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Comprehensive Behavioral Intervention for Tics (CBIT) is a first-line treatment of Tourette syndrome (TS). However, the brain mechanisms involved in CBIT are poorly understood. Enhanced frontomesial EEG coherence during a Go/NoGo task has been suggested as a mechanism involved in voluntary tic control. In the current study, we conducted a randomized controlled trial to assess whether EEG coherence during a Go/NoGo task was associated with CBIT outcome.Thirty-two children with TS were randomly assigned to CBIT or to treatment-as-usual (TAU). Treatment outcome was assessed by a blinded evaluator with the Yale Global Tic Severity Scale (YGTSS) and the Clinical Global Impression - Improvement Scale (CGI-I). EEG was recorded during a Go/NoGo task at baseline and endpoint. EEG coherence was computed in the alpha frequency band between a priori selected channel pairs spanning the frontal and motor areas.Tic severity decreased significantly in the CBIT group. However, CBIT did not impact EEG coherence and baseline EEG coherence did not predict treatment outcome.Although CBIT was superior to TAU on blinded clinical outcomes, EEG coherence during the Go/NoGo task was not associated with change in tic severity.The brain processes involved in the inhibition of motor responses do not appear to be involved in CBIT.

We analyzed 131 human brains (44 neurotypical, 19 with Tourette syndrome, 9 with schizophrenia, and 59 with autism) for somatic mutations after whole genome sequencing to a depth of more than 200×. Typically, brains had 20 to 60 detectable single-nucleotide mutations, but ~6% of brains harbored hundreds of somatic mutations. Hypermutability was associated with age and damaging mutations in genes implicated in cancers and, in some brains, reflected in vivo clonal expansions. Somatic duplications, likely arising during development, were found in ~5% of normal and diseased brains, reflecting background mutagenesis. Brains with autism were associated with mutations creating putative transcription factor binding motifs in enhancer-like regions in the developing brain. The top-ranked affected motifs corresponded to MEIS (myeloid ectopic viral integration site) transcription factors, suggesting a potential link between their involvement in gene regulation and autism.

Mosaic mutations can be used to track cell ancestries and reconstruct high-resolution lineage trees during cancer progression and during development, starting from the first cell divisions of the zygote. However, this approach requires sampling and analyzing the genomes of multiple cells, which can be redundant in lineage representation, limiting the scalability of the approach. We describe a strategy for cost- and time-efficient lineage reconstruction using clonal induced pluripotent stem cell lines from human skin fibroblasts. The approach leverages shallow sequencing coverage to assess the clonality of the lines, clusters redundant lines and sums their coverage to accurately discover mutations in the corresponding lineages. Only a fraction of lines needs to be sequenced to high coverage. We demonstrate the effectiveness of this approach for reconstructing lineage trees during development and in hematologic malignancies. We discuss and propose an optimal experimental design for reconstructing lineage trees.

Tourette syndrome (TS) and attention-deficit/hyperactivity disorder (ADHD) frequently co-occur, especially in children. Reduced inhibitory control abilities has been suggested as a shared phenotype across both conditions but its neural underpinnings remain unclear. Here, we tested the behavioral and electrophysiological correlates of inhibitory control in children with TS, ADHD, TS+ADHD, and typically developing controls (TDC). One hundred and thirty-eight children, aged 7 to 14 years, performed a Go/NoGo task during dense-array EEG recording. The sample included four groups: children with TS only (n = 47), TS+ADHD (n = 32), ADHD only (n = 22), and matched TDC (n = 35). Brain activity was assessed with the means of frontal midline theta oscillations, as well as the N200 and P300 components of the event-related potentials. Our analyses revealed that both groups with TS did not differ from other groups in terms of behavioral performance, frontal midline theta oscillations, and event-related potentials. Children with ADHD-only had worse Go/NoGo task performance, decreased NoGo frontal midline theta power, and delayed N200 and P300 latencies, compared to typically developing controls. In the current study, we demonstrated that children with TS or TS+ADHD do not show differences in EEG during a Go/NoGo task compared to typically developing children. Our findings however suggest that children with ADHD-only have a distinct electrophysiological profile during the Go/NoGo task as indexed by reduced frontal midline theta power and delayed N200 and P300 latencies.

