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B F Pennington

Publications and source records attributed to B F Pennington.

At least 19 recordsLinked to original sources
PubMed2005

Bivariate linkage scan for reading disability and attention-deficit/hyperactivity disorder localizes pleiotropic loci.

BACKGROUND: There is a growing interest in the study of the genetic origins of comorbidity, a direct consequence of the recent findings of genetic loci that are seemingly linked to more than one disorder. There are several potential causes for these shared regions of linkage, but one possibility is that these loci may harbor genes with manifold effects. The established genetic correlation between reading disability (RD) and attention-deficit/hyperactivity disorder (ADHD) suggests that their comorbidity is due at least in part to genes that have an impact on several phenotypes, a phenomenon known as pleiotropy. METHODS: We employ a bivariate linkage test for selected samples that could help identify these pleiotropic loci. This linkage method was employed to carry out the first bivariate genome-wide analysis for RD and ADHD, in a selected sample of 182 sibling pairs. RESULTS: We found evidence for a novel locus at chromosome 14q32 (multipoint LOD=2.5; singlepoint LOD=3.9) with a pleiotropic effect on RD and ADHD. Another locus at 13q32, which had been implicated in previous univariate scans of RD and ADHD, seems to have a pleiotropic effect on both disorders. 20q11 is also suggested as a pleiotropic locus. Other loci previously implicated in RD or ADHD did not exhibit bivariate linkage. CONCLUSIONS: Some loci are suggested as having pleiotropic effects on RD and ADHD, while others might have unique effects. These results highlight the utility of this bivariate linkage method to study pleiotropy.

Adolescent↗
PubMed2002

Evidence for linkage and association with reading disability on 6p21.3-22.

Reading disability (RD), or dyslexia, is a common heterogeneous syndrome with a large genetic component. Several studies have consistently found evidence for a quantitative-trait locus (QTL) within the 17 Mb (14.9 cM) that span D6S109 and D6S291 on chromosome 6p21.3-22. To characterize further linkage to the QTL, to define more accurately the location and the effect size, and to identify a peak of association, we performed Haseman-Elston and DeFries-Fulker linkage analyses, as well as transmission/disequilibrium, total-association, and variance-components analyses, on 11 quantitative reading and language phenotypes. One hundred four families with RD were genotyped with a new panel of 29 markers that spans 9 Mb of this region. Linkage results varied widely in degree of statistical significance for the different linkage tests, but multipoint analysis suggested a peak near D6S461. The average 6p QTL heritability for the 11 reading and language phenotypes was 0.27, with a maximum of 0.66 for orthographic choice. Consistent with the region of linkage described by these studies and others, there was a peak of transmission disequilibrium with a QTL centered at JA04 (chi2=9.48; empirical P=.0033; orthographic choice), and there was strong evidence for total association at this same marker (chi2=11.49; P=.0007; orthographic choice). Although the boundaries of the peak could not be precisely defined, the most likely location of the QTL is within a 4-Mb region surrounding JA04.

Adolescent↗
PubMed2001

A comparison of the neuropsychological profiles of the DSM-IV subtypes of ADHD.

Recent research on the DSM-IV subtypes of attention-deficit/hyperactivity disorder (ADHD) has demonstrated that the subtypes differ in demographic characteristics, types of functional impairment, and profiles of comorbidity with other childhood disorders. However, little research has tested whether the subtypes differ in underlying neuropsychological deficits. This study compared the neuropsychological profiles of children without ADHD (n = 82) and children who met symptom criteria for DSM-IV Predominantly Inattentive subtype (ADHD-IA; n = 67), Predominantly Hyperactive Impulsive subtype (ADHD-HI; n = 14), and Combined subtype (ADHD-C; n = 33) in the areas of processing speed, vigilance, and inhibition. We hypothesized that children with elevations of inattention symptoms (ADHD-IA and ADHD-C) would be impaired on measures of vigilance and processing speed, whereas children with significant hyperactivity/impulsivity (ADHD-HI and ADHD-C) would be impaired on measures of inhibition. Contrary to prediction, symptoms of inattention best predicted performance on all dependent measures, and ADHD-IA and ADHD-C children had similar profiles of impairment. In contrast, children with ADHD-HI were not significantly impaired on any dependent measures once subclinical symptoms of inattention were controlled. Our results do not support distinct neuropsychological deficits in ADHD-IA and ADHD-C children, and suggest that symptoms of inattention, rather than symptoms of hyperactivity/impulsivity, are associated with neuropsychological impairment.

