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PubMed2005

Long-term cardiovascular effects of mixed amphetamine salts extended release in adults with ADHD.

OBJECTIVE: To assess long-term cardiovascular effects of mixed amphetamine salts extended release (MAS XR) in adults with attention-deficit/hyperactivity disorder (ADHD) combined subtype. METHODS: 223 otherwise healthy adults (>or=18 years of age) with ADHD combined subtype were exposed to 480 msec (QTcF [corrected by Fridericia's formula] >454 msec). Seven subjects discontinued due to a cardiovascular adverse event (hypertension, n=5, palpitation/tachycardia, n=2); none of these events was reported as serious. Few subjects with normal baseline vital signs (using approved parameters at the time of study initiation) exhibited clinically significant abnormalities at end point; several subjects with borderline baseline values exhibited shifts to abnormal values during MAS XR therapy. CONCLUSION: Cardiovascular effects of long-term MAS XR (<or=60 mg/day) were minimal in otherwise healthy adults with ADHD. Nevertheless, vital signs should be monitored prior to and during treatment with any stimulant.

Adult↗

PubMed2004

Evaluating the endophenotype model of ADHD neuropsychological deficit: results for parents and siblings of children with ADHD combined and inattentive subtypes.

Neurogenetic models predict neuropsychological weaknesses in the relatives of children with attention-deficit/ hyperactivity disorder (ADHD). The authors examined executive and regulatory measures in 386 relatives (307 parents, 79 siblings) of children with ADHD combined type, ADHD inattentive type, and controls. Predicted deficits were seen on trailmaking (relatives of ADHD combined type only), stop-signal reaction times (relatives of girls only), and response variability (mothers only) but not on naming or output speed. Effects generally held, even with relatives' ADHD status controlled. A neuropsychologically impaired subgroup of children with ADHD had relatives with clear neuropsychological weaknesses. The authors conclude that a neurogenetic model of ADHD etiology is supportable only for a subset of executive functions and that neuropsychological heterogeneity warrants more examination in ADHD.

Adult↗

PubMed1998

Rating scales in attention-deficit/hyperactivity disorder: use in assessment and treatment monitoring.

Rating scales are valuable tools in both assessment and treatment monitoring. However, caution in their use is indicated because of several types of rater errors. Recent large-scale normative studies provide a set of instruments that cover child, adolescent, and adult ages, with separate gender norms and large representative samples. By including DSM-IV symptoms for ADHD in a proposed nationwide standardization of parent, teacher, and self-report scales, it is apparent that the proposed subtypes of ADHD are reasonable; however, item content in this standardization is somewhat broader than that proposed by DSM-IV. Empirical indexes were created and cross-validated, providing powerful discrimination between ADHD and non-ADHD samples. Separate scoring for the traditional DSM subtypes of ADHD allows both categorical and dimensional measures to be used in assessment and treatment monitoring.

Adolescent↗

PubMed2004

[Further contributions to the knowledge about attention deficit hyperactivity disorder. From research to practice].

INTRODUCTION AND DEVELOPMENT: This work is a compendium of the research conducted in recent years by a team from the University of Valencia on attention deficit hyperactivity disorder (ADHD). It describes three large areas of study: the progress made in the differential characterisation of the subtypes of ADHD, as well as its comorbidity profiles, the discriminative capacity of neuropsychological tasks in the evaluation of children with ADHD, and the analysis of how effective multicomponent and multicontextual interventions are in children with ADHD. CONCLUSIONS: The joint analysis of the findings from these studies establishes a series of reflections and guidelines that undoubtedly offer benefits both in delimiting the distinct subtypes of ADHD and in improving intervention procedures.

Attention Deficit Disorder with Hyperactivity↗

PubMed2005

[Attention-deficit hyperactivity disorder comorbidity in a school sample of children].

