Growth hormone and prolactin response to methylphenidate in children with attention deficit disorder

Utilizing a double-blind, drug-placebo design, we examined growth hormone (GH) and prolactin (Pro) response to oral administration of methylphenidate (MPH) in 14 boys (ages 7.0-12.4 years) with Attention Deficit Disorder (ADD). Four conditions representing three different MPH doses (0.3 mg/kg O.D., 0.3 mg/kg B.I.D., 0.6 mg/kg O.D.) and Placebo were compared in each subject, each condition lasting for a period of 3 weeks. GH and Pro response were measured both as maximum peak GH (DGH) or nadir of Pro (DPro) as well as area under the curve for the first four hours after MPH administration (AUCGH, AUCPro). Behavioral measures included parent ratings on the Yale Children's Inventory and teacher ratings on the Yale and Conners Behavior Rating Scales and Kagan's Matching Familiar Figures Test (MFFT). Prolactin response as measured by AUCPro was significantly increased after MPH compared to placebo (t = 2.04, p less than 0.05, placebo vs all doses MPH). This difference observed for AUCPro between placebo and MPH was evident as well when we considered the number of times AUCPro declined after MPH as compared to placebo (p = .018, Fisher's exact test). Within-subjects analysis of covariance demonstrated significant correlations between the improvement in reaction time on the MFFT and 1) GH response (AUCGH, r = .58, p less than .001) and 2) prolactin response (AUCPro, r = .40, p less than .05) and between improvement in attention as measured on the Yale BRS and GH response (AUCGH, r = .57, p less than .05). Our findings suggest that measures other than GH and prolactin may be more desirable measures of brain catecholaminergic functioning.     

Anxiety and methylphenidate in attention deficit hyperactivity disorder: a double-blind placebo-drug trial

To examine the relationship between attention and anxiety and the response to methylphenidate in children with attention deficit hyperactivity disorder (ADHD), a total of 57 boys, between the ages of 7-12?years, were assessed for their attention and level of anxiety. Methylphenidate was administered for a week in a randomized double-blind drug/placebo-drug cross-over design. The levels of anxiety were evenly distributed between the inattentive and hyperactive/impulsive types. Anxiety was significantly correlated with the attention as reported by both teachers and parents. The response to methylphenidate was inversely correlated with the reported anxiety level only in boys with the hyperactive/impulsive and combined types. The higher the level of anxiety, the lower level of response to methylphenidate was observed. In the assessment and treatment of children with ADHD, the level of anxiety should be evaluated and taken into account while planning and monitoring treatment regiment.     

Training of attention functions in children with attention deficit hyperactivity disorder

Pharmacological treatment of children with ADHD has been shown to be successful; however, medication may not normalize attention functions. The present study was based on a neuropsychological model of attention and assessed the effect of an attention training program on attentional functioning of children with ADHD. Thirty-two children with ADHD and 16 healthy children participated in the study. Children with ADHD were randomly assigned to one of the two conditions, i.e., an attention training program which trained aspects of vigilance, selective attention and divided attention, or a visual perception training which trained perceptual skills, such as perception of figure and ground, form constancy and position in space. The training programs were applied in individual sessions, twice a week, for a period of four consecutive weeks. Healthy children did not receive any training. Alertness, vigilance, selective attention, divided attention, and flexibility were examined prior to and following the interventions. Children with ADHD were assessed and trained while on ADHD medications. Data analysis revealed that the attention training used in the present study led to significant improvements of various aspects of attention, including vigilance, divided attention, and flexibility, while the visual perception training had no specific effects. The findings indicate that attention training programs have the potential to facilitate attentional functioning in children with ADHD treated with ADHD drugs.     

Increased oxidative stress in children with attention deficit hyperactivity disorder

Objectives: The purpose of this study was to investigate oxidative stress in children with attention deficit hyperactivity disorder (ADHD).

Methods: Total oxidant status (TOS), total antioxidant status (TAS), paraxonase-1 (PON-1) and arylesterase (ARE) activity were measured in 76 children (44 boys, 32 girls) diagnosed with ADHD according to the DSM-IV and 78 healthy children (46 boys, 32 girls).

Results: Age and sex were similar between the groups (P?>?0.05). TOS and the oxidative stress index (OSI) were higher in the patient group than the control group (P?<?0.001). PON-1 (P?=?0.002), ARE (P?=?0.010) activity and TAS (P?<?0.001) were lower in the patient group than the control group.