Objective In patients with Tourette syndrome and other primary tic disorders (PTDs), tics are typically preceded by premonitory urges (PUs). To date, only a few studies have investigated the location and frequency of PUs, and contrary to clinical experience, the results suggest that PUs are not located in the same anatomic region as the tics. This study aimed to further explore PU location and frequency in detail, differentiating the kind and complexity of the corresponding tics, in a large sample of patients with PTD.Methods A total of 291 adult (≥ 18 years) patients with a confirmed diagnosis of chronic PTD were included. The study was conducted online, assement included tics and the general characterization of PUs and a sophisticated body drawing for locating PUs.Results We found that PUs were located in the same body area as, or in direct proximity to, the corresponding tic. Most frequently, PUs were located in the face and at the head (62.1%). Compared with simple tics, complex (motor and vocal) tics were more often preceded by a PU; but there was no difference in PU frequency observed between motor tics and vocal tics. PUs were more often experienced at the front than at the back of the body (73% vs. 27%), while there was no difference between the right and left sides (41.6% vs. 41.3%).Conclusion The strong association between PU and tic location further supports the hypothesis that PUs represent the core of PTD. Accordingly, future therapies should focus on treating PUs to achieve greater tic reduction.

Background: Tourette syndrome (TS) is a childhood-onset neurodevelopmental disorder of complex genetic architecture and is characterized by multiple motor tics and at least one vocal tic persisting for more than 1 year. Methods: We performed a genome-wide meta-analysis integrating a novel TS cohort with previously published data, resulting in a sample size of 6133 individuals with TS and 13,565 ancestry-matched control participants. Results: We identified a genome-wide significant locus on chromosome 5q15. Integration of expression quantitative trait locus, Hi-C (high-throughput chromosome conformation capture), and genome-wide association study data implicated the NR2F1 gene and associated long noncoding RNAs within the 5q15 locus. Heritability partitioning identified statistically significant enrichment in brain tissue histone marks, while polygenic risk scoring of brain volume data identified statistically significant associations with right and left thalamus volumes and right putamen volume. Conclusions: Our work presents novel insights into the neurobiology of TS, thereby opening up new directions for future studies.

Pediatric obsessive-compulsive disorder (OCD) sometimes appears rapidly, even overnight, often after an infection. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections, or PANDAS, describes such a situation after infection withBinding of IgG to specific neurons in human and mouse brain slices was evaluated ex vivo after incubation with serum from 27 children with rigorously characterized PANDAS, both at baseline and after intravenous immunoglobulin (IVIG) treatment, and 23 matched control subjects. Binding was correlated with symptom measures. Neural activity after serum incubation was assessed in mouse slices using molecular markers and electrophysiological recording.IgG from children with PANDAS bound to CINs, but not to several other neuron types, more than IgG from control subjects, in three independent cohorts of patients. Post-IVIG serum had reduced IgG binding to CINs, and this reduction correlated with symptom improvement. Baseline PANDAS sera decreased activity of striatal CINs, but not of parvalbumin-expressing GABAergic interneurons, and altered their electrophysiological responses, in acute mouse brain slices. Post-IVIG PANDAS sera and IgG-depleted baseline sera did not alter the activity of striatal CINs.These findings provide strong evidence for striatal CINs as a critical cellular target that may contribute to pathophysiology in children with rapid-onset OCD symptoms, and perhaps in other conditions.

This article provides an overview of selected ongoing international efforts that have been inspired by Edward Zigler's vision to improve programs and policies for young children and families in the United States. The efforts presented are in close alignment with three strategies articulated by Edward Zigler: (a) conduct research that will inform policy advocacy; (b) design, implement, and revise quality early childhood development (ECD) programs; and (c) invest in building the next generation of scholars and advocates in child development. The intergenerational legacy left by Edward Zigler has had an impact on young children not only in the United States, but also across the globe. More needs to be done. We need to work together with a full commitment to ensure the optimal development of each child.

