Increased risk of ADHD in families with ASD.

Attention Deficit and Hyperactive Disorder (ADHD) and Autism Spectrum Disorders (ASD) are frequent comorbid neurodevelopmental conditions and the overlap between both disorders remains to be delineated. A more complete understanding of the shared genetic and environmental factors is needed. Using a family-based method, we evaluated the risk of ADHD in a group of relatives with an ASD proband (ASD-) and a group of relatives with an ASD and ADHD proband (ASD+). We enrolled 1245 individuals in the study: 499 probands, their 746 first-degree relatives and 140 controls. We used a multivariate generalized estimating equation (GEE) model, in which the dependent variable was the ADHD diagnosis in the relatives and the independent variable the ASD+ or ASD- in probands. We adjusted for sociodemographic factors (age, sex, IQ) and for the nature of the familial relationship with the affected proband (parent or sibling). Among the probands, there were 287 ASD- and 212 ASD+ individuals. ADHD was more frequent in relatives (19%) than in the control group (7%) (p = 0.001). The risk of ADHD was higher in the ASD+ relatives group than in the ASD- relatives group (GEE model OR 1.58 [95% CI 1.04-2.38], p = 0.032). This result was found in parents (OR 1.96 [95% CI 1.14-3.36], but not in siblings (OR 1.28 [95% CI 0.84-1.94], p = 0.434). Our study provides a representative estimate of the family distribution of ADHD in relatives of ASD probands but supports the modest effect of shared genetic and environmental factors between both disorders.

Motor Abnormalities in Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder Are Associated With Regional Grey Matter Volumes.

Attention-Deficit/Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) are associated with motor impairments, with some children holding a comorbid diagnosis of Developmental Coordination Disorder (DCD). However, DCD is underdiagnosed in these populations and the volume abnormalities that contribute to explaining these motor impairments are poorly understood. In this study, motor abilities as measured by the Developmental Coordination Disorder Questionnaire (DCDQ) were compared between children with ADHD, children with ASD and typically developing (TD) children, aged 8-12 years old. Additionally, the association between the DCDQ scores (general coordination, fine motor/handwriting, control during movement, total) and regional volume abnormalities were explored in 6 regions of interest (pre-central gyrus, post-central gyrus, inferior parietal cortex, superior frontal gyrus, middle frontal gyrus, medial frontal gyrus), within each group and across all participants. Children with ASD and children with ADHD showed impaired motor abilities in all the DCDQ-derived scores compared to TD children. Additionally, most children with ASD or ADHD had an indication or suspicion of DCD. Within the ASD group, coordination abilities were associated with the volume of the right medial frontal gyrus, and within the ADHD group, the total DCDQ score was associated with the volume of the right superior frontal gyrus. This study underlines the importance of routinely checking motor abilities in populations with ASD or ADHD in clinical practise and contributes to the understanding of structural abnormalities subtending motor impairments in these disorders.

Improvement of Pursuit Eye Movement Alterations after Short Visuo-Attentional Training in ADHD.

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder without validated and objective diagnostic procedures. Several neurological dysfunctions in the frontal circuit, in the thalamus, and in the cerebellum have been observed in subjects with ADHD. These cortical and subcortical areas are responsible for eye movement control. Therefore, studying eye movements could be a useful tool to better understand neuronal alterations in subjects with ADHD. The aim of the present study was firstly to compare the quality of pursuit eye movements in a group of 40 children with ADHD (age 8.2 ± 1.2) and in a group of 40 sex-, IQ-, age-matched typically developing (TD) children; secondly, we aimed to examine if a short visuo-attentional training could affect pursuit performances in children with ADHD. Findings showed that children with ADHD presented a greater number of catch-up saccade and lower pursuit gain compared to TD children. Differently to TD children, in children with ADHD, the number of catch-up saccades and the pursuit gain were not significantly correlated with children's age. Furthermore, a short visuo-attentional training period can only slightly improve pursuit performance in children with ADHD, leading to a decrease of the occurrence of catch-up saccades only, albeit the effect size was small. The absence of any improvement in pursuit performance with age could be explained by the fact that the prefrontal and fronto-cerebellar circuits responsible for pursuit triggering are still immature. Pursuit eye movements can be used as a useful tool for ADHD diagnosis. However, attentional mechanisms controlled by these cortical structures could be improved by a short visuo-attentional training period. Further studies will be necessary to explore the effects of a longer visuo-attentional training period on oculomotor tasks in order to clarify how adaptive mechanisms are able to increase the attentional capabilities in children with ADHD.

