Sex and age effects on gray matter volume trajectories in young children with prenatal alcohol exposure.

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.

The effects of prenatal bisphenol A exposure on brain volume of children and young mice.

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.

A functional neuro-anatomical model of human attachment (NAMA): Insights from first- and second-person social neuroscience.

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.

Replication and reproducibility issues in the relationship between C-reactive protein and depression: A systematic review and focused meta-analysis.

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 CRP 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.