Predicting impaired extinction of traumatic memory and elevated startle

Background

Emotionally traumatic experiences can lead to debilitating anxiety disorders, such as phobias and Post-Traumatic Stress Disorder (PTSD). Exposure to such experiences, however, is not sufficient to induce pathology, as only up to one quarter of people exposed to such events develop PTSD. These statistics, combined with findings that smaller hippocampal size prior to the trauma is associated with higher risk of developing PTSD, suggest that there are pre-disposing factors for such pathology. Because prospective studies in humans are limited and costly, investigating such pre-dispositions, and thus advancing understanding of the genesis of such pathologies, requires the use of animal models where predispositions are identified before the emotional trauma. Most existing animal models are retrospective: they classify subjects as those with or without a PTSD-like phenotype long after experiencing a traumatic event. Attempts to create prospective animal models have been largely unsuccessful.

Methodology/Principal Findings

Here we report that individual predispositions to a PTSD-like phenotype, consisting of impaired rate and magnitude of extinction of an emotionally traumatic event coupled with long-lasting elevation of acoustic startle responses, can be revealed following exposure to a mild stressor, but before experiencing emotional trauma. We compare, in rats, the utility of several classification criteria and report that a combination of criteria based on acoustic startle responses and behavior in an anxiogenic environment is a reliable predictor of a PTSD-like phenotype.

Conclusions/Significance

There are individual predispositions to developing impaired extinction and elevated acoustic startle that can be identified after exposure to a mildly stressful event, which by itself does not induce such a behavioral phenotype. The model presented here is a valuable tool for studying the etiology and pathophysiology of anxiety disorders and provides a platform for testing behavioral and pharmacological interventions that can reduce the probability of developing pathologic behaviors associated with such disorders.     

Early Affective Processing in Patients with Acute Posttraumatic Stress Disorder: Magnetoencephalographic Correlates

Background

In chronic PTSD, a preattentive neural alarm system responds rapidly to emotional information, leading to increased prefrontal cortex (PFC) activation at early processing stages (<100 ms). Enhanced PFC responses are followed by a reduction in occipito-temporal activity during later processing stages. However, it remains unknown if this neuronal pattern is a result of a long lasting mental disorder or if it represents changes in brain function as direct consequences of severe trauma.

Methodology

The present study investigates early fear network activity in acutely traumatized patients with PTSD. It focuses on the question whether dysfunctions previously observed in chronic PTSD patients are already present shortly after trauma exposure. We recorded neuromagnetic activity towards emotional pictures in seven acutely traumatized PTSD patients between one and seven weeks after trauma exposure and compared brain responses to a balanced healthy control sample. Inverse modelling served for mapping sources of differential activation in the brain.

Principal Findings

Compared to the control group, acutely traumatized PTSD patients showed an enhanced PFC response to high-arousing pictures between 60 to 80 ms. This rapid prefrontal hypervigilance towards arousing pictorial stimuli was sustained during 120–300 ms, where it was accompanied by a reduced affective modulation of occipito-temporal neural processing.

Conclusions

Our findings indicate that the hypervigilance-avoidance pattern seen in chronic PTSD is not necessarily a product of an endured mental disorder, but arises as an almost immediate result of severe traumatisation. Thus, traumatic experiences can influence emotion processing strongly, leading to long-lasting changes in trauma network activation and expediting a chronic manifestation of maladaptive cognitive and behavioral symptoms.     

Early PTSD Symptom Trajectories: Persistence,Recovery, and Response to Treatment: Results from the Jerusalem Trauma Outreach and Prevention Study (J-TOPS)

Context

Uncovering heterogeneities in the progression of early PTSD symptoms can improve our understanding of the disorder''s pathogenesis and prophylaxis.

Objectives

To describe discrete symptom trajectories and examine their relevance for preventive interventions.

Design

Latent Growth Mixture Modeling (LGMM) of data from a randomized controlled study of early treatment. LGMM identifies latent longitudinal trajectories by exploring discrete mixture distributions underlying observable data.

Setting

Hadassah Hospital unselectively receives trauma survivors from Jerusalem and vicinity.

Participants

Adult survivors of potentially traumatic events consecutively admitted to the hospital''s emergency department (ED) were assessed ten days and one-, five-, nine- and fifteen months after ED admission. Participants with data at ten days and at least two additional assessments (n = 957) were included; 125 received cognitive behavioral therapy (CBT) between one and nine months.

