Editorial: Thinking outside the box - enhancing causal models of neurodevelopmental disorders.

Neurodevelopmental disorders are best conceptualised as the result of multiple risk factors, which accumulate and determine the likelihood of reaching the threshold for fulfilling agreed diagnostic criteria. This multiple-risk framework allows the inclusion of research findings focusing on single disorders, while highlighting the need for extending and specifying existing causal models. Such specifications need to address at least three challenges: First, causal models need to account for the heterogeneity of symptoms within neurodevelopmental disorders, the dissociations between disorders, and also the high comorbidity rates observed between them. Second, causal models need to take into account the fact that associations between risk factors and psychopathology may be developmentally conditioned and are likely to change over time. Third, causal models need to incorporate a better understanding of the causal pathways between neurobiological risk factors and their interaction with environmental risk factors. Several articles in the present issue address these challenges, by assessing the interplay between neurobiological and environmental risk factors, and their impact on psychopathology, and by investigating how this relationship changes over time.

The relationship between bullying, learning disorders and psychiatric comorbidity.

BACKGROUND: Both learning disorders and bullying are major sources of public concern. Children with learning disorders often suffer from social rejection, potentially rendering them more susceptible to bullying involvement. Bullying involvement leads to a higher risk towards developing various problems including self-harm and suicidality. Past research on whether learning disorders are childhood bullying risk factors yielded inconsistent results. METHODS: The current study used path analyses on a representative sample of 2,925 German 3rd and 4th grades to examine whether learning disorders are a direct bullying risk factor, or whether their impact depends on psychiatric comorbidity. More so, the current study sought to examine whether associations differ between children with and without learning disorders, compare different bullying roles (i.e., only victim, only bully, or bully-victim), compare gender, and control for IQ and socioeconomic status. RESULTS: Results indicated that learning disorders are not a direct but rather an indirect childhood risk factor for bully-victim involvement, depending on psychiatric comorbidity with internalizing or externalizing disorders. Regarding the comparison between the samples of children with and without learning disorders, an overall difference and a difference in the path between spelling and externalizing disorders emerged. No difference for different bullying roles (i.e., only victim, only bully) emerged. Negligible differences emerged when IQ and socioeconomic status were controlled. An overall gender difference emerged, compatible with past research, indicating higher bullying involvement among boys compared to girls. CONCLUSION: Children with learning disorders are at a higher risk of having psychiatric comorbidity, which in turn renders them at a higher risk of bullying involvement. Implications for bullying interventions and school professionals are deduced.

Language and reading impairments are associated with increased prevalence of non-right-handedness.

Handedness has been studied for association with language-related disorders because of its link with language hemispheric dominance. No clear pattern has emerged, possibly because of small samples, publication bias, and heterogeneous criteria across studies. Non-right-handedness (NRH) frequency was assessed in N = 2503 cases with reading and/or language impairment and N = 4316 sex-matched controls identified from 10 distinct cohorts (age range 6-19 years old; European ethnicity) using a priori set criteria. A meta-analysis (Ncases  = 1994) showed elevated NRH % in individuals with language/reading impairment compared with controls (OR = 1.21, CI = 1.06-1.39, p = .01). The association between reading/language impairments and NRH could result from shared pathways underlying brain lateralization, handedness, and cognitive functions.

Economic evaluation of dyslexia intervention.

In many countries, intervention costs are not covered by public health care. A critical basis for deciding whether an intervention is covered or not is to analyse the relation between benefits and costs of the intervention, and to quantify the consequential costs. In this study, a cost-utility analysis was computed to investigate the costs of individualized dyslexia intervention while quantifying the benefit in terms of health-related quality of life in a sample of 36 individuals with dyslexia. In addition, educational outcomes and costs of untreated dyslexia for the society were estimated using information for class repetition, school success, and unemployment rates from previous studies and official statistics. A significant increase in quality of life with medium effect sizes was found across all quality-of-life measures. Increases in quality of life were domain-specific, thus occurring specifically in those domains that are affected by learning disorders. The cost-utility ratio was 9,782 Euros per quality adjusted life years (QALYs), which is in line with similar therapy forms, such as speech therapy. The loss of productivity for untreated dyslexia in the German population was estimated for class repetition and reduced income due to lower school degrees. The cost-utility analysis and the calculation of consequential costs suggest that the dyslexia intervention is cost-effective.

Genome-wide association study reveals new insights into the heritability and genetic correlates of developmental dyslexia.