Discussion: We found decreased PON-1, ARE activity and TAS, and increased TOS and OSI in children with ADHD. Our study showed that there is significantly increased oxidative stress in children with ADHD.     

Effects of acute and chronic methylphenidate administration on beta-endorphin, growth hormone, prolactin and cortisol in children with attention deficit disorder and hyperactivity

The effect of 5 mg/p.o. methylphenidate (MPH) challenge on beta-endorphin (beta-EP), growth hormone (GH), prolactin (Prl) and cortisol was investigated in 16 children suffering from attention deficit disorder with hyperactivity (ADDH) before and after 4 weeks MPH treatment. The study population consisted of 13 males and 3 females aged 6-11 years. All patients were drug free for at least 3 months prior to investigation. The severity of ADDH symptomatology and response to MPH chronic treatment was assessed using parent/teacher abbreviated Conners rating scale. Blood samples for beta-EP, cortisol, Prl and GH were drawn before initiation of treatment (basal pre-treatment level), 2 hours after MPH challenge, 4 weeks after MPH treatment (basal post-treatment level) and 2 hours after re-challenge with MPH. Chronic MPH treatment resulted in a decrease in basal Prl levels (5.5 +/- 2.8 vs 3.7 +/- 1.9 ng/ml; p less than 0.05). Pre-treatment challenge stimulates significantly both beta-EP (15.0 +/- 7.5 vs 12.5 +/- 5.3 pmol/l; p less than 0.05) and cortisol secretion (20.6 +/- 6.6 vs 12.6 +/- 5.8 micrograms/dl; p less than 0.05), and suppressed Prl secretion (4.0 +/- 1.5 vs 5.5 +/- 2.8 ng/ml; p less than 0.05). Re-challenge with MPH enhanced beta-EP levels (14.9 +/- 8.6 vs 10.6 +/- 5.0 pmol/l; p less than 0.05) but failed to affect cortisol, Prl and GH secretion. The acute and chronic neuroendocrine effects of MPH administration might be related to its dopaminergic and adrenergic agonistic activity. It might be that the stimulatory effect of single and repeated acute MPH administration on beta-EP release contributes to the beneficial effect of MPH treatment in ADDH children.     

Asymmetry of basal ganglia in children with attention deficit hyperactivity disorder

Attention deficit hyperactivity disorder (ADHD) is a common neuropsychiatry disorder with several key symptoms, such as inattentiveness, impulsivity and hyperactivity. Neuropsychiatry studies have implicated the frontostriatal circuit in the pathological physiology of the disorder. Using magnetic resonance imaging (MRI), we examined the basal ganglia in 13 ADHD patients and eight unaffected comparison children. The volume of caudate, putamen and globus pallidus was measured. In the ADHD patients, we detected an increased left > right asymmetry of the basal ganglia. This reversal of asymmetry in the globus pallidus and caudate nucleus were statistically significant. These finding provide further evidence of morphological brain abnormalities in ADHD.     

Height, weight, IGF-I, IGFBP-3 and thyroid functions in prepubertal children with attention deficit hyperactivity disorder: effect of methylphenidate treatment

OBJECTIVE: To investigate if there are any disease-related or methylphenidate-induced aberrations in growth parameters, growth hormone insulin-like growth factor (IGF)-I, IGFBP-3 axis and the thyroid function tests in children with attention deficit hyperactivity disorder (ADHD). METHODS: Newly diagnosed and untreated prepubertal children with ADHD were longitudinally followed before and approximately every 4 months after methylphenidate treatment for up to 16 months. Height SDS, weight SDS, BMI SDS, serum GH, IGF-I, IGFBP-3, T4, free T4, T3, and TSH were measured at each visit. RESULTS: All of the examined parameters were within normal limits for age before treatment. Methylphenidate treatment did not significantly affect SDS of height, weight, BMI, IGF-I and IGFBP-3 in the long run. Serum T4 and free T4 levels showed modest reductions within normal limits in a time-dependent manner. CONCLUSIONS: Prepubertal children with ADHD had normal height, weight, BMI, serum IGF-I and IGFBP-3 and thyroid functions. Methylphenidate treatment had no sustained effects on growth parameters, IGF-I and IGFBP-3 during the follow-up period of this study. However, it caused a mild decrease in total and free T4 which may warrant further monitoring.     

