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PubMed2005

Tryptophan hydroxylase 2 (TPH2) gene variants associated with ADHD.

Genetic and pharmacological studies have emphasised the role of serotonin 5-hydroxytryptamine (5-HT) as a possible etiologic factor in the development of attention-deficit hyperactivity disorder (ADHD). Tryptophan hydroxylase (TPH) is a rate-limiting enzyme in the biosynthesis of serotonin from tryptophan. Originally, the TPH gene was thought to be widely expressed, but a second form of TPH, TPH2, was recently identified and the TPH2 gene was found to be solely expressed in the brain. We examined eight single nucleotide polymorphisms (SNP) in the TPH2 gene for association with ADHD in 179 Irish nuclear families. Transmission disequilibrium test analysis revealed significant association between the T allele of marker rs1843809 with the disorder (chi2=12.2, P=0.0006, OR=2.36). Stratifying data by the sex of the transmitting parent showed that this association was enhanced when paternal transmission was considered (OR=3.7). In addition, several haplotypes (all including the associated marker) were associated with ADHD. These preliminary findings suggest that TPH2 is a susceptibility locus for ADHD. Further confirmation, preferably from different ethnic groups, is required to firmly implicate TPH2 in the pathophysiology of ADHD.

Attention Deficit Disorder with Hyperactivity↗

PubMed2003

A positron emission tomography study of methylphenidate in adults with ADHD: alterations in resting blood flow and predicting treatment response.

A hallmark symptom of attention-deficit hyperactivity disorder (ADHD) is an excess of motoric behavior or hyperactivity. Methylphenidate (MPH) is known to reduce hyperactivity in individuals with ADHD. Yet little is known about how it alters neural activity and how this relates to its clinical effects. The goal of this study is to examine MPH-induced changes during resting brain metabolism, and to examine how these changes correlate with measures of behavioral response to the drug. Measures of regional cerebral blood flow (rCBF) using positron emission tomography (PET) were acquired at rest for ten adult subjects with ADHD during both an unmedicated state and after a 3-week period of chronic dosing with a clinically optimal dose of MPH. Compared with the on-MPH condition, the off-MPH condition was associated with relative increases in rCBF bilaterally in the precentral gyri, left caudate nucleus, and right claustrum. The on-MPH condition was associated with relative increases in rCBF in the cerebellar vermis. A correlational analysis measured the relation between rCBF in the off-medication condition to change in ADHD ratings between the off- and on-MPH condition to identify brain regions associated with treatment response. The degree of change in the ratings was negatively correlated with rCBF increases in the midbrain, cerebellar vermis, and the precentral and middle frontal gyri in the off-MPH condition. The majority of these brain regions are involved in the planning and execution of motor behavior. These data suggest that MPH modulates brain regions associated with motor function to achieve a reduction in ADHD symptoms.

Adult↗

PubMed2006

Association of 4-repeat allele of the dopamine D4 receptor gene exon III polymorphism and response to methylphenidate treatment in Korean ADHD children.

In the present study, we investigated the association between the 4-repeat allele at the dopamine receptor D4 (DRD4) gene and the response to treatment with methylphenidate (MPH) in Korean children with attention deficit hyperactivity disorder (ADHD). The study subjects were 83 children with ADHD (8.40+/-1.73 years) who were recruited from two child psychiatric clinics in South Korea. All of the drug-naive ADHD children were treated with MPH for about 8 weeks. An improvement of more than or equal to [corrected] 50% in the ADHD Rating Scale-IV (ARS) scores after 8 weeks of treatment compared with the baseline ARS scores before the treatment was considered as a 'good response', whereas an improvement of less than [corrected] 50% was considered as a 'poor response'. After the genotyping for DRD4 was performed, we investigated the association between the genotype at DRD4 and the response to MPH treatment. We performed a comparison of the response to MPH treatment between the two largest groups, viz. the subjects with and without the 4/4 genotype at DRD4. According to the ARS scores of the subjects as assessed by their parents and by their teachers, we found that while 71.1 and 80.0% (32/45 and 24/30), respectively, of those with a good response to MPH treatment showed the 4/4 genotype at DRD4, only 31.6 and 37.7% (12/38 and 20/53), respectively, of those with a poor response to MPH treatment showed the 4/4 genotype at DRD4 (Pearson chi2-values=12.926 and 13.737, respectively, both df=1, and both p<0.01). Our findings support the existence of an association between the 4-repeat allele at DRD4 and good response to MPH in Korean ADHD children.

