Rehearsal Strategies and Recall Performance in Boys With and Without Attention Deficit Hyperactivity Disorder

Examined differences in recall performance and rehearsal strategiesin boys with Attention Deficit Hyperactivity Disorder (ADHD)and comparison boys using an overt rehearsal procedure on aself-paced, multitrial, free recall task. Boys with ADHD recalledfewer words, tended to spend less time rehearsing the items,and spent less time attempting to retrieve them. Although theydid not rehearse items less frequently than comparison boys,they relied almost exclusively on repetition of single items.In contrast, comparison boys showed some evidence of using active,multi-item (cumulative) rehearsal. Despite their failure touse cumulative rehearsal, boys with ADHD identified it as moreeffective than single-item rehearsal in a subsequent forced-choiceassessment of strategy knowledge.     

Methylphenidate improves diminished error and feedback sensitivity in ADHD: An Evoked Heart Rate analysis

Attention Deficit Hyperactivity Disorder (ADHD) is a developmental disorder that has previously been related to a decreased sensitivity to errors and feedback. Supplementary to the traditional performance measures, this study uses autonomic measures to study this decreased sensitivity in ADHD and the modulating effects of medication. Children with ADHD, on and off Methylphenidate (Mph), and typically developing (TD) children performed a selective attention task with three feedback conditions: reward, punishment and no feedback. Evoked Heart Rate (EHR) responses were computed for correct and error trials. All groups performed more efficiently with performance feedback than without. EHR analyses, however, showed that enhanced EHR decelerations on error trials seen in TD children, were absent in the medication-free ADHD group for all feedback conditions. The Mph-treated ADHD group showed ‘normalised’ EHR decelerations to errors and error feedback, depending on the feedback condition. This study provides further evidence for a decreased physiological responsiveness to errors and error feedback in children with ADHD and for a modulating effect of Mph.     

Sleep in adults with attention deficit hyperactivity disorder (ADHD) before and during treatment with methylphenidate: a controlled polysomnographic study

STUDY OBJECTIVES: Sleep problems are frequently associated with childhood ADHD, as indicated by numerous polysomnographic investigations showing increased nocturnal movements, reduced sleep efficiency, and decreased percentage of REM sleep (although findings are not consistent over all studies). Data on objective and subjective sleep parameters in adults with ADHD are sparse, and to date the impact of stimulants, the most widely used pharmacological treatment for ADHD, on sleep in adults with ADHD has not been examined. Thus the objectives of our study were to assess objective and subjective sleep parameters in adults with ADHD and the impact of stimulant medication on sleep. DESIGN: Two-group comparison and open-label therapy study. PARTICIPANTS: We enrolled 34 nonmedicated patients with ADHD, of whom 24 were without current comorbid psychiatric disorders, and 34 sex- and gender-matched control subjects without current psychiatric disorders or psychotropic medication. INTERVENTIONS: Ten patients were treated with methylphenidate over > or =26 days with a mean daily dose of 36.7 +/- 11.2 mg. MEASUREMENTS: Polysomnographic recording over 2 consecutive nights as well as assessments of subjective sleep parameters were performed in all patients and controls before treatment and reassessed in those patients receiving methylphenidate. RESULTS: Compared to controls untreated patients showed increased nocturnal activity, reduced sleep efficiency, more nocturnal awakenings and reduced percentage of REM sleep. Treatment with methylphenidate resulted in increased sleep efficiency as well as a subjective feeling of improved restorative value of sleep. CONCLUSIONS: Sleep problems in patients with ADHD continue from childhood to adulthood, with similar objective sleep characteristics in adults and children with ADHD. Medication with methylphenidate appears to have beneficial effects on sleep parameters in adults with ADHD.     

