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      Maltreatment Exposure, Brain Structure and Fear Conditioning in Children and Adolescents

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          Abstract

          <p class="first" id="d954935e256">Alterations in learning processes and the neural circuitry that supports fear conditioning and extinction represent mechanisms through which trauma exposure might influence risk for psychopathology. Few studies examine how trauma or neural structure relates to fear conditioning in children. Children ( <i>n</i>=94) aged 6–18 years, 40.4% ( <i>n</i>=38) with exposure to maltreatment (physical abuse, sexual abuse, or domestic violence), completed a fear conditioning paradigm utilizing blue and yellow bells as conditioned stimuli (CS+/CS−) and an aversive alarm noise as the unconditioned stimulus. Skin conductance responses (SCR) and self-reported fear were acquired. Magnetic resonance imaging data were acquired from 60 children. Children without maltreatment exposure exhibited strong differential conditioning to the CS+ <i>vs</i> CS−, based on SCR and self-reported fear. In contrast, maltreated children exhibited blunted SCR to the CS+ and failed to exhibit differential SCR to the CS+ <i>vs</i> CS− during early conditioning. Amygdala and hippocampal volume were reduced among children with maltreatment exposure and were negatively associated with SCR to the CS+ during early conditioning in the total sample, although these associations were negative only among non-maltreated children and were positive among maltreated children. The association of maltreatment with externalizing psychopathology was mediated by this perturbed pattern of fear conditioning. Child maltreatment is associated with failure to discriminate between threat and safety cues during fear conditioning in children. Poor threat–safety discrimination might reflect either enhanced fear generalization or a deficit in associative learning, which may in turn represent a central mechanism underlying the development of maltreatment-related externalizing psychopathology in children. </p>

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          Most cited references31

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          Neurobiological basis of failure to recall extinction memory in posttraumatic stress disorder.

          A clinical characteristic of posttraumatic stress disorder (PTSD) is persistently elevated fear responses to stimuli associated with the traumatic event. The objective herein is to determine whether extinction of fear responses is impaired in PTSD and whether such impairment is related to dysfunctional activation of brain regions known to be involved in fear extinction, viz., amygdala, hippocampus, ventromedial prefrontal cortex (vmPFC), and dorsal anterior cingulate cortex (dACC). Sixteen individuals diagnosed with PTSD and 15 trauma-exposed non-PTSD control subjects underwent a 2-day fear conditioning and extinction protocol in a 3-T functional magnetic resonance imaging scanner. Conditioning and extinction training were conducted on day 1. Extinction recall (or extinction memory) test was conducted on day 2 (extinguished conditioned stimuli presented in the absence of shock). Skin conductance response (SCR) was scored throughout the experiment as an index of the conditioned response. The SCR data revealed no significant differences between groups during acquisition and extinction of conditioned fear on day 1. On day 2, however, PTSD subjects showed impaired recall of extinction memory. Analysis of functional magnetic resonance imaging data showed greater amygdala activation in the PTSD group during day 1 extinction learning. During extinction recall, lesser activation in hippocampus and vmPFC and greater activation in dACC were observed in the PTSD group. The magnitude of extinction memory across all subjects was correlated with activation of hippocampus and vmPFC during extinction recall testing. These findings support the hypothesis that fear extinction is impaired in PTSD. They further suggest that dysfunctional activation in brain structures that mediate fear extinction learning, and especially its recall, underlie this impairment.
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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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              Trauma exposure and posttraumatic stress disorder in a national sample of adolescents.

              Although exposure to potentially traumatic experiences (PTEs) is common among youths in the United States, information on posttraumatic stress disorder (PTSD) risk associated with PTEs is limited. We estimate lifetime prevalence of exposure to PTEs and PTSD, PTE-specific risk of PTSD, and associations of sociodemographics and temporally prior DSM-IV disorders with PTE exposure, PTSD given exposure, and PTSD recovery among U.S. adolescents. Data were drawn from 6,483 adolescent-parent pairs in the National Comorbidity Survey Replication Adolescent Supplement (NCS-A), a national survey of adolescents aged 13 through 17 years. Lifetime exposure to interpersonal violence, accidents/injuries, network/witnessing, and other PTEs was assessed along with DSM-IV PTSD and other distress, fear, behavior, and substance disorders. A majority (61.8%) of adolescents experienced a lifetime PTE. Lifetime prevalence of DSM-IV PTSD was 4.7% and was significantly higher among females (7.3%) than among males (2.2%). Exposure to PTEs, particularly interpersonal violence, was highest among adolescents not living with both biological parents and with pre-existing behavior disorders. Conditional probability of PTSD was highest for PTEs involving interpersonal violence. Predictors of PTSD among PTE-exposed adolescents included female gender, prior PTE exposure, and pre-existing fear and distress disorders. One-third (33.0%) of adolescents with lifetime PTSD continued to meet criteria within 30 days of interview. Poverty, U.S. nativity, bipolar disorder, and PTE exposure occurring after the focal trauma predicted nonrecovery. Interventions designed to prevent PTSD in PTE-exposed youths should be targeted at victims of interpersonal violence with pre-existing fear and distress disorders, whereas interventions designed to reduce PTSD chronicity should attempt to prevent secondary PTE exposure. Copyright © 2013 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Neuropsychopharmacology
                Neuropsychopharmacol
                Springer Nature
                0893-133X
                1740-634X
                July 2016
                December 2015
                : 41
                : 8
                : 1956-1964
                Article
                10.1038/npp.2015.365
                4908632
                26677946
                1c21ec24-e804-48ca-b69e-6a566094277b
                © 2016
                History

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