Developmental dyslexia (DD) is a learning disorder affecting the ability to read, with a heritability of 40-60%. A notable part of this heritability remains unexplained, and large genetic studies are warranted to identify new susceptibility genes and clarify the genetic bases of dyslexia. We carried out a genome-wide association study (GWAS) on 2274 dyslexia cases and 6272 controls, testing associations at the single variant, gene, and pathway level, and estimating heritability using single-nucleotide polymorphism (SNP) data. We also calculated polygenic scores (PGSs) based on large-scale GWAS data for different neuropsychiatric disorders and cortical brain measures, educational attainment, and fluid intelligence, testing them for association with dyslexia status in our sample. We observed statistically significant (p < 2.8 × 10-6) enrichment of associations at the gene level, for LOC388780 (20p13; uncharacterized gene), and for VEPH1 (3q25), a gene implicated in brain development. We estimated an SNP-based heritability of 20-25% for DD, and observed significant associations of dyslexia risk with PGSs for attention deficit hyperactivity disorder (at pT = 0.05 in the training GWAS: OR = 1.23[1.16; 1.30] per standard deviation increase; p = 8 × 10-13), bipolar disorder (1.53[1.44; 1.63]; p = 1 × 10-43), schizophrenia (1.36[1.28; 1.45]; p = 4 × 10-22), psychiatric cross-disorder susceptibility (1.23[1.16; 1.30]; p = 3 × 10-12), cortical thickness of the transverse temporal gyrus (0.90[0.86; 0.96]; p = 5 × 10-4), educational attainment (0.86[0.82; 0.91]; p = 2 × 10-7), and intelligence (0.72[0.68; 0.76]; p = 9 × 10-29). This study suggests an important contribution of common genetic variants to dyslexia risk, and novel genomic overlaps with psychiatric conditions like bipolar disorder, schizophrenia, and cross-disorder susceptibility. Moreover, it revealed the presence of shared genetic foundations with a neural correlate previously implicated in dyslexia by neuroimaging evidence.

Language difficulties are a shared risk factor for both reading disorder and mathematics disorder.

Disorders of reading and mathematics co-occur at greater than chance rates, but they are often studied separately. This article reports the reading and arithmetic outcomes at 9 years of age from a longitudinal study of 224 children at high risk for dyslexia. Using a cutoff at the 10th centile, groups of children with reading disorder (RD), mathematics disorder (MD), and comorbid reading disorder and math disorder (RD&MD) were identified. The risk of these disorders was elevated in children selected in preschool with language difficulties or at family risk for dyslexia. There was a high degree of comorbidity between RD and MD, and many cases-particularly in the comorbid group-also reached the diagnostic threshold for developmental language disorder (DLD). On measures of language, phoneme awareness, rapid automatized naming (RAN) digits, and rated inattention, there was a stepwise pattern: RD > MD > RD&MD. Poor language was associated with each disorder and appears to be a cognitive risk factor for RD, MD, and RD&MD. These findings suggest that there are shared genetic risk factors operating for both RD and MD.

Stability of Deficits in Reading Fluency and/or Spelling.

Deficits in reading fluency and in spelling can dissociate during development, resulting in groups with reading deficit only (RD), spelling deficit only (SD) and combined reading and spelling deficit (RSD). The current study investigated the one-to-two-year longitudinal stability of these subgroups in 167 German-speaking children. Reading fluency deficits (irrespective of spelling skills) were stable over time, while spelling deficits were stable in the RSD-group but not in the SD-group. Lower stability in the SD-group resulted from the fact that many children improved their spelling skills over time. Improvement in spelling was associated with good performance in phoneme awareness together with intact RAN and decoding skills.

White matter alterations and tract lateralization in children with dyslexia and isolated spelling deficits.

The present study investigated whether children with a typical dyslexia profile and children with isolated spelling deficits show a distinct pattern of white matter alteration compared with typically developing peers. Relevant studies on the topic are scarce, rely on small samples, and often suffer from the limitations of conventional tensor-based methods. The present Constrained Spherical Deconvolution study includes 27 children with typical reading and spelling skills, 21 children with dyslexia and 21 children with isolated spelling deficits. Group differences along major white matter tracts were quantified utilizing the Automated Fiber Quantification software and a lateralization index was calculated in order to investigate the structural asymmetry of the tracts. The two deficit groups mostly displayed different patterns of white matter alterations, located in the bilateral inferior longitudinal fasciculi, right superior longitudinal fasciculus, and cingulum for the group with dyslexia and in the left arcuate fasciculus for the group with isolated spelling deficits. The two deficit groups differed also with respect to structural asymmetry. Children with dyslexia did not show the typical leftward asymmetry of the arcuate fasciculus, whereas the group with isolated spelling deficits showed absent rightward asymmetry of the inferior fronto-occipital fasciculus. This study adds evidence to the notion that different profiles of combined or isolated reading and spelling deficits are associated with different neural signatures.

