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PubMed2005

Absence of gender effects on attention deficit hyperactivity disorder: findings in nonreferred subjects.

OBJECTIVE: In a previous study, the authors found that, compared with referred boys with attention deficit hyperactivity disorder (ADHD), girls are less likely to manifest comorbid disruptive behavior disorders and learning disabilities--characteristics that could adversely affect identification of ADHD in girls. However, because referral bias can affect outcome, these findings require replication in nonreferred groups of ADHD subjects. METHOD: The authors evaluated gender effects in a large group of nonreferred siblings (N=577) of probands with ADHD and non-ADHD comparison subjects. Ninety-eight of the nonreferred siblings (N=73 males, N=25 females) met the criteria for diagnosis of ADHD, and 479 (N=244 males, N=235 females) did not meet those criteria. All siblings were systematically and comprehensively assessed with measures of emotional, school, intellectual, interpersonal, and family functioning. The assessment battery used for the siblings was the same as that used for the probands. RESULTS: The nonreferred males and females with ADHD did not differ in DSM-IV subtypes of ADHD, psychiatric comorbidity, or treatment history. They also showed similar levels of cognitive, psychosocial, school, and family functioning. CONCLUSIONS: These findings suggest that the clinical correlates of ADHD are not influenced by gender and that gender differences reported in groups of subjects seen in clinical settings may be caused by referral biases.

Adolescent↗

PubMed2004

Family factors and sampling approach differentially influence attention deficit/hyperactivity disorder subtypes.

A widely used statistical method to test for genetic association is the transmission disequilibrium test (TDT) using two parent-proband trios. West et al(1) have presented evidence from clinically ascertained ADHD families that children from trios were less likely to have DSM-IV combined subtype ADHD and conduct disorder. They suggest that the exclusion of parent-proband duos could reduce the power of the TDT and similar tests to detect susceptibility genes for this subtype of ADHD. We sought to test this hypothesis in a population-based sample of twin families, while controlling for the effects of other proband and family characteristics in a multivariant logistic regression framework using both latent class and DSM-IV ADHD subtype definitions. For both latent class and DSM-IV defined combined and inattentive ADHD, sex of the proband and comorbid conduct disorder or oppositional defiant disorder, significantly predicted diagnosis. For latent class and DSM-IV defined combined subtype, younger age also significantly predicted ADHD subtype. Latent class and DSM-IV defined combined subtype ADHD with comorbid conduct disorder was significantly less common in children from trios while conduct disorder without ADHD did not differ in frequency between families with zero, one or two participating parents.

Analysis of Variance↗

PubMed2006

A comparison of North American versus non-North American ADHD study populations.

Few large, prospective clinical studies in Europe have assessed the validity and applicability of research methods used to study ADHD in North America. To assess comparability of study populations, we examined baseline patient characteristics from a group of North American studies against those of a large European/African/Australian study. All studies used identical diagnostic assessments and inclusion criteria, with ADHD diagnosis and the presence of comorbid psychiatric conditions confirmed using the KSADS-PL. Raters were trained and assessed to ensure uniform diagnostic and symptom severity rating standards. Six hundred and four patients (mean age = 10.2 years) enrolled in the non-North American study, and 665 patients (mean age = 10.4 years) enrolled in the North American study. The proportion of girls was higher in the North American studies (29.2% vs. 10.4%, p < 0.001). In both groups, most patients had a positive family history of ADHD and previous stimulant treatment. Fewer had the inattentive subtype of ADHD, and mean severity was slightly higher in the non-North American study. Results demonstrate that, when a uniform set of rigorous, standardized diagnostic criteria are used by skilled clinicians, the patient populations identified are generally similar. This supports the practice of generalizing results from treatment studies across geographies.

Adrenergic Uptake Inhibitors↗

PubMed2003

Can adults with attention-deficit/hyperactivity disorder be distinguished from those with comorbid bipolar disorder? Findings from a sample of clinically referred adults.

