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Biomedical subjects

Bruce F Pennington

Publications and source records attributed to Bruce F Pennington.

At least 19 recordsLinked to original sources
PubMed2007

Executive function in preschoolers with autism: evidence consistent with a secondary deficit.

Recent research on executive function (EF) deficits in autism has led investigators to conclude that EF deficits are secondary to the disorder. The current study has two major goals: (1) Examine whether specific EF deficits are present in the youngest autism group to date (mean=2.9 years), and (2) examine whether such deficits are secondary to autism, or act as an early non-specific cognitive risk factor for autism by comparing EF abilities of this autism group to a CA-matched typically developing group. Results from Experiment 1 suggest no specific EF deficits in autism relative to MA-matched controls, while results from Experiment 2 are consistent with the hypothesis that EF deficits may emerge as a secondary deficit in autism. Alternative hypotheses are also considered.

Aptitude↗
PubMed2006

Deficient implicit phonological representations in children with dyslexia.

This study tested the segmentation hypothesis of dyslexia by measuring implicit phonological representations in reading-disabled 11- to 13-year-olds. Implicit measures included lexical gating, priming, and syllable similarity tasks designed to reduce metalinguistic demands. Children with dyslexia performed consistently worse than CA and RA controls when more segmental representations were required across all three tasks. Implicit phonological representations were correlated with measures of speech perception, phoneme awareness, and phonological short-term memory, but not rapid automatized naming, and accounted for unique variance in predicting reading ability. Results provide strong support for less mature implicit phonological representations in children with dyslexia.

Awareness↗
PubMed2006

From single to multiple deficit models of developmental disorders.

The emerging etiological model for developmental disorders, like dyslexia, is probabilistic and multifactorial while the prevailing cognitive model has been deterministic and often focused on a single cognitive cause, such as a phonological deficit as the cause of dyslexia. So there is a potential contradiction in our explanatory frameworks for understanding developmental disorders. This paper attempts to resolve this contradiction by presenting a multiple cognitive deficit model of developmental disorders. It describes how this model evolved out of our attempts to understand two comorbidities, those between dyslexia and attention deficit hyperactivity disorder (ADHD) and between dyslexia and speech sound disorder (SSD).

Attention Deficit Disorder with Hyperactivity↗
PubMed2006

Breakthroughs in the search for dyslexia candidate genes.

Four genes have recently been proposed as candidates for dyslexia: dyslexia susceptibility 1 candidate 1 (DYX1C1), roundabout Drosophila homolog 1 (ROBO1), doublecortin domain-containing protein 2 (DCDC2) and KIAA0319. Each gene is implicated in global brain-development processes such as neural migration and axonal guidance, with the exception of DYX1C1, the function of which is still unknown. The most immediate clinical prospect of the discovery of these genes is the possibility of early identification of dyslexia via genetic screening. However, research efforts have yet to identify a functional mutation in any of these genes. When causal variants are identified, they will need to be considered within a multifactorial framework, which is likely to involve gene-gene and gene-environment interactions, to make accurate predictions of diagnostic status.

Axons↗
PubMed2006

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↗
PubMed2006

The perception of animacy in young children with autism.

Visual perception may be a developmental prerequisite to some types of social understanding. The ability to perceive social information given visual motion appears to develop early. However, children with autism have profound deficits in social cognitive function and may fail to see social motion in the same way that typically developing children do. We tested the hypothesis that children with autism fail to discriminate animate motion, using a novel paradigm involving simple geometric figures. The subjects were 23 children with autism (c.a. 70.7 mos.), 18 children with other developmental disabilities (c.a. 68.2 mos.), and 18 typically developing children (c.a. 46.4 mos.). Children saw two circles moving on a screen and were rewarded for identifying the one that moved as if animate. A control condition required children to identify the heavier of two objects. Children with autism initially showed a deficit in categorizing objects as animate (though no deficit on the control task), but showed no deficit in this ability after they had reached criterion in the training phase. These results are discussed in terms of the social orienting theory of autism, and the possibility that animacy perception might be preserved in autism, even if it is not used automatically.

Autistic Disorder↗
PubMed2005

DCDC2 is associated with reading disability and modulates neuronal development in the brain.

DYX2 on 6p22 is the most replicated reading disability (RD) locus. By saturating a previously identified peak of association with single nucleotide polymorphism markers, we identified a large polymorphic deletion that encodes tandem repeats of putative brain-related transcription factor binding sites in intron 2 of DCDC2. Alleles of this compound repeat are in significant disequilibrium with multiple reading traits. RT-PCR data show that DCDC2 localizes to the regions of the brain where fluent reading occurs, and RNA interference studies show that down-regulation alters neuronal migration. The statistical and functional studies are complementary and are consistent with the latest clinical imaging data for RD. Thus, we propose that DCDC2 is a candidate gene for RD.

