创伤后应激障碍（PTSD）的生物学研究概述

创伤后应激障碍（posttraumatic stress disorder,PTSD）是灾害后精神及行为障碍的一种重要表现形式,具有发病率及患病率高、病程长、疗效差等特点,严重影响了临床救治。对于创伤后应激障碍发病机制及其防治的研究日益受到关注。致力于PTSD研究的研究者,从行为学、神经内分泌等宏观研究,到形态学、细胞分子生物学等功能研究,再到临床实验研究,做了大量的工作,得到了许多具有实际指导意义的结果。本文针对国内外研究者近年来在这方面的研究现状进行综述,从宏观上为PTSD后续的研究提供一些循证的证据。     

创伤后应激障碍机制的研究进展

创伤后应激障碍(Post-traumatic stress disorder;PTSD)是一种由严重强烈的伤害事件造成的精神障碍,随着近年来社会应激事件的增多和自然灾害的发生,创伤应激障碍的发病率逐渐增高。同时为了研究对应的治疗方法,人们对创伤应激障碍的机制进行了更深入的探索,也有了新的进展。本文着重从激素、神经营养因子、免疫系统等方面来总结创伤后应激障碍发生的生物学机制。激素方面,PTSD主要与交感肾上腺髓质系统(Sympatho-adrenomedullarysystem,SAS)和下丘脑-垂体-肾上腺轴(Hypothalamicpituitary-adrenal axis,HPA)的功能异常有关;神经营养因子方面,其产生与分泌的异常增加或减少可能是PTSD产生的重要机制;免疫系统方面,PTSD可能与免疫系统相关的蛋白质、细胞的数量和功能变化有关。整合神经生物学与分子生物学、表观遗传学、蛋白质组学及分子影像学的成果将对PTSD的研究产生推动作用。     

科研快讯

美国研究者鉴别出了一种与性别有关的脑垂体腺苷酸环化酶激活多肽(PACAP),及其与创伤后应激障碍(PTSD)有关的受体(PAC1),这一成果将对改善这种疾病的诊断和治疗提供帮助。最近出版的《自然》杂志上报告了这一研究成果。创伤后应激障碍(PTSD)又叫创伤后紧张症,是对令人不安的经历作出的一种不良的心理反应,这些经历会对许多人的一生造成影响,但是     

颅脑损伤后创伤后应激障碍的研究进展

创伤后应激障碍(PTSD)是临床上常见的应激后反应,多见于重大创伤后,具有发病率高、临床表现复杂、治疗难度大等特点,已成为世界范围内广泛关注的公共卫生问题。颅脑损伤是引起PTSD的重要因素,近年来针对颅脑损伤后PTSD展开了一系列研究。本文通过回顾近年来有关颅脑损伤后PTSD的基础与临床研究,对颅脑损伤与PTSD相关性的流行病学特征、发病机制、诊断与鉴别以及药物和心理治疗中的进展和面临的困难进行综述,以期为颅脑损伤后PTSD的深入研究提供理论依据和新思路。     

创伤后应激障碍动物模型研究概况

创伤后应激障碍(post-traumatic stress disorder,PTSD)是人体遭遇重大创伤后,出现睡眠障碍、焦虑、恐惧以及认知障碍等症状的一种严重精神障碍。在过去几十年中,国内外已建立了多种的啮齿动物压力模型,用于研究PTSD潜在的病理生理学机制。模型动物会出现类似PTSD的症状,但每种动物模型都不能完整表现出PTSD所有的症状以及生物学变化。因此本文就近几年常用的PTSD模型的造模方法、生理学改变等做出简要的概述总结。     

灾后消防救援人员创伤后应激障碍分析

目的：对地震后消防救援人员创伤后应激障碍（PTSD）的发生率及心理健康状况进行分析。方法：选用创伤后应激评定量表（PCL-C）和中文版事件影响量表（IES-R）,对灾后三个月内消防员310人进行评估。结果：灾后三个月内PTSD症状的总发生率为35.3%;地震救援组和基层消防组IES-R得分显著高于一般院校组,但地震救援组和基层消防组得分无显著差异,PCL-C得分结果与之类似;恐惧、创伤经历和救援失败等是PTSD症状的影响因素。结论：消防员是职业心理创伤的高危人群,地震后消防救援人员PTSD症状发生率较高,应给予及时心理干预。     