BACKGROUND: Despite data describing the overlap of attention deficit hyperactivity disorder (ADHD) and bipolar disorder (BPD) in youth, little is known about adults with these co-occurring disorders. We now evaluate the clinical characteristics of referred adults with (n = 24) and without BPD (n = 27). METHODS: Referred adults to clinical trials of ADHD were evaluated by psychiatric evaluation using DSM-IV criteria. Structured psychiatric interviews were used to systematically assess adult and childhood disorders. RESULTS: The vast majority of patients with ADHD plus BPD had bipolar II disorder (88%). Adults with ADHD plus BPD had higher rates of the combined subtype of ADHD compared to ADHD without BPD (chi(2) = 8.7, p =.003), a greater number of DSM-IV ADHD symptoms (14.8 +/- 2.9 and 11.4 +/- 4.0; t = -3.4, p <.01), more attentional symptoms of ADHD (8.1 +/- 1.4 and 6.8 +/- 2.1; t = -2.5, p <.02; trend), poorer global functioning (47 +/- 5.9 and 52 +/- 7.4, t = 2.6, p <.02; trend), and additional comorbid psychiatric disorders (3.7 +/- 2.5 and 2.0 +/- 1.9; t = -2.9, p <.01). CONCLUSIONS: These results suggest that adults with ADHD plus BPD have prototypic symptoms of both disorders, suggesting that both disorders are present and are distinguishable clinically.

Adult↗

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↗

PubMed2005

Family-based association study of the serotonin transporter gene polymorphisms in Korean ADHD trios.

The dopamine (DA) system has been implicated in attention deficit hyperactivity disorder (ADHD) based on pharmacologic evidence. Because of an interaction between the serotonin (5-HT) and DA systems, the serotonin transporter gene (SLC6A4) has been considered as a candidate ADHD susceptibility gene. Two common polymorphisms, 5-HTTLPR and the intron 2 VNTR, have been studied for association in ADHD, with both positive (increased frequency of long allele of 5-HTTLPR and decreased frequency of 12 repeats of the intron 2 VNTR) and negative findings. However, there has not been an association study in an East Asian ADHD population. In this study, we examined the genotypes of these two polymorphisms in 126 Korean ADHD families and investigated linkage disequilibrium (LD) between SLC6A4 and ADHD, using the transmission disequilibrium test (TDT) and haplotype analysis. Additionally, association with quantitative measures of inattention, hyperactivity-impulsivity, and overall severity was tested using logistic regression and QTDT analysis. TDT of both polymorphisms and haplotype analysis failed to detect LD. However, after excluding ADHD NOS subtype, TDT revealed nominally significant LD between 5-HTTLPR and ADHD (chi2 = 4.9, P = 0.036). QTDT revealed positive association between 12 repeats of the intron 2 VNTR and attention (P = 0.031), but case-control and TDT logistic regression analyses were negative. These markers have low heterozygosity in the Korean population, which would be expected to reduce the power of association. This result suggests that future studies should include more polymorphic markers and subjects to thoroughly investigate a potential association between SLC6A4 and ADHD in the Korean population.

Attention Deficit Disorder with Hyperactivity↗

PubMed1995

Differential effects of methylphenidate on working memory in ADHD children with and without comorbid anxiety.

OBJECTIVE: To examine the effects of methylphenidate (MPH) on working memory and behavior in anxious and nonanxious children with attention-deficit hyperactivity disorder (ADHD). METHOD: A total of 40 ADHD children (22 nonanxious, 18 anxious) completed a randomized, double-blind, placebo-controlled, crossover trial with three doses (0.3, 0.6, 0.9 mg/kg) of MPH. A serial addition task was used to assess working memory; direct observation of motor activity indexed behavior. RESULTS: MPH improved working memory in the nonanxious ADHD group but not in the comorbidity anxious group. By contrast, MPH reduced activity level in both groups. The presence of concurrent learning disabilities did not influence stimulant response. CONCLUSIONS: The presence of comorbid anxiety in children with ADHD predicts a less robust response to stimulant treatment and suggests that ADHD with anxiety may constitute a distinct and clinically meaningful subtype of ADHD.

Anxiety Disorders↗

PubMed2004

Gender differences in a clinic-referred sample of Taiwanese attention-deficit/hyperactivity disorder children.

The purpose of this study was to examine gender differences within a clinic-referred sample of 6-11-year-old Taiwanese children with attention-deficit/hyperactivity disorder (ADHD)- combined subtype. The subjects were 21 girls with a diagnosis of ADHD from the 4th edition of the Diagnostic and Statistical Manual and 21 age-matched boys with ADHD. Comparisons were made of behavioral ratings, cognitive profiles, and vigilance/attention assessments between these two groups. The results found ADHD girls and ADHD boys to be statistically indistinguishable on nearly all measures except the subtests of block design (P = 0.016), the discrepancy between Performance Intelligence Quotient and Verbal Intelligence Quotient (P = 0.019), and the discrepancy between fluid and crystallized IQ (P = 0.041). In the study samples, ADHD girls and ADHD boys were strikingly similar on a wide range of measures. ADHD boys and girls in clinics may be expected to show more similarities than differences in treatment needs. However, these results should be interpreted with caution since data were only from clinic-referred samples.