Alleles↗

PubMed2004

[ADHD and alcohol dependence: a common genetic predisposition?].

INTRODUCTION: Nearly 50 % of subjects with continuing symptoms of attention-deficit hyperactivity disorder (ADHD) in adulthood show a comorbid substance use disorder. Both, ADHD and alcohol dependence have a high genetic load and might even share overlapping sources of genetic liability. METHOD: We investigated phenotype and 5-HTT/5-HT2c allelic characteristics in 314 alcoholics of German descent. RESULT: 21 % of the alcoholics fulfilled DSM-IV-criteria of ADHD with ongoing symptoms in adulthood. There was no significant difference in 5-HTT- or 5-HT2c-allele distribution between alcoholics and matched controls or between alcoholics with or without ADHD. CONCLUSION: In our sample the functional relevant 5-HTT-promoter and the 5-HT2c-receptor Cys23Ser polymorphism do not contribute to the supposed common genetic predisposition of ADHD and alcohol dependence.

Adolescent↗

PubMed2001

Clinical validity and interpretation of the Gordon Diagnostic System in ADHD assessments.

Gordon Diagnostic System (GDS) data were analyzed for 165 referred children with ADHD combined type and 46 referred children without ADHD, 6-16 years of age. Results showed significant differences between children with and without ADHD on the GDS standard scores and the IQ-GDS differences scores. Using a GDS composite standard score of 13 points or more below IQ to classify children as having ADHD resulted in the highest diagnostic accuracy (86%), with positive predictive power equal to 91%, and negative predictive power 67%. Results for the GDS compared favorably with those reported for other continuous performance tests. The findings lend support to the GDS as a clinically useful component of an ADHD evaluation.

Adolescent↗

PubMed2003

Performance of girls with ADHD and comparison girls on the Rey-Osterrieth Complex Figure: evidence for executive processing deficits.

In spite of a multitude of scoring approaches, the ability of the Rey-Osterrieth Complex Figure (ROCF) to measure executive functions versus grapho-motor skill is still open to question. To clarify this issue, we examined the performance of an ethnically and socioeconomically diverse sample of preadolescent girls (ADHD-Combined, n = 93; ADHD-Inattentive, n = 47; and comparison girls, n = 88) on the ROCF, scoring both immediate copy and delayed recall performance. Girls with ADHD performed the task following a stimulant medication washout. Dependent measures were the established Developmental Scoring System variables of Organization, Accuracy, and Style, plus an operationalized and extensively detailed scoring of errors, featuring an error proportion score (EPS). The major finding is that only EPS differentiated girls with ADHD from comparison girls (a) on both immediate and delayed performance and (b) with stringent statistical control of Performance IQ, fine motor speed, and performance on the Porteus Mazes (as well as comorbidities), with effect sizes in the medium range. Perseverative errors contributed significantly to EPS. Overall, error scores on the ROCF appear to tap planning, a key executive function, and are quite sensitive to deficits in this domain for girls with ADHD.

Attention Deficit Disorder with Hyperactivity↗

PubMed1998

Deficits in long-term memory are not characteristic of ADHD. Attention Deficit Hyperactivity Disorder.

To separate the influence of inattentiveness from memory, we examined savings scores on material previously learned in 53 children with Attention Deficit Hyperactivity Disorder (ADHD), 63 with a reading disability (RD), 63 with both ADHD and RD combined, and 112 controls. Children with reading disabilities were impaired in their ability to remember previously-learned material unless it was repeated over four trials, whereas children with only ADHD performed as well as the controls for material presented only once. Children with ADHD did perform poorly on three subtests that are sensitive to attention/ concentration. We conclude that ADHD is associated with impaired initial learning due to attention deficits, but that long-term retention of learned material is normal.