Impairment in Attention Focus During the Posner Cognitive Task in Children With ADHD: An Eye Tracker Study.

Attention is a major cognitive function that allows the individuals to focus selectively on a discrete stimulus while ignoring others. Visual information could be driven endogenously, when the goals or desires are voluntary, or exogenously, in response to salient visual events in the environment. Since subjects with attention deficit hyperactivity disorder (ADHD) show heightened distractibility during activities that require significant attentional engagement, we hypothesized that they may be more severely impaired in their ability to perform endogenous tasks than controls. To elicit endogenous and exogenous shifts of attention, we thus used a modified version of Posner's cueing task. We compared oculomotor performance measured by an eye tracker in a group of 31 children with ADHD (mean age = 9.1 ± 1.3 years) and age-, sex-, and IQ-matched typically developing children. Endogenous and exogenous conditions were explored in three distinct visual sub-conditions (valid, invalid, and neutral). We found that children with ADHD showed longer latency during endogenous conditions compared to TD children in invalid sub-conditions. They also performed more errors than controls, during the endogenous task in neutral sub-conditions and during exogenous task in neutral and invalid sub-conditions. Our study suggests that children with ADHD may allocate their attention resource toward the detection of exogenous targets with a deficit in their ability to perform endogenous task. We suggest also that they have a difficulty in the engagement of the inhibitory control system particularly during voluntary saccade performance. This could result from impaired interactions between the ventral and dorsal attention networks as well as in the frontal eye field, although neuroimaging studies are necessary to validate this hypothesis in the ADHD population.

Disorder-specific brain volumetric abnormalities in Attention-Deficit/Hyperactivity Disorder relative to Autism Spectrum Disorder.

The overlap/distinctiveness between Attention-Deficit/Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) has been increasingly investigated in recent years, particularly since the DSM-5 allows the dual diagnosis of ASD and ADHD, but the underlying brain mechanisms remain unclear. Although both disorders are associated with brain volumetric abnormalities, it is necessary to unfold the shared and specific volume abnormalities that could contribute to explain the similarities and differences in the clinical and neurocognitive profiles between ADHD and ASD. In this voxel-based morphometry (VBM) study, regional grey matter volumes (GMV) were compared between 22 children with ADHD, 18 children with ASD and 17 typically developing (TD) children aged 8 to 12 years old, controlling for age and total intracranial volume. When compared to TD children or children with ASD, children with ADHD had a larger left precuneus, and a smaller right thalamus, suggesting that these brain abnormalities are specific to ADHD relative to ASD. Overall, this study contributes to the delineation of disorder-specific structural abnormalities in ADHD and ASD.

ADHD and ASD: distinct brain patterns of inhibition-related activation?

Attention-deficit/hyperactivity (ADHD) and autism spectrum (ASD) disorders often co-occur. In both cases, response inhibition deficits and inhibition-related atypical brain activation have been reported, although less consistently in ASD. Research exploring the overlap/distinctiveness between ADHD and ASD has significantly increased in recent years, but direct comparison of the inhibition-related neuronal correlates between these disorders are scarce in the literature. This study aimed at disentangling the shared and specific inhibitory brain dysfunctions in ASD and ADHD. Using functional magnetic resonance imaging (fMRI), brain activity was compared between children with ADHD, ASD and typically developing (TD) children aged 8-12 years during an inhibition stop-signal task, using stringent inclusion criteria. At the behavioural level, only children with ADHD exhibited inhibition deficits when compared with the TD group. Distinct patterns of brain activity were observed during successful inhibition. In children with ADHD, motor inhibition was associated with right inferior parietal activation, whereas right frontal regions were activated in children with ASD. Between-group comparisons disclosed higher middle frontal activation in the ASD group compared with the ADHD and the TD groups. Our results evidence different patterns of activation during inhibition in these two disorders, recruiting different regions of the fronto-parietal network associated to inhibition. Besides brain activity differences, behavioural inhibition deficits found only in children with ADHD further suggest that reactive inhibition is one of the core deficits in ADHD, but not in ASD. Our findings provide further evidence contributing to disentangle the shared and specific inhibitory dysfunctions in ASD and ADHD.