Arousal↗

PubMed2003

"Maturational lag" hypothesis of attention deficit hyperactivity disorder: an update.

UNLABELLED: This article discusses the relationship of maturation to ADHD and hyperkinetic disorder (HKD), with an emphasis on current research in ADHD and HKD, persistence and remission of ADHD symptoms over time and brain maturational trajectories. CONCLUSION: ADHD is a broad, heterogeneous syndrome and only a subgroup of subjects has a diagnosis of HKD, which is a subset of individuals with severe ADHD combined subtype. Children showing symptoms above the threshold for a diagnosis of ADHD are at risk of developing comorbid conditions and increasing stress in both parents and teachers. In some subjects, ADHD symptoms can improve over time during maturation and development. These children with a diagnosis of ADHD could be viewed as showing variants of normal childhood behaviour with maturational trajectories that are lagging behind but will catch up. ADHD could therefore represent a continuum from normality at one extreme to a severe disorder, HKD according to ICD-10, at the other extreme.

Adolescent↗

PubMed2006

[The sociometric status of children with the combined subtype of attention deficit hyperactivity disorder].

INTRODUCTION: Different studies show that one of the most important problem associate with ADHD combined subtype is the difficulty to establish appropriate social relationships, being rejected by their schoolmates. AIM: To study interactions of children with ADHD-C at school; specifically the sociometric status and the features of rejected children compared with non rejected children. SUBJECTS AND METHODS: 23 ADHD-C children from 20 primary schools (2nd to 5th degree) of Castellon were examined, using sociometric tasks and behaviour scales for parents and teachers. RESULTS: Sociometric tasks show that the ADHD-C children were preponderantly rejected by their schoolmates, and the reasons of this rejection were disruptive and antisocial behaviour. Furthermore, rejected children weren't aware of this fact. CONCLUSION: Our findings established the severity of social problems in this children al school.

Attention Deficit Disorder with Hyperactivity↗

PubMed2004

Gene-environment interaction in hyperkinetic conduct disorder (HD + CD) as indicated by season of birth variations in dopamine receptor (DRD4) gene polymorphism.

Recently, an interaction between season of birth and the expression of candidate genes has been suggested. Season of birth variations in tryptophan hydroxylase (TPH), the serotonin transporter (5-HTTLPR) and the dopamine D4 receptor (DRD4) gene polymorphisms are different for affective disorders and schizophrenia. The DRD4 gene has been postulated as a candidate gene for attention-deficit-hyperactivity disorder (ADHD), equivalent to hyperkinetic disorder (HD). The seven-repeat long variant of this gene (DRD4*7) in comparison to the short repeat variants of the DRD4 gene polymorphism, has been found to be associated with ADHD. A seasonal pattern of birth has also been proposed for different subtypes of ADHD. Therefore, in a subgroup of children with HD and conduct disorder (CD) and in healthy controls, we investigated a possible association between the DRD4*7 allele and HD + CD in association with the season of birth. Supporting this hypothesis, we found an interaction between the seasons of birth and the expression of the DRD4 candidate gene in children with HD + CD as well as in controls, which differ significantly from each other. Depending on the season of birth, children carrying the DRD4*7R allele showed different relative risks for developing HD + CD.

Adolescent↗

PubMed2004

Behavioral outcomes and evidence of psychopathology among very low birth weight infants at age 20 years.

OBJECTIVE: Information on the mental health of very low birth weight (VLBW; <1500 g) children in young adulthood is sparse. We thus sought to examine gender-specific behavioral outcomes and evidence of psychopathology in a cohort of VLBW young adults at 20 years of age. METHODS: We compared a cohort of 241 survivors among VLBW infants who were born between 1977 and 1979 (mean birth weight: 1180 g; mean gestational age at birth: 29.7 weeks), 116 of whom were men and 125 of whom were women, with 233 control subjects from the same population in Cleveland who had normal birth weights (108 men and 124 women). Young adult behavior was assessed at 20 years of age with the Achenbach Young Adult Self-Report and the Young Adult Behavior Checklist for parents. In addition, the young adults and parents completed the ADHD Rating Scale for Adults. Gender-specific outcomes were adjusted for sociodemographic status. RESULTS: VLBW men reported having significantly fewer delinquent behaviors than normal birth weight (NBW) control subjects, but there were no differences on the Internalizing, Externalizing, or Total Problem Behavior scales. Parents of VLBW men reported significantly more thought problems for their sons than did parents of control subjects. VLBW women reported significantly more withdrawn behaviors and fewer delinquent behavior problems than control subjects. Their rates of internalizing behaviors (which includes anxious/depressed and withdrawn behaviors) above the borderline clinical cutoff were 30% versus 16% (odds ratio: 2.2; 95% confidence interval [CI]: 1.2-4.1). Parents of VLBW women reported significantly higher scores for their daughters on the anxious/depressed, withdrawn, and attention problem subscales compared with control parents. The odds ratios for parent-reported rates above the borderline-clinical cutoff among women for the anxious/depressed subscale was 4.4 (95% CI: 1.4-13.5), for thought problems was 3.7 (95% CI: 1.2-11.6), and for attention problems was 2.4 (95% CI: 1.0-5.5). There were no differences in the young adult self-report of attention-deficit/hyperactivity disorder (ADHD). Parents of VLBW men reported higher mean scores on the attention subtype of ADHD but not higher rates of ADHD. CONCLUSION: The increase in psychopathology among VLBW survivors in young adulthood indicates a need for anticipatory guidance and early intervention that might help to prevent or ameliorate potential psychopathology.