Attention Deficit Disorder with Hyperactivity↗

PubMed2001

Neuropsychological assessment of response inhibition in adults with ADHD.

Several theoretical models suggest that the core deficit of ADHD is a deficiency in response inhibition. While neuropsychological deficits in response inhibition are well documented in ADHD children, research on these deficits in adult ADHD populations is minimal. Twenty-five adult ADHD patients, 15 anxiety-disordered adult patients, and 30 normal adults completed three neuropsychological tests of response inhibition: the Continuous Performance Test, Posner Visual Orienting Test, and the Stop Signal Task. ADHD adults demonstrated response inhibition performance deficits when compared to both normal adults and anxiety disordered adults only on the Continuous Performance Test. A similar pattern of differences was not observed on the other two neuropsychological tests. Differing results between tasks may be due to differences in test reliability, task parameters, or the targeted area of brain functioning assessed by each test.

Adolescent↗

PubMed2003

The stroop color-word interference test as an indicator of ADHD in poor readers.

The performance on the Stroop Color-Word Interference Test of 36 boys with Attention Deficit Hyperactivity Disorder (ADHD) was compared with performances of a matched control sample. The control group outperformed their counterparts on the control and interference conditions of the Stroop test, suggesting ADHD-specific executive and reading deficits. When individuals with both ADHD and reading disorders were excluded from the analysis, the authors found a significant difference between the ADHD group and the control group on the color-word test, indicating that poor reading skills may produce false negatives on the Stroop test. However, fast and slow readers with ADHD did not perform differently from each other on the color-word test. The authors postulated the existence of two different causes of reading problems: phonological deficits and attentional deficits.

Attention↗

PubMed2000

Inhibitory control in children with traumatic brain injury (TBI) and children with attention deficit/hyperactivity disorder (ADHD).

The behavioural and cognitive sequelae of traumatic brain injury (TBI) have features in common with attention deficit/hyperactivity disorder (ADHD), best characterized by deficits in response inhibition.The performance was, therefore, examined of 27 children with TBI, 31 children with developmental ADHD, and 26 matched controls aged 8-12, on two inhibition tasks: the Stop-Signal Task and a Delayed-Response-Task. Children with TBI and children with ADHD showed a pervasive deficit in their inhibitory control processes with respect to inhibition of both pre-potent and on-going responses. In addition, children with TBI were found to suffer from a general slowing of their information processing, which was not correlated with the inhibition deficit. TBI children with and without a secondary ADHD differed only tendentially in their Mean Go-Reaction time in the stop-task. However, subdividing TBI children according to actigraph data into hypo-, hyper- and normokinetic subgroups revealed that the hyperactive TBI children had inhibitory deficit patterns that were similar to children with developmental ADHD. It is concluded that slowing of information processing speed seems to be a general consequence of TBI in childhood, whereas slowing of the stop-processes or inhibitory deficits, specifically, are associated with post-injury hypo- or hyperactivity.

Attention Deficit Disorder with Hyperactivity↗

PubMed2004

Conversational profiles of children with ADHD, SLI and typical development.

Conversational indices of language impairment were used to investigate similarities and differences among children with Attention-Deficit/Hyperactivity Disorder (ADHD), children with Specific Language Impairment (SLI) and children with typical development (TD). Utterance formulation measures (per cent words mazed and average number of words per maze) differentiated the ADHD group from the SLI and TD groups (ADHD>TD=SLI). In contrast, measures of lexical diversity, average sentence length and morphosyntactic development (number of different words, MLU, and composite tense) differentiated the SLI group from the ADHD and TD groups (SLI <ADHD=TD). High levels of within group variation were observed in children's speaking rate (words per minute). Implications for differential diagnosis and the establishment of phenotypes for developmental language disorders are discussed.

Analysis of Variance↗

PubMed2005

Differentiating SLI from ADHD using children's sentence recall and production of past tense morphology.

