scholarly journals Corticolimbic Circuit Structure Moderates an Association Between Early Life Stress and Later Trait Anxiety

2019 ◽  
Author(s):  
M. Justin Kim ◽  
Madeline J. Farber ◽  
Annchen R. Knodt ◽  
Ahmad R. Hariri
Keyword(s):  
Trait Anxiety ◽  
Life Stress ◽  
Early Life ◽  
Emotional Reactivity ◽  
Early Life Stress ◽  
Childhood Adversity ◽  
Structural Features ◽  
Individual Variability ◽  
Future Research ◽  
Wide Range

AbstractChildhood adversity is associated with a wide range of negative behavioral and neurodevelopmental consequences. However, individuals vary substantially in their sensitivity to such adversity. Here, we examined how individual variability in structural features of the corticolimbic circuit, which plays a key role in emotional reactivity, moderates the association between childhood adversity and later trait anxiety in 798 young adult university students. Consistent with prior research, higher self-reported childhood adversity was significantly associated with higher self-reported trait anxiety. However, this association was attenuated in participants with higher microstructural integrity of the uncinate fasciculus and greater thickness of the orbitofrontal cortex. These structural properties of the corticolimbic circuit may capture a neural profile of relative resiliency to early life stress, especially against the negative effects of childhood adversity on later trait anxiety. More generally, our findings highlight the potential utility in the simultaneous consideration of qualitatively different brain structural measures in explaining complex behavioral associations in future research.

Abstract 17: Early Life Stress Sensitizes The Angiotensin II-elicited Hypertensive Response

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Baojian Xue ◽  
Terry Beltz ◽  
Fang Guo ◽  
David M Pollock ◽  
Jennifer S Pollock ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Proinflammatory Cytokines ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Male Rats ◽  
Sprague Dawley ◽  
Cns Inflammation ◽  
Wide Range ◽  
The Brain

Separation of neonatal rodent pups from their mothers has been used as a model to study the effects of early life stress (ELS) on behavioral and physiological responses in adults. Using an Induction-Delay-Expression experimental paradigm, our previous studies demonstrate that a wide range of stressors administered during an induction period produces hypertensive response sensitization (HTRS) in response to a subsequent pro-hypertensive stimulus. HTRS is accompanied by activation of the brain renin-angiotensin system (RAS) and CNS inflammation. The present study investigated whether ELS induces HTRS and changes in brain-related underlying mechanisms. Rat neonates from Sprague-Dawley breeders were subjected to ELS by separating them each morning from their mothers for 3 h on postnatal days 2 to 14. Pups from non-handled litters formed control groups. At 10 weeks of age, male rats were used to evaluate blood pressure and autonomic function using telemetric probes and pharmacological methods. In addition, in separate control and ELS groups, the lamina terminalis (LT) structures and the hypothalamic paraventricular nucleus (PVN) were analyzed for mRNA expression of RAS components and proinflammatory cytokines. Adult ELS rats as compared to non-separated controls exhibited 1) HTRS during expression testing using 2 week ANG II infusions (120 ng/kg/min s.c.; ELS animals, Δ45.5±4.5 mmHg vs. controls, Δ22.4±3.1 mmHg); 2) a greater reduction in mean arterial pressure following ganglionic blockade (hexamethonium, 30 mg/kg, ip), 3) increased sympathetic drive to the heart (atenolol, 8 mg/kg, ip), 4) decreased vagal tone (atropine, 8 mg/kg, ip), and 5) increased mRNA expression of several components of the brain RAS and proinflammatory cytokines in the LT and PVN. These results suggest that maternal ELS may predispose individuals to hypertension that is mediated by upregulation of the brain RAS and proinflammatory cytokines and increased sympathetic drive to the cardiovascular system.

Neurodevelopmental plasticity and psychiatric vulnerability

2015 ◽  
Vol 30 (S2) ◽  
pp. S70-S70
Author(s):  
A. Dayer
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Methylation Status ◽  
Early Life Stress ◽  
Childhood Adversity ◽  
Cellular Level ◽  
Special Focus ◽  
Serotonin System ◽  
Increase Risk

