An Eye-Tracking Study of Attention Biases in Children at High Familial Risk for Depression and Their Parents with Depression.

Attention biases (AB) are a core component of cognitive models of depression yet it is unclear what role they play in the transgenerational transmission of depression. 44 children (9-14 years) with a high familial risk of depression (HR) were compared on multiple measures of AB with 36 children with a low familial risk of depression (LR). Their parents: 44 adults with a history of depression (HD) and 36 adults with no history of psychiatric disorder (ND) were also compared. There was no evidence of group differences in AB; neither between the HR and LR children, nor between HD and ND parents. There was no evidence of a correlation between parent and child AB. The internal consistency of the tasks varied greatly. The Dot-Probe Task showed unacceptable reliability whereas the behavioral index of the Visual-Search Task and an eye-tracking index of the Passive-Viewing Task showed better reliability. There was little correlation between the AB tasks and the tasks showed minimal convergence with symptoms of depression or anxiety. The null-findings of the current study contradict our expectations and much of the previous literature. They may be due to the poor psychometric properties associated with some of the AB indices, the unreliability of AB in general, or the relatively modest sample size. The poor reliability of the tasks in our sample suggest caution should be taken when interpreting the positive findings of previous studies which have used similar methods and populations.

Children with Autism Spectrum Disorder of All Ages, Levels of Symptom Severity and General Cognitive Ability Display Low Processing Speed Index Scores Warranting Special Educational Assistance.

The processing speed index (PSI) of the Wechsler intelligence scale for children (WISC-IV) has been found to predict a child's level of academic functioning. The consistently reported PSI weakness in children with autism spectrum disorder (ASD) therefore warrants special assistance and attempts at compensation for the disadvantages associated with these children's low PSI. We investigated the association of PSI scores with age, general cognitive ability [as measured by full-scale IQ (FSIQ)], symptom severity and discrepancy between the WISC-IV indices verbal comprehension (VCI) and perceptual reasoning (PRI) in 101 school children with ASD. The PSI weakness in children with ASD was not related to age, FSIQ, VCI-PRI discrepancy or any of the symptom measures. These findings suggest that school children with ASD independent of their age, level of cognitive ability, VCI-PRI profile and most notably independent of their symptom severity should be entitled to special assistance and compensation in educational settings.

Emotion Regulation as a Mediator in the Relationship Between Cognitive Biases and Depressive Symptoms in Depressed, At-risk and Healthy Children and Adolescents.

Contemporary cognitive models of depression propose that cognitive biases for negative information at the level of attention (attention biases; AB) and interpretation (interpretation biases; IB) increase depression risk by promoting maladaptive emotion regulation (ER). So far, empirical support testing interactions between these variables is restricted to non-clinical and clinical adult samples. The aim of the current study was to extend these findings to a sample of children and adolescents. This cross-sectional study included 109 children aged 9-14 years who completed behavioural measures of AB (passive-viewing task) and IB (scrambled sentences task) as well as self-report measures of ER and depressive symptoms. In order to maximize the variance in these outcomes we included participants with a clinical diagnosis of depression as well as non-depressed youth with an elevated familial risk of depression and non-depressed youth with a low familial risk of depression. Path model analysis indicated that all variables (AB, IB, adaptive and maladaptive ER) had a direct effect on depressive symptoms. IB and AB also had significant indirect effects on depressive symptoms via maladaptive and adaptive ER. These findings provide initial support for the role of ER as a mediator between cognitive biases and depressive symptoms and provide the foundations for future experimental and longitudinal studies. In contrast to studies in adult samples, both adaptive as well as maladaptive ER mediated the effect of cognitive biases on depressive symptoms. This suggests potentially developmental differences in the role of ER across the lifespan.

Visual word form processing deficits driven by severity of reading impairments in children with developmental dyslexia.

The visual word form area (VWFA) in the left ventral occipito-temporal (vOT) cortex is key to fluent reading in children and adults. Diminished VWFA activation during print processing tasks is a common finding in subjects with severe reading problems. Here, we report fMRI data from a multicentre study with 140 children in primary school (7.9-12.2 years; 55 children with dyslexia, 73 typical readers, 12 intermediate readers). All performed a semantic task on visually presented words and a matched control task on symbol strings. With this large group of children, including the entire spectrum from severely impaired to highly fluent readers, we aimed to clarify the association of reading fluency and left vOT activation during visual word processing. The results of this study confirm reduced word-sensitive activation within the left vOT in children with dyslexia. Interestingly, the association of reading skills and left vOT activation was especially strong and spatially extended in children with dyslexia. Thus, deficits in basic visual word form processing increase with the severity of reading disability but seem only weakly associated with fluency within the typical reading range suggesting a linear dependence of reading scores with VFWA activation only in the poorest readers.

