Developmental Trajectories of Early Life Stress and Trauma: A Narrative Review on Neurobiological Aspects Beyond Stress System Dysregulation

Early life stressors display a high universal prevalence and constitute a major public health problem. Prolonged psychoneurobiological alterations as sequelae of early life stress (ELS) could represent a developmental risk factor and mediate risk for disease, leading to higher physical and mental morbidity rates in later life. ELS could exert a programming effect on sensitive neuronal brain networks related to the stress response during critical periods of development and thus lead to enduring hyper- or hypo-activation of the stress system and altered glucocorticoid signaling. In addition, alterations in emotional and autonomic reactivity, circadian rhythm disruption, functional and structural changes in the brain, as well as immune and metabolic dysregulation have been lately identified as important risk factors for a chronically impaired homeostatic balance after ELS. Furthermore, human genetic background and epigenetic modifications through stress-related gene expression could interact with these alterations and explain inter-individual variation in vulnerability or resilience to stress. This narrative review presents relevant evidence from mainly human research on the ten most acknowledged neurobiological allostatic pathways exerting enduring adverse effects of ELS even decades later (hypothalamic-pituitary-adrenal axis, autonomic nervous system, immune system and inflammation, oxidative stress, cardiovascular system, gut microbiome, sleep and circadian system, genetics, epigenetics, structural, and functional brain correlates). Although most findings back a causal relation between ELS and psychobiological maladjustment in later life, the precise developmental trajectories and their temporal coincidence has not been elucidated as yet. Future studies should prospectively investigate putative mediators and their temporal sequence, while considering the potentially delayed time-frame for their phenotypical expression. Better screening strategies for ELS are needed for a better individual prevention and treatment

The importance of an active case detection (Acd) programme for malaria among migrants from malaria endemic countries: The greek experience in a receptive and vulnerable area

Greecehasbeenmalaria-freesince1974. InOctober2011,followinganoutbreakof36locally acquired malaria (LAM) cases in Evrotas Municipality, a Pro-Active Case Detection (PACD) program for malaria was implemented among migrants from malaria-endemic countries, to support early diagnosis and treatment of cases. We evaluated the PACD program for the years 2012–2017 using indicatorssuchasthenumberoflocallyacquiredcases,thedetectionrate/sensitivityandthetimeliness of diagnosis and treatment. We visited each migrant home every 7–15 days to screen migrants for malaria symptoms, performing Rapid Diagnostic Tests (RDTs) and blood smears on symptomatic patients. We estimated: (i) the number of malaria cases detected by the PACD, divided by the total number of reported malaria cases during the same period among the same population; (ii) the time betweenonsetofsymptoms,diagnosisandinitiationoftreatment. Thetotalnumberofmigrantswho were screened for malaria symptoms for the years 2012–2017 was 5057 with 84,169 fever screenings conducted, while 2288 RDTs and 1736 blood smears were performed. During the same period, 53 imported P. vivax malaria cases were detected, while incidence of malaria among migrants was estimated at 1.8% annually. Ten and one LAM cases were also reportedin 2012 and 2015, respectively. Sensitivity of PACD ranged from 86% to 100%; median timeliness between onset of symptoms and diagnosis decreased from 72 h in 2012 to 12 h in 2017 (83% decrease), while timeliness betweendiagnosis and treatment initiation was 0 h. The implementation of PACD could be considered an effective prevention and response tool against malaria re-introduction

Metabolic syndrome: definitions and controversies

Metabolic syndrome (MetS) is a complex disorder defined by a cluster of interconnected factors that increase the risk of cardiovascular atherosclerotic diseases and diabetes mellitus type 2. Currently, several different definitions of MetS exist, causing substantial confusion as to whether they identify the same individuals or represent a surrogate of risk factors. Recently, a number of other factors besides those traditionally used to define MetS that are also linked to the syndrome have been identified. In this review, we critically consider existing definitions and evolving information, and conclude that there is still a need to develop uniform criteria to define MetS, so as to enable comparisons between different studies and to better identify patients at risk. As the application of the MetS model has not been fully validated in children and adolescents as yet, and because of its alarmingly increasing prevalence in this population, we suggest that diagnosis, prevention and treatment in this age group should better focus on established risk factors rather than the diagnosis of MetS

Stress and Pediatric Obesity: Neurobiology and Behavior

Pediatric and adolescent obesity commonly coexist with stress-related symptoms and disorders. Stress, the state of threatened homeostasis, is associated with the acute activation of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. However, the chronic activation of hypothalamic-pituitary-adrenal and sympathetic nervous system axes during chronic or intense stress can lead to a variety of psychopathological and physical conditions. Behavioral and neurobiological mechanisms link chronic stress with pediatric obesity, in a bidirectional relation. Chronically stressed individuals are characterized by low adherence to a healthy lifestyle and by disturbed eating behaviors, whereas alterations in the secretion of stress hormones might also contribute to obesity and obesity-related complications. Obesity could lead to increased social distress, low self-esteem, and anxiety, thereby contributing to a vicious cycle between distress and obesity and increasing further the risk of cardiometabolic morbidity. This review article summarizes recent research findings and discusses mechanisms linking stress with pediatric obesity

