Effect of Atomoxetine on Hyperactivity in an Animal Model of Attention-Deficit/Hyperactivity Disorder (ADHD)

Background

Hyperactivity related behaviors as well as inattention and impulsivity are regarded as the nuclear symptoms of attention-deficit/hyperactivity disorder (ADHD).

Purpose

To investigate the therapeutic effects of atomoxetine on the motor activity in relation to the expression of the dopamine (DA) D2 receptor based on the hypothesis that DA system hypofunction causes ADHD symptoms, which would correlate with extensive D2 receptor overproduction and a lack of DA synthesis in specific brain regions: prefrontal cortex (PFC), striatum, and hypothalamus.

Methods

Young male spontaneously hypertensive rats (SHR), animal models of ADHD, were randomly divided into four groups according to the daily dosage of atomoxetine and treated for 21 consecutive days. The animals were assessed using an open-field test, and the DA D2 receptor expression was examined.

Results

The motor activity improved continuously in the group treated with atomoxetine at a dose of 1 mg/Kg/day than in the groups treated with atomoxetine at a dose of 0.25 mg/Kg/day or 0.5 mg/Kg/day. With respect to DA D₂ receptor immunohistochemistry, we observed significantly increased DA D₂ receptor expression in the PFC, striatum, and hypothalamus of the SHRs as compared to the WKY rats. Treatment with atomoxetine significantly decreased DA D₂ expression in the PFC, striatum, and hypothalamus of the SHRs, in a dose-dependent manner.

Conclusion

Hyperactivity in young SHRs can be improved by treatment with atomoxetine via the DA D2 pathway.     

Attention-Deficit/Hyperactivity Disorder (ADHD) in Adulthood: Concordance and Differences between Self- and Informant Perspectives on Symptoms and Functional Impairment

Attention-deficit/hyperactivity disorder (ADHD) is a severe mental illness, associated with major impairment and a high comorbidity rate. Particularly undiagnosed ADHD in adulthood has serious consequences. Thus, a valid diagnosis is important. In adulthood, the diagnostic process for ADHD is complicated: symptoms may overlap with comorbid disorders, and the onset and progression of the disorder must be reconstructed retrospectively. Guidelines for the diagnostic process recommend the inclusion of additional informant ratings. Research into the relation between self- and informant ratings shows extremely heterogeneous results. The levels of agreement range from low to high. The focus of this study is the concordance and differences between self- and informant ratings on ADHD symptoms and impairments. In this regard, two possible influencing factors (gender and relationship type) are also examined. 114 people participated in this study, 77 with an ADHD diagnosis and 37 without a diagnosis. For all participants, either parents or partners also rated ADHD symptoms and impairments. Small to moderate concordance was found between self- and informant ratings, with females being slightly more concordant than males, particularly for ratings of problems with self-concept. Examination of the consistency within a particular perspective showed that people with ADHD seemed to be unaware of the causal relation between ADHD symptoms and their impairments. A close investigation found almost no influence of gender and relationship type on differences within perspectives. Based on these results, the implications for the diagnostic process are that additional informant information is clearly necessary and helpful.     

Exploring the Validity of Proposed Transgenic Animal Models of Attention-Deficit Hyperactivity Disorder (ADHD)

Attention-deficit/hyperactivity disorder (ADHD) is a common, behavioral, and heterogeneous neurodevelopmental condition characterized by hyperactivity, impulsivity, and inattention. Symptoms of this disorder are managed by treatment with methylphenidate, amphetamine, and/or atomoxetine. The cause of ADHD is unknown, but substantial evidence indicates that this disorder has a significant genetic component. Transgenic animals have become an essential tool in uncovering the genetic factors underlying ADHD. Although they cannot accurately reflect the human condition, they can provide insights into the disorder that cannot be obtained from human studies due to various limitations. An ideal animal model of ADHD must have face (similarity in symptoms), predictive (similarity in response to treatment or medications), and construct (similarity in etiology or underlying pathophysiological mechanism) validity. As the exact etiology of ADHD remains unclear, the construct validity of animal models of ADHD would always be limited. The proposed transgenic animal models of ADHD have substantially increased and diversified over the years. In this paper, we compiled and explored the validity of proposed transgenic animal models of ADHD. Each of the reviewed transgenic animal models has strengths and limitations. Some fulfill most of the validity criteria of an animal model of ADHD and have been extensively used, while there are others that require further validation. Nevertheless, these transgenic animal models of ADHD have provided and will continue to provide valuable insights into the genetic underpinnings of this complex disorder.     

