Decreased anterior cingulate volume in combat-related PTSD.
ABSTRACT Neuroanatomical data point to functional relationships between the anterior cingulate cortex (ACC) and subcortical centers regulating fear, in particular, the amygdala. Functional brain imaging has disclosed divergent patterns of ACC activation in persons with posttraumatic stress disorder (PTSD). In addition, two preliminary structural imaging studies have found evidence of smaller ACC volume in PTSD. We explored associations between PTSD and ACC volume in a relatively large sample of adult combat veterans in which PTSD, lifetime alcohol abuse/dependence, and Vietnam versus Gulf War service were crossed.
Subjects were US military combat veterans of the Vietnam and Gulf Wars recruited from two metropolitan areas served by allied Department of Veterans Affairs PTSD treatment/research centers. Anterior cingulate cortex volume was analyzed as a function of grouping factors with and without adjustment for body size.
Posttraumatic stress disorder was associated with smaller anterior cingulate cortex volume. This effect persisted in subjects without histories of alcoholism, did not interact with cohort effects, and was not modified by adjustment for body size.
Anterior cingulate cortex volume is substantially smaller in association with combat-related PTSD, a finding broadly consistent with cingulate hypofunctionality in that disorder.
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ABSTRACT: Background In our previous researches, we have found that apoptosis was induced in the medial prefrontal cortex (mPFC) 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) induced apoptosis in the mPFC of PTSD rats by examining the expression levels of ATF6 alpha (ATF6¿), two important downstream molecular chaperones of ATF6¿ in the ER stress: Glucose-regulated protein (GRP) 78 and ERP57, and apoptotic factors caspase 12, caspase 9, and caspase 3.ResultsOur results of Morris Water Maze (MWM) test showed that after SPS exposure, a striking increase of the escape latency was observed in SPS rats at day 1 through day 6, and SPS rats had much less time spent in target quadrant compared to control rats ( P < 0.01). And From immunofluorescence assays, we found that there was a gradual increase on the protein expression of ATF6¿ in response to SPS, which indicated ATF6¿ was activated by SPS. And additionally, immunohistochemistry assays, western blotting and reverse transcription-polymerase chain reaction (RT-PCR) showed that the immunoreactivity, protein and mRNA expression of GRP78 and ERP57 increased on 1, 4 days, and peaked on 7 days after SPS exposure, which revealed that SPS triggered inductions of GRP78 and ERP57 in the mPFC neurons. Moreover, RT-PCR assays demonstrated that there were up-regulations in the transcripts levels of caspase 12, caspase 9, and caspase 3 in response to SPS, which were according with the proteins changes of these apoptotic factors and indicated that ER stress and the activation of caspases contributed to SPS.Conclusion Current data in this study highlight that SPS induced ATF6¿-dependent Endoplasmic reticulum stress and ER-related apoptosis in the mPFC neurons, which indicated that the endoplasmic reticulum pathway may be involved in PTSD-induced apoptosis.BMC Neuroscience 10/2014; 15(1):115. · 2.85 Impact Factor
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ABSTRACT: This study compared the difference in brain structure in 12 mine disaster survivors with chronic post-traumatic stress disorder, 7 cases of improved post-traumatic stress disorder symptoms, and 14 controls who experienced the same mine disaster but did not suffer post-traumatic stress disorder, using the voxel-based morphometry method. The correlation between differences in brain structure and post-traumatic stress disorder symptoms was also investigated. Results showed that the gray matter volume was the highest in the trauma control group, followed by the symptoms-improved group, and the lowest in the chronic post-traumatic stress disorder group. Compared with the symptoms-improved group, the gray matter volume in the lingual gyrus of the right occipital lobe was reduced in the chronic post-traumatic stress disorder group. Compared with the trauma control group, the gray matter volume in the right middle occipital gyrus and left middle frontal gyrus was reduced in the symptoms-improved group. Compared with the trauma control group, the gray matter volume in the left superior parietal lobule and right superior frontal gyrus was reduced in the chronic post-traumatic stress disorder group. The gray matter volume in the left superior parietal lobule was significantly positively correlated with the State-Trait Anxiety Inventory subscale score in the symptoms-improved group and chronic post-traumatic stress disorder group (r = 0.477, P = 0.039). Our findings indicate that (1) chronic post-traumatic stress disorder patients have gray matter structural damage in the prefrontal lobe, occipital lobe, and parietal lobe, (2) after post-traumatic stress, the disorder symptoms are improved and gray matter structural damage is reduced, but cannot recover to the trauma-control level, and (3) the superior parietal lobule is possibly associated with chronic post-traumatic stress disorder. Post-traumatic stress disorder patients exhibit gray matter abnormalities.Neural Regeneration Research 09/2013; 8(26):2405-14. · 0.23 Impact Factor
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ABSTRACT: Substantial evidence has suggested that the brain structures of the medial prefrontal cortex (mPFC) and amygdala (AMYG) are implicated in the pathophysiology of stress-related disorders. However, little is known with respect to the system-level adaptation of their neural circuitries to the perturbations of traumatic stressors. By utilizing behavioral tests and an awake animal imaging approach, in the present study we non-invasively investigated the impact of single-episode predator odor exposure in an inescapable environment on behaviors and neural circuits in rodents. We found that predator odor exposure significantly increased the freezing behavior. In addition, animals exhibited heightened anxiety levels seven days after the exposure. Intriguingly, we also found that the intrinsic functional connectivity within the AMYG-mPFC circuit was considerably compromised seven days after the traumatic event. Our data provide neuroimaging evidence suggesting that prolonged neuroadaptation induced by a single episode of traumatic stress can be non-invasively detected in rodents. These results also support the face validity and construction validity of using the paradigm of single trauma exposure in an inescapable environment as an animal model for post-traumatic stress disorder. Taken together, the present study has opened a new avenue to investigating animal models of stress-related mental disorders by going beyond static neuroanatomy, and ultimately bridging the gap between basic biomedical and human imaging research.NeuroImage 09/2014; · 6.13 Impact Factor