The frequency of restricted and repetitive behaviours in a community sample of 15 month-old infants

Objective: To investigate the frequency and pattern of a wide range of restricted and repetitive behaviors (RRBs) in the second year of life. Method: Parents of 139 15-month-old typically developing infants from a community sample completed the Repetitive Behaviour Questionnaire-2 (RBQ-2), giving information on RRBs (e.g. stereotyped motor movements, sensory interests, routines and rituals and preoccupations with restricted interests) seen in their children. Results: The RBQ-2 was found to be a reliable measure of these behaviors at this age and revealed a high frequency of particular types of repetitive motor movements in 15-month-olds. Conclusion: These findings have implications for the early detection of disorders characterized by high levels of restricted and repetitive behaviors, such as Autism Spectrum Disorder (ASD)

Effects of lay support for pregnant women with social risk factors on infant development and maternal psychological health at 12 months postpartum

Background The ELSIPS (Evaluation of Lay Support in Pregnant Women with Social Risk) RCT showed that lay support for women with social risk had a positive effect on maternal mental health and mother-infant bonding. This exploratory study examined whether these observed benefits would impact infant development at 1 year. Methods A sub-sample of women whose infants were under one year who had participated in the ELSIPS RCT which randomised women to receive either standard care or the services of a Pregnancy Outreach Worker (POW), and who were contactable, were eligible to participate in the follow up. At home visits, the Bayley Scales of Infant Development (3rd Edition) and standardised measures of depression, self efficacy, mind-mindedness and bonding were completed. Results 486 women were eligible for follow up, of whom 154 agreed to participate. 61/273 were successfully followed up in the standard maternity care arm and 51/213 in the POW arm. Women who completed follow up were less depressed and had higher selfefficacy scores at 8–12 weeks postpartum than those who did not complete follow up. There were no significant differences in maternal outcomes, infant cognitive development, receptive communication, expressive communication, fine motor development or social/emotional functioning between groups at 12 month follow up. Infants of mothers who received the POW intervention had significantly better gross motor development than infants whose mothers received standard care (p<0.03)

Translation and preliminary validation of a Korean version of the parental reflective functioning questionnaire

This study aimed to explore the factor structure, reliability, and validity of a Korean translation of the Parental Reflective Functioning Questionnaire (PRFQ). The PRFQ consists of three subscales: prementalizing modes , certainty about mental states , and interest and curiosity in mental states . A convenience sample of 163 Korean parents completed the K‐PRFQ. Exploratory factor analysis showed three factors mapped on to the original PRFQ factors, but items from the original prementalizing modes subscale clustered into two additional factors. Data from a subsample (n = 67) showed that the certainty about mental states and interest and curiosity in mental states subscales correlated positively with more optimal self‐reported parenting. We discuss the validity of using the PRFQ in collectivistic culture

Examining Ecological Constraints on the Intergenerational Transmission of Attachment Via Individual Participant Data Meta-analysis

Parents\u2019 attachment representations and child\u2013parent attachment have been shown to be associated, but these associations vary across populations (Verhage et al., 2016). The current study examined whether ecological factors may explain variability in the strength of intergenerational transmission of attachment, using individual participant data (IPD) meta-analysis. Analyses on 4,396 parent\u2013child dyads (58 studies, child age 11\u201396 months) revealed a combined effect size of r =.29. IPD meta-analyses revealed that effect sizes for the transmission of autonomous-secure representations to secure attachments were weaker under risk conditions and weaker in adolescent parent\u2013child dyads, whereas transmission was stronger for older children. Findings support the ecological constraints hypothesis on attachment transmission. Implications for attachment theory and the use of IPD meta-analysis are discusse

