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PubMed1989

Effect of anxiety on cognition, behavior, and stimulant response in ADHD.

The effect of the comorbidity of overanxious disorder (ANX) in attention deficit hyperactivity disorder (ADHD) on laboratory measures of behavior, cognition, and stimulant response was examined. Seventy-nine children who met DSM-III-R criteria for ADHD were tested further for an oppositional defiant disorder (ODD), conduct disorder (CD), or ANX. Subjects with comorbid ANX showed less impulsiveness on a laboratory measure of behavior and had longer, sluggish reaction times on the Memory Scanning Test than those without ANX. ADHD subjects with comorbid ANX were less frequently diagnosed as CD. Forty-three of the subjects completed a double-blind trial of methylphenidate; subjects with comorbid anxiety had a significantly poorer response to the stimulant than those without anxiety, while the comorbidity of ODD or CD did not affect stimulant response. The results suggest that ADHD with comorbid ANX may represent children with primary anxiety who develop secondary inattentiveness, or they may represent a different subtype of ADHD, perhaps similar to the condition of attention deficit disorder without hyperactivity under DSM-III.

Anxiety Disorders↗

PubMed2006

Long-term stimulant medication treatment of attention-deficit/hyperactivity disorder: results from a population-based study.

The purpose of this study was to offer detailed information about stimulant medication treatment provided throughout childhood to 379 children with research-identified attention-deficit hyperactivity disorder (ADHD) in the 1976-1982 Rochester, MN, birth cohort. Subjects were retrospectively followed from birth until a mean of 17.2 years of age. The complete medical record of each subject was reviewed. The history and results of each episode of stimulant treatment were compared by gender, DSM-IV subtype of ADHD, and type of stimulant medication. Overall, 77.8% of subjects were treated with stimulants. Boys were 1.8 times more likely than girls to be treated. The median age at initiation (9.8 years), median duration of treatment (33.8 months), and likelihood of developing at least one side effect (22.3%) were not significantly different by gender. Overall, 73.1% of episodes of stimulant treatment were associated with a favorable response. The likelihood of a favorable response was comparable for boys and girls. Treatment was initiated earlier for children with either ADHD combined type or ADHD hyperactive-impulsive type than for children with ADHD predominantly inattentive type and duration of treatment was longer for ADHD combined type. There was no association between DSM-IV subtype and likelihood of a favorable response or of side effects. Dextroamphetamine and methylphenidate were equally likely to be associated with a favorable response, but dextroamphetamine was more likely to be associated with side effects. These results demonstrate that the effectiveness of stimulant medication treatment of ADHD provided throughout childhood is comparable to the efficacy of stimulant treatment demonstrated in clinical trials.

Adolescent↗

PubMed2006

Attention-deficit hyperactivity disorder involves differential cortical processing in a visual spatial attention paradigm.

OBJECTIVE: Inattention is undoubtedly one of the main characteristics of Attention-deficit hyperactivity disorder (ADHD). Nevertheless, a growing corpus of evidence shows that not all attentional processes are affected in this condition. This study aimed to explore the distribution of attentional resources in children with ADHD via a spatially shifted double-oddball visual task. METHODS: We recorded event-related potentials (ERPs) for all visual stimuli. Subjects were instructed to allocate attention in a specific area of visual space while ignoring all stimuli presented outside. Ten male children (age: 9-14; mean = 11.6 +/- 2.1) who met DSM-IV criteria for the ADHD combined subtype participated in the study, along with ten age- and sex-matched healthy controls (9-14; mean = 11.2 +/- 2.3). RESULTS: ADHD subjects showed late differential cortical responses to initially suppressed irrelevant stimuli. The amplitude of early N1-P1 components were mainly modulated by stimulus location and showed no significant differences between groups, but a late P300-like positivity was clearly evoked in the ADHD group by peripheral stimuli. CONCLUSIONS: These results suggest that ADHD may not compromise the early attentional spatial filter but rather entails a different distribution of attentional resources at later stages of cortical processing. Perhaps these differences may be attributable to individual differences in attentional mechanisms. SIGNIFICANCE: ADHD may not affect initial focusing of visual attention but rather the allocation of processing resources in later stages.

Adolescent↗

PubMed2006

Possible association of the alpha-2A adrenergic receptor gene (ADRA2A) with symptoms of attention-deficit/hyperactivity disorder.

