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Krystal JH, Neumeister A. Noradrenergic and serotonergic mechanisms in the neurobiology of posttraumatic stress disorder and resilience. Brain Res 1293: 13-23

Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06516, USA.
Brain research (Impact Factor: 2.83). 04/2009; 1293:13-23. DOI: 10.1016/j.brainres.2009.03.044
Source: PubMed

ABSTRACT Posttraumatic stress disorder (PTSD) is characterized mainly by symptoms of re-experiencing, avoidance and hyperarousal as a consequence of catastrophic and traumatic events that are distinguished from ordinary stressful life events. Although extensive research has already been done, the etiology of PTSD remains unclear. Research on the impact of trauma on neurobiological systems can be expected to inform the development of treatments that are directed specifically to symptoms of PTSD. During the past 25 years there has been a dramatic increase in the knowledge about noradrenergic and serotonergic mechanisms in stress response, PTSD and more recently in resilience and this knowledge has justified the use of antidepressants with monoaminergic mechanisms of action for patients with PTSD. Nevertheless, available treatments of PTSD are only to some extent effective and enhanced understanding of the neurobiology of PTSD may lead to the development of improved treatments for these patients. In the present review, we aim to close existing gaps between basic research in psychopathology, neurobiology and treatment development with the ultimate goal to translate basic research into clinically relevant findings which may directly benefit patients with PTSD.

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    • "Also within the context of neurological disorders, abnormalities of the adrenergic systems of astrocytes are probably involved in the pathogenesis of multiple sclerosis, inflammation, malfunction in Alzheimer's disease (AD) and mood disturbances in affective disorders (Hertz et al., 2004). In other brain regions, NA has been involved in the pathological phenomena of post-traumatic stress disorder (Krystal and Neumeister, 2009) and AD (Weinshenker, 2008). "
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    ABSTRACT: Adrenergic receptors belong to the family of the G protein coupled receptors that represent important targets in the modern pharmacotherapies. Studies on different physiological and pathophysiological prop-erties of the adrenergic system have led to novel evidences and theories that suggest novel possible targeting of such system in a variety of pathologies and disorders, even beyond the classical known therapeutic possibilities. Herein, those advances have been illustrated with selected concepts and different ex-amples. Furthermore, we illustrated the applications and the therapeutic implications that such findings and advances might have in the contexts of experimental pharmacology, therapeutics and clinic. We hope that the content of this work will guide researches devoted to the adrenergic aspects that combine neu-rosciences with pharmacology.
    Neuropeptides 11/2014; 49. DOI:10.1016/j.npep.2014.11.003 · 2.55 Impact Factor
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    • "[13] Another important functional pathways involved in stress responses are the hypothalamic pituitary-adrenal axis (HPA), with deregulation in the corticotropin releasing hormone (CRH), [14] as well as the hyper reactivity of the noradrenergic system that has been suggested to mediate the hyper arousal symptoms and the sleep disturbances in PTSD. [15] Another monoaminergic system linked to PTSD is the serotoninergic (5-HT) system, as 5-HT neurotransmission is increased by stress in several forebrain regions, [16] and SSRIs are efficacious in treating the disorder at least in some individuals. For a more comprehensive understanding of the neurobiology of stress responding and fear conditioning in PTSD, we refer the reader to the recent review by Cain and Maynard. "
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    ABSTRACT: Introduction: Post-traumatic stress disorder (PTSD) is a frequent and disabling condition that occurs after exposure to a traumatic event, and Selective Serotonin Reuptake Inhibitors (SSRIs) are considered the first-line treatment approach for this disorder. However, a large proportion of patients remain symptomatic and other pharmacological agents have been investigated, based on the understanding of the underlying biological dysfunctions of PTSD. Methods: We conducted a review of the literature on the pharmacological options for PTSD other than the antidepressants, using MedLine and Web of Science databases, with search terms including the pharmacologic class of each agent plus PTSD, or pharmacotherapy, or fear conditioning. The literature review covered articles published until august 2012, including reviews and original articles. Results: Agents like antipsychotics, anticonvulsants, benzodiazepines, anti-adrenergic agents, have been studied in randomized clinical trials (RCTs), with general positive results for antipsychotics, especially as adjunct therapy, and for prazosin for sleep-related disturbances. However, one important target for novel medications is the modulation of the fear conditioning process, through the alteration of retrieval/reconsolidation or enhancement of fear extinction. This is traditionally targeted in prolonged exposure therapy, but pre-clinical findings from studies investigating agents like propanolol, clonidine, N-Methyl-D-aspartic Acid Receptor (NMDAR) compounds, 3,4-methylenedioxy-N-methylamphetamine (MDMA) and cannabinoids, indicate promising results in affecting the fear conditioning process and thus improving PTSD core symptoms. Discussion: Antipsychotics can be considered a reasonable alternative option to PTSD, with the largest body of evidence for risperidone, even though larger RCTs are warranted. Prazosin is also a promising agent, especially for sleep-related disturbances, while anticonvulsants and benzodiazepines lack empirical support. However, the most promising area for pharmacotherapy in PTSD is the modulation of the fear conditioning process, through agents used in adjunct to exposure therapy.
    02/2013; 10(2). DOI:10.2174/157488471002150723122127
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    • "Among them, the dysregulation of the serotonergic system has long been recognized as an important factor underlying the pathophysiology of PTSD. Many evidence— including decreased serum concentrations of serotonin (5- HT), decreased density of platelet 5-HT uptake sites, and a blunted prolactin response to D-fenfluramine (indicative of central 5-HT hypoactivity)—suggests that 5HT activity is decreased in PTSD patients [5] [6] [7] [8] [9] [10]. Perhaps the best grounds for proposing that a 5-HT dysfunction exists in PTSD resides in the beneficial treatment effects of SSRIs, which, to date, have already been established as the firstline pharmacotherapeutic agents for treating acute and chronic PTSD. "
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    ABSTRACT: The dysregulation of the serotonergic system has long been recognized as an important factor underlying the pathophysiology of PTSD. To date, SSRIs have already been established as the firstline pharmacotherapeutic agents for treating acute and chronic PTSD. However, SSRIs largely have several disadvantages which limit their utility. Our previous study has also shown that administration of the total flavonoids, isolated from the extract of Xiaobuxin-Tang (XBXT, mild mind-easing decoction), comprising four Chinese medicines including Haematitum, Flos Inulae, Folium Phyllostachydis Henonis, and Semen Sojae Preparatum, exerted significant antidepressant-like effect in chronically mildly stressed rats, possibly mediated by serotonergic activation. Since the central serotonergic dysfunction is an important and well-known cause mediating the pathophysiology of trauma-related symptoms in PTSD, it is reasonable to predict that flavonoids may exert therapeutic effects on PTSD in animal models. Therefore, the present study aims to examine the effect of flavonoids in alleviating the enhanced anxiety and fear response induced in two PTSD animal models. Ser, an SSRI, was administered as a positive control. Furthermore, the changes of brain monoaminergic neurotransmitters after chronic flavonoids administration have also been assessed in SPS-treated rats.
    Evidence-based Complementary and Alternative Medicine 12/2012; 2012:623753. DOI:10.1155/2012/623753 · 1.88 Impact Factor
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