Genetic Rearrangements Can Modify Chromatin Features at Epialleles

Analogous to genetically distinct alleles, epialleles represent heritable states of different gene expression from sequence-identical genes. Alleles and epialleles both contribute to phenotypic heterogeneity. While alleles originate from mutation and recombination, the source of epialleles is less well understood. We analyze active and inactive epialleles that were found at a transgenic insert with a selectable marker gene in Arabidopsis. Both converse expression states are stably transmitted to progeny. The silent epiallele was previously shown to change its state upon loss-of-function of trans-acting regulators and drug treatments. We analyzed the composition of the epialleles, their chromatin features, their nuclear localization, transcripts, and homologous small RNA. After mutagenesis by T-DNA transformation of plants carrying the silent epiallele, we found new active alleles. These switches were associated with different, larger or smaller, and non-overlapping deletions or rearrangements in the 3′ regions of the epiallele. These cis-mutations caused different degrees of gene expression stability depending on the nature of the sequence alteration, the consequences for transcription and transcripts, and the resulting chromatin organization upstream. This illustrates a tight dependence of epigenetic regulation on local structures and indicates that sequence alterations can cause epigenetic changes at some distance in regions not directly affected by the mutation. Similar effects may also be involved in gene expression and chromatin changes in the vicinity of transposon insertions or excisions, recombination events, or DNA repair processes and could contribute to the origin of new epialleles

Conceptual comparison of constructs as first step in data harmonization: Parental sensitivity, child temperament, and social support as illustrations

This article presents a strategy for the initial step of data harmonization in Individual Participant Data syntheses, i.e., making decisions as to which measures operationalize the constructs of interest - and which do not. This step is vital in the process of data harmonization, because a study can only be as good as its measures. If the construct validity of the measures is in question, study results are questionable as well. Our proposed strategy for data harmonization consists of three steps. First, a unitary construct is defined based on the existing literature, preferably on the theoretical framework surrounding the construct. Second, the various instruments used to measure the construct are evaluated as operationalizations of this construct, and retained or excluded based on this evaluation. Third, the scores of the included measures are recoded on the same metric. We illustrate the use of this method with three example constructs focal to the Collaboration on Attachment Transmission Synthesis (CATS) study: parental sensitivity, child temperament, and social support. This process description may aid researchers in their data pooling studies, filling a gap in the literature on the first step of data harmonization. • Data harmonization in studies using combined datasets is of vital importance for the validity of the study results. • We have developed and illustrated a strategy on how to define a unitary construct and evaluate whether instruments are operationalizations of this construct as the initial step in the harmonization process. • This strategy is a transferable and reproducible method to apply to the data harmonization process

A Maternal Influence on Reading the Mind in the Eyes Mediated by Executive Function: Differential Parental Influences on Full and Half-Siblings

BACKGROUND: Parent-of-origin effects have been found to influence the mammalian brain and cognition and have been specifically implicated in the development of human social cognition and theory of mind. The experimental design in this study was developed to detect parent-of-origin effects on theory of mind, as measured by the 'Reading the mind in the eyes' (Eyes) task. Eyes scores were also entered into a principal components analysis with measures of empathy, social skills and executive function, in order to determine what aspect of theory of mind Eyes is measuring. METHODOLOGY/PRINCIPAL FINDINGS: Maternal and paternal influences on Eyes scores were compared using correlations between pairs of full (70 pairs), maternal (25 pairs) and paternal siblings (15 pairs). Structural equation modelling supported a maternal influence on Eyes scores over the normal range but not low-scoring outliers, and also a sex-specific influence on males acting to decrease male Eyes scores. It was not possible to differentiate between genetic and environmental influences in this particular sample because maternal siblings tended to be raised together while paternal siblings were raised apart. The principal components analysis found Eyes was associated with measures of executive function, principally behavioural inhibition and attention, rather than empathy or social skills. CONCLUSIONS/SIGNIFICANCE: In conclusion, the results suggest a maternal influence on Eye scores in the normal range and a sex-specific influence acting to reduce scores in males. This influence may act via aspects of executive function such as behavioural inhibition and attention. There may be different influences acting to produce the lowest Eyes scores which implies that the heratibility and/or maternal influence on poor theory of mind skills may be qualitatively different to the influence on the normal range

