阿普唑仑对创伤后应激障碍的预防作用

目的:探讨阿普唑仑(alprazolam,APZ)对PTSD(post traumatic stress disorder)模型大鼠的条件恐惧反应、空间学习记忆能力下降的预防作用。方法:将大鼠随机分为空白对照组、单纯给药组(APZ0.125mg/kg/d,APZ2)、单纯应激组,即单次延长结合足底电击应激(single prolonged stress foot shock,SPSS)、应激给药小剂量组(SPSS+APZ0.06mg/kg/d,SPSS+APZ1)和大剂量组(SPSS+APZ0.125mg/kg/d,SPSS+APZ2)。采用SPSS动物模型,应激后早期将两种不同浓度的APZ饲喂大鼠14d。第14d在电击箱中检测大鼠的条件性恐惧反应,第15～20d在Morris水迷宫中测大鼠的学习记忆能力。结果:同SPSS组相比,应激后早期使用APZ干预14d不能改善大鼠空间学习记忆能力的下降趋势,不能显著缩短大鼠上台的潜伏期和增加大鼠在目标象限的时间百分比(%),可以明显缓解应激大鼠的恐惧行为(P0.05)。结论:应激后早期及时给予APZ干预可明显减轻创伤后应激障碍大鼠的恐惧反应,而对应激造成大鼠的学习记忆能力损伤无缓解作用,这一结果可为临床有效防治创伤后应激障碍提供一条新思路。     

Utility: Sensitivity and specificity in developing diagnostic tests of combat-related post-traumatic stress disorder (PTSD)

This paper summarizes strengths and weaknesses of clinical utility of tests that diagnose Vietnam combat-related Post-Traumatic Stress Disorder (PTSD). Weaknesses reviewed are: excessive reliance upon one kind of measure of Index Diagnosis; failure to control for varying prevalence rates across samples; failure to compare accuracy across response modalities. Strengths that emerge from the review are that self-report measures have proven to be highly sensitive, and psychophysiological measures have been demonstrated as highly specific. Whereas one single "gold standard" measure of PTSD has yet to be devised, clinical researchers can continue to have confidence in the use of multiple measures.     

Implications of neuroscientific evidence for the cognitive models of post‐traumatic stress disorder

Brewin's dual representation theory, Ehlers and Clark's cognitive appraisal model, and Dalgleish's schematic, propositional, analogue and associative representational systems model are considered in the light of recent evidence on the neural substrates of post‐traumatic stress disorder (PTSD). The models' proposals about the cognitive mechanism of memory dysfunction in PTSD are described and evaluated against current knowledge about the neural pathways and functions disrupted in PTSD. A dual pathway model of memory is consistent with neuroscience of memory. The appraisal model also provides an account of the top‐down modulation of memory and arousal problems consistent with current neuroscientific evidence of PTSD. Dalgleish's model is less consistent with the evidence because it relies upon assumptions that cannot yet be tested neuroscientifically. All three models under‐specify the causal and maintaining influence of hyperarousal relative to the role it plays in current neuroscientific models of PTSD. Implications of the evidence for improving treatment and prevention are discussed.     

Flow cytometric determination of glucocorticoid receptor (GCR) expression in lymphocyte subpopulations: lower quantity of GCR in patients with post-traumatic stress disorder (PTSD)

Assessment of the intracellular glucocorticoid receptor (GCR) level may be useful in monitoring functional disturbances of the hypothalamic-pituitary-adrenocortical axis or effects of prolonged steroid therapy. Cytosolic ligand binding assays have recently been supplemented by flow cytometric determination of receptor expression in individual cells. A method based on multiparametric analysis of whole blood by simultaneous labelling of intracellular GCRs and surface markers of lymphocyte subsets is described. We examined 25 healthy male volunteers and 35 age- and sex-matched post-traumatic stress disorder (PTSD) patients within 8 years from traumatic event. PTSD patients had a lower relative quantity of GCR in all lymphocyte populations tested as compared with healthy volunteers. NK cells of both groups showed higher expression of GCR than other lymphocyte subsets. In PTSD patients, the expression of GCR in B lymphocytes was also higher than in T cell. Although serum cortisol level was lower in PTSD patients, there was no correlation between cortisol level and GCR expression. Multiparameter flow cytometric determination of GCR expression in lymphocyte subpopulations may provide a useful tool for monitoring immunoregulatory action of glucocorticoids.     

