Hilde M. Geurts

How specific is a deficit of executive functioning for Attention-Deficit/Hyperactivity Disorder?

A selective review of research in the executive functioning (EF) is given for attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), conduct disorder (CD), higher functioning autism (HFA) and Tourette syndrome. The review is restricted due to changes in the classification of the disorder in recent years and secondly the heterogeneity of EF is restricted to five key areas of concern, inhibition, set shifting, working memory, planning, and fluency. The review makes clear that there are strong differences between child psychopathological groups and controls on these EFs. However, future research will be needed to identify an EF deficit or profile, which is specific for these disorders.

Shared heritability of attention-deficit/hyperactivity disorder and autism spectrum disorder

Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are both highly heritable neurodevelopmental disorders. Evidence indicates both disorders co-occur with a high frequency, in 20–50% of children with ADHD meeting criteria for ASD and in 30-80% of ASD children meeting criteria for ADHD. This review will provide an overview on all available studies [family based, twin, candidate gene, linkage, and genome wide association (GWA) studies] shedding light on the role of shared genetic underpinnings of ADHD and ASD. It is concluded that family and twin studies do provide support for the hypothesis that ADHD and ASD originate from partly similar familial/genetic factors. Only a few candidate gene studies, linkage studies and GWA studies have specifically addressed this co-occurrence, pinpointing to some promising pleiotropic genes, loci and single nucleotide polymorphisms (SNPs), but the research field is in urgent need for better designed and powered studies to tackle this complex issue. We propose that future studies examining shared familial etiological factors for ADHD and ASD use a family-based design in which the same phenotypic (ADHD and ASD), candidate endophenotypic, and environmental measurements are obtained from all family members. Multivariate multi-level models are probably best suited for the statistical analysis.

The top and the bottom of ADHD: A neuropsychological perspective

Five models of attention deficit/hyperactivity disorder (ADHD) are reviewed. It is proposed that the cognitive-energetic model provides a reasonably comprehensive account of ADHD by incorporating the features of both the inhibition and delay aversion models. It is suggested that ADHD can only be accounted for by an analysis at three levels: top-down control, specific cognitive processes and energetic factors. It is argued that a refined and conceptually comprehensive neuropsychological battery is needed to advance research in ADHD. A widely distributed neural network involving frontal, basal ganglia, limbic and cerebellar loci seem implicated in ADHD.

Brain connectivity and high functioning autism: a promising path of research that needs refined models, methodological convergence, and stronger behavioral links.

Here we review findings from studies investigating functional and structural brain connectivity in high functioning individuals with autism spectrum disorders (ASDs). The dominant theory regarding brain connectivity in people with ASD is that there is long distance under-connectivity and local over-connectivity of the frontal cortex. Consistent with this theory, long-range cortico-cortical functional and structural connectivity appears to be weaker in people with ASD than in controls. However, in contrast to the theory, there is less evidence for local over-connectivity of the frontal cortex. Moreover, some patterns of abnormal functional connectivity in ASD are not captured by current theoretical models. Taken together, empirical findings measuring different forms of connectivity demonstrate complex patterns of abnormal connectivity in people with ASD. The frequently suggested pattern of long-range under-connectivity and local over-connectivity is in need of refinement.

The paradox of cognitive flexibility in autism

We present an overview of current literature addressing cognitive flexibility in autism spectrum disorders. Based on recent studies at multiple sites, using diverse methods and participants of different autism subtypes, ages and cognitive levels, no consistent evidence for cognitive flexibility deficits was found. Researchers and clinicians assume that inflexible everyday behaviors in autism are directly related to cognitive flexibility deficits as assessed by clinical and experimental measures. However, there is a large gap between the day-to-day behavioral flexibility and that measured with these cognitive flexibility tasks. To advance the field, experimental measures must evolve to reflect mechanistic models of flexibility deficits. Moreover, ecologically valid measures are required to be able to resolve the paradox between cognitive and behavioral inflexibility.

A review on cognitive and brain endophenotypes that may be common in autism spectrum disorder and attention-deficit/hyperactivity disorder and facilitate the search for pleiotropic genes

We propose to bring together the hitherto rather separate research fields of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), and argue that by contrasting and combining findings of the endophenotypes of ASD and ADHD new insights can be gained into the etiology and pathophysiology of these two disorders. Given the highly heritable nature of both disorders, studies of the genes explaining the shared origins of the two neurodevelopmental disorders seem particularly called for. Instead of the clinical diagnosis, using neurocognitive measures as (endo)phenotypes that index genetic liability appears a powerful tool in gene finding. We, therefore, extensively reviewed the literature and not only included research wherein ASD and ADHD were compared within a single study, but extended our search also to the separate lines of cognitive neuroscience research. We discuss which cognitive and brain measures will be useful in future genetic studies targeting pleiotropic genes for ASD and ADHD. By specifying the most promising endophenotypic measures we chart the future course for endophenotypic research in ASD and ADHD. We also discuss the various models that may explain the frequent co-occurrence of ASD and ADHD.

