Gerd Schulte-Körne

Developmental dyslexia in different languages: Language-specific or universal?

Most of the research on developmental dyslexia comes from English-speaking countries. However, there is accumulating evidence that learning to read English is harder than learning to read other European orthographies (Seymour, Aro, & Erskine, 2003). These findings therefore suggest the need to determine whether the main English findings concerning dyslexia can be generalized to other European orthographies, all of which have less irregular spelling-to-sound correspondences than English. To do this, we conducted a study with German- and English-speaking children (n=149) in which we investigated a number of theoretically important marker effects of the reading process. The results clearly show that the similarities between dyslexic readers using different orthographies are far bigger than their differences. That is, dyslexics in both countries exhibit a reading speed deficit, a nonword reading deficit that is greater than their word reading deficit, and an extremely slow and serial phonological decoding mechanism. These problems were of similar size across orthographies and persisted even with respect to younger readers that were at the same reading level. Both groups showed that they could process larger orthographic units. However, the use of this information to supplement grapheme-phoneme decoding was not fully efficient for the English dyslexics.

Strong genetic evidence of DCDC2 as a susceptibility gene for dyslexia.

We searched for linkage disequilibrium (LD) in 137 triads with dyslexia, using markers that span the most-replicated dyslexia susceptibility region on 6p21-p22, and found association between the disease and markers within the VMP/DCDC2/KAAG1 locus. Detailed refinement of the LD region, involving sequencing and genotyping of additional markers, showed significant association within DCDC2 in single-marker and haplotype analyses. The association appeared to be strongest in severely affected patients. In a second step, the study was extended to include an independent sample of 239 triads with dyslexia, in which the association--in particular, with the severe phenotype of dyslexia--was confirmed. Our expression data showed that DCDC2, which contains a doublecortin homology domain that is possibly involved in cortical neuron migration, is expressed in the fetal and adult CNS, which--together with the hypothesized protein function--is in accordance with findings in dyslexic patients with abnormal neuronal migration and maturation.

Evidence for Linkage of Spelling Disability to Chromosome 15

We are extremely grateful to the families who participated in this work. We appreciate the assistance of Katarina Muller and Wolfgang Deimel (Marburg). This work was supported by Deutsche Forschungsgemeinschaft grants Re 471/9-1 and Schu 988/2-1//2-3.

Evidence for the involvement of genetic variation in the oxytocin receptor gene (OXTR) in the etiology of autistic disorders on high-functioning level.

An increasing number of animal studies advert to a substantial role of the neuropeptide oxytocin in the regulation of social attachment and affiliation. Furthermore, animal studies showed anxiety and stress‐reduced effects of oxytocin. First human studies confirm these findings in animal studies and implicate a crucial role of oxytocin in human social attachment behavior and in social interactions. Thus, the oxytocin system might be involved in the impairment of social interaction and attachment in autism spectrum disorders (ASD). The human oxytocin receptor gene (OXTR) represents a plausible candidate gene for the etiology of ASD. To analyze whether genetic variants in the OXTR gene are associated with ASD we performed family‐based single‐marker and haplotype association analyses with 22 single nucleotide polymorphisms (SNPs) in the OXTR and its 5′ region in 100 families with autistic disorders on high‐functioning level (Asperger syndrome (AS), high‐functioning autism (HFA), and atypical autism (AA)). Single‐marker and haplotype association analyses revealed nominally significant associations of one single SNP and one haplotype with autism, respectively. Furthermore, employing a “reverse phenotyping” approach, patients carrying the haplotype associated with autism showed nominally significant impairments in comparison to noncarriers of the haplotype in items of the Autism Diagnostic Interview‐Revised algorithm describing aspects of social interaction and communication. In conclusion, our results implicate that genetic variation in the OXTR gene might be relevant in the etiology of autism on high‐functioning level.

Speech perception deficit in dyslexic adults as measured by mismatch negativity (MMN)

Deficits in phonological processing are known to play a major role in the aetiology of dyslexia, and speech perception is a prerequisite condition for phonological processing. Significant group differences between dyslexics and controls have been found in the categorical perception of synthetic speech stimuli. In a previous work, we have demonstrated that these group differences are already present at an early pre-attentive stage of signal processing in dyslexic children: the late component of the MMN elicited by passive speech perception was attenuated in comparison to a control group. In this study, 12 dyslexic adults and 13 controls were assessed using a passive oddball paradigm. Mismatch negativity (MMN) was determined for both tone and speech stimuli. The tone stimuli yielded two MMN components, but no group differences. Three components were found for the speech stimuli. Multivariate testing for group differences yielded a significant result, and univariate P values revealed significant differences between dyslexics and controls in two of the three time windows. This suggests that speech perception as measured on an early, pre-attentive level plays a major role in dyslexia not only in children (as shown in our previous study) but also in adults.

