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PubMed1999

Evaluation of ADHD typology in three contrasting samples: a latent class approach.

OBJECTIVE: To identify subtypes of attention-deficit/hyperactivity disorder (ADHD) and characterize them as either categorical or continuous; to investigate familial resemblance for ADHD among sibling pairs; and to test the robustness of all results by using contrasting data sets. METHOD: Latent class analysis was applied to the ADHD symptom profiles obtained from parents or best informant about their offspring in 3 samples: a population-based set of female adolescent twins (724 monozygotic pairs, 594 dizygotic pairs) and male (N = 425) and female (N = 430) child and adolescent offspring ascertained from high-risk alcoholic families. RESULTS: Latent class analysis revealed 2 categories of clinically significant ADHD which were replicated in all 3 study groups: a subtype with high endorsements of ADHD inattention symptoms and a second combined type with high endorsements of both inattention and hyperactivity-impulsivity items. Both appeared to be continuous across all 3 data groups. The high-risk families contained a class in which members heavily endorsed the ADHD "fidget" item but not other ADHD items. A large proportion of the monozygotic sibs (80%) versus a smaller proportion of dizygotic sibs (52%) were assigned to the same latent class. Among the high-risk children and adolescents, 51% of the female and 41% of the male siblings were concordant for class membership. CONCLUSIONS: The pattern of latent classes suggested that ADHD consists of an inattentive and a combined subtype, within each of which lies a dimensional domain. These analyses further support that genetic factors are significant determinants of latent class membership.

Adolescent↗

PubMed2003

[Association studies of dopamine D4 receptor gene and dopamine transporter gene polymorphisms in Han Chinese patients with attention deficit hyperactivity disorder].

OBJECTIVE: To investigate association of the 48 bp variable number of tandem repeat (VNTR) polymorphism in the D4 receptor gene (DRD4) exon 3 and 40 bp VNTR polymorphism in the dopamine transporter gene (DAT1) 3' untranslated region with attention deficit hyperactivity disorder (ADHD) in Han Chinese children. METHODS: The study samples were comprised of 340 ADHD children, 226 unrelated controls and 202 integrated ADHD trios (included proband and biological parents). The polymorphisms consisted of 48 bp VNTR in exon 3 of DRD4, and 40 bp VNTR in the 3' untranslated region of DAT1. Associations of polymorphisms with ADHD and its subtypes were examined by: (i) comparing cases and controls; and (ii) using family-based association study in an extension of exact transmission-disequilibrium test (ETDT) and haplotype-based haplotype relative risk (HHRR). RESULTS: The repeat numbers at the DRD4 48 bp locus ranged from 2-6 repeats in the Han Chinese controls, with the most common being the 4-repeat (77%) and 2-repeat (19.4%) alleles. Neither the 7-repeat allele nor longer repeats were found. For the DAT1, the repeat numbers at the 40 bp locus ranged from 6-7 repeats and 9-11 repeats. The 10-repeat allele was the most frequent (90.7%). The long-repeat alleles of DRD4 (ranging from 4-6 repeats) and DAT1 (ranging from 11-12 repeats), were present more frequently in ADHD probands than in controls. Our primary analyses failed to replicate the associations between ADHD and 7-repeat allele of DRD4 and the 10-repeat allele of DAT1. CONCLUSION: The long-repeat alleles of DRD4 (after a stratification by gender) and DAT1 may increase the risk for ADHD in Han Chinese children.

Alleles↗

PubMed2005

The SNAP25 gene as a susceptibility gene contributing to attention-deficit hyperactivity disorder.

