Prenatal alcohol exposure (PAE) occurs in ~11% of North American pregnancies and is the most common known cause of neurodevelopmental disabilities such as fetal alcohol spectrum disorder (FASD; ~2–5% prevalence). PAE has been consistently associated with smaller gray matter volumes in children, adolescents, and adults. A small number of longitudinal studies show altered gray matter development trajectories in late childhood/early adolescence, but patterns in early childhood and potential sex differences have not been characterized in young children. Using longitudinal T1-weighted MRI, the present study characterized gray matter volume development in young children with PAE (N = 42, 84 scans, ages 3–8 years) compared to unexposed children (N = 127, 450 scans, ages 2–8.5 years). Overall, we observed altered global and regional gray matter development trajectories in the PAE group, wherein they had attenuated age-related increases and more volume decreases relative to unexposed children. Moreover, we found more pronounced sex differences in children with PAE; females with PAE having the smallest gray matter volumes and the least age-related changes of all groups. This pattern of altered development may indicate reduced brain plasticity and/or accelerated maturation and may underlie the cognitive/behavioral difficulties often experienced by children with PAE. In conjunction with previous research on older children, adolescents, and adults with PAE, our results suggest that gray matter volume differences associated with PAE vary by age and may become more apparent in older children.

Background: Brain development during the preschool period is complex and extensive and underlies ongoing behavioral and cognitive maturation. Increasing understanding of typical brain maturation during this time is critical to early identification of atypical development and could inform treatments and interventions. Previous studies have suggested mismatches between brain structural and functional development in later childhood and adolescence. The current study aimed to delineate the developmental matches and mismatches between brain measures from multiple magnetic resonance imaging modalities in young children. Methods: Brain volume, cortical thickness, fractional anisotropy, cerebral blood flow (CBF), amplitude of low-frequency fluctuations (ALFF), regional homogeneity (ReHo), and eigenvector centrality mapping (ECM) were included. Multi-modal neuroimages for 159 datasets from 67 typically developing preschoolers (2.0-7.6 years old) were collected and analyzed. Results: Functional measures (CBF, ECM, ReHo, ALFF) had similar developmental trajectories across regions, whereas development trajectories for brain volumes and cortical thickness were more heterogeneous. Furthermore, within individuals, brain volumes and cortical thickness were very good at predicting individual scans from prior longitudinal scans. Conclusions: These findings provide a more detailed characterization of the complex interplay of different types of brain development in the early years, laying the foundation for future studies on the impact of environmental factors and neurodevelopmental disorders on the development matches/mismatches patterns between brain areas and modalities.

Sex-specific developmental differences in brain structure have been documented in older children and adolescents, with females generally showing smaller overall brain volumes and earlier peak ages than males. However, sex differences in gray matter structural development in early childhood are less studied. We characterized sex-specific trajectories of gray matter volume development in children aged 2-8 years. We acquired anatomical magnetic resonance imaging (MRI) of the brain at the Alberta Children's Hospital in 123 typically developing children. Most children were scanned multiple times, for a total of 393 scans (mean = 3.2 scans/subject). We segmented T1-weighted structural MRI with MaCRUISE to define 116 regions and measured both absolute volumes (mm3) and proportional volumes (percent of intracranial volume). We characterized growth trajectories of gray matter volume for these brain regions between 2 and 8 years using mixed-effects models, showing volume increases, with most posterior and temporo-parietal regions peaking before 8 years. We found widespread main effects of sex, with males having larger volumes in 86% of brain regions. However, there were no significant sex differences in trajectories (age or age2terms) for absolute volume. Proportional volumes of the right occipital fusiform gyrus and left medial postcentral gyrus showed significant age-by-sex interactions where females had steeper volume decreases than males. This study also confirms regional patterns observed in previous studies of older children, such as posterior-to-anterior timing of brain maturation. These results provide a comprehensive picture of gray matter volume development across early childhood, and suggest that sex differences do not emerge until later in development.

