Biomedical subjects
B F Pennington
Publications and source records attributed to B F Pennington.
Attention deficit disorder in reading-disabled twins: evidence for a genetic etiology.
In order to assess the genetic etiology of attention deficit hyperactivity disorder (ADHD), the basic regression model for the analysis of selected twin data (DeFries & Fulker, 1985, 1988) was fitted to questionnaire data (DICA: Diagnostic Interview for Children and Adolescents; Herjanic, Campbell, & Reich, 1982) for 37 identical and 37 fraternal twin pairs tested in the Colorado Reading Project. Results of this analysis suggest that ADHD is highly heritable. Moreover, adjusting DICA scores for either IQ or reading performance differences did not substantially change parameter estimates. In future analyses of larger data sets, distinguishing between possible subtypes of attentional problems (e.g., ADD with or without hyperactivity) may facilitate tests of more searching etiological questions.
Reading disability, immune disorders and non-right-handedness: twin and family studies of their relations.
Geschwind and colleagues discussed associations among learning disorders, immune disorders and non-right-handedness. In this study, we examined the associations between reading disability (RD) and both immune disorders (ID) and non-right-handedness (NRH) in family and twin samples (total N = 1731 cases) identified through an RD proband. We also conducted co-segregation analyses to ascertain the degree to which NRH, ID and RD were biologically related. There was little evidence for an overall association between RD and NRH. There was not convergent evidence across all four samples for an association between RD and ID, although we did find an association between RD and ID in two of four samples. Nor was there strong support for a subtype where RD and NRH, or RD and ID, co-segregate in families. These data suggest that the associations postulated by Geschwind and colleagues are not robust in RD samples, although we cannot completely rule out the possibility of an RD plus ID subtype.
A twin study of the etiology of comorbidity: attention-deficit hyperactivity disorder and dyslexia.
Monozygotic and dizygotic twin pairs, in which at least one member of each pair is reading disabled (RD), were assessed for attention-deficit hyperactivity disorder (ADHD). Within pair cross-concordances of the RD and ADHD qualitative diagnoses for monozygotic twins were larger than for dizygotic twins, although not significantly so (p less than 0.10). Thus, the data suggest that RD and ADHD may be primarily genetically independent. However, trends in the data and subtype analyses suggest that in some cases RD and ADHD may occur together because of a shared genetic etiology and that a genetically mediated comorbid subtype may exist.
Specific frontal lobe deficits among women with the fragile X gene.
The neurocognitive phenotype of fragile X and its relation to cytogenetic expression were examined among 10 fragile X women with > or = 2% expression, 10 0% obligate carriers, and 10 controls. Measures were obtained for intellectual ability, achievement, and verbal, nonverbal, memory, and frontal lobe functions. Results show that no group demonstrated deficits on verbal, nonverbal, or memory measures. In contrast, when controlling for effects of IQ, the expressing fragile X women exhibited (1) deficits on measures of frontal lobe functioning, and (2) enhanced performance on verbal, but not figural, memory. Frontal lobe deficits may account for behavioral and cognitive manifestations of fragile X.
Gender ratios among reading-disabled children and their siblings as a function of parental impairment.
Gender ratios are reported for 374 reading-disabled probands and their 530 siblings included in five independent studies of reading disability. Ratios were tabulated for each study as a function of parental impairment (neither parent affected, mother only affected, father only affected, and both parents affected). Results reveal a small excess of male probands in referred and clinic samples of reading-disabled children, but not in research-identified samples. Gender ratios among siblings of reading-disabled probands are approximately 1:1. In addition, combined results indicate that gender ratios of neither probands nor their siblings vary substantially as a function of parental impairment.
The external validity of age- versus IQ-discrepancy definitions of reading disability: lessons from a twin study.