The synaptosomal-associated protein of 25 kDa gene (SNAP25) has been suggested as a genetic susceptibility factor in attention-deficit hyperactivity disorder (ADHD) based on the mouse strain coloboma. This strain is hemizygous for the SNAP25 gene and displays hyperactivity that responds to dextroamphetamine, but not to methylphenidate. Previously, we reported association of SNAP25 and ADHD using two polymorphisms. To further investigate this gene, we screened the exons for DNA variation and genotyped ten additional polymorphisms in an expanded sample of families from Toronto and a second sample of families collected in Irvine, CA. Significant results were observed in the Toronto sample for four markers, although not in the Irvine sample. The paper discusses the possible influence of the selection criteria on these differential results. The Irvine sample selected subjects that met the DSM-IV combined subtype diagnosis, whereas the Toronto sample included all subtypes. Analysis of the DSM-IV subtypes in the Toronto sample indicated that the differential results were not attributable to ADHD subtype. Differences in ethnicity, differential medication response, and other clinical characteristics of the samples cannot be ruled out at this time. Quantitative analysis of the dimensions of hyperactivity/impulsivity and inattention in the Toronto sample found that both behavioral traits were associated with SNAP25. Our findings continue to support SNAP25 in the susceptibility to ADHD.

Animals↗

PubMed2001

Brain imaging of attention deficit/hyperactivity disorder.

Advances in imaging technology allow unprecedented access to the anatomy and physiology of the living, growing human brain. Anatomical imaging studies of individuals with attention deficit/hyperactivity disorder (ADHD) consistently point to involvement of the frontal lobes, basal ganglia, corpus callosum, and cerebellum. Imaging studies of brain physiology also support involvement of right frontal-basal ganglia circuitry with a powerful modulatory influence from the cerebellum. Although not currently of diagnostic utility, further extension and refinement of these findings may offer hope for greater understanding of the core nature of ADHD and possible subtyping to inform treatment interventions.

Adolescent↗

PubMed2001

Parent stress and coping in relation to child ADHD severity and associated child disruptive behavior problems.

Examined parent role distress and coping in relation to childhood attention deficit hyperactivity disorder (ADHD) in mothers and fathers of 66 children age 7 to 11 (42 boys, 24 girls; mean age = 10.2). Parents of children with ADHD combined and inattentive subtypes expressed more role dissatisfaction than parents of control children. Parents of ADHD combined and inattentive type children did not differ significantly in levels of distress. For mothers, child inattention and oppositional-conduct problems but not hyperactivity contributed uniquely to role distress (dissatisfaction related to parenting or parenting performance). For fathers, parenting role distress was associated uniquely with child oppositional or aggressive behaviors but not with ADHD symptom severity. Parent coping by more use of positive reframing (thinking about problems as challenges that might be overcome) was associated with higher role satisfaction for both mothers and fathers. Community supports were associated with higher distress for mothers only.

Adaptation, Psychological↗

PubMed2006

Differences in academic and executive function domains among children with ADHD Predominantly Inattentive and Combined Types.

Differences between the subtypes of Attention Deficit Hyperactivity Disorder (ADHD) continue to have a place in the clinical and research literature. The purpose of this study was to examine differences specific to academic and executive function deficits in a sample of 40 children, aged 9-15 years. Although there was a tendency for the Predominantly Inattentive (PI) group to evidence lower performance on calculation and written expression tasks, these differences dissipated when IQ was included as a covariate. For executive function domains of set shifting, interference, inhibition, and planning, differences emerged for interference, but only when girls were excluded from the analysis and no control for IQ was made. For parent ratings of executive function, expected differences were found on the Inhibit scale with the Combined Type (CT) group evidencing greater problems in this area; this difference remained even when girls were excluded and IQ was controlled. Implications for research and practice are presented.

Adolescent↗

PubMed2006

Association between tryptophan hydroxylase gene polymorphisms and attention deficit hyperactivity disorder in Chinese Han population.

Attention deficit hyperactivity disorder (ADHD) is a severe behavioral disorder in children known to have a substantial genetic component. Prior studies have implicated serotonin genes in the etiology of ADHD but have not examined tryptophan hydroxylase (TPH), which is a rate-limiting enzyme in serotonin biosynthesis. The current study examined the relationship between the A218C and A-6526G polymorphisms of the TPH gene and ADHD. Three hundred sixty-two unrelated ADHD probands and their biological parents were recruited to participate in this study. No biased transmission of any allele of the two polymorphisms was observed using TDT analysis. However, haplotype analyses found that the rare 218A/-6526G haplotype was significantly not transmitted to probands with ADHD (chi(2) = 4.4995, P = 0.034), regardless of subtype. Although this finding for ADHD in the Chinese Han population.