Prenatal alcohol exposure (PAE) is the leading known cause of birth defects and cognitive disabilities, with impacts on brain development and executive functioning. Abnormalities in structural and functional brain features are well-documented in children with PAE, but the effects of PAE on brain metabolism in children have received less attention. Levels of brain metabolites can be measured non-invasively using magnetic resonance spectroscopy (MRS). Here, we present the first study of PAE-related brain metabolite differences in early childhood (ages 3–8 years) and their associations with cognitive performance, including executive functioning (EF) and pre-reading skills. We measured metabolites in two cohorts of children with PAE and unexposed children using MRS in the anterior cingulate cortex (ACC; cohort 1) and left temporo-parietal cortex (LTP; cohort 2). Total choline (tCho), a marker of membrane/myelin metabolism, was elevated in both regions in children with PAE compared to unexposed children, and glutamate + glutamine (Glx), a marker of excitability, was elevated in the ACC. The PAE group exhibited more difficulties with EF, and higher tCho was associated with better EF in both PAE and unexposed groups. In addition, elevated Glx in the ACC was associated with poorer inhibitory control within the PAE group only. LTP metabolites were not significantly associated with pre-reading skills in PAE or unexposed groups. Together, these findings point to altered membrane metabolism and excitability in young children with PAE. These findings provide new insight to potential mechanisms by which PAE disrupts brain development and cognitive functioning in early childhood.

Bisphenol A (BPA) is a synthetic chemical used for the manufacturing of plastics, epoxy resin, and many personal care products. This ubiquitous endocrine disruptor is detectable in the urine of over 80% of North Americans. Although adverse neurodevelopmental outcomes have been observed in children with high gestational exposure to BPA, the effects of prenatal BPA on brain structure remain unclear. Here, using magnetic resonance imaging (MRI), we studied the associations of maternal BPA exposure with children's brain structure, as well as the impact of comparable BPA levels in a mouse model. Our human data showed that most maternal BPA exposure effects on brain volumes were small, with the largest effects observed in the opercular region of the inferior frontal gyrus (ρ = -0.2754), superior occipital gyrus (ρ = -0.2556), and postcentral gyrus (ρ = 0.2384). In mice, gestational exposure to an equivalent level of BPA (2.25 μg BPA/kg bw/day) induced structural alterations in brain regions including the superior olivary complex (SOC) and bed nucleus of stria terminalis (BNST) with larger effect sizes (1.07≤ Cohens d ≤ 1.53). Human (n = 87) and rodent (n = 8 each group) sample sizes, while small, are considered adequate to perform the primary endpoint analysis. Combined, these human and mouse data suggest that gestational exposure to low levels of BPA may have some impacts on the developing brain at the resolution of MRI.

Most studies on mammalian caregiving and attachment have focused on the mother-child relationship, particularly in humans. Yet, changing societal roles of male caregivers have highlighted the necessity for research with fathers. In this study, we examined the volume of the hypothalamus, an important subcortical brain area for caregiving and attachment, in a sample of N=50 fathering (child age 5-6 years) and N=45 nonfathering men using a novel technique to identify the human hypothalamus in 3T MRI. Furthermore, we employed three self-report measures to assess interindividual differences in adult attachment style across all men and caregiving beliefs in fathers. While we did not observe any significant difference in hypothalamus volume between fathers and non-fathers or associations between hypothalamus volume and self-reported adult attachment style across all men, self-reported caregiving beliefs were positively related to total hypothalamus volume in fathers. A follow-up analysis showed that fathers’ self-reported belief that a father’s role is important to child development was specifically related to tuberal hypothalamus volume, while self-reported enjoyment of spending time with the child was not associated with volume in hypothalamus sub-regions. Together, these findings suggest that interindividual variability in self reported caregiving beliefs in fathers is related to brain structure, warranting further research.

Attachment theory, developed by Mary Ainsworth and John Bowlby about seventy years ago, has become one of the most influential and comprehensive contemporary psychology theories. It predicts that early social interactions with significant others shape the emergence of distinct self- and other-representations, the latter affecting how we initiate and maintain social relationships across the lifespan. A person's attachment history will therefore associate with inter-individual differences in emotional and cognitive mechanisms sustaining representations, modeling, and understanding of others on the biological and brain level. This review aims at summarizing the currently available social neuroscience data in healthy participants on how inter-individual differences in attachment associate with brain anatomy and activity across the lifespan, and to integrate these data into an extended and refined functional neuro-anatomical model of human attachment (NAMA). We first propose a new prototypical initial attachment pathway and its derivatives as a function of attachment security, avoidance, and anxiety. Based on these pathways, we suggest a neural attachment system composed of two emotional mentalization modules (aversion and approach) and two cognitive mentalization modules (emotion regulation and mental state representation) and provide evidence on their functionality depending on inter-individual differences in attachment. We subsequently expand this first-person social neuroscience account by also considering a second-person social neuroscience perspective comprising the concepts of bio-behavioral synchrony and particularly inter-brain coherence. We hope that such extended and refined NAMA can inform attachment theory and ultimately help devising new prevention and intervention strategies for individuals and families at risk for attachment-related psychopathology.

