Somatosensory evoked potentials in attention deficit/hyperactivity disorder and tic disorder.

OBJECTIVE: Both attention deficit/hyperactivity disorder (ADHD) and chronic tic disorder (TD) are hyperkinetic disorders. These disorders often coexist with each other and frequently have sensory components. Therefore, we hypothesized that they might have a common pathophysiology involving the somatosensory system, especially hyper-excitabilities of primary somatosensory area. METHODS: To evaluate sensory system excitability, we examined somatosensory evoked potentials (SEP) elicited by median nerve stimulation in 18 children with ADHD and 18 children with TD. RESULTS: Three children with ADHD and 8 children with TD showed giant SEP and the peak-to-peak amplitude for N20-P25 was also significantly greater than that obtained from normally developing children (P<0.05 for ADHD and P<0.01 for TD). Children with TD had significant left-ward asymmetry of N20-P25 (P<0.01) and higher left-hemispheric N20-P25 than children with ADHD (P<0.05). CONCLUSIONS: Although hyper-excitability of the primary somatosensory area is a common characteristic for ADHD and TD, its severity, especially in the left-hemisphere, differs (i.e. TD has left-ward hyper-excitability). SIGNIFICANCE: The possibility remains that hyper-excitability of the primary somatosensory area is a reason why these disorders often coexist with each other and left-ward hyper-excitability of the primary somatosensory area is a unique feature of TD described for the first time.     

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.     

Once-daily atomoxetine treatment for children and adolescents with attention deficit hyperactivity disorder: a randomized,placebo-controlled study

OBJECTIVE: The authors assessed the efficacy of once-daily atomoxetine administration in the treatment of children and adolescents with attention deficit hyperactivity disorder (ADHD). METHOD: In a double-blind study, children and adolescents with ADHD (N=171, age range=6-16 years) were randomly assigned to receive 6 weeks of treatment with either atomoxetine (administered once daily) or placebo. RESULTS: Outcomes among atomoxetine-treated patients were superior to those of the placebo treatment group as assessed by investigator, parent, and teacher ratings. The treatment effect size (0.71) was similar to those observed in previous atomoxetine studies that used twice-daily dosing. Parent diary ratings suggested that drug-specific effects were sustained late in the day. Discontinuations due to adverse events were low (less than 3%) for both treatment groups, and no serious safety concerns were observed. CONCLUSIONS: Once-daily administration of atomoxetine is an effective treatment for children and adolescents with ADHD.     

Double-blind, placebo-controlled study of zinc sulfate in the treatment of attention deficit hyperactivity disorder

BACKGROUND: The most commonly used medications for attention deficit hyperactivity disorder (ADHD) are the psychostimulants. There is, however, considerable awareness in alternative, nonstimulant therapies, because some patients respond poorly to stimulants or are unable to tolerate them. Some studies suggest that deficiency of zinc play a substantial role in the aetiopathogenesis of ADHD. Therefore, to assess the efficacy of zinc sulfate we conducted treatment trial. METHODS: Patients with a primary DSM-IV diagnosis of ADHD (N=400; 72 girls, 328 boys, mean age=9.61+/-1.7) were randomly assigned in a 1:1 ratio to 12 weeks of double-blind treatment with zinc sulfate (n=202) (150 mg/day) or placebo (n=198). Efficacy was assessed with the Attention Deficit Hyperactivity Disorder Scale (ADHDS), Conners Teacher Questionnaire, and DuPaul Parent Ratings of ADHD. Primary efficacy variables were differences from baseline to endpoint (last observation carried forward) in mean ADHDS and Conners Teacher Questionnaire scores between the zinc sulfate and the placebo groups. Safety evaluations included monitoring of adverse events, vital signs and clinical laboratory values. RESULTS: Zinc sulfate was statistically superior to placebo in reducing both hyperactive, impulsive and impaired socialization symptoms, but not in reducing attention deficiency symptoms, as assessed by ADHDS. However, full therapeutic response rates of the zinc and placebo groups remained 28.7% and 20%, respectively. It was determined that the hyperactivity, impulsivity and socialization scores displayed significant decrease in patients of older age and high BMI score with low zinc and free fatty acids (FFA) levels. Zinc sulfate was well tolerated and associated with a low rate of side effect. CONCLUSIONS: Zinc monotherapy was significantly superior to placebo in reducing symptoms of hyperactivity, impulsivity and impaired socialization in patients with ADHD. Although by themselves, these findings may not be sufficient, it may well be considered that zinc treatment appears to be an efficacious treatment for ADHD patients having older age and high BMI score with low zinc and FFA levels.     

