Disentangling the Overlap between Tourette's Disorder and ADHD

Objective : To identify similarities and differences in neuropsychiatric correlates in children with Tourette's syndrome (TS) and those with ADHD. Method : The sample consisted of children with Tourette's syndrome with ADHD( N = 79), children with Tourette's syndrome without ADHD ( N = 18), children with ADHD ( N = 563), psychiatrically referred children ( N = 212), and healthy controls ( N = 140). Results: Disorders specifically associated with Tourette's syndrome were obsessive compulsive disorder (OCD) and simple phobias. Rates of other disorders, including other disruptive behavioral, mood, and anxiety disorders, neuropsychologic correlates, and social and school functioning were indistinguishable in children with Tourette's and ADHD. However, children with Tourette's syndrome plus ADHD had more additional comorbid disorders overall and lower psychosocial function than children with ADHD. Conclusions: These findings confirm previously noted associations between Tourette's syndrome and OCD but suggest that disruptive behavioral, mood, and anxiety disorders as well as cognitive dysfunctions may be accounted for by comorbidity with ADHD. However, Tourette's syndrome plus ADHD appears to be a more severe condition than ADHD alone.     

The co-occurrence of autism spectrum disorder and attention-deficit/hyperactivity disorder symptoms in parents of children with ASD or ASD with ADHD

Background: Autism spectrum disorder (ASD) and attention‐deficit/hyperactivity disorder (ADHD) share about 50–72% of their genetic factors, which is the most likely explanation for their frequent co‐occurrence within the same patient or family. An additional or alternative explanation for the co‐occurrence may be (cross‐)assortative mating, e.g., the tendency to choose a partner that is similar or dissimilar to oneself. Another issue is that of parent‐of‐origin effect which refers to the possibility of parents differing in the relative quantity of risk factors they transmit to the offspring. The current study sets out to examine (cross‐)assortative mating and (cross‐)parent‐of‐origin effects of ASD and ADHD in parents of children with either ASD or ASD with ADHD diagnosis. Methods: In total, 121 families were recruited in an ongoing autism‐ADHD family genetics project. Participating families consisted of parents and at least one child aged between 2 and 20 years, with either autistic disorder, Asperger disorder or PDD‐NOS, and one or more biological siblings. All children and parents were carefully screened for the presence of ASD and ADHD. Results: No correlations were found between maternal and paternal ASD and ADHD symptoms. Parental ASD and ADHD symptoms were predictive for similar symptoms in the offspring, but with maternal hyperactive‐impulsive symptoms, but not paternal symptoms, predicting similar symptoms in daughters. ASD pathology in the parents was not predictive for ADHD pathology in the offspring, but mother’s ADHD pathology was predictive for offspring ASD pathology even when corrected for maternal ASD pathology. Conclusions: Cross‐assortative mating for ASD and ADHD does not form an explanation for the frequent co‐occurrence of these disorders within families. Given that parental ADHD is predictive of offspring’ ASD but not vice versa, risk factors underlying ASD may overlap to a larger degree with risk factors underlying ADHD than vice versa. However, future research is needed to clarify this issue.     

Etiology and pathogenesis of Attention-deficit Hyperactivity Disorder (ADHD): significance of prematurity and perinatal hypoxic-haemodynamic encephalopathy

Attention-deficit Hyperactivity Disorder (ADHD), defined as a disorder of awareness with impul-sivity, has lately been characterized as a dysfunction of the striatum (neostriatum = globus pallidus + putamen). This structure is in a unique position for contextual analysis and samples information from almost the entire cortex through its spiny neurons. The etiology is heterogeneous, with genetic as well as lesional factors. Among the latter, pre- and perinatal events are prominent. Advances in the understanding of the role of fetal circulatory insufficiency with loss of autoregulation and systemic hypotension have drawn attention to the vulnerability of watershed regions, including the striatum. Not only circulatory facts are important for this selectivity, however. The anatomical characteristics, with convergent glutaminergic afferent synaptic transmission from almost the entire cortex contribute to the vulnerability in ischemia-induced liberation of glutamate: The striatum becomes the victim of its virtue. Repeated hypoxic-ischemic events are particularly common in prematurity, a fact which seems to explain the high incidence of ADHD in this patient group. The magnitude of the problem is increasing with the increased survival rate among premature infants.     