Distal Xq duplication and functional Xq disomy

Distal Xq duplications refer to chromosomal disorders resulting from involvement of the long arm of the X chromosome (Xq). Clinical manifestations widely vary depending on the gender of the patient and on the gene content of the duplicated segment. Prevalence of Xq duplications remains unknown. About 40 cases of Xq28 functional disomy due to cytogenetically visible rearrangements, and about 50 cases of cryptic duplications encompassing the MECP2 gene have been reported. The most frequently reported distal duplications involve the Xq28 segment and yield a recognisable phenotype including distinctive facial features (premature closure of the fontanels or ridged metopic suture, broad face with full cheeks, epicanthal folds, large ears, small and open mouth, ear anomalies, pointed nose, abnormal palate and facial hypotonia), major axial hypotonia, severe developmental delay, severe feeding difficulties, abnormal genitalia and proneness to infections. Xq duplications may be caused either by an intrachromosomal duplication or an unbalanced X/Y or X/autosome translocation. In XY males, structural X disomy always results in functional disomy. In females, failure of X chromosome dosage compensation could result from a variety of mechanisms, including an unfavourable pattern of inactivation, a breakpoint separating an X segment from the X-inactivation centre in cis, or a small ring chromosome. The MECP2 gene in Xq28 is the most important dosage-sensitive gene responsible for the abnormal phenotype in duplications of distal Xq. Diagnosis is based on clinical features and is confirmed by CGH array techniques. Differential diagnoses include Prader-Willi syndrome and Alpha thalassaemia-mental retardation, X linked (ATR-X). The recurrence risk is significant if a structural rearrangement is present in one of the parent, the most frequent situation being that of an intrachromosomal duplication inherited from the mother. Prenatal diagnosis is performed by cytogenetic testing including FISH and/or DNA quantification methods. Management is multi-specialist and only symptomatic, with special attention to prevention of malnutrition and recurrent infections. Educational and rehabilitation support should be offered to all patients

Ex Vivo Treatment with a Novel Synthetic Aminoglycoside NB54 in Primary Fibroblasts from Rett Syndrome Patients Suppresses MECP2 Nonsense Mutations

BACKGROUND: Nonsense mutations in the X-linked methyl CpG-binding protein 2 (MECP2) comprise a significant proportion of causative MECP2 mutations in Rett syndrome (RTT). Naturally occurring aminoglycosides, such as gentamicin, have been shown to enable partial suppression of nonsense mutations related to several human genetic disorders, however, their clinical applicability has been compromised by parallel findings of severe toxic effects. Recently developed synthetic NB aminoglycosides have demonstrated significantly improved effects compared to gentamicin evident in substantially higher suppression and reduced acute toxicity in vitro. RESULTS: We performed comparative study of suppression effects of the novel NB54 and gentamicin on three MECP2 nonsense mutations (R294X, R270X and R168X) common in RTT, using ex vivo treatment of primary fibroblasts from RTT patients harboring these mutations and testing for the C-terminal containing full-length MeCP2. We observed that NB54 induces dose-dependent suppression of MECP2 nonsense mutations more efficiently than gentamicin, which was evident at concentrations as low as 50 µg/ml. NB54 read-through activity was mutation specific, with maximal full-length MeCP2 recovery in R168X (38%), R270X (27%) and R294X (18%). In addition, the recovered MeCP2 was translocated to the cell nucleus and moreover led to parallel increase in one of the most important MeCP2 downstream effectors, the brain derived neurotrophic factor (BDNF). CONCLUSION: Our findings suggest that NB54 may induce restoration of the potentially functional MeCP2 in primary RTT fibroblasts and encourage further studies of NB54 and other rationally designed aminoglycoside derivatives as potential therapeutic agents for nonsense MECP2 mutations in RTT