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      Exploring the impact of trauma type and extent of exposure on posttraumatic alterations in 5-HT1A expression

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          Abstract

          The long-term behavioral, psychological, and neurobiological effects of exposure to potentially traumatic events vary within the human population. Studies conducted on trauma-exposed human subjects suggest that differences in trauma type and extent of exposure combine to affect development, maintenance, and treatment of a variety of psychiatric syndromes. The serotonin 1-A receptor (5-HT1A) is an inhibitory G protein-coupled serotonin receptor encoded by the HTR1A gene that plays a role in regulating serotonin release, physiological stress responding, and emotional behavior. Studies from the preclinical and human literature suggest that dysfunctional expression of 5-HT1A is associated with a multitude of psychiatric symptoms commonly seen in trauma-exposed individuals. Here, we synthesize the literature, including numerous preclinical studies, examining differences in alterations in 5-HT1A expression following trauma exposure. Collectively, these findings suggest that the impact of trauma exposure on 5-HT1A expression is dependent, in part, on trauma type and extent of exposure. Furthermore, preclinical and human studies suggest that this observation likely applies to additional molecular targets and may help explain variation in trauma-induced changes in behavior and treatment responsivity. In order to understand the neurobiological impact of trauma, including the impact on 5-HT1A expression, it is crucial to consider both trauma type and extent of exposure.

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          Most cited references187

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          The link between childhood trauma and depression: insights from HPA axis studies in humans.

          Childhood trauma is a potent risk factor for developing depression in adulthood, particularly in response to additional stress. We here summarize results from a series of clinical studies suggesting that childhood trauma in humans is associated with sensitization of the neuroendocrine stress response, glucocorticoid resistance, increased central corticotropin-releasing factor (CRF) activity, immune activation, and reduced hippocampal volume, closely paralleling several of the neuroendocrine features of depression. Neuroendocrine changes secondary to early-life stress likely reflect risk to develop depression in response to stress, potentially due to failure of a connected neural circuitry implicated in emotional, neuroendocrine and autonomic control to compensate in response to challenge. However, not all of depression is related to childhood trauma and our results suggest the existence of biologically distinguishable subtypes of depression as a function of childhood trauma that are also responsive to differential treatment. Other risk factors, such as female gender and genetic dispositions, interfere with components of the stress response and further increase vulnerability for depression. Similar associations apply to a spectrum of other psychiatric and medical disorders that frequently coincide with depression and are aggravated by stress. Taken together, this line of evidence demonstrates that psychoneuroendocrine research may ultimately promote optimized clinical care and help prevent the adverse outcomes of childhood trauma.
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            National estimates of exposure to traumatic events and PTSD prevalence using DSM-IV and DSM-5 criteria.

            Prevalence of posttraumatic stress disorder (PTSD) defined according to the American Psychiatric Association's Diagnostic and Statistical Manual fifth edition (DSM-5; 2013) and fourth edition (DSM-IV; 1994) was compared in a national sample of U.S. adults (N = 2,953) recruited from an online panel. Exposure to traumatic events, PTSD symptoms, and functional impairment were assessed online using a highly structured, self-administered survey. Traumatic event exposure using DSM-5 criteria was high (89.7%), and exposure to multiple traumatic event types was the norm. PTSD caseness was determined using Same Event (i.e., all symptom criteria met to the same event type) and Composite Event (i.e., symptom criteria met to a combination of event types) definitions. Lifetime, past-12-month, and past 6-month PTSD prevalence using the Same Event definition for DSM-5 was 8.3%, 4.7%, and 3.8% respectively. All 6 DSM-5 prevalence estimates were slightly lower than their DSM-IV counterparts, although only 2 of these differences were statistically significant. DSM-5 PTSD prevalence was higher among women than among men, and prevalence increased with greater traumatic event exposure. Major reasons individuals met DSM-IV criteria, but not DSM-5 criteria were the exclusion of nonaccidental, nonviolent deaths from Criterion A, and the new requirement of at least 1 active avoidance symptom.
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              Disorders of extreme stress: The empirical foundation of a complex adaptation to trauma.

              Children and adults exposed to chronic interpersonal trauma consistently demonstrate psychological disturbances that are not captured in the posttraumatic stress disorder (PTSD) diagnosis. The DSM-IV (American Psychiatric Association, 1994) Field Trial studied 400 treatment-seeking traumatized individuals and 128 community residents and found that victims of prolonged interpersonal trauma, particularly trauma early in the life cycle, had a high incidence of problems with (a) regulation of affect and impulses, (b) memory and attention, (c) self-perception, (d) interpersonal relations, (e) somatization, and (f) systems of meaning. This raises important issues about the categorical versus the dimensional nature of posttraumatic stress, as well as the issue of comorbidity in PTSD. These data invite further exploration of what constitutes effective treatment of the full spectrum of posttraumatic psychopathology.
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                Author and article information

                Contributors
                mlewis1@vt.edu
                Journal
                Transl Psychiatry
                Transl Psychiatry
                Translational Psychiatry
                Nature Publishing Group UK (London )
                2158-3188
                16 July 2020
                16 July 2020
                2020
                : 10
                : 237
                Affiliations
                [1 ]GRID grid.438526.e, ISNI 0000 0001 0694 4940, Virginia Tech, ; Blacksburg, VA USA
                [2 ]GRID grid.47100.32, ISNI 0000000419368710, Yale University, ; New Haven, CT USA
                Author information
                http://orcid.org/0000-0002-3903-9055
                http://orcid.org/0000-0001-7297-710X
                Article
                915
                10.1038/s41398-020-00915-1
                7366706
                32678079
                ecdab08d-c4e5-41f2-a9a2-2571da3c8f10
                © The Author(s) 2020

                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
                : 20 November 2019
                : 15 June 2020
                : 23 June 2020
                Categories
                Review Article
                Custom metadata
                © The Author(s) 2020

                Clinical Psychology & Psychiatry
                pathogenesis,molecular neuroscience
                Clinical Psychology & Psychiatry
                pathogenesis, molecular neuroscience

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