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      Abnormalities of white matter integrity in the corpus callosum of adolescents with PTSD after childhood sexual abuse: a DTI study

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          Abstract

          This study seeks to determine whether white matter integrity in the brain differs between adolescents with post-traumatic stress disorder (PTSD) due to childhood sexual abuse (CSA) and matched healthy adolescents and whether there is a relationship between white matter integrity and symptom severity in the patient group. Using 3T diffusion tensor imaging, we examined fractional anisotropy (FA) in a group of adolescents with CSA-related PTSD ( n = 20) and matched healthy controls ( n = 20), in a region of interest consisting of the bilateral uncinate fasciculus (UF), the genu, splenium and body of the corpus callosum (CC), and the bilateral cingulum. In addition, we performed an exploratory whole brain analysis. Trauma symptomatology was measured with the Trauma Symptom Checklist for Children (TSCC) to enable correlational analyses between FA differences and trauma symptomatology. The PTSD group had significantly lower FA values in the genu, midbody and splenium of the CC in comparison with controls ( p < 0.05, tfce corrected). Post hoc analyses of the eigenvalues of the DTI scan showed increased radial and mean diffusivity in the patient group. In addition, we found a significant negative correlation between scores on the anger subscale of the TSCC and FA values in the left body of the CC in patients ( p < 0.05). Adolescents with CSA-related PTSD show decreased FA in the CC, with abnormalities in the integrity of the left body of the CC being related to anger symptoms. These findings suggest that early trauma exposure affects the development of the CC, which may play a role in the pathophysiology of PTSD in adolescents.

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          The adolescent brain.

          Adolescence is a developmental period characterized by suboptimal decisions and actions that are associated with an increased incidence of unintentional injuries, violence, substance abuse, unintended pregnancy, and sexually transmitted diseases. Traditional neurobiological and cognitive explanations for adolescent behavior have failed to account for the nonlinear changes in behavior observed during adolescence, relative to both childhood and adulthood. This review provides a biologically plausible model of the neural mechanisms underlying these nonlinear changes in behavior. We provide evidence from recent human brain imaging and animal studies that there is a heightened responsiveness to incentives and socioemotional contexts during this time, when impulse control is still relatively immature. These findings suggest differential development of bottom-up limbic systems, implicated in incentive and emotional processing, to top-down control systems during adolescence as compared to childhood and adulthood. This developmental pattern may be exacerbated in those adolescents prone to emotional reactivity, increasing the likelihood of poor outcomes.
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            Smaller hippocampal volume predicts pathologic vulnerability to psychological trauma.

            In animals, exposure to severe stress can damage the hippocampus. Recent human studies show smaller hippocampal volume in individuals with the stress-related psychiatric condition posttraumatic stress disorder (PTSD). Does this represent the neurotoxic effect of trauma, or is smaller hippocampal volume a pre-existing condition that renders the brain more vulnerable to the development of pathological stress responses? In monozygotic twins discordant for trauma exposure, we found evidence that smaller hippocampi indeed constitute a risk factor for the development of stress-related psychopathology. Disorder severity in PTSD patients who were exposed to trauma was negatively correlated with the hippocampal volume of both the patients and the patients' trauma-unexposed identical co-twin. Furthermore, severe PTSD twin pairs-both the trauma-exposed and unexposed members-had significantly smaller hippocampi than non-PTSD pairs.
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              Research review: the neurobiology and genetics of maltreatment and adversity.

              The neurobiological mechanisms by which childhood maltreatment heightens vulnerability to psychopathology remain poorly understood. It is likely that a complex interaction between environmental experiences (including poor caregiving) and an individual's genetic make-up influence neurobiological development across infancy and childhood, which in turn sets the stage for a child's psychological and emotional development. This review provides a concise synopsis of those studies investigating the neurobiological and genetic factors associated with childhood maltreatment and adversity. We first provide an overview of the neuroendocrine findings, drawing from animal and human studies. These studies indicate an association between early adversity and atypical development of the hypothalamic-pituitary-adrenal (HPA) axis stress response, which can predispose to psychiatric vulnerability in adulthood. We then review the neuroimaging findings of structural and functional brain differences in children and adults who have experienced childhood maltreatment. These studies offer evidence of several structural differences associated with early stress, most notably in the corpus callosum in children and the hippocampus in adults; functional studies have reported atypical activation of several brain regions, including decreased activity of the prefrontal cortex. Next we consider studies that suggest that the effect of environmental adversity may be conditional on an individual's genotype. We also briefly consider the possible role that epigenetic mechanisms might play in mediating the impact of early adversity. Finally we consider several ways in which the neurobiological and genetic research may be relevant to clinical practice and intervention. © 2010 The Authors. Journal compilation © 2010 Association for Child and Adolescent Mental Health.
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                Author and article information

                Contributors
                m.a.w.rinne@curium.nl
                Journal
                Eur Child Adolesc Psychiatry
                Eur Child Adolesc Psychiatry
                European Child & Adolescent Psychiatry
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                1018-8827
                1435-165X
                23 December 2015
                23 December 2015
                2016
                : 25
                : 869-878
                Affiliations
                [1 ]Curium-LUMC, Academic Center for Child and Adolescent Psychiatry, Oegstgeest, The Netherlands
                [2 ]Department of Psychiatry, Leiden University Medical Center (LUMC), Leiden, The Netherlands
                [3 ]Leiden Institute for Brain and Cognition (LIBC), Leiden, The Netherlands
                [4 ]Psychotraumacenter and Department of Child and Adolescent Psychiatry, GGZ Rivierduinen, Leiden, The Netherlands
                [5 ]Institute of Psychology and Education, Vrije Universiteit, Amsterdam, The Netherlands
                [6 ]Department of Radiology, Leiden University Medical Center (LUMC), Leiden, The Netherlands
                [7 ]Institute of Psychology, Leiden University, Leiden, The Netherlands
                Article
                805
                10.1007/s00787-015-0805-2
                4967100
                26700102
                91122ad8-465e-487f-8994-510bf7602133
                © The Author(s) 2015

                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.

                History
                : 6 April 2015
                : 28 November 2015
                Funding
                Funded by: National Initiative Brain and Cognition projects
                Award ID: 056-25-010
                Award Recipient :
                Funded by: NWO Vici project
                Award ID: 016130677
                Award Recipient :
                Categories
                Original Contribution
                Custom metadata
                © Springer-Verlag Berlin Heidelberg 2016

                Clinical Psychology & Psychiatry
                ptsd,diffusion tensor imaging,adolescents,sexual abuse,neuroimaging

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