海马突触可塑性与异常记忆

5-羟色胺(5-HT)是中枢神经系统内非常重要的神经递质，广泛参与各种行为和生理过程。5-羟色胺功能低下可导致多种精神类疾病尤其是焦虑、抑郁和创伤后应激障碍等，而这些疾病都伴有学习和记忆的障碍；海马是参与学习记忆的重要脑区。海马接受5-HT神经元的直接投射且富含5-HT受体，因而海马也可以通过5-HT系统调控焦虑、抑郁及学习记忆。海马突触可塑性是学习记忆的细胞分子机制，是学习记忆的基础。我们条件性敲除转录因子Lmx1b得到中枢5-HT缺失小鼠，利用该小鼠进行中枢神经系统5-HT功能的研究。我们发现该小鼠的脑结构和运动能力正常；水迷宫空间学习能力正常，但空间记忆受损；焦虑水平降低，但是环境恐惧学习和记忆能力增强，增强的恐惧记忆能被外源给予的5-HT逆转；在中枢5-HT缺失小鼠中，应激对海马可塑性的作用即损伤LTP易化LTD消失，外源给予5-HT可以恢复应激的效果。这些结果提示应激导致海马LTP损伤可能是保护机制，缺乏这种保护机制可能导致恐惧记忆相关的创伤后应激障碍(PTSD)的易感。成瘾的核心特征是对药物的强迫性渴求和复吸。成瘾与学习记忆有很多共同的脑区和分子通路，它可能通过篡夺正常生理神经通路而产生比正常生理反应更强烈的可塑性，形成有害的异常记忆。以前的报道证实海马的兴奋性突触可塑性在成瘾过程中的适应性改变可能是成瘾的机制；但是成瘾涉及复杂的生物机制，因而不可能仅是兴奋性突触可塑性的贡献。我们研究了5-HT系统和抑制性系统（主要是GABA能系统）在成瘾中的贡献。利用中枢5-HT缺失小鼠，我们发现5-HT缺失小鼠的吗啡显著地易化了5-HT CKO的海马LTP，同时也导致成瘾行为持续不消退；5-HT和5-HT1a受体激动剂能逆转此现象。这提示毒品成瘾可能导致中枢5-HT缺失，进而增强海马LTP，使毒品相关记忆牢固不消退。GABA能系统是中枢神经系统最重要的抑制性系统，我们研究发现一次吗啡对内源性大麻受体（CB1R）依赖的抑制性突触的长时程抑制（Inhibitory long-term depression，I-LTD）没有影响，成瘾后I-LTD抑制，而吗啡成瘾后戒断导致了内源性大麻受体(CB1R)和L-型钙通道(LTCC)依赖的GABA能LTD (I-LTD)，使I-LTD增大了一倍，提示在吗啡成瘾阶段过程中，有组合突触可塑性发生，进而增强了突触可塑性的调控范围。 本论文是对中枢5-HT系统对海马兴奋性突触可塑性在焦虑、应激、成瘾等异常记忆中的调节作用以及海马抑制性系统在成瘾和戒断中的贡献进行研究，表明恐惧记忆和毒品成瘾记忆存在许多共同的细胞分子机理，对今后治疗焦虑、创伤后应激障碍和成瘾提供了新的思路。

汶川地震后青少年创伤后应激障碍症状及其相关因素研究

The present paper studies focus on the symptoms of the post-traumatic stress disorder in adolescents post-disaster. 482 students from 6 secondary schools and 17 primary schools in the extremely severe disaster areas in Mianzhu, Sichuan province and 785 students from 3 primary schools and 9 secondary schools in the severe disaster areas in Baoji, Shaanxi respectively were surveyed on the symptoms of the post-traumatic stress disorder and the extent of disaster exposure after the Wenchuan earthquake. Self-compiled background information questionnaire and CRIES were used for the investigation. In this study, we contrast the extent of disaster exposure in the two areas in order to explore the related factors about the post-traumatic stress disorder in adolescent post-disaster. The main results of this paper can be summarized as follows： 1. There are significant positive corrections between the post-traumatic stress disorder and the extent of disaster exposure(get trapped in the earthquake、relatives and friends have been injured in the earthquake、look at relatives and friends dying in the earthquake).The more exposed in the disaster, the more serious symptom of the post-traumatic stress disorder. The trauma exposure indicators (get trapped in the earthquake, relatives and friends have been injured in the earthquake、look at relatives and friends dying in the earthquake)were all significant predictors for PTSD severity. 2. There are significant sex difference in the extent（F=8.750, p <0.05） and the incidence rate of PTSD（χ =20.735, df=5,p =0.001）, the extent and the incidence rate of girls in Mianzhu is significantly higher than that of boys. 3. The age is also an influence factor of PTSD. The extent （F=7.246, p <0.001）and the incidence rate （χ =20.735, df=5,p =0.001）of PTSD get higher as adolescent in Mianzhu get older. 4. As the extremely severe disaster areas, the extent of disaster exposure of Mianzhu areas significantly higher than that of the severe disaster areas Baoji. However, there are not difference in the extent of PTSD between two areas（t=0.181，df=1265,p=0.857）, there are only significant difference in the incidence rate of PTSD between two areas（χ =8.766，df=1,p=0.003）, the incidence rate of PTSD in Mianzhu areas significantly higher than that of Baoji areas.