A dysfunction of the central noradrenergic system has long been suggested to be involved in attention-deficit/hyperactivity disorder (ADHD). Pharmacological evidence from animal studies and clinical practice has identified the alpha-2A adrenergic receptor gene (ADRA2A) as a candidate gene in ADHD. Some findings from Caucasian populations seem to support a role for this gene in ADHD. The current study first examined the association of the ADRA2A MspI and DraI polymorphisms with ADHD in the Han Chinese population, which differs quite substantially from the Caucasian population in the frequencies of alleles at these polymorphisms. No biased transmission of alleles of either polymorphism was observed using transmission disequilibrium test (TDT) analysis in a sample of 268 nuclear families with an ADHD proband; however, haplotype analysis only identified a trend toward over-transmission of the M/C haplotype to probands with the combined subtype of ADHD (chi(2) = 3.233, P = 0.072). The mm genotype of the MspI polymorphism was also marginally related (P = 0.051) to lower ADHD symptom scores in a sample of 559 Chinese children with ADHD, which is inconsistent with data from Caucasian samples. Our results provide weak evidence for a possible role of ADRA2A in ADHD symptom expression.

Adolescent↗

PubMed1996

Quantitative EEG differences in a nonclinical sample of children with ADHD and undifferentiated ADD.

OBJECTIVE: To use quantitative electroencephalographic (EEG) techniques to identify electrophysiological differences between children with distinct disorders of attention and/or hyperactivity. METHOD: Forty children from a prescreened community sample were evaluated by means of both spectral EEG and evoked response potential (ERP) techniques. The children were 7 to 13 years of age and were selected on the basis of membership in one of the following DSM-III-R categories: attention-deficit hyperactivity disorder (ADHD) (n = 16), undifferentiated attention deficit disorder (UADD) (n = 12), or no disruptive disorder diagnosis (n = 12). RESULTS: Spectral EEG revealed that UADD subjects had less delta band relative percent power (RPP) (p < .01), more beta band RPP (p < .01), and ERP findings of a decreased rare tone P300 amplitude (p < .02) compared with the control group. ADHD subjects had spectral EEG findings of increased beta band RPP (p < .05) and ERP findings of an increased common tone N100 latency (p < .02) and a decreased rare tone P300 amplitude (p < .02). Interhemispheric asymmetries appeared to distinguish the groups: the UADD group had spectral EEG asymmetries; the ADHD group had only ERP asymmetries; and the control group had no asymmetries. CONCLUSION: Quantitative EEG techniques may prove useful in differentiating specific subtypes of ADHD.

Adolescent↗

PubMed2000

Processing speed in children with attention deficit/hyperactivity disorder, inattentive type.

Attention Deficit/Hyperactivity Disorder (ADHD) is among the most common and most often reconceptualized neurobehavioral disorders of childhood. In the most recent DSM-IV, a primarily inattentive subtype of ADHD (AD) has again been identified. This study explores the neuropsychological profile of this group of children. Eighty-two children referred for school-related problems participated. Twenty-five met criteria for AD; 52 met criteria for reading disability (RD); 9 were comorbid for RD and AD. AD children performed poorly on measures of information processing speed. Children with comorbid AD/RD were distinguishable from those with RD on speed of processing measures only. Vulnerability to information processing load may be at the root of many of the behavioral manifestations of AD.

Attention↗

PubMed1998

Attention-deficit hyperactivity disorder subtypes and comorbid disruptive behaviour disorders in a child and adolescent mental health clinic.

OBJECTIVE: To assess demographic characteristics and patterns of comorbid disruptive behavior disorders (oppositional defiant disorder [ODD] or conduct disorder [CD]) in subtypes of attention-deficit hyperactivity disorder (ADHD). METHOD: One hundred youths consecutively referred to a community child and adolescent mental health clinic and subsequently diagnosed with ADHD by the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria were evaluated. The diagnosis was made by a child psychiatrist and was based on information from physicians, parents, teachers, and diagnostic interviews with the youth and their parents. RESULTS: The major findings were: 1) ADHD combined (C) type was diagnosed in 78% of the subjects, while 15% had inattentive (1) type and 7% had hyperactive-impulsive (HI) type; and 2) patterns of comorbid disruptive behavioural disorders significantly differed among subtypes. Specifically, subjects with the I type showed lower rates of comorbid ODD than those with the C type (33% and 85%; P < 0.001) and HI type (33% and 100%; P = 0.005); subjects with the HI type displayed a higher prevalence of CD than those with the I type (57% and 0%; P = 0.005) and C type (57% and 8%; P = 0.003). These results should be considered tentative because the reliability of the diagnostic procedures was not formally assessed and the number of subjects in the I and HI groups was small. CONCLUSION: ADHD subtypes showed significant differences in the distribution of comorbid disruptive behaviour disorders. These results support the utility of ADHD subtypes but should be replicated with a larger sample of I and HI type subjects using more rigorous diagnostic methods.