The early developmental period is characterized by a high degree of plasticity and, consequently, is very sensitive to environmental factors, such as early life stressors (ELS). Exposure to ELS is known to increase risk to psychopathologies such as depression and anxiety disorders later in life . At a cellular level, alterations in the migration and integration of GABAergic interneurons (INs) in cortical circuits have emerged as a key processes involved in the vulnerability to psychiatric disorders . In humans and rodents, ELS interacts with genes regulating the serotonin system to increase risk to stress-related disorders . In addition, ELS is associated to a variety of epigenetic methylation changes in blood DNA from patients displaying a high loading of ELS . Here, we aimed to investigate the role of the ionotropic serotonin 3A receptor (5-HT3AR) at a genetic and epigenetic level in rodent and human models of early-life stress. We will first present data indicating that the 5-HT3AR is specifically expressed in a subset of cortical INs derived from the caudal ganglionic eminence (CGE) and controls early steps of cortical circuit assembly . Interestingly, the migration, transcriptional programs and positioning of 5-HT3AR expressing interneuron subtypes were found to be dysregulated in pathological models of early-life serotonin dysregulation. At a behavioral level, we found that ELS interacts with the 5-HTR3A to modulate social behaviors. Finally, we will present human data indicating that childhood adversity significantly impacts the methylation status of the promoter region of the human 5-HT3AR in an allele-specific manner. Taken together, this presentation will highlight the importance of the serotonin system in early life development and psychopathology with a special focus on the role of the 5-HT3AR in cortical interneuron development.

The adaptive and maladaptive continuum of stress responses – a hippocampal perspective

2015 ◽  
Vol 26 (4) ◽  
Author(s):  
Deepika Suri ◽  
Vidita A. Vaidya
Keyword(s):  
Stress Responses ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Negative Consequences ◽  
Functional Responses ◽  
Physiological Level ◽  
Early Stress ◽  
Wide Range ◽  
Potential Factors

AbstractExposure to stressors elicits a spectrum of responses that span from potentially adaptive to maladaptive consequences at the structural, cellular and physiological level. These responses are particularly pronounced in the hippocampus where they also appear to influence hippocampal-dependent cognitive function and emotionality. The factors that influence the nature of stress-evoked consequences include the chronicity, severity, predictability and controllability of the stressors. In addition to adult-onset stress, early life stress also elicits a wide range of structural and functional responses, which often exhibit life-long persistence. However, the outcome of early stress exposure is often contingent on the environment experienced in adulthood, and could either aid in stress coping or could serve to enhance susceptibility to the negative consequences of adult stress. This review comprehensively examines the consequences of adult and early life stressors on the hippocampus, with a focus on their effects on neurogenesis, neuronal survival, structural and synaptic plasticity and hippocampal-dependent behaviors. Further, we discuss potential factors that may tip stress-evoked consequences from being potentially adaptive to largely maladaptive.

scholarly journals Long-Term Impact of Early-Life Stress on Hippocampal Plasticity: Spotlight on Astrocytes

2020 ◽  
Vol 21 (14) ◽  
pp. 4999
Author(s):  
Gürsel Çalışkan ◽  
Anke Müller ◽  
Anne Albrecht
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Maternal Separation ◽  
Early Life Stress ◽  
Childhood Adversity ◽  
Neuronal Circuits ◽  
Long Term Effects ◽  
Hippocampal Plasticity ◽  
Local Circuits

Adverse experiences during childhood are among the most prominent risk factors for developing mood and anxiety disorders later in life. Early-life stress interventions have been established as suitable models to study the neurobiological basis of childhood adversity in rodents. Different models such as maternal separation, impaired maternal care and juvenile stress during the postweaning/prepubertal life phase are utilized. Especially within the limbic system, they induce lasting alterations in neuronal circuits, neurotransmitter systems, neuronal architecture and plasticity that are further associated with emotional and cognitive information processing. Recent studies found that astrocytes, a special group of glial cells, have altered functions following early-life stress as well. As part of the tripartite synapse, astrocytes interact with neurons in multiple ways by affecting neurotransmitter uptake and metabolism, by providing gliotransmitters and by providing energy to neurons within local circuits. Thus, astrocytes comprise powerful modulators of neuronal plasticity and are well suited to mediate the long-term effects of early-life stress on neuronal circuits. In this review, we will summarize current findings on altered astrocyte function and hippocampal plasticity following early-life stress. Highlighting studies for astrocyte-related plasticity modulation as well as open questions, we will elucidate the potential of astrocytes as new targets for interventions against stress-induced neuropsychiatric disorders.

scholarly journals Long-term aberrations to cerebellar endocannabinoids induced by early-life stress

