Stimulant drug effects on attention deficit/hyperactivity disorder: a review of the effects of age and sex of patients

Objective: As dopamine functioning varies by sex and age it might be expected that the effects of methylphenidate or amfetamine, the psychostimulants used for the treatment of Attention Deficit /Hyperactivity Disorder (ADHD), will also be moderated by these factors. Here we review the published literature on whether stimulant effects in ADHD symptoms vary by age and sex. Method: We searched for studies published from 1989 until October 2009. Databases searched included U. S. National Library of Medicine (PubMed), Medline, EMBASE, PsycINFO and ISI Web of Knowledge. Firstly, we reviewed the effects of stimulant drugs on male and female patients and also patients of pre-school, middle childhood, adolescence and adulthood. Secondly, we reviewed studies that directly tested the moderating effect of age and sex on stimulant treatment outcome. Results: Randomised controlled trials confirm that stimulant medication is efficacious for, and well tolerated by, males and females and patients across the age range; although preschoolers appear to have a less beneficial response and more side effects. Few studies that specifically examined the moderating effect of age and/or sex were identified. For sex, no effects on overall response were found, although one study reported that sex moderated methylphenidate pharmacodynamics. The few effects found for age were small and inconsistent. Conclusions: The available evidence suggests that stimulant medication, when appropriately administered, has efficacy as an ADHD treatment for both sexes and across all ages. There are currently too few published papers examining the effects of sex and age to draw strong conclusions about moderation. Further studies of the pharmacodynamics of stimulants on symptoms measured using objective tests in the laboratory or classroom setting need to be undertaken

No evidence for inhibitory deficits or altered reward processing in ADHD: data from a new integrated incentive delay go/no-go task

Objective: Cognitive and motivational factors differentially affect individuals with mental health problems such as ADHD. Here we introduce a new task to disentangle the relative contribution of inhibitory control and reward anticipation on task performance in children with ADHD and/or autism spectrum disorders (ASD). Method: Typically developing children, children with ADHD, ASD, or both disorders worked during separate sessions for monetary or social rewards in go/no-go tasks with varying inhibitory load levels. Participants also completed a monetary temporal discounting (TD) task. Results: As predicted, task performance was sensitive to both the effects of anticipated reward amount and inhibitory load. Reward amount had different effects depending on inhibitory load level. TD correlated with inhibitory control in the ADHD group. Conclusion: The integration of the monetary incentive delay and go/no-go paradigms was successful. Surprisingly, there was no evidence of inhibitory control deficits or altered reward anticipation in the clinical groups

Different effects of adding white noise on cognitive performance of sub-, normal and super-attentive school children

Objectives: Noise often has detrimental effects on performance. However, because of the phenomenon of stochastic resonance (SR), auditory white noise (WN) can alter the "signal to noise'' ratio and improve performance. The Moderate Brain Arousal (MBA) model postulates different levels of internal "neural noise'' in individuals with different attentional capacities. This in turn determines the particular WN level most beneficial in each individual case-with one level of WN facilitating poor attenders but hindering super-attentive children. The objective of the present study is to find out if added WN affects cognitive performance differently in children that differ in attention ability. Methods: Participants were teacher-rated super-(N = 25); normal-(N = 29) and sub-attentive (N = 36) children (aged 8 to 10 years). Two non-executive function (EF) tasks (a verbal episodic recall task and a delayed verbal recognition task) and two EF tasks (a visuo-spatial working memory test and a Go-NoGo task) were performed under three WN levels. The non-WN condition was only used to control for potential differences in background noise in the group testing situations. Results: There were different effects of WN on performance in the three groups-adding moderate WN worsened the performance of super-attentive children for both task types and improved EF performance in sub-attentive children. The normal-attentive children's performance was unaffected by WN exposure. The shift from moderate to high levels of WN had little further effect on performance in any group. Significance: The predicted differential effect of WN on performance was confirmed. However, the failure to find evidence for an inverted U function challenges current theories. Alternative explanations are discussed. We propose that WN therapy should be further investigated as a possible non-pharmacological treatment for inattention

Altered intrinsic organisation of brain networks implicated in attentional processes in adult attention-deficit/hyperactivity disorder: a resting state study of attention, default mode and salience network connectivity

Deficits in task-related attentional engagement in attention-deficit/hyperactivity disorder (ADHD) have been hypothesized to be due to altered interrelationships between attention, default mode and salience networks. We examined the intrinsic connectivity during rest within and between these networks. Six minutes resting state scans were obtained. Using a network-based approach, connectivity within and between the dorsal and ventral attention, the default mode and the salience networks was compared between the ADHD and control group. The ADHD group displayed hyperconnectivity between the two attention networks and within the default mode and ventral attention network. The salience network was hypoconnected to the dorsal attention network. There were trends towards hyperconnectivity within the dorsal attention network and between the salience and ventral attention network in ADHD. Connectivity within and between other networks was unrelated to ADHD. Our findings highlight the altered connectivity within and between attention networks, and between them and the salience network in ADHD. One hypothesis to be tested in future studies is that individuals with ADHD are affected by an imbalance between ventral and dorsal attention systems with the former playing a dominant role during task engagement making individuals with ADHD highly susceptible to distraction by salient task-irrelevant stimuli

