Background: Recent research has shown that acoustic white noise (80 dB) can improve task performance in people with attention deficits and/or Attention Deficit Hyperactivity Disorder (ADHD). This is attributed to the phenomenon of stochastic resonance in which a certain amount of noise can improve performance in a brain that is not working at its optimum. We compare here the effect of noise exposure with the effect of stimulant medication on cognitive task performance in ADHD. The aim of the present study was to compare the effects of auditory noise exposure with stimulant medication for ADHD children on a cognitive test battery. A group of typically developed children (TDC) took the same tests as a comparison.Methods: Twenty children with ADHD of combined or inattentive subtypes and twenty TDC matched for age and gender performed three different tests  during exposure to white noise (80 dB) and in a silent condition. The ADHD children were tested with and without central stimulant medication.Results: In the spanboard- and the word recall tasks, but not in the 2-back task, white noise exposure led to significant improvements for both non-medicated and medicated ADHD children. No significant effects of medication were found on any of the three tasks.Conclusion: This pilot study shows that exposure to white noise resulted in a task improvement that was larger than the one with stimulant medication thus opening up the possibility of using auditory noise as an alternative, non-pharmacological treatment of cognitive ADHD symptoms. Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common psychiatric disorders worldwide and prevalence estimates range from 3 to 12% . These eStimulant medication, e.g., methylphenidate, can be used to treat behavioral problems in ADHD and can help to improve school performance . MethylpNormally, noise has a detrimental effect on all kinds of cognitive performance but recent research has shown prominent effects of white noise exposure on various cognitive tasks in children with attention deficits  and chilThe aim of the present pilot study was to compare the effects of auditory noise and stimulant medication on cognitive task performance in a group of children diagnosed with ADHD. A group of typically developed children (TDC) took the same tests in noise versus silent condition as a comparison. This is the first time, to our knowledge, that white noise exposure is compared with stimulant medication on a cognitive test battery in a group of children diagnosed with ADHD.In this paper we study the effects of white noise exposure and stimulant medication on a cognitive test battery consisting of three different tasks: (i) a verbal episodic memory task; (ii) a visuo-spatial working memory task; and (iii) a verbal 2-back task. The group of TD children took all three tests in noise vs. silent conditions. Both the verbal- and the visuo-spatial task have shown substantial effects of noise in earlier studies . The verEthical approval was obtained from the Ethical Review Board in Stockholm (EPN 2008/1744 -31). Written consent was obtained from the headmasters of all participating schools and from parents of participating children. All participating children gave oral approval. Prior to the start of the study, parents were sent information forms and were given the possibility to opt their children out of the study at any time without giving reason. For the TDC group headmasters at four schools in the municipality of Skellefteå approached participating children’s parents for approval. The children with an ADHD diagnosis were informed and contacted by the National Association of Attention and the parents that volunteered to participate sent written consent to the research leader.2 = 0.15 -0.39  and presented on a 15′ lap top computer screen. Instructions were given in writing on the screen. Participants sat on a comfortable chair about 70 cm away from the screen. ADHD children and TDC conducted all tasks in either absence or presence of white noise on each occasion. In the noise condition the noise level was set to 80 dB in accordance with findings from earlier studies where noise effects were obtained , 2010 anWord recall; 5 min . Lists oSpanboard; 5 min . Particin-Back task; 5 min . Particigroup (ADHD vs. TDC) and two within subject factors: noise condition (no noise vs. noise) and task . The ANOVA showed a positive main effect of noise . The interaction between task and noise, i.e., noise affected tasks differently, did not reach significance but indicated a trend ; also a trend toward interaction between group and noise was found  indicating a larger noise benefit for ADHD children. The between group factor for overall task performance did not reach significance, however, the TDC group performed tasks marginally superior to the ADHD group .A 2 × 2 × 3 mixed ANOVA was conducted with one between subjects factor: noise (no noise vs. noise), medication (off vs. on medication), and task . This ANOVA showed a strong positive main effect of noise  and no main effect of medication . Further, an interaction between medication and noise, i.e., the benefit of noise was larger than the one of medication , and also an interaction between task and noise was found, noise affected the three tasks differently . The three-way interaction between task, noise, and medication did not reach significance .A second 2 × 2 × 3 ANOVA was conducted, just comprising the ADHD group with three within subjects factors: Post hoc analyses, by using independent samples t-tests task by task, showed noise benefit in the spanboard- and word recall task but not in the 2-back task. In the spanboard task a paired samples t-test showed that performance in terms of successfully recalled dots increased significantly by introduction of noise as compared to no noise in non-medicated ADHD children , as well as in medicated children . A (2 × 2) within subject ANOVA showed a tendency to interaction between noise and medication  in this task .t-test displayed that the TDC superior performance in the spanboard task compared to the ADHD group in the silent condition  disappeared during noise exposure . The medicated children did not fully reach the performance of TDC in no noise condition . There was no significant effect of medication on children with ADHD in no noise condition, the improvement by medication did not reach significance . However, the control group did not differ significantly from the ADHD group in the presence of noise irrespective of medication or not .The control group was not influenced by noise, an independent samples t = (19) = 4.92, p < 0.0005]. In the no noise condition, the non-medicated ADHD group performed worse than the TD group ; however, this difference was eliminated by noise. No effect of medication was found in this task and no effect of noise was found in the ADHD group during medication, or in the control group. Finally we found a significant interaction between noise and medication in this task within the ADHD group  . Table 2 reports performance in raw score in the spanbord- and the word recall tasks for both ADHD- and TDC groups with t-statistics.In the word recall task , a paired samples test showed that noise significantly improved the number of correctly recalled words compared to no noise condition in absence of medication . No interaction between group and noise and no main effect of noise on ADHD was found (p = 0.136). No effect of medication was found. There was a nominal positive effect of noise on the ADHD group but it was far from reaching any significance. However, when looking at the response time we got a significant group difference, as TDC were faster than the ADHD group . The only effect of noise exposure was on the TDC group where noise increased speed on task performance . Noise had little effect on the speed of the ADHD group and the interaction between noise and group indicated a trend . At last, the effect of test occasion was non-significant, but nominally there was a slight improvement for the TDC group in the second test session.In the verbal 2-back task no significant results of either noise or medication was found in either group . The design is quasi experimental and treatments are not blinded or double blinded; in particular, noise is for obvious reasons impossible to blind. We are at this moment running a blinded noise study using stochastic vestibular electric noise (SVS), as this technique allows both participants and experimenters to be blinded. In such a setting, one conducts a proper randomized trial control study to compare the effects of noise with medication while simultaneously controlling the effect of auditory masking. Another obvious limitation to the present study is the small number of participants.In the present pilot study we show that exposure to 80 dB of auditory white background noise can offer a possible non-pharmacological, alternative or complementary treatment to medication when treating inattention in school children.GS planned and designed the experiment, performed the statistical analysis and drafted the manuscript. CB designed the experiment and was responsible for the data collection. PG have been involved in revising the manuscript critically for important intellectual content. All authors read and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Attention Deficit Hyperactivity Disorder (ADHD) and educational achievement are negatively associated in children. Here we test the hypothesis that there is a direct causal effect of ADHD on educational achievement. The causal effect is tested in a genetically sensitive design to exclude the possibility of confounding by a third factor (e.g. genetic pleiotropy) and by comparing educational achievement and secondary school career in children with ADHD who take or do not take methylphenidate. Data on ADHD symptoms, educational achievement and methylphenidate usage were available in a primary school sample of ~10,000 12-year-old twins from the Netherlands Twin Register. A substantial group also had longitudinal data at ages 7–12 years. ADHD symptoms were cross-sectionally and longitudinally, associated with lower educational achievement at age 12. More ADHD symptoms predicted a lower-level future secondary school career at age 14–16. In both the cross-sectional and longitudinal analyses, testing the direct causal effect of ADHD on educational achievement, while controlling for genetic and environmental factors, revealed an association between ADHD symptoms and educational achievement independent of genetic and environmental pleiotropy. These findings were confirmed in MZ twin intra-pair differences models, twins with more ADHD symptoms scored lower on educational achievement than their co-twins. Furthermore, children with ADHD medication, scored significantly higher on the educational achievement test than children with ADHD who did not use medication. Taken together, the results are consistent with a direct causal effect of ADHD on educational achievement.The online version of this article (doi:10.1007/s10519-017-9836-4) contains