Adolescent↗

PubMedDate not supplied

Attention deficit/hyperactivity disorder (ADHD) symptoms and digit ratios in a college sample.

Diagnosticians recognize three subtypes of attention deficit/hyperactivity disorder (ADHD) if there are developmentally inappropriate levels (six or more symptoms) of Hyperactive-Impulsive behavior, or Inattentive behavior, or both (Combined), respectively. ADHD may partly reflect androgen dysfunction, and an arguable proxy for prenatal androgen exposure is the 2D:4D finger ratio set at least as early as week 9 in the fetus; this is lower in men than in women. We examined the relationship between digit ratios and ADHD symptoms representing the three phenotypes: ADHD/Combined as measured by "summarized" (Rasched) scales, i.e., 1) the short version of the Wender Utah Rating Scale (WURS) and a total symptom list derived from the DSM IV, and the subdivided DSM IV into 2) ADHD/Inattentive and 3) ADHD/Hyperactive-Impulsive inventories, in a sample of European-descent college students (135 female, 52 male) not selected for ADHD. All digit ratios were calculated excluding the thumb. There were significant sex differences for the 2D:4D digit ratios of both hands (RH and LH), and between the RH 3D:4D and between the LH 2D:3D ratio. In females, the more masculine the LH 2D:4D ratio, the more the ADHD/Combined symptoms (both WURS and DSM) and the more the ADHD/Inattentive symptoms and ADHD/Hyperactive-Impulsive symptoms. More masculine ratios also correlated between the total WURS and RH 2D:3D, RH 2D:4D, and LH 2D:3D; and between the inattentive DSM symptoms and LH 2D:5D, and between the ADHD/Hyperactive and Impulsive symptoms and RH 3D:4D.

Adolescent↗

PubMed2006

The latent class structure of ADHD is stable across informants.

Previous studies have looked at the structure of attention-deficit/hyperactivity disorder (ADHD) using latent class analysis (LCA) of Child Behavior Checklist (CBCL) or Diagnostic and Statistical Manual of Mental Disorders (DSM) symptom structure. These studies have identified distinct classes of children with inattentive, hyperactive, or combined subtypes and have used these classes to refine genetic analyses. The objective of the current report is to determine if the latent class structure of ADHD subtypes is consistent across informant using the Conners' Rating Scales (CRS). LCA was applied to CRS forms from mother, father, and teacher reports of 1837, 1329 and 1048 latency aged Dutch twins, respectively. The optimal solution for boys was a 5-class solution for mothers, a 3-class solution for fathers, and a 4-class solution for teachers. For girls, a 4-class solution for mothers and a 3-class for fathers and teachers was optimal. Children placed into a class by one informant had markedly increased odds ratio of being placed into the same or similar class by the other informants. Results from LCA using Dutch twins with the CRS show stability across informants suggesting that more stable phenotypes may be accessible for genotyping using a multi-informant approach.

Adult↗

PubMed2004

[Nocturnal polysomnographic study in children with attention deficit hyperactivity disorder].

