1. Processing Speed Deficits in Attention Deficit/Hyperactivity Disorder and Reading Disability.

Shanahan MA, Pennington BF, Yerys BE, Scott A, Boada R, Willcutt EG, Olson RK, Defries JC.

Department of Psychology, University of Denver, 2155 S. Race St., Denver, Colorado, USA, mshanah2@du.edu.

J Abnorm Child Psychol. 2006 Jul 19; [Epub ahead of print]

The goal of the current study was to test whether deficits in processing speed (PS) may be a shared cognitive risk factor in reading disability (RD) and Attention Deficit/Hyperactivity Disorder (ADHD), which are known to be comorbid. Literature on ADHD and RD suggests that deficits on tasks with a speeded component are seen in both of these disorders individually. The current study examined a wide range of speeded tasks in RD, ADHD, comorbid RD+ADHD, and a control group to test whether RD and ADHD have similar profiles of PS deficits, and whether these deficits are shared by the two disorders. The results suggest that a general PS deficit exists in both clinical groups compared to controls, although children with RD demonstrate greater PS deficits than children with ADHD. Two tests (underadditivity and partial correlations) were conducted to test whether these PS deficits are shared. Since we found that PS deficits were underadditive in the comorbid group and that partialling PS reduced the correlation between RD and ADHD, it appears that PS is a shared cognitive risk factor that may help explain the comorbidity of these two disorders.

2. Improvement of neurobehavioral disorders in children supplemented with magnesium-vitamin B6. I. Attention deficit hyperactivity disorders.

Mousain-Bosc M, Roche M, Polge A, Pradal-Prat D, Rapin J, Bali JP.

Explorations Fonctionnelles du Systeme Nerveux, Centre Hospitalier Universitaire Caremeau, Nimes, France.

Magnes Res. 2006 Mar;19(1):46-52.

Some previous studies have reported the involvement of magnesium (Mg) deficiency in children with ADHD syndrome. In this work, 40 children with clinical symptoms of ADHD were followed clinically and biologically during a magnesium-vitamin B6 (Mg-B6) regimen (6 mg/kg/d Mg, 0.6 mg/kg/d vit-B6) which was set up for at least 8 weeks. Symptoms of ADHD (hyperactivity, hyperemotivity/ aggressiveness, lack of attention at school) were scored (0-4) at different times; in parallel, intraerythrocyte Mg2+ (Erc-Mg) and blood ionized Ca2+ (i-Ca) were measured. Children from the ADHD group showed significantly lower Erc-Mg values than control children (n = 36). In almost all cases of ADHD, Mg-B6 regimen for at least two months significantly modified the clinical symptoms of the disease: namely, hyperactivity and hyperemotivity/aggressiveness were reduced, school attention was improved. In parallel, the Mg-B6 regimen led to a significant increase in Erc-Mg values. When the Mg-B6 treatment was stopped, clinical symptoms of the disease reappeared in few weeks together with a decrease in Erc-Mg values. This study brings additional information about the therapeutic role of a Mg-B6 regimen in children with ADHD symptoms.

3. Decreased use of clonidine following treatment with atomoxetine in children with ADHD.

Johnston JA, Ye W, Van Brunt DL, Pohl G, Sumner CR.

US Outcomes Research, Lilly Research Labaroties, Eli Lilly, Indianapolis, NI.

J Clin Psychopharmacol. 2006 Aug;26(4):389-95.