Adult↗

PubMed1995

Genetic heterogeneity in attention-deficit hyperactivity disorder (ADHD): gender, psychiatric comorbidity, and maternal ADHD.

The authors examined the siblings of 140 attention-deficit hyperactivity disorder (ADHD) and 120 control probands and classified families as antisocial if the proband had conduct disorder or a parent had antisocial personality. Partial support was found for the hypothesis that the ADHD gender effect would be limited to antisocial families. Boys had an increased risk for ADHD compared with girls, but only among siblings from antisocial families. The effect size for predicting ADHD in siblings of probands was greater for maternal compared with paternal ADHD, but only for families exhibiting antisocial disorders. Strong support was found for the hypothesis that, compared with siblings from nonantisocial families, those from antisocial families would have more psychopathology (ADHD, depression, substance use, and conduct disorders). The presence of antisocial disorders signals a distinct subtype of ADHD.

Adolescent↗

PubMed2002

Young adults with attention deficit hyperactivity disorder: subtype differences in comorbidity, educational, and clinical history.

The present study sought to examine subtype differences in comorbidity and in antisocial, educational, and treatment histories among young adults (ages 17-27) with attention deficit hyperactivity disorder (ADHD). Comparisons were made between ADHD Combined Type (ADHD-C; N = 60) and Predominantly Inattentive Type (ADHD-I; N = 36) relative to each other and to a community control group of 64 adults. Both ADHD groups had significantly less education, were less likely to have graduated from college, and were more likely to have received special educational placement in high school. Both groups also presented with a greater likelihood of dysthymia, alcohol dependence/abuse, cannabis dependence/abuse, and learning disorders, as well as greater psychological distress on all scales of the SCL-90-R than the control group. Both ADHD groups were more likely to have received psychiatric medication and other mental health services than control adults. In comparison with ADHD-I, adults with ADHD-C differed in only a few respects. The C-type adults were more likely to have oppositional defiant disorder, to experience interpersonal hostility and paranoia, to have attempted suicide, and to have been arrested than the ADHD-I adults. These results are generally consistent with previous studies of ADHD in children, extend these findings to adults with ADHD, and suggest that the greater impulsivity associated with the ADHD-C subtype may predispose toward greater antisocial behavior and its consequences than does ADHD-I type in adults.

Adolescent↗

PubMed1996

Is season of birth a risk factor for attention-deficit hyperactivity disorder?

OBJECTIVE: To investigate seasonal variations in the birth patterns of children with attention-deficit hyperactivity disorder (ADHD) in reference to a group of normal control children, attending to issues of comorbidity, familiality, and learning disability. METHOD: Subjects were boys with DSM-III-R ADHD (n = 140) and normal controls (n = 120). The ADHD children were stratified by the presence of comorbid psychiatric disorders, learning disability, and family history of ADHD, and logistic regression was used to estimate relative risks. RESULTS: No statistically major effect for season of birth was observed in the comparison of ADHD and control children. However, significant effects were found for September births for ADHD children with learning disability (odds ratio = 5.4) and for ADHD children without psychiatric comorbidity (odds ratio = 4.5). A trend was also noted for winter births in ADHD children with learning disabilities, no psychiatric comorbidity, and positive family history for ADHD. CONCLUSIONS: These preliminary results suggest that there may be a seasonal pattern of birth for subtypes of ADHD. If season of birth serves as a proxy for the timing of seasonally mediated viral infections, it may lead to a greater understanding of the etiology and pathophysiology of ADHD.

Adolescent↗

PubMed2003

Attention-deficit-hyperactivity disorder with and without oppositional defiant disorder in 3- to 7-year-old children.

