The Latest Published Research on ADHD

Childhood Attention-Deficit/Hyperactivity Disorder and Future Substance Use Disorders: Comparative Meta-Analyses. Charach, Alice; Yeung, Emanuela; Climans, Troy; Lillie, Erin. Journal of the American Academy of Child & Adolescent Psychiatry, January 2011, v50 n1, pp. 9-21.
In recent years cohort studies have examined childhood attention-deficit/hyperactivity disorder (ADHD) as a risk factor for substance use disorders (SUDs) in adolescence and young adulthood. The long-term risk is estimated for development of alcohol, cannabis, combined alcohol and psychoactive SUDs, combined SUDs (nonalcohol), and nicotine use disorders in children with ADHD.
METHOD: MEDLINE, CINHAL, PsycINFO, and EMBASE were searched through October 2009; reference lists of included studies were hand-searched. Prospective cohort studies were included if they compared children with ADHD to children without, identified cases using standardized criteria by mean age of 12 years, followed participants until adolescence (nicotine use) or young adulthood (psychoactive substance use disorder, with and without alcohol, alcohol use disorder, cannabis use disorder), and reported SUD outcomes. Two independent reviewers examined articles and extracted and cross-checked data. Effects were summarized as pooled odds ratios (ORs) in a random effects model.
RESULTS: Thirteen studies were included. Only two of five meta-analyses, for alcohol use disorder (N = 3,184) and for nicotine use (N = 2,067), estimated ORs showing stability when evaluated by sensitivity analyses. Childhood ADHD was associated with alcohol use disorder by young adulthood (OR = 1.35, 95% confidence interval = 1.11-1.64) and with nicotine use by middle adolescence (OR = 2.36, 95% confidence interval = 1.71-3.27). The association with drug use disorder, nonalcohol (N = 593), was highly influenced by a single study.
CONCLUSIONS: Childhood ADHD is associated with alcohol and drug use disorders in adulthood and with nicotine use in adolescence.

Service Utilization for Lifetime Mental Disorders in U.S. Adolescents: Results of the National Comorbidity Survey-Adolescent Supplement (NCS-A). Merikangas, Kathleen Ries; He, Jian-ping; Burstein, Marcy; Swendsen, Joel; et al. Journal of the American Academy of Child & Adolescent Psychiatry, January 2011, v50 n1, pp. 32-45.
Mental health policy for youth has been constrained by a paucity of nationally representative data concerning patterns and correlates of mental health service utilization in this segment of the population. The objectives of this investigation were to examine the rates and sociodemographic correlates of lifetime mental health service use by severity, type, and number of DSM-IV disorders in the National Comorbidity Survey-Adolescent Supplement.
METHOD: Face-to-face survey of mental disorders from 2002 to 2004 using a modified version of the fully structured World Health Organization Composite International Diagnostic Interview in a nationally representative sample of 6,483 adolescents 13 to 18 years old for whom information on service use was available from an adolescent and a parent report. Total and sector-specific mental health service use was also assessed.
RESULTS: Approximately one third of adolescents with mental disorders received services for their illness (36.2%). Although disorder severity was significantly associated with an increased likelihood of receiving treatment, half of adolescents with severely impairing mental disorders had never received mental health treatment for their symptoms. Service rates were highest in those with attention-deficit/hyperactivity disorder (59.8%) and behavior disorders (45.4%), but fewer than one in five affected adolescents received services for anxiety, eating, or substance use disorders. Comorbidity and severe impairment were strongly associated with service utilization, particularly in youth with behavior disorders. Hispanic and non-Hispanic Black adolescents were less likely than their White counterparts to receive services for mood and anxiety disorders, even when such disorders were associated with severe impairment.
CONCLUSIONS: Despite advances in public awareness of mental disorders in youth, a substantial proportion of young people with severe mental disorders have never received specialty mental health care. Marked racial disparities in lifetime rates of mental health treatment highlight the urgent need to identify and combat barriers to the recognition and treatment of these conditions.