Epidemiology of Treated Attention-Deficit/Hyperactivity Disorder (ADHD) across the Lifespan in Taiwan: A Nationwide Population-Based Longitudinal Study

Objectives

We used insurance claims of a nationally representative population-based cohort to assess the longitudinal treated prevalence and incidence of attention-deficit/hyperactivity disorder (ADHD) in children, adolescents and adults.

Methods

Participants were identified from among National Health Insurance enrollees in Taiwan from 1999 to 2005. We identified study subjects who had at least one service claim during these years with a principal diagnosis of ADHD. A total of 6,173 patients were recorded in the treated ADHD cohort during the 6-year study.

Results

There was a significant increase in the treated prevalence rate of ADHD during the study period, from 64.65 per 100,000 in 2000 to 145.40 per 100,000 in 2005 (p = .001). An increase in the treated incidence rate of ADHD, from 44.67 per 100,000 in 2000 to 81.20 per 100,000 in 2005, was also observed (p = .013). However, the treated prevalence of ADHD was still lower than that of the community data in Taiwan. The peak treated prevalence of ADHD was at age 7–12 years for both males and females, and the peak treated incidence of ADHD was at age 0–6 for females and age 7–12 for males. Overall, the treated incidence and prevalence rates dropped abruptly after age 13–18 (both p<.001) for males and females (p<.001 for both). Male vs. female ratios of treated prevalence and incidence were both above 1 before age 25–30 years, but below 1 thereafter.

Conclusion

Although an increasing number of people with ADHD sought treatment during 1999–2005 in Taiwan, the treated prevalence of ADHD was still lower than that of the community data. The treated incidence and prevalence of ADHD fell dramatically after age 13–18. However, more women than men sought treatment in adulthood. There may be under-diagnosis and under-treatment of ADHD, especially among females and adults.     

Intrinsic Affective Network Is Impaired in Children with Attention-Deficit/Hyperactivity Disorder

Deficits in impulsivity and affect dysregulation are key features of attention-deficit/hyperactivity disorder (ADHD) besides impairing levels of hyperactivity and/or inattention. However, the neural substrates underlying these traits are relatively under-investigated. In this study, we use resting-state functional magnetic resonance imaging to test the hypothesis of diminished functional integration within the affective/limbic network (which includes the amygdala, hippocampus, subgenual cingulate cortex, orbitofrontal cortex and nucleus accumbens) of children with ADHD, which is associated with their behavioral measures of emotional control deficits. Resting state-fMRI data were obtained from 12 healthy control subjects and 15 children with ADHD, all who had a minimum one-month washout period for medications and supplements. Children with ADHD demonstrated less integrated affective network, evidenced by increased bilateral amygdalar and decreased left orbitofrontal connectivity within the affective network compared to healthy controls. The hyper-connectivity at the left amygdalar within the affective network was associated with increased aggressiveness and conduct problems, as well as decline in functioning in children with ADHD. Similar findings in affective network dysconnectivity were replicated in a subset of children with ADHD three months later. Our findings of divergent changes in amygdala and orbitofrontal intrinsic connectivity support the hypothesis of an impaired functional integration within the affective network in childhood ADHD. Larger prospective studies of the intrinsic affective network in ADHD are required, which may provide further insight on the biological mechanisms of emotional control deficits observed in ADHD.     