灾后消防救援人员创伤后应激障碍分析

目的:对地震后消防救援人员创伤后应激障碍(PTSD)的发生率及心理健康状况进行分析。方法:选用创伤后应激评定量表(PCL-C)和中文版事件影响量表(IES-R),对灾后三个月内消防员310人进行评估。结果:灾后三个月内PTSD症状的总发生率为35.3%;地震救援组和基层消防组IES-R得分显著高于一般院校组,但地震救援组和基层消防组得分无显著差异,PCL-C得分结果与之类似;恐惧、创伤经历和救援失败等是PTSD症状的影响因素。结论:消防员是职业心理创伤的高危人群,地震后消防救援人员PTSD症状发生率较高,应给予及时心理干预。     

恐惧记忆消退的表观遗传学机制

恐惧是一种特殊的情感,形成恐惧记忆的能力对于动物及人类检测和应对危险至关重要。近几年研究发现,表观遗传学可以在多个层面调控恐惧记忆,如组蛋白乙酰化与DNA甲基化在恐惧记忆消退过程中发挥重要作用。动物模型中的许多研究表明,适度的表观遗传调节对于学习记忆过程是必要的,表观遗传学机制失调将导致行为水平的认知缺陷,并且表观遗传失调已被越来越多地认为是各种精神疾病的重要因素,如创伤后应激障碍(post-traumatic stress disorder,PTSD)。因此,理解记忆形成的机制具有巨大的科学意义以及社会和医疗效益。     

创伤后应激障碍对慢性不可预见性应激抑郁模型的影响

目的:观察创伤后应激障碍(PTSD)对慢性不可预见性应激(CUS)抑郁模型的影响。方法:采用足底电击的方法建立大鼠创伤后应激障碍模型。成年雄性S-D大鼠40只随机分为四组(n=10):对照组(C组)、PTSD组、CUS组、PTSD+CUS组(P+C组)。在1、7、14、21天测量大鼠体重,并行糖水偏好和强迫游泳实验,在7、14、21天做条件性恐惧实验。结果:与C组相比,CUS组和P+C组体重增加缓慢,PTSD组体重正常。CUS组于第21天出现糖水消耗比例降低,强迫游泳不动时间增加。P+C组于第14天即出现上述抑郁表现。条件性恐惧实验中,PTSD组与PTSD+CUS组僵直时间显著增加,CUS组无明显变化。结论:创伤后应激障碍的动物更易产生抑郁表现。     

《自然》：研究发现创伤后应激障碍相关受体

美国研究者鉴别出了一种与性别有关的脑垂体腺苷酸环化酶激活多肽（PACAP）,及其与创伤后应激障碍（PTSD）有关的受体（PAC1）,这一成果将对改善这种疾病的诊断和治疗提供帮助。最近出版的《自然》杂志上报告了这一研究成果。     

Diagnosis and classification of disorders specifically associated with stress: proposals for ICD‐11

The diagnostic concepts of post‐traumatic stress disorder (PTSD) and other disorders specifically associated with stress have been intensively discussed among neuro‐ and social scientists, clinicians, epidemiologists, public health planners and humanitarian aid workers around the world. PTSD and adjustment disorder are among the most widely used diagnoses in mental health care worldwide. This paper describes proposals that aim to maximize clinical utility for the classification and grouping of disorders specifically associated with stress in the forthcoming 11th revision of the International Classification of Diseases (ICD‐11). Proposals include a narrower concept for PTSD that does not allow the diagnosis to be made based entirely on non‐specific symptoms; a new complex PTSD category that comprises three clusters of intra‐ and interpersonal symptoms in addition to core PTSD symptoms; a new diagnosis of prolonged grief disorder, used to describe patients that undergo an intensely painful, disabling, and abnormally persistent response to bereavement; a major revision of “adjustment disorder” involving increased specification of symptoms; and a conceptualization of “acute stress reaction” as a normal phenomenon that still may require clinical intervention. These proposals were developed with specific considerations given to clinical utility and global applicability in both low‐ and high‐income countries.     