Intrauterine Effects of Maternal Prepregnancy Overweight on Child Cognition and Behavior in 2 Cohorts. Brion, Marie-Jo; Zeegers, Mijke; Jaddoe, Vincent; Verhulst, Frank; et al. Pediatrics, December 27, 2010, Online Early.
Greater maternal prepregnancy adiposity has been associated with behavioral problems, such as attention-deficit/hyperactivity disorder, and lower intellectual function in offspring. However, few studies of humans have explored this, and it is unclear if intrauterine mechanisms or confounding factors drive these associations.
PATIENTS AND METHODS: Parental adiposity and offspring verbal skills, nonverbal skills, and behavioral problems were assessed in the British Avon Longitudinal Study of Parents and Children (N = ~5000) and Dutch Generation R (N = ~2500) cohorts. We aimed to determine the plausibility of intrauterine effects by (1) adjusting for multiple confounders, (2) comparing associations between maternal and paternal overweight with offspring cognition/behaviors, and (3) searching for cross-cohort consistency.
RESULTS: Maternal prepregnancy overweight was associated with reduced child verbal skills (unadjusted). However, after adjusting for confounders, this result was not consistently observed in both cohorts. Maternal overweight was also associated with child total behavior problems and externalizing problems even after adjusting for confounders. However, this was observed in Generation R only and was not replicated in the British Avon Longitudinal Study of Parents and Children. No associations of maternal overweight with child attention problems, emotional/internalizing problems, or nonverbal skills were observed in either cohort. Paternal overweight was not associated with any of the child outcomes but was also less strongly related to potential confounding factors than was maternal overweight.
CONCLUSIONS: Overall, we found little consistent evidence of intrauterine effects of maternal prepregnancy overweight on child cognition and behavior. Some associations initially observed were not consistently replicated across cohorts or robust to adjustment for confounding factors and, thus, are likely to reflect confounding by socioeconomic or postnatal factors.

Association of Parental ADHD and Depression With Externalizing and Internalizing Dimensions of Child Psychopathology
Humphreys, Kathryn L.; Mehta, Natasha; Lee, Steve S. Journal of Attention Disorders, December 20, 2010, Online Early.
To study the independent association of parental depression and ADHD on three dimensions of child psychopathology among 178 children aged 5 to 10 years.
METHOD: Self-reported measures of parental depression and ADHD as well as rating scales and structure diagnostic interviews of child internalizing, ADHD, and externalizing problems were obtained.
RESULTS: Structural equation modeling indicated that parental ADHD was positively associated with a broad child problems factor after a second-order factor of child problems best accounted for the high intercorrelations among the internalizing, ADHD, and externalizing child psychopathology factors. Parental depression did not significantly predict the second-order child problems factor, but it specifically predicted the child internalizing factor.
CONCLUSION: These results suggest that parental ADHD may be a nonspecific risk factor for child psychopathology broadly, whereas parental depression may function as a specific risk factor for child internalizing problems.

Comorbidity of Migraine With ADHD. Fasmer, Ole Bernt; Riise, Trond; Lund, Anders; Dilsaver, Steven C.; Hundal, Oivind; Oedegaard, Ketil J. Journal of Attention Disorders, December 20, 2010, Online Early.
The purpose of this study was to investigate how often drugs used to treat migraine and ADHD are prescribed to the same patients to assess, indirectly, the comorbidity of these disorders.
METHOD: We used data from the Norwegian prescription database for 2006, including the total Norwegian population (N = 4,640,219). RESULTS: Antimigraine drugs were prescribed to 81,225 persons (1.75% of the total population), anti-ADHD drugs to 18,481 persons (0.40%), and 284 persons were prescribed both types of drugs. There was a positive and significant association between prescription of antimigraine and anti-ADHD drugs for all age groups between 20 and 50 for both genders, with odds ratios ranging from 1.76 to 2.81.
CONCLUSION: The prescription patterns for these drugs in adult patients indicate a comorbidity between migraine and ADHD.

Contrasting Parents' and Pediatricians' Perspectives on Shared Decision-Making in ADHD. Fiks, Alexander G.; Hughes, Cayce C.; Gafen, Angela; Guevara, James P.; Barg, Frances K. Pediatrics, December 20, 2010, Online Early.
The goal was to compare how parents and clinicians understand shared decision-making (SDM) in attention-deficit/hyperactivity disorder (ADHD), a prototype for SDM in pediatrics.
METHODS: We conducted semi-structured interviews with 60 parents of children 6 to 12 years of age with ADHD (50% black and 43% college educated) and 30 primary care clinicians with varying experience. Open-ended interviews explored how pediatric clinicians and parents understood SDM in ADHD. Interviews were taped, transcribed, and then coded. Data were analyzed by using a modified grounded theory approach.
RESULTS: Parents and clinicians both viewed SDM favorably. However, parents described SDM as a partnership between equals, with physicians providing medical expertise and the family contributing in-depth knowledge of the child. In contrast, clinicians understood SDM as a means to encourage families to accept clinicians' preferred treatment. These findings affected care because parents mistrusted clinicians whose presentation they perceived as biased. Both groups discussed how real-world barriers limit the consideration of evidence-based options, and they emphasized the importance of engaging professionals, family members, and/or friends in SDM. Although primary themes did not differ according to race, white parents more commonly received support from medical professionals in their social networks.
CONCLUSIONS: Despite national guidelines prioritizing SDM in ADHD, challenges to implementing the process persist. Results suggest that, to support SDM in ADHD, modifications are needed at the practice and policy levels, including clinician training, incorporation of decision aids and improved strategies to facilitate communication, and efforts to ensure that evidence-based treatment is accessible.

