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      Self Reported Childhood Difficulties, Adult Multimorbidity and Allostatic Load. A Cross-Sectional Analysis of the Norwegian HUNT Study

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          Abstract

          Background

          Multimorbidity receives increasing scientific attention. So does the detrimental health impact of adverse childhood experiences (ACE). Aetiological pathways from ACE to complex disease burdens are under investigation. In this context, the concept of allostatic overload is relevant, denoting the link between chronic detrimental stress, widespread biological perturbations and disease development. This study aimed to explore associations between self-reported childhood quality, biological perturbations and multimorbidity in adulthood.

          Materials and Methods

          We included 37 612 participants, 30–69 years, from the Nord-Trøndelag Health Study, HUNT3 (2006–8). Twenty one chronic diseases, twelve biological parameters associated with allostatic load and four behavioural factors were analysed. Participants were categorised according to the self-reported quality of their childhood, as reflected in one question, alternatives ranging from ‘very good’ to ‘very difficult’. The association between childhood quality, behavioural patterns, allostatic load and multimorbidity was compared between groups.

          Results

          Overall, 85.4% of participants reported a ‘good’ or ‘very good’ childhood; 10.6% average, 3.3% ‘difficult’ and 0.8% ‘very difficult’. Childhood difficulties were reported more often among women, smokers, individuals with sleep problems, less physical activity and lower education. In total, 44.8% of participants with a very good childhood had multimorbidity compared to 77.1% of those with a very difficult childhood (Odds ratio: 5.08; 95% CI: 3.63–7.11). Prevalences of individual diseases also differed significantly according to childhood quality; all but two (cancer and hypertension) showed a significantly higher prevalence (p<0.05) as childhood was categorised as more difficult. Eight of the 12 allostatic parameters differed significantly between childhood groups.

          Conclusions

          We found a general, graded association between self-reported childhood difficulties on the one hand and multimorbidity, individual disease burden and biological perturbations on the other. The finding is in accordance with previous research which conceptualises allostatic overload as an important route by which childhood adversities become biologically embodied.

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          Most cited references48

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          Glucocorticoids, prenatal stress and the programming of disease.

          An adverse foetal environment is associated with increased risk of cardiovascular, metabolic, neuroendocrine and psychological disorders in adulthood. Exposure to stress and its glucocorticoid hormone mediators may underpin this association. In humans and in animal models, prenatal stress, excess exogenous glucocorticoids or inhibition of 11β-hydroxysteroid dehydrogenase type 2 (HSD2; the placental barrier to maternal glucocorticoids) reduces birth weight and causes hyperglycemia, hypertension, increased HPA axis reactivity, and increased anxiety-related behaviour. Molecular mechanisms that underlie the 'developmental programming' effects of excess glucocorticoids/prenatal stress include epigenetic changes in target gene promoters. In the case of the intracellular glucocorticoid receptor (GR), this alters tissue-specific GR expression levels, which has persistent and profound effects on glucocorticoid signalling in certain tissues (e.g. brain, liver, and adipose). Crucially, changes in gene expression persist long after the initial challenge, predisposing the individual to disease in later life. Intriguingly, the effects of a challenged pregnancy appear to be transmitted possibly to one or two subsequent generations, suggesting that these epigenetic effects persist. Copyright © 2010 Elsevier Inc. All rights reserved.
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            The concept of allostasis in biology and biomedicine.