综述: 引发“战斗?鄄逃跑”反应的神经环路机制

"战斗-逃跑"反应是人和动物面临生存威胁时,产生的一系列应激行为和生理反应,该反应有助于个体提高战斗或逃跑的能力,以提高生存概率.过度或反复"战斗-逃跑"反应能诱发一类称为创伤后压力应激障碍(post-traumatic stress disorder,PTSD)的精神疾病.频繁的自然灾害和交通事故使我国人口受到PTSD的严重危害.要揭示PTSD的发病机理,首先需要深入地了解引发"战斗-逃跑"反应的脑内神经环路和机制.本文综述了该研究领域的进展和亮点工作,强调了该研究在国家相关领域中的重要性.     

Facial EMG Responses to Combat-Related Visual Stimuli in Veterans With and Without Posttraumatic Stress Disorder

Veterans with (n = 10) and without (n = 10) posttraumatic stress disorder (PTSD) participated in an exploratory study of facial reactivity to neutral slides and to slides depicting unpleasant combat-related material that were previously determined to be emotionally evocative. It was found that the zygomaticus major (cheek), masseter (jaw), and lateral frontalis (forehead) muscles were especially reactive to the combat slides in the veterans with PTSD, suggesting the importance of facial emotional expression in this disorder. The PTSD participants' self-reports of overall distress paralleled these effects. However, autonomic reactivity did not reflect general arousal effects due to the visual stimuli, showing both the sensitivity of facial muscle assessment in this context and the need for further research on the relationship between stimulus modality and physiological trauma reactions. Additional directions for research in this area are discussed including efforts to correlate subjective and physiological reactions.     

Cells, biomarkers, and post-traumatic stress disorder: evidence for peripheral involvement in a central disease

Post-traumatic stress disorder (PTSD) is a complicated CNS syndrome. Looking beyond the CNS, recent studies suggest that peripheral blood mononuclear cells could cause and/or exacerbate PTSD. This review summarizes the literature, describes associations between circulating peripheral blood cells and PTSD, proposes a novel mechanism, and analyzes several biomarkers that appear to associate with PTSD symptoms. Several experimental animal models have shown that peripheral blood mononuclear cell activity can cause hippocampal volume loss and PTSD-like symptoms. Data from these models suggest that a traumatic event and/or traumatic events can trigger peripheral cells to migrate, mediate inflammation, and decrease neurogenesis, potentially leading to CNS volume loss. Biomarkers that associate with PTSD symptoms have the potential to differentiate PTSD from traumatic brain injury, but more work needs to be done. Research examining the mechanism of how traumatic events are linked to peripheral blood mononuclear cell functions and biomarkers may offer improved diagnoses and treatments for PTSD patients.     

Functional rs6265 polymorphism in the brain-derived neurotrophic factor gene confers protection against neurocognitive dysfunction in posttraumatic stress disorder among Chinese patients with hepatocellular carcinoma

Posttraumatic stress disorder (PTSD) is a psychiatric disorder that plagues trauma survivors. Evidence shows that brain-derived neurotrophic factor (BDNF) may be involved in the occurrence and development of PTSD. Here we tried to demonstrate whether BDNF gene polymorphisms are correlated with neurocognitive function following PTSD in patients with hepatocellular carcinoma (HCC). This study included 102 patients with HCC complicated with PTSD, 146 HCC patients, and 152 healthy volunteers. Initially, we evaluated the neurocognitive function of the study subjects. Next, we measured BDNF G11757C and rs6265 polymorphisms by polymerase chain reaction-restriction fragment length polymorphism. The correlation of BDNF polymorphisms and BDNF level with HCC complicated with PTSD was evaluated. The results revealed that HCC complicated with PTSD showed decreased serum BDNF level and Mini-mental state examination (MMSE) score. Serum BDNF level of HCC and HCC complicated with PTSD was positively correlated with MMSE score. GA + AA allele and A allele of rs6265 increased the risk of PTSD among patients with HCC. GA and AA genotypes of rs6265 were correlated with the decreased MMSE score of HCC complicated with PTSD. Haplotype GA of rs6265 and G11757C increased the risk of PTSD for HCC, while haplotype CG decreased this risk. Lastly, the logistic regression analysis suggested that low BDNF level was a contributor to HCC complicated with PTSD, while GG genotype of rs6265 served as a protective factor. Collectively, this study defines the GG genotype of BDNF rs6265 polymorphism as a protector to HCC complicated with PTSD. In addition, these results provided a promising target for PTSD prevention in patients with HCC.     

