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      Biological embedding of childhood adversity: from physiological mechanisms to clinical implications

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          Abstract

          Background

          Adverse psychosocial exposures in early life, namely experiences such as child maltreatment, caregiver stress or depression, and domestic or community violence, have been associated in epidemiological studies with increased lifetime risk of adverse outcomes, including diabetes, heart disease, cancers, and psychiatric illnesses. Additional work has shed light on the potential molecular mechanisms by which early adversity becomes “biologically embedded” in altered physiology across body systems. This review surveys evidence on such mechanisms and calls on researchers, clinicians, policymakers, and other practitioners to act upon evidence.

          Observations

          Childhood psychosocial adversity has wide-ranging effects on neural, endocrine, immune, and metabolic physiology. Molecular mechanisms broadly implicate disruption of central neural networks, neuroendocrine stress dysregulation, and chronic inflammation, among other changes. Physiological disruption predisposes individuals to common diseases across the life course.

          Conclusions

          Reviewed evidence has important implications for clinical practice, biomedical research, and work across other sectors relevant to public health and child wellbeing. Warranted changes include increased clinical screening for exposures among children and adults, scale-up of effective interventions, policy advocacy, and ongoing research to develop new evidence-based response strategies.

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          Most cited references64

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          Early life stress alters behavior, immunity, and microbiota in rats: implications for irritable bowel syndrome and psychiatric illnesses.

          Adverse early life events are associated with a maladaptive stress response system and might increase the vulnerability to disease in later life. Several disorders have been associated with early life stress, ranging from depression to irritable bowel syndrome. This makes the identification of the neurobiological substrates that are affected by adverse experiences in early life invaluable. The purpose of this study was to assess the effect of early life stress on the brain-gut axis. Male rat pups were stressed by separating them from their mothers for 3 hours daily between postnatal days 2-12. The control group was left undisturbed with their mothers. Behavior, immune response, stress sensitivity, visceral sensation, and fecal microbiota were analyzed. The early life stress increased the number of fecal boli in response to a novel stress. Plasma corticosterone was increased in the maternally separated animals. An increase in the systemic immune response was noted in the stressed animals after an in vitro lipopolysaccharide challenge. Increased visceral sensation was seen in the stressed group. There was an alteration of the fecal microbiota when compared with the control group. These results show that this form of early life stress results in an altered brain-gut axis and is therefore an important model for investigating potential mechanistic insights into stress-related disorders including depression and IBS.
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            Childhood adversity and neural development: deprivation and threat as distinct dimensions of early experience.

            A growing body of research has examined the impact of childhood adversity on neural structure and function. Advances in our understanding of the neurodevelopmental consequences of adverse early environments require the identification of dimensions of environmental experience that influence neural development differently and mechanisms other than the frequently-invoked stress pathways. We propose a novel conceptual framework that differentiates between deprivation (absence of expected environmental inputs and complexity) and threat (presence of experiences that represent a threat to one's physical integrity) and make predictions grounded in basic neuroscience principles about their distinct effects on neural development. We review animal research on fear learning and sensory deprivation as well as human research on childhood adversity and neural development to support these predictions. We argue that these previously undifferentiated dimensions of experience exert strong and distinct influences on neural development that cannot be fully explained by prevailing models focusing only on stress pathways. Our aim is not to exhaustively review existing evidence on childhood adversity and neural development, but to provide a novel framework to guide future research.
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              A structural MRI study of human brain development from birth to 2 years.

              Brain development in the first 2 years after birth is extremely dynamic and likely plays an important role in neurodevelopmental disorders, including autism and schizophrenia. Knowledge regarding this period is currently quite limited. We studied structural brain development in healthy subjects from birth to 2. Ninety-eight children received structural MRI scans on a Siemens head-only 3T scanner with magnetization prepared rapid gradient echo T1-weighted, and turbo spin echo, dual-echo (proton density and T2 weighted) sequences: 84 children at 2-4 weeks, 35 at 1 year and 26 at 2 years of age. Tissue segmentation was accomplished using a novel automated approach. Lateral ventricle, caudate, and hippocampal volumes were also determined. Total brain volume increased 101% in the first year, with a 15% increase in the second. The majority of hemispheric growth was accounted for by gray matter, which increased 149% in the first year; hemispheric white matter volume increased by only 11%. Cerebellum volume increased 240% in the first year. Lateral ventricle volume increased 280% in the first year, with a small decrease in the second. The caudate increased 19% and the hippocampus 13% from age 1 to age 2. There was robust growth of the human brain in the first two years of life, driven mainly by gray matter growth. In contrast, white matter growth was much slower. Cerebellum volume also increased substantially in the first year of life. These results suggest the structural underpinnings of cognitive and motor development in early childhood, as well as the potential pathogenesis of neurodevelopmental disorders.
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                Author and article information

                Contributors
                sarah.jensen@childrens.harvard.edu
                charles_nelson@harvard.edu
                Journal
                BMC Med
                BMC Med
                BMC Medicine
                BioMed Central (London )
                1741-7015
                20 July 2017
                20 July 2017
                2017
                : 15
                : 135
                Affiliations
                [1 ]ISNI 0000 0004 0378 8438, GRID grid.2515.3, , Boston Children’s Hospital, ; Boston, Massachusetts USA
                [2 ]ISNI 000000041936754X, GRID grid.38142.3c, , Harvard Medical School, ; Boston, Massachusetts USA
                [3 ]Laboratories of Cognitive Neuroscience, Boston Children’s Hospital/Harvard Medical School, 1 Autumn Street, Boston, 02215 Massachusetts USA
                [4 ]ISNI 000000041936754X, GRID grid.38142.3c, , Graduate School of Education, Harvard University, ; Cambridge, Massachusetts USA
                Article
                895
                10.1186/s12916-017-0895-4
                5518144
                28724431
                aff74bbc-6c70-4e6e-80ec-24912cc0e02a
                © The Author(s). 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 10 March 2017
                : 20 June 2017
                Categories
                Review
                Custom metadata
                © The Author(s) 2017

                Medicine
                adverse childhood experiences,brain development,stress,health promotion,social disparities,primary care

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