Promotion of mental health in young adults via mobile phone app: study protocol of the ECoWeB (emotional competence for well-being in Young adults) cohort multiple randomised trials.

BACKGROUND: Promoting well-being and preventing poor mental health in young people is a major global priority. Building emotional competence (EC) skills via a mobile app may be an effective, scalable and acceptable way to do this. However, few large-scale controlled trials have examined the efficacy of mobile apps in promoting mental health in young people; none have tailored the app to individual profiles. METHOD/DESIGN: The Emotional Competence for Well-Being in Young Adults cohort multiple randomised controlled trial (cmRCT) involves a longitudinal prospective cohort to examine well-being, mental health and EC in 16-22 year olds across 12 months. Within the cohort, eligible participants are entered to either the PREVENT trial (if selected EC scores at baseline within worst-performing quartile) or to the PROMOTE trial (if selected EC scores not within worst-performing quartile). In both trials, participants are randomised (i) to continue with usual practice, repeated assessments and a self-monitoring app; (ii) to additionally receive generic cognitive-behavioural therapy self-help in app; (iii) to additionally receive personalised EC self-help in app. In total, 2142 participants aged 16 to 22 years, with no current or past history of major depression, bipolar disorder or psychosis will be recruited across UK, Germany, Spain, and Belgium. Assessments take place at baseline (pre-randomisation), 1, 3 and 12 months post-randomisation. Primary endpoint and outcome for PREVENT is level of depression symptoms on the Patient Health Questionnaire-9 at 3 months; primary endpoint and outcome for PROMOTE is emotional well-being assessed on the Warwick-Edinburgh Mental Wellbeing Scale at 3 months. Depressive symptoms, anxiety, well-being, health-related quality of life, functioning and cost-effectiveness are secondary outcomes. Compliance, adverse events and potentially mediating variables will be carefully monitored. CONCLUSIONS: The trial aims to provide a better understanding of the causal role of learning EC skills using interventions delivered via mobile phone apps with respect to promoting well-being and preventing poor mental health in young people. This knowledge will be used to develop and disseminate innovative evidence-based, feasible, and effective Mobile-health public health strategies for preventing poor mental health and promoting well-being. TRIAL REGISTRATION: ClinicalTrials.gov ( www.clinicaltrials.org ). Number of identification: NCT04148508 November 2019.

The role of attentional deployment during distancing in adolescents with major depression.

Individuals with major depression (MD) show deficits in cognitive reappraisal. It is yet unexplored how the act of directing visual attention away from/towards emotional aspects impacts on cognitive reappraisal in MD. Thus, we examined the role of attentional deployment during cognitive reappraisal (specifially during distancing) in adolescent MD. 36 MD adolescents and 37 healthy controls (12-18 years) performed a cognitive reappraisal task during which they a) down-regulated self-reported negative affective responses to negative pictures via distancing, or b) simply attended to the pictures. During the task, attentional focus was systematically varied by directing participants' gaze to emotional vs. non-emotional picture aspects. The validity of this experimental manipulation was checked by continuous eye-tracking during the task. Across groups and gaze focus conditions, distancing diminished negative affective responses to the pictures. Regulation success significantly differed between groups dependent on gaze focus: MD adolescents showed relatively less regulation success than controls in the emotional gaze focus condition, while the reverse was true for the non-emotional gaze focus condition. The results suggest that in MD adolescents, an emotional context might interfere with emotion regulatory aims. The findings can provide an important starting point for the development of innovative training regimes that target deficient reappraisal processes in adolescents suffering from MD.

Altered neural processing of reward and punishment in adolescents with Major Depressive Disorder.

