Influence Of Early Life Stress Research Articles

Editorial: Molecular Mechanisms for Reprogramming Hippocampal Development and Function by Early-Life Stress.

Editorial: Molecular Mechanisms for Reprogramming Hippocampal Development and Function by Early-Life Stress.

Influence of early life stress on the chronic pain in maturation period.

Influence of early life stress on the chronic pain in maturation period.

Influence of early life stress on intra- and extra-amygdaloid causal connectivity.

Animal models of early life stress (ELS) are characterized by augmented amygdala response to threat and altered amygdala-dependent behaviors. These models indicate the amygdala is a heterogeneous structure with well-differentiated subnuclei. The most well characterized of these being basolateral (BLA) and central nucleus (CeA). Parallel human imaging findings relative to ELS also reveal enhanced amygdala reactivity and disrupted connectivity but the influence of ELS on amygdala subregion connectivity and modulation of emotion is unclear. Here we employed cytoarchitectonic probability maps of amygdala subregions and Granger causality methods to evaluate task-based intra-amygdaloid and extra-amygdaloid connectivity with the network underlying implicit regulation of emotion in response to unconditioned auditory threat in healthy controls with ELS (N=20) and without a history of ELS (N=14). Groups were determined by response to the Childhood Trauma Questionnaire and threat response determined by unpleasantness ratings. Non-ELS demonstrated narrowly defined BLA-driven intra-amygdaloid paths and concise orbitofrontal cortex (OFC)-CeA-driven extra-amygdaloid connectivity. In contrast, ELS was associated with extensive and robust CeA-facilitated intra- and extra-amygdaloid paths. Non-ELS findings paralleled the known anatomical organization and functional relationships for both intra- and extra-amygdaloid connectivity, while ELS demonstrated atypical intra- and extra-amygdaloid CeA-dominant paths with compensatory modulation of emotion. Specifically, negative causal paths from OFC/BA32 to BLA predicted decreased threat response among non-ELS, while a unique within-amygdala path predicted modulation of threat among ELS. These findings are consistent with compensatory mechanisms of emotion regulation following ELS among resilient persons originating both within the amygdala complex as well as subsequent extra-amygdaloid communication.

Stress, Inflammation, and Cellular Vulnerability during Early Stages of Affective Disorders: Biomarker Strategies and Opportunities for Prevention and Intervention.

The mood disorder prodrome is conceptualized as a symptomatic, but not yet clinically diagnosable stage of an affective disorder. Although a growing area, more focused research is needed in the pediatric population to better characterize psychopathological symptoms and biological markers that can reliably identify this very early stage in the evolution of mood disorder pathology. Such information will facilitate early prevention and intervention, which has the potential to affect a person’s disease course. This review focuses on the prodromal characteristics, risk factors, and neurobiological mechanisms of mood disorders. In particular, we consider the influence of early-life stress, inflammation, and allostatic load in mediating neural mechanisms of neuroprogression. These inherently modifiable factors have known neuroadaptive and neurodegenerative implications, and consequently may provide useful biomarker targets. Identification of these factors early in the course of the disease will accordingly allow for the introduction of early interventions which augment an individual’s capacity for psychological resilience through maintenance of synaptic integrity and cellular resilience. A targeted and complementary approach to boosting both psychological and physiological resilience simultaneously during the prodromal stage of mood disorder pathology has the greatest promise for optimizing the neurodevelopmental potential of those individuals at risk of disabling mood disorders.

EPA-1260 – Gene-environment interplay in the influence of early life stress on emotionality

The emotional behavior is influenced by several factors, including environment, genetic and the interaction between them, which is the aim of this work. Early life stress has been related to the development of emotional disturbances late in life, nevertheless recent studies have showed a new operational model to this relation, depending on the genetic background. Regarding to depression-like behavior, the most recent manuals for diagnosis of this disease highlights the importance of assess the anhedonia, more than the blue mood, to a correct identification of this pathology. Animal models of affective disorders has been developed aiming to access all range of depressive-like behaviors. A behavioral test to evaluate this lowest tendency to attend pleasure situations is the Sucrose Preference Test (SPT). The neonatal maternal separation procedure was carried out with the Carioca rats, an anxiety disorder Wistar rat model, developed through selective lines matching based in a task of contextual fear conditioning, which gives rise to two different lines: CHF (Carioca High Freezing) and CLF (Carioca Low Freezing). Six CHF and 10 CLF animals were used in this work. We also used Maternal Separated AFR (Animal Facility Rearing) (n=15) and Non-separated AFR groups as controls (CTR group, n=8). The rat pups were separated as a litter (8 to 10 animals per dam) from the dam from post natal day (PND) 1–14, daily, for a three-hour period/day (MS-CHF, MS-CLF and MS-AFR groups); the CTR group did not receive any kind of manipulation in these 14 days, exception for the home cage cleaning once a week, performed for all groups. The weaning was performed at PND21. All the animals were tested in the SPT at PND 60, using a 10% sucrose-solution. The animals were grouped in 4–6 animals and were tested in a free choice protocol for 48 hours. In the first 12 hours, the animals were trained with two bottles of water in the cage. After this, there were two bottles for each cage: one with water and the other with the 10% sucrose solution. The bottles' location was changed often to avoid possible position preference. The total liquid consumption and then thee sucrose consumption ratio were measured. The Kruskal-Wallis test was used to evaluate the differences between the three MS groups. The Dunn's post hoc test showed a difference between the groups in relation to relative sucrose consumption: MS-CHF consumed less sucrose solution than the MS-CLF and MS-AFR groups (KW: 24.02; p

