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Xixia Chu, Ying Zhou, Zhiqiang Hu, Jingyu Lou, Wei Song, Jing Li, Xiao Liang, Chen Chen, Shuai Wang, Beimeng Yang, Lei Chen, Xu Zhang, Jinjing Song, Yujie Dong, Shiqing Chen, Lin He, Qingguo Xie, Xiaoping Chen, Weidong Li
There is an increasing risk of mental disorders, such as acute stress disorder (ASD), post-traumatic stress disorder (PTSD) and depression among survivors who were trapped in rubble during earthquake. Such long-term impaction of a single acute restraint stress has not been extensively explored. In this study, we subjected mice to 24-hour-restraint to simulate the trapping episode, and investigated the acute (2 days after the restraint) and long-term (35 days after the restraint) impacts. Surprisingly, we found that the mice displayed depression-like behaviors, decreased glucose uptake in brain and reduced adult hippocampal neurogenesis 35 days after the restraint...
2016: Scientific Reports
Chi-Ya Kao, Zhisong He, Kathrin Henes, John M Asara, Christian Webhofer, Michaela D Filiou, Philipp Khaitovich, Carsten T Wotjak, Christoph W Turck
Posttraumatic stress disorder (PTSD) is a prevalent psychiatric disorder. Several studies have attempted to characterize molecular alterations associated with PTSD, but most findings were limited to the investigation of specific cellular markers in the periphery or defined brain regions. In the current study, we aimed to unravel affected molecular pathways/mechanisms in the fear circuitry associated with PTSD. We interrogated a foot shock-induced PTSD mouse model by integrating proteomics and metabolomics profiling data...
May 2016: Molecular Neuropsychiatry
Daniel J Lee, Carla W Schnitzlein, Jonathan P Wolf, Meena Vythilingam, Ann M Rasmusson, Charles W Hoge
BACKGROUND: Current clinical practice guidelines (CPGs) for posttraumatic stress disorder (PTSD) offer contradictory recommendations regarding use of medications or psychotherapy as first-line treatment. Direct head-to-head comparisons are lacking. METHODS: Systemic review of Medline, EMBASE, PILOTS, Cochrane Central Register of Controlled Trials, PsycINFO, and Global Health Library was conducted without language restrictions. Randomized clinical trials ≥8 weeks in duration using structured clinical interview-based outcome measures, active-control conditions (e...
September 2016: Depression and Anxiety
Chi-Ya Kao, Zhisong He, Anthony S Zannas, Oliver Hahn, Claudia Kühne, Judith M Reichel, Elisabeth B Binder, Carsten T Wotjak, Philipp Khaitovich, Christoph W Turck
Despite intense research efforts the molecular mechanisms affecting stress-vulnerable brain regions in posttraumatic stress disorder (PTSD) remain elusive. In the current study we have applied global transcriptomic profiling to a PTSD mouse model induced by foot shock fear conditioning. We compared the transcriptomes of prelimbic cortex, anterior cingulate cortex (ACC), basolateral amygdala, central nucleus of amygdala, nucleus accumbens (NAc) and CA1 of the dorsal hippocampus between shocked and non-shocked (control) mice, with and without fluoxetine treatment by RNA sequencing...
May 2016: Journal of Psychiatric Research
Zhongli Wang, Kexuan Zhu, Lin Chen, Liufeng Ou Yang, Yufang Huang, Yunan Zhao
We investigated the preventive effects of Rg1 on a model of mouse post-traumatic stress disorder (PTSD) induced by electric shock combined with situation reminder and explored the underlying mechanism. In the experiment, before the PTSD animal model was developed, Rg1 (10, 5, and 2.5mg/kg) was orally administered for one week. After the animal model was established, PTSD-like behavior was observed using elevated plus maze, black and light box, and open field tests. One hour after the behavior test, all mice were sacrificed, and then serum corticosterone (CORT) and hypothalamus corticotrophin-releasing hormone (CRH) assays were performed...
September 25, 2015: Neuroscience Letters
Dorothy Liu-Barbaro, Murray Stein
Despite widespread awareness of their frequent co-occurrence, little is known about treatment of individuals with comorbid posttraumatic stress disorder (PTSD) and dissociative disorders. Patients with dissociative disorders do not respond well to standard exposure therapy, and few psychopharmacologic trials exist. Fluoxetine proved ineffective for depersonalization disorder, but paroxetine showed efficacy in decreasing dissociative symptoms in PTSD patients.
July 2015: Journal of Clinical Psychiatry
Fang Han, Bing Xiao, Lili Wen, Yuxiu Shi
Posttraumatic stress disorder (PTSD) is an anxiety- and memory-based disorder. The hippocampus and amygdala are key areas in mood regulation. Fluoxetine was found to improve the anxiety-related symptoms of PTSD patients. However, little work has directly examined the effects of fluoxetine on the hippocampus and the amygdala. In the present study, male Wistar rats received fluoxetine or vehicle after exposure to a single prolonged stress (SPS), an animal model of PTSD. In vivo proton magnetic resonance spectroscopy ((1)H-MRS) was performed -1, 1, 4, 7 and 14 days after SPS to examine the effects of fluoxetine on neurometabolite changes in amygdala, hippocampus and thalamus...