Chronotype and its relationship with sleep disorders in children with attention deficit hyperactivity disorder

Chronotype can be classified as morningness types, people who prefer morning hours for their physical and mental activities; eveningness types, people who prefer the afternoon or evening hours; and intermediate types, those who show characteristics of both morningness and eveningness types. Attention deficit hyperactivity disorder (ADHD) has been linked with disturbances in chronotype, particularly increased eveningness. Despite the possibility of an association between chronotypes, sleep disturbances and ADHD symptoms, there is little evidence of this association considering the child population. The purpose of this study was to examine chronotype preferences in children aged between 7 and 12 years who were diagnosed as having ADHD in the context of sleep disturbances. The Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime Version, Conner’s Rating Scales, Children’s Sleep Habit Questionnaire and Children’s Chronotype Questionnaire were used for the evaluation of children with ADHD and healthy controls. The ADHD group was 73% combined-type, and the eveningness scores of the ADHD group (n = 52) were significantly higher than the control group (n = 52) (p < 0.01). There was a positive correlation between the higher scores of eveningness and total scores on resistance to sleep time (p < 0.09), respiratory problems during sleep and daytime sleepiness in the ADHD group. CSHQ total score was found to be a predictive factor for eveningness among children with ADHD (p < 0.01). These findings highlight possible reciprocal links between ADHD symptoms, sleep disturbances and chronotype in children aged 7–12 years, which might lead to individualized treatment options.     

Characteristics of attention in children with attention deficit hyperactivity disorder (an analytical review)

The information concerning specific features of different attention components (alertness, sustention and selectivity) in children with attention deficit hyperactivity disorder (ADHD) is analyzed and systematized. According to the data reviewed, behavioral and attention problems described as ADHD are not homogeneous. Literature analysis of attention characteristics in children with ADHD shows that different components can be disrupted if ADHD is diagnosed as inattentive or combined subtype, but the main deficit in this case is that of selective voluntary attention. In case of hyperactivity/impulsivity subtype of ADHD, attention is impaired mainly in its brain activation components.     

Prepotent response inhibition and reaction times in children with attention deficit/hyperactivity disorder from a Caribbean community

Impairment in inhibitory control has been postulated as an underlying hallmark of attention deficit/hyperactivity disorder (ADHD), which can be utilized as a quantitative trait for genetic studies. Here, we evaluate whether inhibitory control, measured by simple automatized prepotent response (PR) inhibition variables, is a robust discriminant function for the diagnosis of ADHD in children and can be used as an endophenotype for future genetic studies. One hundred fifty-two school children (30.9% female, 67.8% with ADHD) were recruited. The ADHD checklist was used as the screening tool, whilst the DSM-IV Mini International Neuropsychiatry Interview, neurologic interview and neurologic examination, and the WISC III FSIQ test were administered as the gold standard procedure to assert ADHD diagnosis. A Go/No-Go task using a naturalistic and automatized visual signal was administered. A linear multifactor model (MANOVA) was fitted to compare groups including ADHD status, age, and gender as multiple independent factors. Linear discriminant analysis and the receiver operating characteristic curve were used to assess the predictive performance of PR inhibition variables for ADHD diagnosis. We found that four variables of prepotent response reaction time- and prepotent response inhibition established statistically significant differences between children with and without ADHD. Furthermore, these variables generated a strong discriminant function with a total classification capability of 73, 84% specificity, 68% sensitivity, and 90% positive predictive value for ADHD diagnosis, which support reaction times as a candidate endophenotype that could potentially be used in future ADHD genetic research.     

Neurofeedback treatment for attention-deficit/hyperactivity disorder in children: a comparison with methylphenidate

Clinical trials have suggested that neurofeedback may be efficient in treating attention-deficit/hyperactivity disorder (ADHD). We compared the effects of a 3-month electroencephalographic feedback program providing reinforcement contingent on the production of cortical sensorimotor rhythm (12–15 Hz) and beta1 activity (15–18 Hz) with stimulant medication. Participants were N = 34 children aged 8–12 years, 22 of which were assigned to the neurofeedback group and 12 to the methylphenidate group according to their parents' preference. Both neurofeedback and methylphenidate were associated with improvements on all subscales of the Test of Variables of Attention, and on the speed and accuracy measures of the d2 Attention Endurance Test. Furthermore, behaviors related to the disorder were rated as significantly reduced in both groups by both teachers and parents on the IOWA-Conners Behavior Rating Scale. These findings suggest that neurofeedback was efficient in improving some of the behavioral concomitants of ADHD in children whose parents favored a nonpharmacological treatment.     

