Impaired working memory in children with attention deficit hyperactivity disorder and their siblings

Introduction: Impairment of working memory in children with attention deficit hyperactivity disorder (ADHD) has been well described. If similar impairment in working memory can be demonstrated among their siblings, this could suggest impaired working memory is a genetic component of ADHD. Methods: Fifty‐seven subjects were recruited: (1) ADHD group (n=21); (2) siblings of ADHD children group (n=15); and (3) non‐ADHD children with chronic medical condition as the control group (n=21). All subjects were aged between 6 and 15 years, and ADHD was diagnosed according to DSM‐IV‐TR. Those with other comorbidity or IQ<70 were excluded. Digit Recall was used for assessment of the phonological loop component, Maze Memory test for the visuospatial sketch pad component and Backward Digit Recall for the central executive component of working memory. Results: ADHD children and their siblings showed similar impairment and both differed from the control group on the Maze Memory test. ADHD children also showed impairment in the Digit Recall test; however, the sibling group did not differ from the control group on this test. The Backward Digit Recall score did not show any significant difference between the three groups. Discussion: Impairment of the visuospatial sketch pad component of working memory seems to cluster in ADHD children and their siblings. Thus, impairment of the visuospatial sketch pad component of working memory may point towards a genetic predisposition of ADHD.     

Somatosensory functioning in children with attention deficit hyperactivity disorder

In older to test the hypothesis that attention deficit hyperactivity disorder (ADHD) is related to deficits in somatosensory processing, 49 ADHD male children and 49 matched controls were tested on a wide range of tactile tasks, and somatosensory evoked potentials (SEP) were also recorded. In addition, parents' and teachers' ratings on the children's typical responses to tactile stimuli were obtained. The results show that the ADHD children were less skilled on suprathreshold, but not on threshold tasks than were the controls. Further, a larger percentage of ADHD children were 'tactile defensive'. Finally, the ADHD children showed Iarger-than-normal amplitudes of late, but not early components of the SEP. These data suggest that some aspects of somatosensory processing by ADHD children are deficient.     

Transferrin in korean children with attention deficit hyperactivity disorder

Objective

The aim of the present study was to investigate the relationship between iron, ferritin, transferrin, total iron binding capacity (TIBC), hemoglobin, mean corpuscular volume (MCV) mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) in children with ADHD.

Methods

MethodsaaThe sample consisted of 48 ADHD children and sex and age matched control children (a couple of 28 boys, 22 girls; age 6-8 years; mean±SD, 6.98±0.39). We diagnosed ADHD according to DSM-IV. ADHD symptoms were evaluated subjectively with Conners'' Parent Rating Scales, Dupaul Parent ADHD Rating Scales. Subjects with ADHD and control were evaluated the hematology test including the iron, transferrin, MCV etc. Paired t test were used to evaluate the relation of a lot of hematology findings between ADHD and control group.

Results

The serum iron, ferritin, transferrin, TIBC, hemoglobin, MCV, MCH, and MCHC of ADHD group were respectively 80.92±33.33 ug/dL, 35.81±16.59 ng/mL, 248.42±44.15 mg/dL, 351.69±102.13 ug/dL, 12.78±0.71 g/dL, 82.94±2.58 fL, 27.18±1.12 uug, 32.79±1.12%. Otherwise the serum iron, ferritin, transferrin, TIBC, hemoglobin, MCV, MCH, and MCHC of control group were respectively 82.04±28.14 ug/dL, 37.05±18.28 ng/mL, 266.27±25.40 mg/dL, 352.77±89.54 ug/dL, 12.77±0.70 g/dL, 81.81±2.96 fL, 26.69±0.99 uug, 32.66±0.96%. A significant difference were found in the transferrin(t=2.63, p=0.011), MCV (t=2.19, p=0.034), and MCH (t=2.18, p=0.034).

Conclusion

These results suggested that lower transferrin levels might be related with ADHD symptoms.     

注意缺陷多动障碍执行功能的研究进展

注意缺陷多动障碍(attention deficit hyperactivity disorder, ADHD)是儿童时期常见的中枢神经系统疾病,其主要表现为注意力不集中、多动及冲动.西方国家患病率为3%～5%之间,国内患病率为3%～10%.ADHD的症状可以造成儿童的学习、人际关系、社交等多个领域的功能明显缺损,部分儿童的症状还可以持续至成年而不愈,成为成人ADHD.     