Adolescent↗

PubMed2002

[Biochemical bases and research in attention-deficit hyperactivity disorder].

INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is a complex neurodevelopmental disorder, which is very common among the school aged population. Its core symptoms are inattention, hyperactivity, and impulsivity. Currently, three principal subtypes of ADHD are recognized: ADHD predominantly inattentive type, ADHD predominantly hyperactive/impulsive type or ADHD combined type. Affected individuals have increased comorbidity risks, often followed by cognitive, emotional and/or social impairments as adults. Stimulants drugs such methylphenidate (Ritalin) or D amphetamine (Dexedrine) represent the first line drugs for the treatment of ADHD. DEVELOPMENT: The clinical features of ADHD were first described by Dr. George Frederick Still for Lancet in 1902, and in spite of the investigations carried out since then, the precise cause is still not clear. The purpose of this review is to describe recent advances of the neurobiological basis of ADHD. CONCLUSIONS: Recent neuroimaging studies in humans indicate a dysfunctions of the frontal striatal circuits in patients with ADHD, which can be improved by pharmacological treatment. Both pre and clinical studies implicate a dysregulation of the dopaminergic and noradrenergic systems, which are known to regulate the functions of these circuits. More recent evidence indicate that some features of ADHD could be linked to alterations in the posterior inferior vermis. These studies also stress the importance of taking into consideration factors such as age, gender and duration of pharmacological treatment when interpreting the results.

Adult↗

PubMed2003

Association analysis of monoamine oxidase A and attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is a highly heritable disorder. Although the causes of ADHD are unknown, dopaminergic, serotonergic and nor-adrenergic pathways have been strongly implicated. Monoamine Oxidase A (MAOA) is involved in the degradation of all three of these neurotransmitters and therefore has been suggested as a strong candidate gene for ADHD. Animal and human studies have implicated MAOA and 5-HT in impulsive and aggressive behavior. We therefore additionally postulated that MAOA might be associated with a subtype of ADHD where aggressive and impulsive features are especially prominent. We have tested this hypothesis by genotyping two polymorphisms (the 30-bp VNTR in the promoter and the Fnu4HI 941T-->G) in MAOA that are associated with altered MAOA function. Our sample consisted of 171 British Caucasian children 6-16 years of age fulfilling DSM-III R, DSM-IV or ICD-10 criteria for ADHD/Hyperkinetic Disorder. Using case control analysis and then the TDT, no association was found between these two MAOA polymorphisms and ADHD. Case control analysis of the VNTR showed an association with a subgroup of children with comorbid conduct problems (OR = 2.0, 95% CI = 1.09, 3.5), and TDT analysis indicated a statistical trend toward association. Our findings highlight the importance of phenotype definition and the need for the MAOA VNTR to be further examined.

Adolescent↗

PubMed2006

Magnetic resonance imaging volumetric analysis of the putamen in children with ADHD: combined type versus control.

OBJECTIVE: Volumetric differences in the putamen of boys with ADHD combined subtype with psychopathic traits and controls are investigated. METHOD: The putamen in 24 archival magnetic resonance imaging scans of 12 boys in residential treatment with symptoms of ADHD and psychopathic traits and 12 community control boys are analyzed using Display software. RESULTS: There are no differences found in the total, left, and right putamen volumes across the ADHD or control group. A significant reversal of asymmetry across groups is found; children with ADHD more frequently have a smaller left putamen than right. In contrast, the control group more frequently has a smaller right than left putamen. CONCLUSION: A reversal of symmetry in the putamen (as found in the caudate) may relate to ADHD symptomology as well as to psychopathic traits.

Adolescent↗

PubMed2001

Excess beta activity in children with attention-deficit/hyperactivity disorder: an atypical electrophysiological group.

Studies of children with attention deficit/hyperactivity disorder (ADHD) have typically found elevated levels of slow wave activity in their EEGs, but in two of our previous studies, a small subset of ADHD children with excess beta activity in the EEG was identified. The aim of this study was to determine whether children with excess beta activity represent a distinct electrophysiological subtype of ADHD, to quantify the differences in their EEGs, and to determine if this group of children with ADHD have behavioural profiles different from other children with ADHD. Results indicated that children with excess beta represent a small independent subset of children diagnosed with ADHD, which primarily consists of children with a diagnosis of ADHD combined type. Behaviourally, this group was similar to other children with ADHD, although the excess-beta group were more prone to temper tantrums and to be moody. The excess in beta activity was found primarily in the frontal regions and may be associated with frontal lobe self-regulation and inhibition control.