DRD4 Rare Variants in Attention-Deficit/Hyperactivity Disorder (ADHD): Further Evidence from a Birth Cohort Study

The dopamine receptor D4 (DRD4) is one of the most studied candidate genes for Attention-Deficit/Hyperactivity Disorder (ADHD). An excess of rare variants and non-synonymous mutations in the VNTR region of 7R allele in ADHD subjects was observed in previous studies with clinical samples. We hypothesize that genetic heterogeneity in the VNTR is an important factor in the pathophysiology of ADHD. The subjects included in the present study are members of the 1993 Pelotas Birth Cohort Study (N=5,249). We conducted an association study with the 4,101 subjects who had DNA samples collected. The hyperactivity-inattention scores were assessed through the parent version of the Strengths and Difficulties Questionnaire at 11 and 15 years of age. The contribution of allele’s length and rare variants to high hyperactivity/inattention scores predisposition was evaluated by multivariate logistic regression. No effect of allele length was observed on high scores of hyperactivity-inattention. By contrast, when resequencing/haplotyping was conducted in a subsample, all 7R rare variants as well as non-synonymous 7R rare variants were associated with high hyperactivity/inattention scores (OR=2.561; P=0.024 and OR=3.216; P=0.008 respectively). A trend for association was observed with 4R rare variants. New coding mutations covered 10 novel motifs and many of them are previously unreported deletions leading to different stop codons. Our findings suggest a contribution of DRD4 7R rare variants to high hyperactivity-inattention scores in a population-based sample from a large birth cohort. These findings provide further evidence for an effect of DRD4 7R rare variants and allelic heterogeneity in ADHD genetic susceptibility.     

Electroencephalographic and Psychometric Differences Between Boys with and Without Attention-Deficit/Hyperactivity Disorder (ADHD): A Pilot Study

Attention-Deficit/Hyperactivity Disorder (ADHD) is reported to have an incidence of 3–5%, and is associated with a variety of interpersonal, academic, and social problem behaviors. There is controversy as to whether ADHD is a learned behavioral or brain dysfunction. Research has explored a variety of measures to assess behavioral and brain dysfunctions in this population, with no consistent and clearly diagnostic results. We investigated whether a new psychometric and a new electroencephalographic procedure would clearly differentiate ADHD. The psychometric was based on DSM-IV criteria and the EEG measure was based on the assumption that ADHD interferes with cognitive transition from one discrete task to another. Parents of four ADHD boys (ages 8–12) and four age- and interest-matched non-ADHD boys completed the ADHD Symptom Inventory, while their sons' EEG was monitored during viewing of a video and reading of a book. For the ADHD boys, this was repeated a second time, 3 months later, to assess test-retest reliability. Both the psychometric and the EEG measures clearly differentiated the two samples (p's < .01) with no overlap in scores, were reliable over 3 months (r = .87), and were significantly correlated with one another (r = .85). While a small sample size, these robust, related and reliable findings suggest that both the psychometric and the psychophysiological EEG measures deserve further replication and exploration.     

Electroencephalographic Biofeedback in the Treatment of Attention-Deficit/Hyperactivity Disorder

Historically, pharmacological treatments for attention-deficit/hyperactivity disorder (ADHD) have been considered to be the only type of interventions effective for reducing the core symptoms of this condition. However, during the past three decades, a series of case and controlled group studies examining the effects of EEG biofeedback have reported improved attention and behavioral control, increased cortical activation on quantitative electroencephalographic examination, and gains on tests of intelligence and academic achievement in response to this type of treatment. This review paper critically examines the empirical evidence, applying the efficacy guidelines jointly established by the Association for Applied Psychophysiology and Biofeedback (AAPB) and the International Society for Neuronal Regulation (ISNR). On the basis of these scientific principles, EEG biofeedback was determined to be “probably efficacious” for the treatment of ADHD. Although significant clinical improvement was reported in approximately 75% of the patients in each of the published research studies, additional randomized, controlled group studies are needed in order to provide a better estimate of the percentage of patients with ADHD who will demonstrate such gains in clinical practice.     

Atomoxetine treatment for children and adolescents with Attention-Deficit/Hyperactivity Disorder (ADHD): a comprehensive meta-analysis of outcomes on parent-rated core symptomatology