Executive dysfunctions in children with attention deficit hyperactivity disorder

One hundred and twenty-four male children ranging in age from seven to 12 years-old were selected. The sample was divided into two groups: (1) sixty-two with attention deficit hyperactivity disorder (ADHD) children; and (2) sixty-two normal matched controls (N-ADHD). Three tests were individually administered: (1) Wisconsin Card Sorting Test (WCST); (2) Verbal fluency and semantics (animals and fruits); and, (3) Picture Arrangement subtest of the WISC-R. For all the test scores, statistically significant differences were found between both ADHD and N-ADHD groups. Two separate factor analyses were performed, using the normal and ADHD groups. Four factors were found for the N-ADHD group, which accounted for 85.7% of the variance. The factor structure presented some similarities in both groups: Factor 2, 3 and 4 in the control group corresponded to factors 1, 2 and 3 in the ADHD group. Nonetheless, in the ADHD group Factor 1 (Abstraction and Flexibility Factor) was absent. Results are interpreted as supporting the hypothesis of executive dysfunction in children with ADHD.     

Treatment of attention deficit hyperactivity disorder in children

Objective The present study investigated the predictive power of anxiety, IQ, severity of ADHD and parental depression on the outcome of treatment in children with ADHD. Method Fifty children with ADHD (ages 8–12) were randomized to a 10-week treatment of methylphenidate or to a treatment of methylphenidate combined with multimodal behavior therapy. Prior to treatment predictors were assessed. Outcome was assessed separately for parents and teachers on a composite measure of inattentive, hyperactive, oppositional- and conduct disorder symptoms. Results There was neither a significant difference between the two treatments at baseline nor did treatment condition predict outcome. Therefore the data were collapsed across the two treatments. A combination of anxiety and IQ predicted teacher-rated outcome, explaining 18% of the variance. Higher anxiety and higher IQ’s indicated better treatment outcome. There were no significant predictors of the parent-rated outcome. Conclusion This study showed a small but significant predictive effect of IQ and anxiety on treatment outcome in children with ADHD. Clinical implications This study supports the idea that for the treatment of ADHD children with comorbid anxiety and higher IQ respond better to the two most used treatments for ADHD.     

Venlafaxine in children and adolescents with attention deficit hyperactivity disorder

The primary purpose of this study was to describe tolerability and efficacy of venlafaxine in the treatment of children and adolescents with attention deficit hyperactivity disorder (ADHD). A 6-week open trial of venlafaxine was conducted in 13 children and adolescents (mean age 9.9 +/- 2.5 years) with ADHD, and without comorbid depression. Venlafaxine was initiated at a dose of 18.75 mg/day and flexibly titrated to 56.25 mg/day. The Conners parent scale and Clinical Global Improvement (CGI) severity item were performed at baseline and at the end of the 6-week trial. All subjects completed the trial. Mean final dose of venlafaxine was 40.3 +/- 7.0. Venlafaxine was significantly effective in reducing the total score of the Conners parent scale from baseline to endpoint (P < 0.002, Z =-3.113) and the CGI severity item (P < 0.05). Transient side-effects such as somnolence (n = 2), stomachache (n = 2), and headache (n = 1) disappeared after second week of treatment. Also three subjects complained of sedation after raising the dose to 56.5 mg/day, therefore the dose was reduced to the previous level. These preliminary data suggest that venlafaxine may be an effective medication in the treatment of some children and adolescents with ADHD. Future double-blind controlled trials should be undertaken.     

Smell identification function in children with attention deficit hyperactivity disorder

Objective

Deficits in olfactory function are common features in neurodegenerative and neuropsychiatric disorders. Olfactory processing is related to dopamine metabolism and orbitofrontal cortex functioning, both known to be involved in the neurobiology of ADHD. Some investigations suggested alterations in olfactory processing (identification and detection threshold) in patients with ADHD. Despite increasing knowledge, controversy about this topic still exists regarding children with ADHD. This study was conducted to help elucidate some of this controversy.

Methods

50 participants (8-15 years, mean=10.70±1.77) with ADHD were compared to 50 controls. The two groups were well matched for age, gender and Mean School Scores (MSS). We assessed odor identification and threshold through a smell test composed of two tests of identification and detection threshold. Odor detection threshold was assessed with the odorant phenyl ethyl alcohol solved in propylene glycol using a single staircase method. Odor identification was assessed with chemical essences of five common odorants.

Results

The mean Sensory Identification Score for children with ADHD and the control groups were 3.76 (1.06) and 4.46 (0.76), respectively (p<0.001). The mean for Sensory Threshold Score for ADHD and control group was 6.4 (3.35) and 9.75 (2.16), respectively (p<0.001).

