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.     

Comorbidity of Mathematics and Reading Deficits: Evidence for a Genetic Etiology

In order to assess the genetic etiology of the comorbidity of reading and mathematics difficulties, data were ascertained from two samples: (1) 102 identical and 77 same-sex fraternal twin pairs in which at least one member of each pair is reading disabled and (2) 42 identical and 23 same-sex fraternal twin pairs in which at least one member is math disabled. Composite reading and mathematics performance data from each sample were fitted to the basic multiple regression model for the analysis of selected twin data and its bivariate extension. Resulting estimates of bivariate heritability and the genetic correlation between the reading and the mathematics performance measures suggest that the comorbidity between mathematics and reading difficulties is due in part to genetic influences.     

The Developmental Etiology of High IQ

The genetic and environmental trends in IQ development were assessed in 483 same-sex twin pairs in the Colorado longitudinal twin study using maximum-likelihood model-fitting analysis. The twins were assessed periodically from ages 1 to 16. Results show a decreasing influence of shared environment and an increasing influence of heritability across development, with large and increasing age to age stability of genetic influences. Non-shared environment contributes almost exclusively to age to age change. Similar analyses were conducted designating the top 15% of the sample as having high IQ at each age. The developmental etiology of high IQ did not significantly differ from that found for the continuous measure in this relatively novel analysis. These results demonstrate early stability in etiological influences on IQ and have potential implications for gene-finding efforts, suggesting that samples selected for high IQ can be used to find genetic variation that will be applicable to the full range of the IQ distribution, although conclusive demonstration that the same genes are indeed involved was beyond the scope of this study. Edited by Robert Plomin.     

Differential genetic etiology of reading component processes as a function of IQ

Results obtained from previous studies of word recognition, reading component skills, and reading composite measures suggest that genetic factors may be more important as a cause for reading disability among children with higher IQ scores than among those with lower IQ scores. To investigate the genetic etiology of reading disability further, measures of word recognition, phonological decoding, orthographic coding, and phoneme awareness were obtained from a total of 465 twin pairs with a positive school history of reading problems. The basic and extended DeFries and Fulker (DF) multiple regression models for the analysis of selected twin data were employed to investigate the etiology of group deficits in reading and language skills, as well as to assess differential genetic etiology for the reading-related measures as a function of IQ. Data from 168 sibling pairs (drawn from the twins' families), including fraternal twin pairs and their siblings, as well as non-twin siblings of identical twins were subjected to single-marker analyses using the DF basic linkage model to examine evidence for linkage of a quantitative-trait locus (QTL) for reading and language deficits to the short arm of chromosome 6. Lastly, to investigate the possible differential influence of this QTL as a function of IQ, the sibling pair data were fitted to an extension of the DF basic linkage model. Results indicated that reading and language deficits are significantly heritable and that differential genetic influences as a function of IQ are evident for measures of word recognition and phonological decoding. Results obtained from linkage analyses confirmed the presence of a QTL on chromosome 6p that influences phonological and orthographic skills, as well as phoneme awareness measures, and suggest that this QTL may influence phoneme awareness differentially as a function of IQ: however, future analyses with considerably larger samples are needed to test the hypothesis of differential QTL influence more rigorously.     

Genetic Covariation Between Brain Volumes and IQ,Reading Performance,and Processing Speed

Although there has been much interest in the relation between brain size and cognition, few studies have investigated this relation within a genetic framework and fewer still in non-adult samples. We analyzed the genetic and environmental covariance between structural MRI data from four brain regions (total brain volume, neocortex, white matter, and prefrontal cortex), and four cognitive measures (verbal IQ (VIQ), performance IQ (PIQ), reading ability, and processing speed), in a sample of 41 MZ twin pairs and 30 same-sex DZ twin pairs (mean age at cognitive test = 11.4 years; mean age at scan = 15.4 years). Multivariate Cholesky decompositions were performed with each brain volume measure entered first, followed by the four cognitive measures. Consistent with previous research, each brain and cognitive measure was found to be significantly heritable. The novel finding was the significant genetic but not environmental covariance between brain volumes and cognitive measures. Specifically, PIQ shared significant common genetic variance with all four measures of brain volume (r _g = .58–.82). In contrast, VIQ shared significant genetic influence with neocortex volume only (r _g = .58). Processing speed was significant with total brain volume (r _g = .79), neocortex (r _g = .64), and white matter (r _g = .89), but not prefrontal cortex. The only brain measure to share genetic influence with reading was total brain volume (r _g = .32), which also shared genetic influences with processing speed.     