Tourette syndrome (TS) is a childhood-onset neurodevelopmental disorder characterized by several motor and phonic tics.In this study, we aimed to compare activated regulatory T cell (Treg) values between patients with TS/chronic tic disorder (CTD) and age- and sex-matched healthy controls (HCs).Patients with TS/CTD and age- and sex-matched HCs were included in the study. The severity of the disease was evaluated using the Yale Global Tic Severity Scale. CD4The study included 48 patients diagnosed with TS/CTD (36 males and 12 females, mean age: 11.58 ± 2.61) and 24 HCs (18 males and 6 females, mean age: 11.63 ± 2.60). The TS/CTD group had significantly higher activated regulatory T percentile with respect to the T helper value compared to the HCs (Our results suggest that Tregs may have a role in the pathogenesis of TS/CTD.

Tourette Syndrome (TS) is a neuropsychiatric disorder thought to involve a reduction of basal ganglia (BG) interneurons and malfunctioning of the BG circuitry. However, whether interneurons fail to develop or are lost postnatally remains unknown. To investigate the pathophysiology of early development in TS, induced pluripotent stem cell (iPSC)-derived BG organoids from TS patients and healthy controls were compared on multiple levels of measurement and analysis. BG organoids from TS individuals manifested an impaired medial ganglionic eminence fate and a decreased differentiation of cholinergic and GABAergic interneurons. Transcriptome analyses revealed organoid mispatterning in TS, with a preference for dorsolateral at the expense of ventromedial fates. Our results point to altered expression of GLI transcription factors downstream of the Sonic Hedgehog signaling pathway with cilia disruption at the earliest stages of BG organoid differentiation as a potential mechanism for the BG mispatterning in TS. This study uncovers early neurodevelopmental underpinnings of TS neuropathological deficits using organoids as a model system.

Cellular and molecular mechanisms involving immune-competent cells can modulate normal brain development, influencing the genesis, refinement, and maintenance of neural circuits. There is increasing evidence in support of the contribution of an early immune priming to the abnormal trajectories of maturation of cortico-subcortical circuits associated with the generation of tics. During postnatal life, the hyperreactivity of systemic immune pathways and neuroinflammation may contribute to natural fluctuations of the behavioral features manifesting in Tourette syndrome and related disorders. Moreover, abnormalities in the parallel development of neural and immune systems, as well as in stress responses, are reflected in the higher risk of autoimmune and allergic illnesses in people with these neurodevelopmental disorders. There is still limited knowledge regarding the efficacy of direct and indirect immune-modulatory interventions in the treatment of these disorders. There are also limitations in knowledge of the key molecular pathways associated with gut dysbiosis that can influence neuroimmune interactions in these disorders. This chapter provides an up-to-date summary of the existing knowledge around these themes, highlighting existing gaps that need to be addressed by future research in order to develop breakthrough, disease-modifying, immunological, hormonal, and microbiota-based therapeutic interventions.

The origin of tics may be related to a heightened and selective sensitivity to cues from within the body or from the outside world, possibly as a result of a reduced ability to suppress irrelevant information in sensory, motor, and cognitive domains. The temporal pattern of tics, which are known to occur in bouts and wax and wane in severity, and their long-term outcome might represent important clues to the neurobiology of tics. Moreover, the role played by the environmental context in modulating tic expression may be key to developing and refining novel behavioral interventions. The association of tics with comorbid behavioral problems has a very strong impact on social, emotional, and academic outcomes in adulthood. This chapter introduces the reader to the wide phenomenological spectrum of Tourette syndrome and other tic disorders. The key phenomenological features of Tourette syndrome and related disorders represent crucial educational objectives for clinicians, teachers, parents, and peers that may lead to better clinical, social, and academic outcomes.

Many children, adolescents, and adults with Tourette syndrome have impairments across various domains of social and adaptive functioning, both as a result of the severity and particular features of tics and as a result of co-occurring disorders such as attention-deficit/hyperactivity disorder and anxiety. The relative contribution of tics and comorbid disorders to these impairments is an area of active investigation. A thorough clinical assessment should also include standardized ratings of adaptive functioning. Psychosocial interventions for tics and associated behavioral disorders are constantly improving and show the potential to reduce symptom severity and associated impairment as well as to improve quality of life and adaptive functioning.