Conclusion

This study replicated altered olfactory performance in ADHD. Substantial olfactory deficits across the two domains of identification and detection threshold are observed in children with ADHD. These deficits do not seem to be a result of olfactory task difficulty and are not influenced by age, gender and MSS. Further studies are required to investigate whether olfactory function can be used as a biological marker for early diagnosis, treatment and prognosis of ADHD.     

Impaired reflexive orienting to social cues in attention deficit hyperactivity disorder

The present study investigated whether another person’s social attention, specifically the direction of their eye gaze, and non-social directional cues triggered reflexive orienting in individuals with Attention Deficit Hyperactivity Disorder (ADHD) and age-matched controls. A choice reaction time and a detection tasks were used in which eye gaze, arrow and peripheral cues correctly (congruent) or incorrectly (incongruent) signalled target location. Independently of the type of the task, differences between groups were specific to the cue condition. Typically developing individuals shifted attention to the location cued by both social and non-social cues, whereas ADHD group showed evidence of reflexive orienting only to locations previously cued by non-social stimuli (arrow and peripheral cues) but failed to show such orienting effect in response to social eye gaze cues. The absence of reflexive orienting effect for eye gaze cues observed in the participants with ADHD may reflect an attentional impairment in responding to socially relevant information.     

Interaction of attention and graphomotor functions in children with attention deficit hyperactivity disorder

The present article provides a review of a series of studies in children with attention deficit hyperactivity disorder (ADHD) concerning (1) the effects of methylphenidate on various attentional functions, (2) the stimulant-induced changes of both qualitative and quantitative (i.e. kinematic) aspects of handwriting, (3) the interaction between conscious control of handwriting and fluency of handwriting movements, and (4) possible therapeutic approaches to graphomotor disturbances. Children with ADHD showed impairments in various aspects of attentional functioning. Pharmacological treatment of ADHD children with methylphenidate resulted in marked improvements of various components of attentional functioning. In comparison to the performance following the withdrawal of methylphenidate, children with ADHD on methylphenidate displayed a significant improvement in task accuracy in the areas of vigilance, divided attention, selective attention (inhibition, focused attention and integration of sensory information) and flexibility. However, the comparison with healthy children revealed considerable deficits regarding vigilance, divided attention, flexibility and selective attention (focused attention and integration of sensory information) in children with ADHD on methylphenidate. The comparison of writing movements of children on and off methylphenidate revealed that medication resulted in a better handwriting, but a deterioration in handwriting fluency as assessed by kinematic analysis. Children with ADHD may use their increased attentional capacities to focus on skills (e.g. handwriting) that are independent of conscious control or may even be disturbed by attention. The findings summarized in this paper indicate, therefore, that administration of methylphenidate alone is insufficient in the treatment of children with ADHD. Children with ADHD may benefit from instructions on how to best use their improved attentional capacities.     

Covert orienting and focusing of attention in children with attention deficit hyperactivity disorder

Performance on the covert visuo-spatial attentional functions of orienting and focusing by a group of ADHD children (n = 20) was compared to that of age and sex-matched control children. In Experiment 1, responses were given to cued targets at valid and invalid locations. In Experiment 2, responses were given to targets presented in small, medium-sized or large visual field locations. For both experiments, the hypotheses that reaction times of ADHD children would be greater than those of control children and that performance would be asymmetrical, were supported. For Experiment 1, ADHD children showed bilaterally greater 'benefits' from having directed attention to the cued location and greater 'costs' in having to relocate the attentional focus than controls. In Experiment 2, the hypothesis that the function of focusing attention by ADHD children may show breakdown in the usual pattern of an increase in reaction time with focus area was partly supported by the finding of similar reaction times to targets presented in medium-sized and large regions of the left visual hemifield. These results have been interpreted as reflecting a stronger anchorage of attention by ADHD children upon a cued location and an inability to shift covert attention easily to an alternative location. The breakdown of the focusing function suggests adoption of similar time response sets across focus area size by the more compromised right hemisphere.     

Administration of moclobemide++ in children with attention deficit hyperactivity disorder

ADHD is a frequent disorder that occurs among approximately 5-10% of school children. Treating this syndrome, pharmacotherapy with different forms of psychotherapy are applied. In many European countries and in the USA the primary medicines are the psychostymulative ones; in Poland, however, they are not registered in the Pharmacopeia. Thus, what seems to be important is seeking other drugs that can be useful in ADHD treatment. In the Child and Adolescent Psychiatry Clinic in Poznań, a group of 15 children (13 boys, 2 girls) at the age of 6-13 were recognised to have ADHD; they were administered moclobemid (Aurorix) in dose of 75-225 mg/d throughout the period of 8 weeks. The medicine efficacy was being estimated with psychometric, questionnaire, and experimental methods. After 4 weeks, the drug ceased to be administered to two children due to complete lack of improvement or deterioration in functioning. It was observed that in the rest of the children their attention and hyperactivity functioning improved significantly. It is essential that the medicine was well tolerated and undesirable symptoms occurred rarely.     