supplementary material, which is available to authorized users. With a prevalence rate of 3–7% in school-aged children, Attention Deficit Hyperactivity Disorder (ADHD) is relatively common in childhood  twin pairs, differences in ADHD symptoms should be associated with differences in educational achievement because confounding by genes and a shared environment is excluded. Twins from MZ pairs, who show more ADHD symptoms than their co-twins should perform worse in school. A non-significant association would indicate that genetic or environmental factors are driving the association , established around 1987 by the department of Biological Psychology at the VU University Amsterdam, registers approximately 40% of all multiple births in the Netherlands , children with data on educational achievement and on ADHD symptoms at one of the ages , children with only data on educational achievement (N = 885) and children with only data on ADHD symptoms . The total sample included 3549 twin pairs of opposite sex. For the same-sex twin pairs, determination of zygosity status was based on DNA polymorphisms (N = 1244) or on the basis of parental report of items on resemblance in appearance (N = 6150). The parental report establishes zygosity with an accuracy of 93% . From the group of children that never took methylphenidate, children with a T-score above 70  were classified as the ADHD group without medication (N = 534) and the children with a T-score below 56  were classified as controls . T-scores of the ADHD index were based on the total sample and were determined separately for boys and girls Conners .ADHD symptoms were assessed, by mothers and teachers, with the short version of the Conners’ Rating Scales - Revised (CRS-R). The CRS-R included scales measuring Inattention , Hyperactivity  and ADHD index  Conners . The CroADHD symptoms were also rated by mothers with the Attention Problems scale  of the Child Behavior Check List (CBCL). These data were available from age 3 onwards, when the children did not yet attend any form of education  as is the test–retest reliability (r = 0.96)  was based on a full description of the occupations of both parents and coded according to the system from the Statistics Netherlands CBS  or by thThe hypothesis of a direct causal effect of ADHD symptoms on educational achievement was tested in four models, i.e. a cross-sectional combined bivariate twin and within-person regression model, a longitudinal combined bivariate twin and within-person regression model, a MZ twin intra-pair differences model and a between groups differences model. All analyses, except for the second, which was based on longitudinal data, were based on the cross-sectional data.In a series of univariate saturated models, means and variances, by zygosity and gender, were estimated by maximum likelihood in the R .The twin correlations as estimated in saturated models are summarized in Table Fitting of the alternative univariate models, ACE and ADE, confirmed that D was important for ADHD symptoms, while C had an effect on educational achievement. Some gender differences in the genetic models were observed, D had a larger effect on ADHD symptoms in girls at age 7 and in boys at age 12. Heritability of educational achievement did not differ between boys and girls. The percentages of the variance in educational achievement explained by the different variance components are reported in Table S3.The cross-sectional phenotypic correlations between ADHD symptoms (CRS-R) and educational achievement are given in Table p < 0.001). For the inattention subtype the direct path was also significant (p < 0.001), but this was not the case for the hyperactivity subtype of symptoms (p = 0.833). Thus, while correcting for possible confounding by genetic and environmental effects, a direct path between ADHD symptoms and educational achievement was present.Table The longitudinal phenotypic correlations between ADHD symptoms (CRS-R) and educational achievement were also significant, ranging from −0.16 to −0.31 for boys and −0.17 to −0.33 for girls, and were rather comparable to the cross-sectional correlations. This means that ADHD symptoms, measured 5 years earlier, are also associated with educational achievement Table .p = 0.034). The direct path between the inattentive symptoms and educational achievement was significant (p < 0.001), but this was not true for the hyperactive symptoms (p = 0.775).The longitudinal genetic and unique environmental correlations and direct paths, with their 95% confidence intervals, between ADHD symptoms at age 7 and educational achievement at age 12 are displayed in Table The associations between MZ twin intra-pair differences in ADHD symptoms and educational achievement are reported in Table Cohen’s D = −0.71, p < 0.001). Teachers also reported fewer inattention symptoms at age 12 in the ADHD group with medication . There were no differences in hyperactive symptoms at age 12, according to mothers  and teachers . The children in the ADHD group with medication did not differ from the children in the ADHD group without medication  with regard to ADHD symptoms at the age of 3 when, in all likelihood, none of the children were yet using methylphenidate.Table Cohen’s D = 0.56, p < 0.001) on the educational achievement test at age 12 and scored almost the same as the no-ADHD group . For more than half of the children there was information on their secondary education level at ages 14 and/or 16, i.e. no-ADHD group , the ADHD group with medication  and the ADHD group without medication . The probability for attending the highest level of education compared to the lower levels was lower for the children in the ADHD group with medication compared to the no-ADHD group , but higher compared to the ADHD group without medication .The ADHD group with medication outperformed the ADHD group without medication , but the odds were lower in the ADHD group with medication compared to the no-ADHD group .Socioeconomic status was assessed for families of children in the no-ADHD group , the ADHD group with medication  and the ADHD group without medication . The odds for belonging to the highest socioeconomic status level compared to the lower levels were similar for the ADHD group with medication and the ADHD group without medication  is shared by the twins this cannot be a potential explanation for differences between children of a twin pair. A promising other new method that might be able to answer the question what the ‘true’ direct causal effect is of ADHD on educational achievement is Mendelian randomization combined with bivariate twin modeling


Changes in cognitive control and timing have both been implicated in ADHD. Both are involved in building and monitoring expectations about the environment, and altering behavior if those expectations are violated. In ADHD, problems with expectations about future events have high face validity, as this would be associated with behavior that is inappropriate only given a certain context, similar to symptoms of the disorder. In this fMRI study, we used a timing manipulated go/nogo task to assess brain activity related to expectations about what (cognitive control) and when (timing) events would occur. We hypothesized that problems in building expectations about the environment are a more general, trans-diagnostic characteristic of children with hyperactive, impulsive and inattentive symptoms. To address this, we included children with ASD and symptoms of ADHD, in addition to children with ADHD and typically developing children. We found between-group differences in brain activity related to expectations about when (timing), but not what events will occur (cognitive control). Specifically, we found timing-related hypo-activity that was in part unique to children with a primary diagnosis of ADHD  and in part shared by children with similar levels of ADHD symptoms and a primary diagnosis of ASD . Moreover, we found poorer task performance related to timing, but only in children with ASD and symptoms of ADHD. Ultimately, such neurobiological changes in children with ADHD symptoms may relate to a failure to build or monitor expectations and thereby hinder the efficiency of their interaction with the environment.The online version of this article (doi:10.1007/s00787-016-0921-7) contains supplementary material, which is available to authorized users. The observation that the behavior of children with attention-deficit/hyperactivity disorder (ADHD) is inappropriate only in certain contexts has led to suggestions that children with ADHD may be particularly impaired in their ability to build expectations about future events . Indeed Nigg and Casey integrated both these neuropsychological characteristics by proposing that ADHD may be characterized by a deficient ability to build expectations about what (cognitive control) and when (timing) events will happen . This tiCognitive control is defined as ‘the ability to override an inappropriate response in favor of another, appropriate one’  and encoAnalogous to cognitive control, timing is an overarching term that encompasses different aspects of temporal processing. A wide variety of timing-related constructs have been assessed in ADHD  and bothNeuropsychological changes found in children with ADHD are not necessarily specific to the diagnosis  and defiA total of 108 right-handed boys, aged 8–12 years were included in the study: 33 typically developing boys and 75 boys with ADHD symptoms. Children with ADHD symptoms were recruited in two groups: 38 with a primary diagnosis of ADHD  and 37 with a primary autism spectrum disorder (ASD) diagnosis. Typically developing children were recruited through schools in the wider Utrecht area. Children with ADHD symptoms were recruited through schools for special education and the University Medical Center Utrecht (UMCU) outpatient clinic for developmental disorders. Only children using no medication or short-acting psychostimulants  were included; all parents were instructed not to administer medication in the 24 h prior to testing. All children completed a timing manipulated go/nogo paradigm . After sInclusion criteria for typically developing children were: no psychiatric diagnoses on the Diagnostic Interview Schedule for Children, Fourth Edition (DISC-IV), interview   questionnaire . This quWe used a timing manipulated go/nogo task . ParticiThe study was run on a 3.0-T Achieva MRI scanner  using an eight-channel sensitivity-encoding (SENSE) parallel imaging head coil. For anatomical reference, we acquired a whole-brain three-dimensional fast field echo T1-weighted scan . In addition, we acquired whole-brain T2*-weighted echo planar images (EPI) with blood-oxygen level-dependent (BOLD) contrast  oriented in a transverse plane. We collected six dummy scans to allow for T1 equilibration effects.http://www.fil.ion.ucl.ac.uk/spm/software/spm8) as implemented in Matlab 7.12 . To correct for between-scan head motion, we realigned all images to the first volume using rigid body transformations. Next, the anatomical image was co-registered