Background
Heavy prenatal alcohol exposure (AE) results in a broad array of neurobehavioral deficits. Recent research has focused on identification of a neurobehavioral profile or profiles that will ...improve the identification of children affected by AE. This study aimed to build on our preliminary neurobehavioral profile to improve classification accuracy and test the specificity of the resulting profile in an alternate clinical group.
Methods
A standardized neuropsychological test battery was administered to 3 groups of children: subjects with AE (n = 209), typically developing controls (CON, n = 185), and subjects with attention‐deficit/hyperactivity disorder (ADHD, n = 74). We assessed a large sample from 6 sites in the United States and South Africa, using standardized methodology. Data were analyzed using 3 latent profile analyses including (i) subjects with fetal alcohol syndrome (FAS) and controls, (ii) subjects with AE without FAS and controls, and (iii) subjects with AE (with or without FAS) and subjects with ADHD.
Results
Classification accuracy was moderate but significant across the 3 analyses. In analysis 1, overall classification accuracy was 76.1% (77.2% FAS, 75.7% CON). In the second analysis, overall classification accuracy was 71.5% (70.1% AE/non‐FAS, 72.4% CON). In the third analysis, overall classification accuracy was 73.9% (59.8% AE, 75.7% ADHD). Subjects that were misclassified were examined for systematic differences from those that were correctly classified.
Conclusions
The results of this study indicate that the neuropsychological effects of AE are clinically meaningful and can be used to accurately distinguish alcohol‐affected children from both typically developing children and children with ADHD. Further, in combination with other recent studies, these data suggest that approximately 70% of children with heavy prenatal alcohol exposure are neurobehaviorally affected, while the remaining 30% are spared these often‐devastating consequences, at least those in the domains under study. Refining the neurobehavioral profile will allow improved identification and treatment development for children affected by prenatal alcohol exposure.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Summary
Adolescents with attention‐deficit/hyperactivity disorder (ADHD) often experience greater sleep difficulties compared to those without. However, findings are mixed, and other mental health ...conditions are often overlooked. This study aimed to examine the relationship between sleep problems, ADHD, and other mental health conditions in a sample of adolescents. Data from 373 adolescents aged 10–19 years was used as part of the wider ‘Healthy Brain Network’ study, which targets children and adolescents experiencing mental health and neurodevelopmental difficulties. Mental health conditions were assessed via a comprehensive assessment. Sleep was measured by self‐ and parent‐report, as well as via up to a month of actigraphy data. Actigraphy data were analysed using mixed‐methods modelling, while subjective sleep data were analysed using multiple regression. Subjectively‐reported sleep was generally worse in adolescents who had ADHD and other mental health conditions compared to those with ADHD but no other conditions. There were no associations between ADHD status and objective sleep measures or self‐reported measures, but a significant association was found between ADHD status and parent‐reported sleep difficulties, even when accounting for other conditions. Parent‐reported sleep problems were associated not only with ADHD, but also with anxiety, depression, and externalising disorders. The strength of association between ADHD and sleep problems is potentially not as strong as previously thought when considering the role of other mental health conditions. Clinicians should consider the role of other mental health conditions when sleep problems are present, and vice versa. The study also highlights the importance of comprehensive, multi‐informant assessment of mental health conditions, including sleep.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Low socioeconomic status (SES) is associated with greater risk for symptoms of attention‐deficit/hyperactivity disorder (ADHD). One mechanism through which SES may confer risk for ADHD is by ...influencing brain structure. Alterations to cortical thickness, surface area and subcortical volume have been associated with low SES and with the presence of ADHD across multiple studies. The current study examined whether cortical thickness, surface area or subcortical volume mediate the associations between SES and ADHD in youth 3–21 years old (N = 874) from the Pediatric Imaging, Neurocognition and Genetics Study. Freesurfer was used to estimate cortical thickness, surface area and subcortical volume from structural magnetic resonance imaging. Parents reported on demographics, family SES, ADHD diagnoses and the presence of child attention problems. Statistical mediation was assessed using a bootstrap resampling procedure. Controlling for parental ADHD, child age, gender, birth weight and scanner, children in low SES families were more likely to be in the ADHD group. Consistent with previous reports in this sample, low SES was associated with reduced surface area across the frontal lobe and reduced subcortical volume in the amygdala, cerebellum, hippocampus and basal ganglia. Of these regions, a significant indirect effect of SES on ADHD status through subcortical volume was observed for the left cerebellum (95% confidence interval: 0.004, 0.022), the right cerebellum (95% confidence interval: 0.006, 0.025), and the right caudate (95% confidence interval: 0.002, 0.022). Environmentally mediated changes in the cerebellum and the caudate may be neurodevelopmental mechanisms explaining elevated risk of ADHD in children in low SES families.