How emotional abilities modulate the influence of early life stress on hippocampal functioning

Early life stress (ELS) is known to have considerable influence on brain development, mental health and affective functioning. Previous investigations have shown that alexithymia, a prevalent personality trait associated with difficulties experiencing and verbalizing emotions, is particularly related to ELS. The aim of the present study was to investigate how neural correlates of emotional experiences in alexithymia are altered in the presence and absence of ELS. Therefore, 50 healthy individuals with different levels of alexithymia were matched regarding ELS and investigated with respect to neural correlates of audio-visually induced emotional experiences via functional magnetic resonance imaging. The main finding was that ELS modulated hippocampal responses to pleasant (>neutral) stimuli in high-alexithymic individuals, whereas there was no such modulation in low-alexithymic individuals matched for ELS. Behavioral and psychophysiological results followed a similar pattern. When considered independent of ELS, alexithymia was associated with decreased responses in insula (pleasant > neutral) and temporal pole (unpleasant > neutral). Our results show that the influence of ELS on emotional brain responses seems to be modulated by an individual's degree of alexithymia. Potentially, protective and adverse effects of emotional abilities on brain responses to emotional experiences are discussed.

Neuroendocrine coupling across adolescence and the longitudinal influence of early life stress

Drawing on conceptual models illustrating the advantages of a multisystemic, interactive, developmental approach to understanding development, the present study examines the covariation of stress and sex hormones across the adolescent transition and the effect of early life stress (ELS) on neuroendocrine coupling to gain insight into atypical development. Morning levels of cortisol, testosterone, and dehydroepiandrosterone (DHEA) were assessed at ages 11, 13, and 15; ELS was assessed during the infancy and preschool periods. Hierarchical linear modeling revealed that cortisol-DHEA coupling patterns progressed to tight, positive coupling across adolescence. Cortisol-testosterone coupling was positive at age 11 but became more negative at ages 13 and 15. Exposure to ELS resulted in more adultlike neuroendocrine coupling patterns earlier in life than non-exposed youth; however the effect of ELS on cortisol-testosterone coupling was unique to girls. Results illustrate trajectories of neuroendocrine coupling that may be unique to adolescence. Moderation by ELS suggests that early stress exposure may prompt earlier adultlike neuroendocrine coupling, particularly within girls, which may contribute to early pubertal development.

Early Life Stress Affects the Serotonergic System Underlying Emotional Regulation

Traumatic events in early life are implicated in an increased risk of psychiatric diseases, such as depression and anxiety disorders. Serotonin is thought to play a central role in stress-induced psychiatric diseases. Serotonergic systems, including neural organization and receptor function, could dramatically change with each developmental stage. Here, we reviewed the persistent influence of early life stress on emotional regulation, focusing on the serotonergic system in rats. An aversive stimulus, foot shock (FS), during the early postnatal period (2-3 weeks after birth) produced behavioral, neuroanatomical and electrophysiological changes accompanied by serotonergic dysfunction, especially functional impairment of the serotonin (5-hydroxytryptamine; 5-HT)1A receptor in the cortico-limbic area. These findings suggest that normalization of the cortico-limbic serotonergic function has therapeutic potential for early stress-induced emotional disturbance.

The Effects of Maternal Separation on Adult Methamphetamine Self-Administration, Extinction, Reinstatement, and MeCP2 Immunoreactivity in the Nucleus Accumbens

The maternal separation (MS) paradigm is an animal model of early life stress. Animals subjected to MS during the first 2 weeks of life display altered behavioral and neuroendocrinological stress responses as adults. MS also produces altered responsiveness to and self-administration (SA) of various drugs of abuse including cocaine, ethanol, and amphetamine. However, no studies have yet examined the effects of MS on methamphetamine (METH) SA. This study was performed to examine the effects of MS on the acquisition of METH SA, extinction, and reinstatement of METH-seeking behavior in adulthood. Given the known influence of early life stress and drug exposure on epigenetic processes, we also investigated group differences in levels of the epigenetic marker methyl CpG binding protein 2 (MeCP2) in the nucleus accumbens (NAc) core. Long–Evans pups and dams were separated on postnatal days (PND) 2–14 for either 180 (MS180) or 15 min (MS15). Male offspring were allowed to acquire METH SA (0.05 mg/kg/infusion) in 15 2-h daily sessions starting at PND67, followed by extinction training and cue-induced reinstatement of METH-seeking behavior. Rats were then assessed for MeCP2 levels in the NAc core by immunohistochemistry. The MS180 group self-administered significantly more METH and acquired SA earlier than the MS15 group. No group differences in extinction or cue-induced reinstatement were observed. MS15 rats had significantly elevated MeCP2-immunoreactive cells in the NAc core as compared to MS180 rats. Together, these data suggest that MS has lasting influences on METH SA as well as epigenetic processes in the brain reward circuitry.