Improving the mental health of children and adolescents is a critical priority in China. However, only minimal information is available concerning the prevalence of mental disorders. In the present study, a two-stage national survey has been completed in five regions of China. In the first stage, data from the Achenbach Child Behavior Checklist (CBCL) were collected for each participant to identify the prevalence of the behavioral and emotional problems in China. A multistage cluster stratified random sampling design was used, and a total of 71,929 individuals aged 6-16 years were collected. In this large cohort, 36,893 (49.86%) were males, and 49,015 (66.24%) were living in urban communities. Overall, 17.6% (90% confidence interval 17.4%, 17.9%) of the children and adolescents were identified as having behavioral and emotional problems. Moreover, age and sex effect was found for the CBCL scores. The boys' cohort had a higher prevalence of behavioral and emotional problems than girls (18.6% versus 16.6%). In the older cohort aged 12-16, the prevalence was higher than for the younger cohort aged 6-11 (19.0% versus 15.9%). Notably, it seems that the prevalence of the behavioral and emotional problems for children and adolescents had a rise in the past 30 years, but the scarcity of pediatric psychiatrists in China needs to be addressed. To reduce the behavioral and emotional problems, the whole society, including mental health providers, educators, and parents, needs to focus on and pay more attention to it. It will have long-term benefits for China.

Environmental factors are at least as important as genetic factors for the development of obsessive–compulsive symptoms (OCS), but the identification of such factors remain a research priority. Our study aimed to investigate the association between a broad scope of potential risk factors and OCS in a large community cohort of children and adolescents. We evaluated 1877 participants and their caregivers at baseline and after 3 years to assess various demographic, prenatal, perinatal, childhood adversity, and psychopathological factors. Mean age at baseline was 10.2 years (SD 1.9) and mean age at follow-up was 13.4 years (SD 1.9). Reports of OCS at baseline and follow-up were analyzed using latent variable models. At preliminary regression analysis, 15 parameters were significantly associated with higher OCS scores at follow-up. At subsequent regression analysis, we found that eight of these parameters remained significantly associated with higher follow-up OCS scores while being controlled by each other and by baseline OCS scores. The significant predictors of follow-up OCS were: lower socioeconomic status (p = 0.033); lower intelligence quotient (p = 0.013); lower age (p

Introducao: O desenvolvimento neural e um processo extremamente complexo e dinâmico. Tao pronto se inicia o desenvolvimento do cerebro, as "celulas imunologicas" desempenham um papel fundamental em varios processos, incluindo a formacao e aperfeicoamento de circuitos neurais, bem como a diferenciacao sexual. Ha um crescente corpo de evidencias de que o sistema imunologico tambem desempenha um papel importante na fidiopatologia de diversos transtornos neurodesenvolvimentais e neuropsiquiatricos. Objetivo: O objetivo deste artigo e revisar os dados atualmente disponiveis sobre o papel do "sistema imunologico" em relacao ao desenvolvimento normal do cerebro, bem como a fisiopatogenia dos transtornos de neurodesenvolvimento e neuropsiquiatricos. Metodologia: Foi realizada uma pesquisa bibliografica tradicional para localizar artigos de revisao relevantes. Resultados: Os processos celulares e moleculares que compoem o nosso "sistema imunologico" sao cruciais para o desenvolvimento normal do cerebro e a formacao e manutencao de circuitos neurais. E cada vez mais evidente que o sistema imunologico e neuroinflamacao desempenham papeis importantes na etiopatogenia de pelo menos um subconjunto de individuos com autismo, esquizofrenia, transtorno obsessivo-compulsivo, sindrome de Tourette, depressao e transtornos do humor, bem como disturbios autoimunes e neurodegenerativos. Evidencias emergentes tambem apontam para a importância do eixo intestino-cerebral e do microbioma de um individuo em relacao a sua saude e bem-estar somatico e mental. Conclusoes: Existem interconexoes multidirecionais entre multiplos sistemas biologicos em nossos cerebros e corpos que sao mediados em parte pelo sistema imunologico. No momento, no entanto, a "promessa" desse campo continua sendo maior do que os "resultados finais". O tempo dira se novas intervencoes serao desenvolvidas que farao uma diferenca positiva no cuidado de nossos pacientes. Tambem e possivel que surjam biomarcadores validos que orientarao uma abordagem mais personalizada ao tratamento.