Elevated circulatory level of GABA(A)--antagonistic neurosteroids in patients with combat-related post-traumatic stress disorder

BACKGROUND: Post-traumatic stress disorder (PTSD) is a multisystem neurobiological disorder with chronic alterations in various neurochemical systems. Levels of the GABA(A)--antagonistic neurosteroids plasma dehydroepiandrosterone (DHEA) and its sulphate derivate, dehydroepiandrosterone sulphate (DHEAS) may be relevant to depressive and anxiety disorders, including PTSD. METHODS: We assessed the circulatory levels of morning plasma DHEA and DHEAS in 21 male outpatients with untreated chronic combat-related PTSD (CR-PTSD), and 18 healthy control male subjects. RESULTS: Compared with the control subjects, the PTSD patients showed significantly higher plasma DHEA and DHEAS levels. CONCLUSIONS: Chronic CR-PTSD may be associated with increased circulatory level of neuroactive steroids with inhibitory activity at the GABA(A) receptors. Neurosteroid-induced decreased GABAergic tone may be relevant to the symptomatology and pathophysiology of chronic PTSD, as well as to the frequent co-morbidity of PTSD with depression and anxiety disorders.     

Insomnia symptoms predict the development of post‐traumatic stress symptoms following an experimental trauma

Insomnia symptoms prior to traumatic event exposure predict the development of post‐traumatic stress symptoms. However, potential mechanisms underlying the association between insomnia and risk for post‐traumatic stress disorder symptoms have not been prospectively tested. The current study used the trauma film paradigm to test whether insomnia symptoms prior to analogue trauma exposure predict subsequent analogue post‐traumatic stress disorder symptoms, and potential mediators of this relationship, among an at‐risk sample of 108 participants. Results indicated that, after covarying for negative affectivity, insomnia symptoms in the 2 weeks prior to analogue trauma exposure significantly predicted increased post‐traumatic stress disorder symptoms 3 days and 1 week post‐exposure. Moreover, distress immediately after exposure and post‐traumatic avoidance mediated the association between insomnia symptoms and post‐traumatic stress disorder symptoms 1 week after exposure. Effect sizes were small. The current study uses an analogue trauma and analogue post‐traumatic stress disorder symptoms to model clinical symptoms, includes an additional intervention prior to analogue trauma, and lacks a control film. Findings suggest increased reactivity to trauma exposure and subsequent reminders, and attempts to suppress trauma memories may be mechanisms in the association between insomnia symptoms and risk for post‐traumatic stress disorder symptoms.     

Disrupted rapid eye movement sleep predicts poor declarative memory performance in post‐traumatic stress disorder

Successful memory consolidation during sleep depends on healthy slow‐wave and rapid eye movement sleep, and on successful transition across sleep stages. In post‐traumatic stress disorder, sleep is disrupted and memory is impaired, but relations between these two variables in the psychiatric condition remain unexplored. We examined whether disrupted sleep, and consequent disrupted memory consolidation, is a mechanism underlying declarative memory deficits in post‐traumatic stress disorder. We recruited three matched groups of participants: post‐traumatic stress disorder (n = 16); trauma‐exposed non‐post‐traumatic stress disorder (n = 15); and healthy control (n = 14). They completed memory tasks before and after 8 h of sleep. We measured sleep variables using sleep‐adapted electroencephalography. Post‐traumatic stress disorder‐diagnosed participants experienced significantly less sleep efficiency and rapid eye movement sleep percentage, and experienced more awakenings and wake percentage in the second half of the night than did participants in the other two groups. After sleep, post‐traumatic stress disorder‐diagnosed participants retained significantly less information on a declarative memory task than controls. Rapid eye movement percentage, wake percentage and sleep efficiency correlated with retention of information over the night. Furthermore, lower rapid eye movement percentage predicted poorer retention in post‐traumatic stress disorder‐diagnosed individuals. Our results suggest that declarative memory consolidation is disrupted during sleep in post‐traumatic stress disorder. These data are consistent with theories suggesting that sleep benefits memory consolidation via predictable neurobiological mechanisms, and that rapid eye movement disruption is more than a symptom of post‐traumatic stress disorder.     

