Daviss WB, Patel NC, Robb AS, McDermott MP, Bukstein OG, Pelham WE Jr, Palumbo D, Harris P, Sallee FR; the CAT STUDY TEAM.

J Am Acad Child Adolesc Psychiatry. 2008 Jan

OBJECTIVE: To examine the safety and tolerability of clonidine used alone or with methylphenidate in children with attention-deficit/hyperactivity disorder (ADHD).

METHOD: In a 16-week multicenter, double-blind trial, 122 children with ADHD were randomly assigned to clonidine (n = 31), methylphenidate (n = 29), clonidine and methylphenidate (n = 32), or placebo (n = 30). Doses were flexibly titrated up to 0.6 mg/day for clonidine and 60 mg/day for methylphenidate (both with divided dosing). Groups were compared regarding adverse events and changes from baseline to week 16 in electrocardiograms and vital signs.

RESULTS: There were more incidents of bradycardia in subjects treated with clonidine compared with those not treated with clonidine (17.5% versus 3.4%; p =.02), but no other significant group differences regarding electrocardiogram and other cardiovascular outcomes. There were no suggestions of interactions between clonidine and methylphenidate regarding cardiovascular outcomes. Moderate or severe adverse events were more common in subjects on clonidine (79.4% versus 49.2%; p =.0006) but not associated with higher rates of early study withdrawal. Drowsiness was common on clonidine, but generally resolved by 6 to 8 weeks.

CONCLUSIONS: Clonidine, used alone or with methylphenidate, appears safe and well tolerated in childhood ADHD. Physicians prescribing clonidine should monitor for bradycardia and advise patients about the high likelihood of initial drowsiness.

2. Evidence for overlapping genetic influences on autistic and ADHD behaviours in a community twin sample.

Ronald A, Simonoff E, Kuntsi J, Asherson P, Plomin R.
Social Genetic and Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, London, UK.

J Child Psychol Psychiatry. 2008 Jan 21

Background: High levels of clinical comorbidity have been reported between autistic spectrum disorders (ASD) and attention deficit hyperactivity
disorder (ADHD). This study takes an individual differences approach to determine the degree of phenotypic and aetiological overlap between autistic
traits and ADHD behaviours in the general population.

Methods: The Twins Early Development Study is a community sample born in England and Wales. Families with twins born in 1994-6 were invited to join;
6,771 families participated in the study when the twins were 8 years old. Parents completed the Childhood Asperger Syndrome Test and the Conners'
DSM-IV subscales. Teacher data were also collected on a sub-sample. High scores on the Conners' subscales were used to identify possible ADHD cases.
Potential ASD cases were interviewed using the Development and Well-Being Assessment. Multivariate structural equation model-fitting was employed, as
well as DeFries Fulker extremes analysis and liability threshold model-fitting.

Results: Significant correlations were found between autistic and ADHD traits in the general population (.54 for parent data, .51 for teacher data). In the bivariate models, all genetic correlations were >.50, indicating a moderate degree of overlap in genetic influences on autistic and ADHD traits, both throughout the general population and at the quantitative extreme. This phenotypic and genetic overlap still held when sex, IQ and conduct problems were controlled for, for both parent and teacher data. There was also substantial overlap in suspected cases (41% of children who met criteria for an ASD had suspected ADHD; 22% with suspected ADHD met criteria for an ASD).

Conclusions: These results suggest there are some common genetic influences operating across autistic traits and ADHD behaviours throughout normal variation and at the extreme. This is relevant for molecular genetic research, as well as for psychiatrists and psychologists, who may have assumed these two sets of behaviours are independent

3. The Impact of Impairment Criteria on Rates of ADHD Diagnoses in Preschoolers.

Healey DM, Miller CJ, Castelli KL, Marks DJ, Halperin JM. Department of Psychology, University of Otago, PO Box 56, Dunedin, 9054, New Zealand,

