Multi-omic brain and behavioral correlates of cell-free fetal DNA methylation in macaque maternal obesity models

Maternal obesity during pregnancy is associated with neurodevelopmental disorder (NDD) risk. We utilized integrative multi-omics to examine maternal obesity effects on offspring neurodevelopment in rhesus macaques by comparison to lean controls and two interventions. Differentially methylated regions (DMRs) from longitudinal maternal blood-derived cell-free fetal DNA (cffDNA) significantly overlapped with DMRs from infant brain. The DMRs were enriched for neurodevelopmental functions, methylation-sensitive developmental transcription factor motifs, and human NDD DMRs identified from brain and placenta. Brain and cffDNA methylation levels from a large region overlapping mir-663 correlated with maternal obesity, metabolic and immune markers, and infant behavior. A DUX4 hippocampal co-methylation network correlated with maternal obesity, infant behavior, infant hippocampal lipidomic and metabolomic profiles, and maternal blood measurements of DUX4 cffDNA methylation, cytokines, and metabolites. Ultimately, maternal obesity altered infant brain and behavior, and these differences were detectable in pregnancy through integrative analyses of cffDNA methylation with immune and metabolic biomarkers.

Validation Study of the Korean Version of Rothbart’s Infant Behavior Questionnaire-Revised

This study presents the psychometric properties of the Infant Behavior Questionnaire-Revised (IBQ-R), including internal consistency, content validity, and construct validity. The IBQ-R is a caregiver (parent) reporting instrument designed to assess temperament in infants (aged 3-12 months). Two groups of participants were included. The first group comprised 92 infants and the second 83 infants, giving a total of 175 infants (M=8.3 months, 80 boys and 95 girls). Their caregivers completed IBQ-R. The IBQ-R subscales demonstrated adequate internal consistency. Also, confirmatory factor analyses of the IBQ-R scale found that three broad dimensions: surgency, negative affectivity, and orientation/regulation. This study confirmed that the IBQ-R is a reliable and valid temperament instrument that can be recommended for evaluating temperament in infants.

Elevated infant cortisol is necessary but not sufficient for transmission of environmental risk to infant social development: Cross-species evidence of mother–infant physiological social transmission

Environmental adversity increases child susceptibility to disrupted developmental outcomes, but the mechanisms by which adversity can shape development remain unclear. A translational cross-species approach was used to examine stress-mediated pathways by which poverty-related adversity can influence infant social development. Findings from a longitudinal sample of low-income mother–infant dyads indicated that infant cortisol (CORT) on its own did not mediate relations between early-life scarcity-adversity exposure and later infant behavior in a mother-child interaction task. However, maternal CORT through infant CORT served as a mediating pathway, even when controlling for parenting behavior. Findings using a rodent “scarcity-adversity” model indicated that pharmacologically blocking pup corticosterone (CORT, rodent equivalent to cortisol) in the presence of a stressed mother causally prevented social transmission of scarcity-adversity effects on pup social behavior. Furthermore, pharmacologically increasing pup CORT without the mother present was not sufficient to disrupt pup social behavior. Integration of our cross-species results suggests that elevated infant CORT may be necessary, but without elevated caregiver CORT, may not be sufficient in mediating the effects of environmental adversity on development. These findings underscore the importance of considering infant stress physiology in relation to the broader social context, including caregiver stress physiology, in research and interventional efforts.

Construct validity of the First-Year Inventory (FYI Version 2.0) in 12-month-olds at high-risk for Autism Spectrum Disorder