The development and psychometric properties of the HIV and Abuse Related Shame Inventory (HARSI).

Shame has been shown to predict sexual HIV transmission risk behavior, medication non-adherence, symptomatic HIV or AIDS, and symptoms of depression and PTSD. However, there remains a dearth of tools to measure the specific constructs of HIV-related and sexual abuse-related shame. To ameliorate this gap, we present a 31-item measure that assesses HIV and sexual abuse-related shame, and the impact of shame on HIV-related health behaviors. A diverse sample of 271 HIV-positive men and women who were sexually abused as children completed the HIV and Abuse Related Shame Inventory (HARSI) among other measures. An exploratory factor analysis supported the retention of three-factors, explaining 56.7% of the sample variance. These internally consistent factors showed good test-retest reliability, and sound convergent and divergent validity using eight well-established HIV specific and general psychosocial criterion measures. Unlike stigma or discrimination, shame is potentially alterable through individually-focused interventions, making the measurement of shame clinically meaningful.

Schema-driven construction of future autobiographical traumatic events: the future is much more troubling than the past.

Research on future episodic thought has produced compelling theories and results in cognitive psychology, cognitive neuroscience, and clinical psychology. In experiments aimed to integrate these with basic concepts and methods from autobiographical memory research, 76 undergraduates remembered past and imagined future positive and negative events that had or would have a major impact on them. Correlations of the online ratings of visual and auditory imagery, emotion, and other measures demonstrated that individuals used the same processes to the same extent to remember past and construct future events. These measures predicted the theoretically important metacognitive judgment of past reliving and future "preliving" in similar ways. On standardized tests of reactions to traumatic events, scores for future negative events were much higher than scores for past negative events. The scores for future negative events were in the range that would qualify for a diagnosis of posttraumatic stress disorder (PTSD); the test was replicated (n = 52) to check for order effects. Consistent with earlier work, future events had less sensory vividness. Thus, the imagined symptoms of future events were unlikely to be caused by sensory vividness. In a second experiment, to confirm this, 63 undergraduates produced numerous added details between 2 constructions of the same negative future events; deficits in rated vividness were removed with no increase in the standardized tests of reactions to traumatic events. Neuroticism predicted individuals' reactions to negative past events but did not predict imagined reactions to future events. This set of novel methods and findings is interpreted in the contexts of the literatures of episodic future thought, autobiographical memory, PTSD, and classic schema theory.

Cumulative exposure to traumatic events in older adults.

OBJECTIVES: The present study examined the impact of cumulative trauma exposure on current posttraumatic stress disorder (PTSD) symptom severity in a nonclinical sample of adults in their 60s. The predictive utility of cumulative trauma exposure was compared to other known predictors of PTSD, including trauma severity, personality traits, social support, and event centrality. METHOD: Community-dwelling adults (n = 2515) from the crest of the Baby Boom generation completed the Traumatic Life Events Questionnaire, the PTSD Checklist, the NEO Personality Inventory, the Centrality of Event Scale, and rated their current social support. RESULTS: Cumulative trauma exposure predicted greater PTSD symptom severity in hierarchical regression analyses consistent with a dose-response model. Neuroticism and event centrality also emerged as robust predictors of PTSD symptom severity. In contrast, the severity of individuals' single most distressing life event, as measured by self-report ratings of the A1 PTSD diagnostic criterion, did not add explanatory variance to the model. Analyses concerning event categories revealed that cumulative exposure to childhood violence and adulthood physical assaults were most strongly associated with PTSD symptom severity in older adulthood. Moreover, cumulative self-oriented events accounted for a larger percentage of variance in symptom severity compared to events directed at others. CONCLUSION: Our findings suggest that the cumulative impact of exposure to traumatic events throughout the life course contributes significantly to posttraumatic stress in older adulthood above and beyond other known predictors of PTSD.

