Maternal Interleukin-6 concentration during pregnancy is associated with variation in frontolimbic white matter and cognitive development in early life

Maternal inflammation during pregnancy can alter the trajectory of fetal brain development and increase risk for offspring psychiatric disorders. However, the majority of relevant research to date has been conducted in animal models. Here, in humans, we focus on the structural connectivity of frontolimbic circuitry as it is both critical for socioemotional and cognitive development, and commonly altered in a range of psychiatric disorders associated with intrauterine inflammation. Specifically, we test the hypothesis that elevated maternal concentration of the proinflammatory cytokine interleukin-6 (IL-6) during pregnancy will be associated with variation in microstructural properties of this circuitry in the neonatal period and across the first year of life. Pregnant mothers were recruited in early pregnancy and maternal blood samples were obtained for assessment of maternal IL-6 concentrations in early (12.6 ± 2.8 weeks [S.D.]), mid (20.4 ± 1.5 weeks [S.D.]) and late (30.3 ± 1.3 weeks [S.D.]) gestation. Offspring brain MRI scans were acquired shortly after birth (N = 86, scan age = 3.7 ± 1.7 weeks [S.D.]) and again at 12-mo age (N = 32, scan age = 54.0 ± 3.1 weeks [S.D.]). Diffusion Tensor Imaging (DTI) was used to characterize fractional anisotropy (FA) along the left and right uncinate fasciculus (UF), representing the main frontolimbic fiber tract. In N = 30 of the infants with serial MRI data at birth and 12-mo age, cognitive and socioemotional developmental status was characterized using the Bayley Scales of Infant Development. All analyses tested for potentially confounding influences of household income, prepregnancy Body-Mass-Index, obstetric risk, smoking during pregnancy, and infant sex, and outcomes at 12-mo age were additionally adjusted for the quality of the postnatal caregiving environment. Maternal IL-6 concentration (averaged across pregnancy) was prospectively and inversely associated with FA (suggestive of reduced integrity under high inflammatory conditions) in the newborn offspring (bi-lateral, p < 0.01) in the central portion of the UF proximal to the amygdala. Furthermore, maternal IL-6 concentration was positively associated with rate of FA increase across the first year of life (bi-lateral, p < 0.05), resulting in a null association between maternal IL-6 and UF FA at 12-mo age. Maternal IL-6 was also inversely associated with offspring cognition at 12-mo age, and this association was mediated by FA growth across the first year of postnatal life. Findings from the current study support the premise that susceptibility for cognitive impairment and potentially psychiatric disorders may be affected in utero, and that maternal inflammation may constitute an intrauterine condition of particular importance in this context

Status of the IUCF Proton Radiation Therapy Facility

This research was sponsored by the National Science Foundation Grant NSF PHY-931478

Neonatal brain volume as a marker of differential susceptibility to parenting quality and its association with neurodevelopment across early childhood

Parenting quality is associated with child cognitive and executive functions (EF), which are important predictors of social and academic development. However, children vary in their susceptibility to parenting behaviors, and the neurobiological underpinnings of this susceptibility are poorly understood. In a prospective longitudinal study, we examined whether neonatal total brain volume (TBV) and subregions of interest (i.e., hippocampus (HC) and anterior cingulate gyrus (ACG)) moderate the association between maternal sensitivity and cognitive/EF development across early childhood. Neonates underwent a brain magnetic resonance imaging scan. Their cognitive performance and EF was characterized at 2.0 ± 0.1 years (N = 53) and at 4.9 ± 0.8 years (N = 36) of age. Maternal sensitivity was coded based on observation of a standardized play situation at 6-mo postpartum. Neonatal TBV moderated the association between maternal sensitivity and 2-year working memory as well as all 5-year cognitive outcomes, suggesting that the positive association between maternal sensitivity and child cognition was observed only among children with large or average but not small TBV as neonates. Similar patterns were observed for TBV-corrected HC and ACG volumes. The findings suggest that larger neonatal TBV, HC and ACG may underlie susceptibility to the environment and affect the degree to which parenting quality shapes long-term cognitive development

Maternal Cortisol Concentrations During Pregnancy and Sex-Specific Associations With Neonatal Amygdala Connectivity and Emerging Internalizing Behaviors