Recent research has raised the question of whether age- and IQ-discrepancy forms of reading disability (RD) are distinguishable in terms of either their underlying linguistic deficit or their response to treatment, thus threatening the external validity of the traditional distinction between specific reading retardation and reading backwardness. The present study pursued the external validity of this distinction in three domains: (a) genetic etiology, (b) sex ratio and clinical correlates, and (c) neuropsychological profiles. Each of these domains was explored in the RD (n = 640) and control (n = 436) twins participating in the Colorado Reading Project (514 males, 562 females, with an overall mean age of 12.42 years). Little evidence for external validity was found in terms of the clinical correlates of attention deficit-hyperactivity disorder (ADHD), immune disorders, or handedness. Most importantly, there was no evidence of differential genetic etiology of the two phenotypes in this sample, in that deficits in both phenotypes were similarly heritable (h2g = .40 and .46 for age and IQ phenotypes, respectively) and the genetic correlation between them was high (rG = .88 to .96). However, the genetic and neuropsychological profile analyses did suggest that age- and IQ-discrepancy definitions of RD may relate differentially to component reading processes, such as phonological awareness and orthographic coding.
Evidence for major gene transmission of developmental dyslexia.
OBJECTIVE: --There is strong evidence that developmental dyslexia is both familial and heritable, but the mode of genetic transmission has remained unclear. In this article, we examine specific genetic hypotheses about the mode of transmission of developmental dyslexia by performing complex segregation analyses. DESIGN: --A family study method was applied, whereby the relatives of dyslexic probands were examined for dyslexia. The families studied represent four independently ascertained samples. SETTING: --The four samples of families were primarily from rural and suburban communities of Colorado, Washington State, and Iowa. PARTICIPANTS: --A total of 204 families and 1698 individuals in the four samples combined. MAIN OUTCOME MEASURES: --The complex segregation program, POINTER, was used to test competing genetic hypotheses of how a categorical trait (dyslexia) is transmitted in families. RESULTS: --The results were consistent with major locus transmission in three of four samples and with polygenic transmission in the fourth. In these three samples, the estimates of penetrance for the AA, Aa, and aa genotypes (where A is the abnormal allele) were, respectively, 1.000, 1.000, and 0.001 to 0.039 in males, and 0.560 to 1.000, 0.550 to 0.897, and 0.000 in females. The estimated gene frequency of the major locus was between 3% and 5%. CONCLUSIONS: --Sex-influenced, additive, or dominant transmission occurs in a significant proportion of dyslexic families. Other evidence indicates, however, that dyslexia is etiologically heterogeneous and that there is genetic heterogeneity even among families selected for apparent dominant transmission. Thus, while no single major locus may account for all of dyslexia, it is important to pursue potential major loci for dyslexia using linkage techniques.
Genetics of learning disabilities.
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Executive function deficits in high-functioning autistic individuals: relationship to theory of mind.
A group of high-functioning autistic individuals was compared to a clinical control group matched on VIQ, age, sex and SES. Significant group differences were found on executive function, theory of mind, emotion perception and verbal memory tests, but not on spatial or other control measures. Second-order theory of mind and executive function deficits were widespread among the autistic group, while first-order theory of mind deficits were found in only a subset of the sample. The relationship of executive function and theory of mind deficits to each other, and their primacy to autism, are discussed.
Asperger's syndrome: evidence of an empirical distinction from high-functioning autism.
This study compared the neuropsychological profiles of individuals with high-functioning autism (HFA) and Asperger's syndrome (AS). In comparison with matched controls, both groups were impaired on executive function tests. Only the HFA group demonstrated deficits in theory of mind and verbal memory, performing more poorly than both controls and AS subjects. These results suggest that: (1) HFA and AS are empirically distinguishable on measures independent of diagnostic criteria, and (2) impairment on theory of mind measures is not universally found among individuals with autistic spectrum conditions. The primacy of executive function and theory of mind deficits to autism is discussed.
Word identification in reading and the promise of subsymbolic psycholinguistics.
The vast literature concerning printed word identification either contradicts or provides ambiguous support for each of the central hypotheses of dual-process theory, the most widely accepted theory of printed word identification. In contrast, clear, positive support exists for an alternative subsymbolic approach that includes a central role for the process of phonologic coding. This subsymbolic account is developed around a covariant learning hypothesis, derived from a design principle common to current learning algorithms within the subsymbolic paradigm. Where this hypothesis applies, and it may apply broadly, it predicts a common empirical profile of development.
