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PubMed2006

Dopamine transporter genotype influences the physiological response to medication in ADHD.

Attention deficit hyperactivity disorder (ADHD) is a complex, multifactorial disorder characterized by physical hyperactivity and behavioural disinhibition. Short interval cortical inhibition (SICI), measured in motor cortex with transcranial magnetic stimulation, is reduced in ADHD and correlates with symptom severity. However, ADHD medication-induced changes in SICI vary widely among normal individuals and have not been well studied in children with ADHD. Therefore, we undertook this study to measure and compare effects of two ADHD medications, methylphenidate (MPH), a psychostimulant, and atomoxetine (ATX), a selective norepinephrine reuptake inhibitor, on SICI in children with ADHD. In addition, we wished to determine whether a genetic variation in the dopamine transporter (DAT1), a site of action of MPH, could influence the effects of MPH or ATX on SICI. We performed a randomized, double-blind, single-dose, crossover study comparing 0.5 mg/kg MPH with 1.0 mg/kg ATX in 16 children with ADHD, aged 8-17. Seven were homozygotes and 9 heterozygotes for the DAT1 variable number of tandem repeats 10-repeat allele. Medication and genotype effects on SICI were estimated with repeated measures, mixed model regression. We found that MPH and ATX had similar effects on SICI. However, medication effects differed significantly by DAT1 genotype [F(2,13) = 13.04, P = 0.0008]. Both MPH and ATX increased SICI in heterozygotes but not in 10-repeat homozygotes. In conclusion, MPH and ATX have similar effects on SICI in children with ADHD. A genetic variation in DAT1, previously linked to ADHD risk and MPH behavioural responses, influences the neurophysiological effects of both MPH and ATX.

Adolescent↗

PubMed1996

A prospective four-year follow-up study of children at risk for ADHD: psychiatric, neuropsychological, and psychosocial outcome.

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is a familial disorder that places the siblings of ADHD children at high risk for ADHD, conduct, mood, and anxiety disorders. Although the pattern of psychiatric risk has been well documented by prior family studies, neither the short- nor long-term outcome of these high-risk siblings has been prospectively examined. OBJECTIVE: To document the 4-year psychiatric, psychosocial, and neuropsychological outcome of the siblings of children with ADHD. METHOD: DSM-III-R structured diagnostic interviews and blind raters were used to conduct a 4-year follow-up of siblings from ADHD and control families. The siblings were also evaluated for cognitive, achievement, social, school, and family functioning. RESULTS: At follow-up, significant elevations of behavioral, mood, and anxiety disorders were found among the siblings of ADHD children. The high-risk siblings had high rates of school failure and showed evidence of neuropsychological and psychosocial dysfunction. These impairments aggregated among the siblings who had ADHD. CONCLUSIONS: The siblings of ADHD children are at high risk for clinically meaningful levels of psychopathology and functional impairment. In addition to supporting hypotheses about the familial transmission of ADHD, the results suggest that the high-risk siblings might be appropriate targets for primary preventive interventions.

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↗

PubMed1997

A pilot study of neuropsychological function in girls with ADHD.

OBJECTIVE: Attention-deficit hyperactivity disorder (ADHD) is known to have neuropsychological consequences that are evident from psychological tests and from measures of school failure. However, most available data are based on studies of boys. Our goal was to assess, in this pilot study, whether ADHD in girls expressed neuropsychological features similar to those found in boys. METHOD: Subjects were 43 girls, aged 6 to 17 years, with DSM-III-R ADHD and 36 comparison girls without ADHD. Information on neuropsychological performance was obtained in a standardized manner blind to clinical status. RESULTS: Girls with ADHD were significantly more impaired on estimated IQ than comparison girls despite being matched on other demographic variables. Relative to comparison girls, the girls with ADHD were also significantly more impaired on the Freedom From Distractibility subtests of the WISC-R and on arithmetic and reading achievement scores. Although their mean performance on executive function tests was generally poorer than that of control girls, there were no statistically significant differences on these measures. CONCLUSIONS: Girls with ADHD have impairments in some tests of attention and achievement. However, neuropsychological performance on tests of executive function was less impaired than that previously documented in boys with ADHD. If confirmed in a larger sample, these findings suggest that girls with ADHD may be less vulnerable to executive function deficits than boys.

