Biological hypersensitivity to environmental stimuli is a fundamental feature of atopy, predisposing individuals to a spectrum of disorders, allergic rhinitis, atopic dermatitis, and allergic asthma. Evidence linking psychological stress to atopy expression has grown with our increased understanding of the natural history and pathophysiology of atopic disorders and the neurobiology of stress. However, the specific pathways involved remain to be elucidated in human studies. Findings suggest that stressors may influence pathogenesis by causing dysregulated biobehavioral states (e.g., depression, PTSD), which exert effects on physiological processes that influence disease risk. Extreme forms of stress exposure (multiple stressors within the same time period, chronic stressors over developmental periods, traumatic events) are more likely to lead to persistent psychological and physiological alterations. Disturbed regulation of endocrine and autonomic systems (e.g., hypothalamic-pituitary-adrenal axis, sympathetic-adrenal-medullary system) may modulate offspring immune functioning beginning in utero. Therefore, understanding maternal dysregulation of these systems in pregnancy may be particularly informative. Non-optimal early caregiving experiences (e.g., maternal psychopathology, maternal insensitivity) may also impact these processes by leading to disrupted infant emotion regulation and neuroimmune development, setting the stage for altered reactivity to stimuli and inflammatory processes, hallmarks of early atopy. Exploring these links may be particularly relevant in urban populations, who are disproportionately burdened by both stress and chronic atopic disorders. We will examine the effects of maternal stress (cumulative perinatal stress, lifetime trauma), on the expression of child atopy in an urban sample (N=275). We will incorporate strategies for studying stress reactivity during pregnancy, infancy, and early childhood to elucidate pathways from stress to a hierarchy of early intermediate phenotypes that may be related to persistent atopic disorders (early sensitization as indexed by IgE expression and skin test reactivity, T-helper cell differentiation, airway resistance, early clinical phenotypes). We will examine how intervening processes may affect these relationships, including how maternal-fetal endocrine indicators of stress (prenatal cortisol, corticotrophin-releasing hormone), pre/postnatal maternal psychological functioning, and postnatal caregiving behaviors impact the infant stress response (cortisol, respiration, sympathetic and parasympathetic autonomic functioning), assessed during a standardized laboratory protocol at age 6 months, and child atopic profiles assessed through 30 months. In this prospective design, we will examine how fetal stress exposure may influence early neuroimmune development and how such effects are independent of or moderated by postnatal factors. We will test the contributions of proximal and lifetime stress exposures on the proposed pathways. The study findings may identify mechanisms that lead to and maintain early predisposition to costly pediatric atopic disorders, informing more efficacious prevention and intervention strategies.
This study may increase our understanding of the effects of perinatal maternal stress on vulnerability to early intermediate phenotypes that may predispose to subsequent risk for developing atopic disorders in childhood. Such knowledge may inform efforts to design programs to prevent the development of atopic disorders, such as asthma, allergic rhinitis and eczema, particularly in high-risk urban populations. Given the enormous cost in the management of atopic patients in the United States, understanding the earliest stages of development offers significant potential benefits to society.
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