Behavioural symptoms of attention deficit/hyperactivity disorder in preterm and term children born small and appropriate for gestational age: A longitudinal study. Heinonen, Kati; Raikkonen, Katri; Pesonen, Anu-Katriina; Andersson, Sture; et al. BMC Pediatrics, December 15, 2010, 10:91.
BACKGROUND: It remains unclear whether it is more detrimental to be born too early or too small in relation to symptoms of attention deficit/hyperactivity disorder (ADHD). Thus, we tested whether preterm birth and small body size at birth adjusted for gestational age are independently associated with symptoms of ADHD in children.
METHODS: A longitudinal regional birth cohort study comprising 1535 live-born infants between 03/15/1985 and 03/14/1986 admitted to the neonatal wards and 658 randomly recruited non-admitted infants, in Finland. The present study sample comprised 828 children followed up to 56 months. The association between birth status and parent-rated ADHD symptoms of the child was analyzed with multiple linear and logistic regression analyses.
RESULTS: Neither prematurity (birth<37 weeks of gestation) nor lower gestational age was associated with ADHD symptoms. However, small for gestational age (SGA<-2 standard deviations [SD] below the mean for weight at birth) status and lower birth weight SD score were significantly, and independently of gestational age, associated with higher ADHD symptoms. Those born SGA, relative to those born AGA, were also 3.60-times more likely to have ADHD symptoms scores above the clinical cut-off. The associations were not confounded by factors implicated as risks for pregnancy and/or ADHD.
CONCLUSIONS: Intrauterine growth restriction, reflected in SGA status and lower birth weight, rather than prematurity or lower gestational age per se, may increase risk for symptoms of ADHD in young children.

Cortical Development in Typically Developing Children With Symptoms of Hyperactivity and Impulsivity: Support for a Dimensional View of Attention Deficit Hyperactivity Disorder. Shaw, Philip; Gilliam, Mary; Liverpool, Maria; Weddle, Catherine; et al. American Journal of Psychiatry, December 15, 2010, Online Early.
There is considerable epidemiological and neuropsychological evidence that attention deficit hyperactivity disorder (ADHD) is best considered dimensionally, lying at the extreme end of a continuous distribution of symptoms and underlying cognitive impairments. The authors investigated whether cortical brain development in typically developing children with symptoms of hyperactivity and impulsivity resembles that found in the syndrome of ADHD. Specifically, they examined whether a slower rate of cortical thinning during late childhood and adolescence, which they previously found in ADHD, is also linked to the severity of symptoms of hyperactivity and impulsivity in typically developing children.
METHOD: In a longitudinal analysis, a total of 193 typically developing children with 389 neuroanatomic magnetic resonance images and varying levels of symptoms of hyperactivity and impulsivity (measured with the Conners' Parent Rating Scale) were contrasted with 197 children with ADHD with 337 imaging scans. The relationship between the rates of regional cortical thinning and severity of symptoms of hyperactivity/impulsivity was determined.
RESULTS: Youth with higher levels of hyperactivity/impulsivity had a slower rate of cortical thinning, predominantly in prefrontal cortical regions, bilaterally in the middle frontal/premotor gyri, extending down the medial prefrontal wall to the anterior cingulate; the orbitofrontal cortex; and the right inferior frontal gyrus. For each increase of one point in the hyperactivity/impulsivity score, there was a decrease in the rate of regional cortical thinning of 0.0054 mm/year (SE=0.0019 mm/year). Children with ADHD had the slowest rate of cortical thinning.
CONCLUSIONS: Slower cortical thinning during adolescence characterizes the presence of both the symptoms and syndrome of ADHD, providing neurobiological evidence for dimensionality of the disorder.