The relationship between chronotype and obesity in children and adolescent with attention deficit hyperactivity disorder

ABSTRACT

Children and adolescents with Attention De?cit Hyperactivity Disorder (ADHD) have a high prevalence of obesity, but the relationship between these two problems is not clear. Chronotype preferences may be one of the possible mechanisms underlying the link between ADHD and obesity. This is the ?rst study to investigate whether chronotype preferences are a mechanism linking ADHD symptoms to obesity in children and adolescents. This cross-sectional study included 110 drug-naive children and adolescents aged 7–17 years with ADHD. The Kiddie Schedule for Affective Disorders and Schizophrenia‐Present and Lifetime Version (K‐SADS‐PL) was used to diagnose ADHD or to exclude psychiatric comorbidity. The Conners’ Parents Rating Scale-Revised Short Version (CPRS-RS) and Children’s Chronotype Questionnaire (CCQ) were used to assess the severity of ADHD symptoms and chronotype preferences. Body mass index (BMI) was calculated and classified according to national age- and gender-specific reference values. The participants were divided into three groups as normal weight (<85%, n = 38), overweight (85%-95%, n = 30) and obesity (>95%, n = 42) according to their BMI percentile. There were statistically significant differences between the three groups in terms of chronotype preference (p = .000). Morningness preference was 86.84% in the normal BMI group and 26.19% in the obese BMI group. Eveningness preference was 7.89% in the normal BMI group and 61.90% in the obese BMI group. There was a correlation between the BMI percentile scores and the morningness/eveningness scale (M/E) scores. Moreover, there was a correlation between the BMI percentile scores and the oppositional and ADHD index scores. According to logistic regression analysis, the odds ratio of having evening type for obesity was 5.66 and the odds ratio of having morning type for normal weight was 13.03. Independently from ADHD symptoms, eveningness was directly related to obesity and morningness was directly related to normal weight. Prospective studies should be performed to better understand the relationship between ADHD, overweight/obesity and chronotype.     

Reduced platelet monoamine oxidase type B activity and lymphocyte muscarinic receptor binding in unmedicated children with attention deficit hyperactivity disorder

Several lines of evidence support the role of monoaminergic and cholinergic dysregulation in attention deficit hyperactivity disorder (ADHD) and the concept that peripheral blood neurotransmission indices may represent valuable surrogate CNS markers. We determined platelet MAO-B activity (p-MAO-B) and lymphocyte muscarinic cholinergic receptor binding (l-MR) in 44 unmedicated ADHD children (aged 9.1?±?2.87 years) and in 26 age-matched controls for comparison. Lower levels of p-MAO-B (~35%) and l-MR (~55%) in ADHD were observed compared with controls. Differences were gender-dependent: p-MAO-B was reduced in males only (5.20?±?2.99 vs 8.46?±?5.1 nmol mg^?1 protein h^?1 in ADHD and controls, respectively) and l-MR in females only (ADHD vs control: 6.63?±?1.75 and 15.30?±?8.35?fmol 10^?6 cells). The clinical significance was corroborated by the correlation between these markers and severity of specific symptoms: lower p-MAO-B associated with increased inattention scores (Conners’ teacher-rating scale); lower l-MR associated with increased score for oppositional-defiant disorder (ODD) (SNAP-IV); and trend towards correlation between increased inattention (SNAP-IV) and lower l-MR.     

注意缺陷多动障碍儿童肠道菌群特点及与行为问题的相关性研究

分析注意缺陷多动障碍（ADHD）儿童肠道菌群特点与行为问题的相关性。

选取2022年1月到2023年5月我院收治的96例ADHD患儿和健康体检的96例儿童,分别作为研究组和对照组。对所有儿童粪便样本进行宏基因组测序并分析肠道菌群特点。采用Conners儿童行为问卷－家长版（PSQ）评估两组儿童的行为。采用Pearson相关性分析肠道菌群分布与行为问题的相关性。

研究组患儿肠道菌群α−多样性低于对照组,肠杆菌属、气味杆菌属和枸橼酸杆菌属相对丰度均高于对照组,韦荣球菌属、拟杆菌属、双歧杆菌属和普氏栖粪杆菌相对丰度均低于对照组,差异均具有统计学意义（P＜0.05）。研究组患儿Conners PSQ问卷评分高于对照组（P＜0.05）。研究组患儿Conners PSQ问卷各因子评分与肠道肠杆菌属、气味杆菌属和枸橼酸杆菌属均呈正相关（P＜0.05）,与韦荣球菌属、拟杆菌属、双歧杆菌属和普氏栖粪杆菌均呈负相关（P＜0.05）。