INTRODUCTION: The main symptoms of attention deficit hyperactivity disorder (ADHD) are attention deficit, hyperactivity and impulsivity. Its prevalence lies between 3 and 5% in schoolchildren. Children with ADHD can present a high prevalence rate of comorbidity. A timely diagnosis and treatment can modify the educational and psychosocial development of most of these children. A number of subjective reports (especially from parents) describe sleep disorders. The objective verification of these disorders and the exact nature of the sleep problems are still to be determined and the purpose of this study is to deal with these issues. PATIENTS AND METHODS: We studied a sample of 48 children (9 females and 39 males) with a mean age of 8 (SD: 2.59) who met DSM IV criteria. They were submitted to a general exploration as well as a neurological exploration, including their patient record, and then they were evaluated using the DSM IV, which was carried out by parents and teachers (in order to evaluate two different environments), and a nocturnal polysomnographic study. In the sample there were 26 children with predominant attention deficit type ADHD (ADHD/AD); 4 children with predominant hyperactivity impulsivity type ADHD (ADHD/H); and 18 children with combined type ADHD (ADHD/C). RESULTS: The most frequently diagnosed subtype is the attention deficit subtype. The sleep architecture of children with ADHD presents the most consistent differences as compared to normal children in an increase in the percentage of phase 3 of sleep and, consequently, an increase in the percentage of slow sleep. Epileptiform type paroxysms were observed in 16.7% of the children who presented symptoms of ADHD. The number of epileptiform paroxysms is more usual in the attention deficit subtype. CONCLUSIONS: The increase in phase 3 may be related to the alterations in noradrenaline and dopamine transmission present in children who suffer from ADHD. Some children with ADHD can have a region of the brain with intense epileptic activity, which does not trigger epileptic seizures but gives rise to behavioural disorders, learning disorders and language problems.

Adolescent↗

PubMed2004

Attention deficit/hyperactivity disorder in children with nocturnal enuresis.

PURPOSE: Although the relationship between enuresis and psychopathology has been studied intensively, little is known about the prevalence of specific psychiatric disorders. We investigate the prevalence of attention deficit/hyperactivity disorder (ADHD) in children with nocturnal enuresis and correlate these data with clinical subtypes of enuresis/incontinence. MATERIALS AND METHODS: A total of 120 children with nocturnal enuresis 6 to 12 years old participated in a prevalence study. A diagnostic interview was conducted with parents, questionnaires were completed by parents and teachers, and medical files were consulted. RESULTS: Of all enuretic children 15% were diagnosed with the full syndrome of ADHD and 22.5% met the criteria of the ADHD inattentive subtype. Data revealed that the older the children (9 to 12 years), the higher prevalence of attention deficit disorder or ADHD. Nocturnal polyuria had a significantly higher incidence in hyperactive/impulsive children but there was no significant difference in bladder function between enuretic children with or without a comorbid diagnosis of ADHD. CONCLUSIONS: The prevalence of attention deficit disorder or ADHD in nocturnal enuresis is significantly increased, especially in older children. The incidence of nocturnal polyuria is slightly increased in children who meet at least the criteria of ADHD hyperactive/impulsive subtype. No other associations between enuresis and ADHD were found.

Attention Deficit Disorder with Hyperactivity↗

PubMed2001

Electroencephalogram differences in two subtypes of attention-deficit/hyperactivity disorder.

This study investigated EEG differences between children with two subtypes of Attention-Deficit/Hyperactivity Disorder (ADHD) and normal control subjects. 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, and the mean frequency for each band was calculated. Ratio coefficients were also calculated between frequency bands. Mean group differences were found in the theta, alpha, and beta bands between all three groups. Similarly, differences were found between all three groups for the theta/alpha and theta/beta ratios and for the mean frequency of the total EEG. These results support a model of ADHD resulting from a developmental deviation rather than a maturational lag in the central nervous system. Differences between the clinical groups in frontal activity suggest that different neuroanatomical systems are involved in the different subtypes of ADHD.

Adolescent↗

PubMed1999

Differential patterns of executive function in children with attention-deficit hyperactivity disorder according to gender and subtype.