Measures of sentence recall and past tense marking were used to examine the similarities and differences between children with Attention Deficit/Hyperactivity Disorder (ADHD), children with specific language impairment (SLI), and typically developing (TD) children. Both SLI and ADHD group means for sentence recall tasks were significantly lower than the TD control group (SLI<ADHD<TD). In contrast, limitations in past tense marking were characteristic of the SLI group (SLI<ADHD=TD). Frequent affix omissions or bare stem errors (e.g. the girl colour the picture; the girl fall in the net) differentiated the SLI group from the other two groups. Over-regularization errors (e.g. the girl falled into the net) did not (SLI=ADHD=TD). Clinical implications are discussed.

Attention Deficit Disorder with Hyperactivity↗

PubMed2006

Reaction time distribution analysis of neuropsychological performance in an ADHD sample.

Differences in reaction time (RT) variability have been documented between children with and without Attention Deficit Hyperactivity Disorder (ADHD). Most previous research has utilized estimates of normal distributions to examine variability. Using a nontraditional approach, the present study evaluated RT distributions on the Conners' Continuous Performance Test in children and adolescents from the Multimodal Treatment Study of ADHD sample compared to a matched sample of normal controls (n = 65 pairs). The ex-Gaussian curve was used to model RT and RT variability. Children with ADHD demonstrated faster RT associated with the normal portion of the curve and a greater proportion of abnormally slow responses associated with the exponential portion of the curve. These results contradict previous interpretation that children with ADHD have slower than normal responding and demonstrate why slower RT is found when estimates of variability assume normal Gaussian distributions. Further, results of this study suggest that the greater number of abnormally long RTs of children with ADHD reflect attentional lapses on some but not all trials.

Attention Deficit Disorder with Hyperactivity↗

PubMed2005

The effect of reinforcement variables on inhibition in children with ADHD.

Behavioral inhibition, often cited as a central deficit in children with ADHD, has been shown to change in response to reinforcement. In this preliminary investigation, children with ADHD (n= 20) and matched controls (ages 7 to 12) completed a new version of the stop signal paradigm, the Fire Fighter Game, a measure of inhibition of a prepotent motor response, under three conditions: (1) no reinforcement; (2) immediate reinforcement; and (3) delayed reinforcement. In all conditions, the stop signal reaction time (SSRT) of children with ADHD was consistently longer than controls. Both groups improved significantly with reinforcement, and there was no strong evidence that immediate reinforcement was more effective than delayed reinforcement. However, it appeared that the reason for the changes in SSRT in response to reinforcement differed between the groups. Children in the control group responded faster on go trials, whereas children with ADHD improved their ability to inhibit responding with shorter stop delays. The relevance of these findings is discussed in terms of current theories of ADHD.

Analysis of Variance↗

PubMedDate not supplied

Safety and tolerability of once versus twice daily atomoxetine in adults with ADHD.

BACKGROUND: Attention-Deficit/Hyperactivity Disorder (ADHD) is a disorder characterized by hyperactivity, impulsiveness, and inattention that affects 4% of adults. Atomoxetine hydrochloride is an FDA-approved treatment for adult ADHD, but no studies have clarified whether there are advantages to once versus twice daily dosing. METHODS: This randomized, double-blind, multicenter study compared safety and tolerability of 80 mg atomoxetine QD versus 40 mg atomoxetine BID in 218 adults with ADHD. Treatment-emergent adverse events (TEAEs), laboratory values, vital signs, weight, electrocardiograms, scores on the Arizona Sexual Experiences Scale, and efficacy (using the Conners' ADHD Rating Scale-Investigator Rated: Screening Version) were assessed. RESULTS: The overall incidence for any one TEAE was low. There was no significant treatment group difference in likelihood of patients experiencing >/=1 of the four most commonly observed TEAEs (dry mouth, insomnia, nausea, and erectile dysfunction). Frequency of nausea was significantly lower in the 40 mg BID group (16.4%) than the 80 mg QD group (32.4%; p = .007). There were no unexpected safety results. Although both QD and BID treatments were efficacious, the reduction in scores was greater for BID treatment. CONCLUSIONS: Data indicate both dosing strategies are safe, well tolerated, and efficacious in the treatment of adult ADHD. Changes in dosing strategy are unlikely to be accompanied by safety risks, implying that there is room for prescribers to use discretion and to base dosing strategies on individual factors.