Understanding comorbidity of learning disorders: task-dependent estimates of prevalence.

BACKGROUND: Reading disorder (RD) and mathematics disorder (MD) frequently co-occur. However, the exact comorbidity rates differ largely between studies. Given that MD is characterised by high heterogeneity on the symptom level, differences in comorbidity rates may result from different mathematical subskills used to define MD. Comorbidity rates with RD are likely to be higher when MD is measured by mathematical subskills that do not only build on number processing, but also require language (i.e. arithmetic fluency), than when measured by magnitude processing skills. METHODS: The association between literacy, arithmetic fluency and magnitude processing as well as the overlap between deficits in these domains were assessed in a representative sample of 1,454 third Graders. RESULTS: Associations were significantly higher between literacy and arithmetic, than between literacy and magnitude processing. This was also reflected in comorbidity rates: comorbidity rates between literacy and arithmetic deficits were four times higher than expected by chance, whereas comorbidity rates between literacy and magnitude processing deficits did not exceed chance rate. Deficits in the two mathematical subskills showed some overlap, but also revealed dissociations, corroborating the high heterogeneity of MD. Results are interpreted within a multiple-deficit framework and implications for diagnosis and intervention are discussed. CONCLUSIONS: The overlap between RD and MD depends on the subskills used to define MD. Due to shared domain-general factors mathematical subskills that draw on language skills are more strongly associated with literacy than those that do not require language. The findings further indicate that the same symptom, such as deficits in arithmetic, can be associated with different cognitive deficits, a deficit in language skills or a deficit in number processing.

Reading strategies of good and poor readers of German with different spelling abilities.

Reading and spelling abilities are thought to be highly correlated during development, and orthographic knowledge is assumed to underpin both literacy skills. Interestingly, recent studies showed that reading and spelling skills can also dissociate. The current study investigated whether spelling skills (indicating orthographic knowledge) are associated with the application of orthographic strategies during reading. We examined eye movements of 137 third- and fourth-graders who were either good or poor readers with or without a spelling deficit: 43 children with typical reading and spelling skills, 28 with isolated spelling deficits, 28 with isolated reading deficits, and 38 with combined reading and spelling deficits. Although we expected to find reduced reliance on orthographic reading processes among poor spellers, this was evident for the group with combined deficits only. Both isolated deficit groups applied sublexical and lexical processes in a similar amount to typically developing children. Our findings suggest that reading rests on orthographic strategies even if lexical representations are poor as indicated by a deficit in spelling skills. Findings also show that dysfluent reading does not result only from overreliance on decoding.

Lexical Reading in Dysfluent Readers of German.

Dyslexia in consistent orthographies like German is characterized by dysfluent reading, which is often assumed to result from failure to build up an orthographic lexicon and overreliance on decoding. However, earlier evidence indicates effects of lexical processing at least in some German dyslexic readers. We investigated variations in reading style in an eye-tracking paradigm with German dysfluent 3rd and 4th graders. Twenty-six TypFix-readers (fixation counts within the range of 47 age-matched typical readers) were compared with 42 HighFix-readers (increased fixation counts). Both groups showed lexical access: Words were read more efficiently than nonwords and pseudohomophones. TypFix-readers showed stronger reliance on lexical reading than HighFix-readers (smaller length effects for number of fixations and total reading time, stronger lexicality effects for gaze duration, stronger word-pseudohomophone effects for mean saccade amplitude). We conclude that in both groups, sublexical and lexical reading processes were impaired due to inefficient visual-verbal integration.

Precursors of Reading Difficulties in Czech and Slovak Children At-Risk of Dyslexia.

