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      Future Directions in the Study of Early-Life Stress and Physical and Emotional Health: Implications of the Neuroimmune Network Hypothesis

      1 , 2 , 2
      Journal of Clinical Child & Adolescent Psychology
      Informa UK Limited

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          Abstract

          Early-life stress is associated with increased vulnerability to physical and emotional health problems across the lifespan. The recently developed neuroimmune network hypothesis proposes that one of the underlying mechanisms for these associations is that early-life stress amplifies bidirectional crosstalk between the brain and the immune system, contributing to several mental and physical health conditions that have inflammatory underpinnings, such as depression and coronary heart disease. Neuroimmune crosstalk is thought to perpetuate inflammation and neural alterations linked to early-life stress exposure, and also foster behaviors that can further compromise health, such as smoking, drug abuse and consumption of high-fat diets. The goal of the present review is to briefly summarize the neuroimmune network hypothesis and use it as a starting point for generating new questions about the role of early-life stress in establishing a dysregulated relationship between neural and immune signaling, with consequences for lifespan physical and emotional health. Specifically, we aim to discuss implications and future directions for theory and empirical research on early-life stress, as well as for interventions that may improve the health and well-being of children and adolescents living in adverse conditions.

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          Most cited references76

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          Cumulative risk and child development.

          Childhood multiple risk factor exposure exceeds the adverse developmental impacts of singular exposures. Multiple risk factor exposure may also explain why sociodemographic variables (e.g., poverty) can have adverse consequences. Most research on multiple risk factor exposure has relied upon cumulative risk (CR) as the measure of multiple risk. CR is constructed by dichotomizing each risk factor exposure (0 = no risk; 1 = risk) and then summing the dichotomous scores. Despite its widespread use in developmental psychology and elsewhere, CR has several shortcomings: Risk is designated arbitrarily; data on risk intensity are lost; and the index is additive, precluding the possibility of statistical interactions between risk factors. On the other hand, theoretically more compelling multiple risk metrics prove untenable because of low statistical power, extreme higher order interaction terms, low robustness, and collinearity among risk factors. CR multiple risk metrics are parsimonious, are statistically sensitive even with small samples, and make no assumptions about the relative strengths of multiple risk factors or their collinearity. CR also fits well with underlying theoretical models (e.g., Bronfenbrenner's, 1979, bioecological model; McEwen's, 1998, allostasis model of chronic stress; and Ellis, Figueredo, Brumbach, & Schlomer's, 2009, developmental evolutionary theory) concerning why multiple risk factor exposure is more harmful than singular risk exposure. We review the child CR literature, comparing CR to alternative multiple risk measurement models. We also discuss strengths and weaknesses of developmental CR research, offering analytic and theoretical suggestions to strengthen this growing area of scholarship. Finally, we highlight intervention and policy implications of CR and child development research and theory. © 2013 American Psychological Association
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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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              Effect of anti-inflammatory treatment on depression, depressive symptoms, and adverse effects: a systematic review and meta-analysis of randomized clinical trials.

              Several studies have reported antidepressant effects of anti-inflammatory treatment; however, the results have been conflicting and detrimental adverse effects may contraindicate the use of anti-inflammatory agents. To systematically review the antidepressant and possible adverse effects of anti-inflammatory interventions. Trials published prior to December, 31, 2013, were identified searching Cochrane Central Register of Controlled Trials, PubMed, EMBASE, PsychINFO, Clinicaltrials.gov, and relevant review articles. Randomized placebo-controlled trials assessing the efficacy and adverse effects of pharmacologic anti-inflammatory treatment in adults with depressive symptoms, including those who fulfilled the criteria for depression. Data were extracted by 2 independent reviewers. Pooled standard mean difference (SMD) and odds ratios (ORs) were calculated. Depression scores after treatment and adverse effects. Ten publications reporting on 14 trials (6262 participants) were included: 10 trials evaluated the use of nonsteroidal anti-inflammatory drugs (NSAIDs) (n=4,258) and 4 investigated cytokine inhibitors (n=2,004). The pooled effect estimate suggested that anti-inflammatory treatment reduced depressive symptoms (SMD, -0.34; 95% CI, -0.57 to -0.11; I2=90%) compared with placebo. This effect was observed in studies including patients with depression (SMD, -0.54; 95% CI, -1.08 to -0.01; I2=68%) and depressive symptoms (SMD, -0.27; 95% CI, -0.53 to -0.01; I2=68%). The heterogeneity of the studies was not explained by differences in inclusion of clinical depression vs depressive symptoms or use of NSAIDs vs cytokine inhibitors. Subanalyses emphasized the antidepressant properties of the selective cyclooxygenase 2 inhibitor celecoxib (SMD, -0.29; 95% CI, -0.49 to -0.08; I2=73%) on remission (OR, 7.89; 95% CI, 2.94 to 21.17; I2=0%) and response (OR, 6.59; 95% CI, 2.24 to 19.42; I2=0%). Among the 6 studies reporting on adverse effects, we found no evidence of an increased number of gastrointestinal or cardiovascular events after 6 weeks or infections after 12 weeks of anti-inflammatory treatment compared with placebo. All trials were associated with a high risk of bias owing to potentially compromised internal validity. Our analysis suggests that anti-inflammatory treatment, in particular celecoxib, decreases depressive symptoms without increased risks of adverse effects. However, a high risk of bias and high heterogeneity made the mean estimate uncertain. This study supports a proof-of-concept concerning the use of anti-inflammatory treatment in depression. Identification of subgroups that could benefit from such treatment might be warranted.
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                Author and article information

                Journal
                Journal of Clinical Child & Adolescent Psychology
                Journal of Clinical Child & Adolescent Psychology
                Informa UK Limited
                1537-4416
                1537-4424
                June 02 2017
                January 02 2018
                January 20 2017
                January 02 2018
                : 47
                : 1
                : 142-156
                Affiliations
                [1 ] Department of Psychology, University of California–Davis
                [2 ] Department of Psychology, Northwestern University
                Article
                10.1080/15374416.2016.1266647
                6100778
                28107039
                848ceab9-72e2-4896-ad5f-a74ff013ac0e
                © 2018
                History

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