J Abnorm Child Psychol. 2008 Jan 26

Behaviors characteristic of ADHD are common among preschool children, and as such, their clinical significance is oftentimes difficult to ascertain. Thus a focus on impairment is essential in determining the clinical significance of these behaviors. In order to explore the impact of impairment criteria on rates of diagnoses in inattentive/hyperactive children aged 36 through 60-months-old, we first developed, and psychometrically evaluated, the Children's Problem Checklist (CPC) which was designed to assess psychosocial impairment associated with ADHD in a community sample of preschoolers (n = 394), and found its reliability and validity to be acceptable. We then examined the impact of the inclusion of various CPC-determined impairment criteria, over and above symptom criteria measured by the ADHD-RS-IV, using various cut points ranging from the 75th to 90th percentile of our community sample. This reduced the number of children meeting criteria for ADHD by 46-77%. These findings are discussed in terms of the importance of using impairment criteria, rather than just severity of inattention, impulsivity and hyperactivity, when diagnosing ADHD in preschool children.

4. The Effects of Methylphenidate on Word Decoding Accuracy in Boys with Attention-Deficit/Hyperactivity Disorder.

Bental B, Tirosh E.
The Hannah Khoushy Child Development Center, Bnai Zion Medical Center; and †Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.

J Clin Psychopharmacol. 2008 Feb; 28(1):89-92.

The investigation aimed to delineate the immediate effect of methylphenidate on decoding in the comorbid condition of attention-deficit/hyperactivity disorder and reading disorder. Boys with attention-deficit/hyperactivity and reading disorders (n = 25) between the ages of 7.9 and 11.7 years, with at least average intelligence and verbal processing abilities participated in a double-blind, acute, randomized, placebo-controlled crossover trial with a single dose of methylphenidate 0.3 to 0.4 mg/kg with weekly intervals between testing sessions. The test battery included tasks of attention/control functions and reading domain functions. Paired comparisons and first trial group comparison comparing performance under placebo and under methylphenidate were used. Methylphenidate selectively improved strategy/set shift (P = 0.004) and facilitated improvement both in rapid naming (P = 0.043) and word/nonword accuracy (P = 0.028/P = 0.035). These findings lend support to a possible influence of methylphenidate on cognitive attention functions related to reading skills in the comorbid group.

5. Association between treatment with central nervous system stimulants and Raynaud's syndrome in children: A retrospective case-control study of rheumatology patients.

Goldman W, Seltzer R, Reuman P. Akron Children's Hospital and Medical Center, Akron, Ohio.

Arthritis Rheum. 2008 Jan 31; 58(2):563-566

OBJECTIVE: To investigate whether central nervous system (CNS) stimulants used for the treatment of attention deficit hyperactivity disorder (ADHD) are associated with the development of Raynaud's syndrome (RS).

METHODS: A case-control design was used for this study. All patients seen in a pediatric rheumatology practice during a 5-year period who had signs and symptoms of RS and met diagnostic criteria for RS as determined by pulse volume recording were studied as cases. Controls were randomly selected patients at the same clinic who did not have signs or symptoms of RS. They were matched to the cases for age, sex, and time of presentation. We tested for associations between various CNS medications and presence of RS. We also evaluated differences in laboratory test results between RS cases and matched controls.

RESULTS: Sixty-four patients were enrolled in the study (32 cases with RS [23 female, 9 male] and 32 control patients). McNemar's test showed a significant association between the presence of RS and past or current use of ADHD stimulants (methylphenidate and dextroamphetamine) (chi(2) = 5.00, P = 0.01). The use of other CNS medications was not found to be significantly associated with RS (chi(2) = 1.33, P = 0.25 by McNemar's test). C-reactive protein levels and erythrocyte sedimentation rates were significantly higher in controls than in cases.

CONCLUSION: The results of this study indicate that there is a significant association between development of RS and therapy with CNS stimulants used for the treatment of ADHD. Although this was a small study, these findings provide preliminary evidence of an adverse effect of CNS stimulant medications in patients seen in rheumatology practice.