Eckart, Cindy
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Magnetic resonance volumetry and spectroscopy of hippocampus and insula in relation to severe exposure of traumatic stress
Severe and chronic stress affects the hippocampus, especially during development. However, studies concerning structural alterations of the hippocampus yielded a rather inconsistent picture. Moreover, further anxiety-relevant brain regions, such as the insula, might be implicated in the pathophysiology of posttraumatic stress disorder (PTSD). We combined magnetic resonance (MR) volumetric and spectroscopic analyses of hippocampus and insula in highly traumatized refugees without a history of alcohol/substance abuse or other comorbid diseases. No PTSD-related difference was apparent in the volumes or neurometabolite levels of bilateral hippocampus or insula. However, an association between left hippocampal N-acetyl-aspartate (NAA) and adverse childhood experiences indicated a potential detrimental effect of the early environment on hippocampal integrity. Our results add to increasing evidence that PTSD-related, morphological alterations in the hippocampus are a consequence of early adversity or may result from other factors, such as extensive use of alcohol.
Association Study of Trauma Load and SLC6A4 Promoter Polymorphism in Posttraumatic Stress Disorder : Evidence From Survivors of the Rwandan Genocide
Objective: As exposure to different types of traumatic stressors increases, the occurrence of posttraumatic stress disorder (PTSD) increases. However, because some people exhibit either surprising resilience or high vulnerability, further influencing factors have been conjectured, such as gene-environment interactions. The SLC6A4 gene, which encodes serotonin transporter, has been identified as predisposing toward differential emotional processing between genotypes of its promoter polymorphism.
Method: We investigated 408 refugees from the Rwandan genocide and assessed lifetime exposure to traumatic events, PTSD (according to DSM-IV) status, and genotype of the SLC6A4 promoter polymorphism. The study was conducted from March 2006 to February 2007.
Results: The prevalence of PTSD approached
100% when traumatic exposure reached extreme levels. However, persons homozygous for the short allele of the SLC6A4 promoter polymorphism showed no dose-response relationship but were at high risk for developing PTSD after very few traumatic events. This genotype influence vanished with increasing exposure to traumatic stressors. Conclusion: We find evidence for a geneenvironment interplay for PTSD and show that genetic influences lose importance when environmental factors cause an extremely high trauma burden to an individual. In the future, it may be important to determine whether the effectiveness of therapeutic interventions in PTSD is also modulated by the SLC6A4 genotype.
Lack of cortisol response in patients with posttraumatic stress disorder (PTSD) undergoing a diagnostic interview
Background
According to DSM-IV, the diagnosis of posttraumatic stress disorder (PTSD) requires the experience of a traumatic event during which the person's response involved intense fear, helplessness, or horror. In order to diagnose PTSD, clinicians must interview the person in depth about his/her previous experiences and determine whether the individual has been traumatized by a specific event or events. However, asking questions about traumatic experiences can be stressful for the traumatized individual and it has been cautioned that subsequent "re-traumatization" could occur. This study investigated the cortisol response in traumatized refugees with PTSD during a detailed and standardized interview about their personal war and torture experiences.
Methods
Participants were male refugees with severe PTSD who solicited an expert opinion in the Psychological Research Clinic for Refugees of the University of Konstanz. 17 patients were administered the Vivo Checklist of War, Detention, and Torture Events, a standardized interview about traumatic experiences, and 16 subjects were interviewed about absorption behavior. Self-reported measures of affect and arousal, as well as saliva cortisol were collected at four points. Before and after the experimental intervention, subjects performed a Delayed Matching-to-Sample (DMS) task for distraction. They also rated the severity of selected PTSD symptoms, as well as the level of intrusiveness of traumatic memories at that time.
Results
Cortisol excretion diminished in the course of the interview and showed the same pattern for both groups. No specific response was detectable after the supposed stressor. Correspondingly, ratings of subjective well-being, memories of the most traumatic event(s) and PTSD symptoms did not show any significant difference between groups. Those in the presumed stress condition did not perform worse than persons in the control condition after the stressor. However, both groups performed poorly in the DMS task, which is consistent with memory and concentration problems demonstrated in patients with PTSD.
Structural alterations in lateral prefrontal, parietal and posterior midline regions of men with chronic posttraumatic stress disorder
Background
So far, the neural network associated with posttraumatic stress disorder (PTSD) has been suggested to mainly involve the amygdala, hippocampus and medial prefrontal cortex. However, increasing evidence indicates that cortical regions extending beyond this network might also be implicated in the pathophysiology of PTSD. We aimed to investigate PTSD-related structural alterations in some of these regions.
Methods
We enrolled highly traumatized refugees with and without (traumatized controls) PTSD and non-traumatized controls in the study. To increase the validity of our results, we combined an automatic cortical parcellation technique and voxel-based morphometry.