Approach

We used LGMM to identify latent parameters of symptom progression and tested the effect of CBT on these parameters. CBT consisted of 12 weekly sessions of either cognitive therapy (n = 41) or prolonged exposure (PE, n = 49), starting 29.8±5.7 days after ED admission, or delayed PE (n = 35) starting at 151.8±42.4 days. CBT effectively reduced PTSD symptoms in the entire sample.

Main Outcome Measure

Latent trajectories of PTSD symptoms; effects of CBT on these trajectories.

Results

Three trajectories were identified: Rapid Remitting (rapid decrease in symptoms from 1- to 5-months; 56% of the sample), Slow Remitting (progressive decrease in symptoms over 15 months; 27%) and Non-Remitting (persistently elevated symptoms; 17%). CBT accelerated the recovery of the Slow Remitting class but did not affect the other classes.

Conclusions

The early course of PTSD symptoms is characterized by distinct and diverging response patterns that are centrally relevant to understanding the disorder and preventing its occurrence. Studies of the pathogenesis of PTSD may benefit from using clustered symptom trajectories as their dependent variables.     

Single-Prolonged Stress Induces Endoplasmic Reticulum - Dependent Apoptosis in the Hippocampus in a Rat Model of Post-Traumatic Stress Disorder

Background

Our previous research indicated that apoptosis induced atrophy in the hippocampus of post-traumatic stress disorder (PTSD) rats. Endoplasmic reticulum (ER) stress-induced apoptosis has been implicated in the development of several disorder diseases. The aim of this study was to investigate whether endoplasmic reticulum-related pathway is involved in single-prolonged stress (SPS) induces apoptosis in the hippocampus of PTSD rats by examining the expression levels of three important indicators in the ER-related apoptotic pathway: Glucose-regulated protein (GRP) 78, caspase-12 and Ca²⁺/CaM/CaMkinaseIIα (CaMkIIα).

Methods

Wistar rats were sacrificed at 1, 4 and 7 days after SPS. SPS is a reliable animal model of PTSD. The apoptotic cells in the hippocampus were assessed by TUNEL method and transmission electron microscopy (TEM). Free intracellular Ca²⁺ concentration was measured. GRP78 expression was examined by immunohistochemistry, western blotting and RT-PCR. mRNA of caspase-12 and CaM/CaMkIIα were determined by RT-PCR.

Results

Our results showed that apoptotic cells were increased in the SPS rats. TEM analysis revealed characteristic morphological changes of apoptosis in these cells. We observed that GRP78 was significantly up-regulated during early PTSD, and then recovered at 7 days after SPS. By RT-PCR, we observed that the change in caspase-12 expression level was similar to that in GRP78. Moreover, the free intracellular Ca²⁺ concentration was significantly higher at 1 day after SPS and decreased in 7 days. CaM expression increased significantly, while CaMKIIα expression decreased significantly in the hippocampus at 1 day after SPS.

Conclusion

SPS induced change in the expression levels of GRP78, caspase-12 and Ca²⁺/CaM/CaMkIIα in the hippocampus of PTSD rats indicated that the endoplasmic reticulum pathway may be involved in PTSD-induced apoptosis.     

Psychometric Properties of the Child PTSD Checklist in a Community Sample of South African Children and Adolescents

Objective

The current study assessed the basic psychometric properties of the Child PTSD Checklist and examined the structure of symptoms of posttraumatic stress disorder (PTSD) in a large sample of South African youth.

Methodology

The checklist was completed by 1025 (540 male; 485 female) South African youth (aged between 10 and 19 years). The factor structure of the scale was assessed with a combination of confirmatory and exploratory techniques. Internal consistencies for the full scale and all subscales were evaluated with Cronbach’s alpha and McDonald’s omega. Validity was assessed by comparing PTSD scores obtained by children who had and had not experienced a traumatic event, and by examining associations between total PTSD scores and known correlates of PTSD.

Results

Scores on the Child PTSD Checklist clearly discriminated between youth who had experienced a traumatic event and those who had not. Internal consistencies for the full scale (and all subscales) were acceptable to good and hypothesized correlations between PTSD, depression, anxiety, somatic symptoms, and age were observed. Two of the reported fit statistics for the tripartite DSM-IV-TR model of PTSD did not meet traditional criteria and further exploratory analyses revealed a four-factor structure (broadly consistent with Simms and colleagues’ Dysphoria Model of PTSD symptoms) which provided a better fit to the observed data.