Adolescent↗
PubMed2001

Understanding of others' intentions in children with autism.

Many studies have shown that children with autism have difficulty understanding the thoughts and beliefs of other people. However, little research has been conducted on what these children understand about simpler mental states such as intentions. The current study tested the understanding of others' intentions in 2 1/2- to 5-year-old children with autism and a control group of children with other developmental delays. We used Meltzoff's (1995) test of understanding of others' unfulfilled intentions in an imitation context, with an additional "End State" condition. We found no significant between-group differences on any measure involving the understanding of others' intentions. Although within-group patterns suggested that children with autism may have a slightly less complex understanding of others' intentions than do other children, it was clear that any deficits these children showed in this area were not as marked as those they typically show on traditional theory of mind tasks.

Autistic Disorder↗
PubMed2001

Etiology of reading difficulties and rapid naming: the Colorado Twin Study of Reading Disability.

Children with reading deficits perform more slowly than normally-achieving readers on speed of processing measures, such as rapid naming (RN). Although rapid naming is a well-established correlate of reading performance and both are heritable, few studies have attempted to assess the cause of their covariation. Measures of rapid naming (numbers, colors, objects, and letters subtests), phonological decoding, orthographic choice, and a composite variable (DISCR) derived from the reading recognition, reading comprehension, and spelling subtests of the Peabody Individual Achievement Test were obtained from a total of 550 twin pairs with a positive school history of reading problems. Basic DeFries and Fulker (DF) multiple regression models for the analysis of selected twin data confirmed the heritable nature of phonological decoding, orthographic choice, DISCR, and rapid-naming composites. Bivariate DF models were employed to examine the extent to which deficits in the three reading-related measures covary genetically with rapid naming. Significant bivariate heritability estimates for each of the reading measures with the numbers and letters rapid-naming composite were also obtained. As expected, univariate sib-pair linkage analyses indicated the presence of a quantitative trait locus (QTL) on chromosome 6p21.3 for phonological decoding and orthographic choice deficits. Bivariate linkage analyses were then conducted to test the hypothesis that this QTL for reading difficulties is pleiotropic for slower performance on RN tasks. The results obtained from these analyses did not provide substantial evidence that the 6p QTL for reading difficulties has significant effects on rapid naming; however, larger samples would be required to test this hypothesis more rigorously.

Adolescent↗
PubMed2001

A comparison of the cognitive deficits in reading disability and attention-deficit/hyperactivity disorder.

This study used a nonreferred sample of twins to contrast the performance of individuals with reading disability (RD; n = 93), attention-deficit/hyperactivity disorder (ADHD; n = 52), RD and ADHD (n = 48), and neither RD nor ADHD (n = 121) on measures of phoneme awareness (PA) and executive functioning (EF). Exploratory factor analysis of the EF measures yielded underlying factors of working memory, inhibition, and set shifting. Results revealed that ADHD was associated with inhibition deficits, whereas RD was associated with significant deficits on measures of PA and verbal working memory. The RD + ADHD group was most impaired on virtually all measures, providing evidence against the phenocopy hypothesis as an explanation for comorbidity between RD and ADHD.

Adolescent↗
PubMed2001

Profile of cognitive functioning in women with the fragile X mutation.

Two studies tested the specificity of the neurocognitive profile of women with fragile X syndrome (FXS). First, women with an FXS full mutation were compared with women with a premutation and women without FXS who grew up in FXS families. Women with FXS had a significantly lower IQ than the other groups, and analyses of subtest profiles showed they had a relative weakness on Arithmetic and strength on Picture Completion. Women with FXS performed worse than the other groups on executive function, spatial ability, and visual memory. Next, women with FXS were compared with women without FXS matched on age and IQ. A similar IQ profile was found, but women with FXS were worse than controls only on executive function. The authors also examined which neurocognitive indices were related to the underlying biology of the disorder. Overall, the results indicated that executive rather than visuospatial deficits were primary in the neurocognitive profile of FXS.