Familial dyslexia: use of genetic linkage data to define subtypes.
Specific reading disability is an example of a complex behavioral disorder which is clinically heterogeneous. It is probably also heterogeneous at the levels of etiology and process (pathogenesis), but there may not be a 1:1:1 mapping of etiology to process to clinical outcome. Thus, classification of cases by clinical features may not lead to discovery of the underlying processes or etiologies, and it may be profitable to define subgroups by etiology. There is evidence for genetic etiology in some cases, but there is genetic heterogeneity as well. Possible genetic models for specific reading disability include polygenic, oligogenic, and single gene inheritance, and there are several types of genetic analysis that can be used to determine which of these modes of inheritance may be present. Identification of individual genes is possible in single gene and oligogenic disorders. Clinical studies and molecular analysis can then be used to determine gene function.
Are there emotion perception deficits in young autistic children?
Two studies were conducted to test the hypothesis that young autistic children are selectively impaired on emotion perception tasks. Results supporting the hypothesis were found on two of the four measures when the controls used were matched on non-verbal mental age; performance on the other tasks was consistent with global deficits across affective and non-affective domains, rather than specific deficits in emotion perception. When the autistic group was compared with controls matched on verbal mental age, no group differences were found. These results suggest that emotion perception impairment is not likely to be the primary underlying deficit in autism. Additional areas for further investigation were suggested.
Neuropsychology of early-treated phenylketonuria: specific executive function deficits.
This study explored the hypothesis that children with early-treated phenylketonuria (PKU) are selectively impaired on executive function measures, even when still on diet. The rationale for this hypothesis is that even mild elevations in phenylalanine (Phe) can lead to lower central levels of biogenic amines, including dopamine (DA). We hypothesize that this mild DA depletion causes subtle prefrontal dysfunction, which in turn affects executive functions such as set maintenance, planning, and organized search. 11 preschool early-treated PKU children (M age = 4.64) and a sample of age- and IQ-matched unaffected peers (n = 11) were evaluated on a battery of executive function (EF) measures. In addition, a "non-executive function" task, recognition memory, was administered to all subjects. Group comparisons demonstrated that PKU children were significantly impaired on an executive function composite score; there were no group differences, however, in recognition memory. These results supported the hypothesized specific deficit in executive function. Furthermore, within the PKU group the executive function composite score was significantly negatively correlated with concurrent phenylalanine levels, even after controlling for the correlation between IQ and executive function skills. This second finding provides support for the proposed biochemical mechanism underlying the specific cognitive deficits.
Phonological processing skills and deficits in adult dyslexics.
This article presents 4 experiments aimed at defining the primary underlying phonological processing deficit(s) in adult dyslexia. 5 phonological processes, all involving spoken language, were studied: phoneme perception, phoneme awareness, lexical retrieval of phonology, articulatory speed, and phonetic coding in verbal short-term memory. 2 differently ascertained adult dyslexic groups, familial dyslexics (n = 15) and clinic dyslexics (n = 15), were the subjects in each experiment. These dyslexic groups were chosen because deficits that persist until adulthood and that are found in differently ascertained dyslexic groups are more likely to be primary. Each dyslexic group was compared to 2 control groups, chronological age (CA) controls who were similar in age and sex, and younger reading age (RA) controls who were similar in reading age and sex. The main finding was a clear deficit in phoneme awareness in both dyslexic groups, with each dyslexic group performing significantly worse than both CA and RA controls. Moreover, performance on the 2 phoneme awareness tasks together uniquely accounted for substantial variance in nonword reading. The clinic but not the familial dyslexics appeared to have an additional deficit in verbal short-term memory. No clear deficits were found in either dyslexic group in phoneme perception, lexical retrieval, or articulatory speed.
Genetic influences on learning disabilities: an update.
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