This study examines the construct validity of the First-Year Inventory 2.0 with respect to other established instruments in a sample of high-risk infant siblings of children with Autism Spectrum Disorder. The First-Year Inventory 2.0 is a parent-report screening instrument designed to identify 12-month-old infants at risk for an eventual diagnosis of Autism Spectrum Disorder and consists of two domains: Social-Communication and Sensory-Regulatory. Although the First-Year Inventory 2.0’s screening psychometrics have been examined, its construct validity has not been investigated. In a sample of 112 high-risk 12-month-olds, we examined the First-Year Inventory 2.0’s associations with the Autism Observation Scale for Infants, an observer-based Autism Spectrum Disorder screener, and with other developmental instruments measuring similar areas in social communication and regulatory functioning in young children. Findings generally supported the First-Year Inventory 2.0 associations with other instruments in expected ways. The First-Year Inventory 2.0 Social-Communication domain was notably associated with the Autism Observation Scale for Infant’s total score and with language and communication domains of the Vineland and the Mullen. The Sensory-Regulatory domain showed minimal associations with other instruments that only had a few sensory items. Considering different objectives and strengths of assessments, researchers and clinicians are encouraged to utilize a variety of instruments in a comprehensive evaluation of a child. Lay abstract The First-Year Inventory 2.0 is a parent-report screening instrument designed to identify 12-month-old infants at risk for an eventual diagnosis of Autism Spectrum Disorder. This instrument focuses on Social-Communication and Sensory-Regulatory areas of infant behavior. Although the First-Year Inventory 2.0 screening performance has been previously studied, its validity has not been examined. Establishing validity of an instrument is important because it supports the effectiveness and the reliability of the instrument. In this study, we examined relationship between the First-Year Inventory 2.0 (Social-Communication and Sensory-Regulatory areas) and other instruments that measure similar areas of infant behavior in a sample of high-risk infant siblings of children with Autism Spectrum Disorder. These other instruments share some common aims and theoretical areas with the First-Year Inventory 2.0: the Autism Observation Scale for Infants, the Mullen Scales of Early Learning, the Vineland Adaptive Behavior Scales-II, and the Infant Behavior Questionnaire. Findings generally supported the validity of the First-Year Inventory 2.0 with other instruments. In particular, the Social-Communication area of the First-Year Inventory 2.0 showed greater commonality with other instruments than in the Sensory-Regulatory area. The Sensory-Regulatory area seemed to be a unique feature of the First-Year Inventory 2.0 instrument. Considering different aims and strengths of assessments, researchers and clinicians are encouraged to utilize a variety of instruments in a comprehensive evaluation of a child.

Epigenetic tuning of brain signal entropy in emergent human social behavior

Background How the brain develops accurate models of the external world and generates appropriate behavioral responses is a vital question of widespread multidisciplinary interest. It is increasingly understood that brain signal variability—posited to enhance perception, facilitate flexible cognitive representations, and improve behavioral outcomes—plays an important role in neural and cognitive development. The ability to perceive, interpret, and respond to complex and dynamic social information is particularly critical for the development of adaptive learning and behavior. Social perception relies on oxytocin-regulated neural networks that emerge early in development. Methods We tested the hypothesis that individual differences in the endogenous oxytocinergic system early in life may influence social behavioral outcomes by regulating variability in brain signaling during social perception. In study 1, 55 infants provided a saliva sample at 5 months of age for analysis of individual differences in the oxytocinergic system and underwent electroencephalography (EEG) while listening to human vocalizations at 8 months of age for the assessment of brain signal variability. Infant behavior was assessed via parental report. In study 2, 60 infants provided a saliva sample and underwent EEG while viewing faces and objects and listening to human speech and water sounds at 4 months of age. Infant behavior was assessed via parental report and eye tracking. Results We show in two independent infant samples that increased brain signal entropy during social perception is in part explained by an epigenetic modification to the oxytocin receptor gene (OXTR) and accounts for significant individual differences in social behavior in the first year of life. These results are measure-, context-, and modality-specific: entropy, not standard deviation, links OXTR methylation and infant behavior; entropy evoked during social perception specifically explains social behavior only; and only entropy evoked during social auditory perception predicts infant vocalization behavior. Conclusions Demonstrating these associations in infancy is critical for elucidating the neurobiological mechanisms accounting for individual differences in cognition and behavior relevant to neurodevelopmental disorders. Our results suggest that an epigenetic modification to the oxytocin receptor gene and brain signal entropy are useful indicators of social development and may hold potential diagnostic, therapeutic, and prognostic value.

An open-source, wireless vest for measuring autonomic function in infants

Infant behavior, like all behavior, is the aggregate product of many nested processes operating and interacting over multiple time scales; the result of a tangle of inter-related causes and effects. Efforts in identifying the mechanisms supporting infant behavior require the development and advancement of new technologies that can accurately and densely capture behavior’s multiple branches. The present study describes an open-source, wireless autonomic vest specifically designed for use in infants 8–24 months of age in order to measure cardiac activity, respiration, and movement. The schematics of the vest, instructions for its construction, and a suite of software designed for its use are made freely available. While the use of such autonomic measures has many applications across the field of developmental psychology, the present article will present evidence for the validity of the vest in three ways: (1) by demonstrating known clinical landmarks of a heartbeat, (2) by demonstrating an infant in a period of sustained attention, a well-documented behavior in the developmental psychology literature, and (3) relating changes in accelerometer output to infant behavior.