Claudia Buss

Children's Brain Development Benefits from Longer Gestation.

Disruptions to brain development associated with shortened gestation place individuals at risk for the development of behavioral and psychological dysfunction throughout the lifespan. The purpose of the present study was to determine if the benefit for brain development conferred by increased gestational length exists on a continuum across the gestational age spectrum among healthy children with a stable neonatal course. Neurodevelopment was evaluated with structural magnetic resonance imaging in 100 healthy right-handed 6- to 10-year-old children born between 28 and 41 gestational weeks with a stable neonatal course. Data indicate that a longer gestational period confers an advantage for neurodevelopment. Longer duration of gestation was associated with region-specific increases in gray matter density. Further, the benefit of longer gestation for brain development was present even when only children born full term were considered. These findings demonstrate that even modest decreases in the duration of gestation can exert profound and lasting effects on neurodevelopment for both term and preterm infants and may contribute to long-term risk for health and disease.

Deactivation of the Limbic System During Acute Psychosocial Stress: Evidence from Positron Emission Tomography and Functional Magnetic Resonance Imaging Studies

BACKGROUND Stress-induced metabolic changes can have detrimental health effects. Newly developed paradigms to investigate stress in neuroimaging environments allow the assessment of brain activation changes in association with the perception of and the metabolic response to stress. METHODS We exposed human subjects to a psychosocial stressor in one positron emission tomography (n = 10) and one functional magnetic resonance imaging (fMRI; n = 40) experiment. RESULTS We observed a profound deactivation of limbic system components including hippocampus, hypothalamus, medio-orbitofrontal cortex and anterior cingulate cortex in subjects who reacted to the stressor with a significant increase of the endocrine stress marker cortisol. Further, in the fMRI study, the degree of deactivation in the hippocampus was correlated with the release of cortisol in response to the stress task. CONCLUSIONS The observed deactivation of limbic system structures suggests elevated activation at rest and during nonstressful situations. A model is proposed where the observed reduction in limbic system activity is essential for the initiation of the stress response.

Maternal cortisol over the course of pregnancy and subsequent child amygdala and hippocampus volumes and affective problems

Stress-related variation in the intrauterine milieu may impact brain development and emergent function, with long-term implications in terms of susceptibility for affective disorders. Studies in animals suggest limbic regions in the developing brain are particularly sensitive to exposure to the stress hormone cortisol. However, the nature, magnitude, and time course of these effects have not yet been adequately characterized in humans. A prospective, longitudinal study was conducted in 65 normal, healthy mother–child dyads to examine the association of maternal cortisol in early, mid-, and late gestation with subsequent measures at approximately 7 y age of child amygdala and hippocampus volume and affective problems. After accounting for the effects of potential confounding pre- and postnatal factors, higher maternal cortisol levels in earlier but not later gestation was associated with a larger right amygdala volume in girls (a 1 SD increase in cortisol was associated with a 6.4% increase in right amygdala volume), but not in boys. Moreover, higher maternal cortisol levels in early gestation was associated with more affective problems in girls, and this association was mediated, in part, by amygdala volume. No association between maternal cortisol in pregnancy and child hippocampus volume was observed in either sex. The current findings represent, to the best of our knowledge, the first report linking maternal stress hormone levels in human pregnancy with subsequent child amygdala volume and affect. The results underscore the importance of the intrauterine environment and suggest the origins of neuropsychiatric disorders may have their foundations early in life.

High pregnancy anxiety during mid-gestation is associated with decreased gray matter density in 6-9-year-old children.

Because the brain undergoes dramatic changes during fetal development it is vulnerable to environmental insults. There is evidence that maternal stress and anxiety during pregnancy influences birth outcome but there are no studies that have evaluated the influence of stress during human pregnancy on brain morphology. In the current prospective longitudinal study we included 35 women for whom serial data on pregnancy anxiety was available at 19 (+/-0.83), 25 (+/-0.9) and 31 (+/-0.9) weeks gestation. When the offspring from the target pregnancy were between 6 and 9 years of age, their neurodevelopmental stage was assessed by a structural MRI scan. With the application of voxel-based morphometry, we found regional reductions in gray matter density in association with pregnancy anxiety after controlling for total gray matter volume, age, gestational age at birth, handedness and postpartum perceived stress. Specifically, independent of postnatal stress, pregnancy anxiety at 19 weeks gestation was associated with gray matter volume reductions in the prefrontal cortex, the premotor cortex, the medial temporal lobe, the lateral temporal cortex, the postcentral gyrus as well as the cerebellum extending to the middle occipital gyrus and the fusiform gyrus. High pregnancy anxiety at 25 and 31 weeks gestation was not significantly associated with local reductions in gray matter volume.This is the first prospective study to show that a specific temporal pattern of pregnancy anxiety is related to specific changes in brain morphology. Altered gray matter volume in brain regions affected by prenatal maternal anxiety may render the developing individual more vulnerable to neurodevelopmental and psychiatric disorders as well as cognitive and intellectual impairment.