ABSTRACT:: The objectives of the present study were to examine clonidine use before and after initiation of atomoxetine in a cohort of children with attention deficit/hyperactivity disorder (ADHD). For this purpose, medical and pharmaceutical claims data for patients from 75 managed health care plans across the United States were extracted to identify a cohort of patients aged 18 years and younger at the time of a first atomoxetine prescription. Clonidine users were characterized on the basis of demographics, comorbid conditions, medication use and provider types, and prescribing patterns before and after the index atomoxetine prescription assessed. Subgroups of patients switching from clonidine to atomoxetine were examined and predictors of ongoing or new clonidine use were assessed. Of patients filling a first prescription for atomoxetine, 9.6% received a prescription for clonidine at some time and 4.3% within the previous 2 months. Children identified with a hyperactive component to their ADHD, those with more complex diagnostic histories, and those with tics and sleep disorders were particularly likely to receive clonidine. More than a third of patients (36.5%) with recent clonidine use subsequently discontinued use, with the pattern of clonidine use before and after atomoxetine use being highly dependent upon the pattern of stimulant prescription. Atomoxetine, in some cases, seems to have replaced clonidine in the treatment of patients with ADHD complicated with comorbid psychiatric disorders. In others, atomoxetine has replaced both stimulant and clonidine in patients previously requiring this combination for the control of symptoms or for the management of stimulantrelated adverse effects.

4. Stimulants: Therapeutic Actions in ADHD.

Arnsten AF.

1Department of Neurobiology, Yale University School of Medicine, New Haven, CT, USA.

Neuropsychopharmacology. 2006 Jul 19; [Epub ahead of print]

Stimulants such as methylphenidate and amphetamine are currently the most common treatment for attention deficit hyperactivity disorder (ADHD). For years, it was assumed that stimulants had paradoxical calming effects in ADHD patients, whereas stimulating 'normal' individuals and producing locomotor activation in rats. It is now known that low doses of stimulants focus attention and improve executive function in both normal and ADHD subjects. Furthermore, the seminal work of Kuczenski and Segal showed that low, oral doses of methylphenidate reduce locomotor activity in rats as well. Berridge et al have now shown that these low doses produce marked increases in norepinephrine and dopamine release in the prefrontal cortex, whereas having only subtle effects on subcortical catecholamine release. ihe prefrontal cortex regulates behavior and attention using representational knowledge, and imaging and neuropsychological studies have shown that the prefrontal cortex is weaker in subjects with ADHD. This cortical area is very sensitive to levels of catecholamines: moderate levels engage postsynaptic alpha2A-adrenoceptors and D1 receptors and improve prefrontal regulation of behavior and attention, while high levels impair prefrontal function via alpha1-adrenoceptors and excessive D1 receptor stimulation. Administering low doses of methylphenidate to rats improves the working memory and attentional functions of the prefrontal cortex, while high doses impair working memory and produce a perseverative pattern of errors similar to that seen in patients. The low dose improvement is hiocked by either an alpha2-adrenoceptor or Dl receptor antagonist, suggesting that both norepinephrine and dopamine contribute to the beneficial actions of stimulant medications.Neuropsychopharmacology advance online publication, 19 July 2006; doi:10.1038/sj.npp.1301164

5. Possible confusion between primary hypersomnia and adult attention-deficit/hyperactivity disorder.

Oosterloo M, Lammers GJ, Overeem S, de Noord I, Kooij JJ.

Department of Neurology, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, The Netherlands.

Psychiatry Res. 2006 Jul 17; [Epub ahead of print]

We explored the possibility of diagnostic confusion between hypersomnias of central origin (narcolepsy and idiopathic hypersomnia, IH) and the adult form of attention-deficit/hyperactivity disorder (ADHD). We included 67 patients with narcolepsy, 7 with IH and 61 with ADHD. All patients completed the Epworth Sleepiness Scale and the ADHD Rating Scale. We found that 18.9% of the hypersomnia patients fulfilled the self-reported criteria for ADHD in adulthood, compared with 77% of the ADHD patients. A score >/=12 on the Epworth Sleepiness Scale (usually regarded to indicate excessive daytime sleepiness) was found in 37.7% of the ADHD patients compared 95.9% of the hypersomnia patients. In ADHD patients, inattention scores correlated with the excessive daytime sleepiness score. We conclude that one should be aware of possible diagnostic confusion between narcolepsy or IH and adult ADHD when using self-report questionnaires. The high percentage of symptom overlap found in our study raises questions about possible misdiagnosing of both conditions, comorbidity with sleep problems in adult ADHD, and the validation of the used scales. It remains unclear whether our findings indicate pathophysiological overlap.