Predictors of antisocial behaviour in children with attention deficit hyperactivity disorder

Abstract Introduction Antisocial behaviour is an important adverse outcome of ADHD. The aim of this review is to examine what is known about the clinical, genetic and environmental factors that contribute to the link between ADHD and antisocial behaviour. Methods Electronic literature searches for the years 1980–2004 and examination of key reference books were undertaken. Results ADHD symptom severity and pervasiveness predict the development of antisocial behaviour. Genetic factors contribute substantially to the risk of developing both problems, although specific genes that influence the development of antisocial behaviour in ADHD have yet to be identified. Some of these genetic effects may be indirectly mediated through environmental risk (gene-environment correlation) or by increasing individual susceptibility to specific environmental adversity (gene-environment interaction). Antisocial behaviour in children with ADHD is also linked with family adversity as well as peer rejection, although some of this adversity may arise as a result of the child’s symptoms. Conclusion Despite the increased risk of antisocial outcomes in those with ADHD, relatively little is known about what risk factors and mechanisms contribute to the link between both these problems. Given the need for appropriate intervention and prevention strategies and targeting resources, more research is needed in this area.     

Atomoxetine pharmacokinetics in children and adolescents with attention deficit hyperactivity disorder

OBJECTIVE: Atomoxetine is indicated for the treatment of attention deficit hyperactivity disorder in children, adolescents, and adults. This study was conducted, in part, to evaluate the single-dose and steady-state pharmacokinetics of atomoxetine in pediatric patients. METHODS: This was an open-label, dose-titration study in pediatric patients with attention deficit hyperactivity disorder. Eligible patients could elect to participate in a single-dose or steady-state discontinuation pharmacokinetic evaluation including serial plasma sample collection over 24 hours. Plasma concentrations of atomoxetine, 4-hydroxyatomoxetine, and N-desmethylatomoxetine were determined using an atmospheric pressure chemical ionization liquid chromatography/mass spectrometry/mass spectrometry assay. Pharmacokinetic parameters were calculated using noncompartmental analysis. RESULTS: Twenty-one cytochrome P450 2D6 extensive metabolizer patients participated in these single-dose and steady-state pharmacokinetic evaluations. Atomoxetine was rapidly absorbed, with peak plasma concentrations occurring 1 to 2 hours after dosing. Half-life averaged 3.12 and 3.28 hours after a single dose and at steady state, respectively. Minimal accumulation occurred in plasma after multiple twice-daily dosing in extensive metabolizer pediatric patients, as expected based on single-dose pharmacokinetics. As the dose (in mg/kg) increased, proportional increases in area under the curve were observed. CONCLUSIONS: The pharmacokinetics of atomoxetine in extensive metabolizer patients were well characterized over a wide range of doses in this study. Atomoxetine pharmacokinetics in pediatric patients and adult subjects were similar after adjustment for body weight.     

No auditory conduction abnormality in children with attention deficit hyperactivity disorder

Attention deficit hyperactivity disorder (ADHD) is a neurobehavioral developmental disorder characterized by lack of sustained attention and hyperactivity. It has been suggested that asymmetrical conduction of the auditory stimulus in the brainstem plays a role in the pathophysiological process of ADHD. In the present study, the functional integrity of the central auditory pathway was assessed using the auditory brainstem response (ABR), mid-latency response (MLR) and slow vertex response (SVR). Twenty ADHD children and twenty controls were recruited for the study and recordings were done on a computerized evoked potential recorder using the 10-20 system of electrode placement. There emerged no significant difference in absolute peak latencies, interpeak latencies and amplitude of ABR or latency of MLR in the ADHD children as compared with the controls. Prolongation of the SVR latency was found in the children with ADHD versus the controls, but the difference was statistically insignificant. The present study does not suggest any auditory conduction abnormality as a contributory factor in ADHD.     

Movement sequencing in children with Tourette's syndrome and attention deficit hyperactivity disorder.