Attention-Deficit/Hyperactivity Disorder (ADHD) impacts a significant number of children and adolescents and often leads to deleterious functional impairment. Psychostimulant medication has historically been the first line of pharmacological intervention, though recent years have seen greater attention paid to non-stimulant alternatives. The objective of the present study was to conduct the most comprehensive meta-analysis to date evaluating the efficacy of atomoxetine in reducing core symptomatology of ADHD according to parent report. Selection criteria were applied, and studies were located by searching electronic databases, review of reference sections, and contact with expert researchers; article searching began on 10/01/2013, and the final search was conducted on 09/01/2014. A total of 42 studies met inclusion criteria—33 with control groups and 9 without—for a total sample of 8398 individuals. For those receiving atomoxetine, the summary pre–post (e.g., standardized mean gain) effect size estimate was 1.37 (95% CI [1.24, 1.51], p < .001); atomoxetine was found to statistically significantly outperform control conditions overall (Z = 4.07, p < .001), though results differed by the type of control group; for instance, when comparing atomoxetine to alternative medications as controls, significant differences were no longer present. The non-stimulant atomoxetine led to significant improvement in core ADHD symptomatology and should be considered as a viable pharmacological treatment option for ADHD.     

Dissociable Patterns in the Control of Emotional Interference in Adults with Attention-Deficit/Hyperactivity Disorder (ADHD) and in Adults with Alcohol Dependence

Objectives

To effectively manage current task demands, attention must be focused on task-relevant information while task-irrelevant information is rejected. However, in everyday life, people must cope with emotions, which may interfere with actual task demands and may challenge functional attention allocation. Control of interfering emotions has been associated with the proper functioning of the dorsolateral prefrontal cortex (DLPFC). As DLPFC dysfunction is evident in subjects with ADHD and in subjects with alcohol dependence, the current study sought to examine the bottom-up effect of emotional distraction on task performance in both disorders.

Methods

Male adults with ADHD (n = 22), male adults with alcohol dependence (n = 16), and healthy controls (n = 30) performed an emotional working memory task (n-back task). In the background of the task, we presented neutral and negative stimuli that varied in emotional saliency.

Results

In both clinical groups, a working memory deficit was evident. Moreover, both clinical groups displayed deficient emotional interference control. The n-back performance of the controls was not affected by the emotional distractors, whereas that of subjects with ADHD deteriorated in the presence of low salient distractors, and that of alcoholics did not deteriorate until high salient distractors were presented. Subsequent to task performance, subjects with ADHD accurately recognized more distractors than did alcoholics and controls. In alcoholics, picture recognition accuracy was negatively associated with n-back performance, suggesting a functional association between the ability to suppress emotional distractors and successful task performance. In subjects with ADHD, performance accuracy was negatively associated with ADHD inattentive symptoms, suggesting that inattention contributes to the performance deficit.

Conclusions

Subjects with ADHD and alcoholics both display an emotional interference control deficit, which is especially pronounced in subjects with ADHD. Beyond dysfunctional attention allocation processes, a more general attention deficit seems to contribute to the more pronounced performance deficit pattern in ADHD.     

Delayed Sleep Timing and Symptoms in Adults With Attention-Deficit/Hyperactivity Disorder: A Controlled Actigraphy Study

Patients with attention-deficit/hyperactivity disorder (ADHD) often exhibit disrupted sleep and circadian rhythms. Determination of whether sleep disturbance and/or circadian disruption are differentially associated with symptom severity is necessary to guide development of future treatment strategies. Therefore, we measured sleep and ADHD symptoms in participants aged 19–65 who met the DSM-IV-TR (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision) criteria for ADHD and insomnia without psychiatric comorbidities by monitoring actigraphy and daily sleep logs for 2 wks, as well as the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), the ADHD Rating Scale (ADHD-RS), and a clinic-designed sleep behavior questionnaire. Principal components analysis identified correlated circadian- and sleep-related variables in all participants with ADHD who completed the study (n?=?24). The identified components were entered into a backwards stepwise linear regression analysis, which indicated that delayed sleep timing and increased sleepiness (ESS) (but not sleep duration or sleep efficiency) significantly predicted greater severity of both hyperactive-impulsive and inattentive ADHD symptoms (p <?.05 for partial regression coefficients). In addition, combined subtypes had the most impaired age-adjusted sleep quality (PSQI scores; p?<?.05 compared with healthy controls; n?=?13), and 91.7% of them reported going to bed late due to being “not tired/too keyed up to sleep” compared with 57.2% and 50% of inattentive and symptom-controlled participants, respectively (p?<?.05). In conclusion, the results of this study suggest that ADHD symptom severity correlates with delayed sleep timing and daytime sleepiness, suggesting that treatment interventions aimed at advancing circadian phase may improve daytime sleepiness. In addition, ADHD adults with combined hyperactive-impulsive and inattentive symptoms have decreased sleep quality as well as the delayed sleep timing of predominately inattentive subtypes. (Author correspondence: rfargason@uab.edu)     

