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      Childhood adversity, externalizing behavior, and substance use in adolescence: Mediating effects of anterior cingulate cortex activation during inhibitory errors

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          Abstract

          Childhood adversity can negatively impact development across various domains, including physical and mental health. Adverse childhood experiences have been linked to aggression and substance use; however, developmental pathways to explain these associations are not well characterized. Understanding early precursors to later problem behavior and substance use can inform preventive interventions. The aim of the current study was to examine neurobiological pathways through which childhood adversity may lead to early adolescent problem behavior and substance use in late adolescence by testing two prospective models. Our first model found that early adolescent externalizing behavior mediates the association between childhood adversity and alcohol, cigarette, and marijuana use in late adolescence. Our second model found that activation in the anterior cingulate cortex (ACC) during an inhibitory control task mediates the association between childhood adversity and early adolescent externalizing behavior, with lower ACC activation associated with higher levels of adversity and more externalizing behavior. Together these findings indicate that the path to substance use in late adolescence from childhood adversity may operate through lower functioning in the ACC related to inhibitory control and externalizing behavior. Early life stressors should be considered an integral component in the etiology and prevention of early and problematic substance use.

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          Most cited references37

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          The role of the medial frontal cortex in cognitive control.

          Adaptive goal-directed behavior involves monitoring of ongoing actions and performance outcomes, and subsequent adjustments of behavior and learning. We evaluate new findings in cognitive neuroscience concerning cortical interactions that subserve the recruitment and implementation of such cognitive control. A review of primate and human studies, along with a meta-analysis of the human functional neuroimaging literature, suggest that the detection of unfavorable outcomes, response errors, response conflict, and decision uncertainty elicits largely overlapping clusters of activation foci in an extensive part of the posterior medial frontal cortex (pMFC). A direct link is delineated between activity in this area and subsequent adjustments in performance. Emerging evidence points to functional interactions between the pMFC and the lateral prefrontal cortex (LPFC), so that monitoring-related pMFC activity serves as a signal that engages regulatory processes in the LPFC to implement performance adjustments.
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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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              Epigenetics and the biological definition of gene x environment interactions.

              Variations in phenotype reflect the influence of environmental conditions during development on cellular functions, including that of the genome. The recent integration of epigenetics into developmental psychobiology illustrates the processes by which environmental conditions in early life structurally alter DNA, providing a physical basis for the influence of the perinatal environmental signals on phenotype over the life of the individual. This review focuses on the enduring effects of naturally occurring variations in maternal care on gene expression and phenotype to provide an example of environmentally driven plasticity at the level of the DNA, revealing the interdependence of gene and environmental in the regulation of phenotype.
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                Author and article information

                Journal
                8910645
                20550
                Dev Psychopathol
                Dev. Psychopathol.
                Development and psychopathology
                0954-5794
                1469-2198
                13 July 2018
                October 2019
                01 April 2020
                : 31
                : 4
                : 1439-1450
                Affiliations
                [a ]Robert Stempel College of Public Health & Social Work, Florida International University, 11200 SW 8 th Street, AHC-5, Miami, FL, USA, 33134
                [b ]Center for Children and Families, Florida International University, 11200 SW 8 th Street, AHC-1, Miami, FL, USA, 33134
                [c ]Department of Psychology, Florida International University, 11200 SW 8 th Street, AHC-1, Miami, FL, USA, 33134
                [d ]Department of Psychiatry, University of Michigan, 4250 Plymouth Rd., Ann Arbor, MI, USA, 48109
                Author notes
                Correspondence concerning this article should be addressed to Nicole M. Fava, Florida International University, 11200 S.W. 8th Street, AHC5-566, Miami, FL, 33199, Phone: 305-348-4568, Fax: 305-348-5312, nfava@ 123456fiu.edu .
                Article
                PMC6594917 PMC6594917 6594917 nihpa981007
                10.1017/S0954579418001025
                6594917
                30585564
                fe23e383-96c3-4bed-93d6-5ef0482cb5ef
                History
                Categories
                Article

                inhibitory control,childhood adversity,externalizing behavior,anterior cingulate cortex,substance use

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