Most studies on mammalian caregiving and attachment have focused on the mother-child relationship, particularly in humans. Yet, recent re-considerations of attachment theory and changing societal roles of male caregivers have highlighted the necessity for research with fathers. In this pre-registered study (https://aspredicted.org/5uj5y.pdf), we examined the structure of the hypothalamus – an important subcortical brain area for caregiving and attachment behavior – in a sample of N=95 fathering (child age 5-6 years) and non-fathering men. To do so, we used a recently developed technique to accurately and efficiently identify the human hypothalamus in 3T MRI and calculate hypothalamus volume. Furthermore, we employed several self-report measures to assess interindividual differences in attachment style across all men, and caregiving specifically in fathers. While we found no difference in hypothalamus volume between fathers and non-fathers, fathers' interindividual variation in caregiving style was related to hypothalamus volume. Specifically, we observed that fathers who held greater belief in the importance of their role as a father and reported more enjoyment of interacting with their child had greater total hypothalamus volume. This finding suggests that there is interindividual variability in the association between brain structure and caregiving style in fathers, warranting further research.

Attachment theory, developed by Mary Ainsworth and John Bowlby about seventy years ago, has become one of the most influential and comprehensive contemporary psychology theories. It predicts that early social interactions with significant others shape the emergence of distinct self- and other-representations, the latter affecting how we initiate and maintain social relationships across the lifespan. A person's attachment history will therefore associate with inter-individual differences in emotional and cognitive mechanisms sustaining representations, modeling, and understanding of others on the biological and brain level. This review aims at summarizing the currently available social neuroscience data in healthy participants on how inter-individual differences in attachment associate with brain anatomy and activity across the lifespan, and to integrate these data into an extended and refined functional neuro-anatomical model of human attachment (NAMA). We first propose a new prototypical initial attachment pathway and its derivatives as a function of attachment security, avoidance, and anxiety. Based on these pathways, we suggest a neural attachment system composed of two emotional mentalization modules (aversion and approach) and two cognitive mentalization modules (emotion regulation and mental state representation) and provide evidence on their functionality depending on inter-individual differences in attachment. We subsequently expand this first-person social neuroscience account by also considering a second-person social neuroscience perspective comprising the concepts of bio-behavioral synchrony and particularly interbrain coherence. We hope that such extended and refined NAMA can inform attachment theory and ultimately help devising new prevention and intervention strategies for individuals and families at risk for attachment-related psychopathology. (C) 2020 The Author(s). Published by Elsevier Ltd.

One of the most common inflammatory markers examined in depression is C-reactive protein (CRP). However, the magnitude of the association between CRP and depression when controlling for potentially confounding factors such as age, sex, socio-economic status, body mass index, medication and other substance use, and medical illness, is unclear. Inconsistencies in other methodological practices, such as sample collection, assaying, and data cleaning and transformation, may contribute to variations in results. We aggregate studies that examined the association between CFtP and depression in two ways. First, a systematic review summarizes how studies of CRP and depression have reported on methodological issues. Second, a tiered meta-analysis aggregates studies that have adhered to various levels of methodological rigor. Findings from the systematic review indicate a lack of protocol detail provided. The effect between depression and CRP was small, but highly significant across all stages of the meta-analysis (p < 0.01). The effect size in the most methodologically rigorous stage of the meta-analysis, which included studies controlling for age, sex, obesity, medical conditions and substance, medication, or psychosocial factors, was small (r = 0.05). There were also only 26 articles in this stage (13% of studies from the systematic review), suggesting that more studies that consistently account for these confounding factors are needed. Additionally, an a priori quality score of methodological rigor was a significant moderator in this stage of the meta-analysis. The effect size was strikingly attenuated (r = 0.005) and non-significant in studies with higher quality scores. We describe a set of recommended guidelines for future research to consider, including sample collection and assaying procedures, data cleaning and statistical methods, and control variables to assess.