Background: Maternal cortisol during pregnancy has the potential to influence rapidly developing fetal brain systems that are commonly altered in neurodevelopmental and psychiatric disorders. Research examining maternal cortisol concentrations across pregnancy and offspring neurodevelopment proximal to birth is needed to advance understanding in this area and lead to insight into the etiology of these disorders. Methods: Participants were 70 adult women recruited during early pregnancy and their infants born after 34 weeks gestation. Maternal cortisol concentrations were assessed serially over 4 days in early, mid, and late gestation. Resting state functional connectivity magnetic resonance imaging of the neonatal amygdala was examined. Mothers reported on children's internalizing behavior problems at 24 months of age. Results: Maternal cortisol concentrations during pregnancy were significantly associated with neonatal amygdala connectivity in a sex-specific manner. Elevated maternal cortisol was associated with stronger amygdala connectivity to brain regions involved in sensory processing and integration, as well as the default mode network in girls, and with weaker connectivity to these brain regions in boys. Elevated maternal cortisol was associated with higher internalizing symptoms in girls only, and this association was mediated by stronger neonatal amygdala connectivity. Conclusions: Normative variation in maternal cortisol during pregnancy is associated with the coordinated functioning of the amygdala soon after birth in a sex-specific manner. The identified pathway from maternal cortisol to higher internalizing symptoms in girls via alterations in neonatal amygdala connectivity may be relevant for the etiology of sex differences in internalizing psychiatric disorders, which are more prevalent in women

Maternal Systemic Interleukin-6 During Pregnancy Is Associated With Newborn Amygdala Phenotypes and Subsequent Behavior at 2 Years of Age

Background Maternal inflammation during pregnancy increases the risk for offspring psychiatric disorders and other adverse long-term health outcomes. The influence of inflammation on the developing fetal brain is hypothesized as one potential mechanism but has not been examined in humans. Methods Participants were adult women (N = 86) who were recruited during early pregnancy and whose offspring were born after 34 weeks’ gestation. A biological indicator of maternal inflammation (interleukin-6) that has been shown to influence fetal brain development in animal models was quantified serially in early, mid-, and late pregnancy. Structural and functional brain magnetic resonance imaging scans were acquired in neonates shortly after birth. Infants’ amygdalae were individually segmented for measures of volume and as seeds for resting state functional connectivity. At 24 months of age, children completed a snack delay task to assess impulse control. Results Higher average maternal interleukin-6 concentration during pregnancy was prospectively associated with larger right amygdala volume and stronger bilateral amygdala connectivity to brain regions involved in sensory processing and integration (fusiform, somatosensory cortex, and thalamus), salience detection (anterior insula), and learning and memory (caudate and parahippocampal gyrus). Larger newborn right amygdala volume and stronger left amygdala connectivity were in turn associated with lower impulse control at 24 months of age, and mediated the association between higher maternal interleukin-6 concentrations and lower impulse control. Conclusions These findings provide new evidence in humans linking maternal inflammation during pregnancy with newborn brain and emerging behavioral phenotypes relevant for psychiatric disorders. A better understanding of intrauterine conditions that influence offspring disease susceptibility is warranted to inform targeted early intervention and prevention efforts

Impact of gonadectomy on maturational changes in brain volume in adolescent macaques

Adolescence is a transitional period between childhood and adulthood characterized by significant changes in global and regional brain tissue volumes. It is also a period of increasing vulnerability to psychiatric illness. The relationship between these patterns and increased levels of circulating sex steroids during adolescence remains unclear. The objective of the current study was to determine whether gonadectomy, prior to puberty, alters adolescent brain development in male rhesus macaques. Ninety-six structural MRI scans were acquired from 12 male rhesus macaques (8 time points per animal over a two-year period). Six animals underwent gonadectomy and 6 animals underwent a sham operation at 29 months of age. Mixed-effects models were used to determine whether gonadectomy altered developmental trajectories of global and regional brain tissue volumes. We observed a significant effect of gonadectomy on the developmental trajectory of prefrontal gray matter (GM), with intact males showing peak volumes around 3.5 years of age with a subsequent decline. In contrast, prefrontal GM volumes continued to increase in gonadectomized males until the end of the study. We did not observe a significant effect of gonadectomy on prefrontal white matter or on any other global or regional brain tissue volumes, though we cannot rule out that effects might be detected in a larger sample. Results suggest that the prefrontal cortex is more vulnerable to gonadectomy than other brain regions

Early-branching gut fungi possess a large, comprehensive array of biomass-degrading enzymes