Angiogenic,neurotrophic, and inflammatory system SNPs moderate the association between birth weight and ADHD symptom severity

Low birth weight is associated with increased risk for Attention‐Deficit/Hyperactivity Disorder (ADHD); however, the etiological underpinnings of this relationship remain unclear. This study investigated if genetic variants in angiogenic, dopaminergic, neurotrophic, kynurenine, and cytokine‐related biological pathways moderate the relationship between birth weight and ADHD symptom severity. A total of 398 youth from two multi‐site, family‐based studies of ADHD were included in the analysis. The sample consisted of 360 ADHD probands, 21 affected siblings, and 17 unaffected siblings. A set of 164 SNPs from 31 candidate genes, representing five biological pathways, were included in our analyses. Birth weight and gestational age data were collected from a state birth registry, medical records, and parent report. Generalized Estimating Equations tested for main effects and interactions between individual SNPs and birth weight centile in predicting ADHD symptom severity. SNPs within neurotrophic (NTRK3) and cytokine genes (CNTFR) were associated with ADHD inattentive symptom severity. There was no main effect of birth weight centile on ADHD symptom severity. SNPs within angiogenic (NRP1 & NRP2), neurotrophic (NTRK1 & NTRK3), cytokine (IL16 & S100B), and kynurenine (CCBL1 & CCBL2) genes moderate the association between birth weight centile and ADHD symptom severity. The SNP main effects and SNP × birth weight centile interactions remained significant after adjusting for multiple testing. Genetic variability in angiogenic, neurotrophic, and inflammatory systems may moderate the association between restricted prenatal growth, a proxy for an adverse prenatal environment, and risk to develop ADHD. © 2014 Wiley Periodicals, Inc.     

Differential behavioral responses of the spontaneously hypertensive rat to methylphenidate and methamphetamine: lack of a rewarding effect of repeated methylphenidate treatment

Several questions remain unanswered concerning the effects of long-term methylphenidate treatment in individuals with attention-deficit/hyperactivity disorder (ADHD). It has been speculated that repeated methylphenidate treatment may facilitate abuse of the drug or psychological dependence. In the present study, we conducted conditioned place preference (CPP) tests to investigate whether the repeated treatment of methylphenidate results to greater "liking" of the drug. We compared the effect of methylphenidate with that of methamphetamine, a drug with high abuse and dependence liability; also used as a treatment of ADHD. Prior to CPP tests, adolescent spontaneously hypertensive rats (SHR) (putative rodent model of ADHD) and Wistar rats (strain used to represent the "normal" heterogeneous population) were administered intraperitoneally with methylphenidate (1.25, 5 and 20 mg/kg) or methamphetamine (1.25 and 5 mg/kg) for 14 days in their home cages. CPP tests were commenced and rats were conditioned with the two stimulants at the doses stated. We found that (1) repeated administration of methylphenidate and methamphetamine was rewarding in Wistar rats (2) stimulant-treated SHR showed CPP only to methamphetamine but not to methylphenidate. The observation that Wistar rats, but not SHR showed CPP to methylphenidate indicates vulnerability of "normal" individuals to methylphenidate abuse and dependence following repeated exposure or administration of the drug. The findings in SHR suggest the safety of methylphenidate as an ADHD intervention insofar as its behavioral effects are compared with those of methamphetamine, and to the extent that the SHR appropriately models ADHD in humans.     

Topographic Study of Auditory Event-Related Potentials in Normal Boys and Boys with Attention Deficit Disorder with Hyperactivity

Auditory evoked potentials were recorded from 19 electrode sites in 20 children with Attention Deficit Disorder with Hyperactivity and 20 normal subjects in a two-choice discrimination task. N2 and Nd were found to be significantly smaller in subjects with Attention Deficit Disorder with Hyperactivity. The N2 abnormalities are discussed in relationship to the mismatch negativity component of the orienting response, poor discrimination of salient stimuli, neurotransmitter deficiency, and theories of “arousal.’Nd findings are related to findings from studies of cerebral blood flow in children diagnosed as having Attention Deficit Disorder with Hyperactivity. These results suggest a problem with both automatic (not under conscious control) and controlled (under voluntary control) processing in children with Attention Deficit Disorder with Hyperactivity.     