to the first fMRI image using the mutual information criteria method and subsequently normalized to Montreal Neurological Institute (MNI) space using unified segmentation. We then resliced the image at a voxel size of 1.0 × 1.0 × 1.0 mm. Functional images were normalized using the normalization parameters generated in this step, the images were resliced at a voxel size of 3.0 × 3.0 × 3.0 mm. Finally, we spatially smoothed the fMRI images using a Gaussian kernel with a full width at half maximum (FWHM) of 6 mm. In addition, we assessed scan-to-scan movement using ArtRepair [We analyzed FMRI data using SPM8 (r4290) (rtRepair . Scans wexpected-go), baseline standard deviation of response times (SDRTexpected-go); percentage of correct go trials (accuracygo), percentage of correct nogo trials (accuracynogo) and response time benefit (RTbenefit). RTbenefit denotes the difference in MRT between expected and unexpected go trials. This difference is expressed in the number of standard deviations of MRTexpected-go (MRTexpected-go − MRTunexpected-go)/SDRTexpected-go. After testing for normality (Shapiro–Wilk test) and homogeneity of variances (Levene’s test), analysis of covariance (ANCOVA) was conducted with diagnosis as factor. If age or IQ significantly covaried with a measure of task performance, analyses were run, reported and interpreted both with and without the covariate for additional insight. If they did not, the covariates were left out of the final model. Where group differences were found, we performed post hoc testing using Fisher’s least significant difference (LSD). Moreover, we followed up with dimensional analyses by testing for an effect of attention problems  or hyperactivity/impulsivity  on these performance measures, within the combined clinical group and the control group separately. Where no group differences were found, correlational analyses were run on the entire sample. Results were corrected for multiple comparisons using False Discovery Rate (FDR) correction on the separate ANCOVA results (per task performance measure) using the Benjamini-Hoghberg method [We tested for an effect of diagnosis on five measures of task performance: baseline mean response times . Main effects of expectancy and inhibition were analyzed in typically developing children using a single-factor analysis of variance (ANOVA). For all ROIs, we performed a two-factor repeated measures ANOVA using activity related to the four different conditions of interest separately to test for two- and three-way interactions between group status, expectancy and inhibition. To test for group differences in brain activity we conducted an ANCOVA per ROI with diagnosis as factor. Where age and IQ significantly covaried with activity in an ROI, analyses were run, reported and interpreted both with and without the covariate for- additional insight. If not, the covariates were left out of the final model. Where group differences were found we performed post hoc testing using Fisher’s least significant difference (LSD) to compare the three groups. In a follow-up analysis, nogo accuracy and RTbenefit were included as an additional performance-related covariate. In further follow-up analyses, we tested for effects of ADHD symptoms  on brain activity (using ANCOVA) within the combined clinical group and control group separately. If group differences were not found, correlational analyses were run on the entire sample. Results were corrected for multiple comparisons using False Discovery Rate (FDR) correction on the separate ANCOVA results (per ROI) using the Benjamini-Hoghberg method [Statistical analyses of fMRI data were performed in a two-level procedure within the framework of the general linear model. First, for each subject, we modeled the blood oxygenation level dependent (BOLD) activation invoked by task cues as conditions of interest, and realignment parameters as potential confounders (condition of no interest). We modeled cue onset of four different cues as conditions of interest: expected go trials, unexpected go trials, expected nogo trials and unexpected nogo trials. Regressors were created by convolving delta functions coding for cue onset with a canonical hemodynamic response function (as implemented in SPM8) for each cueing category separately. The estimated regression coefficients for the different cues were then contrasted, resulting in two first-level contrast images for each subject: go versus nogo trials and expected versus unexpected trials. Data were high-pass filtered using discrete cosine basis functions with a 128-s cut-off. The analysis focused on average activity in a priori specified regions of interests (ROIs). We used regions that are considered part of fronto-striato-cerebellar loops involved in motor control and, more specifically, in response inhibition and temporal processing , 22. ROIg method . In addiANOVA showed group differences on the inattention scale of the SWAN and the hyperactivity/impulsivity scale of the SWAN (see Table expectedgo), standard deviation of response times (SDRTexpectedgo), percentage of correct go trials (Accuracygo) and response time benefit (RTbenefit)  = 13.23, p = 0.001; Accuracygo: H(2) = 8.73, p = 0.13). Post hoc testing showed that compared to typically developing children, both clinical groups had longer response times (high MRTexpectedgo); higher variability of response times (SDRTexpectedgo) and lower go-trial accuracy (Accuracygo). Furthermore, children with combined ASD and ADHD symptoms benefitted less from trials with expected timing than controls and children with ADHD (lower RTbenefit).ANOVA showed between-group differences on mean response times  = 10.65, p = 0.002; left putamen: F = 8.41, p = 0.005; right putamen: F = 7.83, p = 0.007). We found no three-way (inhibition by expectancy by group) interactions for activity in any of the ROIs.Typically developing children showed a main effect of temporal expectancy in all ROIs except cerebellar vermis and right inferior frontal gyrus, . A main effect of stimulus type was found in bilateral supramarginal gyrus, bilateral anterior cingulate, bilateral vermis and right pallidum. We found an inhibition by expectancy interaction for activity in bilateral pallidum and putamen  = 5.07, p = 0.005) and left pallidum  = 5.36, p = 0.007)  had less activation than typically developing children . Notably, in left pallidum, we found a dissociation between the clinical groups, with children with ADHD showing less activation  than both typically developing children  and children with ASD and ADHD symptoms . Because there was an interaction between inhibition and expectancy in pallidum, we also tested for an effect of expectancy in go and nogo conditions separately. The group difference in brain activity related to expectancy, only retained significance for the nogo condition, again with children with ADHD showing less activation  than both typically developing children  and children with ASD and ADHD symptoms .We found between-group differences in brain activation related to temporal expectancy in left STN  = 5.72, RTbenefit) significantly covaried with activity in left pallidum and left putamen . We found that with RTbenefit as covariate in the model, between-group differences in left STN and left pallidum retained significance and an additional between-group difference was found in left putamen  = 5.67, p = 0.005).We found no associations between any of the questionnaire measures and any of the brain activity measures. In a follow-up analysis, we found that task performance (i.e. when events will occur (timing). We found that two brain regions in children with ADHD showed hypo-activity related to the timing of events. Children with ADHD and children with ASD and ADHD symptoms both showed timing-related hypo-activity in the left subthalamic nucleus. However, timing-related hypo-activity in left pallidum was only found in children with a primary diagnosis of ADHD. Children with ASD and ADHD symptoms benefitted less in terms of their response time from trials with expected timing, than typically developing children and children with ADHD. We found no between-group differences in brain activity or task performance related to expectations about what events will occur.We used task-based fMRI to investigate how children with symptoms of ADHD build and monitor expectations about what events will occur (cognitive control) and Nigg and Casey have hypothesized that children with ADHD may show a context-dependent deficit in generating or monitoring predictions . Indeed,We hypothesized that any deficits found would not be specific to children with ADHD, but would be apparent in both groups of children with ADHD symptoms. Indeed, we found subthalamic hypo-activity in children with ASD and ADHD symptoms and in children with ADHD. However, hypo-activity in left putamen was only found in children with a primary diagnosis of ADHD. We did not expect to find such a clear categorical difference in brain activity between two groups with similar levels of ADHD symptoms. Notably, this finding is in line with reasoning that was made explicit in DSM-IV, where it states that, although symptoms of inattention, hyperactivity and impulsivity may appear alike in children with ADHD and children with ASD, they stem from different neuropsychological problems and should thus be approached differentially. In addition, similar hypo-activity in subthalamic nucleus in children with ADHD and in children with ASD and ADHD symptoms could not be explained in a trans-diagnostic way  and was not reflected in task performance. This suggests that the mechanisms underlying subthalamic hypo-activity might differ between children with ASD and children with ADHD. Deficient temporal processing in ASD has been found in several studies e.g. , 36 and We did not find differences in inhibitory performance or brain activity related to the ‘what’ component of expectancy in children with ADHD symptoms . This is unexpected, as several meta-analyses have reported hypo-activity during response inhibition tasks in children with ADHD –17. Our Problems in building and monitoring expectations about future environmental events have high face validity for children with ADHD symptoms, as they would be expected to lead to behavior that is inappropriate only given a certain context, similar to what is seen in the disorder. An example of this contextual deficit is the class room environment, in which simple actions such as moving and talking are allowed only under strict  conditions. If neurobiological changes in children with ADHD symptoms indeed relate to problems with building or monitoring predictive models, this could provide an impulse for behavioral interventions to directly target expectation building or predictability.In this study, we focused on thirteen a priori regions of interest. In the cerebellum, we chose to analyze only the cerebellar vermis, as meta-analytical studies have found this region to be smaller  and lessSupplementary material 1 (DOCX 2124 kb)Below is the link to the electronic supplementary material.


