factors, and thus provide a mechanism by which the environment can lead to long‐term alterations in phenotype. In this article we hypothesise that epigenetic dysregulation may mediate the association observed between early‐development environmental insults and ADHD. We propose that understanding the epigenetic processes involved in linking specific environmental pathogens to an increased risk for ADHD may offer new possibilities for preventative and therapeutic intervention.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) may be a risk factor for neurodevelopmental deficits and disorders, but evidence is inconsistent.
We investigated whether prenatal ...exposure to PFAS were associated with childhood diagnosis of attention-deficit/hyperactivity disorder (ADHD) or autism spectrum disorder (ASD).
This study was based on the Norwegian Mother, Father and Child Cohort Study and included n = 821 ADHD cases, n = 400 ASD cases and n = 980 controls. Diagnostic cases were identified by linkage with the Norwegian Patient Registry. In addition, we used data from the Medical Birth Registry of Norway. The study included the following PFAS measured in maternal plasma sampled mid-pregnancy: Perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), perfluorohexane sulfonate (PFHxS), perfluoroheptanesulfonic acid (PFHpS), and perfluorooctane sulfonate (PFOS). Relationships between individual PFAS and ADHD or ASD diagnoses were examined using multivariable adjusted logistic regression models. We also tested for possible non-linear exposure-outcome associations. Further, we investigated the PFAS mixture associations with ASD and ADHD diagnoses using a quantile-based g-computation approach.
Odds of ASD was significantly elevated in PFOA quartile 2 OR = 1.71 (95% CI: 1.20, 2.45) compared to quartile 1, and PFOA appeared to have a non-linear, inverted U-shaped dose-response relationship with ASD. PFOA was also associated with increased odds of ADHD, mainly in quartile 2 OR = 1.54 (95% CI: 1.16, 2.04) compared to quartile 1, and displayed a non-linear relationship in the restricted cubic spline model. Several PFAS (PFUnDA, PFDA, and PFOS) were inversely associated with odds of ADHD and/or ASD. Some of the associations were modified by child sex and maternal education. The overall PFAS mixture was inversely associated with ASD OR = 0.76 (95% CI: 0.64, 0.90) as well as the carboxylate mixture OR = 0.79 (95% CI: 0.68, 0.93) and the sulfonate mixture OR = 0.84 (95% CI: 0.73, 0.96).
Prenatal exposure to PFOA was associated with increased risk of ASD and ADHD in children. For some PFAS, as well as their mixtures, there were inverse associations with ASD and/or ADHD. However, the inverse associations reported herein should not be interpreted as protective effects, but rather that there could be some unresolved confounding for these relationships. The epidemiologic literature linking PFAS exposures with neurodevelopmental outcomes is still inconclusive, suggesting the need for more research to elucidate the neurotoxicological potential of PFAS during early development.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Pediatric headaches have been linked to adverse life events or psychological factors in children and their families, with a complex and bidirectional association. Moreover, it is well-known that ...psychological stress can trigger headaches.
We searched three databases for studies focusing on headaches and adverse events or psychological factors in children up to 12 years old or in their caregivers.
We included 28 studies. Child psychological factors, including internal and external symptoms, were commonly associated with all types of headaches. Sleep disturbances showed a positive association with headaches in 3 out of 5 studies. Family conflict and unhappiness were frequently found in children suffering with headaches, while single-parent families and divorce were not associated. Stressful environments and adverse life events, particularly bullying, were also found to be linked with headaches.
Childhood headaches represent an alarm bell for clinicians to investigate and treat psychological or psychiatric disorders in children and their family. Further studies are needed to elucidate the role of early-life adverse events in children and their families.
•Evidences show connections between childhood headache and adverse childhood experiences.•Headache is associated to school-related stress and being bullied.•Family conflict and unhappiness are associated with headache.•Single-parent family and divorce are not connected with headache.•Internalising symptoms were frequently found in children with headache.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In youth, ADHD is more commonly diagnosed in males than females, but higher male-to-female ratios are found in clinical versus population-based samples, suggesting a sex bias in the process of ...receiving a clinical diagnosis of ADHD. This study investigated sex differences in the severity and presentation of ADHD symptoms, conduct problems, and learning problems in males and females with and without clinically diagnosed ADHD. We then investigated whether the predictive associations of these symptom domains on being diagnosed and treated for ADHD differed in males and females. Parents of 19,804 twins (50.64% male) from the Swedish population completed dimensional assessments of ADHD symptoms and co-occurring traits (conduct and learning problems) when children were aged 9 years. Children from this population sample were linked to Patient Register data on clinical ADHD diagnosis and medication prescriptions. At the population level, males had higher scores for all symptom domains (inattention, hyperactivity/impulsivity, conduct, and learning problems) compared to females, but similar severity was seen in clinically diagnosed males and females. Symptom severity for all domains increased the likelihood of receiving an ADHD diagnosis in both males and females. Prediction analyses revealed significant sex-by-symptom interactions on diagnostic and treatment status for hyperactivity/impulsivity and conduct problems. In females, these behaviours were stronger predictors of clinical diagnosis (hyperactivity/impulsivity: OR 1.08, 95% CI 1.01, 1.15; conduct: OR 1.43, 95% CI 1.09, 1.87), and prescription of pharmacological treatment (hyperactivity/impulsivity: OR 1.24, 95% CI 1.02, 1.50; conduct: OR 2.20, 95% CI 1.05, 4.63). Females with ADHD may be more easily missed in the ADHD diagnostic process and less likely to be prescribed medication unless they have prominent externalising problems.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, ODKLJ, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
Objectives
Attention‐deficit/hyperactivity disorder (ADHD) persists into old age, with prevalence rates of 2.8% to 3.3% in adults over 60 years of age. Most diagnostic assessment tools are not ...validated for older adults. The Quantified behavioral Test (QbTest) is an objective assessment for the core symptoms of ADHD and is validated for children and younger adults. We investigated whether the QbTest can be used to differentiate between older adults with ADHD and healthy controls.