Conclusion

Given the continued use of the Child PTSD Checklist in South Africa, findings offer an important first step in establishing the reliability and validity of the checklist for use with South African youth. However, further evaluation of the checklist in South African samples is clearly required before conclusions regarding its use as diagnostic tool in this context can be made.     

Chronic exercise improves repeated restraint stress-induced anxiety and depression through 5HT1A receptor and cAMP signaling in hippocampus

[Purpose]

Mood disorders such as anxiety and depression are prevalent psychiatric illness, but the role of 5HT1A in the anti-depressive effects of exercise has been rarely known yet. We investigated whether long-term exercise affected a depressive-like behavior and a hippocampal 5HT1A receptor-mediated cAMP/PKA/CREB signaling in depression mice model.

[Methods]

To induce depressive behaviors, mice were subjected to 14 consecutive days of restraint stress (2 hours/day). Depression-like behaviors were measured by forced swimming test (TST), and anxiety-like behavior was assessed by elevated plus maze (EPM). Treadmill exercise was performed with 19 m/min for 60 min/day, 5 days/week from weeks 0 to 8. Restraint stress was started at week 6 week and ended at week 8. To elucidate the role of 5HT1A in depression, the immunoreactivities of 5HT1A were detected in hippocampus using immunohistochemical technique.

[Results]

Chronic/repeated restraint stress induced behavioral anxiety and depression, such as reduced time and entries in open arms in EPM and enhanced immobility time in FST. These anxiety and depressive behaviors were ameliorated by chronic exercise. Also, these behavioral changes were concurrent with the deficit of 5HT1A and cAMP/PKA/CREB cascade in hippocampus, which was coped with chronic exercise.

[Conclusion]

These results suggest that chronic exercise may improve the disturbance of hippocampal 5HT1A-regulated cAMP/PKA/CREB signaling in a depressed brain, thereby exerting an antidepressive action.     

The effects of voluntary, involuntary, and forced exercises on brain-derived neurotrophic factor and motor function recovery: a rat brain ischemia model

Background

Stroke rehabilitation with different exercise paradigms has been investigated, but which one is more effective in facilitating motor recovery and up-regulating brain neurotrophic factor (BDNF) after brain ischemia would be interesting to clinicians and patients. Voluntary exercise, forced exercise, and involuntary muscle movement caused by functional electrical stimulation (FES) have been individually demonstrated effective as stroke rehabilitation intervention. The aim of this study was to investigate the effects of these three common interventions on brain BDNF changes and motor recovery levels using a rat ischemic stroke model.

Methodology/Principal Findings

One hundred and seventeen Sprague-Dawley rats were randomly distributed into four groups: Control (Con), Voluntary exercise of wheel running (V-Ex), Forced exercise of treadmill running (F-Ex), and Involuntary exercise of FES (I-Ex) with implanted electrodes placed in two hind limb muscles on the affected side to mimic gait-like walking pattern during stimulation. Ischemic stroke was induced in all rats with the middle cerebral artery occlusion/reperfusion model and fifty-seven rats had motor deficits after stroke. Twenty-four hours after reperfusion, rats were arranged to their intervention programs. De Ryck''s behavioral test was conducted daily during the 7-day intervention as an evaluation tool of motor recovery. Serum corticosterone concentration and BDNF levels in the hippocampus, striatum, and cortex were measured after the rats were sacrificed. V-Ex had significantly better motor recovery in the behavioral test. V-Ex also had significantly higher hippocampal BDNF concentration than F-Ex and Con. F-Ex had significantly higher serum corticosterone level than other groups.

Conclusion/Significance

Voluntary exercise is the most effective intervention in upregulating the hippocampal BDNF level, and facilitating motor recovery. Rats that exercised voluntarily also showed less corticosterone stress response than other groups. The results also suggested that the forced exercise group was the least preferred intervention with high stress, low brain BDNF levels and less motor recovery.     

