Elevated plasma corticotrophin-releasing hormone levels in veterans with posttraumatic stress disorder

Kloet, Carien S. de; Vermetten, Eric; Geuze, Elbert; Lentjes, Eef G.W.M.; Heijnen, Cobi J.; Stalla, G. K.; Westenberg, H.G.M.

doi:10.1016/s0079-6123(07)67025-3

Cited by 105 publications

(55 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Regardless of the equivocal nature of findings describing differences in basal cortisol levels in individuals with PTSD, more consistent are the findings that PTSD is associated with enhanced glucocorticoid negative-feedback inhibition of the HPA axis as evidenced by increased suppression of cortisol levels following a dexamethasone-suppression test (Yehuda et al, 1995). Heightened levels of peripheral and central corticotropin-releasing hormone (CRH; Baker et al, 2005;de Kloet et al, 2008) and elevated glucocorticoid receptor (GR) expression levels in lymphocytes (Matic et al, 2013) occur in tandem with enhanced glucocorticoid sensitivity in PTSD.…”

Section: Mechanisms Of Increased Inflammation In Fearand Anxiety-basementioning

confidence: 99%

Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond

Michopoulos

Powers

Gillespie

et al. 2016

Neuropsychopharmacol

544

376

View full text Add to dashboard Cite

The study of inflammation in fear-and anxiety-based disorders has gained interest as growing literature indicates that proinflammatory markers can directly modulate affective behavior. Indeed, heightened concentrations of inflammatory signals, including cytokines and C-reactive protein, have been described in posttraumatic stress disorder (PTSD), generalized anxiety disorder (GAD), panic disorder (PD), and phobias (agoraphobia, social phobia, etc.). However, not all reports indicate a positive association between inflammation and fear-and anxiety-based symptoms, suggesting that other factors are important in future assessments of inflammation's role in the maintenance of these disorders (ie, sex, co-morbid conditions, types of trauma exposure, and behavioral sources of inflammation). The most parsimonious explanation of increased inflammation in PTSD, GAD, PD, and phobias is via the activation of the stress response and central and peripheral immune cells to release cytokines. Dysregulation of the stress axis in the face of increased sympathetic tone and decreased parasympathetic activity characteristic of anxiety disorders could further augment inflammation and contribute to increased symptoms by having direct effects on brain regions critical for the regulation of fear and anxiety (such as the prefrontal cortex, insula, amygdala, and hippocampus). Taken together, the available data suggest that targeting inflammation may serve as a potential therapeutic target for treating these fear-and anxiety-based disorders in the future. However, the field must continue to characterize the specific role pro-inflammatory signaling in the maintenance of these unique psychiatric conditions.

show abstract

Section: Mechanisms Of Increased Inflammation In Fearand Anxiety-basementioning

confidence: 99%

Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond

Michopoulos

Powers

Gillespie

et al. 2016

Neuropsychopharmacol

544

376

View full text Add to dashboard Cite

show abstract

“…Physiologically, PTSD patients experience hyperarousal, hypervigilance, and exaggerated startle responses and insomnia. Patients with severe PTSD also show hypothalamic-pituitary-adrenal (HPA) alterations such as elevated corticotropin-releasing factor (CRF) levels (Bremner et al, 1997;de Kloet et al, 2008), blunted adrenocorticotropic hormone (ACTH) response (Ströhle et al, 2008;Yehuda et al, 2004), and hypocortisolemia (for review, see Yehuda, 2009). …”

Section: Introductionmentioning

confidence: 99%

Susceptibility to PTSD-Like Behavior Is Mediated by Corticotropin-Releasing Factor Receptor Type 2 Levels in the Bed Nucleus of the Stria Terminalis