Attachment organization in Arabic-speaking refugees with post traumatic stress disorder

As a part of an ongoing clinical study of refugees with post traumatic stress disorder (PTSD), the primary objective of the current study was to examine and describe the distribution of adult attachment patterns as assessed by the Adult Attachment Interview (AAI) in Arabic-speaking refugees. A total of 43 adult male and female refugees with Iraqi and Palestinian backgrounds completed the AAI. Sixty-seven percent of the sample was classified as Unresolved with respect to loss or trauma and a substantial proportion of insecure attachment representations (14% Secure-Autonomous, 39% Dismissing, 42% Preoccupied, 5% Cannot Classify) was found, in addition to high intake levels of post traumatic stress symptoms and comorbidity. Findings are compared with AAI studies of other PTSD or trauma samples, and the paper elaborates upon the methodological challenges in administering the AAI in a context of simultaneous translation.     

Generalization of fear in post-traumatic stress disorder

Overgeneralization (i.e., the transfer of fear to stimuli not related to an aversive event) is part of alterations in associative fear learning in mental disorders. In the present experimental study, we investigated whether this holds true for post-traumatic stress disorder (PTSD) related to childhood abuse. We expected that fear generalization under experimental conditions reflects generalization of aversive stimuli to different social domains in real life. Sixty-four women with PTSD after childhood abuse and 30 healthy participants (HC) underwent a differential fear conditioning and generalization paradigm. Online risk ratings, reaction time, and fear-potentiated startle served as dependent variables. Based on the subjectively assessed generalization of triggered intrusions across different domains of life, PTSD participants were split into two groups reporting low (low-GEN) and high (high-GEN) generalization. PTSD patients reported a higher expectation of an aversive event. During fear conditioning, they assessed the risk of danger related to a safety cue slower and showed a blunted fear-potentiated startle toward the danger cue. During generalization testing, reaction time increased in the high-GEN patients and decreased in the HC group with increasing similarity of a stimulus with the conditioned safety cue. Alterations of fear learning in PTSD suggest impaired defensive responses in case of a high threat probability. Moreover, our findings bridge the gap between the generalization of aversive cues during everyday life and laboratory-based experimental parameters: impairments in the processing of cues signaling safety generalize particularly in those patients who report a spreading of PTSD symptoms across different domains of everyday life.     

Eye movement and electrodermal responses to threat stimuli in post-traumatic stress disorder

A core feature of post-traumatic stress disorder (PTSD) is hypervigilence to threatening material. This study measured processing of threat material in PTSD with simultaneously acquired initial eye movements and electrodermal activity, following presentation of threatening and neutral words. Ten PTSD subjects and 10 controls were presented with 4 words in parafoveal range. On trials in which a threat word was present, PTSD subjects demonstrated initial eye fixations on the threat word more than controls. PTSD subjects also demonstrated more orienting responses on all trials than controls. These results suggest that processing of threat information in PTSD can be usefully investigated with convergent psychophysiological methodologies.     

