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Biomedical subjects

Erik G Willcutt

Publications and source records attributed to Erik G Willcutt.

14 recordsLinked to original sources

Processing speed deficits in attention deficit/hyperactivity disorder and reading disability.

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.

Adolescent↗

Causal heterogeneity in attention-deficit/hyperactivity disorder: do we need neuropsychologically impaired subtypes?

Before assigning full etiologic validity to a psycopathologic disorder, disease theory suggests that a causal dysfunction in a mechanism within the affect individuals must be identified. Existing theories on attention-deficit/hyperactivity disorder (ADHD) suggest such dysfunctions in cognitive, neuropsychological, or motivational processes in the child. To date, researchers have tested these theories by comparing groups with DSM-defined ADHD to children without ADHD. Using executive functioning as an illustration of an issue that exists across all such theories, this article describes substantial overlaps in the group performance data. Thus only a subgroup may have executive deficits. Noted are other supportive data suggesting multiple pathways to ADHD. The article explores implications and recommends that future theory and research give more consideration to the probability that only a subset of behaviorally defined children will have a deficit in a given neurocognitive mechanism believed to contribute to the disorder. Creation of a provisional set of criteria in DSM-V for defining an "executive deficit type" could stimulate research to validate the first etiologic subtype of ADHD and spur the development of more sophisticated causal models, which in the longer term may give clinicians ways to target and tailor treatments.

Attention Deficit Disorder with Hyperactivity↗

Validity of the executive function theory of attention-deficit/hyperactivity disorder: a meta-analytic review.

One of the most prominent neuropsychologic theories of attention-deficit/hyperactivity disorder (ADHD) suggests that its symptoms arise from a primary deficit in executive functions (EF), defined as neurocognitive processes that maintain an appropriate problem-solving set to attain a later goal. To examine the validity of the EF theory, we conducted a meta-analysis of 83 studies that administered EF measures to groups with ADHD (total N = 3734) and without ADHD (N = 2969). Groups with ADHD exhibited significant impairment on all EF tasks. Effect sizes for all measures fell in the medium range (.46-.69), but the strongest and most consistent effects were obtained on measures of response inhibition, vigilance, working memory, and planning. Weaknesses in EF were significant in both clinic-referred and community samples and were not explained by group differences in intelligence, academic achievement, or symptoms of other disorders. ADHD is associated with significant weaknesses in several key EF domains. However, moderate effect sizes and lack of universality of EF deficits among individuals with ADHD suggest that EF weaknesses are neither necessary nor sufficient to cause all cases of ADHD. Difficulties with EF appear to be one important component of the complex neuropsychology of ADHD.

Algorithms↗

Attention-deficit/hyperactivity disorder endophenotypes.

Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable disorder with a multifactorial pattern of inheritance. For complex conditions such as this, biologically based phenotypes that lie in the pathway from genes to behavior may provide a more powerful target for molecular genetic studies than the disorder as a whole. Although their use in ADHD is relatively new, such "endophenotypes" have aided the clarification of the etiology and pathophysiology of several other conditions in medicine and psychiatry. In this article, we review existing data on potential endophenotypes for ADHD, emphasizing neuropsychological deficits because assessment tools are cost effective and relatively easy to implement. Neuropsychological impairments, as well as measures from neuroimaging and electrophysiological paradigms, show correlations with ADHD and evidence of heritability, but the familial or genetic overlap between these constructs and ADHD remains unclear. We conclude that these endophenotypes will not be a quick fix for the field but offer potential if careful consideration is given to issues of heterogeneity, measurement and statistical power.

Adoption↗

Testing hypotheses regarding the causes of comorbidity: examining the underlying deficits of comorbid disorders.

The authors examined the validity of a method commonly used to test alternative hypotheses regarding the causes of comorbidity: the examination of underlying deficits of comorbid disorders. The authors simulated data in which the true causes of comorbidity were known, then compared the patterns of underlying deficits of the comorbid disorders found in the simulated data with the predicted results. The method of examining the underlying deficits of comorbid disorders could distinguish between several comorbidity models, including those that could not be distinguished well using other methods. The ability to distinguish the correct model decreased as the sample size and the correlation between the underlying deficits and the symptom scores decreased, suggesting that the issue of power should be considered carefully.

Adult↗

Are endophenotypes based on measures of executive functions useful for molecular genetic studies of ADHD?

