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      Mechanisms of neuroplasticity linking early adversity to depression: developmental considerations

      review-article
      1 , , 2 , 3
      Translational Psychiatry
      Nature Publishing Group UK
      Neuroscience, Psychology, Biomarkers

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          Abstract

          Early exposure to psychosocial adversity is among the most potent predictors of depression. Because depression commonly emerges prior to adulthood, we must consider the fundamental principles of developmental neuroscience when examining how experiences of childhood adversity, including abuse and neglect, can lead to depression. Considering that both the environment and the brain are highly dynamic across the period spanning gestation through adolescence, the purpose of this review is to discuss and integrate stress-based models of depression that center developmental processes. We offer a general framework for understanding how psychosocial adversity in early life disrupts or calibrates the biobehavioral systems implicated in depression. Specifically, we propose that the sources and nature of the environmental input shaping the brain, and the mechanisms of neuroplasticity involved, change across development. We contend that the effects of adversity largely depend on the developmental stage of the organism. First, we summarize leading neurobiological models that focus on the effects of adversity on risk for mental disorders, including depression. In particular, we highlight models of allostatic load, acceleration maturation, dimensions of adversity, and sensitive or critical period s. Second, we expound on and review evidence for the formulation that distinct mechanisms of neuroplasticity are implicated depending on the timing of adverse experiences, and that inherent within certain windows of development are constraints on the sources and nature of these experiences. Finally, we consider other important facets of adverse experiences (e.g., environmental unpredictability, perceptions of one’s experiences) before discussing promising research directions for the future of the field.

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          Most cited references215

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          Synaptic pruning by microglia is necessary for normal brain development.

          Microglia are highly motile phagocytic cells that infiltrate and take up residence in the developing brain, where they are thought to provide a surveillance and scavenging function. However, although microglia have been shown to engulf and clear damaged cellular debris after brain insult, it remains less clear what role microglia play in the uninjured brain. Here, we show that microglia actively engulf synaptic material and play a major role in synaptic pruning during postnatal development in mice. These findings link microglia surveillance to synaptic maturation and suggest that deficits in microglia function may contribute to synaptic abnormalities seen in some neurodevelopmental disorders.
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            Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner.

            Microglia are the resident CNS immune cells and active surveyors of the extracellular environment. While past work has focused on the role of these cells during disease, recent imaging studies reveal dynamic interactions between microglia and synaptic elements in the healthy brain. Despite these intriguing observations, the precise function of microglia at remodeling synapses and the mechanisms that underlie microglia-synapse interactions remain elusive. In the current study, we demonstrate a role for microglia in activity-dependent synaptic pruning in the postnatal retinogeniculate system. We show that microglia engulf presynaptic inputs during peak retinogeniculate pruning and that engulfment is dependent upon neural activity and the microglia-specific phagocytic signaling pathway, complement receptor 3(CR3)/C3. Furthermore, disrupting microglia-specific CR3/C3 signaling resulted in sustained deficits in synaptic connectivity. These results define a role for microglia during postnatal development and identify underlying mechanisms by which microglia engulf and remodel developing synapses. Copyright © 2012 Elsevier Inc. All rights reserved.
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              Gender differences in depression in representative national samples: Meta-analyses of diagnoses and symptoms.

              In 2 meta-analyses on gender differences in depression in nationally representative samples, we advance previous work by including studies of depression diagnoses and symptoms to (a) estimate the magnitude of the gender difference in depression across a wide array of nations and ages; (b) use a developmental perspective to elucidate patterns of gender differences across the life span; and (c) incorporate additional theory-driven moderators (e.g., gender equity). For major depression diagnoses and depression symptoms, respectively, we meta-analyzed data from 65 and 95 articles and their corresponding national data sets, representing data from 1,716,195 and 1,922,064 people in over 90 different nations. Overall, odds ratio (OR) = 1.95, 95% confidence interval (CI) [1.88, 2.03], and d = 0.27 [0.26, 0.29]. Age was the strongest predictor of effect size. The gender difference for diagnoses emerged earlier than previously thought, with OR = 2.37 at age 12. For both meta-analyses, the gender difference peaked in adolescence (OR = 3.02 for ages 13-15, and d = 0.47 for age 16) but then declined and remained stable in adulthood. Cross-national analyses indicated that larger gender differences were found in nations with greater gender equity, for major depression, but not depression symptoms. The gender difference in depression represents a health disparity, especially in adolescence, yet the magnitude of the difference indicates that depression in men should not be overlooked. (PsycINFO Database Record
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                Author and article information

                Contributors
                tiffany.ho@ucsf.edu
                Journal
                Transl Psychiatry
                Transl Psychiatry
                Translational Psychiatry
                Nature Publishing Group UK (London )
                2158-3188
                9 October 2021
                9 October 2021
                2021
                : 11
                : 517
                Affiliations
                [1 ]GRID grid.266102.1, ISNI 0000 0001 2297 6811, Department of Psychiatry and Behavioral Sciences and Weill Institute for Neurosciences, , University of California, ; San Francisco, CA USA
                [2 ]GRID grid.265219.b, ISNI 0000 0001 2217 8588, Department of Psychiatry and Behavioral Sciences, , Tulane University School of Medicine, ; New Orleans, LA USA
                [3 ]GRID grid.89336.37, ISNI 0000 0004 1936 9924, Department of Psychology, , University of Texas at Austin, ; Austin, TX USA
                Author information
                http://orcid.org/0000-0002-4500-6364
                Article
                1639
                10.1038/s41398-021-01639-6
                8501358
                34628465
                fb623964-9c33-4a2e-b3dc-8852f54782af
                © The Author(s) 2021

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 26 March 2021
                : 11 September 2021
                : 23 September 2021
                Funding
                Funded by: FundRef https://doi.org/10.13039/100000025, U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH);
                Award ID: K01MH117442
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/100001945, American Psychological Foundation (American Psychological Foundation, Inc.);
                Funded by: FundRef https://doi.org/10.13039/100000093, U.S. Department of Health & Human Services | NIH | Center for Information Technology (Center for Information Technology, National Institutes of Health);
                Award ID: F32HD105385
                Award Recipient :
                Categories
                Review Article
                Custom metadata
                © The Author(s) 2021

                Clinical Psychology & Psychiatry
                neuroscience,psychology,biomarkers
                Clinical Psychology & Psychiatry
                neuroscience, psychology, biomarkers

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