托莫西汀治疗儿童注意力缺陷多动障碍研究进展

为探讨托莫西汀对儿童注意力缺陷多动障碍(ADHD)的疗效,本文对托莫西汀治疗儿童ADHD的研究进行综述。通过阐述ADHD发病机制和治疗方案,总结托莫西汀治疗儿童ADHD的效果和安全性,并与哌甲酯、安慰剂治疗的效果进行比较,为ADHD临床治疗提供参考。     

Impaired habituation in children with attention deficit hyperactivity disorder.

OBJECTIVE: To investigate whether children with attention deficit hyperactivity disorder show impaired habituation to peripheral stimuli. METHOD: We compared the Troxler effect (the ability to habituate to a peripheral visual stimulus when presented with a competing central visual stimulus) in groups of 23 children with attention deficit hyperactivity disorder and 15 controls matched for age, gender, and IQ. RESULTS: Regression analyses revealed a statistically significant effect of diagnosis on fading (P = 0.03), with attention deficit hyperactivity disorder subjects taking longer to fade to a peripheral stimulus than controls. Additional analyses revealed a significant interaction between diagnosis and visual field; control subjects showed similar fading times to stimuli presented in the right and left visual fields (13.25 vs. 12.96 seconds), while the attention deficit hyperactivity disorder group showed much slower fading in the right than in the left visual field (18.64 vs. 15.00 seconds). CONCLUSIONS: Our results suggest that children with attention deficit hyperactivity disorder have impaired visual habituation. The findings provide evidence of frontal dysfunction in attention deficit hyperactivity disorder and suggest that impaired habituation contributes to off-task behavior in children with the disorder.     

A double-blind, placebo-controlled withdrawal trial of dexmethylphenidate hydrochloride in children with attention deficit hyperactivity disorder

OBJECTIVES: d,l-threo-methylphenidate HCl (D,L-MPH) is the most common treatment of attention deficit hyperactivity disorder (ADHD). A previous report showed placebo-controlled efficacy for the purified d-isomer (dexmethylphenidate hydrochloride, d-MPH, Focalin) with a 2:1 potency compared to dl, and suggested a 6-hour duration of action. This study complements that report by studying the effect of placebo-controlled discontinuation and retesting the duration of action. METHODS: A 6-week, open-label titration of d-MPH (2.5-10 mg twice-a-day) was followed by a double-blind, placebo-controlled, 2-week withdrawal study of responders. RESULTS: In the open titration, 82% of the 89 enrolled patients achieved a Clinical Global Impression-Improvement (CGI-I) rating of much or very much improved. Only 5 patients discontinued for adverse events. Seventy-five patients continued into the placebo-controlled discontinuation. For the randomly assigned d-MPH (n=35) and placebo (n=40) groups, mean ages, respectively, were 10.1 +/- 2.9 and 9.9 +/- 2.7 years, 86% and 78% were male, and 70.6% and 80.0% took the ceiling dose of 10 mg twice-daily, respectively. Each group had 80% combined type ADHD and 20% inattentive type. By the end of the 2-week, placebo-masked withdrawal, significantly more placebo patients (24 of 39) than d-MPH continuers (6 of 35) relapsed (61.5% versus 17.1%, p=0.001). Compared to d-MPH continuers, placebo patients deteriorated significantly more in the 2-week period on teacher ratings of the 18 ADHD symptoms rated 0-3 (p=0.028), the 3 p.m. and 6 p.m. parent ADHD symptom ratings (p=0.0026 and p=0.0381, respectively), and clinic (2-3 p.m.) and home (6 p.m.) Math Tests (p=0.024 and p<0.0001, respectively). The 6 p.m. scores replicated the significant effect at 6 hours reported in the previous study. CONCLUSIONS: d-MPH is safe, tolerable, and effective, with a 6-hour duration of effect suggested by the significant difference from placebo at 6 hours on a double-blind discontinuation.     