OBJECTIVE: To evaluate the frequency of conduct disorder (CD), oppositional defiant disorder (ODD) and obsessive-compulsive disorder (OCD) in children with attention-deficit hyperactivity disorder (ADHD). METHOD: This study was performed with children between 7 and 11 years old who fit the DSM-IV diagnostic criteria (n=35) to ADHD, normal neurologic examination and abnormal evolutionary neurological examination (ENE) by Lefèvre. Parents answered a questionnaire with DSM-IV criteria to ADHD and comorbidities. RESULT: ADHD combined subtype was the most prevalent (51.4%). Fourteen (40%) had CD, including two with both CD and OCD. Five (14.2%) had only ODD and one (2.8%) only OCD. Eleven of fourteen children (78.5%) with CD had also ADHD combined subtype, with significant statistical difference (p<0.05). Eleven of fifteen children (73.3%) without comorbidity had inattentive or hyperactive subtype (p<0.05). CONCLUSION: The frequency of association between CD and ADHD was high, much more in combined subtype.

Attention Deficit Disorder with Hyperactivity↗

PubMed2006

Attention deficit hyperactivity disorder among Nigerian primary school children: prevalence and co-morbid conditions.

OBJECTIVE: This study aimed to determine the prevalence of ADHD and co-morbid conditions in a sample of primary school children aged 7-12 years in Nigeria. METHOD: A two-staged procedure in which primary school pupils aged 6-12 years (n = 1112) were assessed for DSM-IV criteria of attention deficit hyperactivity disorder (ADHD) by their teachers in the first stage and their parents in the second stage. A flexible criterion was used for estimating the prevalence. RESULTS: The prevalence of ADHD was 8.7%. The prevalence of the subtypes were: predominantly Inattentive 4.9%, predominantly hyperactive/impulsive 1.2% and combined 2.6%. The male to female ratio was 2:1 for all the subtypes of ADHD except hyperactive/impulsive which was 3.2:1. The co-morbid conditions include oppositional defiant disorder (ODD - 25.8%), conduct disorder (CD - 9.3%) and anxiety/depression (20.6%). While ODD and CD were associated with the hyperactive/impulsive subtype, anxiety/depression was associated with inattentive subtype. CONCLUSION: Our findings support the notion that ADHD occurs across cultures. Given the prevalent rate, efforts should be made to map out strategies for early identification and referral of these children for proper evaluation and treatment. This study can serve as a platform for future analytical studies about this challenging research issue in sub-Saharan Africa.

Attention Deficit Disorder with Hyperactivity↗

PubMed2004

[Effects of distractors on sustained attention in children with attention-deficit hyperactive disorder].

OBJECTIVE: Using an experimental design combining the sustained attention task (CPT, SART) and the flanker task, we investigated: 1) whether children with attention-deficit hyperactive disorder (ADHD) have deficits in their sustained attention; 2) whether distractors have different effects on response to targets at different sustained attention levels; 3) whether different subtypes of ADHD children show different patterns in sustained attention. METHODS: Subjects were recruited from elementary school (Grade 2 - 6). Twenty seven ADHD children (23 male, 4 female) and 29 normal controls (24 male, 5 female) were matched by IQ and age. The cognitive experiment measuring reaction times and error rates was conducted on a computer using DMDX software. ADHD and normal children's performance in sustained attention and the effect of distractors were analyzed, and the results of subtypes of ADHD were compared. RESULTS: ADHD children and normal children did not show significant differences in error rates in their response to dominant (non-attentional) item. However, distractors impaired ADHD children's response to targets. ADHD children also showed more errors than normal children in the sustained attention task, but compared with the non-distractor condition, distractors facilitated their response. CONCLUSIONS: ADHD children have deficits in their sustained attention, reflecting the deficits in brain development. More importantly, this study found that the effects of distractors in sustained attention can be dissociated according to the level of demand on sustained attention: distractors interfered with responses to targets when the demand on sustained attention was low, and they facilitated responses to targets when the demand on sustained attention was high. There were no significant differences between ADHD-inattentive type and ADHD-combined type in their deficits in sustained attention.