ADHD儿童肠道菌群构成与健康儿童不同,不同肠道菌群与患儿行为问题有相关性。

     

Evaluation of oxidative stress status in children with pervasive developmental disorder and attention deficit hyperactivity disorder using urinary-specific biomarkers

Pervasive developmental disorder (PDD) and attention deficit hyperactivity disorder (ADHD) are likely to be associated with increased oxidative stress, particularly that of lipid peroxidation. We evaluated the oxidative stress status of pediatric PDD and ADHD patients using their urine samples. Urinary acrolein-lysine levels in 11 PDD and 10 ADHD children (205 ± 97 and 234 ± 75 nmol/mg Cr, respectively) appeared higher than those of the control subjects (155 ± 59 nmol/mg Cr). Measurement of urinary specific biomarkers is comfortable, non-invasive, and easy to perform in children. Our findings might provide a scientific guide for use in further clinical and biochemical studies of these disorders.     

Cognitive effects of polyunsaturated fatty acids in children with attention deficit hyperactivity disorder symptoms: a randomised controlled trial

This study investigated effects of PUFA and micronutrient supplementation on cognition in children with ADHD symptoms. In a randomised controlled trial, 7-12-year-old children with symptoms 2 S.D. on Conners' ADHD Index were given PUFA, PUFA+multivitamins/minerals (MVM), or placebo for 15 weeks, and then all children were given PUFA+MVM for an additional 15 weeks. After 15 weeks there were improvements in a test of the ability to switch and control attention (Creature Counting) in the PUFA groups compared to placebo (N=129, p=0.002). This improvement was also observed in the placebo group after taking PUFA from weeks 16 to 30 (N=104). There were no significant improvements in other cognitive measures, or with additional micronutrient supplementation. However, improvements in cognitive performance mediated previous parent-reported improvements in inattention, hyperactivity and impulsivity [N. Sinn, J. Bryan, Effect of supplementation with polyunsaturated fatty acids and micronutrients on ADHD-related problems with attention and behaviour, J. Dev. Behav. Pediatr. 28 (2) (2007) 82-91], suggestive of a common neurological mechanism for these symptoms.     

Atomoxetine response in the inattentive and combined subtypes of attention deficit hyperactivity disorder: a retrospective chart review

The DSM-IV-TR (Diagnostic and Statistical Manual of Mental Disorders, 1994, American Psychiatric Association) describes attention deficit hyperactivity disorder (ADHD) as a heterogeneous disorder; providing diagnostic criteria for three subtypes: hyperactive/impulsive (ADHD/HI), inattentive (ADHD/I), and combined type (ADHD/C). Differences among the subtypes are well defined, but there may be also differences in terms of treatment responses. The aim of this study is to assess the responses of ADHD/I and ADHD/C to atomoxetine treatment. The medical records of the January–June 2012 term, first time referrals to outpatient clinic, were reviewed, and 37 ADHD diagnosed primary school age children (18 ADHD/I, 19 ADHD/C) that were treated with atomoxetine were determined. Thirty-five of them who completed 8 weeks of treatment duration were recruited for the study. The children with an ADHD medication use history in 2 months time prior to onset of treatment and/or the children receiving additional psychopharmacologic treatment to atomoxetine were excluded. Baseline and eighth week assessment, records were evaluated. Efficacy assessments included Turgay DSM-IV ADHD Screening and Rating Scale parent and teacher forms (T-DSM-IV) and Clinical Global Impression Scale-Severity and Improvement subscales. Safety assessments included laboratory and body weight assessments, ECG, heart rate, and blood pressure evaluations (baseline and eighth week) along a scale filled by the parents at the eighth week to review side effects. Atomoxetine was found to be effective in both ADHD/I and ADHD/C groups. Atomoxetine also decreased the opposition defiance subscale scores of T-DSM-IV (both parent and teacher forms), whereas it was not found to make statistically significant difference in the conduct disorder subscale scores. Mean difference in 8-week time in T-DSM-IV hyperactivity subscale and total scores of parent and teacher forms; inattention subscale scores of only parent forms and the CGI- severity subscale scores; differed significantly among the ADHD/I and ADHD/C groups; that ADHD/C types responded better to medication. Results of this study revealed that atomoxetine is effective both in ADHD/I and ADHD/C subtypes. ADHD/C types may be responding better to atomoxetine treatment than the ADHD/I subtypes.