This study systematically reviewed the literature in order to determine the effect of Attention-Deficit Hyperactivity Disorder (ADHD) on injuries and assessed the magnitude of the potential association.A systematic review of the studies examining the association of ADHD and injuries was carried out across multiple databases. Odds ratios and standardized mean differences were pooled. A total of 35 studies were selected for quantitative analysis. The association of ADHD and injuries was confirmed over the meta-analysis of eligible studies. The odds ratio pooled over all comparative studies was 1.96(95% CI: 1.6-2.4) using random effects model. Pooled odds ratio of 2.1 and 2.17 were calculated respectively when cohort and case-control studies or just cohort studies were included. The pooled odds ratio reduced to 1.8(CI:1.45-2.3) when studies on specific injuries were removed. For studies comparing scores of rating scales, the pooled standardized mean difference was 0.61(95% CI: 0.03-1.2).Those with ADHD are nearly two times more likely to be injured. Psychologi-cal factors have always been a matter of interest in the field of injury research. Attention-deficit hyperactivity disorder (ADHD) is a childhood-onset psychiatric disor-der. However, it is also relatively common among adults, with a prevalence reaching up to 5% in the general population. 6Injuries are considered a major public health problem. They are the leading cause of death among young adults in United States and above 28 million injuries occur annually requiring emergency medical care.10 Several studies have also been specifically conducted to show an association between ADHD and various types of injuries in childhood. It has been reported that ADHD may be associated with burns, 11 fractures,13 dental trauma 15 and traffic injuries. 16 ADHD is a treatable and easily detectable condition and if its potential role in injuries is clearly and trustfully determined, international safety promotion plans can largely benefit from the synthesized evidence. The aim of this study was to systematically review the available literature in order to determine the effect of ADHD on injuries and assess the magnitude of the potential association between unintentional or undescribed injuries and ADHD when assuming ADHD as a risk indicator of injuries.Studies have shown that the injuries are associated with ADHD.This study is a systematic review of all published peer reviewed articles in the period from 2000 to 2014 that have examined the association between ADHD and injuries regardless of the age group or the injury mechanisms. Exposure and outcome:With respect to the aim of the study, the exposure was defined as having ADHD diagnosis of any subtype  or to meet accepted criteria for clinical levels of symptoms on validated ADHD rating scales. The average scores on validated ADHD rating scales were considered the exposure of interest. The outcome of interest was being injured through an accidental or undescribed injury mechanism. Various types of injury mechanisms according to the international classification of diseases, such as traffic injuries, burns, falls, occupational injuries etc., were included.Eligibility criteria and selection of studies:The authors planned to include studies with a controlled design (including cohort and case-control studies) that were published in peer-reviewed journals at any time from 2000 to 2014.To ensure minimum methodological standards, only the studies published in peer-reviewed journals were included. Moreover, studies with low reported quality of conduction ,assessed by an expert epidemiologist, were excluded from the study. The main items of interest in assessing the quality of published articles and risks of bias included; valid assessments of the exposure ; valid assessments of the outcome; risk of selection bias; risk of information bias; ability of the study to exclude reverse causality detection between ADHD and injuries; statistical validity and quality of reporting.  We defined the participants enrolled in various studies to have either a diagnosis of ADHD or to meet the accepted criteria for clinical levels of symptoms on validated ADHD rating scales. We also included the studies comparing the participants according to their screening score on clinical levels of symptoms on validated ADHD rating scales even if the participants were not categorized to have ADHD. Studies in which the enrollment depended on the presence of rare comorbid conditions were excluded. Studies specifically conducted to assess the association of ADHD and brain traumatic injuries were excluded. No age, gender and injury mechanism restriction was applied in this review, however, only the studies written in English were enrolled. Articles were initially screened on the basis of titles and abstracts, while the assessment of articles for final inclusion was based on full text papers assessed independently by two of the authors. Disagreements were all resolved through discussion or joint reexamination of the articles.Search Strategy:A broad range of electronic databases were searched. OVID SP, PubMed, Medline, Science Direct and EMBASE data sources were searched using MESH terms and free keywords as following ("Attention Deficit Disorder with Hyperactivity"[Mesh]) AND In free keyword search, the exposure terms were combined with outcome terms using AND operator to search for relevant literature. The exposure terms used included ADHD and all its variants such as hyperactive, diskinetic and attention deficit. The outcome related terms included injuries, accidents, burn*, fall*, traffic injuries; traffic accidents; transport accidents/injuries; fractures; lacerations; drowning; scalds and occupational/work related injuries. The design terms were controlled study; controlled clinical trial; case-control studies; cohort studies, and comparative studies.Data Extraction:Data were extracted by a two of the authors who were a psychology researcher and a psychiatry resident (Abdi & Nazari) and were also trained to do so by the study leaders (Amiri & Sadeghi) who supervised the process and conducted the quality check for the selected full text articles. Statistical AnalysisMeta-analysis was conducted through three different analysis plans. Plan 1 was conducted on all the comparative studies with acceptable quality. In plan 2 however, the cohort studies alone or together with case-control studies that were least likely of leading to biased pooled effect size due to reverse causality potential were analyzed. Odds ratios were pooled as the effect size both in plan 1 and plan 2. Standardized mean differences of ADHD rating scales were pooled as the overall effect size in plan 3 of the meta-analysis using the Galss method to calculate standardized mean. Most studies had defined ADHD as a dichotomous measure of having or lacking ADHD. The effect size of interest for these studies was quantified through the meta-analysis by odds ratios (OR) with 95% confidence intervals (plans 1& 2). Considering the high heterogeneity observed among the studies, the random effects model was applied to do the meta-analysis. Statistical heterogeneity was investigated through I2 statistic quantifying the amount of variation attributable to heterogeneity. I2 is calculated in a formula containing Cochrane’s heterogeneity statistic Q but with some advantages over Q. An I2>75% was considered to indicate high heterogeneity.17 As some studies had compared the mean difference of scores belonging to valid ADHD rating scales between the injured and uninjured subjects, a separate meta-analysis was done for these studies using standardized mean differences (plan 3).A funnel plot was used to evaluate the presence of publication bias plotting study’s log OR as a function of its standard error. The asymmetry of funnel plot was tested assessed using Begg’s test of heterogeneity and graphical assessment. Statistical analysis was done using Stata 11 statistical package. A total of 35 studies were finally selected for quantitative analysis . When inAs a conservative way of analysis through plan 2 of meta-analysis, only the cohort studies (7 studies) or cohort studies together with case-control studies(13 studies) which have assessed ADHD as a dichotomous variable were analyzed . The pooled effect didn’t vary much from the full model yielding a pooled odds ratio of 2.1 and 2.17 respectively when both cohort and case-control studies or only cohort studies were included using random effects model .Descriptions of the included case-control and cohort studies are given in Begg’s test for exploring potential publication bias was not statistically significant with a borderline p-value and slight asymmetry was observed in graphical assessment of the funnel plot .Most of the studies included in full meta-analysis model (30 studies) have investigated the association of ADHD with injuries regardless of the injury type, while others have focused on specific types of injuries such as fractures, burns, traffic injuries, motorcycle traffic injuries and dental injuries. A subgroup meta-analysis was done showing that the pooled odds ratio could be reduced by 1.8(1.45-2.3) when assessing the association of ADHD with injuries regardless of the injury type or injury mechanism.Some studies have assessed the relationship between injuries and scores of ADHD rating scales such as CAARS or other rating scales and have reported the difference in these screening scores between the injury victims and non-injured controls. The mean standardized effect sizes were found to be nearly high (Pooled SMD=0.61) through the meta-analysis , but the validity of model results couldn’t be well accepted due to data limitations such as small number of studies and potential publication bias .To compare the age groups with respect to the potential association of ADHD and injuries, a subgroup meta-analysis was run showing that studies restricted to children had the highest pooled odds ratio equal to 2.04 .18 The hyperactivity part of ADHD although not plausible to have a direct effect on driving risks seems to be of importance in childhood burns. Considering that it is a common risk in some developing countries where children are overcrowded in small living areas and some traditional heaters with a boiling kettle or pot on them are usually set in the center of living room, hyperactivity shows its plausible role to increase the risk of getting burned children with a higher chance of running around frequently. No doubt the situation gets more risky when attention deficit is added to the scenario.21The present systematic review revealed a strong association between ADHD and injuries. Some characteristics of patients with ADHD could reasonably explain such association. First of all, it could be the risk-taking behaviors that are much more prominent in ADHD. Risk-taking, a well-known predictor in road