No association between TPH2 gene polymorphisms and ADHD in a UK sample

Tryptophan Hydroxylase 2 (TPH2) is the rate-limiting enzyme in the biosynthesis of serotonin which is exclusively expressed in the brain. Recent molecular studies reported significant association between markers mapped to TPH2 and psychiatric conditions including ADHD. We have examined four single nucleotide polymorphisms (SNPs) two of which (rs1843809, rs1386493) were reported to associate with ADHD in an Irish ADHD sample. Transmission disequilibrium analysis revealed no significant association between any of these markers and ADHD. Dividing by the sex of the transmitting parent has also failed to replicate the previously reported paternal over-transmission of the associated alleles to ADHD probands. A larger sample size will be required to clarify if TPH2 alleles are or are not associated with ADHD.     

Using freelisting to understand shared decision making in ADHD: Parents’ and pediatricians’ perspectives

Objective

To compare and contrast notions of ADHD among pediatricians and parents of affected children to understand the perspectives they bring to shared decision making (SDM).

Methods

In this freelisting study, 60 parents of children with ADHD and 30 primary care pediatricians listed words reflecting their understanding of (1) Attention Deficit Hyperactivity Disorder (ADHD), (2) getting/offering help for ADHD, (3) talking to doctors/families about ADHD, and (4) “mental health.” Smith's salience score established terms that were salient and cultural consensus analysis identified variation within subgroups of participants.

Results

Parents’ terms reflected ADHD's effects on the child and family, while clinicians often mentioned school. Lists suggested differing needs and goals for clinicians and subgroups of parents in SDM: “time” for clinicians, “learning” and “understanding” for non-college educated parents, and “comfort” and “relief” for college educated parents. Neither parents nor clinicians framed ADHD in the same way as “mental health.”

Conclusion

Parents and clinicians, who conceptualize ADHD differently, should negotiate a shared understanding of ADHD as a basis for SDM. Treatment discussions should be tailored to encompass families’ varied emotional and educational needs.

Practice implications

Fostering SDM in primary care is consonant with notions of ADHD as distinct from mental health.     

Negative effects of chronic oral chlorpromazine and olanzapine treatment on the performance of tasks designed to assess spatial learning and working memory in rats

Learning potential and memory capacity are factors that strongly predict the level of rehabilitation and the long-term functional outcome in patients with schizophrenia. Unfortunately, however, the effects of antipsychotic drugs (i.e. the primary treatments for schizophrenia) on these components of cognition are unclear, particularly when they are administered chronically (i.e. a standard clinical practice). In this rodent study we evaluated the effects of different time periods (ranging from 2 weeks to 6 months) of oral treatment with the first generation antipsychotic chlorpromazine (10.0 mg/kg/day), or the second generation antipsychotic olanzapine (10.0 mg/kg/day) on the repeated acquisition of a water maze task (i.e. a method of assessing spatial learning potential in a repeated testing format). We assessed locomotor function (in an open field) and employed a radial arm maze (RAM) task to assess antipsychotic effects (5.0 and 10.0 mg/kg/day doses) on spatial working memory during the treatment period between 15 days and 2 months. Finally, we conducted experiments using liquid chromatography/tandem mass spectrometry (LC-MS/MS) to evaluate the therapeutic relevance of our method of drug delivery (oral administration in drinking water). In the water maze experiments, both antipsychotics were associated with impairments in acquisition in the earlier test sessions that could eventually be overcome with repeated testing while olanzapine also impaired retention in probe trials. Both antipsychotics were also associated with impairments in delayed non-match-to-position trials in the RAM and some impairments of motor function (especially in the case of olanzapine) as indicated by slightly reduced swim speeds in the water maze and decreased activity in some components of the open field assessment. Finally, LC-MS/MS studies indicated that the method of antipsychotic administration generated clinically relevant plasma levels in the rat. These animal data indicate that chronic oral treatment with chlorpromazine or olanzapine can impair the performance of tasks designed to assess specific components of cognition that are affected in schizophrenia.