The Effects of Classroom Interventions on Off-Task and Disruptive Classroom Behavior in Children with Symptoms of Attention-Deficit/Hyperactivity Disorder: A Meta-Analytic Review

Children with attention-deficit/hyperactivity disorder (ADHD) often exhibit problem behavior in class, which teachers often struggle to manage due to a lack of knowledge and skills to use classroom management strategies. The aim of this meta-analytic review was to determine the effectiveness of several types of classroom interventions (antecedent-based, consequence-based, self-regulation, combined) that can be applied by teachers in order to decrease off-task and disruptive classroom behavior in children with symptoms of ADHD. A second aim was to identify potential moderators (classroom setting, type of measure, students’ age, gender, intelligence, and medication use). Finally, it was qualitatively explored whether the identified classroom interventions also directly or indirectly affected behavioral and academic outcomes of classmates. Separate meta-analyses were performed on standardized mean differences (SMDs) for 24 within-subjects design (WSD) and 76 single-subject design (SSD) studies. Results showed that classroom interventions reduce off-task and disruptive classroom behavior in children with symptoms of ADHD (WSDs: M_SMD = 0.92; SSDs: M_SMD = 3.08), with largest effects for consequence-based (WSDs: M_SMD = 1.82) and self-regulation interventions (SSDs: M_SMD = 3.61). Larger effects were obtained in general education classrooms than in other classroom settings. No reliable conclusions could be formulated about moderating effects of type of measure and students’ age, gender, intelligence, and medication use, mainly because of power problems. Finally, classroom interventions appeared to also benefit classmates’ behavioral and academic outcomes.     

Potential hormonal mechanisms of Attention-Deficit/Hyperactivity Disorder and Major Depressive Disorder: A new perspective

Hormonal influences on the organization of behavior are apparent to neuroendocrinologists but under-examined in relation to childhood and adolescent mental disorders. A central mystery in the field of developmental psychopathology is the preferential male vulnerability to behavior disorders in childhood and female vulnerability to emotional disorders in adolescence. Relative neglect of a hormonal explanation may be due to lack of simple or unifying conceptual paradigms to guide studies. This paper seeks to stimulate research in this area by drawing upon clinical psychology and neuroscience literatures to offer a heuristic paradigm for clinical research. Two syndromes are selected here for illustration: Attention-Deficit/Hyperactivity Disorder (ADHD) and Major Depressive Disorder (MDD), because they have opposite gender risk profiles. Two guiding theories are evaluated. First, prenatal organizational effects of testosterone may modulate striatally-based dopaminergic circuits in such a way as to place boys at greater risk for early developing inattention and disruptive behavioral disorders. Second, activational effects of estradiol at puberty may modulate amygdalar and other circuitry, with particular effects on serotonergic pathways, in such a way as to place girls at greater risk for internalizing and mood disorders. Hypotheses from these theories are evaluated based on the current available literature, and limitations of, and future directions for, this literature are discussed.     

On the Temporal Characteristics of Performance Variability in Attention Deficit Hyperactivity Disorder (ADHD)

Increased intra-subject variability of reaction times (ISV-RT) is one of the most consistent findings in attention-deficit/hyperactivity disorder (ADHD). Although the nature of this phenomenon is still unclear, it has been hypothesised to reflect interference from the Default Mode Network (DMN). So far, ISV-RT has been operationally defined either as a frequency spectrum of the underlying RT time series, or as a measure of dispersion of the RT scores distribution. Here, we use a novel RT analysis framework to link these hitherto unconnected facets of ISV-RT by determining the sensitivity of different measures of RT dispersion to the frequency content of the underlying RT time series. N=27 patients with ADHD and N=26 healthy controls performed several visual N-back tasks. Different measures of RT dispersion were repeatedly modelled after individual frequency bands of the underlying RT time series had been either extracted or suppressed using frequency-domain filtering. We found that the intra-subject standard deviation of RT preserves the “1/f noise” characteristic typical of human RT data. Furthermore and most importantly, we found that the ex-Gaussian parameter τ is rather exclusively sensitive to frequencies below 0.025 Hz in the underlying RT time series and that the particularly slow RTs, which nourish τ, occur regularly as part of an quasi-periodic, ultra-slow RT fluctuation. Overall, our results are compatible with the idea that ISV-RT is modulated by an endogenous, slowly fluctuating process that may reflect DMN interference.     