traffic injuries, could easily increase the risks of other types of injuries such as either falls or burns. Psychological explanations for risky behavior among young people have been discussed from various perspectives, including the psychodynamic approach, the cognitive approach, and the character and human motivation approach. Secondly, it is the loss of concentration which seems to have the most prominent role on traffic and occupational as well as other types of injuries. Moreover, it seems quite easy for a talkative driver to lose concentration on driving when he/she finds a co-traveler eager to listen. Actually the three factors as errors, lapses and violations are the points of importance when investigating the risks of driving among ADHD patients. Simulation studies have shown that the driving performance of ADHD patients may be improved regarding these elements after pharmacologic treatment; however, there is not a solid evidence on the efficacy of cognitive, behavioral or educational programs in reducing the driving risks of patients with ADHD. 23 To avoid the reverse causality problem in introducing bias in assessment of the effect of ADHD, we excluded the studies specifically conducted on the association of ADHD and traumatic brain injuries. However, as other studies might also have included brain traumas without a reference to that, we conducted a secondary meta-analysis restricting the studies only to cohort and case control studies at analysis plan 2 in which the direction of association could be interpreted and this confirmed the overall finding of the meta-analysis as in plan 1 conducted on all included studies. The detection of the cause-effect temporality direction is quite straightforward in cohort studies and all the cohort studies in this review supported the evidence on effect of ADHD. In classic case-control studies, the detection of the direction of associations could be biased when the outcome of interest is a disease with long variant latency or incubation period and/or the exposure is a transient hard to retrospectively measure condition. However, for assessing the association of ADHD and injuries, this is of little concern due to the fact that injuries are sudden outcomes without a long latency prior to the event and ADHD is a chronic nearly stable exposure existing from childhood. If the symptoms of ADHD are assessed soon after an injury occurs with reference to the time before the injury incidence, the detection of the direction of ADHD and injury events will not be a problem. Nevertheless, selection bias and information bias are always source of concern in case-control studies.This systematic review was interested in investigating the association of ADHD and injuries and looking for the evidence whether ADHD can affect the occurrence of injuries. The association between ADHD and injuries could be ambi-directional in case of traumatic brain injuries. It has been suggested that traumatic brain injury may also cause ADHD and this should be carefully addressed while investigating the association of ADHD and injuries.26 Regardless of the variety in rating scales used by different studies, the point in such assessment is that these studies just assess the association of the ADHD rating score with injuries rather than association of ADHD and injuries unless a cutoff point is used to dichotomize the score or the patients with higher scores are later assessed for the diagnosis of ADHD through clinical interviews done by a psychiatrist. However, the research question may also be different whether people with higher scores, regardless of their final diagnosis, are at higher risk of injuries or not. The use of a numeric scale in this manner may even affect the statistical power.The way ADHD is assessed is another issue to be discussed. Few of the studies on association of ADHD and injuries were case-control studies which assessed the ADHD status through rating scales such as Conner’s scales.Although not in line with the research question in this study, we found through the methodological assessment of articles that some studies published as case-control studies or stated to be case-control studies had a cross-sectional design. The authors of current review categorized these studies according to the design distinguished through the methodological assessment by an epidemiologist rather than the terminology used by the authors of the original studies.Those with ADHD are nearly two times more likely to be injured. Children, adolescents and adults with ADHD are all at higher risks of various types of mostly unintentional injuries. Clinicians and health care providers who are in contact with people having ADHD should inform them about increased risk of injuries. Health policy makers should consider public management of ADHD in order to decrease risk of injuries at the community. Improving public knowledge on symptoms, consequences, and the management of ADHD is strongly recommended.


Objective: The Positivity and Rules program (PR program), a low-level behavioral teacher program targeting symptoms of attention-deficit/hyperactivity disorder (ADHD), has shown positive effects on teacher-rated ADHD symptoms and social functioning. This study aimed to assess whether program effects could be confirmed by instruments assessing classroom behavior other than teacher-ratings, given teachers’ involvement with the training.Methods: Participants were 114 primary school children (age = 6–13) displaying ADHD symptoms in the classroom, who were randomly assigned to the treatment (n = 58) or control group (n = 65). ADHD symptoms were measured using classroom observations and actigraphy, and peer acceptance was measured using peer ratings. Intention-to-treat multilevel analyses were conducted to assess program effects.Results: No beneficial program effects were found for any of the measures.Conclusion: The earlier beneficial program effects on both ADHD symptoms and social functioning reported by teachers, may be explained by a change in the perception of teachers rather than changes in the child’s behavior. Other methodological explanations are also discussed, such as differences between instruments in the sensitivity to program-related changes. The current study underlines the importance of using different measures of classroom behavior to study program effects.ClinicalTrials.gov registration number: NCT02518711 Attention-deficit/hyperactivity disorder (ADHD) is characterized by age-inappropriate, pervasive and persistent hyperactivity/impulsivity and inattention, resulting in a daily impairment in multiple settings . ApproxiFor the management of ADHD symptoms in the classroom, behavioral programs are generally preferred by teachers over medication . HoweverThe current study examined whether the teacher observed beneficial effects of the PR program on ADHD symptoms and social functioning could be confirmed by other measures of classroom functioning, as teachers may have been biased due to treatment involvement . Meta-anClassroom observations are frequently used to assess disruptive classroom behavior and are regarded as the gold standard in research into classroom behavior . A majorAnother example of an instrument that can be used to assess ADHD symptoms in the classroom is actigraphy. Actigraphs are wrist-worn monitors registering movement-induced accelerations used to assess daytime hyperactivity, sleep, and circadian activity rhythms, and are free from many biases associated with classroom observations or questionnaires, such as social desirability, child reactivity or halo effects . ActigraPeer ratings might be used to assess program effects on classroom social functioning. While teachers using the PR program have not observed effects on peer problems, improvements have been found on teacher-rated social functioning . Given tThe current study was designed to assess whether earlier effects of the PR program on teacher-rated ADHD symptoms and social functioning could be confirmed by other classroom measures, using actigraphy, classroom observations, and peer-ratings. Based on the teacher-reported improvements on ADHD symptoms , a reducn = 58 from 44 classrooms of 30 schools; 91% male), or the control group  that was allowed to receive care as usual.The study sample comprised 114 primary school children (6–13 years) displaying high levels of ADHD symptoms in the classroom . ParticiFigure 1 displays the flowchart of participants.Inclusion criteria were: (a) high levels of ADHD symptoms (>90th percentile) as reported by the child’s teacher on the Hyperactivity/Impulsivity and/or Inattention scale of the Disruptive Behavior Disorders Rating Scale DBDRS; , and (b)The PR program consists of a behavioral teacher program addressing ADHD symptoms in the classroom through a teacher manual without additional expert training see also . The 18-Actigraphy and classroom observations were used to assess the effects of the PR program on ADHD symptoms in the classroom, while peer ratings were used to assess whether peer acceptance improved after use of the program.Hyperactivity at school was measured by small (37 mm × 29 mm × 10 mm), light-weight (16 g) actigraphs , detecting the highest movement-induced accelerations (0.5–7.0 Hz) during 15-s intervals, generating a transient voltage signal proportionate to the acceleration rate . Good inThe actigraphs were worn on the non-dominant hand during seven consecutive days, of which the five school days were used to assess hyperactivity at school. As school hours are similar across schools in the Netherlands, the selected hours for data-analysis were kept similar for every child: 9:00–15:00 on Monday, Tuesday, Thursday and Friday, and 9:00–12:00 on Wednesday. For Grade 1 and 2 , data from Friday afternoon (12:00–15:00) were excluded because at most schools, school ends at 12.00 on Fridays in these grades. Data for days on which scores were missing  or special non-academic events  were also excluded. This resulted in 25.5% missing data, which is similar to other studies using actigraphy . AverageChildren were observed in the classroom during structured academic lessons  using the COC . The COCin vivo. The COC has been shown to discriminate children with ADHD from typically developing peers  and validity of peer ratings as measure of social acceptance is adequate when compared to teacher-rated social acceptance  to 5  was administered at the end of each week to acquire an indication of implementation fidelity. This checklist contains 13 items on a 3-point Likert scale, requiring teachers in the treatment group to indicate whether and to what extent they used each of the program elements during that week . The average item score was calculated based on all weekly checklists. Internal consistency for this measure was acceptable (Cronbach’s α = 0.67).o; week 0), 6 weeks after starting the PR program (T1), and after 18 weeks at the