Assessment of HPA-axis function in posttraumatic stress disorder: Pharmacological and non-pharmacological challenge tests, a review

Kloet, Carien S. de; Vermetten, Eric; Geuze, Elbert; Kavelaars, Annemieke; Heijnen, Cobi J.; Westenberg, H.G.M.

doi:10.1016/j.jpsychires.2005.08.002

Cited by 428 publications

(257 citation statements)

References 66 publications

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“…SKA2 methylation does not explain (mediate) the effects of childhood trauma on stress responsivity. The association of SKA2 methylation with several other HPA-axis related symptoms such as depression, neuroticism and suicide is consistent with the central role of stress-induced alterations in HPA-axis reactivity in PTSD and many other disorders (Mehta and Binder, 2012;De Kloet et al, 2006;Yehuda et al, 1991) and points to a role of SKA2 methylation as a general stress responsivity biomarker.…”

Section: Discussionsupporting

confidence: 73%

“…In their study, SKA2 methylation levels predicted suicide and were also related to lower levels of the stress hormone cortisol, consistent with a role in glucocorticoid receptor transactivation (Rice et al, 2008). As PTSD is associated with enhanced GR sensitivity and lower physiological hypothalamic-pituitary-adrenal (HPA) axis activity (Mehta and Binder, 2012;De Kloet et al, 2006;Yehuda et al, 1991) as well as with higher suicide rates (Schoenbaum et al, 2014), these findings raise the question whether the epigenetic SKA2 biomarker can also be of use for detecting who is at risk for PTSD. We hypothesize that changes in SKA2 methylation are dissimilar between PTSD-susceptible individuals and those who are resilient.…”

Section: Introductionmentioning

confidence: 82%

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SKA2 Methylation is Involved in Cortisol Stress Reactivity and Predicts the Development of Post-Traumatic Stress Disorder (PTSD) After Military Deployment

Boks

Rutten

Geuze

et al. 2015

Neuropsychopharmacol

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Genomic variation in the SKA2 gene has recently been identified as a promising suicide biomarker. In light of its role in glucocorticoid receptor transactivation, we investigated whether SKA2 DNA methylation influences cortisol stress reactivity and is involved in the development of post-traumatic stress disorder (PTSD). Increased SKA2 methylation was significantly associated with lower cortisol stress reactivity in 85 healthy individuals exposed to the Trier Social Stress Test (B = − 173.40, t = − 2.324, p-value = 0.023). Next, we observed that longitudinal decreases in SKA2 methylation after deployment were associated with the emergence of post-deployment PTSD symptoms in a Dutch military cohort (N = 93; B = − 0.054, t = − 3.706, p-value = 3.66 × 10 − 4 ). In contrast, exposure to traumatic stress during deployment by itself resulted in longitudinal increases in SKA2 methylation (B = 0.037, t = 4.173, p-value = 6.98 × 10 − 5 ). Using predeployment SKA2 methylation levels and childhood trauma exposure, we found that the previously published suicide prediction rule significantly predicted post-deployment PTSD symptoms (AUC = 0.66, 95% CI: 0.53-0.79) with an optimal sensitivity of 0.81 and specificity of 0.91. Permutation analysis using random methylation loci supported these findings. Together, these data establish the importance of SKA2 for cortisol stress responsivity and the development of PTSD and provide further evidence that SKA2 is a promising biomarker for stress-related disorders including PTSD.

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Section: Discussionsupporting

confidence: 73%

Section: Introductionmentioning

confidence: 82%

SKA2 Methylation is Involved in Cortisol Stress Reactivity and Predicts the Development of Post-Traumatic Stress Disorder (PTSD) After Military Deployment

Boks

Rutten

Geuze

et al. 2015

Neuropsychopharmacol

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“…Of course, there is an extensive pre-clinical and clinical literature showing abnormalities in neuroendocrine function in PTSD, review of which is beyond the focus of this paper (de Kloet et al, 2006;Krystal and Neumeister, 2009). Plasma melatonin levels collected 48 h after a trauma in Australian troops are reported to predict later PTSD, but, a recent study that assessed polysomnography with simultaneous blood sampling in returning Dutch troops observed no PTSD-related plasma melatonin abnormalities, despite sleep disturbance van Liempt et al, 2013).…”