The study examined the relationship between family socioeconomic status, alterations in brain structure, and ADHD status in youth. Subcortical volume in the cerebellum and the caudate mediated the relationship between low socioeconomic status and ADHD in children.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Data from the 2003 and 2007 National Survey of Children's Health (NSCH) reflect the increasing prevalence of parent-reported attention-deficit/hyperactivity disorder (ADHD) diagnosis and treatment by ...health care providers. This report updates these prevalence estimates for 2011 and describes temporal trends.
Weighted analyses were conducted with 2011 NSCH data to estimate prevalence of parent-reported ADHD diagnosis, current ADHD, current medication treatment, ADHD severity, and mean age of diagnosis for U.S. children/adolescents aged 4 to 17 years and among demographic subgroups. A history of ADHD diagnosis (2003-2011), as well as current ADHD and medication treatment prevalence (2007-2011), were compared using prevalence ratios and 95% confidence intervals.
In 2011, 11% of children/adolescents aged 4 to 17 years had ever received an ADHD diagnosis (6.4 million children). Among those with a history of ADHD diagnosis, 83% were reported as currently having ADHD (8.8%); 69% of children with current ADHD were taking medication for ADHD (6.1%, 3.5 million children). A parent-reported history of ADHD increased by 42% from 2003 to 2011. Prevalence of a history of ADHD, current ADHD, medicated ADHD, and moderate/severe ADHD increased significantly from 2007 estimates. Prevalence of medicated ADHD increased by 28% from 2007 to 2011.
Approximately 2 million more U.S. children/adolescents aged 4 to 17 years had been diagnosed with ADHD in 2011, compared to 2003. More than two-thirds of those with current ADHD were taking medication for treatment in 2011. This suggests an increasing burden of ADHD on the U.S. health care system. Efforts to further understand ADHD diagnostic and treatment patterns are warranted.
Background
Until now, working memory training has not reached sufficient evidence as effective treatment for ADHD core symptoms in children with ADHD; for young children with ADHD, no studies are ...available. To this end, a triple‐blind, randomized, placebo‐controlled study was designed to assess the efficacy of Cogmed Working Memory Training (CWMT) in young children with ADHD.
Methods
Fifty‐one children (5–7 years) with a DSM‐IV‐TR diagnosis of ADHD (without current psychotropic medication) were randomly assigned to the active (adaptive) or placebo (nonadaptive) training condition for 25 sessions during 5 weeks. The compliance criterion (>20 sessions) was met for 47 children. The primary outcome measure concerned the core behavioural symptoms of ADHD, measured with the ADHD Rating Scale IV (ADHD‐RS). Secondary outcome measures were neurocognitive functioning, daily executive functioning, and global clinical functioning. The influence of the increase in difficulty level (Index‐Improvement) for the treatment group was also analysed. Clinical trial registration information – ‘Working Memory Training in Young ADHD Children’; www.clinicaltrials.gov; NCT00819611.
Results
A significant improvement in favour of the active condition was found on a verbal working memory task (p = .041; adapted Digit Span WISC‐III, backward condition). However, it did not survive correction for multiple testing. No significant treatment effect on any of the primary or other secondary outcome measurements was found. The Index‐Improvement significantly contributed to ADHD‐RS and the Behavior Rating Inventory of Executive Function, both rated by the teacher, but revealed no significant group difference.
Conclusions
This study failed to find robust evidence for benefits of CMWT over the placebo training on behavioural symptoms, neurocognitive, daily executive, and global clinical functioning in young children with ADHD.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Teachers play an essential role in supporting children with attention‐deficit hyperactivity disorder (ADHD) and are often responsible for implementing the classroom‐based interventions designed to ...bolster the academic and behavioral success, and the socio‐emotional development of children with ADHD in schools. Unfortunately, several studies suggest teachers are inadequately prepared to take on this role. Evidence suggests there are widespread gaps in teacher knowledge about the meaning of a diagnosis of ADHD and evidence‐based interventions used to support children with ADHD in schools. The main purpose of this study is to examine the effectiveness of a virtual, self‐paced professional development seminar for preservice teachers. The webinar will be aimed at improving preservice teacher knowledge about the diagnosis of ADHD, characteristics of students with ADHD in the classroom, and evidence‐based interventions that can be used to alleviate academic and behavioral problems often experienced by students with ADHD. The webinar also aims to increase preservice teachers' self‐efficacy as it relates to supporting children with ADHD.
Practitioner points
Preservice teachers who participated in the webinar showed improvement in preservice teacher knowledge of ADHD identification and intervention.
Preservice teachers' self‐efficacy significantly increased following participation in the webinar.