大鼠PTSD后蓝斑核 β-catenin的表达下降伴随细胞凋亡

目的 探讨创伤后应激障碍( PTSD) 大鼠蓝斑神经元β-catenin(β-连环蛋白)的表达变化.方法 采用国际认定的SPS方法刺激建立大鼠PTSD模型,取成年健康雄性Wistar 大鼠100 只,随机分为连续单一刺激( single prolonged stress,SPS) 模型1 d、4 d、7 d、14 d 组和对照组,应用免疫组化、免疫印迹方法检测PTSD 大鼠蓝斑神经元β-catenin的表达变化;透射电镜观察PTSD大鼠蓝斑神经元的超微结构变化.结果 经SPS 刺激后大鼠蓝斑神经元细胞内β-catenin于1d开始逐渐减少,14d表达最少;蓝斑神经元出现细胞凋亡改变.结论 蓝斑神经元细胞凋亡可能是导致PTSD 患者蓝斑功能失调的重要原因之一.     

Cardiovascular Correlates of Motor Vehicle Accident Related Posttraumatic Stress Disorder and its Successful Treatment

Persons with posttraumatic stress disorder (PTSD) have been shown to display elevated baseline cardiovascular activity and a heightened physiological reactivity to trauma-related stimuli. Study 1 examined differences in baseline heart rate (HR) and HR reactivity in 68 survivors of motor vehicle accidents (MVAs) and healthy controls without MVA. MVA survivors with PTSD (n=26), subsyndromal PTSD (n=22), traumatized controls without PTSD (non-PTSD with MVA, n=20) and healthy controls without MVA (HC, n=27) underwent measurement of HR during baseline and exposure to a neutral, positive, negative, and trauma-related picture. PTSD patients showed elevated baseline HR and increased HR reactivity only during exposure to the trauma-related picture. Study 2 investigated whether the elevated physiological responses observed in Study 1 normalized after cognitive behavioral therapy (CBT). We conducted a randomized, controlled treatment trial comparing CBT (n=17) to a Wait-list condition (WLC, n=18). Results showed a greater decrease in HR reactivity for CBT than for WLC. The change in HR reactivity was associated with clinical improvement.     

创伤后应激障碍大鼠蓝斑核神经元细胞凋亡的实验研究

目的探讨创伤后应激障碍(PTSD)大鼠蓝斑核神经元Caspase-3和Caspase-9的表达变化。方法成年健康雄性Wistar大鼠50只,随机分为连续单一刺激(single prolonged stress,SPS)模型1d、4d、7d、14d组和对照组,应用免疫组化、免疫荧光和RT-PCR方法检测PTSD大鼠蓝斑核神经元Caspase-3和Caspase-9的表达变化。结果SPS刺激后1d,4d,Caspase-9的表达逐渐增强,7d和14d逐渐下降,Caspase-3于SPS刺激后7d表达最多,14d出现下降。结论蓝斑神经元细胞凋亡可能是导致PTSD患者蓝斑功能失调的重要原因之一。     

Neurobiology of comorbid post‐traumatic stress disorder and alcohol‐use disorder

Post‐traumatic stress disorder (PTSD) and alcohol‐use disorder (AUD) are highly comorbid in humans. Although we have some understanding of the structural and functional brain changes that define each of these disorders, and how those changes contribute to the behavioral symptoms that define them, little is known about the neurobiology of comorbid PTSD and AUD, which may be due in part to a scarcity of adequate animal models for examining this research question. The goal of this review is to summarize the current state‐of‐the‐science on comorbid PTSD and AUD. We summarize epidemiological data documenting the prevalence of this comorbidity, review what is known about the potential neurobiological basis for the frequent co‐occurrence of PTSD and AUD and discuss successes and failures of past and current treatment strategies. We also review animal models that aim to examine comorbid PTSD and AUD, highlighting where the models parallel the human condition, and we discuss the strengths and weaknesses of each model. We conclude by discussing key gaps in our knowledge and strategies for addressing them: in particular, we (1) highlight the need for better animal models of the comorbid condition and better clinical trial design, (2) emphasize the need for examination of subpopulation effects and individual differences and (3) urge cross‐talk between basic and clinical researchers that is reflected in collaborative work with forward and reverse translational impact.