Children with preschool language difficulties are at high risk of literacy problems; however, the nature of the relationship between delayed language development and dyslexia is not understood. Three hundred eight Slovak and Czech children were recruited into three groups: family risk of dyslexia, speech/language difficulties and controls, and were assessed three times from kindergarten until Grade 1. There was a twofold increase in probability of reading problems in each risk group. Precursors of 'dyslexia' included difficulties in oral language and code-related skills (phoneme awareness, letter-knowledge and rapid automatized naming); poor performance in phonological memory and vocabulary was observed in both affected and unaffected high-risk peers. A two-group latent variable path model shows that early language skills predict code-related skills, which in turn predict literacy skills. Findings suggest that dyslexia in Slavic languages has its origins in early language deficits, and children who succumb to reading problems show impaired code-related skills before the onset of formal reading instruction. Copyright © 2016 John Wiley & Sons, Ltd.

Effects of orthographic consistency on eye movement behavior: German and English children and adults process the same words differently.

The current study investigated the time course of cross-linguistic differences in word recognition. We recorded eye movements of German and English children and adults while reading closely matched sentences, each including a target word manipulated for length and frequency. Results showed differential word recognition processes for both developing and skilled readers. Children of the two orthographies did not differ in terms of total word processing time, but this equal outcome was achieved quite differently. Whereas German children relied on small-unit processing early in word recognition, English children applied small-unit decoding only upon rereading-possibly when experiencing difficulties in integrating an unfamiliar word into the sentence context. Rather unexpectedly, cross-linguistic differences were also found in adults in that English adults showed longer processing times than German adults for nonwords. Thus, although orthographic consistency does play a major role in reading development, cross-linguistic differences are detectable even in skilled adult readers.

Early language and executive skills predict variations in number and arithmetic skills in children at family-risk of dyslexia and typically developing controls.

Two important foundations for learning are language and executive skills. Data from a longitudinal study tracking the development of 93 children at family-risk of dyslexia and 76 controls was used to investigate the influence of these skills on the development of arithmetic. A two-group longitudinal path model assessed the relationships between language and executive skills at 3-4 years, verbal number skills (counting and number knowledge) and phonological processing skills at 4-5 years, and written arithmetic in primary school. The same cognitive processes accounted for variability in arithmetic skills in both groups. Early language and executive skills predicted variations in preschool verbal number skills, which in turn, predicted arithmetic skills in school. In contrast, phonological awareness was not a predictor of later arithmetic skills. These results suggest that verbal and executive processes provide the foundation for verbal number skills, which in turn influence the development of formal arithmetic skills. Problems in early language development may explain the comorbidity between reading and mathematics disorder.

Predictors of developmental dyslexia in European orthographies with varying complexity.

BACKGROUND: The relationship between phoneme awareness, rapid automatized naming (RAN), verbal short-term/working memory (ST/WM) and diagnostic category is investigated in control and dyslexic children, and the extent to which this depends on orthographic complexity. METHODS: General cognitive, phonological and literacy skills were tested in 1,138 control and 1,114 dyslexic children speaking six different languages spanning a large range of orthographic complexity (Finnish, Hungarian, German, Dutch, French, English). RESULTS: Phoneme deletion and RAN were strong concurrent predictors of developmental dyslexia, while verbal ST/WM and general verbal abilities played a comparatively minor role. In logistic regression models, more participants were classified correctly when orthography was more complex. The impact of phoneme deletion and RAN-digits was stronger in complex than in less complex orthographies. CONCLUSIONS: Findings are largely consistent with the literature on predictors of dyslexia and literacy skills, while uniquely demonstrating how orthographic complexity exacerbates some symptoms of dyslexia.

Approximate number sense, symbolic number processing, or number-space mappings: what underlies mathematics achievement?

In this study, the performance of typically developing 6- to 8-year-old children on an approximate number discrimination task, a symbolic comparison task, and a symbolic and nonsymbolic number line estimation task was examined. For the first time, children's performances on these basic cognitive number processing tasks were explicitly contrasted to investigate which of them is the best predictor of their future mathematical abilities. Math achievement was measured with a timed arithmetic test and with a general curriculum-based math test to address the additional question of whether the predictive association between the basic numerical abilities and mathematics achievement is dependent on which math test is used. Results revealed that performance on both mathematics achievement tests was best predicted by how well childrencompared digits. In addition, an association between performance on the symbolic number line estimation task and math achievement scores for the general curriculum-based math test measuring a broader spectrum of skills was found. Together, these results emphasize the importance of learning experiences with symbols for later math abilities.

The role of syllables and morphemes in silent reading: An eye-tracking study.

