Guilherme Vanoni Polanczyk

Background: Maltreatment is strongly associated with adverse childhood outcomes. Yet, despite infants’ greater developmental vulnerability, prospective data characterizing maltreatment throughout the first years of life remain scarce. We aimed to examine the distribution and trajectories of exposure to maltreatment across infancy and toddlerhood in two socioeconomically distinct Brazilian populations. Methods: We analyzed data on 681 children from two longitudinal studies. Maltreatment was assessed from infancy through toddlerhood using 3-5 repeated measures of the Conflict Tactics Scales: Parent-child Version and operationalized as cumulative exposure. Trajectories were estimated using monotonic integrated P-splines and group differences were assessed using likelihood ratio tests. Findings: Maltreatment was already reported at 3 months. Psychological aggression was the most prevalent subtype, reported in 26% of children by 3 months and in around 90% of both groups by 24 months. Corporal punishment was substantially more frequent in the socioeconomically vulnerable population (LR = 45·94, p < 0·002). At 24 months, more than 95% of all children had been ever exposed to at least one subtype maltreatment behaviour. Co-occurrence was more common than isolated exposure by 12 months (60·3% and 79·7% of exposed infants), a pattern that continued to increase by 24 months (81·3% and 92·8%). Interpretation: Maltreatment rapidly accumulates during the first childhood years across different socioeconomic contexts. While socioeconomic vulnerability was substantially associated with corporal punishment, the results suggest an important role of culture in caregiving practices overall. Preventive efforts should begin during pregnancy and address maltreatment as a continuum of practices.

Background: Irritability affects one‐third of children and adolescents with attention‐deficit/hyperactivity disorder (ADHD) and is associated with negative outcomes. The family environment plays a prominent role in the child's development, and therefore on the risk for irritability, especially during the preschool period. The aim of this study was to investigate the association between multiple family environmental factors and irritability in preschool children with ADHD. Methods: This is a cross‐sectional analysis nested within a randomized clinical trial with preschool children with ADHD—the MAPPA study. Here, 128 children (107 males, 21 females) aged 3–5 years with complete data were included. Irritability was measured by the Affective Reactivity Index. Three dimensions of family environmental factors were considered: parenting, family environment, and maternal characteristics (comprising maternal psychopathology, temperament, and cognitive ability). Analyses were conducted to evaluate the association of individual factors with irritability, followed by a multiple linear regression model. Results: Associations were found between irritability and both parenting and maternal characteristics, particularly psychopathology and temperament. The multiple linear regression model revealed a greater frequency of negative over positive comments in the Preschool Five‐Minute Speech Sample alongside less positive parenting practices and maternal ADHD symptoms as the family environmental factors significantly associated with child irritability. Findings remained significant after controlling for child sex and child ADHD symptom severity. Conclusion: Our findings indicated that maternal individual characteristics and parenting practices are associated with irritability in preschool children with ADHD, supporting the importance of family environment in understanding this condition. A thorough assessment of parenting practices and parental psychopathology is relevant when planning interventions aimed at reducing irritability in preschoolers with ADHD.

Phelan-McDermid Syndrome (PMS), primarily linked to SHANK3 haploinsufficiency, presents with complex neurodevelopmental features, including developmental regression, whose underlying mechanisms are poorly understood. This study investigated the impact of SHANK3 disruption across multiple levels, from gene expression in patient-derived iPSC neurons to in vivo brain network activity. RNA-sequencing of iPSC-derived neurons from PMS patients with SHANK3 disruption only (n = 9) and controls (n = 7) revealed dysregulation in differential gene expression and co-expression modules linked to cell cycle, RNA metabolism, and metabolic pathways in SHANK3 -mutated neurons. All modules were correlated with PMS regression and enriched for genes implicated in neurodevelopmental or neurodegenerative disorders, such as autism, ADHD, and Alzheimer’s disease. At the cellular level, SHANK3 -mutated cultures exhibited increased proliferation of neural progenitors and intermediate progenitor markers. Differentiated neurons showed reduced morphological complexity, specific changes in postsynaptic marker density and puncta size, and electrophysiological characteristics suggestive of neuronal hyperexcitability. Electroencephalography (EEG) in a PMS patient cohort (n = 20) compared to controls (n = 30) demonstrated hyperconnectivity and excessive high-frequency oscillations, suggesting altered neural network dynamics. In summary, the use of different analytical approaches suggested that SHANK3 haploinsufficiency disrupts neurodevelopmental trajectories and revealed that regression in PMS may share common genes and pathways with neurodegeneration. We also characterized molecular and neurophysiological markers that can be useful in therapeutic protocols for PMS.