Adolescent↗
PubMed2000

Twin study of the etiology of comorbidity between reading disability and attention-deficit/hyperactivity disorder.

This study utilized a sample of 313 eight- to sixteen-year-old same-sex twin pairs (183 monozygotic, 130 dizygotic) to assess the etiology of comorbidity between reading disability (RD) and attention-deficit/hyperactivity disorder (ADHD). RD was assessed by a discriminant function score based on the Peabody Individual Achievement Test, a standardized measure of academic achievement. The DSM-III version of the Diagnostic Interview for Children and Adolescents was used to assess symptoms of ADHD, and separate factor scores were computed for inattention and hyperactivity/impulsivity (hyp/imp). Individuals with RD were significantly more likely than individuals without RD to exhibit elevations on both symptom dimensions, but the difference was larger for inattention than hyp/imp. Behavior genetic analyses indicated that the bivariate heritability of RD and inattention was significant (h(2)(g(RD/Inatt)) = 0.39), whereas the bivariate heritability of RD and hyp/imp was minimal and nonsignificant (h(2)(g(RD/Hyp)) = 0.05). Approximately 95% of the phenotypic covariance between RD and symptoms of inattention was attributable to common genetic influences, whereas only 21% of the phenotypic overlap between RD and hyp/imp was due to the same genetic factors.

Adolescent↗
PubMed2000

Etiology of inattention and hyperactivity/impulsivity in a community sample of twins with learning difficulties.

A community sample of 373 8 to 18 year-old twin pairs in which at least one twin in each pair exhibited a history of learning difficulties was utilized to examine the etiology of inattention and hyperactivity/impulsivity (hyp/imp). Symptoms of attention-deficit/hyperactivity disorder (ADHD) were assessed by the DSM-III Diagnostic Interview for Children and Adolescents. Inattention and hyp/imp composite scores were created based on results of a factor analysis. Results indicated that extreme ADHD scores were almost entirely attributable to genetic influences across several increasingly extreme diagnostic cutoff scores. Extreme inattention scores were also highly heritable whether or not the proband exhibited extreme hyp/imp. In contrast, the heritability of extreme hyp/imp increased as a linear function of the number of inattention symptoms exhibited by the proband. This finding suggests that extreme hyp/imp may be attributable to different etiological influences in individuals with and without extreme inattention. If this result can be replicated in other samples, it would provide evidence that the hyp/imp symptoms exhibited by individuals with Combined Type ADHD and Predominantly Hyp/Imp Type ADHD may be attributable to different etiological influences.

Achievement↗
PubMed2000

A twin MRI study of size variations in human brain.

Although it is well known that there is considerable variation among individuals in the size of the human brain, the etiology of less extreme individual differences in brain size is largely unknown. We present here data from the first large twin sample (N=132 individuals) in which the size of brain structures has been measured. As part of an ongoing project examining the brain correlates of reading disability (RD), whole brain morphometric analyses of structural magnetic response image (MRI) scans were performed on a sample of adolescent twins. Specifically, there were 25 monozygotic (MZ) and 23 dizygotic (DZ) pairs in which at least one member of each pair had RD and 9 MZ and 9 DZ pairs in which neither member had RD. We first factor-analyzed volume data for 13 individual brain structures, comprising all of the neocortex and most of the subcortex. This analysis yielded two factors ("cortical" and "subcortical") that accounted for 64% of the variance. We next tested whether genetic and environmental influences on brain size variations varied for these two factors or by hemisphere. We computed intraclass correlations within MZ and DZ pairs in each sample for the cortical and subcortical factor scores, for left and right neocortex, and for the total cerebral volume. All five MZ correlations were substantial (r's=.78 to.98) and significant in both samples, as well as being larger than the corresponding DZ correlations, (r's=0.32 to 0.65) in both samples. The MZ-DZ difference was significant for 3 variables in the RD sample and for one variable in the smaller control sample. These results indicate significant genetic influences on these variables. The magnitude of genetic influence did not vary markedly either for the 2 factors or the 2 hemispheres. There was also a positive correlation between brain size and full-scale IQ, consistent with the results of earlier studies. The total cerebral volume was moderately correlated (r=.42, p<.01, two-tailed) with full-scale IQ in the RD sample; there was a similar trend in the smaller control sample (r=.31, p<.07, two-tailed). Corrections of similar magnitude were found between the subcortical factor and full-scale IQ, whereas the results for the cortical factor (r=.16 and.13) were smaller and not significant. In sum, these results provide evidence for the heritability of individual differences in brain size which do not vary markedly by hemisphere or for neocortex relative to subcortex. Since there are also correlations between brain size and full-scale IQ in this sample, it is possible that genetic influences on brain size partly contribute to individual differences in IQ.

