Latest Published Studies on ADHD


Associations between problems with crying, sleeping and/or feeding in infancy and long-term behavioural outcomes in childhood: a meta-analysis.
Hemmi, Mirja Helen; Wolke, Dieter; Schneider, Silvia.
Archives of Disease in Childhood, April 20, 2011, Online Early.
Excessive crying, sleeping or feeding problems are found in approximately 20% of infants and may predict behavioural problems in childhood.
METHODS: A quantitative meta-analysis of 22 longitudinal studies from 1987 to 2006 that statistically tested the association between infant regulatory problems and childhood internalising, externalising and attention-deficit/hyperactivity disorder (ADHD) problems was carried out; 1935 children with regulatory problems were tested. Cohen's d was used to express the association between regulatory problems and behavioural problems. Heterogeneity of the effect sizes was assessed using the I² statistic and meta-analysis of variance and meta-regressions were conducted to assess the influence of moderators. Rosenthal's classic fail-safe N and correlation of sample sizes to effect sizes were used to assess publication bias.
RESULTS: The weighted mean effect size for the main regulatory problems--behavioural problems association was 0.41 (95% CI 0.28 to 0.54), indicating that children with previous regulatory problems have more behavioural problems than controls. Externalising and ADHD problems were the strongest outcome of any regulatory problem, indicated by the highest fail-safe N and lowest correlation of sample size to effect size. Meta-analyses of variance revealed no significant moderating influences of regulatory problem comorbidity (I² = 44.0, p>0.05), type (I² =41.8, p>0.05) or duration (I² =44.0, p>0.05). However, cumulative problems and clinical referral increased the risk of behavioural problems.
CONCLUSIONS: The meta-analyses suggest that children with previous regulatory problems have more behavioural problems than controls, particularly in multi-problem families. Further studies are required to assess the behavioural outcomes of previously sleep, feeding or multiply disturbed children.

Preterm Birth and Attention-Deficit/Hyperactivity Disorder in Schoolchildren
Lindström, Karolina; Lindblad, Frank; Hjern, Anders.
Pediatrics, April 18, 2011, Online Early.
Previous studies have demonstrated an increased risk for attention-deficit/hyperactivity disorder (ADHD) in follow-up studies of preterm survivors from NICUs. In this study we analyzed the effect of moderate as well as extreme preterm birth on the risk for ADHD in school age, taking into account genetic, perinatal, and socioeconomic confounders.
METHODS: Register study in a Swedish national cohort of 1,180 616 children born between 1987 and 2000, followed up for ADHD medication in 2006 at the age of 6 to 19 years. Logistic regression was used to test hypotheses. A within-mother-between-pregnancy design was used to estimate the importance of genetic confounding in a subpopulation of offspring (N = 34,334) of mothers who had given birth to preterm (34 weeks) as well as term infants.
RESULTS: There was a stepwise increase in odds ratios for ADHD medication with increasing degree of immaturity at birth; from 2.1 (1.4-2.7) for 23 to 28 weeks' gestation, to 1.6 (1.4-1.7) for 29 to 32 weeks', 1.4 (1.2-1.7) for 33 to 34 weeks', 1.3 (1.1-1.4) for 35 to 36 weeks', and 1.1 (1.1-1.2) for 37 to 38 weeks' gestation compared with infants born at 39 to 41 weeks' gestation in the fully adjusted model. The odds ratios for the within-mother-between-pregnancy analysis were very similar. Low maternal education increased the effect of moderate, but not extreme, preterm birth on the risk for ADHD.
CONCLUSIONS: Preterm and early term birth increases the risk of ADHD by degree of immaturity. This main effect is not explained by genetic, perinatal, or socioeconomic confounding, but socioeconomic context modifies the risk of ADHD in moderately preterm births.