end of the program (T2). Financial compensation was given to all participating teachers . This study was carried out in accordance with the recommendations of the medical ethical committee of the Vrije Universiteit Amsterdam with written informed consent from all subjects. All subjects gave written informed consent in accordance with the Declaration of Helsinki. The protocol was approved by the medical ethical committee of the Vrije Universiteit Amsterdam (reference number 2011/196).This study was conducted in the Netherlands between September 2011 and July 2014. Teachers and parents were recruited through educational consultant associations, the national parent association for children with developmental problems, and the study’s website. Teachers and parents showing interest in participating in the study received an information letter explaining the research aim and responsibilities of all parties involved. In case teachers were interested in participating, they enlisted one or two children displaying ADHD symptoms in their classroom. Written informed consent was obtained from all parents, teachers, and children older than 11 years. Children were screened for eligibility by the first author BV. ML, not in contact with any of the children, was responsible for the subsequent computer-generated randomization  to allocate children to the treatment or control group. Although teachers in the treatment group used the universal program in the entire classroom, the effectiveness of the PR program was only investigated for the participating children displaying ADHD symptoms. Dependent variables were measured at baseline . Assuming a moderate effect size of 0.50, a sample size of 116 was calculated to be sufficient for a repeated-measures multilevel analysis with a maximum of two participants per classroom, using an alpha of 0.05, a power of 80% and a intraclass correlation of 0.10.0, T1, and T2, respectively). The interaction between group and time was used to evaluate whether behavior of children in the treatment group improved more over time compared to children in the control group. Analyses controlled for baseline levels of the dependent variables and for gender differences , inserting gender as fixed factor (with boys as reference group). The Likelihood Ratio Test and Akaike’s Information Criteria (AIC) were used to determine whether random time slopes at student-, classroom- or school-level needed to be included for providing better model fit . However, children in the treatment group were more likely to be boys , and received higher ratings of hyperactive/impulsive behavior on the TTI . All subsequent analyses controlled for gender differences and controlled for baseline levels of the dependent variable (see below).Sample characteristics of the treatment and control group are displayed in M = 78% of the time; SD = 23%). The helpdesk was consulted by 30% of the teachers and mainly received questions regarding the use of the time-out and the reward system for the entire classroom or individual children. Satisfaction rate was high: 98% of the teachers intended to use the entire program or most important program elements in the future .Most teachers (81%) reported adequate or good implementation of the universal reward system during the entire program, with the remaining 19% reporting inadequate implementation in 1 or 2 weeks during the course of the entire 18 weeks. Teachers reported to have used all elements of the DRC adequately most of the 18 weeks . Hyperactivity did not change over time , nor were time slopes significantly different for children in the treatment group and control group (p = 0.864) when controlling for baseline hyperactivity and gender differences.At baseline, children in the treatment group showed similar levels of hyperactivity as assessed by actigraphy compared to controls (p = 0.300). ADHD problems did not change over time (p = 0.555), nor were time slopes significantly different for children in the treatment group and control group (p = 0.693) when controlling for baseline ADHD symptoms and gender differences.Results on the classroom-observed ADHD-composite showed that children in the treatment and control group displayed similar levels of ADHD symptoms at baseline (p = 0.628). Peer acceptance improved over time (p = 0.008), but this improvement was similar for children in the treatment group and control group (p = 0.760) when controlling for peer acceptance at baseline and gender differences.Children in the treatment and control group displayed similar levels of peer acceptance at baseline . As actigraphy measures hyperactivity rather than general ADHD symptoms, the correlation between actigraphic hyperactivity and the SWAN Hyperactivity/Impulsivity scale (teacher version) was also assessed, yielding a significant, small-to-moderate correlation . Results revealed a large and significant correlation between peer acceptance and teacher-rated peer problems , and a medium to large correlation between peer acceptance and teacher-rated general social functioning .To study the inconsistency between the positive effects of the PR program on teacher ratings and the classroom measures showing no effects in the current study, exploratory correlational analyses were performed at baseline between ADHD measures of this study and of our previous study . Hence, This study aimed to assess whether earlier reported teacher-rated effects of the PR program on ADHD symptoms and social functioning  could beOur results suggest that the teacher-reported effects might reflect a change in perception of the teacher regarding the child’s functioning, rather than actual behavioral changes within a child, which could not be captured by the other measures used in the current study . This change in teachers’ perception could be explained by teachers being biased due to their investment in the program and subsequent positive treatment expectations . An alteOne partial explanation for the absence of significant program effects in the current study, might be related to the degree of severity of our sample. Children in our study all showed high levels of ADHD symptoms, but children receiving treatment for ADHD were excluded. As a result, only 10% were diagnosed with ADHD and 2% had a comorbid psychiatric diagnosis. Consequently, the room for improvement in terms of ADHD symptoms was lower in our sample compared to clinical ADHD samples, which may have added to the non-significant treatment effects for the current dependent variables.Another methodological explanation for the lack of significant program effects on the ADHD measures should also be considered. The low correlations between teacher-rated ADHD measure in our previous study and the ADHD measures of the current study (classroom observation and actigraphy) suggest that these measures pertain to different aspects of the child’s behavior. With regard to the wrist-worn actigraphs, this measure mainly registers upper limb movements , whereasThe lack of program effects on peer acceptance in our current study is in line with the lack of effects of the PR program on teacher-rated peer problems and could have been expected as the PR program focused on improving ADHD symptoms rather than improving peer problems . These fIt could be argued that additional expert involvement could have improved the effectiveness of the PR program, but literature on this topic is inconsistent. While a review on the effectiveness of self-help interventions for parents of children with behavior problems suggests that adding minimal levels of therapeutic support improves child outcomes , anotherA few limitations of our study should be noted. First, observers were not blind to treatment allocation due to the visibility of some program elements within the classroom. Although this could have resulted in observer’s bias, results were probably not influenced because no program-related effects in favor of the treatment group were found. Another limitation of the PR program is that implementation fidelity of teachers was measured by self-report instead of independent classroom observations see also . Third, This study is unique in its use of classroom observations, actigraphy and peer ratings to investigate whether earlier teacher-reported effects of the PR teacher program on ADHD symptoms and social functioning could be confirmed by other classroom measures. Results showed that improvements in teacher-rated ADHD symptoms were not confirmed by either actigraphy or by classroom observations. Possibly, the PR program improves teachers’ perception of a child’s behavior, rather than the child’s behavior. However, the possibility that the current measures assess different aspects of classroom behavior than teacher ratings should not be ruled out either, nor the potential influence of other methodological explanations . Either way, improving teachers’ perception may be an important step to enhance teacher–child interaction, which is in turn essential for the child’s behavioral, social and academic functioning at school and thus for future success in life . Future BV: Data collection, statistical analyses, literature review, writing entire manuscript. ML and JO: Article revision.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The association of attention deficit/hyperactivity disorder (ADHD) and fetal alcohol spectrum disorders (FASD) results in a complex constellation of symptoms that complicates the successful diagnosis and treatment of the affected individual. Current literature lacks formal guidelines, randomized control trials, and evidence-based treatment plans for individuals with ADHD and associated FASD. Therefore, a meeting of professional experts was organized with the aim of producing a consensus on identification and treatment guidelines that will aid clinicians in caring for this unique patient population.www.UKADHD.com) in June 2015. The meeting provided the opportunity to address the complexities of ADHD and FASD from different perspectives and included presentations, discussions, and group work. The attendees worked towards producing a consensus for a unified approach to ADHD and associated FASD.Experts from multiple disciplines in the fields of ADHD and FASD convened in London, United Kingdom, for a meeting hosted by the United Kingdom ADHD Partnership  unique ‘red flags’, which when identified in the ADHD population can lead to an accurate associated FASD diagnosis, 2) a treatment decision tree, and 3) recommendations for multiagency care management.While clinically useful guidelines were achieved, more research is still needed to contribute to the knowledge base about the diagnosis, treatment, and management of those with ADHD and associated FASD. Approximately 5 % of the population world-wide is reported to have a diagnosis of attention deficit/hyperactivity disorder (ADHD) , a disorIn this article we refer to the co-existence