Neural networks supporting autobiographical memory retrieval in posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) affects the functional recruitment and connectivity between neural regions during autobiographical memory (AM) retrieval that overlap with default and control networks. Whether such univariate changes relate to potential differences in the contributions of the large-scale neural networks supporting cognition in PTSD is unknown. In the present functional MRI study, we employed independent-component analysis to examine the influence of the engagement of neural networks during the recall of personal memories in a PTSD group (15 participants) as compared to non-trauma-exposed healthy controls (14 participants). We found that the PTSD group recruited similar neural networks when compared to the controls during AM recall, including default-network subsystems and control networks, but group differences emerged in the spatial and temporal characteristics of these networks. First, we found spatial differences in the contributions of the anterior and posterior midline across the networks, and of the amygdala in particular, for the medial temporal subsystem of the default network. Second, we found temporal differences within the medial prefrontal subsystem of the default network, with less temporal coupling of this network during AM retrieval in PTSD relative to controls. These findings suggest that the spatial and temporal characteristics of the default and control networks potentially differ in a PTSD group versus healthy controls and contribute to altered recall of personal memory.

Measuring the Severity of Negative and Traumatic Events.

We devised three measures of the general severity of events, which raters applied to participants' narrative descriptions: 1) placing events on a standard normed scale of stressful events, 2) placing events into five bins based on their severity relative to all other events in the sample, and 3) an average of ratings of the events' effects on six distinct areas of the participants' lives. Protocols of negative events were obtained from two non-diagnosed undergraduate samples (n = 688 and 328), a clinically diagnosed undergraduate sample all of whom had traumas and half of whom met PTSD criteria (n = 30), and a clinically diagnosed community sample who met PTSD criteria (n = 75). The three measures of severity correlated highly in all four samples but failed to correlate with PTSD symptom severity in any sample. Theoretical implications for the role of trauma severity in PTSD are discussed.

The Frequency and Impact of Exposure to Potentially Traumatic Events Over the Life Course.

We examined the frequency and impact of exposure to potentially traumatic events among a nonclinical sample of older adults (n = 3,575), a population typically underrepresented in epidemiological research concerning the prevalence of traumatic events. Current PTSD symptom severity and the centrality of events to identity were assessed for events nominated as currently most distressing. Approximately 90% of participants experienced one or more potentially traumatic events. Events that occurred with greater frequency early in the life course were associated with more severe PTSD symptoms compared to events that occurred with greater frequency during later decades. Early life traumas, however, were not more central to identity. Results underscore the differential impact of traumatic events experienced throughout the life course. We conclude with suggestions for further research concerning mechanisms that promote the persistence of post-traumatic stress related to early life traumas and empirical evaluation of psychotherapeutic treatments for older adults with PTSD.

Peace and war: trajectories of posttraumatic stress disorder symptoms before, during, and after military deployment in Afghanistan.

In the study reported here, we examined posttraumatic stress disorder (PTSD) symptoms in 746 Danish soldiers measured on five occasions before, during, and after deployment to Afghanistan. Using latent class growth analysis, we identified six trajectories of change in PTSD symptoms. Two resilient trajectories had low levels across all five times, and a new-onset trajectory started low and showed a marked increase of PTSD symptoms. Three temporary-benefit trajectories, not previously described in the literature, showed decreases in PTSD symptoms during (or immediately after) deployment, followed by increases after return from deployment. Predeployment emotional problems and predeployment traumas, especially childhood adversities, were predictors for inclusion in the nonresilient trajectories, whereas deployment-related stress was not. These findings challenge standard views of PTSD in two ways. First, they show that factors other than immediately preceding stressors are critical for PTSD development, with childhood adversities being central. Second, they demonstrate that the development of PTSD symptoms shows heterogeneity, which indicates the need for multiple measurements to understand PTSD and identify people in need of treatment.

Autobiographical memory for stressful events: the role of autobiographical memory in posttraumatic stress disorder.

To provide the three-way comparisons needed to test existing theories, we compared (1) most-stressful memories to other memories and (2) involuntary to voluntary memories (3) in 75 community dwelling adults with and 42 without a current diagnosis of posttraumatic stress disorder (PTSD). Each rated their three most-stressful, three most-positive, seven most-important and 15 word-cued autobiographical memories, and completed tests of personality and mood. Involuntary memories were then recorded and rated as they occurred for 2 weeks. Standard mechanisms of cognition and affect applied to extreme events accounted for the properties of stressful memories. Involuntary memories had greater emotional intensity than voluntary memories, but were not more frequently related to traumatic events. The emotional intensity, rehearsal, and centrality to the life story of both voluntary and involuntary memories, rather than incoherence of voluntary traumatic memories and enhanced availability of involuntary traumatic memories, were the properties of autobiographical memories associated with PTSD.