Association between suicidal spectrum behaviors and Attention-Deficit/Hyperactivity Disorder: A systematic review and meta-analysis.

The relationship between ADHD and suicidal spectrum behaviors (SSBs) remains uncertain. We conducted the first meta-analysis on the association between ADHD and SSBs taking possible confounders into account. Based on a pre-registered protocol (PROSPERO-CRD42018093003), we searched Pubmed, Ovid and Web of Knowledge databases through April 6th, 2018, with no language/publication type restrictions, and contacted study authors for unpublished data/information. From a pool of 2798 references, we retained 57 studies. Random-effects models were performed. Study quality was rated using the Newcastle-Ottawa Scale. After pooling crude ORs, we found a significant association between ADHD and suicidal attempts (2.37, 95% CI = 1.64-3.43; I2 = 98.21), suicidal ideations (3.53, 2.94-4.25; I2 = 73.73), suicidal plans (4.54, 2.46-8.37; I2 = 0), and completed suicide (6.69, 3.24-17.39; I2 = 87.53). Results did not substantially change when pooling adjusted ORs. Findings were also in general robust to sensitivity analyses to assess possible moderators. Awareness of the association between ADHD and SSBs should contribute to more effectively prevent SSBs.

The Effect of Dual Task on Attentional Performance in Children With ADHD.

Attention-deficit/hyperactivity disorder (ADHD) is a common psychiatric disorder without validated objective markers. Oculomotor behavior and executive motor control could potentially be used to investigate attention disorders. The aim of this study was to explore an oculomotor and postural dual task in children with ADHD. Forty-two children were included in the study, gathering children with ADHD (n = 21) (mean 8.15 age ± years 0.36) and sex-, age-, and IQ-matched typically developing children (TD). Children performed two distinct fixation tasks in three different postural conditions. Eye movements and postural body sway were recorded simultaneously, using an eye tracker and a force platform. Results showed that children with ADHD had poor fixation capability and poor postural stability when compared to TD children. Both groups showed less postural control on the unstable platform and displayed more saccades during the fixation task. Surprisingly, in the dual unstable platform/fixation with distractor task, the instability of children with ADHD was similar to that observed in TD children. "Top-down" dys-regulation mediated by frontal-striatal dysfunction could be at the origin of both poor inhibitory oculomotor deficits and impaired body stability reported in children with ADHD. Finally, we could assume that the fact both groups of children focused their attention on a secondary task led to poor postural control. In the future it could be interesting to explore further this issue by developing new dual tasks in a more ecological situation in order to gain more insight on attentional processes in children with ADHD. HIGHLIGHTS - Children with ADHD showed poor fixation capability when compared to TD children. - "Top-down" dys-regulation mediated by frontal-striatal dysfunction could be at the origin of both poor inhibitory oculomotor deficits and impaired body stability reported in children with ADHD. - Both groups of children focused their attention on the visual fixation task leading to poor postural control. - In the future it could be interesting to develop new dual tasks in an ecological situation in order to gain more insight on attentional processes in children with ADHD.

Interactions between eye movements and posture in children with neurodevelopmental disorders.

In everyday life, our activities frequently involve the simultaneous performance of two or more tasks. Sharing attention between two concurrent tasks may result in a decrease in performance specifically among children with neurodevelopmental disorders. The objective of the study was to determine whether the influence of postural conditions (sitting condition, single task; standing condition, dual task) on eye movement performances on three visual tasks with high attentional load (visually-guided saccade task, memory-guided saccade task and fixation task) was different in children with neurodevelopmental disorders (attention deficit and hyperactive disorder, dyslexia, and high functioning autism spectrum disorder) when compared to typically developing children. One hundred and four children (26 per group, sex-age- and IQ-matched groups) were evaluated. We found that for the fixation task only, the three groups of children with neurodevelopmental disorders had poorer eye movements performances in the standing condition compared to the sitting condition while no such difference was found for typically developing children. We suggest that children with neurodevelopmental disorders have fewer attentional resources available for performing correctly oculomotor tasks with high attentional load leading to impairment of these tasks for maintaining a good level of postural stability.