May 30, 2015: Psychiatry Research
Mathew Hoskins, Jennifer Pearce, Andrew Bethell, Liliya Dankova, Corrado Barbui, Wietse A Tol, Mark van Ommeren, Joop de Jong, Soraya Seedat, Hanhui Chen, Jonathan I Bisson
BACKGROUND: Pharmacological treatment is widely used for post-traumatic stress disorder (PTSD) despite questions over its efficacy. AIMS: To determine the efficacy of all types of pharmacotherapy, as monotherapy, in reducing symptoms of PTSD, and to assess acceptability. METHOD: A systematic review and meta-analysis of randomised controlled trials was undertaken; 51 studies were included. RESULTS: Selective serotonin reuptake inhibitors were found to be statistically superior to placebo in reduction of PTSD symptoms but the effect size was small (standardised mean difference -0...
February 2015: British Journal of Psychiatry: the Journal of Mental Science
S Aga-Mizrachi, A Cymerblit-Sabba, O Gurman, A Balan, G Shwam, R Deshe, L Miller, N Gorodetsky, N Heinrich, O Tzezana, S Zubedat, D Grinstein, A Avital
Antidepressant medication constitutes the first line pharmacological treatment for posttraumatic stress disorder (PTSD), however, because many patients display no beneficial drug effects it has been suggested that combinations of antidepressants with additional drugs may be necessary. The defining symptoms of PTSD include re-experiencing, avoidance and hyperarousal. In addition, PTSD patients were shown to become easily distracted and often suffer from poor concentration together with indications of comorbidity with attention-deficit hyperactivity disorder (ADHD)...
2014: Translational Psychiatry
Roberto Carlos Agis-Balboa, Alessandro Guidotti, Graziano Pinna
RATIONALE: The implications of the neurosteroid 3α-hydroxy-5α-pregnan-20-one [allopregnanolone (Allo)] in neuropsychiatric disorders have been highlighted in several recent clinical investigations. For instance, Allo levels are decreased in the cerebrospinal fluid (CSF) of patients with posttraumatic stress disorder (PTSD) and major unipolar depression. Neurosteroidogenic antidepressants [i.e., selective brain steroidogenic stimulants (SBSSs)], including fluoxetine and analogs, correct this decrease in a manner that correlates with improved depressive symptoms...
September 2014: Psychopharmacology
Ulrike Schmidt, Leonie Herrmann, Kathrin Hagl, Bozidar Novak, Christine Huber, Florian Holsboer, Carsten T Wotjak, Dominik R Buell
MicroRNAs (miRNA) are a class of small non-coding RNAs that have recently emerged as epigenetic modulators of gene expression in psychiatric diseases like schizophrenia and major depression. So far, miRNAs have neither been studied in patients suffering from posttraumatic stress disorder (PTSD) nor in PTSD animal models. Here, we present the first study exploring the connection between miRNAs and PTSD. Employing our previously established PTSD mouse model, we assessed miRNA profiles in prefrontal cortices (PFCs) dissected from either fluoxetine or control-treated wildtype C57BL/6N mice 74 days after their subjection to either a single traumatic electric footshock or mock-treatment...
2013: Frontiers in Psychiatry
Bradley V Watts, Paula P Schnurr, Lorna Mayo, Yinong Young-Xu, William B Weeks, Matthew J Friedman
OBJECTIVE: Posttraumatic stress disorder (PTSD) is an important mental health issue in terms of the number of people affected and the morbidity and functional impairment associated with the disorder. The purpose of this study was to examine the efficacy of all treatments for PTSD. DATA SOURCES: PubMed, MEDLINE, PILOTS, and PsycINFO databases were searched for randomized controlled clinical trials of any treatment for PTSD in adults published between January 1, 1980, and April 1, 2012, and written in the English language...
June 2013: Journal of Clinical Psychiatry
Anu Joseph, Mingxi Tang, Takayoshi Mamiya, Qian Chen, Ling-Ling Yang, Jianwei Jiao, Na Yu, Ya-Ping Tang
Adolescent trauma (AT) is a common risk factor for adult-onset posttraumatic stress disorder (PTSD). However, the vulnerability to AT among different individuals varies dramatically, indicating that other cofactors are important. Despite extensive studies, the identification of those cofactors has had little success. Here, we found that after subjected to traumatic stress at postnatal day 25 (P25), a stage that is comparable to the human adolescent period, inducible/reversible forebrain-specific cholecystokinin receptor-2 transgenic (IF-CCKR-2 tg) mice exhibited a significantly higher level of PTSD-like behavior at a later life (adult) stage compared with their wild-type littermates...