Attention-deficit-hyperactivity disorder (ADHD) is a common neurodevelopmental disorder with a high degree of associated behavioural problems. In order to study characteristics of ADHD with and without oppositional defiant disorder (ODD) in a representative group of young children with clinical impairment in Sweden, 131 children (101 males, 30 females) with ADHD (mean age 5 years, SD 1 year 5 months; range 3 to 7 years) were clinically examined, and their parents interviewed. Independent questionnaire data (Child Behavior Checklist, ADHD Rating Scale-IV, ODD Rating Scale-IV, Conners Hyperactivity Index) were collected. For comparison 131 children without ADHD were matched for sex, age, marital status, and socioeconomic status (115 males, 16 females; mean age 4 years 10 months, SD 1 year 5 months; range 3 to 7 years). Sixty percent of those with ADHD met full DSM-IV criteria for ODD. Only 10 of the 131 children with ADHD had no symptoms of ODD at all. The rate of children meeting full diagnostic criteria for ODD was similar across all age cohorts. Males were overrepresented in ODD, as were children of divorced parents and of mothers with low socioeconomic status. ADHD combined subtype was a stable independent factor influencing the diagnosis of ODD, regardless of psychosocial factors. Those with ADHD with ODD consistently showed higher rates of ADHD symptoms than did those with ADHD without ODD. The prevalent comorbidity of ADHD with ODD indicates that all children presenting with ADHD or ODD symptoms need to be assessed with a view to exploring both types of problem behaviours. The link between ODD and some psychosocial variables indicates the need to address these, possibly by measures such as parent training and network support.

Attention Deficit Disorder with Hyperactivity↗

PubMed2002

Influence of gender on attention deficit hyperactivity disorder in children referred to a psychiatric clinic.

OBJECTIVE: The substantial discrepancy in the male-to-female ratio between clinic-referred (10 to 1) and community (3 to 1) samples of children with attention deficit hyperactivity disorder (ADHD) suggests that gender differences may be operant in the phenotypic expression of ADHD. In this study the authors systematically examined the impact of gender on the clinical features of ADHD in a group of children referred to a clinic. METHOD: The study included 140 boys and 140 girls with ADHD and 120 boys and 122 girls without ADHD as comparison subjects. All subjects were systematically assessed with structured diagnostic interviews and neuropsychological batteries for subtypes of ADHD as well as emotional, school, intellectual, interpersonal, and family functioning. RESULTS: Girls with ADHD were more likely than boys to have the predominantly inattentive type of ADHD, less likely to have a learning disability, and less likely to manifest problems in school or in their spare time. In addition, girls with ADHD were at less risk for comorbid major depression, conduct disorder, and oppositional defiant disorder than boys with ADHD. A statistically significant gender-by-ADHD interaction was identified for comorbid substance use disorders as well. CONCLUSIONS: The lower likelihood for girls to manifest psychiatric, cognitive, and functional impairment than boys could result in gender-based referral bias unfavorable to girls with ADHD.

Adolescent↗

PubMed1998

Association and linkage of the dopamine transporter gene and attention-deficit hyperactivity disorder in children: heterogeneity owing to diagnostic subtype and severity.

Attention-deficit hyperactivity disorder (ADHD) affects approximately 3%-5% of children in the United States. In the current psychiatric nomenclature, ADHD comprises three subtypes: inattentive, hyperactive-impulsive, and combined. In this study, we used four analytic strategies to examine the association and linkage of the dopamine transporter gene (DAT1) and ADHD. Our sample included 122 children referred to psychiatric clinics for behavioral and learning problems that included but were not limited to ADHD, as well as their parents and siblings. Within-family analyses of linkage disequilibrium, using the transmission disequilibrium test (TDT), confirmed the 480-bp allele as the high-risk allele. In between-family association analyses, levels of hyperactive-impulsive symptoms but not inattentive symptoms were related to the number of DAT1 high-risk alleles. Siblings discordant for the number of DAT1 high-risk alleles differed markedly in their levels of both hyperactive-impulsive and inattentive symptoms, such that the sibling with the higher number of high-risk alleles had much higher symptom levels. Within-family analyses of linkage disequilibrium, using the TDT, suggested association and linkage of ADHD with DAT1 and that this relation was especially strong with the combined but not the inattentive subtype. The relation of DAT1 to ADHD increased monotonically, from low to medium to high levels of symptom severity. Our results replicate and extend previous findings of the association between the DAT1 gene and childhood ADHD. This represents one of the first replicated relations of a candidate gene and a psychiatric disorder in children.

Alleles↗