Methods
Older adults aged 55 to 79 years with (n = 97) or without (n = 112) ADHD were assessed with the QbTest. They also rated their ADHD symptom severity. QbTest raw scores were compared between groups. Factor scores were computed using factor loadings from a confirmatory factor analysis (CFA). Multilevel regressions were used to determine effects of background characteristics and comorbidity. Logistic regressions were performed to determine whether the QbTest differentiated between patients with ADHD and healthy controls.
Results
The factor structure of the CFA was comparable with that of younger age groups. Older age was associated with higher Inattention score. Parameters comprising the factors Hyperactivity and Inattention, but not Impulsivity, were shown to contribute significantly in differentiating between the groups. The QbTest had a correct classification rate of 70%, which was increased to 91% when combining QbTest scores and self‐reports of ADHD symptom severity.
Conclusions
The QbTest is feasible for older adults, and the factors Hyperactivity and Inattention are valid parameters for the diagnostic assessment of ADHD in older adults, when used in addition to self‐reports.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Attention-deficit hyperactivity disorder (ADHD) is becoming more commonly diagnosed in women, consequently, more women of reproductive age are taking ADHD medication, such as dexamphetamine. However, ...the safety associated with continuing or ceasing dexamphetamine during pregnancy is unclear. This study investigates outcomes associated with the continuation of dexamphetamine during pregnancy compared to those who ceased or were unexposed.
A population-based retrospective cohort of women from Western Australia who had been dispensed dexamphetamine during pregnancy and gave birth between 2003 and 2018. Women had either continued to take dexamphetamine throughout pregnancy (continuers, n = 547) or ceased dexamphetamine before the end of the second trimester (ceasers, n = 297). Additionally, a matched (1:1) comparison group of women who were dispensed an ADHD medication prior to pregnancy but not during pregnancy (unexposed) was included in the study (n = 844). Multivariable generalised linear models were used to compare maternal and neonatal health outcomes.
Compared to continuers, ceasers had greater odds of threatened abortion (OR: 2.28; 95%CI: 1.00, 5.15; p = 0.049). The unexposed had some benefits compared to the continuers, which included lower risk of preeclampsia (OR: 0.58; 95%CI: 0.35, 0.97; p = 0.037), hypertension (OR: 0.32; 95%CI: 0.11, 0.93; p = 0.036), postpartum haemorrhage (OR: 0.57; 95%CI: 0.41, 0.80; p = 0.001), neonatal special care unit admittance (OR: 0.16; 95%CI: 0.12, 0.20; p < 0.001) and fetal distress (OR: 0.73; 95%CI: 0.54, 0.99; p = 0.042).
Continuing dexamphetamine throughout pregnancy was not associated with an increase in adverse neonatal and maternal health outcomes compared to ceasing. Ceasing dexamphetamine during pregnancy was associated with increased odds of threatened abortion compared with continuing dexamphetamine. However, this is something that requires further investigation due to the small sample size, difficulties examining timing, and the inability to examine spontaneous abortions. The unexposed showed some benefits compared to the continuers, suggesting that where possible the cessation of dexamphetamine prior to pregnancy may be advisable.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Fossil fuel combustion by-products, including particulate matter (PM2.5), polycyclic aromatic hydrocarbons (PAH), nitrogen dioxide (NO2) and carbon dioxide (CO2), are a significant threat to ...children's health and equality. Various policies to reduce emissions have been implemented to reduce air pollution and mitigate climate change, with sizeable estimated health and economic benefits. However, only a few adverse outcomes in children have been considered, resulting in an undercounting of the benefits to this vulnerable population.
Our goal was to expand the suite of child health outcomes addressed by programs to assess health and economic benefits, such as the Environmental Protection Agency (EPA) Benefits Mapping and Analysis Program (BenMAP), by identifying concentration-response (C-R) functions for six outcomes related to PM2.5, NO2, PAH, and/or PM10: preterm birth (PTB), low birthweight (LBW), autism, attention deficit hyperactivity disorder, IQ reduction, and the development of childhood asthma.
We conducted a systematic review of the literature published between January 1, 2000 and April 30, 2018 to identify relevant peer-reviewed case-control and cohort studies and meta–analyses. In some cases meta-analyses were available that provided reliable C-R functions and we assessed their consistency with subsequent studies. Otherwise, we reviewed all eligible studies published between our search dates.
For each pollutant and health outcome, we present the characteristics of each selected study. We distinguish between C-R functions for endpoints having a causal or likely relationship (PTB, LBW, autism, asthma development) with the pollutants for incorporation into primary analyses and endpoints having a suggestive causal relationship with the pollutants (IQ reduction, ADHD) for secondary analyses.
We have identified C-R functions for a number of adverse health outcomes in children associated with air pollutants largely from fossil fuel combustion. Their incorporation into expanded assessments of health benefits of clean air and climate mitigation policies will provide an important incentive for preventive action.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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