April 16, 2013: Proceedings of the National Academy of Sciences of the United States of America
Leonie Herrmann, Irina A Ionescu, Kathrin Henes, Yulia Golub, Nancy Xin Ru Wang, Dominik R Buell, Florian Holsboer, Carsten T Wotjak, Ulrike Schmidt
Despite intensive research efforts, the molecular pathogenesis of posttraumatic stress disorder (PTSD) and especially of the hippocampal volume loss found in the majority of patients suffering from this anxiety disease still remains elusive. We demonstrated before that trauma-induced hippocampal shrinkage can also be observed in mice exhibiting a PTSD-like syndrome. Aiming to decipher the molecular correlates of these trans-species posttraumatic hippocampal alterations, we compared the expression levels of a set of neurostructural marker proteins between traumatized and control mice at different time points after their subjection to either an electric footshock or mock treatment which was followed by stressful re-exposure in several experimental groups...
2012: PloS One
Alicia R Maher, George Theodore
BACKGROUND: Conventional and atypical antipsychotic medications are approved by the FDA for treatment of schizophrenia and bipolar disorder. Over many decades, the widespread use of conventional antipsychotics produced various side effects requiring additional medications, such as the atypical antipsychotics. Beginning in 2006, 9 atypical antipsychotic drugs have been approved by the FDA for indications that were previously off-label uses: aripiprazole (as augmentation for major depressive disorder [MDD] and for autism spectrum disorders), asenapine, clozapine, iloperidone, olanzapine (in combination with fluoxetine for MDD and bipolar depression), paliperidone, quetiapine (quetiapine and quetiapine XR [extended release] as monotherapy in bipolar depression and quetiapine XR as augmentation for MDD), risperidone (for autism spectrum disorders), and ziprasidone...
June 2012: Journal of Managed Care Pharmacy: JMCP
Mauricio Schüler Nin, Luis A Martinez, Fabio Pibiri, Marianela Nelson, Graziano Pinna
The pharmacological action of selective serotonin reuptake inhibitor antidepressants may include a normalization of the decreased brain levels of the brain-derived neurotrophic factor (BDNF) and of neurosteroids such as the progesterone metabolite allopregnanolone, which are decreased in patients with depression and posttraumatic stress disorders (PTSD). The allopregnanolone and BDNF level decrease in PTSD and depressed patients is associated with behavioral symptom severity. Antidepressant treatment upregulates both allopregnanolone levels and the expression of BDNF in a manner that significantly correlates with improved symptomatology, which suggests that neurosteroid biosynthesis and BDNF expression may be interrelated...
2011: Frontiers in Endocrinology
Xueqing Hu, Yan Li, Zhiying Hu, John A Rudd, Shucai Ling, Fangzhen Jiang, Henry Davies, Marong Fang
5-HT receptor changes remain controversial in posttraumatic stress disorder (PTSD) models. This study looks at the relationship between traumatic injuries and the alterations in 5-HT(2A) and 5-HT(2C) receptors in the goldfish brain. The effect of treatment with doxepin and fluoxetine, known to be selective serotonin reuptake inhibitor (SSRI) antidepressants, on 5-HT receptor expression in goldfish with fin ablation was also investigated. We demonstrated that fin ablation induced anxiety-like behavioural alterations and significant up-regulation of c-fos expression in goldfish cerebellum...
July 2012: Neurochemistry International
Thieza G Melo, Geison S Izídio, Luane S Ferreira, Diego S Sousa, Priscila T Macedo, Alícia Cabral, Alessandra M Ribeiro, Regina H Silva
Treatment of major depression, posttraumatic stress disorder and other psychopathologies with antidepressants can be associated with improvement of the cognitive deficits related to these disorders. Although the mechanisms of these effects are not completely elucidated, alterations in the extinction of aversive memories are believed to play a role in these psychopathologies. We have recently verified that female rats present low levels of extinction when submitted to the plus-maze discriminative avoidance task...
April 27, 2012: Progress in Neuro-psychopharmacology & Biological Psychiatry
Graziano Pinna, Ann M Rasmusson
Benzodiazepines remain the most frequently used psychotropic drugs for the treatment of anxiety spectrum disorders; however, their use is associated with the development of tolerance and dependence. Another major hindrance is represented by their lack of efficacy in many patients, including patients with post-traumatic stress disorder (PTSD). For these nonresponders, the use of selective serotonin reuptake inhibitors (SSRIs) has been the therapy of choice. In the past decade, clinical studies have suggested that the pharmacological action of SSRIs may include the ability of these drugs to normalise decreased brain levels of neurosteroids in patients with depression and PTSD; in particular, the progesterone derivative allopregnanolone, which potently, positively and allosterically modulates the action of GABA at GABA(A) receptors...
January 2012: Journal of Neuroendocrinology
Tanja Frančišković, Zoran Suković, Sanja Janović, Aleksandra Stevanović, Iva Nemčić-Moro, Ika Rončević-Gržeta, Marina Letica-Crepulja
BACKGROUND: The aim of this study was to evaluate the efficacy of tianeptine, an antidepressant that acts by increasing serotonin reuptake, in the treatment of posttraumatic stress disorder and to compare the effects of tianeptine and fluoxetine, an antidepressant from the selective serotonin reuptake inhibitors class. SUBJECTS AND METHODS: 43 war veterans suffering from posttraumatic stress disorder were included in the study. During the 5.5 months of treatment 21 patients were receiving tianeptine and 22 were receiving fluoxetine...
September 2011: Psychiatria Danubina
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