BACKGROUND: Behavioral genetic studies provide strong evidence that attention-deficit/hyperactivity disorder (ADHD) has a substantial genetic component. Yet, due to the complexity of the ADHD phenotype, questions remain as to the specific genes that contribute to this condition as well as the pathways from genes to behavior. Endophenotypes, or phenotypes that are more closely linked to the neurobiological substrate of a disorder, offer the potential to address these two issues simultaneously (Freedman, Adler, & Leonard, 1999). Thus far, potential endophenotypes for ADHD have not been systematically studied. METHOD: The current paper reviews evidence supporting the use of deficits on neurocognitive measures of executive functions for this purpose. RESULTS: Such deficits are a correlate of ADHD and show preliminary evidence of heritability and association with relevant candidate genes. Nonetheless, studies that have assessed the familial and genetic overlap of neurocognitive impairments with ADHD have yielded inconsistent results. CONCLUSIONS: In order for executive function deficits to be used as an endophenotype for ADHD, we recommend greater attention to the neurocognitive heterogeneity of this disorder and to the precision of measurement of the neuropsychological tests employed. We also discuss empirical strategies that may be necessary to allow such research to progress prior to full resolution of the pathophysiological basis of ADHD.

Attention Deficit Disorder with Hyperactivity↗

Collaborative analysis of DRD4 and DAT genotypes in population-defined ADHD subtypes.

BACKGROUND: It has been proposed that some of the variability in reporting of associations between attention deficit hyperactivity disorder (ADHD) and candidate genes may result from mixing of genetically heterogeneous forms of ADHD using DSM-IV criteria. The goal of the current study is to test whether population-based ADHD subtypes defined by latent class analysis help resolve issues of variable findings across individual gene association studies. METHODS: Three studies which had previously reported no associations between polymorphisms of the DRD4 and DAT genes and DSM-IV defined ADHD were reanalyzed using population-based and DSM-IV defined ADHD subtypes. RESULTS: Across studies no significant associations were found for either DRD4 or DAT polymorphisms using DSM-IV ADHD subtypes. In contrast, a significant association was found between the combined data set for the 440 base pair 3' DAT VNTR polymorphism and population-defined severe combined ADHD (OR=1.25, p=.01). A marginally significant association was also found between the 7 repeat DRD4 allele and population-defined severe combined ADHD. CONCLUSION: Use of alternative population-based defined ADHD subtypes may help resolve some of the variable results presented for candidate gene association studies in ADHD.

Adolescent↗

Neuropsychological analyses of comorbidity between reading disability and attention deficit hyperactivity disorder: in search of the common deficit.

Measures of component reading and language skills, executive functions, and processing speed were administered to groups of children with attention deficit hyperactivity disorder (ADHD; n = 113), reading disability (RD; n = 109), both RD and ADHD (n = 64), and neither RD nor ADHD (n = 151). Groups with RD exhibited pronounced deficits on all measures of component reading and language skills, as well as significant weaknesses on measures of verbal working memory, processing speed, and response inhibition. Groups with ADHD exhibited weaknesses on all response-inhibition and processing speed tasks and were impaired on some measures of component reading skills and verbal working memory. The group with comorbid RD and ADHD exhibited the combination of the deficits in the RD-only and ADHD-only groups, providing evidence against the phenocopy and cognitive subtype hypotheses as explanations for the co-occurrence of RD and ADHD. Slow and variable processing speed was characteristic of all 3 clinical groups, suggesting that measures of this domain may be useful for future studies that search for the common genes that increase susceptibility to RD and ADHD.

Adolescent↗

The relation between sluggish cognitive tempo and DSM-IV ADHD.

To test the relation between sluggish cognitive tempo (SCT) and DSM-IV ADHD symptoms, parent and teacher ratings of the 18 DSM-IV ADHD items and five potential SCT items were obtained in a community sample of 8-18 year-old twins that was overselected for ADHD and learning disabilities (n = 296). Confirmatory factor analyses revealed that a three-factor model provided the best fit to the data for both parent and teacher ratings. DSM-IV inattention and hyperactivity-impulsivity symptoms loaded on two factors consistent with the DSM-IV model, and five SCT symptoms loaded primarily on a third factor. The SCT and inattention factors were highly correlated, whereas SCT and hyperactivity-impulsivity were weakly related. Both raters indicated that children meeting symptom criteria for the combined and inattentive subtypes exhibited significantly more SCT symptoms than those meeting symptom criteria for hyperactive-impulsive type and the comparison group without ADHD. Children meeting symptom criteria for the inattentive type exhibited significantly more SCT symptoms than those meeting criteria for the combined type, based on teacher ratings. These results suggest that SCT is an internally consistent construct that is significantly associated with DSM-IV inattention.

Attention↗

Three-year predictive validity of DSM-IV attention deficit hyperactivity disorder in children diagnosed at 4-6 years of age.