ADHD-associated risk taking is linked to exaggerated views of the benefits of positive outcomes

Attention deficit and hyperactivity disorder (ADHD) is often assumed to be associated with increased engagement in risk-taking behaviors. The current study sought to understand the mental processes underlying this association using a theory-driven behavioral economics perspective. Psychological risk-return models suggest that risk and benefit are inherently subjective, and risk taking is best understood as the interplay between cognitions and motivations regarding the benefits and risks of alternatives. A sample of 244 adults was assessed for ADHD symptoms. The likelihood of engagement in a range of risky behaviors (e.g., driving without wearing a seat belt), the magnitude of perceived benefit and risk ascribed to these behaviors, and benefit and risk attitudes of each participant were extracted from the Domain Specific Risk Taking (DOSPERT) scales. ADHD symptoms were correlated with more risky behaviors and perception of greater benefits from engaging in these behaviors, but were not correlated with risk perception. Mediation analysis revealed that the association between ADHD symptoms and engagement in risk taking was mediated by perceived benefits. These findings highlight the idea that people with high level ADHD symptoms tend to engage in risky behaviors because they find such behavior particularly appealing, rather than because they seek risk per se

Does comorbid anxiety counteract emotion recognition deficits in conduct disorder?

Background: Previous research has reported altered emotion recognition in both conduct disorder (CD) and anxiety disorders (ADs) - but these effects appear to be of different kinds. Adolescents with CD often show a generalised pattern of deficits, while those with ADs show hypersensitivity to specific negative emotions. Although these conditions often cooccur, little is known regarding emotion recognition performance in comorbid CD+ADs. Here, we test the hypothesis that in the comorbid case, anxiety-related emotion hypersensitivity counteracts the emotion recognition deficits typically observed in CD. Method: We compared facial emotion recognition across four groups of adolescents aged 12-18 years: those with CD alone (n = 28), ADs alone (n = 23), cooccurring CD+ADs (n = 20) and typically developing controls (n = 28). The emotion recognition task we used systematically manipulated the emotional intensity of facial expressions as well as fixation location (eye, nose or mouth region). Results: Conduct disorder was associated with a generalised impairment in emotion recognition; however, this may have been modulated by group differences in IQ. AD was associated with increased sensitivity to low-intensity happiness, disgust and sadness. In general, the comorbid CD+ADs group performed similarly to typically developing controls. Conclusions: Although CD alone was associated with emotion recognition impairments, ADs and comorbid CD+ADs were associated with normal or enhanced emotion recognition performance. The presence of comorbid ADs appeared to counteract the effects of CD, suggesting a potentially protective role, although future research should examine the contribution of IQ and gender to these effects

Empirical tests of natural selection-based evolutionary accounts of ADHD : a systematic review

Objective ADHD is a prevalent and highly heritable mental disorder associated with significant impairment, morbidity and increased rates of mortality. This combination of high prevalence and high morbidity/mortality seen in ADHD and other mental disorders presents a challenge to natural selection-based models of human evolution. Several hypotheses have been proposed in an attempt to resolve this apparent paradox. The aim of this study was to review the evidence for these hypotheses. Methods We conducted a systematic review of the literature on empirical investigations of natural selection-based evolutionary accounts for ADHD in adherence with the PRISMA guideline. The PubMed, Embase, and PsycINFO databases were screened for relevant publications, by combining search terms covering evolution/selection with search terms covering ADHD. Results The search identified 790 records. Of these, 15 full-text articles were assessed for eligibility, and three were included in the review. Two of these reported on the evolution of the seven-repeat allele of the ADHD-associated dopamine receptor D4 gene, and one reported on the results of a simulation study of the effect of suggested ADHD-traits on group survival. The authors of the three studies interpreted their findings as favouring the notion that ADHD-traits may have been associated with increased fitness during human evolution. However, we argue that none of the three studies really tap into the core symptoms of ADHD, and that their conclusions therefore lack validity for the disorder. Conclusions This review indicates that the natural selection-based accounts of ADHD have not been subjected to empirical test and therefore remain hypothetical

Beyond the dual pathway model : evidence for the dissociation of timing, inhibitory, and delay-related impairments in attention-deficit/hyperactivity disorder

Objective: The dual pathway model explains neuro-psychological heterogeneity in Attention Deficit/Hyperactivity Disorder (ADHD) in terms of dissociable cognitive and motivational deficits each affecting some but not other patients. We explore whether deficits in temporal processing might constitute a third dissociable neuropsychological component of ADHD. Method: Nine tasks designed to tap three domains (inhibitory control, delay aversion and temporal processing) were administered to ADHD probands (n=71; ages 6 to 17 years), their siblings (n=71; 65 unaffected by ADHD) and a group of non-ADHD controls (n=50). IQ and working memory were measured. Results: Temporal processing, inhibitory control and delay-related deficits represented independent neuropsychological components. ADHD children differed from controls on all factors. For ADHD patients, the co-occurrence of inhibitory, temporal processing and delay-related deficits was no greater than expected by chance with substantial groups of patients showing only one problem. Domain-specific patterns of familial co-segregation provided evidence for the validity of neuropsychological subgroupings. Conclusion: The current results illustrate the neuropsychological heterogeneity in ADHD and initial support for a triple pathway model. The findings need to be replicated in larger samples