Attention↗

PubMed2003

The genetics of pediatric-onset bipolar disorder.

Although bipolar disorder in adults has been extensively studied, early-onset forms of the disorder have received less attention. We review several lines of evidence indicating that pediatric- and early adolescent-onset bipolar disorder cases may prove the most useful for identifying susceptibility genes. Family studies have consistently found a higher rate of bipolar disorder among the relatives of early-onset bipolar disorder patients than in relatives of later-onset cases, which supports the notion of a larger genetic contribution to the early-onset cases. Comorbid pediatric bipolar disorder and attention-deficit/hyperactivity disorder (ADHD) may also define a familial subtype of ADHD or bipolar disorder that is strongly influenced by genetic factors and may, therefore, be useful in molecular genetic studies. There are no twin and adoption studies of pediatric bipolar disorder, but the heritability of this subtype is expected to be high given the results from family studies. Thus, pediatric- and early adolescent-onset bipolar disorder may represent a genetically loaded and homogeneous subtype of bipolar disorder, which, if used in genetic linkage and association studies, should increase power to detect risk loci and alleles.

Adolescent↗

PubMed1999

Mother and teacher reports of ADHD symptoms: DSM-IV Questionnaire data.

OBJECTIVE: Diagnosis of attention-deficit/hyperactivity disorder (ADHD) is thought to be best accomplished by a multimodal approach. In many research and clinical settings, such extensive procedures may not be feasible. A screening instrument that could identify children meeting necessary (but not sufficient) criteria would permit selection of subgroups for more resource-intensive diagnostic procedures. METHOD: The Diagnostic Rating Scale (DRS) was completed by the mothers and teachers of 124 children referred to hospital-based clinics and 225 nonreferred children. The authors performed principal components analysis (PCA) on the questionnaire, compared the scores obtained by children from the 2 samples, and examined age and gender effects. Diagnoses derived from the DRS were not validated against structured diagnostic interviews. RESULTS: PCAs replicated the DSM-IV symptom combinations. Children from the referred sample exhibited more symptoms (p < .001) than children from the community sample. Boys were overrepresented among the children who received DRS-derived ADHD diagnoses. Girls were more likely (92%) to receive a diagnosis of ADHD, predominantly inattentive subtype, than other ADHD diagnoses. CONCLUSIONS: The results of this study provide preliminary support for the validity of the parent and teacher DRS as time- and resource-efficient screening instruments for examining symptoms associated with ADHD.

Attention Deficit Disorder with Hyperactivity↗

PubMed2005

The validity of the DSM-IV subtypes of attention-deficit/hyperactivity disorder.

OBJECTIVE: To examine the validity of the three subtypes of ADHD defined by DSM-IV. METHOD: Studies published in English were identified through searches of literature databases. RESULTS: Estimates of the prevalence of ADHD have increased as a result of the introduction of DSM-IV criteria. Factor analytical and genetic studies provide some support for the validity of the distinction between the three subtypes. However, diagnosis of the combined subtype seems more reliable than the other two subtypes, although reliability is largely unknown for the latter. The hyperactive-impulsive subtype, the least common, differs from the other two subtypes in age distribution, association with other factors and neuropsychological parameters. Almost all treatment trials are based on participants with the combined type. CONCLUSION: Data supporting the validity of the inattentive and hyperactive-impulsive subtypes of ADHD a decade after the publication of DSM-IV are still scarce. Given that inattention is the hypothesized core ADHD symptom, it remains to be demonstrated that hyperactive-impulsive children who are not inattentive have the same condition. One of the main research deficits refers to data on treatment of the inattentive and hyperactive-impulsive subtypes.

Achievement↗

PubMed2003

The dopamine transporter and neuroimaging in attention deficit hyperactivity disorder.