The fungal kingdom is the source of almost all industrial enzymes in use for lignocellulose bioprocessing. We developed a systems-level approach that integrates transcriptomic sequencing, proteomics, phenotype, and biochemical studies of relatively unexplored basal fungi. Anaerobic gut fungi isolated from herbivores produce a large array of biomass-degrading enzymes that synergistically degrade crude, untreated plant biomass and are competitive with optimized commercial preparations from Aspergillus and Trichoderma. Compared to these model platforms, gut fungal enzymes are unbiased in substrate preference due to a wealth of xylan-degrading enzymes. These enzymes are universally catabolite-repressed and are further regulated by a rich landscape of noncoding regulatory RNAs. Additionally, we identified several promising sequence-divergent enzyme candidates for lignocellulosic bioprocessing

Time dependent mean field theory of the superfluid-insulator phase transition

We develop a time-dependent mean field approach, within the time-dependent variational principle, to describe the Superfluid-Insulator quantum phase transition. We construct the zero temperature phase diagram both of the Bose-Hubbard model (BHM), and of a spin-S Heisenberg model (SHM) with the XXZ anisotropy. The phase diagram of the BHM indicates a phase transition from a Mott insulator to a compressibile superfluid phase, and shows the expected lobe-like structure. The SHM phase diagram displays a quantum phase transition between a paramagnetic and a canted phases showing as well a lobe-like structure. We show how the BHM and Quantum Phase model (QPM) can be rigorously derived from the SHM. Based on such results, the phase boundaries of the SHM are mapped to the BHM ones, while the phase diagram of the QPM is related to that of the SHM. The QPM's phase diagram obtained through the application of our approach to the SHM, describes the known onset of the macroscopic phase coherence from the Coulomb blockade regime for increasing Josephson coupling constant. The BHM and the QPM phase diagrams are in good agreement with Quantum Monte Carlo results, and with the third order strong coupling perturbative expansion.Comment: 15 pages, 8 figures. To be published in Phys. Rev.

Deriving the mass of particles from Extended Theories of Gravity in LHC era

We derive a geometrical approach to produce the mass of particles that could be suitably tested at LHC. Starting from a 5D unification scheme, we show that all the known interactions could be suitably deduced as an induced symmetry breaking of the non-unitary GL(4)-group of diffeomorphisms. The deformations inducing such a breaking act as vector bosons that, depending on the gravitational mass states, can assume the role of interaction bosons like gluons, electroweak bosons or photon. The further gravitational degrees of freedom, emerging from the reduction mechanism in 4D, eliminate the hierarchy problem since generate a cut-off comparable with electroweak one at TeV scales. In this "economic" scheme, gravity should induce the other interactions in a non-perturbative way.Comment: 30 pages, 1 figur

Meeting reports: Research on Coupled Human and Natural Systems (CHANS): Approach, Challenges, and Strategies

Understanding the complexity of human–nature interactions is central to the quest for both human well-being and global sustainability. To build an understanding of these interactions, scientists, planners, resource managers, policymakers, and communities increasingly are collaborating across wide-ranging disciplines and knowledge domains. Scientists and others are generating new integrated knowledge on top of their requisite specialized knowledge to understand complex systems in order to solve pressing environmental and social problems (e.g., Carpenter et al. 2009). One approach to this sort of integration, bringing together detailed knowledge of various disciplines (e.g., social, economic, biological, and geophysical), has become known as the study of Coupled Human and Natural Systems, or CHANS (Liu et al. 2007a, b). In 2007 a formal standing program in Dynamics of Coupled Natural and Human Systems was created by the U.S. National Science Foundation. Recently, the program supported the launch of an International Network of Research on Coupled Human and Natural Systems (CHANS-Net.org). A major kick-off event of the network was a symposium on Complexity in Human–Nature Interactions across Landscapes, which brought together leading CHANS scientists at the 2009 meeting of the U.S. Regional Association of the International Association for Landscape Ecology in Snowbird, Utah. The symposium highlighted original and innovative research emphasizing reciprocal interactions between human and natural systems at multiple spatial, temporal, and organizational scales. The presentations can be found at ‹http://chans- net.org/Symposium_2009.aspx›. The symposium was accompanied by a workshop on Challenges and Opportunities in CHANS Research. This article provides an overview of the CHANS approach, outlines the primary challenges facing the CHANS research community, and discusses potential strategies to meet these challenges, based upon the presentations and discussions among participants at the Snowbird meeting