Functional neuroimaging of emotionally intense autobiographical memories in post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) affects regions that support autobiographical memory (AM) retrieval, such as the hippocampus, amygdala and ventral medial prefrontal cortex (PFC). However, it is not well understood how PTSD may impact the neural mechanisms of memory retrieval for the personal past. We used a generic cue method combined with parametric modulation analysis and functional MRI (fMRI) to investigate the neural mechanisms affected by PTSD symptoms during the retrieval of a large sample of emotionally intense AMs. There were three main results. First, the PTSD group showed greater recruitment of the amygdala/hippocampus during the construction of negative versus positive emotionally intense AMs, when compared to controls. Second, across both the construction and elaboration phases of retrieval the PTSD group showed greater recruitment of the ventral medial PFC for negatively intense memories, but less recruitment for positively intense memories. Third, the PTSD group showed greater functional coupling between the ventral medial PFC and the amygdala for negatively intense memories, but less coupling for positively intense memories. In sum, the fMRI data suggest that there was greater recruitment and coupling of emotional brain regions during the retrieval of negatively intense AMs in the PTSD group when compared to controls.

The coherence of memories for trauma: evidence from posttraumatic stress disorder.

Participants with posttraumatic stress disorder (PTSD) and participants with a trauma but without PTSD wrote narratives of their trauma and, for comparison, of the most-important and the happiest events that occurred within a year of their trauma. They then rated these three events on coherence. Based on participants' self-ratings and on naïve-observer scorings of the participants' narratives, memories of traumas were not more incoherent than the comparison memories in participants in general or in participants with PTSD. This study comprehensively assesses narrative coherence using a full two (PTSD or not) by two (traumatic event or not) design. The results are counter to most prevalent theoretical views of memory for trauma.

Two versions of life: emotionally negative and positive life events have different roles in the organization of life story and identity.

Over 2,000 adults in their sixties completed the Centrality of Event Scale (CES) for the traumatic or negative event that now troubled them the most and for their most positive life event, as well as measures of current PTSD symptoms, depression, well-being, and personality. Consistent with the notion of a positivity bias in old age, the positive events were judged to be markedly more central to life story and identity than were the negative events. The centrality of positive events was unrelated to measures of PTSD symptoms and emotional distress, whereas the centrality of the negative event showed clear positive correlations with these measures. The centrality of the positive events increased with increasing time since the events, whereas the centrality of the negative events decreased. The life distribution of the positive events showed a marked peak in young adulthood whereas the life distribution for the negative events peaked at the participants' present age. The positive events were mostly events from the cultural life script-that is, culturally shared representations of the timing of major transitional events. Overall, our findings show that positive and negative autobiographical events relate markedly differently to life story and identity. Positive events become central to life story and identity primarily through their correspondence with cultural norms. Negative events become central through mechanisms associated with emotional distress.

The normative and the personal life: individual differences in life scripts and life story events among USA and Danish undergraduates.

Life scripts are culturally shared expectations about the order and timing of life events in a prototypical life course. American and Danish undergraduates produced life story events and life scripts by listing the seven most important events in their own lives and in the lives of hypothetical people living ordinary lives. They also rated their events on several scales and completed measures of depression, PTSD symptoms, and centrality of a negative event to their lives. The Danish life script replicated earlier work; the American life script showed minor differences from the Danish life script, apparently reflecting genuine differences in shared events as well as less homogeneity in the American sample. Both consisted of mostly positive events that came disproportionately from ages 15 to 30. Valence of life story events correlated with life script valence, depression, PTSD symptoms, and identity. In the Danish undergraduates, measures of life story deviation from the life script correlated with measures of depression and PTSD symptoms.

Contrasting Models of Posttraumatic Stress Disorder: Reply to Monroe and Mineka (2008)

The authors address the 4 main points in S. M. Monroe and S. Mineka's (2008) comment. First, the authors show that the Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; American Psychiatric Association, 2000) posttraumatic stress disorder (PTSD) diagnosis includes an etiology and that it is based on a theoretical model with a distinguished history in psychology and psychiatry. Two tenets of this theoretical model are that voluntary (strategic) recollections of the trauma are fragmented and incomplete while involuntary (spontaneous) recollections are vivid and persistent and yield privileged access to traumatic material. Second, the authors describe differences between their model and other cognitive models of PTSD. They argue that these other models share the same 2 tenets as the diagnosis and show that these 2 tenets are largely unsupported by empirical evidence. Third, the authors counter arguments about the strength of the evidence favoring the mnemonic model. Fourth, they show that concerns about the causal role of memory in PTSD are based on views of causality that are generally inappropriate for the explanation of PTSD in the social and biological sciences. © 2008 American Psychological Association.