Economic burden and comorbidities of attention-deficit/hyperactivity disorder among pediatric patients hospitalized in the United States. Meyers, Juliana L.; Classi, Peter M.; Wietecha, Linda A.; Candrilli, Sean D. Child and Adolescent Psychiatry and Mental Health, December 14, 2010, 4:31.
This retrospective database analysis used data from the Healthcare Cost and Utilization Project's Nationwide Inpatient Sample (NIS) to examine common primary diagnoses among children and adolescents hospitalized with a secondary diagnosis of attention- deficit/hyperactivity disorder (ADHD) and assessed the burden of ADHD.
METHODS: Hospitalized children (aged 6-11 years) and adolescents (aged 12-17 years) with a secondary diagnosis of ADHD were identified. The 10 most common primary diagnoses (using the first 3 digits of the ICD-9-CM code) were reported for each age group. Patients with 1 of these conditions were selected to analyze demographics, length of stay (LOS), and costs. Control patients were selected if they had 1 of the 10 primary diagnoses and no secondary ADHD diagnosis. Patient and hospital characteristics were reported by cohort (i.e., patients with ADHD vs. controls), and LOS and costs were reported by primary diagnosis. Multivariable linear regression analyses were undertaken to adjust LOS and costs based on patient and hospital characteristics.
RESULTS: A total of 126,056 children and 204,176 adolescents were identified as having a secondary diagnosis of ADHD. Among children and adolescents with ADHD, the most common diagnoses tended to be mental health related (i.e., affective psychoses, emotional disturbances, conduct disturbances, depressive disorder, or adjustment reaction). Other common diagnoses included general symptoms, asthma (in children only), and acute appendicitis. Among patients with ADHD, a higher percentage were male, white, and covered by Medicaid. LOS and costs were higher among children with ADHD and a primary diagnosis of affective psychoses (by 0.61 days and $51), adjustment reaction (by 1.71 days and $940), or depressive disorder (by 0.41 days and $124) versus controls. LOS and costs were higher among adolescents with ADHD and a primary diagnosis of affective psychoses (by 1.04 days and $353), depressive disorder (by 0.94 days and $517), conduct disturbances (by 0.86 days and $1,330), emotional disturbances (by 1.45 days and $1,626), adjustment reaction (by 1.25 days and $702), and neurotic disorders (by 1.60 days and $541) versus controls.
CONCLUSION: Clinicians and health care decision makers should be aware of the potential impact of ADHD on hospitalized children and adolescents.

Differences between children and adolescents in treatment response to atomoxetine and the correlation between health-related quality of life and Attention Deficit/Hyperactivity Disorder core symptoms: Meta-analysis of five atomoxetine trials. Wehmeier, Peter M.; Schacht, Alexander; Escobar, Rodrigo; Savill, Nicola; Harpin, Val. Child and Adolescent Psychiatry and Mental Health, December 6, 2010, 4(1):30.
OBJECTIVES: To explore the influence of age on treatment responses to atomoxetine and to assess the relationship between core symptoms of attention deficit/hyperactivity disorder (ADHD) and health-related quality of life (HR-QoL) outcomes.
DATA SOURCES: Data from five similar clinical trials of atomoxetine in the treatment of children and adolescents with ADHD were included in this meta-analysis.
STUDY SELECTION: Atomoxetine studies that used the ADHD Rating Scale (ADHD-RS) and the Child Health and Illness Profile Child Edition (CHIP-CE) as outcome measures were selected.
INTERVENTIONS: Treatment with atomoxetine. MAIN OUTCOME MEASURES: Treatment group differences (atomoxetine vs placebo) in terms of total score, domains, and subdomains of the CHIP-CE were compared across age groups, and correlations between ADHD-RS scores and CHIP-CE scores were calculated by age.
RESULTS: Data of 794 subjects (611 children, 183 adolescents) were pooled. At baseline, adolescents showed significantly (p<0.05) greater impairment compared with children in the Family Involvement, Satisfaction with Self, and Academic Performance subdomains of the CHIP-CE. Treatment effect of atomoxetine was significant in both age groups for the Risk Avoidance domain and its subdomains. There was a significant age-treatment interaction with greater efficacy seen in adolescents in both the Risk Avoidance domain and the Threats to Achievement subdomain. Correlations between ADHD-RS and CHIP-CE scores were generally low at baseline and moderate in change from baseline and were overall similar in adolescents and children.
CONCLUSIONS: Atomoxetine was effective in improving some aspects of HR-QoL in both age groups. Correlations between core symptoms of ADHD and HR-QoL were low to moderate.