Adolescent↗
PubMed2000

Etiology of neuroanatomical correlates of reading disability.

The heritable nature of reading disability has been well documented (DeFries & Alarcón, 1996), and possible abnormalities of brain structures have been associated with the disorder (Filipek, 1995). However, the etiology of individual differences in morphological brain measures has not been examined extensively. The purpose of this study was to apply behavioral genetic methods to assess the etiology of individual differences in neuroanatomical structures. Measures of reading performance, cognitive ability, and magnetic resonance imaging scans were obtained from 25 monozygotic (MZ) and 23 same-sex dizygotic (DZ) twin pairs with reading disability, and 9 MZ and 9 DZ control twin pairs participating in the Colorado Learning Disabilities Research Center. Results obtained from multiple regression analyses (DeFries & Fulker, 1985, 1988) of these twin data indicated that individual differences in the size of most cortical and subcortical structures were largely due to heritable influences. Moreover, estimates of heritability did not change appreciably after controlling for IQ and total brain size.

Adolescent↗
PubMed2000

Psychiatric comorbidity in children and adolescents with reading disability.

This study investigated the association between reading disability (RD) and internalizing and externalizing psychopathology in a large community sample of twins with (N = 209) and without RD (N = 192). The primary goals were to clarify the relation between RD and comorbid psychopathology, to test for gender differences in the behavioral correlates of RD, and to test if common familial influences contributed to the association between RD and other disorders. Results indicated that individuals with RD exhibited significantly higher rates of all internalizing and externalizing disorders than individuals without RD. However, logistic regression analyses indicated that RD was not significantly associated with symptoms of aggression, delinquency, oppositional defiant disorder, or conduct disorder after controlling for the significant relation between RD and ADHD. In contrast, relations between RD and symptoms of anxiety and depression remained significant even after controlling for comorbid ADHD, suggesting that internalizing difficulties may be specifically associated with RD. Analyses of gender differences indicated that the significant relation between RD and internalizing symptoms was largely restricted to girls, whereas the association between RD and externalizing psychopathology was stronger for boys. Finally, preliminary etiological analyses suggested that common familial factors predispose both probands with RD and their non-RD siblings to exhibit externalizing behaviors, whereas elevations of internalizing symptomatology are restricted to individuals with RD.

Adolescent↗
PubMed1999

Brain morphometry in reading-disabled twins.

OBJECTIVE: To test for brain structure differences in reading disability (RD) by means of MRI-based morphometry. BACKGROUND: Consensus is lacking on the brain structural correlates of RD. The current study reports on a wider set of structures in the largest sample yet studied, controlling for age, gender, IQ, and attention deficit hyperactivity disorder (ADHD). METHODS: A case-control study was performed that was comprised of 75 individuals with RD (mean age, 17.43+/-4.29 years) and 22 control subjects without RD (mean age, 18.69+/-3.75 years), each a single member of a twin pair. The two groups were similar in age, gender, and handedness, but differed in full-scale IQ (FSIQ), with the RD group having a lower mean FSIQ (101.8+/-9.9 versus 118.3+/-10.3). Using three group-by-structure analyses of covariance, groups were compared in terms of volume (in cubic centimeters) of major neocortical subdivisions, subcortical structures, and midsagittal areas (in square millimeters) of three subdivisions of the corpus callosum. RESULTS: Controlling for age, gender, and IQ, the authors found a significant group-by-structure interaction for the major neocortical subdivisions (p = 0.002), reflecting a different developmental pattern in the RD group, with the insula and anterior superior neocortex being smaller and the retrocallosal cortex being larger in the RD group. In contrast, they found no group main or interaction effects for the subcortical or callosal structures. The pattern of results was essentially the same in subjects without ADHD. CONCLUSIONS: Most brain structures do not differ in size in RD, but cortical development is altered subtly. This study replicates in a larger sample previous findings of insular differences in RD and demonstrates further that those differences are not attributable to comorbid ADHD.