OBJECTIVE: Predictive validity is a fundamental consideration in evaluating the DSM-IV diagnostic criteria for attention deficit hyperactivity disorder (ADHD), particularly for younger children. METHOD: The authors conducted four annual assessments of ADHD and functional impairment using multiple informants in 255 probands and matched comparison children who were 4-6 years old in wave 1. RESULTS: Nearly all children who met full criteria for ADHD in wave 1 met full criteria for ADHD over the next 3 years and continued to display marked functional impairment relative to comparison children, even when intelligence, co-occurring psychopathology, and demographic characteristics were controlled. CONCLUSIONS: These findings support the validity of the DSM-IV diagnosis of ADHD in younger children by demonstrating that the symptoms and associated impairment are likely to persist well into elementary school.

Age Factors↗

Etiology of the comorbidity between RD and ADHD: exploration of the non-random mating hypothesis.

The present research sought to test the validity of the non-random mating hypothesis in a community sample in order to determine whether it contributes significantly to the comorbidity between attention-deficit/hyperactivity disorder (ADHD) and reading disability (RD) and to test whether the two disorders segregate independently. Data were gathered from 394 twin participants of the Colorado Learning Disabilities Research Center (CLDRC) and their biological parents. Parents were asked to complete retrospective questionnaires regarding their own ADHD and RD symptomatology as children, as well as rate their children on DSM-IV ADHD symptomatology before age 12. Twin RD was assessed by a composite score consisting of several reading measures. Chi-square and correlational analyses assessed the presence of non-random mating, as well as whether the two disorders were transmitted independently. Non-random mating between those with ADHD and those with RD did not significantly contribute to the comorbidity of the two disorders. Furthermore, there was some evidence that these two disorders did not segregate independently in this sample. These results are consistent with recent evidence that ADHD and RD are often comorbid because of significant genetic overlap. There was little evidence to support that non-random mating also contributes to this comorbidity in the present sample.

Adolescent↗

Quantitative trait locus for reading disability on chromosome 6p is pleiotropic for attention-deficit/hyperactivity disorder.

Comorbidity is pervasive among both adult and child psychiatric disorders; however, the etiological mechanisms underlying the majority of comorbidities are unknown. This study used genetic linkage analysis to assess the etiology of comorbidity between reading disability (RD) and attention-deficit hyperactivity disorder (ADHD), two common childhood disorders that frequently co-occur. Sibling pairs (N = 85) were ascertained initially because at least one individual in each pair exhibited a history of reading difficulties. Univariate linkage analyses in sibling pairs selected for ADHD from within this RD-ascertained sample suggested that a quantitative trait locus (QTL) on chromosome 6p is a susceptibility locus for ADHD. Because this QTL is in the same region as a well-replicated QTL for reading disability, subsequent bivariate analyses were conducted to test if this QTL contributed to comorbidity between the two disorders. Analyses of data from sib pairs selected for reading deficits revealed suggestive bivariate linkage for ADHD and three measures of reading difficulty, indicating that comorbidity between RD and ADHD may be due at least in part to pleiotropic effects of a QTL on chromosome 6p.

Analysis of Variance↗

Big five dimensions and ADHD symptoms: links between personality traits and clinical symptoms.

Attention-deficit/hyperactivity disorder (ADHD) in adulthood is conceptualized as originating in childhood. Despite considerable theoretical interest, little is known about how ADHD symptoms relate to normal personality traits in adults. In 6 studies, the Big Five personality dimensions were related to ADHD symptoms that adults both recalled from childhood and reported concurrently (total N = 1,620). Substantial effects emerged that were replicated across samples. First, the ADHD symptom cluster of inattention-disorganization was substantially related to low Conscientiousness and, to a lesser extent, Neuroticism. Second, ADHD symptom clusters of hyperactivity-impulsivity and oppositional childhood and adult behaviors were associated with low Agreeableness. Results were replicated with self-reports and observer reports of personality in community and clinical samples. Findings support theoretical connections between personality traits and ADHD symptoms.

Adult↗

Sex differences in young children who meet criteria for attention deficit hyperactivity disorder.

Examined sex differences in a mostly clinic-referred sample of 127 children (22 girls, 105 boys) who met Diagnostic and Statistical Manual of Mental Disorders (4th ed.; [DSM-IV], American Psychiatric Association, 1994) criteria for attention deficit hyperactivity disorder (ADHD) and 125 comparison children (24 girls, 101 boys) matched on age, sex, and race-ethnicity. Children in both groups ranged in age from 3 years, 10 months to 7 years, 0 months. Both girls and boys who met criteria for ADHD were more impaired than same-sex controls on a variety of measures when intelligence and other types of psychopathology were controlled. Teachers reported that boys with ADHD were more inattentive and more hyperactive/impulsive than girls with ADHD. These findings suggest that the diagnosis of ADHD is valid for both girls and boys in this young age range. Young girls and boys who meet DSM-IV criteria for ADHD are more similar than different, but boys tend to display more symptoms of ADHD, particularly in school.

Attention Deficit Disorder with Hyperactivity↗