Neuromagnetic Indication of Dysfunctional Emotion Regulation in Affective Disorders

Dysfunctional emotion regulation is often reported in affective disorders, but it is unclear whether this dysfunction concerns initial processing of emotional input or regulation of resulting emotion. The present study addressed these aspects in 27 depressive and 15 borderline personality disorder patients and 28 healthy controls who were instructed to either passively view unpleasant and neutral pictures or downregulate emotional responses by reappraisal, while neuromagnetic brain activity was measured. All three groups showed more early response to unpleasant than to neutral pictures, whereas patients failed to show subsequent activity suppression under instructions to down-regulate. This deficient emotion regulation was evident primarily in those subjects reporting high childhood adversity. Results support intact emotional input processing but impaired emotion regulation in affective disorders and indicate a moderating influence of early life stress.

Influence of early life stress on later hypothalamic–pituitary–adrenal axis functioning and its covariation with mental health symptoms: A study of the allostatic process from childhood into adolescence

The hypothalamic-pituitary-adrenal (HPA) axis is a primary mechanism in the allostatic process through which early life stress (ELS) contributes to disease. Studies of the influence of ELS on children's HPA axis functioning have yielded inconsistent findings. To address this issue, the present study considers multiple types of ELS (maternal depression, paternal depression, and family expressed anger), mental health symptoms, and two components of HPA functioning (traitlike and epoch-specific activity) in a long-term prospective community study of 357 children. ELS was assessed during the infancy and preschool periods; mental health symptoms and cortisol were assessed at child ages 9, 11, 13, and 15 years. A three-level hierarchical linear model addressed questions regarding the influences of ELS on HPA functioning and its covariation with mental health symptoms. ELS influenced traitlike cortisol level and slope, with both hyper- and hypoarousal evident depending on type of ELS. Further, type(s) of ELS influenced covariation of epoch-specific HPA functioning and mental health symptoms, with a tighter coupling of HPA alterations with symptom severity among children exposed previously to ELS. Results highlight the importance of examining multiple types of ELS and dynamic HPA functioning in order to capture the allostatic process unfolding across the transition into adolescence.

Electrophysiological insights into the enduring effects of early life stress on the brain

Increasing evidence links exposure to stress early in life to long-term alterations in brain function, which in turn have been linked to a range of psychiatric and neurological disorders in humans. Electrophysiological approaches to studying these causal pathways have been relatively underexploited. Effects of early life stress on neuronal electrophysiological properties offer a set of potential mechanisms for these susceptibilities, notably in the case of epilepsy. Thus, we review experimental evidence for altered cellular and circuit electrophysiology resulting from exposure to early life stress. Much of this work focuses on limbic long-term potentiation, but other studies address alterations in electrophysiological properties of ion channels, neurotransmitter systems, and the autonomic nervous system. We discuss mechanisms which may mediate these effects, including influences of early life stress on key components of brain synaptic transmission, particularly glutamate, GABA and 5-HT receptors, and influences on neuroplasticity (primarily neurogenesis and synaptic density) and on neuronal network activity. The existing literature, although small, provides strong evidence that early life stress induces enduring, often robust effects on a range of electrophysiological properties, suggesting further study of enduring effects of early life stress employing electrophysiological methods and concepts will be productive in illuminating disease pathophysiology.

Associations between theCOMT Val/Metpolymorphism, early life stress, and personality among healthy adults

Efforts to identify genetic factors that confer an increased risk for the expression of psychiatric symptoms have focused on polymorphisms in variety of candidate genes, including the catechol-O-methyltransferase (COMT) gene. Results from previous studies that have examined associations between the functional COMT polymorphism (Val158Met) and mental health have been mixed. In the present study, we examined the relationships between COMT, early life stress, and personality in a healthy adult sample. Consistent with previous studies, we hypothesized that individuals with the low-activity genotype would have higher neuroticism and lower extraversion and that this effect would be more pronounced in females. In addition, we extended the previous literature by investigating the potential influence of early life stress. A total of 486 healthy adults underwent genetic testing and personality assessment. Results revealed that individuals homozygous for the COMT low enzyme activity allele had lower extraversion on the NEO-FFI and demonstrated a trend toward greater neuroticism. These relationships were not influenced by sex or the presence of reported early life stress. The finding that COMT genotype was associated with extraversion, and more weakly with neuroticism, is consistent with previous studies. Future research to clarify the influence of sex and gene-environmental interactions is warranted.

Childhood Stress and Family Environment

L'etude menee aupres des enfants d'un village rural sur la cote orientale de Dominique montre la relation entre le stress et la composition du groupe domestique (âge, sexe, relation intergenerationnelle, nombre de personnes). Les enfants vivant dans des foyers ou prendre soin d'eux est une attitude frequente et stable ont un niveau de cortisol modere contrairement aux enfants connaissant des evenements familiaux traumatiques