            Living organisms have regular patterns and routines that involve obtaining food and carrying out life history stages such as breeding, migrating, molting, and hibernating. The acquisition, utilization, and storage of energy reserves (and other resources) are critical to lifetime reproductive success. There are also responses to predictable changes, e.g., seasonal, and unpredictable challenges, i.e., storms and natural disasters. Social organization in many populations provides advantages through cooperation in providing basic necessities and beneficial social support. But there are disadvantages owing to conflict in social hierarchies and competition for resources. Here we discuss the concept of allostasis, maintaining stability through change, as a fundamental process through which organisms actively adjust to both predictable and unpredictable events. Allostatic load refers to the cumulative cost to the body of allostasis, with allostatic overload being a state in which serious pathophysiology can occur. Using the balance between energy input and expenditure as the basis for applying the concept of allostasis, we propose two types of allostatic overload. Type 1 allostatic overload occurs when energy demand exceeds supply, resulting in activation of the emergency life history stage. This serves to direct the animal away from normal life history stages into a survival mode that decreases allostatic load and regains positive energy balance. The normal life cycle can be resumed when the perturbation passes. Type 2 allostatic overload begins when there is sufficient or even excess energy consumption accompanied by social conflict and other types of social dysfunction. The latter is the case in human society and certain situations affecting animals in captivity. In all cases, secretion of glucocorticosteroids and activity of other mediators of allostasis such as the autonomic nervous system, CNS neurotransmitters, and inflammatory cytokines wax and wane with allostatic load. If allostatic load is chronically high, then pathologies develop. Type 2 allostatic overload does not trigger an escape response, and can only be counteracted through learning and changes in the social structure.
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              Early childhood adversity, toxic stress, and the role of the pediatrician: translating developmental science into lifelong health.

              Advances in a wide range of biological, behavioral, and social sciences are expanding our understanding of how early environmental influences (the ecology) and genetic predispositions (the biologic program) affect learning capacities, adaptive behaviors, lifelong physical and mental health, and adult productivity. A supporting technical report from the American Academy of Pediatrics (AAP) presents an integrated ecobiodevelopmental framework to assist in translating these dramatic advances in developmental science into improved health across the life span. Pediatricians are now armed with new information about the adverse effects of toxic stress on brain development, as well as a deeper understanding of the early life origins of many adult diseases. As trusted authorities in child health and development, pediatric providers must now complement the early identification of developmental concerns with a greater focus on those interventions and community investments that reduce external threats to healthy brain growth. To this end, AAP endorses a developing leadership role for the entire pediatric community-one that mobilizes the scientific expertise of both basic and clinical researchers, the family-centered care of the pediatric medical home, and the public influence of AAP and its state chapters-to catalyze fundamental change in early childhood policy and services. AAP is committed to leveraging science to inform the development of innovative strategies to reduce the precipitants of toxic stress in young children and to mitigate their negative effects on the course of development and health across the life span.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                18 June 2015
                2015
                : 10
                : 6
                : e0130591
                Affiliations
                [1 ]Department of Family Medicine, University of Iceland and Primary Health Care of the Capital Area, Reykjavik, Iceland
                [2 ]General Practice Research Unit, Department of Public Health and General Practice, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
                [3 ]Department of General Practice, UiT The Arctic University, Tromsø, Norway
                [4 ]HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology (NTNU), Levanger, Norway
                [5 ]Laboratory of Neuroendocrinology, The Rockefeller University, New York, New York, United States of America
                Central South University, CHINA
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: LG ALK IH JAS MOT. Performed the experiments: SK. Analyzed the data: JAS HP MOT. Wrote the paper: MOT JAS HP LG ALK SK BM IH.

                Article
                PONE-D-14-38700
                10.1371/journal.pone.0130591
                4472345
                26086816
                0fefde0e-daf9-4625-bef8-b74b20e7f46f
                Copyright @ 2015

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                : 28 August 2014
                : 22 May 2015
                Page count
                Figures: 3, Tables: 4, Pages: 16
                Funding
                The HUNT3 Survey was mainly funded by the Norwegian Ministry of Health, the Norwegian University of Science and Technology, the Norwegian Research Council (the FUGE program), Central Norway Regional Health Authority, the Nord-Trøndelag County Council and the Norwegian Institute of Public Health. The present analysis received support from the Research Fund of the Icelandic College of Family Physicians. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Custom metadata
                Due to restrictions related to patient consent and Norweign privacy laws, data are available upon request. More information is available at the following URL ( http://www.ntnu.edu/hunt/data) and interested parties may contact Dr. Steinar Kronstad ( steinar.krokstad@ 123456ntnu.no ) with further questions.

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