of ADHD and FASD as—ADHD and associated FASD—and not FASD with associated or co-morbid ADHD because: 1) most alcohol affected individuals present with and are initially evaluated for attention and executive function deficits , 5; 2) mADHD is a childhood onset, diagnosable neurobiological disorder with genetic and environmental origins  characteth edition, (DSM-5) [th edition, (ICD-10) [Clear diagnostic criteria for ADHD are listed in the Diagnostic and Statistical Manual of Mental Disorders, 5 (DSM-5)  and the (ICD-10)  (note th(ICD-10) , DSM- 5 (ICD-10) .FASD is a non-diagnostic descriptive term referring to the full range of diagnosable conditions caused by the deleterious effects of prenatal alcohol exposure (PAE), including neuropsychological, behavioral, and physical abnormalities . The ranThe implications of heavy PAE are long term and pervasive, affecting the individual, mother, family, and community throughout one’s lifespan –26. FASDThere is a high prevalence of co-morbid conditions in individuals with FASD . Long teThe diagnostic criteria for FAS is well established in the ICD-10 and DSM-5, but the diagnostic criteria for PAE conditions other than FAS are less precise and subject to considerable debate due to lack of available published evidence . SeveralIndividuals with histories of heavy PAE or ADHD are at risk for a wide range of impairments including behavioral and neuropsychological deficits , 45, 46.th of June 2015 in London, United Kingdom, for a meeting hosted by United Kingdom ADHD Partnership . The meeting included presentations with electronic slides, discussions, and group work; and was recorded and later transcribed. Psychiatrists, neuro-developmental pediatricians, psychologists, education experts, researchers, and others having personal experience with the impact of ADHD and/or FASD, engaged in lively thought provoking discussions throughout the day, with the aim of reaching consensus.Experts from multiple disciplines in the fields of ADHD and FASD convened on the 27ADHD and FAS: The Clinical PresentationAlcohol Exposure and Risk for Development of FASPsycho-pharmacotherapy Interventions for Co-morbid ADHD/FASEducation Interventions for Co-morbid ADHD/FASThe Criminal Justice PerspectiveThe meeting commenced with five presentations (including case studies) on the following topics, where each was followed by a question and answer session:Identification and AssessmentInterventions and TreatmentsMultiagency Liaisons and Care ManagementFollowing the presentations, all attendees separated into three breakout session groups  to produce a framework of guidelines with specific regards to:The discussions during the breakout sessions were facilitated by group leaders and summarized by note takers. The group leaders then presented their group’s framework of guidelines in a feedback session to all the meeting attendees for another round of discussion and debate. The medical writer consolidated the meeting transcription, electronic slide presentations, and breakout session notes into the manuscript. Lastly, the meeting transcription and manuscript were circulated to all authors for review to ensure agreement and a final consensus for a unified approach to ADHD and associated FASD was reached.The authors successfully produced identification and treatment guidelines for children and adults with ADHD and associated FASD, to aid clinicians in caring for this unique patient population, and the results follow below. Due to the nature of the co-existing disorders, it was recognized that services beyond medical care are required for the vast majority of patients.When considering the possibility of ADHD co-existing with FASD it is essential to investigate, with hopes of obtaining, an accurate and detailed PAE history. It is also important to routinely screen for FASD when ADHD is identified or for ADHD when FASD is identified; the DSM-5 and ICD-10 criteria sets are to be utilized for diagnosing ADHD and FAS, and we advocate the use of the 2005 Canadian guidelines for diagnosing all other FASD until the DSM-5 and ICD-11 criteria sets are further established. It is important to recognize the unique characteristics or ‘red flags’ that may be present in the individual with ADHD, which may assist in the identification of co-existing FASD. Prevalence rates of ADHD are known to be high in certain high-risk populations such as prisoners, ‘looked after’ children, adoptees, and individuals born prematurely. Efforts should be made among medical, social, educational, and criminal justice services to increase awareness of the need for appropriate referrals for individuals in these high-risk groups. They should be referred to suitable local pathways for either ADHD or FASD, based upon their primary presenting condition. It is recognized that individuals with subtle presentation may fail to meet the threshold for ADHD and are likely to be missed with this approach; ideally, the development of locally based complex neuro-developmental services is recommended. Neuro-developmental services could help identify and further assess affected individuals, which could potentially minimize the secondary health and social disabilities associated with ADHD and FASD.Maternal alcohol use during pregnancy should be included in a standard interview for those being assessed for ADHD. The World Health Organization’s Alcohol Use Disorders Identification Test offers a simple method of screening for excessive drinking and assists in making a brief assessment . It is rIf the child or adult has been previously diagnosed with ADHD then the clinician should routinely screen for FASD and likewise FASD for ADHD. A diagnosis of FAS should be made according to DSM-5 and ICD-10 criteria sets and all other FASD should be assessed using the 2005 Canadian guidelines. A diagnosis of ADHD should be made according to DSM-5 and ICD-10 criteria sets, utilizing standard screening and diagnostic tools: Conners’ Rating Scales; Swanson, Nolan, and Pelham-IV (SNAP-IV); and ADHD Rating Scale-IV. It is recommended that the affected individual be referred, when appropriate, to neuro-developmental services for additional assessments in adaptive behavioral functioning, executive function, and communication abilities.Possible or confirmed history of maternal alcohol consumption during pregnancy,Predominant presentation with inattentive subtype of ADHD, in addition to some impulsive behaviors,Failure to respond to, or increased behavioral disturbance when prescribed methylphenidate,Poor psychostimulant response in children with IQ under 50,Physical indicators of FAS or pFAS, including delayed growth and/or specific facial features , and/or aLack of response to typical behavioral interventions.We recognize a number of unique characteristics or ‘red flags’, which when present in individuals with ADHD, may assist in the identification of associated FASD. These ‘red flags’ can be considered as potential risk factors for having FASD. Clinicians are to be alerted if any of the following unique characteristics are identified in patients with ADHD:Treatments for ADHD and associated FASD require an individualized approach, as do all neuro-psychiatric disorders. Clinicians should refer for multi-modal assessments , when necessary, to assist them in treatment plan development. The Centers for Disease Control offers guidelines to service providers in making referral decisions specific to individuals with FAS , but canFamily support is usually necessary, and oftentimes special support may be required for the birth mother, because she may need therapy to cope with possible feelings of guilt and shame relating to alcohol use during pregnancy. Educating and encouraging the birth mother may result in reduced or no alcohol use in subsequent pregnancies. It is also important to recognize the particular needs of adoptive parents and additionally to recognize the ongoing impact of the child’s condition on the family because they may need support groups or respite services.Treatment should be delivered primarily via the parents and/or care givers by educating them in healthcare and child training strategies, and techniques about the best ways to care for and help their child. It is important for affected children, and especially for those with additional co-existing learning difficulties, to be fully assessed. It may be necessary to develop a formal individualized educational plan to access additional services to address the need for educational supports.Treatment can be delivered directly to the individual. With regards to treatment decisions, however, it must be first established whether or not the individual has the capacity to make such decisions and whether or not it is appropriate to have the family involved as part of a shared plan or agreement. Safeguarding issues need to be taken into account when dealing with children, adolescents, and vulnerable adults. These individuals are capable of attending and benefiting from group treatment/therapy sessions. Symptoms and their associated impairments can become more marked in older children as they progress into adulthood, thus key topics that should be included in therapy, group or otherwise, are: risk taking behaviors, inappropriate sexual behaviors, problem solving skills, social skills, and sleep hygiene techniques. It is of high importance to note that risk taking behaviors and problem-solving deficits in combination with impulsivity may increase the risk of suicide.It is important to carefully monitor progress and measure the effects of non-pharmacological treatments through goal-based outcomes. If the co-existing disorders are still causing significant impairment, after a short period of one to three months, then a progression to the use of medication should be made. It is recognized that family involvement with regular and frequent follow-up visits are essential to successful pharmacological treatment. If a child resides within a chaotic family it will be especially necessary to assess whether a responsible adult is correctly administering the medication.The need to physiologically assess the individual and run baseline tests is emphasized as highly important for this group. The NICE treatment guidelines for ADHD recommend the monitoring of blood pressure, pulse, height, weight, and the investigation of cardiovascular history with an ECG prior to medication use. The following additional baseline tests should ideally be ordered, to investigate the possible damaging effects of PAE: full blood count (FBC), thyroid function test (TFT), liver function test (LFT), blood sugar, folate, gamma-glutamyltransferase , blood pressure, and renal function test (RFT); these baseline tests should be repeated if indicated clinically. Additionally, care should be taken to obtain a full clinical seizure history, if indicated clinically.Currently developed medication can treat the symptoms of ADHD, but