Results
In all, 39 refugees (20 with and 19 without PTSD) and 13 controls participated in the study. Participants were middle-aged men who were free of psychoactive substances and consumed little to no alcohol. Patients with PTSD (and to a lesser extent traumatized controls) showed reduced volumes in the right inferior parietal cortex, the left rostral middle frontal cortex, the bilateral lateral orbitofrontal cortex and the bilateral isthmus of the cingulate. An influence of cumulative traumatic stress on the isthmus of the cingulate and the lateral orbitofrontal cortex indicated that, at least in these regions, structural alterations might be associated with repeated stress experiences. Voxel-based morphometry analyses produced largely consistent results, but because of a poorer signal-to-noise ratio, conventional statistics did not reach significance.
Limitations
Although we controlled for several important confounding variables (e.g., sex, alcohol abuse) with our particular sample, this might limit the generalizibility of our data. Moreover, high comorbidity of PTSD and major depression hinders a definite separation of these conditions in our findings. Finally, the results concerning the lateral orbitofrontal cortex should be interpreted with caution, as magnetic resonance imaging acquisition in this region is affected by a general signal loss.
Conclusion
Our results indicate that lateral prefrontal, parietal and posterior midline structures are implicated in the pathophysiology of PTSD. As these regions are particularly involved in episodic memory, emotional processing and executive control, this might have important implications for the understanding of PTSD symptoms.
No PTSD-related differences in diurnal cortisol profiles of genocide survivors
Posttraumatic stress disorder (PTSD) has been associated with reduced cortisol levels. Opposing results have been interpreted as resulting from methodological differences between studies.We investigated the diurnal profile of salivary cortisol in a population of highly traumatized adult males from Rwanda with and without PTSD, who spent the whole day of examination together under amaximally standardized schedule. Besides the detection of PTSDrelated alterations in cortisol release we aimed at determining physiologically relevant effects of cumulative trauma exposure on HPA functioning in interaction with or independent of diagnosis. There were no differences in the diurnal pattern of cortisol release between subjects with and without PTSD. We observed an increasing prevalence of PTSD with increasing number of different traumatic event types experienced, replicating earlier results on a building-block effect of multiple traumatization. However, size of cumulative exposure was not related to any of the cortisol measures. The results suggest that besides methodological constraints also confounding factors not previously controlled for, e.g., sex differences or current life stress, might contribute to the diverging results of lowered, unchanged or enhanced cortisol secretion in PTSD. Future research should therefore closely monitor these possible confounds to optimize models for cortisol in research on stress-dependent illnesses.
Spontaneous Remission From PTSD Depends on the Number of Traumatic Event Types Experienced
As exposure to different types of traumatic stressors increases, the prevalence of PTSD increases. However, little is known about the effects of cumulative exposure to traumatic stress on the maintenance and remission from PTSD. In 2006/2007, we investigated 444 refugees from the 1994 Rwandan genocide, assessing exposure to traumatic events, current and lifetime PTSD, and PTSD symptom severity. Higher trauma exposure was associated with higher prevalence of current and lifetime PTSD, with lower probability of spontaneous remission from PTSD, and with higher current and lifetime PTSD symptom severity in clear dose-response effects. The results suggest traumatic load as a root cause of both PTSD chronicity and symptom severity and support the hypothesis of a neural fear network in the etiology of PTSD.
Neuroendocrinological and brain structural alterations in Posttraumatic Stress Disorder (PTSD)
A neurobiological model of posttraumatic stress disorder (PTSD) associates its specific symptoms with a memory network that is mainly composed of amygdala, hippocampus and medial prefrontal cortex. According to that framework, a core problem in PTSD consists in the excessive formation of amygdaloid fear networks that cannot be sufficiently inhibited by hippocampus and prefrontal cortex. A reason for this disturbed inhibition was suggested in the cortisol-mediated atrophy of hippocampal tissue. However, there is still no entirely unambiguous empirical support for this theory. Particularly methodological differences between studies have been discussed as potential reason for existing inconsistencies.
Study 1: Potential PTSD-associated differences in basal cortisol levels were elucidated within an investigation of the diurnal cortisol release of highly traumatized, Rwandese refugees. Both, the study design and the choice of the population allowed a maximal control of methodological confounds. Notwithstanding, no PTSD-related alterations in cortisol profiles were revealed. Study 2: Potential brain structural alterations of regions associated with episodic memory networks were investigated in a sample of traumatized refugees with and without PTSD. Specific volume changes were revealed in the right inferior parietal cortex, the bilateral later prefrontal cortex and the bilateral isthmus of the cingulate. Study 3: The specific role of hippocampus and insula in the pathophysiology of PTSD was clarified in a combined volumetry/spectroscopy investigation of the same sample. In both structures neither volume reductions nor changes in neuronal density were revealed. An association between left hippocampal metabolite concentration and the occurrence of negative childhood experiences suggests that these experiences might have a particular influence on hippocampal integrity.
In light of the present results, it seems unlikely that PTSD-related alterations in cortisol release might result in atrophies within hippocampal tissue. Morphological alterations in this structure might rather be the consequence of negative childhood experiences or develop secondary to other factors, as e.g. excessive alcohol abuse. Moreover, an extension of the conventional neurobiological model of PTSD seems reasonable. Particularly cortical regions that have been associated with the volitional control of memory processes and the regulation of emotional conditions showed PTSD-specific structural volume reductions. The contribution of these structures in the pathophysiology of PTSD should be the focus of future research.