There are few effective pharmacological treatments for Tourette's syndrome. Many patients with Tourette's syndrome experience impairing tic symptoms despite use of available evidence-based treatments. The investigators conducted a small, uncontrolled trial to examine the safety, tolerability, and dosing of THX-110, a combination of ΔA 12-week uncontrolled trial of THX-110 (maximum daily ΔTic symptoms significantly improved over time with THX-110 treatment. Improvement in tic symptoms was statistically significant within 1 week of starting treatment compared with baseline. THX-110 treatment led to an average improvement in tic symptoms of more than 20%, or a 7-point decrease in the YGTSS score. Twelve of the 16 participants elected to continue to the extension phase, and only two participants dropped out early. Side effects were common but were generally managed by decreasing ΔAlthough the initial data from this trial in adults with refractory Tourette's syndrome are promising, future randomized double-blind placebo-controlled trials are necessary to demonstrate efficacy of THX-110 treatment. The challenges raised by the difficulty in blinding trials due to the psychoactive properties of many cannabis-derived compounds need to be further appreciated in these trial designs.

Poverty and teenage pregnancy are common in low‐and‐middle‐income countries and can impede the development of healthy parent‐child relationships. This study aimed to test whether a home‐visiting intervention could improve early attachment relationships between adolescent mothers and their infants living in poverty in Brazil. Analyses were conducted on secondary outcomes from a randomized controlled trial (NCT0280718) testing the efficacy of a home‐visiting program, Primeiros Laços, on adolescent mothers’ health and parenting skills and their infants’ development. Pregnant youth were randomized to intervention (n = 40) or care‐as‐usual (CAU, n = 40) from the first trimester of pregnancy until infants were aged 24 months. Mother‐infant attachment was coded during a mother‐infant interaction when the infants were aged 12 months. Electrophysiological correlates of social processing (mean amplitude of the Nc component) were measured while infants viewed facial images of the mother and a stranger at age 6 months. Infants in the intervention group were more securely attached and more involved with their mothers than those receiving CAU at 12 months. Smaller Nc amplitudes to the mother's face at 6 months were associated with better social behavior at 12 months. Our findings indicate that the Primeiros Laços Program is effective in enhancing the development of mother‐infant attachment.

BACKGROUND To date, no national-scale psychiatric epidemiological survey for children and adolescents has been conducted in China. In order to inform government officials and policymakers and to develop a comprehensive plan for service providers, there was a clear need to conduct an up-to-date systematic nationwide psychiatric epidemiological survey. METHODS We conducted a two-stage large-scale psychiatric point prevalence survey. Multistage cluster stratified random sampling was used as the sampling strategy. Five provinces were selected by comprehensively considering geographical partition, economic development, and rural/urban factors. In Stage 1, the Child Behavior Checklist was used as the screening tool. In Stage 2, Mini-International Neuropsychiatric Interview for Children and Adolescents and a diagnostic process based on the Diagnostic and Statistical Manual were used to make the diagnoses. Sampling weights and poststratification weights were employed to match the population distributions. Exploratory analyses were also performed using socio-demographic factors. Prevalence in socio-demographic factor subgroups and overall were estimated. Rao-Scott adjusted chi-square tests were utilized to determine if between-group differences were present. Factor interactions were checked by logistic regression analyses. RESULTS A total of 73,992 participants aged 6-16 years of age were selected in Stage 1. In Stage 2, 17,524 individuals were screened and diagnosed. The weighted prevalence of any disorder was 17.5% (95% CI: 17.2-18.0). Statistically significant differences in prevalence of any psychiatric disorder were observed between sexes [χ2 (1, N = 71,929) = 223.0, p