The neurobiology and genetics of Attention-Deficit/Hyperactivity Disorder (ADHD): what every clinician should know

This review, addressed mainly to clinicians, considers commonly asked questions related to the neuroimaging, neurophysiology, neurochemistry and genetics of Attention-Deficit/Hyperactivity Disorder (ADHD). It provides answers based on the most recent meta-analyses and systematic reviews, as well as additional relevant original studies. Empirical findings from neurobiological research into ADHD reflect a shift in the conceptualisation of this disorder from simple theoretical views of a few isolated dysfunctions to more complex models integrating the heterogeneity of the clinical manifestations of ADHD. Thus, findings from structural and functional neuroimaging suggest the involvement of developmentally abnormal brain networks related to cognition, attention, emotion and sensorimotor functions. Brain functioning alterations are confirmed by neurophysiological findings, showing that individuals with ADHD have elevated theta/beta power ratios, and less pronounced responses and longer latencies of event-related potentials, compared with controls. At a molecular level, alterations in any single neurotransmitter system are unlikely to explain the complexity of ADHD; rather, the disorder has been linked to dysfunctions in several systems, including the dopaminergic, adrenergic, serotoninergic and cholinergic pathways. Genetic studies showing a heritability of ～60-75% suggest that a plethora of genes, each one with a small but significant effect, interact with environmental factors to increase the susceptibility to ADHD. Currently, findings from neurobiological research do not have a direct application in daily clinical practice, but it is hoped that in the near future they will complement the diagnostic process and contribute to the long-term effective treatment of this impairing condition.     

A TRIAL SEPTAL DEFECT (ASD)

Intracardiac recordings in patients with primum- and secundum-type atrial septal defects display no definite differences, except when the primum defect is associated with some lesion in the atrioventricular valves which produces a murmur.
The intensity of the pulmonary component of the second sound grows with the pressure in the pulmonary artery. Murmurs are louder in patients with relative pulmonary stenosis than in other cases.
No definite conclusions concerning the severity of the defect can he drawn from the intensity of the systolic murmur or the occurrence of a diastolic murmur.
The murmur recorded most intensely in the second left intercostal space on the chest has its origin in the pulmonary artery.
A case of atrioventricularis communis may be distinguished from a primum-type defect by the holosystolic murmur heard in the ventricle of a patient with this condition.
Intracardiac phonocardiography is not of clinical value for patients with atrial septal defects, except to confirm or exclude an additional lesion (e.g. ventricular septal defect).     

Stimulation seeking and hyperactivity in children with ADHD. Attention Deficit Hyperactivity Disorder

Thirty hyperactive and 30 non-hyperactive children were confronted with a delay, consisting of a waiting situation of 15 minutes, either with or without extra stimulation provided by the presentation of a videotape. The behaviour of the child during the waiting period was videotaped and later coded by two naive observers. In line with theories that emphasise the stimulation-seeking function of hyperactive behaviours, such as the optimal stimulation account and the delay aversion theory, a group by stimulation effect was hypothesised. For two categories of activity this was found, with ADHD children displaying more activity than non-ADHD children in the no-stimulation but not in the stimulation condition. These data provide support for the stimulation-seeking function of certain features of ADHD hyperactivity.     

Per-Catheter ASD Closure

Per-catheter devices for atrial septal defect (ASD) closure have been evolving since 1974. The four major devices available for use on a limited basis in early 1997 are reviewed. These include (in alphabetical order) the Angel Wing device, the ASDOS device, the Buttoned device, and the CardioSeal device (successor to the Clamshell). Sufficient data have been collected to indicate that transcatheter ASD closure is a viable alternative to surgery in selected patients. The advantages of the concept of per-catheter closure over surgical closure should lead to the continued development of devices and techniques for per-catheter treatment of ASD and other septal defects in the years to come.     