Vitamin D Status at Birth and Future Risk of Attention Deficit/Hyperactivity Disorder (ADHD)

Objective

To investigate whether children with Attention Deficit/Hyperactivity Disorder have lower levels of Vitamin D₃ at birth than matched controls.

Material

Umbilical cord blood samples collected at birth from 202 children later diagnosed with Attention Deficit/Hyperactivity Disorder were analysed for vitamin D content and compared with 202 matched controls. 25-OH vitamin D₃ was analysed by liquid chromatography tandem mass spectrometry.

Results

No differences in cord blood vitamin D concentration were found between children with Attention Deficit/Hyperactivity Disorder (median 13.0 ng/ml) and controls (median 13.5 ng/ml) (p = 0.43). In a logistic regression analysis, Attention Deficit/Hyperactivity Disorder showed a significant association with maternal age (odds ratio: 0.96, 95% confidence interval: 0.92–0.99) but not with vitamin D levels (odds ratio: 0.99, 95% confidence interval: 0.97–1.02).

Conclusion

We found no difference in intrauterine vitamin D levels between children later developing Attention Deficit/Hyperactivity Disorder and matched control children. However, the statistical power of the study was too weak to detect an eventual small to medium size association between vitamin D levels and Attention Deficit/Hyperactivity Disorder.     

Laminar Thickness Alterations in the Fronto-Parietal Cortical Mantle of Patients with Attention-Deficit/Hyperactivity Disorder

Although Attention-Deficit/Hyperactivity Disorder (ADHD) was initially regarded as a disorder exclusive to childhood, nowadays its prevalence in adulthood is well established. The development of novel techniques for quantifying the thickness of the cerebral mantle allows the further exploration of the neuroanatomical profiles underlying the child and adult form of the disorder. To examine the cortical mantle in children and adults with ADHD, we applied a vertex-wise analysis of cortical thickness to anatomical brain MRI scans acquired from children with (n = 43) and without ADHD (n = 41), as well as a group of adult neurotypical individuals (n = 31), adult patients with a history of stimulant treatment (n = 31) and medication-naïve adults with ADHD (n = 24). We observed several clusters of reduced laminar cortical thickness in ADHD patients in comparison to neurotypical individuals. These differences were primarily located in the dorsal attention network, including the bilateral inferior and superior parietal cortex and a section of the frontal cortex (centered on the superior frontal and precentral gyrus bilaterally). Further laminar thickness deficits were observed in the bilateral orbitofrontal cortex and medial occipital cortex. The deficits in the cortical surface were especially pronounced in the child sample, while adult patients showed a more typical laminar thickness across the cerebral mantle. These findings show that the neuroanatomical profile of ADHD, especially the childhood form of the disorder, involves robust alterations in the cortical mantle, which are most prominent in brain regions subserving attentional processing.     

Association of Symptoms of Attention-Deficit/Hyperactivity Disorder with Physical Activity,Media Time,and Food Intake in Children and Adolescents

Introduction

The aim of the study was to assess the association between attention deficit/hyperactivity disorder (ADHD) symptoms and potentially obesogenic behaviors.

Methods

Data of 11,676 German children and adolescents (6–17 years) were analyzed. Television/video exposure, physical activity, food frequency and portion size were assessed using questionnaires. A dietary quality index, energy density and volumes of consumed food, and total energy intake were calculated. The parent-rated hyperactivity/inattention subscale of the Strengths and Difficulties Questionnaire (SDQ-HI) was used as a continuous measure of ADHD symptoms. Associations were analyzed with general linear models adjusting for sex, age, socioeconomic status, migrant status, parental BMI, and parental smoking.

