Jaap J. van der Meere

Information processing and energetic factors in attention deficit hyperactivity disorder

Currently, children and adolescents with an excess of hyperactive, inattentive, and impulsive behavior are diagnosed as Attention-Deficit/ Hyperactivity Disorder (ADHD; see the Diagnostic and Statistical Manual of Mental Disorders {DSM-IV}, American Psychiatric Association, 1994, and chapter 1, this volume).

Performance variability, impulsivity errors and the impact of incentives as gender-independent endophenotypes for ADHD.

BACKGROUND Attention-deficit hyperactivity disorder (ADHD) is one of the most common and highly heritable child psychiatric disorders. There is strong evidence that children with ADHD show slower and more variable responses in tasks such as Go/Nogo tapping aspects of executive functions like sustained attention and response control which may be modulated by motivational factors and/or state-regulation processes. The aim of this study was (1) to determine if these executive functions may constitute an endophenotype for ADHD; (2) to investigate for the first time whether known modulators of these executive functions may also be familial; and (3) to explore whether gender has an impact on these measures. METHODS Two hundred and five children with ADHD combined type, 173 nonaffected biological siblings and 53 controls with no known family history of ADHD were examined using a Go/Nogo task in the framework of a multi-centre study. Performance-measures and modulating effects of event-rate and incentives were examined. Shared familial effects on these measures were assessed, and the influence of gender was tested. RESULTS Children with ADHD responded more slowly and variably than nonaffected siblings or controls. Nonaffected siblings showed intermediate scores for reaction-time variability, false alarms and omission errors under fast and slow event-rates. A slower event-rate did not lead to reduced performance specific to ADHD. In the incentive condition, mean reaction-times speeded up and became less variable only in children with ADHD and their nonaffected siblings, while accuracy was improved in all groups. Males responded faster, but also committed more false alarms. There were no interactions of group by gender. CONCLUSIONS Reaction-time variability and accuracy parameters could be useful neuropsychological endophenotypes for ADHD. Performance-modulating effects of incentives suggested a familially driven motivational dysfunction which may play an important role on etiologic pathways and treatment approaches for ADHD. The effects of gender were independent of familial effects or ADHD-status, which in turn suggests that the proposed endophenotypes are independent of gender.

Separation of Cognitive Impairments in Attention-Deficit/Hyperactivity Disorder Into 2 Familial Factors

CONTEXT Attention-deficit/hyperactivity disorder (ADHD) is associated with widespread cognitive impairments, but it is not known whether the apparent multiple impairments share etiological roots or separate etiological pathways exist. A better understanding of the etiological pathways is important for the development of targeted interventions and for identification of suitable intermediate phenotypes for molecular genetic investigations. OBJECTIVES To determine, by using a multivariate familial factor analysis approach, whether 1 or more familial factors underlie the slow and variable reaction times, impaired response inhibition, and choice impulsivity associated with ADHD. DESIGN An ADHD and control sibling-pair design. SETTING Belgium, Germany, Ireland, Israel, Spain, Switzerland, and the United Kingdom. PARTICIPANTS A total of 1265 participants, aged 6 to 18 years: 464 probands with ADHD and 456 of their siblings (524 with combined-subtype ADHD), and 345 control participants. MAIN OUTCOME MEASURES Performance on a 4-choice reaction time task, a go/no-go inhibition task, and a choice-delay task. RESULTS The final model consisted of 2 familial factors. The larger factor, reflecting 85% of the familial variance of ADHD, captured 98% to 100% of the familial influences on mean reaction time and reaction time variability. The second, smaller factor, reflecting 13% of the familial variance of ADHD, captured 62% to 82% of the familial influences on commission and omission errors on the go/no-go task. Choice impulsivity was excluded in the final model because of poor fit. CONCLUSIONS The findings suggest the existence of 2 familial pathways to cognitive impairments in ADHD and indicate promising cognitive targets for future molecular genetic investigations. The familial distinction between the 2 cognitive impairments is consistent with recent theoretical models--a developmental model and an arousal-attention model--of 2 separable underlying processes in ADHD. Future research that tests the familial model within a developmental framework may inform developmentally sensitive interventions.

CONTROLLED PROCESSING AND VIGILANCE IN HYPERACTIVITY - TIME WILL TELL

This paper reviews the concept of sustained attention, placing it within a theoretical framework in which deficits of attention are conceived of as deficits of controlled information processing. Two types of deficit of sustained attention are distinguished: perceptual sensitivity and perceptual criterion. These two deficits are linked to a model of human performance that links controlled processes to the energetic pools: arousal and activation. Perceptual sensitivity (d′) deficits are said to reflect arousal deficiencies, especially when observed in the early period of a vigil. Perceptual criterion deficits are associated with the activation pool and the response criterion measure β. Despite clear evidence of perceptual deficiency in the hyperactive children to a greater extent than in the control group, and that performance in d′ declined with time on task, a significant interaction failed to occur between group classification and time on task. Thus, the results failed to support the hypothesis of a sustained attention deficit in hyperactives, since if hyperactives have a sustained attention deficit, both d′ and β should have shown a significantly greater decline in the hyperactive group than in the controls with time on task.