Stress regulation in the central nervous system: evidence from structural and functional neuroimaging studies in human populations - 2008 Curt Richter Award Winner

The metabolic effects of stress are known to have significant health effects in both humans and animals. Most of these effects are mediated by the major stress hormonal axis in the body, the hypothalamic-pituitary-adrenal (HPA) axis. Within the central nervous system (CNS), the hippocampus, the amygdala and the prefrontal cortex as part of the limbic system are believed to play important roles in the regulation of the HPA axis. With the advent of structural and functional neuroimaging techniques, the role of different CNS structures in the regulation of the HPA axis can be investigated more directly. In the current paper, we summarize the findings obtained in our laboratory in the context of stress and HPA axis regulation. Our laboratory has developed and contributed to the development of manual and automated segmentation protocols from structural magnetic resonance imaging (MRI) scans for assessment of hippocampus, amygdala, medial temporal lobe and frontal lobe structures. Employing these protocols, we could show significant age-related changes in HC volumes, which were different between men and women, with pre-menopausal women showing smaller age-related volume decline compared to men. We could recently extent these findings by showing how estrogen therapy after menopause leads to higher volumes in the HC. Investigating possible neurotoxicity effects of steroids, we showed effects of long-term steroid exposure on HC volumes, and investigated variability of HC volumes in relation to HPA axis regulation in young and elderly populations. Here, we were able to follow-up from non-imaging studies showing that subjects low in self-esteem have higher cortisol stress responses, and the HC emerged as the critical link between these variables. Recently, we have made two more important discoveries with regard to HC volume: we could show that HC volume is as variable in young as it is in older adults, in subjects ranging in age from 18 to 80 years. Also, we have linked birth weight and maternal care to HC volumes in young adults, demonstrating the effects of variations in maternal care on the integrity of the CNS. Besides structural assessments, there is increasing interest in functional techniques to investigate possible links between CNS activity and HPA axis regulation. These two approaches complement each other; some aspects of HPA axis regulation might be linked to the integrity of a specific CNS structure, while other aspects might be linked to the function of a specific structure with no involvement of CNS morphology. Thus, we have developed a mental arithmetic stress task that can be employed in functional neuroimaging studies, and have used it in a number of functional neuroimaging studies. Employing positron emission tomography (PET), we were able to demonstrate that stress causes dopamine release if subjects reported low maternal care early in life. Finally, employing the task in functional magnetic resonance imaging (fMRI), we could show how exposure to stress and activation of the HPA axis are associated with decreased activity in major portions of the limbic system, a result that allows to speculate on the effects of stress on cognitive and emotional regulation in the brain. Taken together, the use of neuroimaging techniques in Psychoneuroendocrinology opens exciting new possibilities for the investigation of stress effects in the central nervous system.

Maternal Care Modulates the Relationship between Prenatal Risk and Hippocampal Volume in Women But Not in Men

Smaller hippocampal volume is associated with psychiatric disorders. Variations in hippocampal volume are discussed as both a consequence of the neurotoxic effects of stress and as a pre-existing condition leading to increased vulnerability for cognitive and emotional impairments. To investigate whether early experience can account for variability in hippocampal volume in adulthood (vulnerability hypothesis), we assessed the relationship between birth weight and hippocampal volume in 44 subjects. The reported quality of maternal care in early childhood, as evaluated by the Parental Bonding Inventory, was used as index of the quality of the postnatal environment. Hippocampal volume was assessed from magnetic resonance images using a manual segmentation protocol. We show that birth weight significantly predicts hippocampal volume in adulthood only in female subjects reporting low maternal care. The results suggest that the postnatal environment modulates the neurodevelopmental consequences of prenatal risk and that this effect is sex-specific.