There is evidence that abnormalities within the dopamine system in the brain play a major role in the pathophysiology of attention deficit hyperactivity disorder (ADHD). For instance, dopaminergic psychostimulants, the drugs of first choice in ADHD, interact directly with the dopamine transporter (DAT). Molecular genetic studies suggest involvement of a polymorphism of the DAT gene in ADHD. More recent imaging studies show abnormalities in various brain structures, but particularly in striatal regions. In the current paper we review recent studies in this area. First in vivo measurements of DAT with single photon emission computed tomography (SPECT) in ADHD patients revealed an elevation of striatal DAT density. No differences in DAT density between the left and right side and between putamen and caudate nucleus have been found in [99mTc]TRODAT-1 SPECT of ADHD patients. Patients with ADHD and with a history of nicotine abuse both displayed lower values of DAT density in [99mTc]TRODAT-1 SPECT than non-smokers with ADHD. DAT seem to be elevated in non-smoking ADHD patients suffering from the purely inattentive subtype of ADHD as well as in those with the combined or purely hyperactive/impulsive subtype.

Attention Deficit Disorder with Hyperactivity↗

PubMed1997

The overlap of attention deficit hyperactivity disorder with other common mental disorders.

OBJECTIVE: The literature on the overlap (co-morbidity) of attention deficit hyperactivity disorder (ADHD) with conduct disorder, specific learning disability, and anxiety disorders was reviewed to examine: (i) the evidence for ADHD being a syndrome distinct from the other conditions; and (ii) the evidence for co-morbid patterns representing meaningful subtypes of ADHD. METHODOLOGY: Narrative review of the literature. CONCLUSIONS: Conduct disorder is distinguished from ADHD by prognosis, patterns of association and familial aggregation. Pure' disorders are uncommon, however, and there is little evidence to support a distinct co-morbid subtype. There are few data that reliably distinguish ADHD from specific learning disabilities, but there are weaknesses in research to date. A specific ADHD+learning disabled subtype may exist, but as yet the implications for treatment are not known. Attention deficit hyperactivity disorder is distinguished from anxiety by symptom discrimination, factor analysis, patterns of association, familial aggregation and treatment response. There is evidence for a distinct ADHD+anxiety subtype.

Anxiety↗

PubMed2004

[Association of dopamine beta-hydroxylase polymorphism with attention deficit hyperactivity disorder in children].

OBJECTIVE: To study the association of dopamine beta-hydroxylase gene 5' flanking region polymorphism-1021 C-->T with attention deficit hyperactivity disorder (ADHD) in Han children. METHODS: ADHD was diagnosed according to the DSM-IV criteria. DNA was extracted and PCR was performed to examine the DBH-1021C-->T polymorphism. HHRR was used to test the association of dopamine beta-hydroxylase gene with different subtypes of ADHD. RESULTS: HHRR results showed this polymorphism had a tendency to be associated with the inattention subtype (P=0.067) and the combined subtype (P=0.076). The T allele was the protective factor of the inattentive subtype (P=0.07), and the risk factor of the combined subtype (P=0.08). After dividing the 292 nuclear families according to sex, DBH-1021C-->T polymorphism was found to be associated with the combined subtype (P=0.04) with the T allele as the risk factor (P=0.02). There were no positive findings among the girl nuclear families of ADHD. CONCLUSION: DBH gene is related to ADHD combined subtype and inattention subtype. The genetic basis of ADHD combined subtype and is inattention is different, and is influenced by sex factor.

Adolescent↗

PubMed1999

Sleep problems in children with attention-deficit/hyperactivity disorder: impact of subtype, comorbidity, and stimulant medication.