22q11.2 deletion syndrome (22q11.2DS) is the most common recurrent microdeletion in humans and a prototypical high-risk neurogenetic copy number variant (CNV) associated with a broad spectrum of neurodevelopmental and psychiatric disorders, including intellectual disability (ID), autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), anxiety, and psychotic symptoms. This hemizygous deletion encompasses multiple genes involved in brain development and neural circuit function, contributing to marked phenotypic variability and multisystem involvement. In pediatric populations, deficits in adaptive functioning are frequently reported and may occur independently of global intellectual impairment, reflecting broader behavioral vulnerabilities within this genetic risk architecture. Background/Objectives: This study aimed to characterize the sociodemographic, clinical, and intellectual profiles of children and adolescents with 22q11.2DS and to examine adaptive functioning and its associations with behavioral difficulties. Methods: Thirty-four patients aged 1–17 years with a confirmed molecular diagnosis of 22q11.2DS were assessed. Standardized instruments were used to evaluate cognitive performance, adaptive functioning, and behavioral outcomes. Results: Intellectual disability was highly prevalent, with most participants showing combined cognitive and adaptive impairments. Adaptive functioning was compromised across domains, with relatively higher socialization scores compared to other areas, such as daily living skills. Multivariate analyses indicated associations between sociodemographic factors and behavioral difficulties, as well as between social problems and lower global adaptive functioning. Conclusions: Together, these findings contribute to the characterization of the adaptive and behavioral phenotype associated with a high-risk neurogenetic CNV and highlight the relevance of adaptive functioning as a key outcome for early evaluation and intervention in pediatric 22q11.2DS.

The autonomic nervous system, relatively understudied compared to the central nervous system, is thought to play a key role in supporting attentional engagement, a cornerstone of cognitive control in early development. To address the non-trivial challenges that complex autonomic signals present to traditional modeling, we leverage recurrence quantification analysis (RQA), an established nonlinear approach for quantifying the temporal organization of heart-rate dynamics. Here, we compute recurrence metrics to examine trait, or participant level (across the task), and state level (moment-by-moment) autonomic recurrence patterns in relation to infants’ multimodal attentional engagement with objects in a cross-cultural sample from Singapore and Brazil (N = 78, Age = 8.63 - 25.32 months). Across both countries, at the trait level, we observe that for most metrics, lower participant-level autonomic recurrence is related to higher infant attentional engagement and higher parent-reported regulatory capacity. Similarly, at the state level, all recurrence metrics are lower during moments of attentional engagement compared to disengagement. Further, certain metrics show sensitivity to attentional transitions and differentiate between different types of attentional engagement. Findings suggest that reduced autonomic recurrence, indicative of enhanced autonomic flexibility and stronger parasympathetic contributions, supports early attentional engagement.

Exclusive breastfeeding (EBF) plays a crucial role in infant gut microbiome assembly and development. However, few studies have investigated the effects of EBF in restoring a perturbed microbiome. In this study, we applied whole metagenomic sequencing to assess the gut microbiome assembly in 525 Brazilian infants from 3 to 9 months of age of the Germina Cohort, demonstrating the early determinants of microbial taxonomy and function modulation. Our analysis shows that EBF alters the relative abundance of genes related to the microbiome taxonomy and function, with effects varying by delivery mode. EBF alters the pattern of carbohydrates, lipid metabolism, and cell structure pathways depending on the delivery mode. The microbiome age is closer to chronological infant age in EBF than in non-EBF infants, meaning a lower microbiome maturation index (MMI). Using a complementary machine learning approach, we show that Escherichia coli, Ruminococcus gnavus, and Clostridium neonatale, as well as vitamin K and o-antigen pathways contribute strongly to EBF prediction. Moreover, EBF influences the microbiome maturation in early life, toward a microbiome age more similar to the chronological infant's age.