Adolescent↗

PubMed2000

National Institutes of Health Consensus Development Conference Statement: diagnosis and treatment of attention-deficit/hyperactivity disorder (ADHD)

Attention-deficit/hyperactivity disorder (ADHD) is a commonly diagnosed behavioral disorder of childhood that represents a costly major public health problem. Despite progress, ADHD and its treatment have remained controversial, especially the use of psychostimulants for both short- and long-term treatment. Although an independent diagnostic test for ADHD does not exist, there is evidence supporting the validity of the disorder. Studies (primarily short-term, approximately 3 months), including randomized clinical trials, have established the efficacy of stimulants and psychosocial treatments for alleviating the symptoms of ADHD and associated aggressiveness and have indicated that stimulants are more effective than psychosocial therapies in treating these symptoms. Because of the lack of consistent improvement beyond the core symptoms and the paucity of long-term studies (beyond 14 months), there is a need for longer-term studies with drugs and behavioral modalities and their combination. Although trials are under way, conclusive recommendations concerning treatment for the long term cannot be made at present. There are wide variations in the use of psychostimulants across communities and physicians, suggesting no consensus regarding which ADHD patients should be treated with psychostimulants, and thus the need for improved assessment, treatment, and follow-up. Furthermore, the lack of insurance coverage, preventing the appropriate diagnosis and treatment of ADHD, and the lack of integration with educational services are substantial barriers and represent considerable long-term costs for society. Finally, after years of clinical research and experience with ADHD, knowledge about the cause or causes of ADHD remain largely speculative. Consequently, there are no documented strategies for the prevention of ADHD.

Attention Deficit Disorder with Hyperactivity↗

PubMed2000

Does actigraphy differentiate ADHD subtypes in a clinical research setting?

OBJECTIVE: To compare subtypes of attention-deficit/hyperactivity disorder (ADHD) (predominantly inattentive and combined types) and a comparison group on an objective measure of activity level (actigraphy). METHOD: Actigraphs were worn by 64 children (49 boys, 15 girls) during a full-day clinical diagnostic assessment; 20 subjects had a diagnosis of ADHD predominantly inattentive type, 22 had ADHD combined type, and 22 were non-ADHD controls. Mean actigraph scores were calculated for two 2-hour intervals, comprising, respectively, a psychometric evaluation in the morning and the completion of a speech and language assessment and research measures in the afternoon. RESULTS: There were no significant group differences in activity level in the morning session. During the afternoon session, children with ADHD were significantly more active than controls, but there were no differences between ADHD subtypes. CONCLUSIONS: These data partially support specifications in the DSM-IV regarding hyperactivity in ADHD; however, they also indicate that situational and/or temporal factors may affect the degree to which hyperactivity is expressed. Furthermore, the findings contradict specifications in the DSM-IV that suggest that children with ADHD combined type should be more hyperactive than children with ADHD predominantly inattentive type.

Attention↗

PubMed2000

Beyond words: how do children with ADHD and/or conduct problems process nonverbal information about affect?

OBJECTIVE: To study nonverbal social cue perception in children with attention-deficit/hyperactivity disorder (ADHD; n = 86), conduct problems (CP; n = 24), or both disorders (ADHD + CP; n = 63), as well as normal controls (n = 27). METHOD: Using a standardized test of receptive nonverbal processing abilities, participants were required to interpret emotional cues from pictures of facial expressions and recordings of voices. RESULTS: As predicted, children with CP and ADHD were significantly less accurate at interpreting emotions than normal controls. However, children with CP and ADHD differed in the type of errors made: the ADHD group's errors were generally random in nature, whereas the CP group tended to misinterpret emotions as anger. Contrary to our hypothesis, the ADHD + CP group performed better than the ADHD and CP groups, was as accurate as the control group, and displayed a unique pattern of errors. CONCLUSIONS: These results support the idea that social deficiencies associated with CP arise from a biased perception of emotion, whereas social problems in ADHD originate from a failure to attend to the appropriate cues of affect. The findings also support the theory that comorbid ADHD + CP is a distinct disorder.

Attention Deficit Disorder with Hyperactivity↗

PubMed2000

Adoptive and biological families of children and adolescents with ADHD.

OBJECTIVE: Using an adoption study design, the authors addressed the issue of genetics in attention-deficit hyperactivity disorder (ADHD). METHOD: This study examined the rates of ADHD and associated disorders in the first-degree adoptive relatives of 25 adopted probands with ADHD and compared them with those of the first-degree biological relatives of 101 nonadopted probands with ADHD and 50 nonadopted, non-ADHD control probands. RESULTS: Six percent of the adoptive parents of adopted ADHD probands had ADHD compared with 18% of the biological parents of nonadopted ADHD probands and 3% of the biological parents of the control probands. CONCLUSION: Results of this study lend support to the hypothesis that ADHD has a genetic component.