Adolescent↗
PubMed1999

Quantitative-trait locus for specific language and reading deficits on chromosome 6p.

Reading disability (RD), or dyslexia, is a complex cognitive disorder manifested by difficulties in learning to read, in otherwise normal individuals. Individuals with RD manifest deficits in several reading and language skills. Previous research has suggested the existence of a quantitative-trait locus (QTL) for RD on the short arm of chromosome 6. In the present study, RD subjects' performance in several measures of word recognition and component skills of orthographic coding, phonological decoding, and phoneme awareness were individually subjected to QTL analysis, with a new sample of 126 sib pairs, by means of a multipoint mapping method and eight informative DNA markers on chromosome 6 (D6S461, D6S276, D6S105, D6S306, D6S258, D6S439, D6S291, and D6S1019). The results indicate significant linkage across a distance of at least 5 cM for deficits in orthographic (LOD = 3.10) and phonological (LOD = 2.42) skills, confirming previous findings.

Adult↗
PubMed1999

Psychiatric comorbidity associated with DSM-IV ADHD in a nonreferred sample of twins.

OBJECTIVE: To test the external validity of the dimensions and subtypes of DSM-IV attention-deficit/hyperactivity disorder (ADHD) by assessing the prevalence of psychiatric comorbidity. METHOD: Eight- to 18-year-old twins with ADHD (n = 105) and without ADHD (n = 95) were recruited through local school districts. Comorbid disorders were assessed by structured diagnostic interviews with the parent and child and by a behavioral rating scale completed by the child's classroom teacher. RESULTS: Symptoms of inattention were associated with lower intelligence and higher levels of depression, whereas symptoms of hyperactivity-impulsivity were associated more strongly with symptoms of oppositional defiant disorder (ODD) and conduct disorder (CD). All DSM-IV subtypes were associated with higher rates of ODD and CD in comparison with controls, and the combined type was associated with more disruptive behavior disorder symptoms than the other 2 subtypes. The combined type and predominantly inattentive type were associated with more symptoms of depression than controls or the predominantly hyperactive-impulsive type. CONCLUSIONS: These results provide support for the discriminant validity of the dimensions and subtypes of DSM-IV ADHD and suggest that clinicians should carefully screen for comorbid disorders as part of a comprehensive assessment of ADHD.

Adolescent↗
PubMed1998

A twin and family study of the association between immune system dysfunction and dyslexia using blood serum immunoassay and survey data.

We conducted a study of the association between developmental reading disability (DRD) and immune disorders (ID) using both survey and immunoassay data in two separate samples of families. One sample was made up of twins and their parents and was ascertained through a population-based sampling scheme. The other sample was a set of extended pedigrees selected for apparent autosomal dominant transmission of DRD. We failed to find an association between DRD and ID in either sample, regardless of the method used to assess immune system function. Even though our twin sample provided evidence that both DRD and immune conditions were significantly heritable, there was no evidence for a genetic correlation between ID and DRD nor was there any clear indication that a special subgroup of individuals may be comorbid for these conditions because of genetic reasons. How these negative findings can be reconciled with the developmental hypothesis of Geschwind, Behan, Galaburda, and colleagues, and how they may relate to the gene locus influencing DRD that has been recently located in the HLA region of the short arm of chromosome 6 is discussed.

Adolescent↗
PubMed1998

Phenotypic involvement in females with the FMR1 gene mutation.

Fragile X syndrome is the most common from of inherited mental retardation. Approximately half of females with the full mutation have significant cognitive deficits, whereas females with the premutation do not. Phenotypic effects seen in 281 females (IQs from 64 to 139) were analyzed. Results showed that females with the full mutation differ significantly from controls on selected anthropometric measurements, physical index score, and various behavioral features. Females with the premutation differed significantly from controls in regards to a few anthropometric measurements and the physical index score but not in behavioral features. These results suggest that phenotypic effects of the FMR1 mutation are not only common in females with the full mutation, but in females with the premutation as well.

Adolescent↗