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      Post-traumatic stress disorder: the neurobiological impact of psychological trauma Translated title: Trastomo por estrés postraumático: el impacto neurobiológico del trauma psiquico Translated title: État de stress post-traumatique: impact neurobiologique du traumatisme psychologique

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          Abstract

          The classic fight-or-flight response to perceived threat is a reflexive nervous phenomenon thai has obvious survival advantages in evolutionary terms. However, the systems that organize the constellation of reflexive survival behaviors following exposure to perceived threat can under some circumstances become dysregulated in the process. Chronic dysregulation of these systems can lead to functional impairment in certain individuals who become “psychologically traumatized” and suffer from post-traumatic stress disorder (PTSD), A body of data accumulated over several decades has demonstrated neurobiological abnormalities in PTSD patients. Some of these findings offer insight into the pathophysiology of PTSD as well as the biological vulnerability of certain populations to develop PTSD, Several pathological features found in PTSD patients overlap with features found in patients with traumatic brain injury paralleling the shared signs and symptoms of these clinical syndromes.

          Translated abstract

          La clâsica respuesta de ataque o huida ante la perceptión de una amenaza es un fenómeno nervioso reflejo que, obviamente en términos evolutivos, tiene ventajas para la supervivencia. Sin embargo, los sistemas que organizan la constelación de conductas reflejas de supervivencia que siguen a la exposición a la amenaza percibida en algunas circunstancias pueden constituirse en procesos mal regulados. La mala regulatión crónica de estos sistemas puede llevar a un deterioro funcional en ciertos individuos quienes pueden convertirse en “traumatizados psicológicamente” y presentar un trastorno por estrés postraumático (TEPT), Una gran cantidad de informatión acumulada en varias décadas ha demostrado alteraciones neurobiológicas en los patientes con TEPT, Algunos de estos hallazgos permiten adentrarse en la fisiopatologia asi como en la vulnerabilidad biológica de ciertas poblaciones que van a desarrollar un TEPT Algunas caracteristicas patológicas encontradas en patientes con TEPT se sobreponen con caracteristicas de patientes con daño cerebral traumático, estableciendo un paralelo de signos y sintomas compartidos entre estos sindromes clinicos.

          Translated abstract

          La réponse classique de lutte ou de fuite à une menace perçue est un phénomène nerveux réflexe dont les avantages pour la survie sont évidents en termes d'évolution. Cependant, les systèmes organisés en constellation de comportements réflexes de survie après exposition à une menace perçue peuvent se déréguler dans certaines circonstances. Une dysregulation chronique de ces systèmes peut entraîner un déficit fonctionnel chez certains sujets qui deviennent « psychologiquement traumatisés » ef souffrent de l'état de stress posi-traumatique (ESPT), Des données recueillies pendant des dizaines d'années montrent des anomalies neurobiologiques chez les patients souffrant d'ESPT, ce qui permet de mieux comprendre la physiopathologie de l'ESPT ainsi que la vulnérabilité biologique de certaines populations à développer un ESPT, Certaines caractéristiques pathologiques de l'ESPT se superposent à celles trouvées chez des patients atteints de lésion cérébrale traumatique, en parallèle avec les signes et les symptômes partagés par ces deux syndromes.

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          Most cited references94

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          Serotonin transporter genetic variation and the response of the human amygdala.

          A functional polymorphism in the promoter region of the human serotonin transporter gene (SLC6A4) has been associated with several dimensions of neuroticism and psychopathology, especially anxiety traits, but the predictive value of this genotype against these complex behaviors has been inconsistent. Serotonin [5- hydroxytryptamine, (5-HT)] function influences normal fear as well as pathological anxiety, behaviors critically dependent on the amygdala in animal models and in clinical studies. We now report that individuals with one or two copies of the short allele of the serotonin transporter (5-HTT) promoter polymorphism, which has been associated with reduced 5-HTT expression and function and increased fear and anxiety-related behaviors, exhibit greater amygdala neuronal activity, as assessed by BOLD functional magnetic resonance imaging, in response to fearful stimuli compared with individuals homozygous for the long allele. These results demonstrate genetically driven variation in the response of brain regions underlying human emotional behavior and suggest that differential excitability of the amygdala to emotional stimuli may contribute to the increased fear and anxiety typically associated with the short SLC6A4 allele.
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            Neurocircuitry models of posttraumatic stress disorder and extinction: human neuroimaging research--past, present, and future.

