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      Stress: Influence of sex, reproductive status and gender

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          Abstract

          Emerging evidence from the preclinical and human research suggests sex differences in response to different types of stress exposure, and that developmental timing, reproductive status, and biological sex are important factors influencing the degree of HPA activation/function. Here we review data regarding: i) sex differences in behavioral and neural responses to uncontrollable and controllable stressors; ii) distinct trajectories of behavioral development and HPA-axis function in male and female rats following adolescent stress exposure; iii) normative changes in behavior and dopamine function in early postpartum rats; iv) aberrant HPA-axis function and its link to abnormal behaviors in two independent, preclinical mouse models of postpartum depression; and, v) data indicating that gender, in addition to sex, is an important determinant of stress reactivity in humans. Based on these findings, we conclude it will be important for future studies to investigate the short and long-term effects of a wide variety of stressors, how these effects may differ according to developmental timing and in relation to gonadal function, the relationship between aberrant HPA-axis activity during the postpartum and mood disorders, and influences of both sex and gender on stress reactivity in humans.

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          Depression: a new animal model sensitive to antidepressant treatments.

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            Stress and the individual. Mechanisms leading to disease.

            This article presents a new formulation of the relationship between stress and the processes leading to disease. It emphasizes the hidden cost of chronic stress to the body over long time periods, which act as a predisposing factor for the effects of acute, stressful life events. It also presents a model showing how individual differences in the susceptibility to stress are tied to individual behavioral responses to environmental challenges that are coupled to physiologic and pathophysiologic responses. Published original articles from human and animal studies and selected reviews. Literature was surveyed using MEDLINE. Independent extraction and cross-referencing by us. Stress is frequently seen as a significant contributor to disease, and clinical evidence is mounting for specific effects of stress on immune and cardiovascular systems. Yet, until recently, aspects of stress that precipitate disease have been obscure. The concept of homeostasis has failed to help us understand the hidden toll of chronic stress on the body. Rather than maintaining constancy, the physiologic systems within the body fluctuate to meet demands from external forces, a state termed allostasis. In this article, we extend the concept of allostasis over the dimension of time and we define allostatic load as the cost of chronic exposure to fluctuating or heightened neural or neuroendocrine response resulting from repeated or chronic environmental challenge that an individual reacts to as being particularly stressful. This new formulation emphasizes the cascading relationships, beginning early in life, between environmental factors and genetic predispositions that lead to large individual differences in susceptibility to stress and, in some cases, to disease. There are now empirical studies based on this formulation, as well as new insights into mechanisms involving specific changes in neural, neuroendocrine, and immune systems. The practical implications of this formulation for clinical practice and further research are discussed.
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              Sex differences in anxiety and depression clinical perspectives.

              Sex differences are prominent in mood and anxiety disorders and may provide a window into mechanisms of onset and maintenance of affective disturbances in both men and women. With the plethora of sex differences in brain structure, function, and stress responsivity, as well as differences in exposure to reproductive hormones, social expectations and experiences, the challenge is to understand which sex differences are relevant to affective illness. This review will focus on clinical aspects of sex differences in affective disorders including the emergence of sex differences across developmental stages and the impact of reproductive events. Biological, cultural, and experiential factors that may underlie sex differences in the phenomenology of mood and anxiety disorders are discussed.
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                Author and article information

                Contributors
                Journal
                Neurobiol Stress
                Neurobiol Stress
                Neurobiology of Stress
                Elsevier
                2352-2895
                09 March 2019
                February 2019
                09 March 2019
                : 10
                : 100155
                Affiliations
                [a ]Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA
                [b ]Department of Pharmacology and Systems Physiology, University of Cincinnati, Cincinnati, OH, USA
                [c ]Department of Psychiatry, Université de Montréal, Montréal, Québec, Canada
                [d ]Department of Neuroscience, Tufts University School of Medicine, Boston, MA, USA
                [e ]Department of Psychology, Northeastern University, Boston, MA, USA
                Author notes
                []Corresponding author. Department of Neuroscience, A210 Langley Hall, University of Pittsburgh, Pittsburgh, PA, 15260, USA. mir69@ 123456pitt.edu
                Article
                S2352-2895(18)30115-2 100155
                10.1016/j.ynstr.2019.100155
                6430637
                30949564
                7ab0ddb7-98af-43e1-94fa-467adf3fbe29
                © 2019 The Authors. Published by Elsevier Inc.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 24 December 2018
                : 25 February 2019
                : 5 March 2019
                Categories
                Article from the Special Issue on Stress Neurobiology Workshop 2018; Edited by Lawrence Reagan,Richard Hunter and Matthew N. Hill

                sex differences,stress,animal models,hpa-axis,development,postpartum

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