A social validity measure indicated the webinar was an acceptable and useful intervention to improve knowledge about ADHD.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
There is evidence to suggest that the broad discrepancy in the ratio of males to females with diagnosed ADHD is due, at least in part, to lack of recognition and/or referral bias in females. Studies ...suggest that females with ADHD present with differences in their profile of symptoms, comorbidity and associated functioning compared with males. This consensus aims to provide a better understanding of females with ADHD in order to improve recognition and referral. Comprehensive assessment and appropriate treatment is hoped to enhance longer-term clinical outcomes and patient wellbeing for females with ADHD.
The United Kingdom ADHD Partnership hosted a meeting of experts to discuss symptom presentation, triggers for referral, assessment, treatment and multi-agency liaison for females with ADHD across the lifespan.
A consensus was reached offering practical guidance to support medical and mental health practitioners working with females with ADHD. The potential challenges of working with this patient group were identified, as well as specific barriers that may hinder recognition. These included symptomatic differences, gender biases, comorbidities and the compensatory strategies that may mask or overshadow underlying symptoms of ADHD. Furthermore, we determined the broader needs of these patients and considered how multi-agency liaison may provide the support to meet them.
This practical approach based upon expert consensus will inform effective identification, treatment and support of girls and women with ADHD. It is important to move away from the prevalent perspective that ADHD is a behavioural disorder and attend to the more subtle and/or internalised presentation that is common in females. It is essential to adopt a lifespan model of care to support the complex transitions experienced by females that occur in parallel to change in clinical presentation and social circumstances. Treatment with pharmacological and psychological interventions is expected to have a positive impact leading to increased productivity, decreased resource utilization and most importantly, improved long-term outcomes for girls and women.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in childhood. The psychostimulant methylphenidate is the most frequently used medication to treat ...it. Several studies have investigated the benefits of methylphenidate, showing possible favourable effects on ADHD symptoms, but the true magnitude of the effect is unknown. Concerning adverse events associated with the treatment, our systematic review of randomised clinical trials (RCTs) demonstrated no increase in serious adverse events, but a high proportion of participants suffered a range of non‐serious adverse events.
Objectives
To assess the adverse events associated with methylphenidate treatment for children and adolescents with ADHD in non‐randomised studies.
Search methods
In January 2016, we searched CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, 12 other databases and two trials registers. We also checked reference lists and contacted authors and pharmaceutical companies to identify additional studies.
Selection criteria
We included non‐randomised study designs. These comprised comparative and non‐comparative cohort studies, patient‐control studies, patient reports/series and cross‐sectional studies of methylphenidate administered at any dosage or formulation. We also included methylphenidate groups from RCTs assessing methylphenidate versus other interventions for ADHD as well as data from follow‐up periods in RCTs. Participants had to have an ADHD diagnosis (from the 3rd to the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders or the 9th or 10th edition of theInternational Classification of Diseases, with or without comorbid diagnoses. We required that at least 75% of participants had a normal intellectual capacity (intelligence quotient of more than 70 points) and were aged below 20 years. We excluded studies that used another ADHD drug as a co‐intervention.
Data collection and analysis
Fourteen review authors selected studies independently. Two review authors assessed risk of bias independently using the ROBINS‐I tool for assessing risk of bias in non‐randomised studies of interventions. All review authors extracted data. We defined serious adverse events according to the International Committee of Harmonization as any lethal, life‐threatening or life‐changing event. We considered all other adverse events to be non‐serious adverse events and conducted meta‐analyses of data from comparative studies. We calculated meta‐analytic estimates of prevalence from non‐comparative cohorts studies and synthesised data from patient reports/series qualitatively. We investigated heterogeneity by conducting subgroup analyses, and we also conducted sensitivity analyses.
Main results
We included a total of 260 studies: 7 comparative cohort studies, 6 of which compared 968 patients who were exposed to methylphenidate to 166 controls, and 1 which assessed 1224 patients that were exposed or not exposed to methylphenidate during different time periods; 4 patient‐control studies (53,192 exposed to methylphenidate and 19,906 controls); 177 non‐comparative cohort studies (2,207,751 participants); 2 cross‐sectional studies (96 participants) and 70 patient reports/series (206 participants). Participants' ages ranged from 3 years to 20 years. Risk of bias in the included comparative studies ranged from moderate to critical, with most studies showing critical risk of bias. We evaluated all non‐comparative studies at critical risk of bias. The GRADE quality rating of the evidence was very low.
Primary outcomes
In the comparative studies, methylphenidate increased the risk ratio (RR) of serious adverse events (RR 1.36, 95% confidence interval (CI) 1.17 to 1.57; 2 studies, 72,005 participants); any psychotic disorder (RR 1.36, 95% CI 1.17 to 1.57; 1 study, 71,771 participants); and arrhythmia (RR 1.61, 95% CI 1.48 to 1.74; 1 study, 1224 participants) compared to no intervention.