Predictors of Parent-Reported Attention-Deficit/Hyperactivity Disorder in Children Aged 6-7 years: A National Longitudinal Study
Sciberras, Emma; Ukoumunne, Obioha C.; Efron, Daryl.
Journal of Abnormal Child Psychology, April 12, 2011, Online Early.
This study examined the prenatal, postnatal and demographic predictors of parent-reported attention-deficit/hyperactivity disorder (ADHD) in an Australian population-based sample. Participants were families participating in the Longitudinal Study of Australian Children. There were approximately even numbers of males (51%) and females (49%) in the sample. Predictors of parent-reported ADHD status at Wave 2 (children aged 6-7 years) which were measured at Wave 1 (children aged 4-5 years) included cigarette smoking and alcohol use during pregnancy (prenatal factors); maternal postnatal depression, intensive care at birth, birth weight, and gestation (postnatal factors); and child gender, primary caregiver education, income, family composition, and maternal age at childbirth (socio-demographic factors). We found that male gender, cigarette smoking during pregnancy, and maternal postnatal depression were the only significant predictors (at the 5% level) of ADHD in the adjusted analysis (N=3,474). Our results are consistent with previous findings that male gender and cigarette smoking during pregnancy are risk factors for ADHD. In addition, we found that postnatal depression was predictive of parent-reported ADHD.

The impact of study design and diagnostic approach in a large multi-centre ADHD study: Part 2: Dimensional measures of psychopathology and intelligence
Muller, Ueli C.; Asherson, Philip; Banaschewski, Tobias; Buitelaar, Jan K.; et al.
BMC Psychiatry, April 7, 2011, v11 n1:55
The International Multi-centre ADHD Genetics (IMAGE) project with 11 participating centres from 7 European countries and Israel has collected a large behavioural and genetic database for present and future research. Behavioural data were collected from 1068 probands with ADHD and 1446 unselected siblings. The aim was to describe and analyse questionnaire data and IQ measures from all probands and siblings. In particular, to investigate the influence of age, gender, family status (proband vs. sibling), informant, and centres on sample homogeneity in psychopathological measures.
METHODS: Conners' Questionnaires, Strengths and Difficulties Questionnaires, and Wechsler Intelligence Scores were used to describe the phenotype of the sample. Data were analysed by use of robust statistical multi-way procedures.
RESULTS: Besides main effects of age, gender, informant, and centre, there were considerable interaction effects on questionnaire data. The larger differences between probands and siblings at home than at school may reflect contrast effects in the parents. Furthermore, there were marked gender by status effects on the ADHD symptom ratings with girls scoring one standard deviation higher than boys in the proband sample but lower than boys in the siblings sample. The multi-centre design is another important source of heterogeneity, particularly in the interaction with the family status. To a large extent the centres differed from each other with regard to differences between proband and sibling scores.
CONCLUSIONS: When ADHD probands are diagnosed by use of fixed symptom counts, the severity of the disorder in the proband sample may markedly differ between boys and girls and across age, particularly in samples with a large age range. A multi-centre design carries the risk of considerable phenotypic differences between centres and, consequently, of 4 additional heterogeneity of the sample even if standardized diagnostic procedures are used. These possible sources of variance should be counteracted in genetic analyses either by using age and gender adjusted diagnostic procedures and regional normative data or by adjusting for design artefacts by use of covariate statistics, by eliminating outliers, or by other methods suitable for reducing heterogeneity.

Relation Between Outcomes on a Continuous Performance Test and ADHD Symptoms Over Time
Vaughn, Aaron J.; Epstein, Jeffery N.; Rausch, Joseph; Altaye, Mekibib; et al.
Journal of Abnormal Child Psychology, April 8, 2011, Online Early.
This study examined the relationship between the developmental trajectories of neuropsychological functioning and ADHD symptomatology in a longitudinal sample of children ages 9 to 14. Participants and measures were derived from the Multimodal Treatment Study for ADHD including 534 MTA participants and 254 normal controls. Despite improvement over time, MTA participants continued to receive higher ratings of ADHD symptomatology and exhibit greater difficulties across the majority of neuropsychological outcomes. No relations were found between improvements in neuropsychological functioning and ADHD symptomatology over time. Findings provide support for the persistence of neuropsychological functioning and ADHD symptomatology. Findings did not support the hypothesized relation between improvements in frontally-mediated neuropsychological functioning and ADHD symptomatology possibly due to the brief 1-year lag and limited assessment battery. Findings are discussed in relation to neuropsychological development including recommendations for future research.