Language Profiles in ASD, SLI, and ADHD

Developmental disorders might differ in their language profiles when using parent reports. The first study indicated that school aged children with ASD have similar language profiles as children with ADHD. Both groups had relatively more difficulties with pragmatics than with structural language aspects. The second study indicated that both preschoolers with ASD and those with SLI show the opposite pattern, thus having relatively more difficulties with structural language aspects than with pragmatics. Finally, an increase in the presence of ADHD characteristics of impulsivity in these preschoolers is associated with an increase in language difficulties, while there is no such relation with inattention. It seems useful to evaluate the communication abilities of children regularly in the course of development and take ADHD characteristics into account. Finally recommendations on clinical use of the Children’s Communication Checklist-2 (CCC-2, Bishop 2003) are discussed.

Intra-Individual Variability in ADHD, Autism Spectrum Disorders and Tourette's Syndrome.

The potential for response variability to serve as an endophenotype for attention deficit hyperactivity disorders (ADHD) rests, in part, upon the development of reliable and valid methods to decompose variability. This study investigated the specificity of intra-individual variability (IIV) in 53 children with ADHD by comparing them with 25 children with high functioning autism (HFA), 32 children with autism spectrum disorders (ASD), who also were comorbid for ADHD (ASD+ADHD), 21 children with Tourettes syndrome (TS), and 85 typically developing controls (TD). In order to decompose the variability of the reaction times, we applied three distinct techniques: ex-Gaussian modeling, intra-individual variability analysis, and spectral analysis. Our data revealed that children with HFA and children with ASD+ADHD exhibited substantial IIV compared with ADHD and TD children. We argue that: (1) all three methods lead to a single consistent conclusion; (2) careful documentation of the analytic steps used in spectral analysis is mandatory for comparison between studies; (3) the presence of comorbidities may constitute an important factor in the observed response variability in previous studies of ADHD.

Executive functioning in children with autism and Tourette syndrome.

The main aims of this study were to investigate if children with high-functioning autism (HFA) and children with Tourette syndrome (TS) can be differentiated in their executive functioning (EF) profile compared to normal controls (NCs) and compared to each other and to investigate whether children with HFA or children with TS and a comorbid group of children with both disorders are distinct conditions in terms of EF, Four groups of children participated in this study: HFA, TS, comorbid HFA + TS, and a NC group. All children were in the age range of 6 to 13 years. The groups were compared on five major domains of EF: inhibition, visual working memory, planning, cognitive flexibility, and verbal fluency. Children with HFA scored lower than NC children on all the EFs measured. Children with TS and NC children showed the same EF profile. The HFA group scored lower than the TS group for inhibition of a prepotent response and cognitive flexibility. Children with HFA performed poorer than children with comorbid HFA + TS on all functions, with the exception of inhibiting an ongoing response, interference control, and verbal fluency. Children with TS and children with comorbid HFA + TS could not be differentiated from one another in terms of EF. This study indicates that EF deficits are highly characteristic of children with HFA in comparison to children with TS and NC. The results suggest that for the comparison between HFA and TS groups, it is important to take into account comorbidity. A reevaluation of the EF hypothesis in children with TS is suggested.

Low basal salivary cortisol is associated with teacher-reported symptoms of conduct disorder

Cortisol has been implicated in psychobiological explanations of antisocial behavior. This study measured basal salivary cortisol in a sample of 25 children (age range 6 to 12 years) selected to vary in levels of antisocial behavior. Regression analyses were used to predict cortisol concentrations from parent- and teacher-reported symptoms. Parent-reported symptoms did not predict basal cortisol. Teacher-reported conduct disorder (CD) symptoms explained 38% of the variance in the cortisol concentrations, with high symptom severity associated with low cortisol. When a distinction was made between aggressive and non-aggressive CD symptoms, aggressive CD symptoms were more clearly related to low cortisol than non-aggressive CD symptoms. In contrast to previous research, no evidence was found for a mediating role of anxiety symptoms in the relationship between CD and cortisol. The results support biologically based models of antisocial behavior in children that involve reduced autonomic activity.