Growth hormone response to guanfacine in boys with attention deficit hyperactivity disorder: a preliminary study

OBJECTIVE: This preliminary study evaluated a method for assessing central noradrenergic function in children via the growth hormone response to a single dose of the alpha-2 adrenergic receptor agonist guanfacine and examined whether this measure distinguishes between attention deficit hyperactivity disorder (ADHD) boys with and without reading disabilities (RD). METHODS: Plasma growth hormone was assessed before and after the oral administration of guanfacine and placebo in boys with ADHD who were divided into subgroups based on the presence (n = 3) or absence (n = 5) of RD. RESULTS: Guanfacine and placebo conditions did not differ at baseline, but peak growth hormone was significantly higher following guanfacine. The increase in growth hormone following guanfacine was significantly greater in boys without RD as compared to those with RD, with no overlap between the groups. CONCLUSIONS: Consistent with findings using peripheral measures of noradrenergic function, these preliminary data suggest that ADHD boys with and without RD may differ in central noradrenergic function.     

A controlled study of nortriptyline in children and adolescents with attention deficit hyperactivity disorder

OBJECTIVES: To study the efficacy and tolerability of nortriptyline (NT) in the treatment of pediatric attention deficit hyperactivity disorder (ADHD). METHODOLOGY: Subjects were outpatient children and adolescents with ADHD ascertained from clinical referrals. Subjects were enrolled in a 6-week open study in which NT was titrated to 2 mg/kg/day as tolerated over 2 weeks. Using either a 30 % reduction in the ADHD rating scale or a score of 1 or 2 on the Clinical Global Impression (CGI) scale for ADHD improvement, responders to treatment were then randomized into a 3-week, controlled discontinuation phase. During this phase, subjects either continued on their current dose of NT or were tapered to placebo under double-blind conditions. Subjects were monitored for symptoms of ADHD, oppositionality, anxiety, and depression. RESULTS: Of the 35 subjects enrolled in the study, 32 completed the open phase and 23 completed the discontinuation phase. The mean dose of NT was 80 mg (1.8 mg/kg/day), resulting in a serum level of 81 ng/ml. At the conclusion of the open 6-week study, NT was related to a significant reduction in ADHD (p < 0.001) and oppositional symptoms (p < 0.001). At the conclusion of the discontinuation phase, the 12 subjects randomized to NT had significantly lower scores on the DSM-IV ADHD symptom checklist than those 11 subjects randomized to placebo (31 versus 21; t = 2.2; p < 0.04). No significant adverse events were observed, and children were noted to have weight gain during the trial. CONCLUSIONS: These data suggest that NT is effective in reducing symptoms not only of ADHD but also of oppositionality. This group of children and adolescents tolerated robust dosing of NT well, with few clinical or cardiovascular adverse events.     

Pharmacologic treatment of attention deficit hyperactivity disorder.

This article describes the role of psychostimulant medication in the treatment of attention deficit hyperactivity disorder. Included are the drugs' putative mechanisms of action, pharmacology, toxicology, indications for their use, short-term and long-term actions, adverse effects, specific dosing regimens, therapeutic monitoring techniques, alternative medications, and drug interactions.     

注意缺陷多动障碍血小板单胺氧化酶活性测定的初步研究

本文测定了注意缺陷多动障碍（ＡＤＨＤ）患者血小板单胺氧化酶活性，结果显示ＡＤＨＤ时该酶活性明显低于对照组，而在经哌醋甲酯治疗后无明显改变，与Ｃｏｎｎｅｒｓ量表也未显示出明显相关。文中还对单胺氧化酶与治疗的关系进行了讨论。     

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.     

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.     

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.