In the non‐comparative cohort studies, the proportion of participants on methylphenidate experiencing any serious adverse event was 1.20% (95% CI 0.70% to 2.00%; 50 studies, 162,422 participants). Withdrawal from methylphenidate due to any serious adverse events occurred in 1.20% (95% CI 0.60% to 2.30%; 7 studies, 1173 participants) and adverse events of unknown severity led to withdrawal in 7.30% of participants (95% CI 5.30% to 10.0%; 22 studies, 3708 participants).
Secondary outcomes
In the comparative studies, methylphenidate, compared to no intervention, increased the RR of insomnia and sleep problems (RR 2.58, 95% CI 1.24 to 5.34; 3 studies, 425 participants) and decreased appetite (RR 15.06, 95% CI 2.12 to 106.83; 1 study, 335 participants).
With non‐comparative cohort studies, the proportion of participants on methylphenidate with any non‐serious adverse events was 51.2% (95% CI 41.2% to 61.1%; 49 studies, 13,978 participants). These included difficulty falling asleep, 17.9% (95% CI 14.7% to 21.6%; 82 studies, 11,507 participants); headache, 14.4% (95% CI 11.3% to 18.3%; 90 studies, 13,469 participants); abdominal pain, 10.7% (95% CI 8.60% to 13.3%; 79 studies, 11,750 participants); and decreased appetite, 31.1% (95% CI 26.5% to 36.2%; 84 studies, 11,594 participants). Withdrawal of methylphenidate due to non‐serious adverse events occurred in 6.20% (95% CI 4.80% to 7.90%; 37 studies, 7142 participants), and 16.2% were withdrawn for unknown reasons (95% CI 13.0% to 19.9%; 57 studies, 8340 participants).
Authors' conclusions
Our findings suggest that methylphenidate may be associated with a number of serious adverse events as well as a large number of non‐serious adverse events in children and adolescents, which often lead to withdrawal of methylphenidate. Our certainty in the evidence is very low, and accordingly, it is not possible to accurately estimate the actual risk of adverse events. It might be higher than reported here.
Given the possible association between methylphenidate and the adverse events identified, it may be important to identify people who are most susceptible to adverse events. To do this we must undertake large‐scale, high‐quality RCTs, along with studies aimed at identifying responders and non‐responders.
•Exposure to metals/elements may be a risk factor for neurodevelopmental disorders.•We examined gestational levels of metals/elements and ADHD and autism in children.•Several metals and elements ...appeared to increase ADHD or autism risk.•Population levels of these chemicals may adversely affect neurodevelopment.
Prenatal exposure to toxic metals or variations in maternal levels of essential elements during pregnancy may be a risk factor for neurodevelopmental disorders such as attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in offspring.
We investigated whether maternal levels of toxic metals and essential elements measured in mid-pregnancy, individually and as mixtures, were associated with childhood diagnosis of ADHD or ASD.
This study is based on the Norwegian Mother, Father and Child Cohort Study and included 705 ADHD cases, 397 ASD cases and 1034 controls. Cases were identified through linkage with the Norwegian Patient Registry. Maternal concentrations of 11 metals/elements were measured in blood at week 17 of gestation; cadmium; cesium; cobalt; copper; lead; magnesium; manganese; selenium; zinc; total arsenic; and total mercury. Multivariable adjusted logistic regression models were used to examine associations between quartile levels of individual metals/elements and outcomes. We also investigated non-linear associations using restricted cubic spline models. The joint effects of the metal/element mixture on ASD and ADHD diagnoses were estimated using a quantile-based g-computation approach.
For ASD, we identified positive associations (increased risks) in the second quartile of arsenic OR = 1.77 (CI: 1.26, 2.49) and the fourth quartiles of cadmium and manganese OR = 1.57 (CI: 1.07 2.31); OR = 1.84 (CI: 1.30, 2.59), respectively. In addition, there were negative associations between cesium, copper, mercury, and zinc and ASD. For ADHD, we found increased risk in the fourth quartiles of cadmium and magnesium OR = 1.59 (CI: 1.15, 2.18); OR = 1.42 (CI: 1.06, 1.91). There were also some negative associations, among others with mercury. In addition, we identified non-linear associations between ASD and arsenic, mercury, magnesium, and lead, and between ADHD and arsenic, copper, manganese, and mercury. There were no significant findings in the mixture approach analyses.
Results from the present study show several associations between levels of metals and elements during gestation and ASD and ADHD in children. The most notable ones involved arsenic, cadmium, copper, mercury, manganese, magnesium, and lead. Our results suggest that even population levels of these compounds may have negative impacts on neurodevelopment. As we observed mainly similarities among the metals’ and elements’ impact on ASD and ADHD, it could be that the two disorders share some neurochemical and neurodevelopmental pathways. The results warrant further investigation and replication, as well as studies of combined effects of metals/elements and mechanistic underpinnings.
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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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