2019 ◽  
Author(s):  
Alexandra B. Moussa-Tooks ◽  
Eric Larson ◽  
Alex F. Gimeno ◽  
Emma Leishman ◽  
Lisa A. Bartolomeo ◽  
...  
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Cannabinoid Receptors ◽  
Early Life Stress ◽  
Future Research ◽  
Developmental Stress ◽  
Specific Effects ◽  
Effects Of Stress ◽  
Arachidonoyl Glycerol

AbstractStudies of early-life stress traditionally focus on glucocorticoid signaling as a modulator of neurodevelopmental risk, but emerging evidence points to the role of the endocannabinoid system in long-term stress-induced neural remodeling. Existing studies on stress-induced endocannabinoid dysregulation have focused on changes to cerebrum that are temporally proximal to stressors, but little is known about temporally distal effects, especially in cerebellum, which is vulnerable to early developmental stress and is dense with cannabinoid receptors. Further, sex-specific effects of stress on cerebellar endocannabinoid tone are understudied. Following a naturalistic rodent model of early-life stress, limited bedding at postnatal days 2-9, adult (postnatal day 70) cerebellar and hippocampal endocannabinoids and related lipids and mRNA were assessed, and behavioral performance was evaluated. Regional and sex-specific effects were present at baseline and following early-life stress. Limited bedding impaired peripherally-measured basal corticosterone in adult males only. In the CNS, early-life stress (1) decreased 2-arachidonoyl glycerol and arachidonic acid in the cerebellar deep nuclei in males only; (2) decreased 2-arachidonoyl glycerol in females only in cerebellar Crus I; and (3) increased dorsal hippocampus prostaglandins in males only. Transcriptomics for cerebellar interpositus nucleus revealed substantial sex effects, with minimal effects of stress. Stress did impair novel object recognition in both sexes and social preference in females. Taken together, the cerebellar endocannabinoids system exhibits robust sex-specific differences, malleable through early-life stress and perhaps also contributing to sexual differentiation of the brain. The current study may foster future research into stress as a risk factor for cerebellar-related dysfunctions.

scholarly journals Corticolimbic circuit structure moderates an association between early life stress and later trait anxiety

2019 ◽  
Vol 24 ◽  
pp. 102050 ◽  
Author(s):  
M. Justin Kim ◽  
Madeline J. Farber ◽  
Annchen R. Knodt ◽  
Ahmad R. Hariri
Keyword(s):  
Trait Anxiety ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Circuit Structure

scholarly journals Early life stress, FK506 binding protein 5 gene (FKBP5) methylation, and inhibition-related prefrontal function: A prospective longitudinal study

2017 ◽  
Vol 29 (5) ◽  
pp. 1895-1903 ◽  
Author(s):  
Madeline B. Harms ◽  
Rasmus Birn ◽  
Nadine Provencal ◽  
Tobias Wiechmann ◽  
Elisabeth B. Binder ◽  
...  
Keyword(s):  
Inhibitory Control ◽  
Life Stress ◽  
Early Life ◽  
Binding Protein ◽  
Early Life Stress ◽  
Stress Exposure ◽  
Childhood Stress ◽  
Fk506 Binding Protein ◽  
Wide Range ◽  
Prospective Longitudinal

AbstractIndividuals who have experienced high levels of childhood stress are at increased risk for a wide range of behavioral problems that persist into adulthood, yet the neurobiological and molecular mechanisms underlying these associations remain poorly understood. Many of the difficulties observed in stress-exposed children involve problems with learning and inhibitory control. This experiment was designed to test individuals' ability to learn to inhibit responding during a laboratory task. To do so, we measured stress exposure among a community sample of school-aged children, and then followed these children for a decade. Those from the highest and lowest quintiles of childhood stress exposure were invited to return to our laboratory as young adults. At that time, we reassessed their life stress exposure, acquired functional magnetic resonance imaging data during an inhibitory control task, and assayed these individuals' levels of methylation in the FK506 binding protein 5 (FKBP5) gene. We found that individuals who experienced high levels of stress in childhood showed less differentiation in the dorsolateral prefrontal cortex between error and correct trials during inhibition. This effect was associated only with childhood stress exposure and not by current levels of stress in adulthood. In addition, FKBP5 methylation mediated the association between early life stress and inhibition-related prefrontal activity. These findings are discussed in terms of using multiple levels of analyses to understand the ways in which adversity in early development may affect adult behavioral adaptation.