Genetic and Environmental Sources of Covariance Between Reading Tests Used in Neuropsychological Assessment and IQ Subtests

In this study, we examined genetic and environmental influences on covariation among two reading tests used in neuropsychological assessment (Cambridge Contextual Reading Test [CCRT], [Beardsall, L., and Huppert, F. A. (1994). J. Clin. Exp. Neuropsychol. 16:232-242], Schonell Graded Word Reading Test [SGWRT], [Schonell, F. J., and Schonell, P. E. (1960). Diagnostic and attainment testing. Edinburgh: Oliver and Boyd.]) and among a selection of IQ subtests from the Multidimensional Aptitude Battery (MAB), [Jackson, D. N. (1984). Multidimensional aptitude battery, Ontario: Research Psychologists Press.] and the Wechsler Adult Intelligence Scale-Revised (WAIS-R) [Wechsler, D. (1981). Manual for the Wechsler Adult Intelligence Scale-Revised (WAIS-R). San Antonio: The Psychological Corporation]. Participants were 225 monozygotic and 275 dizygotic twin pairs aged from 15 years to 18 years (mean, 16 years). For Verbal IQ subtests, phenotypic correlations with the reading tests ranged from 0.44 to 0.65. For Performance IQ subtests, phenotypic correlations with the reading tests ranged from 0.23 to 0.34. Results of Structural Equation Modeling (SEM) supported a model with one genetic General factor and three genetic group factors (Verbal, Performance, Reading). Reading performance was influenced by the genetic General factor (accounting for 13% and 20% of the variance for the CCRT and SGWRT, respectively), the genetic Verbal factor (explaining 17% and 19% of variance for the CCRT and SGWRT), and the genetic Reading factor (explaining 21% of the variance for both the CCRT and SGWRT). A common environment factor accounted for 25% and 14% of the CCRT and SGWRT variance, respectively. Genetic influences accounted for more than half of the phenotypic covariance between the reading tests and each of the IQ subtests. The heritabilities of the CCRT and SGWRT were 0.54 and 0.65, respectively. Observable covariance between reading assessments used by neuropsychologists to estimate IQ and IQ subtests appears to be largely due to genetic effects.     

The Role of the Supplementary Motor Region in Overt Reading: Evidence for Differential Processing in SMA-Proper and Pre-SMA as a Function of Task Demands

A differentiation in function between the pre-SMA (i.e., cognitive load) and the SMA-proper (i.e., motor execution) has been described (Zhang et al., Cereb Cortex 22:99–111, 2012). These differential SMA functions may be influential in overt reading tasks. The present study examined the relationships between various segments of the SMA and overt reading through the modulation of task demands in an effort to explore the complexity of the print-to-speech network. Skilled reading adults (N?=?15) took part in five overt reading tasks: pure regular word reading, pure exception word reading, mixed regular word and exception word reading, go/no-go reading with nonword foils and go/no-go reading with pseudohomophone foils. Five regions of interest that spanned the pre-SMA to the SMA-proper were isolated. Behaviour-function relationships were tested to examine the associations between performance (response time) and brain activity (percent signal change). Further, the coherence between feedforward (SMA) and feedback (supramarginal gyrus) regions were explored to further refine the print-to-speech network. We found that the pre-SMA was related to cognitively demanding tasks (go/no-go with pseudohomophones), whereas the SMA-proper was related to an automatized task (pure regular words). Notably, only those tasks that required information from the feedback system (i.e., mixed word lists, go/no-go tasks) showed connections between SMA regions and the supramarginal gyrus, which is in line with the role of feedback and feedforward systems in the print-to-speech network. Together, these results support the notion that the pre-SMA and SMA-proper are sensitive to reading tasks that differentially invoke higher cognitive resources (mixed word lists, go/no-go) versus automatized articulation (pure lists), respectively. We discuss our findings in the context of print-to-speech neural networks.     

Hypertension: An Update

Current advances in hypertension are examined from the perspectives of both the individual patient and the community at large. Great progress has been made in the control of hypertension using a multipronged approach beginning with public and professional education. The recent nationwide fall in cardiovascular mortality is due at least in part to progress in hypertension control. There remain, however, segments of our population that are hard to reach and will continue to require community screening and special treatment programs. Governmental budgeting restraints should not be permitted to jeopardize our highly successful hypertension control and research programs.     

Genetic priming of a proinflammatory profile predicts low IQ in octogenarians

The purpose of the study was to test the hypothesis that single nucleotide polymorphisms (SNPs) within interleukin (IL)-18, TNF-alpha, IL-6 and IL-10 gene promoter regions are risk factors for cognitive decline in healthy octogenarians, and to isolate the strongest inflammatory biomarkers of cognitive function in the peripheral blood. The Wechsler Adult Intelligence Scale was administered to 112 individuals at ages 80 and 85. An IL-18 haplotype was an independent risk factor of poor Performance IQ. The TNF-308GA genotype was related to individual declines in Verbal IQ, and the IL-10-592 CC genotype was related to better Verbal IQ at the age of 80. Circulating levels of TNF-alpha, sTNFRs, and IL-6 were negatively correlated with IQ at age 85 and less strongly to IQ at age 80 with activation of the TNF system as the strongest biomarker. In conclusion, SNPs related to high proinflammatory or low anti-inflammatory activity are independent risk factors of reduced cognitive function in octogenarians. Only the IL-18 haplotype was associated with inflammation in the peripheral blood and only with regard to circulating TNF-alpha.     

