Positron Emission Tomography Measurement of Cerebral Metabolic Correlates of Yohimbine Administration in Combat-Related Posttraumatic Stress Disorder

Bremner, J. Douglas; Innis, Robert B.; Ng, Chin K.; Staib, Lawrence H.; Salomon, Ronald M.; Bronen, Richard A.; Duncan, James S.; Southwick, Steven M.; Krystal, John H.; Rich, D. R.; Zubal, George; Dey, Holley M.; Soufer, Robert; Charney, Dennis S.

doi:10.1001/archpsyc.1997.01830150070011

Cited by 277 publications

(170 citation statements)

References 80 publications

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“…Moreover, the reduction and increase of noradrenergic activity attenuated and precipitated, respectively, some of the symptoms in PTSD patients (Boehnlein and Kinzie, 2007;Bremner et al, 1997;Raskind et al, 2007;Southwick et al, 1993;Taylor et al, 2008). Evidence of noradrenaline dysregulation have been also shown in several studies measuring noradrenaline in the urinary system and in plasma of PTSD patients (reviewed in (Strawn and Geracioti, 2008).…”

Section: Discussionmentioning

confidence: 89%

“…It has been proposed that an altered noradrenergic activity may contribute to the hyperarousal symptoms associated with PTSD (Krystal and Neumeister, 2009;O'Donnell et al, 2004;Southwick et al, 1999;Strawn and Geracioti, 2008). This proposal is based on studies showing that the reduction and increase of noradrenergic activity attenuated and precipitated, respectively, some of the symptoms in PTSD patients (Boehnlein and Kinzie, 2007;Bremner et al, 1997;Raskind et al, 2007;Southwick et al, 1993;Taylor et al, 2008). Additionally, the systemic treatment with pharmacological agents that reduce noradrenergic transmission normalized acoustic startle response in mice previously exposed to inescapable foot-shock (IFS) (Olson et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

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Enhanced noradrenergic activity in the amygdala contributes to hyperarousal in an animal model of PTSD

Ronzoni

Arco

Mora

et al. 2016

Psychoneuroendocrinology

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SummaryIncreased activity of the noradrenergic system in the amygdala has been suggested to contribute to the hyperarousal symptoms associated with post-traumatic stress disorder (PTSD). However, only two studies have examined the content of noradrenaline or its metabolites in the amygdala of rats previously exposed to traumatic stress showing inconsistent results. The aim of this study was to investigate the effects of an inescapable foot shock (IFS) procedure 1) on reactivity to novelty in an open-field (as an index of hyperarousal), and 2) on noradrenaline release in the amygdala during an acute stress. To test the role of noradrenaline in amygdala, we also investigated the effects of microinjections of propranolol, a β-adrenoreceptor antagonist, and clenbuterol, a β-adrenoreceptor agonist, into the amygdala of IFS and control animals. Finally, we evaluated the expression of mRNA levels of β-adrenoreceptors (β1 and β2) in the amygdala, the hippocampus and the prefrontal cortex. Male Wistar rats (3 months) were stereotaxically implanted with bilateral guide cannulae. After recovering from surgery, animals were exposed to IFS (10 shocks, 0.86 mA, and 6 seconds per shock) and seven days later either microdialysis or microinjections were performed in amygdala. Animals exposed to IFS showed a reduced locomotion compared to IFS modified the mRNA expression of β1 and β2 adrenoreceptors in the prefrontal cortex and the hippocampus. These results suggest that an increased noradrenergic activity in the amygdala contributes to the expression of hyperarousal in an animal model of PTSD.