German skilled readers have been found to engage in morphological and syllable-based processing in visual word recognition. However, the relative reliance on syllables and morphemes in reading multi-syllabic complex words is still unresolved. This study aimed to unveil which of these sublexical units are the preferred units of reading by employing eye-tracking technology. Participants silently read sentences while their eye-movements were recorded. Words were visually marked using colour alternation (Experiment 1) or hyphenation (Experiment 2)-at syllable boundary (e.g., Kir-schen), at morpheme boundary (e.g., Kirsch-en), or within the units themselves (e.g., Ki-rschen). A control condition without disruptions was used as a baseline (e.g., Kirschen). The results of Experiment 1 showed that eye-movements were not modulated by colour alternations. The results of Experiment 2 indicated that hyphens disrupting syllables had a larger inhibitory effect on reading times than hyphens disrupting morphemes, suggesting that eye-movements in German skilled readers are more influenced by syllabic than morphological structure.

Effects of complexity and unpredictability on the learning of an artificial orthography.

Orthographies vary in complexity (the number of multi-letter grapheme-phoneme rules describing print-to-speech regularities) and unpredictability (the number of words which cannot be read correctly, even with at-ceiling knowledge of the rules). To assess how these constructs affect reading acquisition, we used an artificial orthography learning paradigm, where participants learn to read pseudowords written in unfamiliar symbols, and subsequently read aloud novel words written in the same symbols (generalisation). In three experiments (third experiment pre-registered), we manipulated the consistency of symbol-to-sound mappings: in the first inconsistent condition, vowel pronunciation depended on the subsequent letter (condition complexity), and in the second inconsistent condition, vowel pronunciation was unpredictable from the context (condition unpredictability). Across experiments, we found that pseudowords with inconsistent mappings are more difficult to learn than pseudowords with consistent mappings only, regardless of whether the inconsistency is due to complexity or unpredictability. Numerically, participants learning orthographies containing unpredictable correspondences seem to be less likely to form rules, either for simple or for complex correspondences. We propose that rule extraction and distributional learning happens simultaneously during reading acquisition: in a mathematical model, we show that distributional learning may lead to more complete knowledge than rule extraction for orthographies that are high in unpredictability.

What Do Artificial Orthography Learning Tasks Actually Measure? Correlations Within and Across Tasks.

Artificial Orthography Learning (AOL) may act as a possible candidate to model the learning of print-to-speech correspondences. In order to serve as an adequate task, however, we need to establish whether AOL can be reliably measured. In the current study, we report the correlations between the learning of two different artificial orthographies by the same 55 participants. We also explore the correlation between AOL skill and other participant-level variables, namely Paired Associate Learning (PAL) performance, word and nonword reading ability, and age. We find high correlations between learning of two different artificial orthographies. Correlations with reading fluency and PAL are low. These results leave questions about the link between reading acquisition and AOL. At the same time, they show that AOL ability can be reliably measured and justify its use for future studies.

Comorbidity of learning disorders: prevalence and familial transmission.

BACKGROUND: In order to fully specify the profiles of risk and protective factors of developmental disorders, a better understanding of the conditions under which they co-occur is required. So far, empirical evidence on comorbidities of specific learning disorders in arithmetic, reading and spelling is scarce. METHODS: Prevalence and gender ratios of specific learning disorders in arithmetic (AD), reading (RD), and spelling (SD) and their co-occurrence were assessed in a large (N = 2586) population-based sample of elementary school children and in a subsample of 293 children with at least one learning disorder (LD-sample). A questionnaire on familial transmission was given to a subsample of 256 parents of children with a learning disorder and 146 typically developing children. RESULTS: The rates of deficits in arithmetic, reading, or spelling were four to five times higher in samples already experiencing marked problems in one academic domain compared to the full population. Thus, comorbidity of learning disorders was confirmed in a fairly standard school population. Rates of co-occurrence decreased for AD and RD, but not isolated SD when more stringent cutoff criteria were applied, suggesting that the comorbidity of arithmetic and spelling disorder may be more strongly biologically mediated than the comorbidity of arithmetic and reading disorder. We found a preponderance of girls with AD and boys with SD. These imbalanced gender ratios were especially marked for isolated problems, while for comorbid problems gender ratios were mostly balanced with the exception of deficits in arithmetic and reading (but not spelling) which were more typical for girls. The parental questionnaire provided evidence for disorder-specific familial transmission and co-segregation of arithmetic and literacy deficits. CONCLUSIONS: Comorbidities of learning disorders are not artificial. They are the result of a complex interplay between both general and disorder-specific aetiological factors.