Attention Deficit Disorder with Hyperactivity↗

PubMed2005

Stopping and changing in adults with ADHD.

BACKGROUND: A lack of inhibitory control has been suggested to be the core deficit in children with attention deficit hyperactivity disorder (ADHD). This means that a primary deficit in behavioral inhibition mediates a cascade of secondary deficits in other executive functions, such as arousal regulation. Clinical observations have revealed that with increasing age symptoms of hyperactivity and impulsivity decline at a higher rate than those of inattention. This might imply that a deficit in attention rather than a lack of inhibitory control is the major feature in adult ADHD. METHOD: To study whether an attentional or inhibitory deficit predominates, the stop-signal task and the stop-change task were presented to 24 adults with ADHD combined subtype and 24 controls. RESULTS: Relative to controls, the stop-signal reaction time (SSRT) was significantly more prolonged than the go-stimulus reaction time (RT) in patients with ADHD. This disproportionate elongation of the SSRT was comparable across tasks, even though the stop-change task exerted more complex (or at least different) demands on the inhibitory system than the stop-signal task. ADHD patients had a higher proportion of choice errors, possibly reflecting more premature responses. Specifically in the stop-change task, patients had more variable choice responses and made more inappropriate change responses, which may also reflect enhanced impulsivity. CONCLUSIONS: The results support a core deficit in behavioral inhibition in adults with ADHD. We further suggest that there is more evidence for a critical role of deficient inhibitory control in adults than in children with ADHD.

Adolescent↗

PubMed2006

Having a co-twin with attention-deficit hyperactivity disorder.

Attention-deficit hyperactivity disorder (ADHD) is a common childhood disorder which occurs more often in twins than singletons. This article focuses on the psychosocial consequences of having a co-twin with ADHD. Specifically, the level of anxiety (generalized and separation) in non-ADHD children who have a co-twin with ADHD is examined using data from the Australian Twin ADHD Project (ATAP). Parental report data on 501 dizygotic (DZ) twin pairs aged 6 to 15 and their siblings were used to examine (i) anxiety symptoms in twin pairs discordant for ADHD, (ii) how the effects of an ADHD twin on their co-twin and siblings are related to the type of ADHD, and (iii) whether the effects are greater for the nonaffected twin than nontwin siblings. Results show that anxiety was high in co-twins of children with the combined subtype of ADHD, with increased symptoms of both generalized and separation anxiety. Inattentive ADHD had smaller effects, which were confined to generalized anxiety and were specific to the co-twin rather than other siblings. These results have clinical implications in managing the entire multiple birth family where one twin has ADHD, and also has implications for genetic analysis in modeling the relationship of ADHD to internalizing disorders.

Adolescent↗

PubMed2005

Predictors of attention-deficit/hyperactivity disorder within 6 months after pediatric traumatic brain injury.

OBJECTIVE: To assess the phenomenology and predictive factors of attention-deficit/hyperactivity disorder (ADHD) after traumatic brain injury (TBI), also called secondary ADHD (SADHD). METHOD: Children without preinjury ADHD 5-14 years old with TBI from consecutive admissions (n = 143) to five trauma centers were observed prospectively for 6 months (baseline and 6 months), with semistructured psychiatric interviews. Injury severity, lesion characteristics, and preinjury variables including psychiatric disorder, family psychiatric history, family psychiatric history of ADHD, family function, socioeconomic status, psychosocial adversity, and adaptive function were assessed with standardized instruments. RESULTS: SADHD in the first 6 months after injury occurred in 18 of 115 (16%) of returning participants. All subtypes of ADHD occurred. Socioeconomic status (p = .041) and orbitofrontal gyrus lesions (p = .005) independently significantly predicted SADHD. CONCLUSIONS: These findings are consistent with research on developmental ADHD that implicate psychosocial factors and prefrontal structural and functional differences between those with and without the disorder.

Adolescent↗

PubMed2002

Effects of stimulant medications on the EEG of children with attention-deficit/hyperactivity disorder.