Oculomotor Abnormalities in Children with Attention-Deficit/Hyperactivity Disorder Are Improved by Methylphenidate.

BACKGROUND: There are relatively few studies of saccadic eye movements in children with attention-deficit/hyperactivity disorder (ADHD). The aim of this study was to examine inhibitory abilities of eye movements in children with ADHD and to explore the effect of methylphenidate (MPH) on eye movement performance. METHODS: Thirty-one children with ADHD (mean age 9.9 ± 0.4 years) and 31 sex-, age-, and IQ-matched children with normal development were examined. Saccades elicited not only by the gap, step, overlap, and antisaccade paradigms but also a simple fixation paradigm have been recorded using an eye tracker. The latency of each type of saccade, the error rate of antisaccades, and the number of saccades made during fixation have been measured. RESULTS: Children with ADHD and naive to treatment with respect to controls showed significantly shorter mean latency of voluntary saccades (overlap paradigm), more frequent errors during the antisaccade paradigm, and higher number of saccades made during fixation. After 1 month of MPH treatment, all these parameters changed significantly and reached control values. CONCLUSION: Taken together, these results suggest that oculomotor abilities are poor in children with ADHD, which may correlate with deficits in inhibitory mechanisms. Treatment with MPH improves oculomotor performances through adaptive strategies, which may involve brain structures related to cognitive inhibition.

Attentional control of emotional interference in children with ADHD and typically developing children: An emotional N-back study.

Emotional interference control refers to the ability to remain focused on goal-oriented processes when confronted with disrupting but irrelevant emotional stimuli, a process that may be impaired in children and adults with attention deficit/hyperactivity disorder (ADHD). However, emotional interference levels are known to be associated with trait anxiety, and patients with ADHD often display elevated levels of trait anxiety, such as these may have confounded previous findings of decreased emotional interference control in this population. In the present study, male and female 8-13 years old (mean =11.0 years) children with ADHD (n=33) and typically developing (TD) children (n=24) performed a visual emotional working memory (n-back) task with 2 memory loads and three different background pictures (neutral/positive/negative), and trait anxiety measures were obtained. Children with ADHD performed less well, and displayed increased emotional interference in the presence of aversive distractors when compared with TD children. Contrary to our expectations, trait anxiety did not mediate the association between diagnostic group membership and the degree of emotional interference control; however, co-morbid ODD was associated with decreased levels of emotional interference in ADHD. Future research should aim at characterizing the mechanisms subtending decreased emotional interference control in the ADHD population.

Structural correlates of COMT Val158Met polymorphism in childhood ADHD: a voxel-based morphometry study.

OBJECTIVES: The Val158-allele of the catechol-O-methyltransferase (COMT) Val158Met (rs4680) functional polymorphism has been identified as a risk factor for antisocial behaviour in attention-deficit/hyperactivity disorder (ADHD). Here, we used voxel-based morphometry to investigate the effects of Val158Met polymorphism on grey matter (GM) volumes in a sample of 7-13-year-old children. METHODS: MRI and genotype data were obtained for 38 children with combined-type ADHD and 24 typically developing (TD) children. Four regions of interest were identified: striatum, cerebellum, temporal lobe and inferior frontal gyrus (IFG). RESULTS: When compared to TD children, those with ADHD had a significant decrease of GM volume in the IFG. Volume in this region was negatively correlated with ratings of hyperactivity/impulsivity symptoms. Furthermore, the smaller GM volume in the IFG was attributed to the presence of the Met158-allele, as only children with ADHD carrying a Met158-allele exhibited such decrease in the IFG. Children with ADHD homozygotes for the Val158-allele presented increased GM volume in the caudate nucleus when compared with TD children. CONCLUSIONS: This study provides the first evidence of a modulation of ADHD-related GM volume alterations by Val158Met in two key regions, possibly mediating the relationship between Val158Met polymorphism and antisocial behaviour in children with ADHD.