BACKGROUND: Altered reward and punishment function has been suggested as an important vulnerability factor for the development of Major Depressive Disorder (MDD). Prior ERP studies found evidence for neurophysiological dysfunctions in reinforcement processes in adults with MDD. To date, only few ERP studies have examined the neural underpinnings of reinforcement processing in adolescents diagnosed with MDD. The present event-related potential (ERP) study aimed to investigate neurophysiological mechanisms of anticipation and consumption of reward and punishment in adolescents with MDD in one comprehensive paradigm. METHOD: During ERP recording, 25 adolescents with MDD and 29 healthy controls (12-17 years) completed a Monetary Incentive Delay Task comprising both a monetary reward and a monetary punishment condition. During anticipation, the cue-P3 signaling attentional allocation was recorded. During consumption, the feedback-P3 and Reward Positivity (RewP) were recorded to capture attentional allocation and outcome evaluation, respectively. RESULTS: Compared to controls, adolescents with MDD showed prolonged cue-P3 latencies to reward cues. Furthermore, unlike controls, adolescents with MDD displayed shorter feedback-P3 latencies in the reward versus punishment condition. RewPs did not differ between groups. LIMITATIONS: It remains unanswered whether the observed alterations in adolescent MDD represent a state or trait. CONCLUSIONS: Delayed neural processing of reward cues corresponds to the clinical presentation of adolescent MDD with reduced motivational tendencies to obtain rewards. Relatively shorter feedback-P3 latencies in the reward versus punishment condition could indicate a high salience of performance-contingent reward. Frequent exposure of negatively biased adolescents with MDD to performance-contingent rewards might constitute a promising intervention approach.

Auditory selective attention in adolescents with major depression: An event-related potential study.

BACKGROUND: Major depression (MD) is associated with deficits in selective attention. Previous studies in adults with MD using event-related potentials (ERPs) reported abnormalities in the neurophysiological correlates of auditory selective attention. However, it is yet unclear whether these findings can be generalized to MD in adolescence. Thus, the aim of the present ERP study was to explore the neural mechanisms of auditory selective attention in adolescents with MD. METHODS: 24 male and female unmedicated adolescents with MD and 21 control subjects were included in the study. ERPs were collected during an auditory oddball paradigm. RESULTS: Depressive adolescents tended to show a longer N100 latency to target and non-target tones. Moreover, MD subjects showed a prolonged latency of the P200 component to targets. Across groups, longer P200 latency was associated with a decreased tendency of disinhibited behavior as assessed by a behavioral questionnaire. LIMITATIONS: To be able to draw more precise conclusions about differences between the neural bases of selective attention in adolescents vs. adults with MD, future studies should include both age groups and apply the same experimental setting across all subjects. CONCLUSIONS: The study provides strong support for abnormalities in the neurophysiolgical bases of selective attention in adolecents with MD at early stages of auditory information processing. Absent group differences in later ERP components reflecting voluntary attentional processes stand in contrast to results reported in adults with MD and may suggest that adolescents with MD possess mechanisms to compensate for abnormalities in the early stages of selective attention.

The temporal dynamics of coherent motion processing in autism spectrum disorder: evidence for a deficit in the dorsal pathway.

Individuals with autism spectrum disorder (ASD) show impairments in processing coherent motion which have been proposed to be linked to a general deficit in the dorsal visual pathway. However, few studies have investigated the neural mechanisms underlying coherent motion processing in ASD. Thus, the aim of this study was to further test the hypothesis of a dorsal pathway deficit in ASD using visual evoked potentials (VEPs). 16 children and adolescents with ASD and 12 typically developing controls were examined with VEPs elicited by a random dot kinematogram. After an initial experimental sequence, where subjects were presented randomly moving dots, a fraction of the dots moved coherently (dependent on the level of coherence, 20%, 40%, or 60% of the dots) to the left or right side. Subjects were asked to detect the direction of coherent motion via button press. On the behavioural level, no significant group differences emerged. On the neural level, coherently moving dots elicited a N200 followed by a late positive potential (P400). ASD subjects exhibited a reduced N200 amplitude compared to controls. Moreover, in the ASD group, a trend for a negative relationship between N200 amplitude and a measure of autistic pathology was revealed. The present study provides strong support of a dorsal stream deficiency in the disorder and renders alternative explanations for impaired coherent motion processing in ASD less likely. Together with findings from related research fields, our data indicate that deviances in the N200 during coherent motion perception might be fundamental to ASD.

A common variant in myosin-18B contributes to mathematical abilities in children with dyslexia and intraparietal sulcus variability in adults.

The ability to perform mathematical tasks is required in everyday life. Although heritability estimates suggest a genetic contribution, no previous study has conclusively identified a genetic risk variant for mathematical performance. Research has shown that the prevalence of mathematical disabilities is increased in children with dyslexia. We therefore correlated genome-wide data of 200 German children with spelling disability, with available quantitative data on mathematic ability. Replication of the top findings in additional dyslexia samples revealed that rs133885 was a genome-wide significant marker for mathematical abilities (P(comb) = 7.71 × 10(-10), n = 699), with an effect size of 4.87%. This association was also found in a sample from the general population (P = 0.048, n = 1080), albeit with a lower effect size. The identified variant encodes an amino-acid substitution in MYO18B, a protein with as yet unknown functions in the brain. As areas of the parietal cortex, in particular the intraparietal sulcus (IPS), are involved in numerical processing in humans, we investigated whether rs133885 was associated with IPS morphology using structural magnetic resonance imaging data from 79 neuropsychiatrically healthy adults. Carriers of the MYO18B risk-genotype displayed a significantly lower depth of the right IPS. This validates the identified association between rs133885 and mathematical disability at the level of a specific intermediate phenotype.