Signs of mood and anxiety disorders in chimpanzees

Background

In humans, traumatic experiences are sometimes followed by psychiatric disorders. In chimpanzees, studies have demonstrated an association between traumatic events and the emergence of behavioral disturbances resembling posttraumatic stress disorder (PTSD) and depression. We addressed the following central question: Do chimpanzees develop posttraumatic symptoms, in the form of abnormal behaviors, which cluster into syndromes similar to those described in human mood and anxiety disorders?

Methodology/Principal Findings

In phase 1 of this study, we accessed case reports of chimpanzees who had been reportedly subjected to traumatic events, such as maternal separation, social isolation, experimentation, or similar experiences. We applied and tested DSM-IV criteria for PTSD and major depression to published case reports of 20 chimpanzees identified through PrimateLit. Additionally, using the DSM-IV criteria and ethograms as guides, we developed behaviorally anchored alternative criteria that were applied to the case reports. A small number of chimpanzees in the case studies met DSM-IV criteria for PTSD and depression. Measures of inter-rater reliability, including Fleiss'' kappa and percentage agreement, were higher with use of the alternative criteria for PTSD and depression. In phase 2, the alternative criteria were applied to chimpanzees living in wild sites in Africa (n = 196) and chimpanzees living in sanctuaries with prior histories of experimentation, orphanage, illegal seizure, or violent human conflict (n = 168). In phase 2, 58% of chimpanzees living in sanctuaries met the set of alternative criteria for depression, compared with 3% of chimpanzees in the wild (p = 0.04), and 44% of chimpanzees in sanctuaries met the set of alternative criteria for PTSD, compared with 0.5% of chimpanzees in the wild (p = 0.04).

Conclusions/Significance

Chimpanzees display behavioral clusters similar to PTSD and depression in their key diagnostic criteria, underscoring the importance of ethical considerations regarding the use of chimpanzees in experimentation and other captive settings.     

Amantadine Ameliorates Dopamine-Releasing Deficits and Behavioral Deficits in Rats after Fluid Percussion Injury

Aims

To investigate the role of dopamine in cognitive and motor learning skill deficits after a traumatic brain injury (TBI), we investigated dopamine release and behavioral changes at a series of time points after fluid percussion injury, and explored the potential of amantadine hydrochloride as a chronic treatment to provide behavioral recovery.

Materials and Methods

In this study, we sequentially investigated dopamine release at the striatum and behavioral changes at 1, 2, 4, 6, and 8 weeks after fluid percussion injury. Rats subjected to 6-Pa cerebral cortical fluid percussion injury were treated by using subcutaneous infusion pumps filled with either saline (sham group) or amantadine hydrochloride, with a releasing rate of 3.6mg/kg/hour for 8 weeks. The dopamine-releasing conditions and metabolism were analyzed sequentially by fast scan cyclic voltammetry (FSCV) and high-pressure liquid chromatography (HPLC). Novel object recognition (NOR) and fixed-speed rotarod (FSRR) behavioral tests were used to determine treatment effects on cognitive and motor deficits after injury.

Results

Sequential dopamine-release deficits were revealed in 6-Pa-fluid-percussion cerebral cortical injured animals. The reuptake rate (tau value) of dopamine in injured animals was prolonged, but the tau value became close to the value for the control group after amantadine therapy. Cognitive and motor learning impairments were shown evidenced by the NOR and FSRR behavioral tests after injury. Chronic amantadine therapy reversed dopamine-release deficits, and behavioral impairment after fluid percussion injuries were ameliorated in the rats treated by using amantadine-pumping infusion.

Conclusion

Chronic treatment with amantadine hydrochloride can ameliorate dopamine-release deficits as well as cognitive and motor deficits caused by cerebral fluid-percussion injury.     

Life events, coping, and posttraumatic stress symptoms among Chinese adolescents exposed to 2008 Wenchuan Earthquake, China

Purpose

To examine the relationship between negative life events, coping styles, and symptoms of post-traumatic stress disorder (PTSD) among adolescent survivors exposed to 2008 Wenchuan Earthquake, China.

Methods

A survey was conducted in a sample of 2250 adolescent students from two schools in Dujiangyan District, a seriously damaged area, 20 kilometers away from the epicenter, 6 months after the earthquake. Participants completed a self-administered questionnaire including demographics, negative life events, coping styles, and PTSD symptoms.

Results

Academic pressure was the strongest predictor of adolescents'' PTSD symptoms among all negative life events. Main effects of negative life events, positive coping and negative coping on PTSD symptoms were significant in both younger adolescents and older adolescents, while the moderator effects of two coping styles were found significant only within older adolescents.