Hepatocellular Carcinoma: An Update

Hepatocellular carcinoma (HCC) is the most common malignant tumor of males in the world, with an incidence of 1,000,000 new cases a year. It is endemic in Southeast Asia and Sub-Saharan Africa. Risk factors include chronic infection with hepatitis B virus (HBV) and hepatitis C virus (HCV), Aflatoxin B1 uptake, hemochromatosis, and &#102 1-antitripsin deficiency. Epidemiological studies provide evidence for the association of HCC with HBV infection. The incidence of HCC is high in regions hyperendemic for HBV. Chronic carrier state and maternal-infant transmission are important factors in the development of HCC. Evidence of direct oncogenic effect of HBV is well established, HCCs contain viral DNA sequences integrated into hepatocyte DNA that act as random insertional mutagens, and these sites are near genes involved in the control of proliferation and differentiation. The mechanism of hepatitis C virus in hepatocarcinogenesis is still imprecise but a high percentage of cases are related to this virus. Chronic alcohol consumption and cirrhosis are cofactors that increase the development of HCC in patients with chronic viral infection. In experimental carcinogenesis a multipotential element called oval cell proliferates in the early stages. The cellular events are accompanied by increased expression of several growth factors that enhance the survival of carcinogen-activated cells by suppressing apoptosis and increasing elements entering the cell cycle. Hepatic carcinogenesis is a complex process associated with accumulation of genetic and epigenetic changes that run through steps of initiation, promotion and progression. Activation of oncogenes of the "ras" family and others has been detected during chemically-induced HCC in rodents, but there is little evidence of such activation in human tumors. The role of tumor supressor genes such as retinoblastoma (RB) and P53 genes has been documented. Aflatoxin B1 that contaminates foods in endemic areas has a clear role in hepatocarcinogenesis. Metabolites of this toxin promote apurinic sites and G to T mutations in chromosomal DNA, the third base of codon 249 of the P53 gene is preferentially targeted to form aducts with aflatoxin B1, and this mutation has been specifically identified in HBV infection. Histological and cytological criteria for the diagnosis of HCC are well established and are based in architectural and cytological changes. An important issue is the diagnosis of liver "nodules" detected by image, from which small biopsies or aspiration material is obtained. Special studies such as reticulin, CD34, cytokeratin profile, and MOC-31 can be very useful for the differential diagnosis of primary and metastatic tumors. Telomerase activity has been found in HCC and negative in pericancerous tissue. It is more pronounced in poorly differentiated tumors and correlates with factors of clinical importance, such as prognosis and recurrences. Cells of well-differentiated HCC have an ultrastructural appearance similar to normal hepatocytes. During the process of dedifferentiation, there is progressive loss of organization of intracellular organelles. The cell cohesion is lost, intercellular gaps with microvilli appear, the sinusoids become capillarized, and reparative changes are seen in the spaces of Disse. A variety of inclusions, such as Mallory bodies, granular material, secondary lysosomes, and Dubin-Johnson pigment, have been described. Fibrolamellar carcinoma has a characteristic histological picture and ultrastructurally oncocytic features. Neuroendocrine granules and combination of HCC with bile duct carcinoma are seen by electron microscopy.     

Reading on the Wide Range Achievement Test-Revised and parental education as predictors of IQ: comparison with the Barona formula.

It is frequently necessary in research and clinical evaluations to obtain estimates of premorbid intelligence (IQ) which are separate from measured IQ. There is evidence that word reading may be useful in this aim. In order to determine the potential of the Wide Range Achievement Test-Revised (WRAT-R) reading subtest (READ) as an estimate of premorbid IQ, the present study examined the relationship between READ and IQ in healthy subjects. Consistent with other findings, READ accounted for a significant amount of variance in Verbal, Performance, and Full Scale IQ. Race and parental education, the latter being a variable not previously examined in this literature, accounted for incrementally valid variance in IQ beyond READ. The predictive power of these variables compares favorably with estimates made by the Barona IQ estimation formula, which uses only demographic information.     

IQ as a prognostic indicator in adult psychiatric first-admissions

This study used IQ, along with measures of premorbid adjustment, health-sickness, symptom level, diagnostic severity and demographic data, to predict to 2-year outcome measures of level of functioning, health-sickness, and symptoms for a sample of 145 adult psychiatric first-admissions. It was hypothesized that IQ as an indicator of cognitive ability, or of general ability to adapt, would predict positively to improvement over the 2-year period. Data analysis was conducted with bivariate correlations and multiple regressions, using both absolute-level and residualized outcome variables. IQ showed modest, significant relationships with all absolute outcome indices and six of seven residualized measures, especially for a subsample of those with non-average IQ scores. Regressions showed that IQ provided independent prediction of symptom outcomes.     

