Maternal Interleukin-6 Is Associated With Macaque Offspring Amygdala Development and Behavior.

Human and animal cross-sectional studies have shown that maternal levels of the inflammatory cytokine interleukin-6 (IL-6) may compromise brain phenotypes assessed at single time points. However, how maternal IL-6 associates with the trajectory of brain development remains unclear. We investigated whether maternal IL-6 levels during pregnancy relate to offspring amygdala volume development and anxiety-like behavior in Japanese macaques. Magnetic resonance imaging (MRI) was administered to 39 Japanese macaque offspring (Female: 18), providing at least one or more time points at 4, 11, 21, and 36 months of age with a behavioral assessment at 11 months of age. Increased maternal third trimester plasma IL-6 levels were associated with offspring's smaller left amygdala volume at 4 months, but with more rapid amygdala growth from 4 to 36 months. Maternal IL-6 predicted offspring anxiety-like behavior at 11 months, which was mediated by reduced amygdala volumes in the model's intercept (i.e., 4 months). The results increase our understanding of the role of maternal inflammation in the development of neurobehavioral disorders by detailing the associations of a commonly examined inflammatory indicator, IL-6, on amygdala volume growth over time, and anxiety-like behavior.

Unmasking the Effects of L-DOPA on Rapid Dopamine Signaling with an Improved Approach for Nafion Coating Carbon-Fiber Microelectrodes.

L-DOPA has been the gold standard for symptomatic treatment of Parkinson's disease. However, its efficacy wanes over time as motor complications develop. Very little is known about how L-DOPA therapy affects the dynamics of fluctuating dopamine concentrations in the striatum on a rapid time scale (seconds). Electrochemical studies investigating the effects of L-DOPA treatment on electrically evoked dopamine release have reported conflicting results with significant variability. We hypothesize that the uncertainty in the electrochemical data is largely due to electrode fouling caused by polymerization of L-DOPA and endogenous catecholamines on the electrode surface. Thus, we have systematically optimized the procedure for fabricating cylindrical, Nafion-coated, carbon-fiber microelectrodes. This has enabled rapid and reliable detection of L-DOPA's effects on striatal dopamine signaling in intact rat brain using fast-scan cyclic voltammetry. An acute dose of 5 mg/kg L-DOPA had no significant effect on dopamine dynamics, demonstrating the highly efficient regulatory mechanisms at work in the intact brain. In contrast, administration of 200 mg/kg L-DOPA significantly increased the amplitude of evoked dopamine release by ∼200%. Overall, this work describes a reliable tool that allows a better measure of L-DOPA augmented dopamine release in vivo, measured using fast-scan cyclic voltammetry. It provides a methodology that improves the stability and performance of the carbon-fiber microelectrode when studying the molecular mechanisms underlying L-DOPA therapy and also promises to benefit a wide variety of studies because Nafion is so commonly used in electroanalytical chemistry.

Maternal Perinatal Stress Trajectories and Negative Affect and Amygdala Development in Offspring.

OBJECTIVE: Maternal psychological stress during pregnancy is a common risk factor for psychiatric disorders in offspring, but little is known about how heterogeneity of stress trajectories during pregnancy affect brain systems and behavioral phenotypes in infancy. This study was designed to address this gap in knowledge. METHODS: Maternal anxiety, stress, and depression were assessed at multiple time points during pregnancy in two independent low-risk mother-infant cohorts (N=115 and N=2,156). Trajectories in maternal stress levels in relation to infant negative affect were examined in both cohorts. Neonatal amygdala resting-state functional connectivity MRI was examined in a subset of one cohort (N=60) to explore the potential relationship between maternal stress trajectories and brain systems in infants relevant to negative affect. RESULTS: Four distinct trajectory clusters, characterized by changing patterns of stress over time, and two magnitude clusters, characterized by severity of stress, were identified in the original mother-infant cohort (N=115). The magnitude clusters were not associated with infant outcomes. The trajectory characterized by increasing stress in late pregnancy was associated with blunted development of infant negative affect. This relationship was replicated in the second, larger cohort (N=2,156). In addition, the trajectories that included increasing or peak maternal stress in late pregnancy were related to stronger neonatal amygdala functional connectivity to the anterior insula and the ventromedial prefrontal cortex in the exploratory analysis. CONCLUSIONS: The trajectory of maternal stress appears to be important for offspring brain and behavioral development. Understanding heterogeneity in trajectories of maternal stress and their influence on infant brain and behavioral development is critical to developing targeted interventions.

Persistently low readiness to vaccinate young children against COVID among vaccine adherent mothers in Vermont, USA.

Young children (0-4 years) represent the next population in whom the SARS-CoV-2 (COVID) vaccine will be available. Addressing parental feelings about vaccination will be important to optimize uptake. In this study, online surveys were administered in 78 perinatal women in the Northeast United States (Vermont) between January and July 2021. Women reported vaccine intention by indicating their plans to have their child vaccinated. Response choices included vaccinate as soon as possible, vaccinate but not immediately, or no intention to vaccinate. Subsequently, women rated their readiness to vaccinate children if offered the COVID vaccine tomorrow on an 11-point scale from 0 (definitely not get the vaccine) to 10 (definitely get the vaccine). Factors influencing ratings were measured categorically. General vaccine hesitancy was measured with the Parent Attitudes about Childhood Vaccinations scale. While many individual participants changed readiness to vaccinate children between baseline and follow-up; readiness in the study cohort remained unchanged. Approximately 50% of participants were likely to have their young children vaccinated. Concerns about vaccine safety was the largest driver of hesitancy. Importantly, even in a cohort highly adherent to childhood vaccines, hesitancy toward general childhood vaccines predicted decreased readiness for young children to receive the COVID vaccine. Our data provide evidence that maternal attitudes about the COVID vaccine are not fixed but overall readiness remains low, that prior adherence to childhood vaccine schedules will not predict vaccine behavior related to the COVID vaccine, and that public health messaging should emphasize messaging targeting vaccine safety in children.

Newborn amygdala connectivity and early emerging fear.

Connectivity between the amygdala, insula (Amygdala-aI) and ventral medial prefrontal cortex (Amygdala-vmPFC) have been implicated in individual variability in fear and vulnerability to psychiatric disorders. However, it is currently unknown to what extent connectivity between these regions in the newborn period is relevant for the development of fear and other aspects of negative emotionality (NE), such as sadness. Here, we investigate newborn Am-Ins and Am-vmPFC resting state functional connectivity in relation to developmental trajectories of fear and sadness over the first two years of life using data from the Infant Behavior Questionnaire Revised (IBQ-R) and Early Childhood Behavior Questionnaire (ECBQ) (N=62). Stronger newborn amygdala connectivity predicts higher fear and sadness at 6-months-of-age and less change from 6 to 24-months-of-age. Interestingly, Am-Ins connectivity was specifically relevant for fear and not sadness, while Am-vmPFC was associated only with sadness. Associations remained consistent after considering variation in maternal sensitivity and maternal postnatal depressive symptomology. Already by the time of birth, individual differences in amygdala connectivity are relevant for the expression of fear over the first two-years-of-life. Additionally, specificity is observed, such that connections relevant for fear development are distinct from those predicting sadness trajectories.