Conclusions

Coping may play a role to moderate the relationship between post-earthquake negative life events and PTSD symptom, but the function seems to depend on the age of participants. Psychosocial coping skills training may be important in the prevention and intervention of mental health problems in adolescent survivors of traumatic earthquake.     

Decreased premotor cortex volume in victims of urban violence with posttraumatic stress disorder

Background

Studies addressing posttraumatic stress disorder (PTSD) have demonstrated that PTSD patients exhibit structural abnormalities in brain regions that relate to stress regulation and fear responses, such as the hippocampus, amygdala, anterior cingulate cortex, and ventromedial prefrontal cortex. Premotor cortical areas are involved in preparing to respond to a threatening situation and in representing the peripersonal space. Urban violence is an important and pervasive cause of human suffering, especially in large urban centers in the developing world. Violent events, such as armed robbery, are very frequent in certain cities, and these episodes increase the risk of PTSD. Assaultive trauma is characterized by forceful invasion of the peripersonal space; therefore, could this traumatic event be associated with structural alteration of premotor areas in PTSD?

Methodology/Principal Findings

Structural magnetic resonance imaging scans were acquired from a sample of individuals that had been exposed to urban violence. This sample consisted of 16 PTSD patients and 16 age- and gender-matched controls. Psychometric questionnaires differentiated PTSD patients from trauma-exposed controls with regard to PTSD symptoms, affective, and resilience predispositions. Voxel-based morphometric analysis revealed that, compared with controls, the PTSD patients presented significant reductions in gray matter volume in the ventral premotor cortex and in the pregenual anterior cingulate cortex.

Conclusions

Volume reduction in the premotor cortex that is observed in victims of urban violence with PTSD may be associated with a disruption in the dynamical modulation of the safe space around the body. The finding that PTSD patients presented a smaller volume of pregenual anterior cingulate cortex is consistent with the results of other PTSD neuroimaging studies that investigated different types of traumatic events.     

Mental health problems among children one-year after Sichuan earthquake in China: a follow-up study

Background

On May 12, 2008, a destructive earthquake registering 8.0 on the Richter scale struck Sichuan Province, southwest China. Beichuan County was the epicenter which was one of the areas nearly completely destroyed by the earthquake. In Beichuan, about 15000 people died and 3000 people were missing. Specially, the earthquake took 1587 students'' and 214 teachers'' lives from the elementary and middle schools there. The main purpose of the study was to provide a better understanding of mental health problems and associated risk factors among children after earthquake.

Method

Three hundred and thirty grades 3–5 children completed the questionnaire of disaster –related experience and the Trauma Symptom Checklist for Children-Alternate Version (TSCC-A). The first survey was carried out six months after the earthquake, and the second one was carried out six months later. The measurements and methodology applied in the two sessions were identical.

Results

The prevalence rates of the problems at two time-points were 23.3% and 22.7% for anxiety, 14.5% and 16.1% for depression, and 11.2% and 13.4% for PTSD, respectively. Among demographic variables, no significant age difference existed, while it was found that 6 months after the earthquake, symptoms of anxiety, depression and PTSD were significantly more common among students in grades 4 and 5 than those in grade 3, Initial exposure to death, bereavement and extreme fear were significant predictive factors for the occurrence of anxiety, depression and PTSD.

Conclusions

Findings of this study suggest that posttraumatic mental health problems after natural disaster in children may have reached epidemic proportions and remain high for a long period. Psychologist and social workers should pay more attention to children who experienced more traumatic stresses and provide appropriate mental health interventions. Implications and limitations of these findings were discussed.     

Cysteamine attenuates the decreases in TrkB protein levels and the anxiety/depression-like behaviors in mice induced by corticosterone treatment

Objective

Stress and glucocorticoid hormones, which are released into the circulation following stressful experiences, have been shown to contribute significantly to the manifestation of anxiety-like behaviors observed in many neuropsychiatric disorders. Brain-derived neurotrophic factor (BDNF) signaling through its receptor TrkB plays an important role in stress-mediated changes in structural as well as functional neuroplasticity. Studies designed to elucidate the mechanisms whereby TrkB signaling is regulated in chronic stress might provide valuable information for the development of new therapeutic strategies for several stress-related psychiatric disorders.