Medication Costs to Private Insurers of Diversion of Medications for Attention-Deficit Hyperactivity Disorder
Aldridge, Arnie P.; Kroutil, Larry A.; Cowell, Alexander J.; Reeves, Daniel B.; Van Brunt, David L.
PharmacoEconomics, April 7, 2011, Online Early.

BACKGROUND: The diversion of prescription stimulants for misuse, particularly those used in the treatment of attention-deficit hyperactivity disorder (ADHD), is potentially a significant problem for public health and for healthcare funding and delivery. Most prior research on the diversion of prescription stimulants for misuse, particularly those used in the treatment of ADHD, has focused on the 'end users' of diverted medications rather than the suppliers. Furthermore, little is known about the direct costs of diversion for third-party insurance payers in the US. OBJECTIVES: The objectives of this study were to estimate the prevalence in the US of people whose private insurance paid costs for ADHD prescriptions that they gave or sold to another person (diversion), and to estimate medication costs of diversion to private insurers.
METHODS: Estimates are from a cross-sectional survey of respondents from two Internet survey panels targeting individuals aged 18-49 years in the civilian, noninstitutionalized US population, principally for those who filled prescriptions for ADHD medications in the past 30 days that were covered by private health insurance. Analysis weights were post-stratified to control totals from the Current Population Survey and National Health Interview Survey. Weighted prevalence rates and standard errors for diversion are reported, as are the costs of diverted pills using drug prices reported in the 2008 Thomson Reuters RED BOOK?. Sensitivity analyses were conducted that varied the cost assumptions for medications.
RESULTS: Among individuals aged 18-49 years whose private insurance paid some costs for ADHD medications in the past 30 days, 16.6% diverted medications from these prescriptions. Men aged 18-49 years for whom private insurance paid some costs of ADHD drugs in the past 30 days were more than twice as likely as their female counterparts to divert medications from these prescriptions (22.5% vs 9.1%; p?=?0.03). After a pro-rated co-payment share was subtracted,the estimated value of diverted medications in a 30-day period was $US8.0 million. Lower- and upper-bound estimates were $US 6.9 million to $US17 million, for a range of $US83 million to $US204 million annually. Overall, diversion accounted for about 3.6% of the total costs that private insurers paid for ADHD medications (range: 3.5-4.5%). The percentages varied by medication category, although relative differences were sensitive to inclusion of a pro-rated co-payment. A higher percentage of the costs of extended-release (XR) medications was lost to diversion compared with that for immediate-release (IR) medications.
CONCLUSIONS: Costs of ADHD medications paid for by private insurers that were lost to diversion were small relative to the total estimated medication costs and relative to total estimated healthcare costs for treating ADHD. Nevertheless, there may be significant cost savings for insurers if diversion can be reduced, particularly for XR medications. These findings represent a first step to informing policies to reduce diversion both in the interest of public health and for direct and indirect cost savings to insurers.