Evidence for the involvement of ZNF804A in cognitive processes of relevance to reading and spelling.

Previous studies have shown that individuals with schizophrenia and dyslexia display common neurocognitive abnormalities. The aim of the present study was to determine whether known schizophrenia-risk genes contribute to dyslexia risk or to disease-relevant cognitive functions. For this purpose, we genotyped the schizophrenia-associated risk variants within zinc-finger protein 804A (ZNF804A), transcription-factor 4 and neurogranin in a large dyslexia case-control sample. We tested all variants for association with dyslexia (927 cases, 1096 controls), and with eight language-relevant cognitive processes (1552 individuals). We observed six significant associations between language-relevant traits and the ZNF804A-variant rs1344706. Interestingly, the ZNF804A schizophrenia risk variant was associated with a better cognitive performance in our data set. This finding might be consistent with a previously reported ZNF804A association in schizophrenia, in which patients carrying the schizophrenia-risk allele at rs1344706 showed a better performance in two memory tests. In conclusion, the present study provides evidence that ZNF804A might have a role in cognitive traits of relevance to reading and spelling, and underlines the phenotypic complexity that might be associated with ZNF804A.

First genome-wide association scan on neurophysiological endophenotypes points to trans-regulation effects on SLC2A3 in dyslexic children.

Dyslexia is one of the most common learning disorders affecting about 5% of all school-aged children. It has been shown that event-related potential measurements reveal differences between dyslexic children and age-matched controls. This holds particularly true for mismatch negativity (MMN), which reflects automatic speech deviance processing and is altered in dyslexic children. We performed a whole-genome association analysis in 200 dyslexic children, focusing on MMN measurements. We identified rs4234898, a marker located on chromosome 4q32.1, to be significantly associated with the late MMN component. This association could be replicated in an independent second sample of 186 dyslexic children, reaching genome-wide significance in the combined sample (P = 5.14e-08). We also found an association between the late MMN component and a two-marker haplotype of rs4234898 and rs11100040, one of its neighboring single nucleotide polymorphisms (SNPs). In the combined sample, this marker combination withstands correction for multiple testing (P = 6.71e-08). Both SNPs lie in a region devoid of any protein-coding genes; however, they both show significant association with mRNA-expression levels of SLC2A3 on chromosome 12, the predominant facilitative glucose transporter in neurons. Our results suggest a possible trans-regulation effect on SLC2A3, which might lead to glucose deficits in dyslexic children and could explain their attenuated MMN in passive listening tasks.

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. A broad spectrum of dyslexia related phenotypes, including phonological decoding, phoneme awareness, orthographic processing, short-term memory, rapid naming and basic mathematical abilities, were investigated in large sample of 287 German dyslexia families. We explored the interrelationship between the component phenotypes using correlation and principal component analyses (PCA). In addition, we estimated familiality for phenotypes as well as for the factors suggested by PCA. The correlation between the component phenotypes varied between -0.1 and 0.7. The PCA resulted in three factors: a general dyslexia factor, a speed of processing factor and a mathematical abilities factor. The familiality estimates of single components and factors ranged between 0.25 and 0.63. Instead of analyzing single dyslexia-related components, multivariate analyses including factor analytic approaches may help in the identification of susceptibility genes.

Linkage analyses of chromosomal region 18p11-q12 in dyslexia.

Dyslexia is characterized as a significant impairment in reading and spelling ability that cannot be explained by low intelligence, low school attendance or deficits in sensory acuity. It is known to be a hereditary disorder that affects about 5% of school aged children, making it the most common of childhood learning disorders. Several susceptibility loci have been reported on chromosomes 1, 2, 3, 6, 15, and 18. The locus on chromosome 18 has been described as having the strongest influence on single word reading, phoneme awareness, and orthographic coding in the largest genome wide linkage study published to date (Fisher et al., 2002). Here we present data from 82 German families in order to investigate linkage of various dyslexia-related traits to the previously described region on chromosome 18p11-q12. Using two- and multipoint analyses, we did not find support for linkage of spelling, single word reading, phoneme awareness, orthographic coding and rapid naming to any of the 14 genotyped STR markers. Possible explanations for our non-replication include differences in study design, limited power of our study and overestimation of the effect of the chromosome 18 locus in the original study.