The Contribution of Maternal Stress to Preterm Birth: Issues and Considerations

Preterm birth represents the most significant problem in maternal-child health, with maternal stress identified as a variable of interest. The effects of maternal stress on risk of preterm birth may vary as a function of context. This article focuses on select key issues and questions highlighting the need to develop a better understanding of which particular subgroups of pregnant women may be especially vulnerable to the potentially detrimental effects of maternal stress, and under what circumstances and at which stages of gestation. Issues related to the characterization and assessment of maternal stress and candidate biologic mechanisms are addressed.

Exposure to Prenatal Psychobiological Stress Exerts Programming Influences on the Mother and Her Fetus

Background/Aims: Accumulating evidence from a relatively small number of prospective studies indicates that exposure to prenatal stress profoundly influences the developing human fetus with consequences that persist into childhood and very likely forever. Methods: Maternal/fetal dyads are assessed at ∼20, ∼25, ∼31 and ∼36 weeks of gestation. Infant assessments begin 24 h after delivery with the collection of cortisol and behavioral responses to the painful stress of the heel-stick procedure and measures of neonatal neuromuscular maturity. Infant cognitive, neuromotor development, stress and emotional regulation are evaluated at 3, 6 12 and 24 months of age. Maternal psychosocial stress and demographic information is collected in parallel with infant assessments. Child neurodevelopment is assessed with cognitive tests, measures of adjustment and brain imaging between 5 and 8 years of age. Results:Psychobiological markers of stress during pregnancy, especially early in gestation, result in delayed fetal maturation, disrupted emotional regulation and impaired cognitive performance during infancy and decreased brain volume in areas associated with learning and memory in 6- to 8-year-old children. We review findings from our projects that maternal endocrine alterations that accompany pregnancy and influence fetal/infant/child development are associated with decreased affective responses to stress, altered memory function and increased risk for postpartum depression. Conclusions: Our findings indicate that the mother and her fetus both are influenced by exposure to psychosocial and biological stress. The findings that fetal and maternal programming occur in parallel may have important implications for long-term child development and mother/child interactions.

Prenatal stress and developmental programming of human health and disease risk: concepts and integration of empirical findings.

Purpose of reviewThe concept of the developmental origins of health and disease susceptibility is rapidly attracting interest and gaining prominence as a complementary approach to understanding the causation of many complex common disorders that confer a major burden of disease; however several important issues and questions remain to be addressed, particularly in the context of humans. Recent findingsIn this review we enunciate some of these questions and issues, review empirical evidence primarily from our own recent studies on prenatal stress and stress biology, and discuss putative maternal–placental–fetal endocrine and immune/inflammatory candidate mechanisms that may underlie and mediate short-term and long-term effects of prenatal stress on the developing human embryo and fetus, with a specific focus on body composition, metabolic function, and obesity risk. SummaryThe implications for research and clinical practice are discussed with a summary of recent advances in noninvasive methods to characterize fetal, newborn, infant, and child developmental and health-related processes that, when coupled with available state-of-the-art statistical modeling approaches for longitudinal, repeated measures time series analysis, now afford unprecedented opportunities to explore and uncover the developmental origins of human health and disease.

Maternal pregnancy-specific anxiety is associated with child executive function at 6–9 years age

Because fetal brain development proceeds at an extremely rapid pace, early life experiences have the potential to alter the trajectory of neurodevelopment, which may increase susceptibility for developmental and neuropsychiatric disorders. There is evidence that prenatal maternal stress and anxiety, especially worries specifically related to being pregnant, influence neurodevelopmental outcomes. In the current prospective longitudinal study, we included 89 women for whom serial data were available for pregnancy-specific anxiety, state anxiety, and depression at 15, 19, 25, 31, and 37 weeks gestation. When the offspring from the target pregnancy were between 6 and 9 years of age, their executive function was assessed. High levels of mean maternal pregnancy-specific anxiety over the course of gestation were associated with lower inhibitory control in girls only and lower visuospatial working memory performance in boys and girls. Higher-state anxiety and depression also were associated with lower visuospatial working memory performance. However, neither state anxiety nor depression explained any additional variance after accounting for pregnancy-specific anxiety. The findings contribute to the literature supporting an association between pregnancy-specific anxiety and cognitive development and extend our knowledge about the persistence of this effect until middle childhood.