Psychomotor Functioning and Alertness with Guanfacine Extended Release in Subjects with Attention-Deficit/Hyperactivity Disorder
Kollins, Scott H.; López, Frank A.; Vince, Bradley D.; Turnbow, John M.; et al.
Journal of Child and Adolescent Psychopharmacology, April 2011, v21 n2, pp. 111-120.
To determine whether treatment with guanfacine extended release (GXR) in subjects with attention-deficit/hyperactivity disorder (ADHD) disrupted psychomotor functioning and alertness, or impacted daytime sleepiness.
METHOD: This was a randomized, double-blind, placebo-controlled, multicenter, phase 2, dose-optimization, noninferiority, laboratory classroom study of GXR (1, 2, and 3mg/day) in 182 subjects aged 6 to 17 years with ADHD. Psychomotor functioning and alertness were assessed through several measures, including the Choice Reaction Time (CRT) test from the Cambridge Neuropsychological Test Automated Battery. Sedative effects were examined via spontaneously reported adverse events of sedation, somnolence, and hypersomnia as well as fatigue and lethargy, and with two validated subject- and observer-rated sleepiness scales. Standard efficacy measures for ADHD also were included. Cardiovascular and laboratory parameters were assessed.
RESULTS: There were no significant differences between the GXR and placebo groups on measures of psychomotor functioning or alertness from the CRT at endpoint (least-square mean difference: 2.5 [95% confidence interval (CI): -22.9, 28.0], p=0.8 for CRT; 2.5 [95% CI: -21.5, 26.4], p=0.84 for correct responses; 15.5 [95% CI: -45.1, 14.1], p=0.30 for movement time; and -8.2 [95% CI: -54.1, 37.6] p=0.72 for total time). Most sedative adverse events were mild to moderate, occurred during dose titration, decreased with dose maintenance, and resolved during the study period. One subject in the GXR group discontinued due to fatigue and somnolence. GXR was not associated with increased daytime sleepiness. GXR treatment was associated with significant improvement in ADHD symptoms (6.3 [95% CI: 2.7, 9.8], p=0.001 for ADHD Rating Scale IV total scores at endpoint).
CONCLUSIONS: At doses that resulted in significant improvement in ADHD symptoms, impairment on cognitive tasks was not observed. Daytime sleepiness did not differ with GXR compared with placebo.  Results suggest that the beneficial effects of GXR on ADHD symptoms are independent of sedation.

Scales for the identification of adults with attention deficit hyperactivity disorder (ADHD): A systematic review
Taylor, Abigail; Deb, Shoumitro; Unwin, Gemma.
Research Developmental Disabilities, May-June 2011, v32 n3, pp. 924-938.
Attention deficit hyperactivity disorder (ADHD) is prevalent in the adult population. The associated co-morbidities and impairments can be relieved with treatment. Therefore, several rating scales have been developed to identify adults with ADHD who may benefit from treatment. No systematic review has yet sought to evaluate these scales in more detail. The present systematic review was undertaken to describe the properties, including psychometric statistics, of the currently available adult ADHD rating scales and their scoring methods, along with the procedure for development. Descriptive synthesis of the data is presented and study quality has been assessed by an objective quality assessment tool. The properties of each scale are discussed to make judgements about their validity and usefulness. The literature search retrieved 35 validation studies of adult ADHD rating scales and 14 separate scales were identified. The majority of studies were of poor quality and reported insufficient detail. Of the 14 scales, the Conners' Adult ADHD Rating scale and the Wender Utah Rating Scale (short version) had more robust psychometric statistics and content validity. More research into these scales, with good quality studies, is needed to confirm the findings of this review. Future studies of ADHD rating scales should be reported in more detail so that further reviews have more support for their findings.;
Research highlights; ► A variety of scales are available for identifying ADHD in adults. ► Psychometric properties vary across studies and across scales. ► The CAARS and WURS currently have the most evidence to support their use. ► Further research is needed that assesses measurement properties of such scales.