Dose sparing strategy with intradermal influenza vaccination in patients with solid cancer

Influenza vaccine is considered to reduce influenza‐related morbidity and mortality in patients with underlying chronic medical conditions. Because of fear of vaccine shortage during an influenza pandemic, several antigen sparing strategies have been investigated. The immunogenicity of intradermal influenza vaccination with one half the antigenic contents was compared to that of conventional intramuscular vaccination in patients with solid cancer, and adverse events were assessed after vaccination. There was no significant difference between the injection routes in the hemagglutinin inhibition (HI) response and increase in the titer of A/H1N1, A/H3N2, and B 4–6 weeks after the vaccination; seroconversion factors increased by more than 2.5‐fold. Seroresponse rates were more than 40% and seroprotection rates were above 70% against all three influenza strains irrespective of the vaccination routes. No serious events were observed, and local skin reactions were more frequent in the intradermal injection recipients than in the intramuscular recipients (32.7% vs. 9.1%). This study shows that intradermal injection of one half the dose of a commercial influenza vaccine elicits immune responses comparable to those elicited by a full dose of intramuscular vaccine among cancer patients, and it can be tolerated without serious adverse reactions. J. Med. Virol. 81:722–727, 2009 © 2009 Wiley‐Liss, Inc.     

Prevalence of post-traumatic stress disorder in patients with previous myocardial infarction consulting in general practice.

Reported prevalence of myocardial infarction-related post-traumatic stress disorder (PTSD) varies from 0 to 25%. PTSD after myocardial infarction may affect quality of life, cardiovascular outcomes, and health service usage. Of 164 patients with previous myocardial infarction, 111 participated in the study and 36 had PTSD, giving a prevalence of 32%; the lowest possible estimate being 22%. PTSD was associated with significantly worse general health than that of individuals without PTSD. Prevalence of PTSD did not vary with time since myocardial infarction. PTSD was not associated with adverse risk factors for future myocardial infarction, such as smoking, high blood pressure, and poor compliance with medication. PTSD after myocardial infarction may be a common, persistent, and overlooked cause of psychological morbidity.     

Quantitative electroencephalography during rapid eye movement (REM) and non‐REM sleep in combat‐exposed veterans with and without post‐traumatic stress disorder

Sleep disturbances are a hallmark feature of post‐traumatic stress disorder (PTSD), and associated with poor clinical outcomes. Few studies have examined sleep quantitative electroencephalography (qEEG), a technique able to detect subtle differences that polysomnography does not capture. We hypothesized that greater high‐frequency qEEG would reflect ‘hyperarousal’ in combat veterans with PTSD (n = 16) compared to veterans without PTSD (n = 13). EEG power in traditional EEG frequency bands was computed for artifact‐free sleep epochs across an entire night. Correlations were performed between qEEG and ratings of PTSD symptoms and combat exposure. The groups did not differ significantly in whole‐night qEEG measures for either rapid eye movement (REM) or non‐REM (NREM) sleep. Non‐significant medium effect sizes suggest less REM beta (opposite to our hypothesis), less REM and NREM sigma and more NREM gamma in combat veterans with PTSD. Positive correlations were found between combat exposure and NREM beta (PTSD group only), and REM and NREM sigma (non‐PTSD group only). Results did not support global hyperarousal in PTSD as indexed by increased beta qEEG activity. The correlation of sigma activity with combat exposure in those without PTSD and the non‐significant trend towards less sigma activity during both REM and NREM sleep in combat veterans with PTSD suggests that differential information processing during sleep may characterize combat‐exposed military veterans with and without PTSD.     

创伤后应激障碍大鼠海马神经元自噬增强

目的:观察创伤后应激障碍(PTSD)模型大鼠海马神经元自噬的改变,探讨PTSD致海马体积异常的可能机制。方法:成年健康雄性SD大鼠20只,随机被分为对照组和模型组。采用改良的单一连续应激后给予不可逃避足底电击方法制备PTSD大鼠模型;采用透射电镜技术观察海马神经元超微结构,Western blot方法检测海马微管相关蛋白轻链3(microtube-associated protein 1 light chain 3,LC-3)和Beclin-1的表达水平。结果:模型组海马神经元自噬体增多;海马组织LC3-Ⅱ/LC3-Ⅰ比值和Beclin-1表达水平高于对照组(P<0.05)。结论:PTSD模型大鼠海马神经元存在明显的细胞自噬,可能与海马体积异常变化有关。