Materials and Methods

We examined the potential of cysteamine, a neuroprotective compound to attenuate anxiety and depression like behaviors in a mouse model of anxiety/depression induced by chronic corticosterone exposure.

Results

Cysteamine administration (150 mg/kg/day, through drinking water) for 21 days significantly ameliorated chronic corticosterone-induced decreases in TrkB protein levels in frontal cortex and hippocampus. Furthermore, cysteamine treatment reversed the anxiety and depression like behavioral abnormalities induced by chronic corticosterone treatment. Finally, mice deficient in TrkB, showed a reduced response to cysteamine in behavioral tests, suggesting that TrkB signaling plays an important role in the antidepressant effects of cysteamine.

Conclusions

The animal studies described here highlight the potential use of cysteamine as a novel therapeutic strategy for glucocorticoid-related symptoms of psychiatric disorders.     

Alterations in Low-Level Perceptual Networks Related to Clinical Severity in PTSD after an Earthquake: A Resting-State fMRI Study

Background

Several task-based functional MRI (fMRI) studies have highlighted abnormal activation in specific regions involving the low-level perceptual (auditory, visual, and somato-motor) network in posttraumatic stress disorder (PTSD) patients. However, little is known about whether the functional connectivity of the low-level perceptual and higher-order cognitive (attention, central-execution, and default-mode) networks change in medication-naïve PTSD patients during the resting state.

Methods

We investigated the resting state networks (RSNs) using independent component analysis (ICA) in 18 chronic Wenchuan earthquake-related PTSD patients versus 20 healthy survivors (HSs).

Results

Compared to the HSs, PTSD patients displayed both increased and decreased functional connectivity within the salience network (SN), central executive network (CEN), default mode network (DMN), somato-motor network (SMN), auditory network (AN), and visual network (VN). Furthermore, strengthened connectivity involving the inferior temporal gyrus (ITG) and supplementary motor area (SMA) was negatively correlated with clinical severity in PTSD patients.

Limitations

Given the absence of a healthy control group that never experienced the earthquake, our results cannot be used to compare alterations between the PTSD patients, physically healthy trauma survivors, and healthy controls. In addition, the breathing and heart rates were not monitored in our small sample size of subjects. In future studies, specific task paradigms should be used to reveal perceptual impairments.

Conclusions

These findings suggest that PTSD patients have widespread deficits in both the low-level perceptual and higher-order cognitive networks. Decreased connectivity within the low-level perceptual networks was related to clinical symptoms, which may be associated with traumatic reminders causing attentional bias to negative emotion in response to threatening stimuli and resulting in emotional dysregulation.     

Human stiff-person syndrome IgG induces anxious behavior in rats

Background

Anxiety is a heterogeneous behavioral domain playing a role in a variety of neuropsychiatric diseases. While anxiety is the cardinal symptom in disorders such as panic disorder, co-morbid anxious behavior can occur in a variety of diseases. Stiff person syndrome (SPS) is a CNS disorder characterized by increased muscle tone and prominent agoraphobia and anxiety. Most patients have high-titer antibodies against glutamate decarboxylase (GAD) 65. The pathogenic role of these autoantibodies is unclear.

Methodology/Principal Findings

We re-investigated a 53 year old woman with SPS and profound anxiety for GABA-A receptor binding in the amygdala with (11)C-flumazenil PET scan and studied the potential pathogenic role of purified IgG from her plasma filtrates containing high-titer antibodies against GAD 65. We passively transferred the IgG fraction intrathecally into rats and analyzed the effects using behavioral and in vivo electrophysiological methods. In cell culture, we measured the effect of patient IgG on GABA release from hippocampal neurons. Repetitive intrathecal application of purified patient IgG in rats resulted in an anxious phenotype resembling the core symptoms of the patient. Patient IgG selectively bound to rat amygdala, hippocampus, and frontal cortical areas. In cultured rat hippocampal neurons, patient IgG inhibited GABA release. In line with these experimental results, the GABA-A receptor binding potential was reduced in the patient''s amygdala/hippocampus complex. No motor abnormalities were found in recipient rats.

Conclusion/Significance

The observations in rats after passive transfer lead us to propose that anxiety-like behavior can be induced in rats by passive transfer of IgG from a SPS patient positive for anti-GAD 65 antibodies. Anxiety, in this case, thus may be an antibody-mediated phenomenon with consecutive disturbance of GABAergic signaling in the amygdala region.     