Personal Space as a Function of Infant Illness: An Application of Multidimensional Scaling

This study compares the impact that chronic or acutely ill infantshave upon the personal space perception of their mothers. Subjectswere mothers of healthy infants and mothers of infants witheither a ventricular septal defect or a hernia. Mothers wereasked to position family and medical support figures arounda hospital bed containing a figure representing their infant.A distance measure was obtained between all pairs of figures.Multidimensional scaling and hierarchical clustering analysesrevealed intrapersonal relationships unique to the three differenthealth conditions. Compared to the mothers of healthy infants,mothers of infants with ventricular septal defect emphasizedlong-term and overall medical/spiritual support. The mothersof infants with hernias emphasized immediate caretaking action;long-term support was not as yet a primary concern.     

Sickle Cell Trait: An Update

A review of the literature on sickle cell trait was completed by Sears in 1978. Since that time, several papers have been published concerning the possible health risks of sickle cell trait. Data presented from these studies show that there is no association with sickle cell trait and overall survival, overall mortality, overall morbidity, frequency and length of hospitalization, short-term survival of renal transplant recipient, and inheritance of glucose-6-phosphate dehydrogenase. Association with sickle cell trait is very likely in the following: splenic infarction at high altitudes (over 10,000 feet), in unpressurized airplane flight and mountain climbing, bacteriuria and pyelonephritis in pregnancy, hyposthenuria, hematuria, and delayed resolution of anterior chamber hyphema. Although these conditions have a statistical significant association with sickle cell trait, they occur quite infrequently. Thus, when they are observed, other causes should be sought before attributing them to sickle cell trait. Reduced mortality from Plasmodium falciparum infection also shows significant association with sickle cell trait.     

儿童阅读困难病因及机制的研究进展

阅读困难或阅读障碍 (ｄｙｓｌｅｘｉａ)属于儿童心理发育障碍。国际疾病分类诊断第 10版 (ＩＣＤ -10 )的精神与行为障碍分类把阅读困难描述为 :“特定性阅读技能发育显著损害 ,并且不能完全归因于智力水平、视力问题或教育不当。阅读理解技能、阅读中单词的辨认、朗读技能以及完成需有阅读参与的作业的能力都可受累。”阅读困难已引起儿童神经精神病学家、儿童行为与发展学家、教育工作者、心理语言工作者和神经生理学家的广泛兴趣。近 10年来 ,西方国家关于阅读困难的病因及机制的研究取得了较大的进展 ,主要集中在家族遗传、神经结构功…     

Genetic divergence in relatives of PKU's: low IQ correlation among normal siblings

The IQ frequency distribution of 78 unaffected siblings of patients with phenylketonuria (PKU) differed significantly from the normal population (X² = 43.42, df = 5, p < .0001). The excessive number of superior IQ'_s of this distribution apparently was not a function of superior families. The low intersibling correlation, r = .13, suggests a difference between carriers and noncarriers of the disease PKU. Because the proportion of high IQ's approaches the expected percentage of homozygotes or noncarriers for the disease, heterozygotes for PKU may be suffering a functional disadvantage. A theory is presented on the possible importance of genetic-recessive diseases whose carriers are at an intellectual disadvantage, thereby requiring compensatory genetic mechanisms.     

Wechsler performance IQ greater than Verbal IQ index in a forensic sample: a reconsideration

Explored the relationships of the Performance IQ (PIQ) greater than Verbal IQ (VIQ) to type of crime, ethnicity, and reading disability in a corrections sample of 70 adult males incarcerated on felony charges. The PIQ greater than VIQ sign was not related to Full Scale IQ or to violent vs. nonviolent crime, per se. The PIQ greater than VIQ sign showed a trend toward association with Ethnicity (black vs. white) and was related significantly to reading disability, with the reading disabled inmates more likely to show the sign, and to type of crime, with perpetrators of sex crimes most likely (87%) to show the sign and those incarcerated for murder or attempted murder least likely (33%) to show it. The difference in the proportion of inmates who showed the sign in these two classes of violent crimes (murder and sex crimes) was significant, and further analysis showed that with murder excluded, PIQ greater than VIQ occurred significantly more frequently in those accused of violent crimes than for nonviolent crimes. The latter findings suggested that differences between studies in the relationship of PIQ greater than VIQ and violence may be the result of differences in the proportion of murderers in the violent samples. Additional analyses indicated that the significant relationships between PIQ greater than VIQ and both type of crime and reading disability were most likely independent of ethnicity and each other.