The present investigation examined differential patterns in executive functions of children with attention-deficit hyperactivity disorder (ADHD; no diagnosed comorbid disorders) according to subtype and gender, and identified instrumentation sensitive to executive function in children aged 6 to 12 years with ADHD. Data were obtained from 94 children diagnosed with ADHD (predominantly inattentive, n = 32, ADHD combined, n = 62), and from 28 controls. Participants with ADHD, who were unmedicated at the time of testing, were administered five tests of executive function (the Wisconsin Card Sorting Test, the Stroop Color-Word Test, the Matching Familiar Figures Test, the Trail Making Test, and the Tower of London). A two-way multivariate analysis of covariance with age as the covariate and subtype and gender as the independent variables was conducted on all of the tests administered. While children with ADHD predominantly inattentive and those with ADHD combined differed from controls, it was only the latter subtype that differed significantly in perseveration and response inhibition. The absence of diagnosed comorbidity in the children with ADHD at the time of test administration demonstrates that the impairments in executive function are clearly located in ADHD, particularly in the ADHD combined subtype, thus providing support for Barkley's proposed unifying theory of ADHD.

Attention Deficit Disorder with Hyperactivity↗

PubMed1998

Psychiatric, neuropsychological, and psychosocial features of DSM-IV subtypes of attention-deficit/hyperactivity disorder: results from a clinically referred sample.

OBJECTIVE: To assess the validity of the DSM-IV subtypes of attention-deficit/hyperactivity disorder (ADHD). METHOD: Using structured diagnostic interviews and psychometric measures of cognitive and social functioning, the authors assessed 413 children and adolescents consecutively referred to a pediatric psychopharmacology clinic since 1991. RESULTS: Marked psychiatric differences were found among DSM-IV subtypes of ADHD, but few differences were found in cognitive or psychosocial functioning. The greatest psychiatric differences were found between the combined-type subjects (who tended to show more impairment in multiple domains) and the other two subgroups. The inattentive patients, however, were more likely to have required extra help in school. The hyperactive-impulsive patients were not different from controls on rates of depression, Child Behavior Checklist measures of social functioning, or psychometric measures of intellectual functioning and academic achievement. CONCLUSIONS: The results suggest that, regarding clinical features, combined-type patients have a more severe disorder than the other DSM-IV subtypes.

Adolescent↗

PubMed2007

[Effect of subtype and psychiatric comorbidities on methylphenidate treatment in adults with attention-deficit hyperactivity disorder].

The present study was intended to examine the efficacy of immediate-release methylphenidate (MPH IR) in the treatment of adults with attention-deficit hyperactivity disorder (ADHD) under consideration of subtype according to DSM-IV criteria and psychiatric comorbidity. After baseline assessment over 3 weeks, 47 patients aged 18-59 years with combined ADHD (ADHD-C) (n=27) and predominantly inattentive ADHD (ADHD-I; n=20) were treated in an open, uncontrolled design with an average dose of 0.5 mg MPH IR per kg over 7 weeks. Thirty-nine patients finished the study. The two groups did not differ in response to treatment with regard to ADHD symptoms (very good to good outcome in ADHD-C 73.9%, in ADHD-I 66.7%) or cognitive measures (sustained attention, information processing speed, divided attention). However, ADHD patients with psychiatric comorbidities had significantly worse outcome: total ADHS scores on the T2 Brown Attention Deficit Disorder Scales (BADDS) were 66.2+/-15.5 with psychiatric comorbidity and 51.7+/-13.7 without (P=0.04), despite significantly higher doses of MPH IR (0.56+/-0.17 mg/kg vs 0.46+/-0.13 mg/kg; P=0.004). This effect was mainly seen in the patients with clinically significant depressive symptoms (Beck Depression Inventory > or =18), who clearly benefited less from treatment (total T2 BADDS scores with depressive symptoms 70.7+/-15.9 and without depressive symptoms 48.1+/-21.2; P=0.001).

Adolescent↗

PubMed1997

ADHD is associated with early initiation of cigarette smoking in children and adolescents.