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Section: Discussionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Enhanced noradrenergic activity in the amygdala contributes to hyperarousal in an animal model of PTSD

Ronzoni

Arco

Mora

et al. 2016

Psychoneuroendocrinology

View full text Add to dashboard Cite

show abstract

“…[40][41][42][43][44] Across these studies, however, dysfunctional alterations occurred in different parts of the prefrontal cortex, indicating that failure of prefrontal inhibition in PTSD needs to be clarified in the future. In the present study, a reduction of GABA A -benzodiazepine BP throughout the frontal cortex was found.…”

Section: Discussionmentioning

confidence: 90%

Reduced GABAA benzodiazepine receptor binding in veterans with post-traumatic stress disorder

et al. 2007

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c-Aminobutyric acid (GABA A ) receptors are thought to play an important role in modulating the central nervous system in response to stress. Animal data have shown alterations in the GABA A receptor complex by uncontrollable stressors. SPECT imaging with benzodiazepine ligands showed lower distribution volumes of the benzodiazepine-GABA A receptor in the prefrontal cortex of patients with post-traumatic stress disorder (PTSD) in one, but not in another study. The objective of the present study was to assess differences in the benzodiazepine-GABA A receptor complex in veterans with and without PTSD using [ 11 C]flumazenil and positron emission tomography (PET). Nine drug naive male Dutch veterans with deployment related PTSD and seven male Dutch veterans without PTSD were recruited, and matched for age, region and year of deployment. Each subject received a [ 11 C]flumazenil PET scan and a structural magnetic resonance imaging scan. Dynamic 3D PET scans with a total duration of 60 min were acquired, and binding in template based and manually defined regions of interest (ROI) was quantified using validated plasma input and reference tissue models. In addition, parametric binding potential images were compared on a voxel-by-voxel basis using statistical parametric mapping (SPM2). ROI analyses using both template based and manual ROIs showed significantly reduced [ 11 C]flumazenil binding in PTSD subjects throughout the cortex, hippocampus and thalamus. SPM analysis confirmed these results. The observed global reduction of [ 11 C]flumazenil binding in patients with PTSD provides circumstantial evidence for the role of the benzodiazepine-GABA A receptor in the pathophysiology of PTSD and is consistent with previous animal research and clinical psychopharmacological studies.

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“…Other PET trials found that, compared with controls, PTSD subjects show reduced blood flow in the middle temporal gyrus when applying symptom-provoking tasks (traumatic pictures, sounds, trauma-related psychological images and administration of yohimbine) [28,50,51] . The middle temporal gyrus can inhibit the function of the amygdala, facilitate the extinction of fear conditioning [52,53] , and is linked to episodic memory as well as language processing [54] .…”

Section: Discussionmentioning

confidence: 99%

Altered regional homogeneity in post-traumatic stress disorder: a restingstate functional magnetic resonance imaging study

et al. 2012

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Objective Little is known about the brain systems that contribute to vulnerability to post-traumatic stress disorder (PTSD). Comparison of the resting-state patterns of intrinsic functional synchronization, as measured by functional magnetic resonance imaging (fMRI), between groups with and without PTSD following a traumatic event can help identify the neural mechanisms of the disorder and targets for intervention. Methods Fifty-four PTSD patients and 72 matched traumatized subjects who experienced the 2008 Sichuan earthquake were imaged with blood oxygen level-dependent (BOLD) fMRI and analyzed using the measure of regional homogeneity (ReHo) during the resting state. Results PTSD patients presented enhanced ReHo in the left inferior parietal lobule and right superior frontal gyrus, and reduced ReHo in the right middle temporal gyrus and lingual gyrus, relative to traumatized individuals without PTSD. Conclusion Our findings showed that abnormal brain activity exists under resting conditions in PTSD patients who had been exposed to a major earthquake. Alterations in the local functional connectivity of cortical regions are likely to contribute to the neural mechanisms underlying PTSD.

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Positron Emission Tomography Measurement of Cerebral Metabolic Correlates of Yohimbine Administration in Combat-Related Posttraumatic Stress Disorder

Abstract: These findings are consistent with our previous hypothesis of enhanced norepinephrine release in the brain with yohimbine in patients with PTSD.

Cited by 277 publications

References 80 publications

Enhanced noradrenergic activity in the amygdala contributes to hyperarousal in an animal model of PTSD

Enhanced noradrenergic activity in the amygdala contributes to hyperarousal in an animal model of PTSD

Reduced GABAA benzodiazepine receptor binding in veterans with post-traumatic stress disorder

Altered regional homogeneity in post-traumatic stress disorder: a restingstate functional magnetic resonance imaging study

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