OBJECTIVE: To determine the relationship of sleep problems to attention-deficit/hyperactivity disorder (ADHD), diagnostic subtype, comorbid disorders, and the effects of stimulant treatment. METHOD: On the basis of clinical diagnostic interviews, children aged 6 to 12 years were assigned to 4 groups: unmedicated ADHD (n = 79), medicated ADHD (n = 22), clinical comparison (n = 35), and healthy nonclinical comparison (n = 36). These groups were compared on 2 sleep questionnaires completed by the parents that assessed current sleep problems and factors associated with sleep difficulties (i.e., sleep routines, sleep practices, child and family sleep history). RESULTS: Factor analysis revealed 3 sleep problem categories: dyssomnias, parasomnias, and sleep-related involuntary movements. Linear regression analyses showed that (1) dyssomnias were related to confounding factors (i.e., comorbid oppositional defiant disorder and stimulant medication) rather than ADHD; (2) parasomnias were similar in clinical and nonclinical children; and (3) the DSM-IV combined subtype of ADHD was associated with sleep-related involuntary movements. However, sleep-related involuntary movements were more highly associated with separation anxiety. CONCLUSIONS: The results suggest that the relationship between sleep problems and ADHD is complex and depends on the type of sleep problem assessed as well as confounding factors such as comorbid clinical disorders and treatment with stimulant medication.

Attention Deficit Disorder with Hyperactivity↗

PubMed2000

Evidence for linkage of a tandem duplication polymorphism upstream of the dopamine D4 receptor gene (DRD4) with attention deficit hyperactivity disorder (ADHD).

Attention deficit hyperactivity disorder (ADHD) is a common childhood-onset neurodevelopmental disorder. Evidence from twin, adoption, and family studies provide support for a genetic contribution to the etiology of ADHD. Several candidate gene studies have identified an association between a 7-repeat variant in exon 3 of the dopamine 4 receptor gene (DRD4) and ADHD. However, in spite of the positive reports finding association of the exon 3 VNTR with ADHD, several other polymorphisms within DRD4 have been identified that conceivably could contribute to risk for ADHD. Recently, another common polymorphism of the DRD4 gene has been described involving a 120-bp repeat element upstream of the 5' transcription initiation site. In this report, we describe results of analysis of the DRD4 120-bp repeat promoter polymorphism in a sample of 371 children with ADHD and their parents, using the transmission disequilibrium test (TDT). Results showed a significant preferential transmission of the 240-bp (long) allele with ADHD. Exploratory analyses of the Inattentive phenotypic subtype of ADHD strengthened the evidence for linkage. These data add further support for the role of DRD4 variants conferring increased risk for ADHD, and imply that additional studies of DRD4 and other related genes are needed.

Adolescent↗

PubMed2003

The influence of gender in the familial association between ADHD and major depression.

This study estimated the impact of gender on the familial associations between attention-deficit/hyperactivity disorder (ADHD) and major depression (MD). The risk for ADHD and MD in first degree relatives was stratified by the presence of MD in boy and girl ADHD probands. In families ascertained via boy probands, the risk for MD was greater in the relatives of both the depressed ADHD and nondepressed ADHD probands. In families ascertained via girl probands, there was cosegregation and the risk of MD was greater only for those relatives of depressed ADHD probands. The results indicate that there may be two mechanisms underlying MD in ADHD families: 1) an etiologically distinct familial subtype of ADHD and MD that is more evident in females, and 2) a familial, gender-specific susceptibility to nonfamilial risk factors that mediate the onset of either ADHD or MD in males and females.

Adolescent↗

PubMed2005

Association and linkage of alpha-2A adrenergic receptor gene polymorphisms with childhood ADHD.

Attention-deficit hyperactivity disorder (ADHD) is a heritable disorder, prevalent from childhood through adulthood. Although the noradrenergic (NA) system is thought to mediate a portion of the pathophysiology of ADHD, genes in this pathway have not been investigated as frequently as those in the dopaminergic system. Previous association studies of one candidate gene in the NA system, ADRA2A, showed inconsistent results with regard to an MspI polymorphism. In the current study, two nearby single-nucleotide polymorphisms, which define HhaI and DraI restriction fragment length polymorphisms, were also genotyped and were in significant linkage disequilibrium with the MspI RFLP. Transmission disequilibrium tests (TDTs) in a sample of 177 nuclear families showed significant association and linkage of the DraI polymorphism with the ADHD combined subtype (P=0.03), and the quantitative TDT showed association of this polymorphism with the inattentive (P=0.003) and hyperactive-impulsive (P=0.015) symptom dimensions. The haplotype that contained the less common allele of the DraI polymorphism likewise showed a strong relationship with the inattentive (P=0.001) and hyperactive-impulsive (P=0.004) symptom dimensions. This study supports the hypothesis that an allele of the ADRA2A gene is associated and linked with the ADHD combined subtype and suggests that the DraI polymorphism of ADRA2A is linked to a causative polymorphism.