cannot cure the disorder. Medication can improve attention and reduce hyperactivity and impulsivity, thereby allowing the individual to effectively manage their difficulties, access and engage with suitable therapies, and build upon their skills. Management of the core symptoms may improve learning, minimize their potential impact, and ameliorate the common secondary disabilities associated with FASD. Case study 1 see Fig.  reveals The side effects of medication use, among individuals with ADHD and associated FASD, may be similar when compared with individuals with ADHD, but more marked due to the abnormal physiological aspects of the disorder. Some stimulant medications can lead to more pronounced anxiety, appetite, and sleep problems; they may also affect growth hormones and may increase the prevalence of tics. The response to medication can be idiosyncratic and unpredictable because some medications may cause a regression of behavior. In particular, high doses of atomoxetine (ATX) may cause liver damage, therefore low doses are recommended initially. Before increasing a medication dosage it is recommended that the non-pharmacological strategies are revisited and additional assessments are made to account for any under or misdiagnosed co-existing conditions. The individual should be re-evaluated and monitored frequently throughout the intervention process.Short-acting stimulants are typically trialed first in patients with ADHD to examine tolerance before progressing to long-acting stimulants. This treatment can be problematic, however, in adolescents with ADHD and associated FASD because short-acting stimulants may potentially contribute to the development of addictive disorders during the teenage years. Therefore, long-acting/biphasic stimulants or atomoxetine (which do not give an immediate ‘buzz’) are recommended because they are less likely to contribute to the development of an addictive disorder.The effects of ADHD and associated FASD are lifelong and pervasive, affecting the individual, mother, family, and community. Therefore, it is extremely important that interventions are comprehensive, continue throughout the lifespan, and extend beyond medical care to include when necessary: social, educational, mental health, employment, and criminal justice services. These interventions are likely to be productive when service agencies collaborate with each other. The coordinated efforts of service professionals should support not only affected individuals, but their families as well. In addition to multi-agency collaboration, it is important that each agency offers distinct services designed to enhance quality of life and long term outcomes. While the non-pharmacological treatments previously mentioned cover some of these aspects, there are many additional services that may need to be accessed and managed at different phases of life.If there is suspected or confirmed PAE and/or subsequent failure to engage with professionals, social service referrals for the mother and developing child may need to start prior to birth. Because affected children often display challenging behaviors, social service professionals can offer parents, caregivers, and siblings, training and/or support for managing those behaviors, thereby bolstering family resilience. Family resilience is also likely to be enhanced with the provision of respite services and group support. Social service professionals should routinely review the needs of the family, including possible financial needs, in order to provide timely and comprehensive services, which is especially important during key transition times.Young children would benefit from preschool placements, where staff have an understanding of FASD and ADHD, and can offer an appropriate environment to meet the developmental needs of the child; and may be referred for specialized stimulating play therapy and/or other preschool services. It may be required that pediatric medical, mental health, social care, and educational professionals coordinate their services  to ensure coherent and consistent support. It is important to recognize the potential need for intervention by local authorities or the need for a referral to an adoption specialist. Given the high incidence of placement breakdown, and the subsequent impact of repeated failure on the child and care system, commissioning officers should carefully evaluate the relative merits of foster and adoption placements against more specialized and perhaps resilient services. When children with ADHD and associated FASD are separated from their birth mothers and moved through the care system, they are often inaccurately identified as having insecure or disorganized attachment disorders, instead of being accurately identified as having developmental, emotional, and behavioral difficulties attributed to PAE. In addition, safeguarding issues should be assessed and, in cases of abuse and exploitation, child protection services should be informed and accessed.Social services may need to be accessed because puberty is a particularly vulnerable phase of development. Many young people affected by PAE may crave friendship and a sense of belonging, but often lack the skills required to achieve these. Supported social groups may therefore assist in establishing meaningful relationships with peers within the local community, which is thought to be a protective factor in averting deterioration in mental health, and enhance quality of life. It is important to recognize breakdowns and/or transitions in living accommodations, education placement and treatment plans for these young adults. It is also important to recognize the increased risk of drug and alcohol abuse or misuse during adolescence. The clinician may have a key role regarding safeguarding issues by screening for abuse and exploitation, and accessing child protection services if necessary.Additional support for the child may be necessary starting in preschool. It is important to recognize the need for child friendly, age-appropriate tasks and activities. It is also important that young children receive broad assessments of needs across multiple measures, and particularly in language comprehension. The pre-school and young primary school child, and family, may benefit from home-visits from educational services to help parents to understand the developmental benefits of learning through play, methods for encouraging and enhancing verbal and non-verbal communication, and in managing challenging behaviors.It is important to obtain a comprehensive assessment of needs and functional analysis of behavior, and to consider the possible impact of deprivation and limitations unique to these children. It may be necessary to make a referral for the development of an individualized education plan with track-able goals  to document progress. Education planning should include input from students themselves, parents and/or caregivers, and teaching professionals. The assessments and individualized education plan are helpful in determining the student’s best learning environment  and may be required to access education supports and appropriate placement. It is essential for all involved to recognize that these students often benefit most from a strengths-based approach and from differentiated learning. Teachers and educational psychologists will most likely require training to develop relevant assessments and educational strategies specific to this population. Staff awareness, understanding, and competence are key factors in a student’s progress.Teaching professionals need to consider not only the curricular and staffing requirements of affected students, but also their sensory and social needs. Teachers and support staff need to identify the student’s possible barriers to effective engagement with peers , and provide supportive environments in which social skills may be developed or enhanced. Individuals having difficulty with arousal and mood self-regulation may find mainstream settings too overwhelming and may benefit from a more supported special education setting. Nevertheless, even severely affected individuals can be successfully mainstreamed with support  of the young person. Affected individuals may require staged transitions into employment via work experience, supported with mentors or job coaches, and college link courses in order to fulfill their vocational potential. The identification of specific barriers  may be more beneficial than the provision of generic support.The clinician may have a role in helping affected children or adults by recommending an appropriate representative to interface with the criminal justice system and/or by referring for the development of an identification card indicating the presence of a disability that the affected individual can present to criminal justice service personnel if necessary. According to the National Organization on Fetal Alcohol Syndrome, “The criminal justice system can help FASD-affected individuals by: educating judges, lawyers, and parole officers about the characteristics and behaviors of individuals with FASD, establishing a screening and referral process for those with ADHD and FASD who enter the juvenile justice or adult criminal justice system, establishing/utilizing alternative sentencing programs for affected individuals who have committed non-violent offenses, offering referral information for the children of incarcerated women who may have been prenatally exposed to alcohol.” . These aCase study 3 see Fig.  illustraAlthough more research is needed to identify, treat, and manage affected individuals, the authors successfully came to a consensus for a more unified approach to ADHD and associated FASD. The authors agreed that there is a need to increase the number and training of clinicians and to expand services for this unique population. The authors also agreed upon the need to develop complex neuro-developmental services that could help identify and further assess affected individuals, and intervention services that could help divert affected individuals away from the criminal justice system, when appropriate. It is likely that governmental support will be necessary in the development of these services.The most significant outcome of the collaborative efforts amongst the multi-disciplinary professionals was the production of clinically meaningful guidelines, based upon consensus. Included in the guidelines are unique ‘red flags’, which when identified in the ADHD population can lead to an accurate associated FASD diagnosis, a treatment decision tree, and recommendations for multi-agency care management. Given the lifelong, pervasive nature of the associated disorders, the authors’ emphasized that a lifespan approach to treatment needs to be adopted by all involved. The implementation of these guidelines has the potential of making a significant, positive impact on affected individuals.