Parental and Professional Beliefs on the Treatment and Management of ADHD
Dryer, Rachel; Kiernan, Michael J.; Tyson, Graham A.
Journal of Attention Disorders, April 13, 2011, Online Early.
This study examined parental and professional beliefs about the efficacy of various treatment strategies for ADHD.
METHOD: Parents of children with and without ADHD and seven medical and nonmedical professional groups(N = 673) completed a questionnaire examining their beliefs about the efficacy of various treatment regimes.
RESULTS: Principle component analysis identified four factors--school-based interventions, medical and allied health interventions, parent interventions, and nontraditional interventions. Although there were some group differences in the level of endorsement for these factors, there was a high degree of concordance between the groups. The school-based interventions factor was the most highly endorsed, whereas the nontraditional interventions factor was the least endorsed by the sample as a whole.
CONCLUSION: The results suggest that the low level of interdisciplinary interaction that has been reported in the literature is not due to differences in beliefs about the efficacy of various treatment strategies for ADHD.

PAH/Aromatic DNA Adducts in Cord Blood and Behavior Scores in New York City Children
Perera, Frederica P.; Wang, Shuang; Vishnevetsky, Julia; Zhang, Bingzhi;  et al.
Environmental Health Perspectives, April 12, 2011, Online Early.
Airborne polycyclic aromatic hydrocarbons (PAH) are widespread urban pollutants that can bind to DNA to form PAH-DNA adducts. Prenatal PAH exposure measured by personal monitoring has been linked to cognitive deficits in childhood in a prospective study conducted by the Columbia Center for Children’s Environmental Health (CCCEH). OBJECTIVES: We measured PAH-DNA and other bulky aromatic adducts in umbilical cord white blood cells using the 32P-postlabeling assay to determine the association between this molecular dosimeter and behavioral/attention problems in childhood.
METHODS: Children born to nonsmoking African-American and Dominican women residing in New York City (NYC) were followed from in utero to 7-8 years of age. At two time points prior to age 8 (mean ages 4.8 years and 7 years), child behavior was assessed using the Child Behavior Checklist (CBCL). To estimate and test the association between adducts and behavioral outcomes, both CBCL continuous raw scores and dichotomized T-scores were analyzed.
RESULTS: Higher cord adducts were associated with higher symptom scores of Anxious/Depressed at 4.8 years and Attention Problems at 4.8 and 7 years, and with Diagnostic and Statistical Manual of Mental Disorders (DSM) oriented Anxiety Problems at the 4.8 years.
CONCLUSIONS: These results suggest that PAH exposure, measured by DNA adducts, may adversely affect child behavior, potentially affecting school performance.

A Double-Blind, Placebo-Controlled Study of Atomoxetine in Young Children With ADHD
Kratochvil, Christopher J.; Vaughan, Brigette S.; Stoner, Julie A.; Daughton, Joan M.; et al.
Pediatrics, April 2011, v127 n4, pp. e862-e868 [March 21, 2011, Online Early]
To evaluate the efficacy and tolerability of atomoxetine for the treatment of attention-deficit/hyperactivity disorder (ADHD) in 5- and 6-year-old children.
METHODS: This was an 8-week, double-blind, placebo-controlled randomized clinical trial of atomoxetine in 101 children with ADHD. Atomoxetine or placebo was flexibly titrated to a maximum dose of 1.8 mg/kg per day. The pharmacotherapist reviewed psychoeducational material on ADHD and behavioral-management strategies with parents during each study visit.
RESULTS: Significant mean decreases in parent (P = .009) and teacher (P = .02) ADHD-IV Rating Scale scores were demonstrated with atomoxetine compared with placebo. A total of 40% of children treated with atomoxetine met response criteria (Clinical Global Impression-Improvement Scale indicating much or very much improved) compared with 22% of children on placebo, which was not significant (P = .1). Decreased appetite, gastrointestinal upset, and sedation were significantly more common with atomoxetine than placebo. Although some children demonstrated a robust response to atomoxetine, for others the response was more attenuated. Sixty-two percent of subjects who received atomoxetine were moderately, markedly, or severely ill according to the Clinical Global Impression-Severity Scale at study completion.
CONCLUSIONS: To our knowledge, this is the first randomized controlled trial of atomoxetine in children as young as 5 years. Atomoxetine generally was well tolerated and reduced core ADHD symptoms in the children on the basis of parent and teacher reports. Reductions in the ADHD-IV Rating Scale scores, however, did not necessarily translate to overall clinical and functional improvement, as demonstrated on the Clinical Global Impression-Severity Scale and the Clinical Global Impression-Improvement Scale. Despite benefits, the children in the atomoxetine group remained, on average, significantly impaired at the end of the study.