Stress and obesity/metabolic syndrome in childhood and adolescence

Chronic distress contributes to the development of obesity and comorbid states. Stress is the disturbance of the complex dynamic equilibrium that all organisms must maintain, and is associated with activation of the Stress system comprising of the hypothalamic-pituitary-adrenal axis and the arousal/sympathetic nervous systems. The stress system functions in a baseline circadian fashion and interacts with other systems of the organism to regulate a variety of behavioral, endocrine, metabolic, immune and cardiovascular functions. The experience of perceived or real uncontrollable intense and/or chronic stress (distress) may lead to several psychopathologic conditions, including anxiety, depressive and psychosomatic disorders, substance abuse, obesity and the metabolic syndrome, and osteoporosis, as well as impaired reproductive and immune functions. Developing children and adolescents are particularly vulnerable to the effects of chronic stress. Both behavioral and biological pathways are involved in the connection between chronic stress and obesity in adults and children. Emotional “comfort” eating, lack of sleep, impulsive behaviours and selection of specific foods often characterize stressed individuals. In addition to specific behaviours, dysregulation of the stress system through increased secretion of cortisol and catecholamines, especially in the evening hours, and in concert with concurrently elevated insulin concentrations, leads to development of central obesity, insulin resistance and the metabolic syndrome. In children, chronic alterations in cortisol secretion may have additional effects on cognitive and emotional development, timing of puberty and final stature. Obese children and adolescents are frequently entangled in a vicious cycle between distress, impairing self-image and distorted self-image, maintaining and worsening distress

Posttraumatic Stress Disorder in Children and Adolescents: Neuroendocrine Perspectives

Posttraumatic stress disorder (PTSD) is a syndrome of distress that develops after exposure to traumatic life experiences. Dysregulation of both the hypothalamic-pituitary-adrenal (HPA) axis and the locus caeruleus/norepinephrine-sympathetic nervous system (LC/NE-SNS) is associated with the pathophysiology of the disorder. Studies have demonstrated a neuroendocrine profile unique to adults with PTSD, with centrally elevated corticotropin-releasing hormone (CRH), low cortisol in the periphery, and elevated catecholamines. Traumatic stress experiences in early life are strong predisposing factors for later PTSD development. In addition, early life stress programs the developing brain to overreact to future stressors. In children and adolescents involved in motor vehicle accidents, we found that high evening salivary cortisol and morning serum interleukin 6 concentrations were predictive of PTSD development 6 months later. We demonstrated a progressive divergence of the HPA and LC/NE-SNS axes of the stress system, which may be part of the pathophysiologic mechanism responsible for PTSD maintenance. An initial elevation of cortisol in the aftermath of the trauma, followed by a gradual normalization and finally low cortisol secretion, together with a gradual elevation of catecholamines over time, may represent the natural history of neuroendocrine changes in pediatric PTSD. Thus, the low cortisol concentrations found in adults with PTSD may reflect prior trauma and might represent a biologic vulnerability factor for later PTSD development

Metabolic consequences of stress during childhood and adolescence

Stress, that is, the state of threatened or perceived as threatened homeostasis, is associated with activation of the stress system, mainly comprised by the hypothalamic-pituitary-adrenal axis and the arousal/sympathetic nervous systems. The stress system normally functions in a circadian manner and interacts with other systems to regulate a variety of behavioral, endocrine, metabolic, immune, and cardiovascular functions. However, the experience of acute intense physical or emotional stress, as well as of chronic stress, may lead to the development of or may exacerbate several psychologic and somatic conditions, including anxiety disorders, depression, obesity, and the metabolic syndrome. In chronically stressed individuals, both behavioral and neuroendocrine mechanisms promote obesity and metabolic abnormalities: unhealthy lifestyles in conjunction with dysregulation of the stress system and increased secretion of cortisol, catecholamines, and interleukin-6, with concurrently elevated insulin concentrations, lead to development of central obesity, insulin resistance, and the metabolic syndrome. Fetal life, childhood, and adolescence are particularly vulnerable periods of life to the effects of intense acute or chronic stress. Similarly, these life stages are crucial for the later development of behavioral, metabolic, and immune abnormalities. Developing brain structures and functions related to stress regulation, such as the amygdala, the hippocampus, and the mesocorticolimbic system, are more vulnerable to the effects of stress compared with mature structures in adults. Moreover, chronic alterations in cortisol secretion in children may affect the timing of puberty, final stature, and body composition, as well as cause early-onset obesity, metabolic syndrome, and type 2 diabetes mellitus. The understanding of stress mechanisms leading to metabolic abnormalities in early life may lead to more effective prevention and intervention strategies of obesity-related health problems. (C) 2012 Elsevier Inc. All rights reserved

Early Life Stress and Pediatric Posttraumatic Stress Disorder

Traumatic stress exposure during critical periods of development may have essential and long-lasting effects on the physical and mental health of individuals. Two thirds of youth are exposed to potentially traumatic experiences by the age of 17, and approximately 5% of adolescents meet lifetime criteria for posttraumatic stress disorder (PTSD). The role of the stress system is the maintenance of homeostasis in the presence of real/perceived and acute/chronic stressors. Early-life stress (ELS) has an impact on neuronal brain networks involved in stress reactions, and could exert a programming effect on glucocorticoid signaling. Studies on pediatric PTSD reveal diverse neuroendocrine responses to adverse events and related long-term neuroendocrine and epigenetic alterations. Neuroendocrine, neuroimaging, and genetic studies in children with PTSD and ELS experiences are crucial in understanding risk and resilience factors, and also the natural history of PTSD