Adolescent↗

PubMed2001

Attention-Deficit Hyperactivity Disorder (ADHD) symptoms and smoking patterns among participants in a smoking-cessation program.

Previous research has suggested an increased liability to smoking among individuals with Attention-Deficit Hyperactivity Disorder (ADHD). This link is thought to be attributable, in part, to nicotine's beneficial effects on attention and performance. In the present study, we examined the association of ADHD symptoms of inattention and hyperactivity with smoking behavior in a sample of 226 male and female smokers ages 18 and older who were enrolled in a smoking-cessation program. Prior to treatment, they completed measures of ADHD symptoms and standardized measures of smoking patterns. Hierarchical linear regression models were used to characterize the smoking patterns associated with ADHD inattention and hyperactivity symptoms, controlling for potential confounder variables. Smoking for stimulation purposes and the urge to smoke to minimize withdrawal symptoms were the primary patterns associated with ADHD inattention symptoms, while hyperactivity symptoms were not associated with smoking patterns. Consistent with a self-medication hypothesis, these results suggest that smokers with frequent symptoms of inattention may use nicotine as a stimulant drug to help manage these symptoms. Future studies of the role of inattention symptoms in response to smoking treatment are warranted.

Adolescent↗

PubMed2004

Novel strategy for the analysis of CPT data provides new insight into the effects of methylphenidate on attentional states in children with ADHD.

Continuous performance tasks (CPTs) provide a method for studying some components of attention, but do not take into account that attention fluctuates from moment to moment. To address this issue, CPT performance was classified into one of four states (on-task, impulsive, distracted, or randomly responding) every 30 seconds, based on commission and omission error rates. We evaluated this method on 60 boys (10.6 +/- 1.1 years) with attention-deficit hyperactivity disorder (ADHD)-Combined subtype, tested before and after a dose of methylphenidate (MPH, 0.4 mg/kg), and 8 unmedicated healthy control boys (11.3 +/- 2.0 years of age). Healthy controls were on-task during 82.4% of the 30-second epochs, and made an average of 5.4 attention shifts. In contrast, children with ADHD were only on-task during 42.6% of the epochs (p = 0.0006), and they made an average of 12.8 attention shifts (p = 0.00004). These state measures provided more robust indicators of the difference between children with ADHD and controls than did traditional CPT measures of error rates, latency, and variability. The new state measures were also more significantly affected by MPH. MPH produced a 77% increase in the percent of time children with ADHD spent on-task (p < 10(12)). Conversely, MPH reduced time spent in the distracted, impulsive, and random response states by 79%, 44.5%, and 69.2%, respectively (all p values < 0.0002). Unlike errors of omission and commission, which are highly correlated (r = 0.722, n = 60, p < 10(-11)), the percent of epochs spent in impulsive, distracted, and random response states were uncorrelated, and loaded onto discrete independent factors on principal component analysis. The level of activity during the CPT correlated with the degree of distraction, but not with the degree of impulsivity. Children with ADHD could be subtyped according to the nature of their attention performance problems, and these subtypes differed in levels of hyperactivity and degrees of response to MPH.

Attention↗

PubMed1999

Do stimulants improve self-esteem in children with ADHD and peer problems?

The self-esteem of children with Attention Deficit Hyperactivity Disorder (ADHD) has been shown to be low. The effects of stimulant medication upon their self-esteem have not been systematically studied. The present study employed a reliable self-report instrument to measure the self-esteem of children with ADHD medicated with stimulants vs. those who were unmedicated. Results showed that stimulants were associated with significantly higher self-esteem. Children with ADHD prescribed stimulants reported feeling more intelligent and more popular than unmedicated children with ADHD. Children with ADHD and Oppositional Defiant Disorder (ODD) prescribed stimulants reported feeling better behaved. Significant correlations indicated that higher doses were associated with higher self-esteem. The present results suggest a need for a well-controlled study to determine if stimulants were responsible for the observed differences in self-esteem.

Analysis of Variance↗