Little research has been conducted to examine sequential motor functioning of children with Tourette's syndrome (TS) and attention deficit hyperactivity disorder (ADHD). Movement sequencing performance for a group of 12 children with TS and 24 children with ADHD children (12 taking and 12 not taking stimulant medication) and matched control subjects was examined using a serial choice reaction time button-pressing procedure. Aspects of movement preparation and execution were measured for 10 sequential two-way choice points along a response board that extinguished the illuminated target buttons at certain specific times contingent on the previous button press or release. The level of advance information was systematically reduced to provide three levels of reduction of advance information, including no reduction, moderate reduction, and high reduction. Children with TS and ADHD (unmedicated) showed larger increases in down time, reflecting aspects of movement preparation, for the highest level of reduction of advance information than did their respective control groups. These deficits are suggestive of underlying frontostriatal dysfunction. Furthermore, the normalization of performance for children with ADHD taking stimulant medication assists in the confirmation of the validity of such a clinical diagnosis and seems to add to the clinical efficacy of this form of treatment, which has previously been associated with improvements for predominantly attentional and inhibitory symptoms of ADHD.     

Response to methylphenidate in children with attention deficit hyperactivity disorder and manic symptoms in the multimodal treatment study of children with attention deficit hyperactivity disorder titration trial

OBJECTIVE: Recent reports raise concern that children with attention deficit hyperactivity disorder (ADHD) and some manic symptoms may worsen with stimulant treatment. This study examines the response to methylphenidate in such children. METHODS: Data from children participating in the 1-month methylphenidate titration trial of the Multimodal Treatment Study of Children with ADHD were reanalyzed by dividing the sample into children with and without some manic symptoms. Two "mania proxies" were constructed using items from the Diagnostic Interview Schedule for Children (DISC) or the Child Behavior Checklist (CBCL). Treatment response and side effects are compared between participants with and without proxies. RESULTS: Thirty-two (11%) and 29 (10%) participants fulfilled criteria for the CBCL mania proxy and DISC mania proxy, respectively. Presence or absence of either proxy did not predict a greater or lesser response or side effects. CONCLUSION: Findings suggest that children with ADHD and manic symptoms respond robustly to methylphenidate during the first month of treatment and that these children are not more likely to have an adverse response to methylphenidate. Further research is needed to explore how such children will respond during long-term treatment. Clinicians should not a priori avoid stimulants in children with ADHD and some manic symptoms.     

Gait in attention deficit hyperactivity disorder

Abstract Background Cognitive function and the loading of attention presumably play an important role in gait as well as in fall risk, but previous work has not demonstrated this in any cause-and-effect way. Objectives To gain insight into the relationship between gait and cognitive function, we sought: (1) To compare the gait rhythmicity (stride time variability) of children with attention deficit hyperactivity disorder (ADHD) to controls, (2) To test the hypothesis that dual tasking leads to increased stride-to-stride variability in ADHD, and (3) To test whether pharmacological treatment that relieves ADHD symptoms reduces stride-to-stride variability. Patients and Methods Gait was quantified in children with ADHD and in age-matched healthy controls under single task and dual task conditions on three occasions: off medications (both groups) and, in the ADHD group, after double blinded, randomized administration of methylphenidate (MPH) or placebo. Results At baseline, children with ADHD tended to walk with increased stride-to-stride variability compared to the controls during the single task condition (p = 0.09). During dual task walking, stride time variability was significantly reduced in the children with ADHD (p < 0.004), but not in the controls. In the children with ADHD, the placebo did not significantly affect stride-to-stride variability or the dual tasking response. In contrast, stride time variability was significantly reduced on MPH (p < 0.001) such that dual tasking no longer affected variability. Conclusions The present findings demonstrate alterations in the gait of children with ADHD, support a cause and effect link between cognitive function and gait, and suggest that enhancement of attention abilities may, in certain populations, improve gait rhythmicity.     

Treatment of attention deficit hyperactivity disorder with neurotherapy.

Significant public health concerns exist regarding our current level of success in treating ADHD. Medication management is very helpful in 60-70% of patients. Side effects, lack of compliance and the fact that stimulant medications cannot be given late in the day limit the benefits largely to school hours. While stimulants improve behavior and attention, less of an effect has been noted on academic and social performance. Continuing concerns exist about long-term safety, and studies on long-term cardiovascular and neurophysiological effects have not been carried out. Neurotherapy for ADHD offers an effective alternate for patients whose treatment is limited by side effects, poor medication response and in cases in which the patients and/or their parents refuse to consider medications. Studies indicate clinical improvement is largely related to measurable improvements in the EEG signature, evidenced by declining theta/beta ratios over frontal/central cortex and/or reduced theta/alpha band amplitudes.