scholarly journals Early Life Stress and Child Temperament Style as Predictors of Childhood Anxiety and Depressive Symptoms: Findings from the Longitudinal Study of Australian Children

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Andrew J. Lewis ◽  
Craig A. Olsson
Keyword(s):  
Depressive Symptoms ◽  
Longitudinal Study ◽  
Life Stress ◽  
Early Life ◽  
Parental Education ◽  
Early Life Stress ◽  
Childhood Anxiety ◽  
Infant Temperament ◽  
Future Research ◽  
Stress Exposure

Objective. The purpose of this study was to determine whether the relationship between stressful infant environments and later childhood anxiety and depressive symptoms varies as a function of individual differences in temperament style.Methods. Data was drawn from the Longitudinal Study of Australian Children (LSAC). This study examined 3425 infants assessed at three time points, at 1-year, at 2/3 years and at 4/5 years. Temperament was measured using a 12-item version of Toddler Temperament Scale (TTS) and was scored for reactive, avoidant, and impulsive dimensions. Logistic regression was used to model direct relationships and additive interactions between early life stress, temperament, and emotional symptoms at 4 years of age. Analyses were adjusted for socioeconomic status, parental education, and marital status.Results. Stressful family environments experienced in the infant's first year of life (high versus low) and high reactive, avoidant, and impulsive temperament styles directly and independently predicted anxiety and depressive problems in children at 4 years of age. There was no evidence of interaction between temperament and family stress exposure.Conclusions. Both infant temperament and stress exposures are independent and notable predictors of later anxiety and depressive problems in childhood. The risk relationship between stress exposure in infancy and childhood emotion problems did not vary as a function of infant temperament. Implications for preventive intervention and future research directions are discussed.

scholarly journals Serotonin-related pathways and developmental plasticity: relevance for psychiatric disorders

2014 ◽  
Vol 16 (1) ◽  
pp. 29-41 ◽  
Keyword(s):  
Psychiatric Disorders ◽  
Neural Plasticity ◽  
Life Stress ◽  
Early Life ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Developmental Plasticity ◽  
Neural Circuit ◽  
Early Life Stress ◽  
Early Life Adversity ◽  
Wide Range

Risk for adult psychiatric disorders is partially determined by early-life alterations occurring during neural circuit formation and maturation. In this perspective, recent data show that the serotonin system regulates key cellular processes involved in the construction of cortical circuits. Translational data for rodents indicate that early-life serotonin dysregulation leads to a wide range of behavioral alterations, ranging from stress-related phenotypes to social deficits. Studies in humans have revealed that serotonin-related genetic variants interact with early-life stress to regulate stress-induced cortisol responsiveness and activate the neural circuits involved in mood and anxiety disorders. Emerging data demonstrate that early-life adversity induces epigenetic modifications in serotonin-related genes. Finally, recent findings reveal that selective serotonin reuptake inhibitors can reinstate juvenile-like forms of neural plasticity, thus allowing the erasure of long-lasting fear memories. These approaches are providing new insights on the biological mechanisms and clinical application of antidepressants.

scholarly journals Early life stress and development: potential mechanisms for adverse outcomes

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Karen E. Smith ◽  
Seth D. Pollak
Keyword(s):  
Individual Differences ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Adverse Outcomes ◽  
Stressful Events ◽  
Negative Effects ◽  
Extreme Stress ◽  
Wide Range ◽  
Stress Influences

Abstract Background Chronic and/or extreme stress in early life, often referred to as early adversity, childhood trauma, or early life stress, has been associated with a wide range of adverse effects on development. However, while early life stress has been linked to negative effects on a number of neural systems, the specific mechanisms through which early life stress influences development and individual differences in children’s outcomes are still not well understood. Main text The current paper reviews the existing literature on the neurobiological effects of early life stress and their ties to children’s psychological and behavioral development. Conclusions Early life stress has persistent and pervasive effects on prefrontal–hypothalamic–amygdala and dopaminergic circuits that are at least partially mediated by alterations in hypothalamic–pituitary–adrenal axis function. However, to date, this research has primarily utilized methods of assessment that focus solely on children’s event exposures. Incorporating assessment of factors that influence children’s interpretation of stressors, along with stressful events, has the potential to provide further insight into the mechanisms contributing to individual differences in neurodevelopmental effects of early life stress. This can aid in further elucidating specific mechanisms through which these neurobiological changes influence development and contribute to risk for psychopathology and health disorders.

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