Adolescent↗

PubMed2006

A post hoc subgroup analysis of an 18-day randomized controlled trial comparing the tolerability and efficacy of mixed amphetamine salts extended release and atomoxetine in school-age girls with attention-deficit/hyperactivity disorder.

BACKGROUND: Because the scientific literature on the pharmacotherapy of attention-deficit/hyperactivity disorder (ADHD) is almost entirely based on the results of studies in samples consisting primarily of boys, much is unknown about the treatment response in girls. OBJECTIVE: This post hoc analysis compared the efficacy, tolerability, and time course of the effect of mixed amphetamine salts extended release (MAS XR) and atomoxetine in school-age girls with ADHD. METHODS: This was an intent-to-treat subanalysis of the data from girls enrolled in a multicenter, 18-day, randomized, double-blind, parallel-group, forced dose-titration, laboratory school study enrolling boys and girls aged 6 to 12 years with ADHD. The study compared the efficacy, tolerability, and time course of the effect of increasing doses of MAS XR (10, 20, and 30 mg/d) and atomoxetine (0.5 and 1.2 mg/kg per day). The laboratory school sessions were organized in cycles to include 12 hours of observation. Efficacy measures included the SKAMP (Swanson, Kotkin, Agler, M-Flynn, and Pelham) deportment rating subscale, the SKAMP attention rating subscale, and academic testing (number of math problems attempted and answered correctly). Adverse events were assessed throughout the study period. Tolerability and efficacy measures were assessed during laboratory school visits on days 7, 14, and 21. RESULTS: This subanalysis included 57 girls (median age, 9 years; 49.1% white, 22.8% black, 17.5% Hispanic) with a diagnosis of ADHD, combined subtype. Twenty-six girls were randomized to receive MAS XR and 31 were randomized to receive atomoxetine. Mean SKAMP deportment and attention subscale scores in the 2 groups were similar at baseline. Mean changes from baseline were significantly greater for MAS XR compared with atomoxetine on the SKAMP deportment score (-0.48 vs -0.04, respectively; P<0.001) and SKAMP attention score (-0.45 vs -0.05; P<0.001). The time course of medication effect, based on change from baseline in SKAMP deportment scores, indicated 12-hour efficacy for MAS XR at hours 2, 4.5, 7, 9.5, and 12 (all time points, P<0.01 vs baseline) but not for atomoxetine. At the end of the study, both treatment groups had a significant increase from baseline in the mean number of math problems attempted and answered correctly (P<0.001). Girls who received MAS XR attempted significantly greater numbers of problems compared with those who received atomoxetine (P=0.04). Both MAS XR and atomoxetine were well tolerated. The most frequently occurring treatment-related adverse events in girls receiving MAS XR were decreased appetite (40.7%), upper abdominal pain (29.6%), insomnia (25.9%), and headache (14.8%). The most frequently occurring treatment-related adverse events in girls receiving atomoxetine were somnolence (28.1%), upper abdominal pain (15.6%), vomiting (15.6%), nausea (12.5%), and decreased appetite (12.5%). CONCLUSION: This post hoc analysis in a subpopulation of girls with ADHD, combined subtype, found that 18-day treatment with MAS XR was significantly more effective than atomoxetine in terms of ratings of classroom behavior, attention, and academic productivity.

Adrenergic Uptake Inhibitors↗