Spatial-frequency- and contrast-dependent visible persistence and reading disorder: no evidence for a basic perceptual deficit.

The aetiology of dyslexia is still unclear, the most widely and controversially discussed theory is the magnocellular deficit hypothesis. One of the first and most influential paradigms used to investigate this visual deficit in dyslexia is the visible persistence (VP). However results on VP are decisively influenced by the method measuring VP. Lovegrove et al. (1986) repeatedly found a longer VP in reading disabled children which is significantly influenced by spatial frequency and contrast. However, these results were not investigated with the same method to date. Seventy-six unselected 2nd grade students (41 boys, 35 girls) of a rural primary school were investigated with an identical experimental design comparable to the Lovegrove et al. (1986) studies. Comparing reading disabled (n = 17) with controls (n = 34) no evidence for a longer VP in the reading disabled group was found. Additionally, correlation analysis revealed no evidence for a significance of VP for spelling, phoneme awareness and speech discrimination. This study does not encourage either a magnocellular nor parvocellular deficit in dyslexia.

Neurophysiological correlates of word recognition in dyslexia.

The neurobiological basis of learning word spellings and recognition of recently learned words was assessed in a learning experiment in 9 dyslexics and 9 controls male adolescents. In a recognition paradigm previously learned pseudowords and graphic symbols were presented 50 times each interspersed pseudo-randomly between 3 unlearned items which were repeated 50 times and 150 filler pseudowords. The electrophysiological correlate of recognition of learned pseudowords and graphic symbols was a positivity around 600 ms. For pseudowords the amplitude of this ERP component was significantly attenuated in the dyslexic group, no differences between the groups were found for recognition of graphic material. These data suggest that dyslexic children are able to learn the spelling of simple words, however, the neurophysiological correlate of recognition of these learned words is significantly attenuated. This result strengthens the view that dyslexic children are not generally impaired in recognition memory but specific for linguistic material like words.

[Follow-up of a sample of children with reading-spelling disorders in adulthood]. / Nachuntersuchung einer Stichprobe von leserechtschreibgestörten Kindern im Erwachsenenalter.

OBJECTIVE: Only a few studies--especially in Germany--deal with the long-term outcome for dyslexic children. The aim of our study was to assess a group of former students of a boarding school for dyslexic children (Chrisophorus School Oberurff). METHODS: 29 adults with spelling disorder were examined 20 years after they had left school. Their spelling ability was measured with the Mannheimer Spelling Test (MRT), psychiatric symptoms with the Symptom Checklist by Derogatis (SCL-90), occupational status with the Wegener "Magnitude-Prestigeskala" (Magnitude of Prestige Scale), and intelligence with the Culture Fair Intelligence Test (CFT 20). A self-constructed questionnaire was used to assess subjects' self-perception of their reading and spelling abilities, the role of reading and spelling in their work, and the influence of reading and spelling on their choice of employment. RESULTS: Spelling skills at follow-up were more than 0.5 standard deviations above the spelling skills measured at school. The occupational status is rather high at 75% above average. There is no evidence of a significant load of psychiatric symptoms among the dyslexic adults. CONCLUSIONS: The general finding is a favorable development of children with spelling disorder 20 years after attendance at a special boarding school for dyslexic children. High IQ, the high socioeconomic status of the probands and their parents, and the long-lasting remedial work at school are most likely the relevant factors for this development.

[Practice in spelling in remedial groups--results of an evaluation study in secondary education]. / Rechtschreibtraining in schulischen Fördergruppen--Ergebnisse einer Evaluationsstudie in der Primarstufe.

OBJECTIVE: This study aims to evaluate in a school-based tutoring setting a training program for spelling (Marburger Rechtschreibtraining) that has proven effective in non-school settings. A spelling training program already in use at the school serves as the control condition. METHODS: A total of 37 second- and third-graders rated by their teachers as spelling disabled participated in the study. In addition to their regular lessons, the children received two added lessons in small tutoring groups each week. RESULTS: The skills of the children in the tutoring program had increased significantly two years later regardless of the method used. This effect was confirmed both by tests as well as by teachers' and parental reports. However, the children's emotional attitudes towards school failed to change significantly. The control group that had received no tutoring improved as well. CONCLUSIONS: Tutoring spelling disabled children in small groups is an effective method for improving their reading and spelling abilities. Nevertheless, the fact that the skills of children in the control group without any tutoring also improved raises a number of questions. The choice of method in our study had no effect on the outcome. Our study was unable to systematically evaluate a number of potential influences (such as sample selection); these should be investigated further.