Adolescent↗

PubMed2001

Psychophysiological responses in ADHD boys with and without conduct disorder: implications for adult antisocial behavior.

OBJECTIVE: Several studies have demonstrated that the presence of attention-deficit/hyperactivity disorder (ADHD) in childhood increases the risk of antisocial behavior developing in adulthood. However, because previous research did not consider comorbid conduct disorder (CD), the question of whether ADHD by itself or only the association of ADHD with CD implies a risk of adult antisocial behavior developing is still under discussion. METHOD: Because several characteristics of psychophysiological response had been shown to be associated with future increased likelihood of adult antisocial behavior, autonomic arousal as well as electrodermal responses to orienting and aversive stimuli were assessed in 26 boys with ADHD+CD compared with 21 boys with ADHD alone and 21 controls. RESULTS: Boys with a comorbid condition of ADHD+CD showed a decrement of autonomic responses and a more rapid habituation to orienting and aversive startling stimuli compared with age-matched children with ADHD alone. CONCLUSIONS: Boys with ADHD+CD show a psychophysiological response pattern that is very similar to that reported in antisocial personalities. These findings give further support for a high persistence of antisocial behavior from childhood to adulthood, while no evidence was found that ADHD itself is associated with a predisposition to antisocial behavior.

Adolescent↗

PubMed2005

Gender differences in ADHD subtype comorbidity.

OBJECTIVE: To examine gender differences in attention-deficit/hyperactivity disorder ("ADHD") symptom comorbidity with "oppositional defiant disorder", "conduct disorder", "separation anxiety disorder", "generalized anxiety disorder", speech therapy, and remedial reading in children. METHOD: From 1994 to 1995, data from a large sample (N = 4,371) of twins and siblings studied in the Australian Twin ADHD Project were obtained by mailed DSM-IV-based questionnaires, investigating patterns of comorbidity in the three subtypes of "ADHD": "inattentive", "hyperactive/impulsive", and "combined". A total of 1,550 questionnaires were returned (87%) over the next 12 to 18 months. RESULTS: Analysis of variance showed significant between-group differences in males and females for inattention and hyperactive/impulsive symptom counts with higher rates of "oppositional defiant disorder" and "conduct disorder" in males, and higher rates of "separation anxiety disorder" in females indicating internalizing disorders are more common in females and externalizing disorders are occurring more often in males. Differences were found between the "ADHD" subtypes and the no ADHD category for all comorbid conditions, for both males and females. Children without ADHD consistently had fewer symptoms, while children with the combined subtype showed consistently more comorbid symptoms indicating a strong relationship between high rates of externalizing symptoms and high rates of internalizing symptoms. Gender differences in speech therapy were significant only for the children without ADHD. The rates of "separation anxiety disorder" were higher in females with the "inattention" subtype and the rate of "generalized anxiety disorder" higher for females with the "combined" subtype, indicating that the subtypes of ADHD were associated with these internalizing disorders in different ways. CONCLUSIONS: Although comorbidity differs among ADHD subtypes, there were no significant gender differences in comorbidity for externalizing disorders. Inattentive girls may present with anxiety. Clinical approaches for both males and females should be sensitive to possible language and reading problems.

Analysis of Variance↗

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↗

PubMed2004

Can the Children's Communication Checklist differentiate between children with autism, children with ADHD, and normal controls?

BACKGROUND: The Children's Communication Checklist (CCC; Bishop, 1998) is a questionnaire that was developed to measure pragmatic language use and may be completed by parents and teachers. Two studies are reported, which were designed to investigate: (1) whether children with Attention Deficit Hyperactivity Disorder (ADHD) encounter pragmatic language problems in comparison with normal controls (NC), (2) whether children with ADHD and children with High Functioning Autism (HFA) can be differentiated using the CCC, (3) the usefulness of the CCC for parents and teachers in a clinical and in a research setting, and (4) the role of age in pragmatic language use in ADHD and HFA. METHOD: In the first study (clinical sample) 50 children with ADHD, 50 children with HFA, and 50 NC were compared to each other using the CCC. In the second study (research sample) CCC data was gathered on 23 children with ADHD (without co-morbid disorders), 42 children with HFA, and 35 NC. RESULTS: Compared to NC, children with HFA showed pragmatic deficits on all CCC scales. Children with ADHD demonstrated deficits compared to NC as well. Moreover, the ADHD and HFA groups differed from each other on most of the scales. Discriminant analyses showed that CCC scales were relevant for case identification in these samples. Furthermore, profiles of impairment seen in children with HFA and ADHD did not vary with age. CONCLUSION: Pragmatic difficulties do occur in both HFA and ADHD. The present studies indicate that the CCC is a useful instrument to obtain information concerning pragmatic language use in both a clinical and a research setting. Although the information of parents is more tightly linked to the diagnosis, combining the information of both parent and teacher slightly improves case identification.