Pre-attentive processing of auditory patterns in dyslexic human subjects

It has been hypothesized that auditory temporal processing plays a major role in the aetiology of dyslexia. Event-related brain potentials (mismatch negativity, MMN) of auditory temporal processing were assessed in 15 dyslectic adults and 20 controls. A complex tonal pattern was used where the difference between standard and deviant stimuli was the temporal, not the frequency structure. Dyslexics had a significantly smaller MMN in the time window of 225-600 ms. This result shows that dyslexics have a significant pre-attentive deficit in processing of rapid temporal patterns suggesting that it may be the temporal information embedded in speech sounds, rather than phonetic information per se, that resulted in the attenuated MMN found in dyslexics in previous studies. MMN scalp topographies were similar for both groups, showing a maximum over fronto-central leads.

Genetic linkage analysis with dyslexia: evidence for linkage of spelling disability to chromosome 15.

Dyslexia (reading and spelling disability) is one of the most frequently diagnosed disorders in childhood. Twin studies of dyslexia have indicated that deficits in spelling are substantially heritable and that the heritability of spelling deficits is higher than the heritability of reading deficits. We conducted a linkage study for spelling disability in seven multiplex families from Germany. Following previously reported linkage findings of components of dyslexia to chromosome 6p21–p22 and 15q21, we genotype 26 microsatellite markers covering all of chromosome 6, and 13 microsatellite markers covering all of chromosome 15. While the chromosome 6 data were negative, results from chromosome 15 markers supported a locus on 15q21. The highest two-point LOD score was 1.26 with marker D15S143 at θ=0. A multipoint LOD score of 1.78 (p=0.0042) was achieved with a maximum at D15S132. Thus, our results provide independent support for a dyslexia gene on the long arm of chromosome 15.

Developmental Dyslexia – Recurrence Risk Estimates from a German Bi-Center Study Using the Single Proband Sib Pair Design

Objective: Several studies have demonstrated a genetic component for dyslexia. However, both segregation and linkage analyses show contradictory results pointing at the necessity of an optimal ascertainment scheme for molecular genetic studies. Previously, we have argued that the single proband sib pair design (SPSP) would be optimal. The aims of this paper therefore are to demonstrate the practicability of the SPSP design and the estimation of recurrence risks for reading and writing. Methods: We assessed spelling and reading in a family sample ascertained through the SPSP design. 287 families with at least two siblings and their parents were recruited. At least one child was affected with spelling disorder according to a one standard deviation (1SD) discrepancy criterion. Results: Mean values for probands and their siblings were different for both the spelling and the reading phenotype. For the probands, variances of the phenotype spelling were smaller. These effects became stronger with more extreme selection criteria. Both siblings fulfilled the 1SD criterion for spelling and reading in 60.3 and 28.9% of the families, respectively, indicating a low cost efficiency of the double proband sib pair approach. A recurrence risk of 4.52 (CI: 4.07–4.93) was obtained for spelling when the 1SD criterion was applied to both siblings. Recurrence risk estimates were similar for reading. Conclusion: The study demonstrates the suitability of the SPSP design for genetic analysis of dyslexia. The recurrence risk estimates may be used for determining sample sizes in gene mapping studies.

Motion-onset VEPs in dyslexia. Evidence for visual perceptual deficit.

The magnocellular deficit theory is one of the prominent theories in dyslexia. However, recent studies have produced conflicting results. In order to assess the validity of this theory, 8 dyslexic children and 14 controls were examined with a motion-onset visual evoked potential (VEP) paradigm at three different velocities (2, 8, and 16u2009deg/s). VEP elicited by stationary gratings served as a control condition. Amplitudes of motion-onset VEP components (P100, P200) but not of the stationary VEP are significantly attenuated in dyslexic children. Further, there is an interaction of group and velocity for the P200 in the way that group differences are more pronounced for higher velocities than for lower velocities. These results support the hypothesis of an impairment of a specific magnocellular function in dyslexia.

Interrelationship and Familiality of Dyslexia Related Quantitative Measures

Dyslexia is a complex gene‐environment disorder with poorly understood etiology that affects about 5% of school‐age children. Dyslexia occurs in all languages and is associated with a high level of social and psychological morbidity for the individual and their family; approximately 40‐50% have persistent disability into adulthood. The core symptoms are word reading and spelling deficits, but several other cognitive components influence the core phenotype.