BackgroundThe symptoms of obsessive−compulsive disorder (OCD) are highly heterogeneous and it is unclear what is the optimal way to conceptualize this heterogeneity. This study aimed to establish a comprehensive symptom structure model of OCD across the lifespan using factor and network analytic techniques.MethodsA large multinational cohort of well-characterized children, adolescents, and adults diagnosed with OCD (N = 1366) participated in the study. All completed the Dimensional Yale-Brown Obsessive−Compulsive Scale, which contains an expanded checklist of 87 distinct OCD symptoms. Exploratory and confirmatory factor analysis were used to outline empirically supported symptom dimensions, and interconnections among the resulting dimensions were established using network analysis. Associations between dimensions and sociodemographic and clinical variables were explored using structural equation modeling (SEM).ResultsThirteen first-order symptom dimensions emerged that could be parsimoniously reduced to eight broad dimensions, which were valid across the lifespan: Disturbing Thoughts, Incompleteness, Contamination, Hoarding, Transformation, Body Focus, Superstition, and Loss/Separation. A general OCD factor could be included in the final factor model without a significant decline in model fit according to most fit indices. Network analysis showed that Incompleteness and Disturbing Thoughts were most central (i.e. had most unique interconnections with other dimensions). SEM showed that the eight broad dimensions were differentially related to sociodemographic and clinical variables.ConclusionsFuture research will need to establish if this expanded hierarchical and multidimensional model can help improve our understanding of the etiology, neurobiology and treatment of OCD.

BACKGROUND: Tourette syndrome (TS) is a neurodevelopmental disorder involving chronic motor and phonic tics. Most individuals with Tourette syndrome can suppress their tics for at least a short period of time. Yet, the brain correlates of tic suppression are still poorly understood. METHODS: In the current study, high-density electroencephalography (EEG) was recorded during a resting-state and a tic suppression session in 72 children with TS. Functional connectivity between cortical regions was assessed in the alpha band (8-13 Hz) using an EEG source connectivity method. Graph theory and network-based statistics were used to assess the global network topology and to identify brain regions showing increased connectivity during tic suppression. RESULTS: Graph theoretical analyses revealed distinctive global network topology during tic suppression, relative to rest. Using network-based statistics, we found a subnetwork of increased connectivity during tic suppression (p < .001). That subnetwork encompassed many cortical areas, including the right superior frontal gyrus and the left precuneus, which are involved in the default mode network. We also found a condition by age interaction, suggesting age-mediated increases in connectivity during tic suppression. CONCLUSIONS: These results suggest that children with TS suppress their tics through a brain circuit involving distributed cortical regions, many of which are part of the default mode network. Brain connectivity during tic suppression also increases as youths with TS mature. These results highlight a mechanism by which children with TS may control their tics, which could be relevant for future treatment studies.

Millions of children worldwide will not reach their potential in terms of education and development. However, it is widely known that investment in high-quality early childhood development (ECD) pays rich dividends throughout the lifespan of an individual, impacting their own lives, families, and communities in a positive way. Further evidence points to the importance of ECD in delivering the United Nations’ Sustainable Development Goals (SDGs). The multi-sectoral, integrated provision of ECD services is ideally placed to facilitate holistic positive change and enhance social cohesion in some of the most inequitable and vulnerable contexts. The LINKS project brings together an international network of researchers, who work in strategic partnership with United Nations Children’s Fund (UNICEF) and Early Years the Organisation for Young Children in Northern Ireland to support the development, implementation, and evaluation of ECD programs in low- and middle-income countries impacted by divisions and conflict. The project is designed to contribute to the international evidence base on ECD for social cohesion and sustaining peace to make a real difference in the lives of children, caregivers, and communities.