RATIONALE: Stimulant medications are the most commonly used treatments for attention deficit/hyperactivity disorder (ADHD) in North America and Australia, although it is still not entirely known how these medications work. OBJECTIVES: This study aimed to investigate the effects of stimulant medications on the EEG of children with the Combined subtype of ADHD. METHOD: An initial EEG was recorded during an eyes-closed resting condition and Fourier transformed to provide absolute and relative power estimates for the delta, theta, alpha and beta bands. Theta/alpha and theta/beta ratios were also calculated. Subjects were placed on a 6-month trial of a stimulant and a second EEG was recorded at the end of the trial. RESULTS: The ADHD group had significantly greater absolute delta and theta, less posterior absolute beta, more relative theta, and less relative alpha than the control group, which is typical of EEG studies of children with ADHD. The use of stimulant medications resulted in normalisation of the EEG, primarily evident in changes in the theta and beta bands. CONCLUSIONS: These results suggest that stimulants act to increase cortical arousal in children with ADHD, normalising their brain activity.

Adolescent↗

PubMed2006

ADHD with comorbid anxiety: a review of the current literature.

OBJECTIVE/METHOD: ADHD is often comorbid with anxiety disorders, with rates approaching 25% in many samples. This current review's goal is to examine the literature on ADHD with comorbid anxiety from 1998 to the present. RESULTS: Recent studies indicate that anxiety in ADHD may a) partially inhibit the impulsivity and response inhibition deficits, b) make working memory deficits worse, and c) may be qualitatively different from more phobic types of anxiety seen in pure anxiety samples. In examining subtypes of ADHD, measures of sluggish cognitive tempo show strong correlations with anxiety measures. Insights into the nature of the comorbidity between ADHD and anxiety may be gained by examining the possible comorbidity between Obsessive Compulsive Disorder and ADHD, shared risk factors for ADHD and anxiety, and the current pathogenic models of ADHD. CONCLUSION: The article concludes with a synthesis of the above work, along with directions for future research.

Anxiety Disorders↗

PubMed2005

Long-term safety and effectiveness of mixed amphetamine salts extended release in adults with ADHD.

OBJECTIVE: Assess the long-term safety and effectiveness of mixed amphetamine salts extended release (MAS XR) in adults with attention-deficit/hyperactivity disorder (ADHD) combined subtype. METHODS: A 24-month, open-label extension of a 4-week, multicenter, double-blind, placebo-controlled, parallel-group, forced-dose-escalation study of MAS XR in adults (>or=18 years of age) with ADHD. The 223 enrolled subjects started treatment at 20 mg/day for 1 week, with subsequent titration up to 60 mg/day for optimal therapeutic effects. At monthly visits, efficacy was assessed based on the ADHD Rating Scale IV (ADHD-RS-IV). Safety assessments included spontaneously reported adverse events, laboratory assessments, and monitoring of vital signs. FINDINGS: ADHD symptoms significantly improved for all subjects as measured by change from baseline in mean ADHD-RS-IV total scores (-7.2+/-13.04 unit points; P<.001); this was sustained for up to 24 months. The most common treatment-related adverse events were dry mouth (43% of subjects reporting at least one occurrence), infection (33%), insomnia (32%), anorexia/decreased appetite (32%), headache (30%), and nervousness (26%). Most adverse events were mild to moderate in intensity. CONCLUSION: Treatment with MAS XR 20-60 mg/day for adult ADHD was generally well tolerated and was associated with sustained symptomatic improvement for up to 24 months.

Administration, Oral↗

PubMed2001

Deficient inhibition as a marker for familial ADHD.

OBJECTIVE: The authors investigated whether deficient inhibitory control, as measured by the stop-signal paradigm, delineates a familial subgroup of attention deficit hyperactivity disorder (ADHD). METHOD: Subjects were 54 ADHD children defined as having poor or good inhibition (on the basis of stop-signal paradigm performance) and 26 healthy comparison children. Family history of ADHD and measures of neurobiological and psychosocial risk were compared among the three groups. RESULTS: ADHD was significantly more prevalent in the families of the children with ADHD who exhibited poor inhibition (48.1%) than in the families of those exhibiting good inhibition (18.5%) or in the families of healthy comparison children (7.7%). No differences in neurobiological or psychosocial risk were found for the three groups. CONCLUSIONS: Deficient inhibition delineates a familial subtype of ADHD. Psychosocial and neurobiological factors did not account for inclusion in the good inhibition group and did not act conjointly with inhibition to increase the risk for ADHD in the poor inhibition group. This study demonstrates that cognitive measures such as a laboratory measure of inhibition can serve as phenotype markers for genetic analyses.

Analysis of Variance↗