Mental Health Problems among the Survivors in the Hard-Hit Areas of the Yushu Earthquake

Background

On April 14, 2010, an earthquake registering 7.1 on the Richter scale shook Qinghai Province in southwest China. The earthquake caused numerous casualties and much damage. The epicenter, Yushu County, suffered the most severe damage. As a part of the psychological relief work, the present study evaluated the mental health statuses of the people affected and identified the mental disorder risk factors related to earthquakes.

Methods

Five hundred and five earthquake survivors living in Yushu County were investigated 3–4 months after the earthquake. Participant demographic data including gender, age, marital status, ethnicity, educational level, and religious beliefs were collected. The Earthquake-Specific Trauma Exposure Indicators assessed the intensity of exposure to trauma during the earthquake. The PTSD Checklist-Civilian version (PCL-C) and the Hopkins Symptoms Checklist-25 (HSCL-25) assessed the symptoms and prevalence rates of probable Posttraumatic Stress Disorder (PTSD) as well as anxiety and depression, respectively. The Perceived Social Support Scale (PSSS) evaluated subjective social support.

Results

The prevalence rates of probable PTSD, anxiety, and depression were 33.7%, 43.8% and 38.6%, respectively. Approximately one fifth of participants suffered from all three conditions. Individuals who were female, felt initial fear during the earthquake, and had less social support were the most likely to have poor mental health.

Conclusions

The present study revealed that there are serious mental problems among the hard–hit survivors of the Yushu earthquake. Survivors at high risk for mental disorders should be specifically considered. The present study provides useful information for rebuilding and relief work.     

Different Regional Gray Matter Loss in Recent Onset PTSD and Non PTSD after a Single Prolonged Trauma Exposure

Objective

Gray matter loss in the limbic structures was found in recent onset post traumatic stress disorder (PTSD) patients. In the present study, we measured regional gray matter volume in trauma survivors to verify the hypothesis that stress may cause different regional gray matter loss in trauma survivors with and without recent onset PTSD.

Method

High resolution T1-weighted magnetic resonance imaging (MRI) were obtained from coal mine flood disaster survivors with (n = 10) and without (n = 10) recent onset PTSD and 20 no trauma exposed normal controls. The voxel-based morphometry (VBM) method was used to measure the regional gray matter volume in three groups, the correlations of PTSD symptom severities with the gray matter volume in trauma survivors were also analyzed by multiple regression.

Results

Compared with normal controls, recent onset PTSD patients had smaller gray matter volume in left dorsal anterior cingulate cortex (ACC), and non PTSD subjects had smaller gray matter volume in the right pulvinar and left pallidum. The gray matter volume of the trauma survivors correlated negatively with CAPS scores in the right frontal lobe, left anterior and middle cingulate cortex, bilateral cuneus cortex, right middle occipital lobe, while in the recent onset PTSD, the gray matter volume correlated negatively with CAPS scores in bilateral superior medial frontal lobe and right ACC.

Conclusion

The present study identified gray matter loss in different regions in recent onset PTSD and non PTSD after a single prolonged trauma exposure. The gray matter volume of left dorsal ACC associated with the development of PTSD, while the gray matter volume of right pulvinar and left pallidum associated with the response to the severe stress. The atrophy of the frontal and limbic cortices predicts the symptom severities of the PTSD.     

A Systematic Review of PTSD Prevalence and Trajectories in DSM-5 Defined Trauma Exposed Populations: Intentional and Non-Intentional Traumatic Events

Objective

We conducted a systematic review of the literature to explore the longitudinal course of PTSD in DSM-5-defined trauma exposed populations to identify the course of illness and recovery for individuals and populations experiencing PTSD.

Methods

We reviewed the published literature from January 1, 1998 to December 31, 2010 for longitudinal studies of directly exposed trauma populations in order to: (1) review rates of PTSD in the first year after a traumatic event; (2) examine potential types of proposed DSM-5 direct trauma exposure (intentional and non-intentional); and (3) identify the clinical course of PTSD (early onset, later onset, chronicity, remission, and resilience). Of the 2537 identified articles, 58 articles representing 35 unique subject populations met the proposed DSM-5 criteria for experiencing a traumatic event, and assessed PTSD at two or more time points within 12 months of the traumatic event.