Detection of Response Bias and Noncredible Performance in Adult Attention-Deficit/Hyperactivity Disorder
Young, J. Christopher; Gross, Alan M.
Archives of Clinical Neuropsychology, March 25, 2011, Online Early.
Adults with attention-deficit/hyperactivity disorder (ADHD) are frequently prescribed stimulant medication and eligible for accommodations at work or school that serve as potent incentives to feign ADHD symptoms. The current investigation examined the predictive validity of Minnesota Multiphasic Personality Inventory-2 (MMPI-2) validity scales in detecting and accurately classifying individuals attempting to feign ADHD. An archival ADHD clinical group (n = 34), normal control group (n = 37), and group instructed to feign ADHD symptoms (n = 32) completed the MMPI-2 and ADHD Current and Childhood Symptoms Scales. Behavior rating scales were unable to differentiate the clinical group from the simulated malingering group. Logistic regressions revealed that Infrequency-Psychopathology scale best detected response bias, followed by Infrequency scale, Back-Infrequency scale, Response Bias Scale (RBS), Henry-Heilbronner Index scale (HHI), and Fake Bad Scale (FBS). Results also indicate that recommended cutoffs for HHI, RBS, and FBS display inadequate sensitivity and specificity. Nevertheless, the MMPI-2 offers a number of validity indices that may assist in detecting individuals attempting to feign ADHD.

Developmental trajectories of DSM-IV symptoms of attention-deficit/hyperactivity disorder: genetic effects, family risk and associated psychopathology
Larsson, Henrik; Dilshad, Rezin; Lichtenstein, Paul; Barker, Edward D.
Journal of Child Psychology and Psychiatry, March 16, 2011, Online Early.
DSM-IV specifies three ADHD subtypes; the combined, the hyperactive-impulsive and the inattentive. Little is known about the developmental relationships underlying these subtypes. The objective of this study was to describe the development of parent-reported hyperactivity-impulsivity and inattention symptoms from childhood to adolescence and to study their associations with genetic factors, family risk, and later adjustment problems in early adulthood.
METHOD: Data in this study comes from 1,450 twin pairs participating in a population-based, longitudinal twin study. Developmental trajectories were defined using parent-ratings of hyperactivity-impulsivity and inattention symptoms at age 8-9, 13-14, and 16-17. Twin methods were used to explore genetic influences on trajectories. Family risk measures included low socioeconomic status, large family size and divorce. Self-ratings of externalizing and internalizing problems in early adulthood were used to examine adjustment problems related to the different trajectory combinations.
RESULTS: We found two hyperactivity-impulsivity trajectories (low, high/decreasing) and two inattention trajectories (low, high/increasing). Twin modeling revealed a substantial genetic component underlying both the hyperactivity-impulsivity and the inattention trajectory. Joint trajectory analyses identified four groups of adolescents with distinct developmental patterns of hyperactivity-impulsivity and inattention: a low/low group, a primarily hyperactive, a primarily inattentive and a combined (high/high) trajectory type. These trajectory combinations showed discriminant relations to adjustment problems in early adulthood. The hyperactive, inattentive and combined trajectory subtypes were associated with higher rates of family risk environments compared to the low/low group.
CONCLUSION: Study results showed that for those on a high trajectory, hyperactivity decreased whereas inattention increased. The combinations of these trajectories lend developmental insight into how children shift from (i) a combined to inattentive subtype, and (ii) a hyperactive-impulsive to a combined subtype. This study suggests that ADHD subtypes cannot be viewed as discrete and stable categories.

Posted in: Research