Replication of the latent class structure of Attention-Deficit/Hyperactivity Disorder (ADHD) subtypes in a sample of Australian twins

BACKGROUND: Previous efforts to subtype Attention-Deficit/Hyperactivity Disorder (ADHD) using latent class analysis (LCA) applied to DSM-IV symptom profiles of adolescent female twins from Missouri (USA) have identified distinct classes within the domains of inattention, hyperactivity-impulsivity and combined-type problems. The objective of the current report is to determine if the latent class structure of ADHD subtypes can be replicated in a culturally distinct sample of female and male Australian twins. METHOD: LCA was applied to parent-report DSM-IV ADHD symptom profiles of N=2,848 child and adolescent Australian twins and compared to North American findings. Separate models were fitted for females (N= 1,432) and males (N= 1,416). RESULTS: The most congruent latent ADHD classes across samples included a non-symptomatic class, three mild-moderate and two severe classes. Also present within samples was a rare hyperactive-impulsive class and a unique class, the structure of which was idiosyncratic across samples. Mean symptom endorsement and individual symptom endorsement probabilities for each of the stable classes were similar across samples. Consistent with previous findings, there was substantial overlap between the DSM-IV inattentive and combined subtypes with the severe inattentive and severe combined latent classes. However, DSM-IV inattentive and combined subtypes were distributed over several latent classes in each sample, and a substantial proportion of individuals with no DSM-IV diagnosis were also assigned to these severe classes. CONCLUSIONS: Results from LCA using an Australian twin sample replicate six of the eight latent class subtypes previously reported using Missouri female twins and extend the findings to male twins. LCA and DSM-IV systems of ADHD classification identify different phenotypic groups, and the basis of this disparity merits further investigation.     

Perinatal risk factors interacting with catechol O‐methyltransferase and the serotonin transporter gene predict ASD symptoms in children with ADHD

Background: Symptoms of autism spectrum disorder (ASD) and attention‐deficit/hyperactivity disorder (ADHD) often co‐occur. Given the previously found familiality of ASD symptoms in children with ADHD, addressing these symptoms may be useful for genetic association studies, especially for candidate gene findings that have not been consistently replicated for ADHD. Methods: We studied the association of the catechol O‐methyltransferase (COMT) Val158Met polymorphism and the serotonin transporter (SLC6A4/SERT/5‐HTT) 5‐HTTLPR insertion/deletion polymorphism with ASD symptoms in children with ADHD, and whether these polymorphisms would interact with pre‐ and perinatal risk factors, i.e., maternal smoking during pregnancy and low birth weight. Analyses were performed using linear regression in 207 Dutch participants with combined type ADHD of the International Multicenter ADHD Genetics (IMAGE) study, and repeated in an independent ADHD sample (n = 439) selected from the TRracking Adolescents’ Individual Lives Survey (TRAILS). Dependent variables were the total and subscale scores of the Children’s Social Behavior Questionnaire (CSBQ). Results: No significant main effects of COMT Val158Met, 5‐HTTLPR, maternal smoking during pregnancy and low birth weight on ASD symptoms were found. However, the COMT Val/Val genotype interacted with maternal smoking during pregnancy in increasing stereotyped behavior in the IMAGE sample (p = .008); this interaction reached significance in the TRAILS sample after correction for confounders (p = .02). In the IMAGE sample, the 5‐HTTLPR S/S genotype interacted with maternal smoking during pregnancy, increasing problems in social interaction (p = .02), and also interacted with low birth weight, increasing rigid behavior (p = .03). Findings for 5‐HTTLPR in the TRAILS sample were similar, albeit for related CSBQ subscales. Conclusions: These findings suggest gene–environment interaction effects on ASD symptoms in children with ADHD.     

全生物可降解型房间隔缺损封堵器封堵猪房间隔缺损的实验研究

目的评估全生物可降解型房间隔缺损(ASD)封堵器封堵猪ASD的疗效、并发症、生物相容性等。方法房隔穿刺及Rashkind球囊房隔造口术构建猪ASD模型成功后,即刻在透视及经食管超声心动图引导下用所设计全生物可降解型ASD封堵器封堵所构建ASD。术后1周、1个月、3个月和6个月处死实验猪,并行大体标本肉眼观察研究。结果共对10只制备好ASD模型的实验猪进行了封堵,技术成功率100%;术中及术后均未出现残余分流、心律失常、感染等并发症;大体解剖标本见内膜组织从边缘逐渐完全覆盖装置表面,未见装置表面赘生物及血栓形成,装置均未发生移位。结论全生物可降解型ASD封堵器关闭猪ASD技术成功率高、动物实验结果与金属ASD封堵器相仿,是一种安全、有效、可行的方法。其远期及对中、大型ASD的封堵疗效还有待进一步研究。     