To test the efficacy of a nurse home visiting program (HVP) on child development, maternal and environmental outcomes in the first years of life. We conducted a randomized controlled trial to test the efficacy of Primeiros Laços, a nurse HVP for adolescent mothers living in a poor urban area of São Paulo, Brazil. Eighty adolescent mothers were included and randomized to receive either Primeiros Laços (intervention group, n = 40) or healthcare as usual (control group, n = 40). Primeiros Laços is a home visiting intervention delivered by trained nurses that starts during the first 16 weeks of pregnancy and continues to the child’s age of 24 months. Participants were assessed by blind interviewers at 8–16 weeks of pregnancy (baseline), 30 weeks of pregnancy, and 3, 6, 12, and 24 months of child’s age. We assessed oscillatory power in the mid-range alpha frequency via electroencephalography when the children were aged 6 months. Child development was measured by the Bayley Scales of Infant Development Third Edition (BSID-III). Weight and length were measured by trained professionals and anthropometric indexes were calculated. The home environment and maternal interaction with the child was measured by the Home Observation and Measurement of the Environment. Generalized estimating equation models were used to examine intervention effects on the trajectories of outcomes. Standardized effect sizes (Cohen’s d) were calculated using marginal means from endpoint assessments of all outcomes. The trial was registered at clinicaltrial.gov: NCT02807818. Our analyses showed significant positive effects of the intervention on child expressive language development (coefficient = 0.89, 95% CI [0.18, 1.61], p = 0.014), maternal emotional/verbal responsivity (coefficient = 0.97, 95% CI [0.37, 1.58], p = 0.002), and opportunities for variety in daily stimulation (coefficient = 0.37, 95% CI [0.09, 0.66], p = 0.009). Standardized effect sizes of the intervention were small to moderate. Primeiros Laços is a promising intervention to promote child development and to improve the home environment of low-income adolescent mothers. However, considering the limitations of our study, future studies should be conducted to assess Primeiros Laços potential to benefit this population.Clinical Trial Registration: The study was registered at clinicaltrial.gov (Registration date: 21/06/2016 and Registration number: NCT02807818).

The present study objectives were to examine the performance of the new M-CHAT-R algorithm to the original M-CHAT algorithm. The main purpose was to examine if the algorithmic changes increase identification of children later diagnosed with ASD, and to examine if there is a trade-off when changing algorithms. We included 54,463 screened cases from the Norwegian Mother and Child Cohort Study. Children were screened using the 23 items of the M-CHAT at 18 months. Further, the performance of the M-CHAT-R algorithm were compared to the M-CHAT algorithm on the 23-items. In total, 337 individuals were later diagnosed with ASD. Using M-CHAT-R algorithm decreased the number of correctly identified ASD children by 12 compared to M-CHAT, with no children with ASD screening negative on the M-CHAT criteria subsequently screening positive utilizing the M-CHAT-R algorithm. A non-parametric McNemar’s test determined a statistically significant difference in identifying ASD utilizing the M-CHAT-R algorithm. The present study examined the application of 20-item MCHAT-R scoring criterion to the 23-item MCHAT. We found that this resulted in decreased sensitivity and increased specificity for identifying children with ASD, which is a trade-off that needs further investigation in terms of cost-effectiveness. However, further research is needed to optimize screening for ASD in the early developmental period to increase identification of false negatives.

Objective To test the efficacy of a nurse home visiting program (HVP) on child development, maternal and environmental outcomes in the first years of life.Methods We conducted a randomized controlled trial to test the efficacy of Primeiros Laços, a nurse HVP for adolescent mothers living in a poor urban area of São Paulo, Brazil. Eighty adolescent mothers were included and randomized to receive either Primeiros Laços (intervention group, n = 40) or healthcare as usual (control group, n = 40) groups. Primeiros Laços is a home visiting intervention delivered by trained nurses that starts during the first 16 weeks of pregnancy and continues to the child’s age of 24 months. Participants were assessed by blind interviewers at 8–16 weeks of pregnancy (baseline), 30 weeks of pregnancy, 3, 6, and 12 months of child’s age. Child development was measured by the Bayley Scales of Infant Development Third Edition (BSID-III). Weight and length were measured by trained professionals and anthropometric indexes were calculated. The home environment and maternal interaction with the child was measured by the Home Observation and Measurement of the Environment (HOME). Generalized estimating equation (GEE) models were used to examine intervention effects on the trajectories of outcomes. Standardized effect sizes (Cohen’s d) were calculated using marginal means from endpoint assessments of all outcomes. The trial was registered at clinicaltrial.gov: NCT02807818.Results Our analyses showed significant positive effects of the intervention on child expressive language development (coefficient = 0.89, 95% CI [0.18, 1.61], p = 0.014), maternal emotional/verbal responsivity (coefficient = 0.97, 95% CI [0.37, 1.58], p = 0.002), and opportunities for variety in daily stimulation (coefficient = 0.37, 95% CI [0.09, 0.66], p = 0.009). Standardized effect sizes of the intervention were small to moderate.Conclusions Primeiros Laços is a promising intervention to promote child development and to improve the home environment of low-income adolescent mothers.