            The prevailing neurocircuitry models of anxiety disorders have been amygdalocentric in form. The bases for such models have progressed from theoretical considerations, extrapolated from research in animals, to in vivo human imaging data. For example, one current model of posttraumatic stress disorder (PTSD) has been highly influenced by knowledge from rodent fear conditioning research. Given the phenomenological parallels between fear conditioning and the pathogenesis of PTSD, we have proposed that PTSD is characterized by exaggerated amygdala responses (subserving exaggerated acquisition of fear associations and expression of fear responses) and deficient frontal cortical function (mediating deficits in extinction and the capacity to suppress attention/response to trauma-related stimuli), as well as deficient hippocampal function (mediating deficits in appreciation of safe contexts and explicit learning/memory). Neuroimaging studies have yielded convergent findings in support of this model. However, to date, neuroimaging investigations of PTSD have not principally employed conditioning and extinction paradigms per se. The recent development of such imaging probes now sets the stage for directly testing hypotheses regarding the neural substrates of fear conditioning and extinction abnormalities in PTSD.
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              Association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults.

              In addition to trauma exposure, other factors contribute to risk for development of posttraumatic stress disorder (PTSD) in adulthood. Both genetic and environmental factors are contributory, with child abuse providing significant risk liability. To increase understanding of genetic and environmental risk factors as well as their interaction in the development of PTSD by gene x environment interactions of child abuse, level of non-child abuse trauma exposure, and genetic polymorphisms at the stress-related gene FKBP5. A cross-sectional study examining genetic and psychological risk factors in 900 nonpsychiatric clinic patients (762 included for all genotype studies) with significant levels of childhood abuse as well as non-child abuse trauma using a verbally presented survey combined with single-nucleotide polymorphism (SNP) genotyping. Participants were primarily urban, low-income, black (>95%) men and women seeking care in the general medical care and obstetrics-gynecology clinics of an urban public hospital in Atlanta, Georgia, between 2005 and 2007. Severity of adult PTSD symptomatology, measured with the modified PTSD Symptom Scale, non-child abuse (primarily adult) trauma exposure and child abuse measured using the traumatic events inventory and 8 SNPs spanning the FKBP5 locus. Level of child abuse and non-child abuse trauma each separately predicted level of adult PTSD symptomatology (mean [SD], PTSD Symptom Scale for no child abuse, 8.03 [10.48] vs > or =2 types of abuse, 20.93 [14.32]; and for no non-child abuse trauma, 3.58 [6.27] vs > or =4 types, 16.74 [12.90]; P < .001). Although FKBP5 SNPs did not directly predict PTSD symptom outcome or interact with level of non-child abuse trauma to predict PTSD symptom severity, 4 SNPs in the FKBP5 locus significantly interacted (rs9296158, rs3800373, rs1360780, and rs9470080; minimum P = .0004) with the severity of child abuse to predict level of adult PTSD symptoms after correcting for multiple testing. This gene x environment interaction remained significant when controlling for depression severity scores, age, sex, levels of non-child abuse trauma exposure, and genetic ancestry. This genetic interaction was also paralleled by FKBP5 genotype-dependent and PTSD-dependent effects on glucocorticoid receptor sensitivity, measured by the dexamethasone suppression test. Four SNPs of the FKBP5 gene interacted with severity of child abuse as a predictor of adult PTSD symptoms. There were no main effects of the SNPs on PTSD symptoms and no significant genetic interactions with level of non-child abuse trauma as predictor of adult PTSD symptoms, suggesting a potential gene-childhood environment interaction for adult PTSD.
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                Author and article information

                Contributors
                Department of Psychiatry and Behavioral Sciences, University of Miami, Leonard M. Miller School of Medicine, Miami, Florida, USA; Department of Mental Health and Behavioral Sciences, Miami VA Healthcare System, Miami, Florida, USA
                Department of Psychiatry and Behavioral Sciences, University of Miami, Leonard M. Miller School of Medicine, Miami, Florida, USA
                Journal
                Dialogues Clin Neurosci
                Dialogues Clin Neurosci
                Dialogues in Clinical Neuroscience
                Les Laboratoires Servier (France )
                1294-8322
                1958-5969
                September 2011
                September 2011
                : 13
                : 3
                : 263-278
                Affiliations
                Department of Psychiatry and Behavioral Sciences, University of Miami, Leonard M. Miller School of Medicine, Miami, Florida, USA; Department of Mental Health and Behavioral Sciences, Miami VA Healthcare System, Miami, Florida, USA
                Department of Psychiatry and Behavioral Sciences, University of Miami, Leonard M. Miller School of Medicine, Miami, Florida, USA
                Author notes
                Article
                10.31887/DCNS.2011.13.2/jsherin
                3182008
                22034143
                a061ba19-b96b-435f-93d7-ae4f89cf4de9
                Copyright: © 2011 LLS

                This is an open-access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by-nc-nd/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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                Categories
                State of the Art

                Neurosciences
                traumatic brain injury,psychological trauma,stress,psychopathology,ptsd,pathophysiology,biological markers

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