Results

The mean prevalence of PTSD across all studies decreases from 28.8% (range  = 3.1–87.5%) at 1 month to 17.0% (range  = 0.6–43.8%) at 12 months. However, when traumatic events are classified into intentional and non-intentional, the median prevalences trend down for the non-intentional trauma exposed populations, while the median prevalences in the intentional trauma category steadily increase from 11.8% to 23.3%. Across five studies with sufficient data, 37.1% of those exposed to intentional trauma develop PTSD. Among those with PTSD, about one third (34.8%) remit after 3 months. Nearly 40% of those with PTSD (39.1%) have a chronic course, and only a very small fraction (3.5%) of new PTSD cases appears after three months.

Conclusions

Understanding the trajectories of PTSD over time, and how it may vary by type of traumatic event (intentional vs. non-intentional) will assist public health planning and treatment.     

Depression, comorbid anxiety disorders, and heart rate variability in physically healthy, unmedicated patients: implications for cardiovascular risk

Context

There is evidence that heart rate variability (HRV) is reduced in major depressive disorder (MDD), although there is debate about whether this effect is caused by medication or the disorder per se. MDD is associated with a two to fourfold increase in the risk of cardiac mortality, and HRV is a robust predictor of cardiac mortality; determining a direct link between HRV and not only MDD, but common comorbid anxiety disorders, will point to psychiatric indicators for cardiovascular risk reduction.

Objective

To determine in physically healthy, unmedicated patients whether (1) HRV is reduced in MDD relative to controls, and (2) HRV reductions are driven by MDD alone, comorbid generalized anxiety disorder (GAD, characterized by anxious anticipation), or comorbid panic and posttraumatic stress disorders (PD/PTSD, characterized by anxious arousal).

Design, Setting, and Patients

A case-control study in 2006 and 2007 on 73 MDD patients, including 24 without anxiety comorbidity, 24 with GAD, and 14 with PD/PTSD. Seventy-three MDD and 94 healthy age- and sex-matched control participants were recruited from the general community. Participants had no history of drug addiction, alcoholism, brain injury, loss of consciousness, stroke, neurological disorder, or serious medical conditions. There were no significant differences between the four groups in age, gender, BMI, or alcohol use.

Main Outcome Measures

HRV was calculated from electrocardiography under a standardized short-term resting state condition.

Results

HRV was reduced in MDD relative to controls, an effect associated with a medium effect size. MDD participants with comorbid generalized anxiety disorder displayed the greatest reductions in HRV relative to controls, an effect associated with a large effect size.

Conclusions

Unmedicated, physically healthy MDD patients with and without comorbid anxiety had reduced HRV. Those with comorbid GAD showed the greatest reductions. Implications for cardiovascular risk reduction strategies in otherwise healthy patients with psychiatric illness are discussed.     

Long-term impact of war on healthcare costs: an eight-country study

Objective

Exposure to war can negatively affect health and may impact on healthcare costs. Estimating these costs and identifying their predictors is important for appropriate service planning. We aimed to measure use of health services in an adult population who had experienced war in the former-Yugoslavia on average 8 years previously, and to identify characteristics associated with the use and costs of healthcare.

Method

War-affected community samples in Bosnia-Herzegovina, Croatia, Kosovo, FYR Macedonia, and Serbia were recruited through a random walk technique. Refugees in Germany, Italy and the UK were contacted through registers, organisations and networking. Current service use was measured for the previous three months and combined with unit costs for each country for the year 2006/7. A two-part approach was used, to identify predictors of service use with a multiple logistic regression model and predictors of cost with a generalised linear regression model.

Results

3,313 participants were interviewed in Balkan countries and 854 refugees in Western European countries. In the Balkan countries, traumatic events and mental health status were related to greater service use while in Western countries these associations were not found. Participants in Balkan countries with post traumatic stress disorder (PTSD) had costs that were 63% higher (p = 0.005) than those without PTSD. Distress experienced during the most traumatic war event was associated with higher costs (p = 0.013). In Western European countries costs were 76% higher if non-PTSD anxiety disorders were present (0.027) and 63% higher for mood disorders (p = 0.006).

Conclusions

War experiences and their effects on mental health are associated with increased health care costs even many years later, especially for those who stayed in the area of conflict. Focussing on the mental health impact of war is important for many reasons including those of an economic nature.