Adolescent↗

PubMed2005

Randomized, placebo-controlled trial of mixed amphetamine salts for symptoms of comorbid ADHD in pediatric bipolar disorder after mood stabilization with divalproex sodium.

OBJECTIVE: The purpose of this study was to determine whether adjunctive use of a psychostimulant (mixed amphetamine salts) was safe and efficacious for treatment of symptoms of attention deficit hyperactivity disorder (ADHD) in pediatric outpatients with bipolar I or bipolar II disorder and concurrent ADHD whose manic symptoms had been stabilized through treatment with divalproex sodium. METHOD: An 8-week open-label trial of divalproex sodium to control manic symptoms and to discern the effect of divalproex sodium on ADHD was followed by a 4-week randomized, double-blind, placebo-controlled crossover trial to determine if mixed amphetamine salts was safe and effective for treatment of ADHD symptoms. Patients in the crossover trial continued to receive divalproex sodium. Diagnoses, made by clinical interview, were confirmed with the Washington University in St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia. The Young Mania Rating Scale (for manic symptoms) and the Clinical Global Impression of improvement (for ADHD symptoms) were the primary outcome measures. RESULTS: Forty subjects ages 6-17 years with bipolar I disorder (77.5%) or bipolar II disorder (22.5%) and a Young Mania Rating Scale score > or =14 entered open treatment with divalproex sodium. With divalproex sodium, 32 subjects achieved > or =50% reduction in Young Mania Rating Scale baseline scores, but only three participants had significant improvement in ADHD symptoms. For the 30 subjects who entered the placebo-controlled crossover trial, mixed amphetamine salts was significantly more effective than placebo for ADHD symptoms. No significant side effects or worsening of manic symptoms was observed. CONCLUSIONS: Pediatric patients with bipolar disorder and concurrent ADHD can be safely and effectively treated with mixed amphetamine salts after their manic symptoms are stabilized with divalproex sodium. Divalproex sodium alone (8-week trial) is not an effective treatment for ADHD in the context of bipolar disorder.

Adolescent↗

PubMed2005

A comparison of service use and costs among adults with ADHD and adults with other chronic diseases.

OBJECTIVE: This study compared health service use and costs among adults with attention-deficit hyperactivity disorder (ADHD) and adults with depression, diabetes, or seasonal allergic rhinitis (seasonal allergy). METHODS: Pharmacy and medical claims data from January 1, 1999, to December 31, 2001, were obtained from a large U.S. managed care plan. Patients were divided into one of four mutually exclusive cohorts (ADHD, depression, diabetes, or seasonal allergy) on the basis of their diagnosis or prescriptions. Age, gender, comorbid conditions, and type of dominant provider were compared for the four groups. Thereafter, general linear models with post-hoc multiple comparison tests were used to compare health service use and costs by site of service. RESULTS: The study population included 143,561 patients. The four mutually exclusive groups included 58,017 with depression, 45,479 with diabetes, 33,272 with a seasonal allergy, and 6,793 had ADHD. Comorbid mental health conditions occurred with significantly greater frequency among patients with ADHD and among those with depression than among patients in the other groups. Patients with ADHD and those with depression received care from a mental health provider significantly more often than those with diabetes or a seasonal allergy. Patients with ADHD had fewer average outpatient, inpatient, and emergency department visits than patients with depression or diabetes, and office visit frequency for patients with ADHD was significantly different from that of patients with a seasonal allergy. Annual total costs were lowest among patients with a seasonal allergy ($2,743), which were not significantly different than the costs for patients with ADHD ($3,020). CONCLUSIONS: Adult ADHD poses an economic burden that is less than that of depression or diabetes but greater than that of a seasonal allergy.

Adult↗

PubMedDate not supplied

Motor correlates of ADHD: contribution of reading disability and oppositional defiant disorder.