Results

SDQ-HI scores correlated positively with physical activity, average energy density of food, volume of beverages, total energy intake, and television exposure and negatively with the nutritional quality score (HuSKY) even after adjustment for parental variables (BMI, smoking, socioeconomic status, migrant status), age, sex, as well as the other SDQ subscales. The adjusted association of the SDQ-HI scores with the nutritional quality score was stronger in girls and the associations with food volume, food energy, and total energy intake was significant only in girls.

Conclusions

Poor nutritional quality, high energy intake and television exposure appear to be independently associated with ADHD symptoms. The relationship between food energy intake and ADHD symptoms was especially pronounced in girls and this may help to explain the reported association of ADHD symptoms with overweight in adolescent girls.     

Effect of Treatment Modality on Long-Term Outcomes in Attention-Deficit/Hyperactivity Disorder: A Systematic Review

BackgroundEvaluation of treatments for attention-deficit/hyperactivity disorder (ADHD) previously focused on symptom control, but attention has shifted to functional outcomes. The effect of different ADHD treatment periods and modalities (pharmacological, non-pharmacological, and combination) on long-term outcomes needs to be more comprehensively understood.MethodsA systematic search of 12 literature databases using Cochrane’s guidelines yielded 403 English-language peer-reviewed, primary studies reporting long-term outcomes (≥2 years). We evaluated relative effects of treatment modalities and durations and effect sizes of outcomes reported as statistically significantly improved with treatment.ResultsThe highest proportion of improved outcomes was reported with combination treatment (83% of outcomes). Among significantly improved outcomes, the largest effect sizes were found for combination treatment. The greatest improvements were associated with academic, self-esteem, or social function outcomes. A majority of outcomes improved regardless of age of treatment initiation (60%–75%) or treatment duration (62%–72%). Studies with short treatment duration had shorter follow-up times (mean 3.2 years total study length) than those with longer treatment durations (mean 7.1 years total study length). Studies with follow-up times <3 years reported benefit with treatment for 93% of outcomes, whereas those with follow-up times ≥3 years reported treatment benefit for 57% of outcomes. Post-hoc analysis indicated that this result was related to the measurement of outcomes at longer periods (3.2 versus 0.4 years) after treatment cessation in studies with longer total study length.ConclusionsWhile the majority of long-term outcomes of ADHD improve with all treatment modalities, the combination of pharmacological and non-pharmacological treatment was most consistently associated with improved long-term outcomes and large effect sizes. Older treatment initiation age or longer durations did not markedly affect proportion of improved outcomes reported, but measurement of outcomes long periods after treatment cessation may attenuate results.     

注意缺损多动障碍的X染色体基因组扫描分析

摘 要：注意缺损多动障碍（ADHD）是儿童期多见行为障碍。男孩发病多于女孩。家系、双生儿和寄养子研究显示该障碍发生具有遗传基础。但是病因尚不清楚。分子遗传学和药理学研究表明ADHD涉及到多巴胺和去甲肾上腺素等神经递质系统,一系列报告发现ADHD与多巴胺D4受体（DRD4）、多巴胺转运体（DAT1）和儿茶酚-O-甲基转移酶（COMT）等基因相关联。我们以往研究表明ADHD与X染色体上DXS7位点和MAOA基因相关联,而DXS7是紧密连锁于MAO基因。依此假设,我们应用基因组扫描技术探讨ADHD在X染色体上易感位点。采用TDT方法分析X染色体上48个DNA标志的多态性与中国人群中84个ADHD核心家系间的连锁关系,ADHD诊断依据DSM-III-R标准。TDT分析结果观察到如下位点与ADHD相连锁,DXS1214(TDT:χ2=18.1,df=7, P<0.01), DXS8102(TDT: χ2=7.9, df=3, P<0.05),DXS1068(TDT: χ2=21.9, df=9, P<0.01), DXS8015(TDT:χ2=14.6, df=7, P<0.05),DXS1059(TDT: χ2=27.8, df=10, P<0.01) 和DXS8088(TDT:χ2=20.4, df=3, P<0.01).研究资料提示X染色体上Xp11.4-Xp21和Xq23区域可能存在ADHD的易感基因。