Lebow¹,

Neufeld-Cohen²,

Kuperman³

et al. 2012

J. Neurosci.

122

View full text Add to dashboard Cite

Posttraumatic stress disorder (PTSD) is a debilitating disease, which affects 8 -10% of the population exposed to traumatic events. The factors that make certain individuals susceptible to PTSD and others resilient are currently unknown. Corticotropin-releasing factor receptor type 2 (CRFR2) has been implicated in mediating stress coping mechanisms. Here, we use a physiological PTSD-like animal model and an in-depth battery of tests that reflect the symptomology of PTSD to separate mice into subpopulations of "PTSD-like" and "Resilient" phenotypes. PTSD-like mice are hypervigilant, hyperalert, insomniac, have impaired attention and risk assessment, as well as accompanying attenuated corticosterone levels. Intriguingly, PTSD-like mice show long-term robust upregulation of BNST-CRFR2 mRNA levels, and BNST-CRFR2-specific lentiviral knockdown reduces susceptibility to PTSD-like behavior. Additionally, using a BNST mRNA expression array, PTSD-like mice exhibit a general transcriptional attenuation profile, which was associated with upregulation of the BNST-deacetylation enzyme, HDAC5. We suggest PTSD to be a disease of maladaptive coping.

show abstract

“…CRF is a neuropeptide that is released in the brain in response to stress (Koob, 1999). Administration of CRF produces many of the same physiological and behavioral effects as stress in people and laboratory animals (Hauger et al, 2009), and people with stress-related psychiatric illness have higher levels of CRF in cerebrospinal fluid (CSF) and blood (Bremner et al, 1997;Sautter et al, 2003;de Kloet et al, 2008). Although much is known about the neural mechanisms by which CRF regulates stress (Bangasser and Valentino, 2012), it has remained difficult to develop clinically effective antistress agents that act directly at CRF receptors (Zorrilla and Koob, 2010).…”

Section: Introductionmentioning

confidence: 99%

Corticotropin-Releasing Factor (CRF)-Induced Disruption of Attention in Rats Is Blocked by the κ-Opioid Receptor Antagonist JDTic

Veer

Yano

Carroll

et al. 2012

Neuropsychopharmacol

View full text Add to dashboard Cite

Stress often disrupts behavior and can lead to psychiatric illness. Considerable evidence suggests that corticotropin-releasing factor (CRF) plays an important role in regulating the effects of stress. CRF administration produces stress-like effects in humans and laboratory animals, and CRF levels are elevated in individuals with stress-related illness. Recent work indicates that k-opioid receptor (KOR) antagonists can block CRF effects, raising the possibility that at least some of the effects of stress are mediated via KORs. Here we examined the effects of CRF on performance in the 5-choice serial reaction time task (5CSRTT), a test used to quantify attention in rodents, as well as functional interactions between CRF and KORs. Male Sprague-Dawley rats were trained in the 5CSRTT and then each was implanted with an intracerebroventricular (ICV) cannula. After recovery and restabilization of performance, they received a single intraperitoneal (IP) injection of vehicle or JDTic (10 mg/kg), a KOR antagonist with long-lasting (414 days) effects. In subsequent sessions, rats received ICV infusions of CRF (0.25-1.0 mg) or vehicle and were tested 60 min later. CRF dose-dependently disrupted performance as reflected by decreases in correct responding, increases in omission errors, increases in latencies to respond correctly, and increases in time to complete the session. JDTic attenuated each of these CRF-induced deficits while having no effects on its own. The persistent ability of JDTic to disrupt KOR function was confirmed using the tail immersion assay. These findings indicate that KOR antagonists can prevent acute stress-related effects that degrade performance in tasks requiring attention.

show abstract

Elevated plasma corticotrophin-releasing hormone levels in veterans with posttraumatic stress disorder

Cited by 105 publications

References 14 publications

Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond

Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond

Susceptibility to PTSD-Like Behavior Is Mediated by Corticotropin-Releasing Factor Receptor Type 2 Levels in the Bed Nucleus of the Stria Terminalis

Corticotropin-Releasing Factor (CRF)-Induced Disruption of Attention in Rats Is Blocked by the κ-Opioid Receptor Antagonist JDTic

Contact Info

Product

Resources

About