Associations between cerebral blood-flow measured by single photon emission computed tomography (SPECT), electro-encephalogram (EEG), behaviour symptoms, cognition and neurological soft signs in children with attention-deficit hyperactivity disorder (ADHD)

Twenty-eight children with attention-deficit hyperactivity disorder (ADHD) were examined with SPECT (single photon emission computed tomography). Seven of the children had abnormal distribution of the regional cerebral blood-flow (rCBF) on visual evaluation and 10 had abnormal EEG findings. The only clinical finding that differentiated the group with normal from abnormal rCBF was behaviour symptom load. A factor analysis of the rCBF in different regions of interest yielded one factor with low rCBF in the temporal and cerebellar regions and high rCBF in the subcortical and thalamic regions, which was significantly associated with the degree of motor impairment and results on a cognitive test (WISC). Another factor consisting of high rCBF in frontal and parietal regions had a significant negative correlation with the degree of behaviour symptoms. There was a negative correlation between the rCBF in the right frontal regions and the degree of behaviour symptoms. The number of minor physical anomalies (MPA) was negatively correlated to the rCBF in the frontal lobes bilaterally. These results suggest that there may be at least two functional disturbances in ADHD, one specific neurodevelopmentally determined disturbance of the frontal lobes, especially of the right hemisphere, related to behaviour deviance, and another disturbance of the integration of the temporal lobes, the cerebellum and subcortical structures, related to motor planning and aspects of cognition.     

Visual behaviour of ADHD children during an attention test: an almost forgotten variable. Attention-Deficit Hyperactivity Disorder

The goal of this study was to examine whether looking away behaviour of ADHD children interferes with their test performance. ADHD and normal children carried out two continuous performance tests (CPTs): one with a regular interstimulus interval (ISI), and the other with an irregular ISI. Children were instructed to push a response button when a target stimulus was presented on the monitor. The children's visual behaviour was recorded and scored offline. A micro-analysis of the visual behaviour indicated that ADHD children timed their looking away behaviour in the regular CPT: i.e. they looked away from the monitor and back in the interval between two succeeding stimuli. As a result they did not miss stimuli. Timing of looking away was less possible in the CPT with the irregular ISI. In this condition, looking away interfered with the ADHD children's task accuracy. In sum, looking away behaviour had a negative effect on the accuracy of test performance of ADHD children when stimuli were unpredictable. Looking away behaviour was not associated with the slower reaction times of the ADHD children. Hence, the often reported slowness of ADHD children is not to be explained by their visual behaviour.     

The Differential Assessment of Children''s Attention: The Test of Everyday Attention for Children (TEA-Ch), Normative Sample and ADHD Performance

"Attention" is not a unitary brain process. Evidence from adult studies indicates that distinct neuroanatomical networks perform specific attentional operations and that these are vulnerable to selective damage. Accordingly, characterising attentional disorders requires the use of a variety of tasks that differentially challenge these systems. Here we describe a novel battery, the Test of Everyday Attention for Children (TEA-Ch), comprising nine subtests adapted from the adult literature. The performance of 293 healthy children between the ages of 6 and 16 is described together with the relationships to IQ, existing measures of attention, and scholastic attainment. This large normative sample also allows us to test the fit of the adult model of functionally separable attention systems to the observed patterns of variance in children's performance. A Structural Equation Modelling approach supports this view. A three-factor model of sustained and selective attention and higher-level "executive" control formed a good fit to the data, even in the youngest children. A single factor model was rejected. There are behavioural and anatomical grounds to believe that Attention Deficit Disorder (ADD) is particularly associated with poor self-sustained attention and behavioural control. The TEA-Ch performance of 24 boys diagnosed with ADD presented here is consistent with this view. When performance levels on WISC-III subtests were taken into account, specific deficits in sustained attention were apparent while selective attention performance was within the normal range.