Adult↗
PubMed2005

TDT-association analysis of EKN1 and dyslexia in a Colorado twin cohort.

A candidate gene, EKN1, was recently described in a cohort from Finland for the dyslexia locus on chromosome 15q, DYX1. This report described a (2;15) (q11;21) translocation disrupting EKN1 that cosegregated with dyslexia in a two-generation family. It also characterized a sequence polymorphism in the 5' untranslated region and a missense mutation that showed significant association in 109 dyslexics compared to 195 controls (p=0.002 and p=0.006, respectively). To confirm these results we interrogated the same polymorphisms in a cohort of 150 nuclear families with dyslexia ascertained through the Colorado Learning Disabilities Research Center. Using QTDT analysis with nine individual quantitative tasks and two composite measures of reading performance, we could not replicate the reported association. We conclude that the polymorphisms identified in the Finland sample are unlikely to be functional DNA changes contributing to dyslexia, and that if variation in EKN1 is causal such changes are more likely to be in regulatory regions that were not sequenced in this study. Alternatively, the published findings of association with markers in EKN1 may reflect linkage disequilibrium with variation in another gene(s) in the region.

Base Sequence↗
PubMed2005

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↗
PubMed2005

Spatial cognition in autism spectrum disorders: superior, impaired, or just intact?

The profile of spatial ability is of interest across autism spectrum disorders (ASD) because of reported spatial strengths in ASD and due to the recent association of Asperger's syndrome with Nonverbal Learning Disability. Spatial functions were examined in relation to two cognitive theories in autism: the central coherence and executive function (EF) theories. Performance on spatial tasks, EFs, and global/local processing was compared in children with ASD and controls. While the ASD group had faster reaction times on the Embedded Figures task, spatial performance was intact, but not superior, on other tasks. There was no evidence for impairments in EF or in processing global/local information, therefore contradicting these two theories. The implications of these results for these two theories are discussed.

Adolescent↗
PubMed2005

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↗
PubMed2005

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↗
PubMed2005

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↗
PubMed2005

Linkage of speech sound disorder to reading disability loci.

BACKGROUND: Speech sound disorder (SSD) is a common childhood disorder characterized by developmentally inappropriate errors in speech production that greatly reduce intelligibility. SSD has been found to be associated with later reading disability (RD), and there is also evidence for both a cognitive and etiological overlap between the two disorders. The present study tested whether SSD is linked to replicated risk loci for RD. METHOD: One hundred and eleven probands with SSD and their 76 siblings were tested with measures of speech, phonological memory (Nonword Repetition-NWR), and phonological awareness and genotyped for linkage markers on chromosomes 1p36, 6p22, and 15q21. Both single point and multipoint linkage were tested with multiple methods. RESULTS: The speech and NWR phenotypes were linked to the RD loci on chromosomes 6 and 15, with suggestive results for the RD locus on chromosome 1. CONCLUSIONS: It now appears that several RD loci are pleiotropic for SSD, extending the findings of Stein et al. (2004) for the RD locus on Chromosome 3.

Articulation Disorders↗
PubMed2005

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↗
PubMed2004

A 77-kilobase region of chromosome 6p22.2 is associated with dyslexia in families from the United Kingdom and from the United States.

Several quantitative trait loci (QTLs) that influence developmental dyslexia (reading disability [RD]) have been mapped to chromosome regions by linkage analysis. The most consistently replicated area of linkage is on chromosome 6p23-21.3. We used association analysis in 223 siblings from the United Kingdom to identify an underlying QTL on 6p22.2. Our association study implicates a 77-kb region spanning the gene TTRAP and the first four exons of the neighboring uncharacterized gene KIAA0319. The region of association is also directly upstream of a third gene, THEM2. We found evidence of these associations in a second sample of siblings from the United Kingdom, as well as in an independent sample of twin-based sibships from Colorado. One main RD risk haplotype that has a frequency of approximately 12% was found in both the U.K. and U.S. samples. The haplotype is not distinguished by any protein-coding polymorphisms, and, therefore, the functional variation may relate to gene expression. The QTL influences a broad range of reading-related cognitive abilities but has no significant impact on general cognitive performance in these samples. In addition, the QTL effect may be largely limited to the severe range of reading disability.

Chromosome Mapping↗