FOCUSED ATTENTION IN PERVASIVELY HYPERACTIVE-CHILDREN

This experiment was designed to investigate the hypothesized distractibility of hyperactive children in a focused attention task. Distractibility was defined in terms of Shiffrin and Schneiders model of focused attention as the ability to ignore irrelevant in favor of relevant information. Failure to inhibit processing of irrelevant information indicates a focused attention deficit. Task efficiency in all children decreased when irrelevant information was presented. The mean reaction time, within-subject variance of reaction time, and error percentage all increased compared with a nondistraction condition. Thus, the demands of focused attention, as formulated in the model, were measured optimally. Since hyperactives and controls did not differ significantly with respect to task efficiency in the distraction condition, a focused attention deficit in hyperactives was not demonstrated. The hyperactives did nevertheless make more errors and their responding was more variable than the controls. However, the difference in error percentages between hyperactives and controls was associated with the difference in IQ. It is speculated that the variable responding in hyperactives is caused by a less optimal state of performance unrelated to distractibility.

Motor control and state regulation in children with ADHD: a cardiac response study.

The goal of the current study was to investigate whether poor motor control in children with Attention-Deficit Hyperactivity Disorder (ADHD) was associated with a state regulation deficit. For this purpose, 28 ADHD and 22 healthy children carried out two Go No-Go tests: one with a fast stimulus presentation rate, and the other with a slow stimulus presentation rate. Groups were compared on RT performance and on specific cardiac measures, reflecting arousal, motor activation/inhibition, and effort allocation. No group difference in the arousal measure (mean heart rate) was found. Further, groups did not differ with respect to response inhibition: in both the fast and slow condition, ADHD children made comparable numbers of errors of commission to the control group, and the groups did not differ with respect to the heart rate deceleration after the onset of the No-Go signal, reflecting motor inhibition. Group differences were found with respect to motor activation and effort allocation in the condition with a slow presentation rate. In this condition: (1) ADHD children reacted more slowly to Go signals than control children, suggesting poor motor activation; (2) the heart rate deceleration before the onset of Go signals, which is believed to reflect motor preparation, was less pronounced in the ADHD children; (3) after Go signals, where a response was given, the cardiac shift from deceleration to acceleration, indicating response initiation, was delayed in ADHD children; and (4) ADHD children had greater heart rate variability (0.10 Hz component) than the control group, indicating that less effort was allocated. No group differences in motor activation and effort allocation were found in the condition with a fast presentation rate of stimuli. We conclude, therefore, that a slow presentation rate of stimuli brings the ADHD child in a non-optimal activation state.

What happens after a hyperactive child commits an error

Children with a diagnosis of attention deficit disorder with hyperactivity can correct errors, just as controls can. They differ from controls in how they adjust the speed of processing on a trial after they have committed an error. Controls are fast in responding after an error when cognitive load is small. When cognitive load is high, however, they take considerable time to ensure, after an error has occurred, that a correct response is given. After an error has been committed, hyperactive children, irrespective of the demands of load, have no response adjustment and maintain a constant rate of processing.

Why cognitive performance in ADHD may not reveal true potential: Findings from a large population-based sample

Focusing on symptoms of attention deficit hyperactivity disorder (ADHD) in a sample obtained from the general population, we aimed to investigate the effects of incentives and event rate on reaction time (RT) performance and response inhibition. We assessed 1156 children, at a mean age of 8 years, on their performance on an inhibition task and a RT task under different experimental conditions that manipulated event rate and incentives. Children with high ADHD (ADHD-H) symptoms showed cognitive performance deficits only under some of the experimental conditions compared to a control group. The fast-incentive condition of the RT task succeeded in normalizing the RT variability, as well as the slow overall speed, in the ADHD-H group. Analyses of ADHD symptom scores as a quantitative trait in the total sample were overall consistent with these findings. The findings suggest that at least some cognitive performance deficits in children with high ADHD symptoms do not reflect stable cognitive deficits. The degree to which cognitive impairments in ADHD can be modulated by energetic or motivational factors has important implications for clinical and educational interventions.

A Divided Attention Experiment with Pervasively Hyperactive Children.

Task performance of 12 pervasive hyperactives and controls was studied in a divided attention reaction time experiment. The two groups differed with respect to task efficiency. The hyperactives were slower than controls, had more variable reaction times, and made more frequent errors. Task inefficiency could not be explained by a deficiency in divided attention or impulsive responding in the hyperactive group. Further, the observed differences in IQ between the groups could not account for the differential performance finding. It is concluded that input and/or output processes, probably in combination with energetical factors, might be disturbed in hyperactive children.

The heritability of depressive symptoms: multiple informants and multiple measures

BACKGROUND Earlier research suggests large rater differences in heritability estimates of childrens depressive symptoms in the context of significant age and sex-limitation effects. METHODS With data from an ongoing, population-based twin-family study, we estimated genetic and environmental influences on childrens depression with models allowing for sex-specific effects. Our assessments of twins included self-reports and ratings made by their classmate peers, their parents and their teachers, allowing estimates of genetic and environmental effects with data from different informants. Model-fitting used maximum likelihood estimation of log-transformed data from a sample of 1,366 11- and 12-year-old twin pairs. RESULTS Estimates of additive genetic effects were significant for both boys and girls across all four informants, and, standardized to reflect the percentage of phenotypic variance accounted for, those estimates ranged from .28 to .71. Significant effects from common environmental sources were found in ratings of teachers and parents, where, typically, one individual rated both co-twins, but neither in peer nominations nor self-ratings. The correlation of teacher and parent ratings was modest, and bivariate model-fitting found no correlation in either genetic or shared environmental effects between teacher and parental ratings. At this young age, sex-limitation effects were found only in teacher ratings, where genetic effects were greater in girls than in boys. CONCLUSIONS Results underscore the utility of using multiple informants to measure childrens behavior and provide a foundation for follow-up of these twins in later adolescence.