Dietary Sensitivities and ADHD Symptoms: Thirty-five Years of Research. Stevens, Laura J.; Kuczek, Thomas; Burgess, John R.; Hurt, Elizabeth; Arnold, L. Eugene. Clinical Pediatrics, December 2, 2010, Online Early.
Artificial food colors (AFCs) have not been established as the main cause of attention-deficit hyperactivity disorder (ADHD), but accumulated evidence suggests that a subgroup shows significant symptom improvement when consuming an AFC-free diet and reacts with ADHD-type symptoms on challenge with AFCs. Of children with suspected sensitivities, 65% to 89% reacted when challenged with at least 100 mg of AFC. Oligoantigenic diet studies suggested that some children in addition to being sensitive to AFCs are also sensitive to common nonsalicylate foods (milk, chocolate, soy, eggs, wheat, corn, legumes) as well as salicylate-containing grapes, tomatoes, and orange. Some studies found "cosensitivity" to be more the rule than the exception. Recently, 2 large studies demonstrated behavioral sensitivity to AFCs and benzoate in children both with and without ADHD. A trial elimination diet is appropriate for children who have not responded satisfactorily to conventional treatment or whose parents wish to pursue a dietary investigation.

Quality of care for childhood attention-deficit/hyperactivity disorder in a managed care medicaid program. Zima, Bonnie T.; Bussing, Regina; Tang, Lingqi; Zhang, Lily; et al. Journal of the American Academy of Child & Adolescent Psychiatry, December 2010, v49 n12, pp. 1225-1237.e11.
To examine whether clinical severity is greater among children receiving attention-deficit/hyperactivity disorder (ADHD) care in primary care compared with those in specialty mental health clinics, and to examine how care processes and clinical outcomes vary by sector across three 6-month time intervals.
METHOD: This was a longitudinal cohort study of 530 children aged 5 to 11 years receiving ADHD care in primary care or specialty mental health clinics from November 2004 through September 2006 in a large, countywide managed care Medicaid program.
RESULTS: Clinical severity at study entry did not differ between children who received ADHD care in solely primary or specialty mental health care clinics. At three 6-month intervals, receipt of no care ranged from 34% to 44%, and unmet need for mental health services ranged from 13% to 20%. In primary care, 80% to 85% of children had at least one stimulant prescription filled and averaged one to two follow-up visits per year. Less than one-third of children in specialty mental health clinics received any stimulant medication, but all received psychosocial interventions averaging more than five visits per month. In both sectors, stimulant medication refill prescription persistence was poor (31%-49%). With few exceptions, ADHD diagnosis, impairment, academic achievement, parent distress, and parent-reported treatment satisfaction, perceived benefit, and improved family functioning did not differ between children who remained in care and those who received no care.
CONCLUSION: Areas for quality improvement are alignment of clinical severity with provider type, follow-up visits, stimulant use in specialty mental health, agency data infrastructure to document delivery of evidence-based psychosocial treatment, and stimulant medication refill prescription persistence.

Task-related default mode network modulation and inhibitory control in ADHD: effects of motivation and methylphenidate. Liddle, Elizabeth B.; Hollis, Chris; Batty, Martin J.; Groom, Madeleine J.; et al. Journal of Child Psychology and Psychiatry, November 12, 2010, Online Early.
Deficits characteristic of attention deficit/hyperactivity disorder (ADHD), including poor attention and inhibitory control, are at least partially alleviated by factors that increase engagement of attention, suggesting a hypodopaminergic reward deficit. Lapses of attention are associated with attenuated deactivation of the default mode network (DMN), a distributed brain system normally deactivated during tasks requiring attention to the external world. Task-related DMN deactivation has been shown to be attenuated in ADHD relative to controls. We hypothesised that motivational incentives to balance speed against restraint would increase task engagement during an inhibitory control task, enhancing DMN deactivation in ADHD. We also hypothesised that methylphenidate, an indirect dopamine agonist, would tend to normalise abnormal patterns of DMN deactivation.
METHOD: We obtained functional magnetic resonance images from 18 methylphenidate-responsive children with ADHD (DSM-IV combined subtype) and 18 pairwise-matched typically developing children aged 9-15 years while they performed a paced Go/No-go task. We manipulated motivational incentive to balance response speed against inhibitory control, and tested children with ADHD both on and off methylphenidate.
RESULTS: When children with ADHD were off-methylphenidate and task incentive was low, event-related DMN deactivation was significantly attenuated compared to controls, but the two groups did not differ under high motivational incentives. The modulation of DMN deactivation by incentive in the children with ADHD, off-methylphenidate, was statistically significant, and significantly greater than in typically developing children. When children with ADHD were on-methylphenidate, motivational modulation of event-related DMN deactivation was abolished, and no attenuation relative to their typically developing peers was apparent in either motivational condition.
CONCLUSIONS: During an inhibitory control task, children with ADHD exhibit a raised motivational threshold at which task-relevant stimuli become sufficiently salient to deactivate the DMN. Treatment with methylphenidate normalises this threshold, rendering their pattern of task-related DMN deactivation indistinguishable from that of typically developing children.

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