OBJECTIVE: The association between attention-deficit hyperactivity disorder (ADHD) and cigarette smoking in children and adolescents was evaluated. METHOD: Subjects were 6- to 17-year-old boys with DSM-III-R ADHD (n = 128) and non-ADHD comparison boys (n = 109) followed prospectively for 4 years into mid-adolescence. Information on cigarette smoking was obtained in a standardized manner blind to the proband's clinical status. Cox proportional hazard models were used to predict cigarette smoking at follow-up using baseline characteristics as predictors. RESULTS: ADHD was a significant predictor of cigarette smoking at follow-up into mid-adolescence. Our findings also revealed that ADHD was associated with an early initiation of cigarette smoking. This was the case even after controlling for socioeconomic status, IQ, and psychiatric comorbidity. In addition, among children with ADHD, there was a significant positive association between cigarette smoking and conduct, major depressive, and anxiety disorders. CONCLUSIONS: ADHD, particularly the comorbid subtype, is a significant risk factor for early initiation of cigarette smoking in children and adolescents. Considering the prevalence and early childhood onset of ADHD, these findings highlight the importance of smoking prevention and cessation programs for children and adolescents with ADHD.

Adolescent↗

PubMed1998

Comorbidity of attention-deficit/hyperactivity disorder with psychiatric disorder: an overview.

Attention-deficit/hyperactivity disorder (ADHD) has been noted to be comorbid with a variety of psychiatric disorders. These include oppositional defiant and conduct disorders, as well as affective, anxiety, and learning disorders. Considerable debate has revolved as to the meaning of this overlap. Does it occur by chance or is it an artifact of referral bias? Are the comorbid conditions secondary to the ADHD, or can other psychiatric disorders masquerade as attentional problems? Alternatively, ADHD may exist as distinct subtypes, each with its specific comorbidity. Studies that have examined the comorbidity of oppositional, conduct, affective, anxiety, and learning disorders in ADHD are reviewed. ADHD and ADHD with conduct disorder appear to be distinct subtypes, possibly with different etiologies. While the short-term response to stimulants is the same in these two groups, children with ADHD and conduct disorder children have higher rates of antisocial personality as adults. Coexisting anxiety appears to attenuate impulsivity in ADHD, and stimulant response is poorer in ADHD children with comorbid anxiety. Anxiety and ADHD appear to be inherited independently. A subset of ADHD children also meet criteria for bipolar disorder, although the exact prevalence of this diagnosis in ADHD children is strongly debated. Regardless of prevalence, this is a severely impaired group of ADHD children, with high rates of aggression and psychiatric disorder in their families. The comorbidity of ADHD and major depression is much less studied, and few firm conclusions can be made about it. Finally, about 20%-25% of ADHD children meet criteria for a learning disorder, but learning disorders appear to be independent of ADHD.

Adolescent↗

PubMed2006

NREM sleep instability is reduced in children with attention-deficit/hyperactivity disorder.

STUDY OBJECTIVES: To evaluate non-rapid eye movement sleep instability (NREM), as measured by the cyclic alternating pattern (CAP), in a cohort of children with attention-deficit/hyperactivity disorder (ADHD) and normal controls. DESIGN: Prospective study. SETTINGS: Sleep laboratory. PARTICIPANTS: Twenty consecutive outpatients with ADHD (18 boys and 2 girls; age range 6-13 years, mean age 9.3 years) and 20 normal children matched for age and socioeconomic status underwent polysomnographic recordings for 2 consecutive nights in a standard laboratory setting. Sleep was visually scored for sleep macrostructure and CAP, according to standard criteria. MEASUREMENTS AND RESULTS: Children with ADHD showed significantly reduced sleep duration and increased rate of stage shifts. All children with ADHD had an apnea-hypopnea index less than 1. Those with ADHD presented lower total CAP rates and lower CAP rates during sleep stage 2 than did normal controls. Moreover, in children with ADHD, we found a lower number of CAP sequences and a reduced total A1 index, mainly in light sleep (sleep stages 1 and 2). We did not find differences in A subtype percentages, but there was a longer duration of A1 subtypes in children with ADHD. CONCLUSIONS: Children with ADHD showed a lower CAP rate and a lower number of CAP sequences; this supports the hypothesis of the existence of a hypoarousal state in these patients.

Adolescent↗