This study investigated whether the likelihood of motor impairment in children with attention-deficit/hyperactivity disorder (ADHD) increases with the presence of other disorders, and whether the co-occurring diagnoses of reading disability (RD) and oppositional defiant disorder (ODD) account for the motor deficits seen in ADHD. A total of 291 children (218 boys, 73 girls) participated. Six groups of children were compared: ADHD only (n = 29); RD only (n = 63); ADHD and RD (n = 47); ADHD and ODD (n = 19); ADHD, RD, and ODD (n = 21); and typically developing control children (n = 112). Motor skills were assessed with the Bruininks-Oseretsky Test of Motor Proficiency and the Beery Test of Visual-Motor Integration. We found that the motor skills of the ADHD-only group did not differ from the typical control group. Furthermore, motor impairment in ADHD increased as a function of co-occurring disorders, and the presence of RD rather than ADHD predicted motor impairment.

Adolescent↗

PubMed1992

A developmental index using the Wechsler Intelligence Scale for Children: implications for the diagnosis and nature of ADHD.

The possible utility of Wechsler's Deterioration Index (WDI) in analyzing children's Wechsler Intelligence Scale for Children-Revised (WISC-R) results was explored in this study. Clinical records of children with learning disabilities (LD) and children with attention deficit-hyperactivity disorder (ADHD) were reviewed to determine if the WDI predicted the presence or severity of the disorders. The ages of the children ranged from 6 to 14. In two independent samples of children with LD (n = 35 and n = 26), the WDI did not predict LD status or severity. The LD samples were mostly male--85% and 57%, respectively. However, the WDI scores did significantly distinguish children with ADHD (n = 10) from nondisabled children (n = 10). The results were cross-validated on an independent sample of children with ADHD (n = 17) when compared to non-ADHD children (n = 22) who experienced significant behavioral difficulties. The ADHD samples were also mostly male--90% and 89%, respectively. The WDI classified only 59% of the children with ADHD and 86% of the non-ADHD children correctly. It is recommended that the WDI be considered a developmental index rather than a deterioration index in children. It is also recommended that significant WDI elevation (greater than .20) be considered to raise the question of ADHD, rather than simply yielding a diagnosis of ADHD.

Achievement↗

PubMed2006

ADHD and infant disorganized attachment: a prospective study of children next-born after stillbirth.

OBJECTIVE: To examine whether infant disorganized attachment predicts ADHD at school age. METHOD: A cohort of 53 children who had been identified as having significant levels of disorganized attachment in infancy is compared to a control group. Symptoms and signs of ADHD at age 7 are evaluated together with a range of relevant maternal variables. RESULTS: An association is found between infant disorganized attachment scores and teacher-rated symptoms of ADHD (but not ADHD caseness). Probable ADHD caseness in the child is associated with self-rated retrospective ADHD scores in mothers. Possible ADHD caseness is associated with a measure of unresolved mourning in mothers. Mother-rated ADHD in the child was associated with low overall maternal psychosocial functioning. CONCLUSION: The finding of a link between scores for disorganized attachment at 1 year and later teacher-rated symptoms of ADHD suggests the need for further studies.

Attention Deficit Disorder with Hyperactivity↗

PubMed2005

Testing assumptions for endophenotype studies in ADHD: reliability and validity of tasks in a general population sample.

BACKGROUND: Advances in both genetic and cognitive-experimental studies on attention deficit hyperactivity disorder (ADHD) have opened new opportunities for cognitive endophenotype research. In such genetic designs the focus is on individual differences in characteristics, associated with ADHD, that can be measured reliably over time. Genetic studies that take a 'quantitative trait loci' approach hypothesise that multiple susceptibility genes contribute to a continuous dimension of ADHD symptoms. As an important initial step, we aimed to investigate the underlying assumptions that (1) key cognitive-experimental tasks indicate adequate test-retest reliability and (2) ADHD symptom scores in a general population sample are associated with performance on these tasks. METHODS: Forty-nine children were assessed on a go/no-go task and a reaction time task (the 'fast task') that included manipulations with event rate and incentives. The children were assessed twice, with a test-retest interval of two weeks. RESULTS: The majority of the task variables demonstrated moderate-to-good test-retest reliability. The correlations between teacher ratings of ADHD symptoms and key task variables were .4-.6: ADHD symptoms were associated with poor performance (especially high reaction time variability) in a slow baseline condition, whereas there was low or no association in conditions with a faster event rate or incentives. In contrast, no clear pattern of findings emerged based on parent ratings of ADHD symptoms. CONCLUSION: The data support the usefulness of the go/no-go and fast tasks for genetic studies, which require reliable and valid indices of individual differences. The overall pattern of associations between teacher ratings of ADHD symptoms and task variables is consistent with effects of event rate and incentives on performance, as predicted by the model of activation and arousal regulation. The lack of a clear pattern of findings with parent ratings of ADHD symptoms warrants further study.

Adolescent↗