Section: Clinicalmentioning

confidence: 99%

“…Serum levels of melatonin can probably contribute to long-term sleep disturbances in TBI patients (Seifman et al, 2014). It has been observed that pituitary dysfunction may be one of the consequences of blast TBI (Baxter et al, 2013) and this observation should be analyzed also in experimental models for blast.Of course, there is an extensive pre-clinical and clinical literature showing abnormalities in neuroendocrine function in PTSD, review of which is beyond the focus of this paper (de Kloet et al, 2006;Krystal and Neumeister, 2009). Plasma melatonin levels collected 48 h after a trauma in Australian troops are reported to predict later PTSD, but, a recent study that assessed polysomnography with simultaneous blood sampling in returning Dutch troops observed no PTSD-related plasma melatonin abnormalities, despite sleep disturbance van Liempt et al, 2013).…”

mentioning

confidence: 99%

The role of biomarkers and MEG-based imaging markers in the diagnosis of post-traumatic stress disorder and blast-induced mild traumatic brain injury

Huang

Risling

Baker

2016

Psychoneuroendocrinology

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SummaryBackground: Pervasive use of improvised explosive devices (IEDs), rocket-propelled grenades, and land mines in the recent conflicts in Iraq and Afghanistan has brought traumatic brain injury (TBI) and its impact on health outcomes into public awareness. Blast injuries have been deemed signature wounds of these wars. War-related TBI is not new, having become prevalent during WWI and remaining medically relevant in WWII and beyond. Medicine's past attempts to accurately diagnose and disentangle the pathophysiology of war-related TBI parallels current lines of inquiry and highlights limitations in methodology and attribution of symptom etiology, be it organic, psychological, or behavioral. New approaches and biomarkers are needed. Preclinical: Serological biomarkers and biomarkers of injury obtained with imaging techniques represent cornerstones in the translation between experimental data and clinical observations. Experimental models for blast related TBI and PTSD can generate critical data on injury threshold, for example for white matter injury from acceleration. Carefully verified and validated models can be evaluated with gene expression arrays and proteomics to identify new candidates for serological biomarkers. Such models can also be analyzed with diffusion MRI and microscopy in order to identify criteria for detection of diffuse white matter injuries, such as DAI (diffuse axonal injury). The experimental models can also be analyzed with focus on injury outcome in brain stem regions, such as locus coeruleus or nucleus raphe magnus that can be involved in response to anxiety changes. * Corresponding author at: UCSD Radiology Imaging Laboratory, San Diego, CA 92121, USA. Tel.: +1 858 534 1254; fax: +1 8585346046. E-mail address: mxhuang@ucsd.edu (M. Huang). Clinical: Mild (and some moderate) TBI can be difficult to diagnose because the injuries are often not detectable on conventional MRI or CT. There is accumulating evidence that injured brain tissues in TBI patients generate abnormal low-frequency magnetic activity (ALFMA, peaked at 1-4 Hz) that can be measured and localized by magnetoencephalography (MEG). MEG imaging detects TBI abnormalities at the rates of 87% for the mild TBI, group (blast-induced plus non-blast causes) and 100% for the moderate group. Among the mild TBI patients, the rates of abnormalities are 96% and 77% for the blast and non-blast TBI groups, respectively. There is emerging evidence based on fMRI and MEG studies showing hyper-activity in the amygdala and hypo-activity in prefrontal cortex in individuals with PTSD. MEG signal may serve as a sensitive imaging marker for mTBI, distinguishable from abnormalities generated in association with PTSD. More work is needed to fully describe physiological mechanisms of post-concussive symptoms.Published by Elsevier Ltd. BackgroundBlast injuries are deemed the signature wounds of the first wars (Afghanistan and Iraq) of the 21st century (Lancet, 2007;Galarneau et al., 2008). According to a recent U.S. Department Veterans Affairs (DVA) ...

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“…A number of physiological differences are reported in persons with PTSD, including disturbances in neurological integration of the fear circuitry [34], reduced serotoninergic modulation of the fear response in key areas such as the amygdala [35], and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. Abnormal HPA axis function is often expressed by lower baseline cortisol levels and excessive suppression of the HPA axis by exogenous steroids [36][37][38]. Studies on blood pressure and other measures of sympathetic nervous system arousal at rest in patients with PTSD have been inconsistent but show increased resting heart rate and muscle tension.…”

Section: Initiating Effective Pharmacotherapymentioning

confidence: 99%

Pharmacotherapy for posttraumatic stress disorder: Review with clinical applications

Jeffreys

Capehart²,

Friedman³

2012

JRRD

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Abstract-Posttraumatic stress disorder (PTSD) is a prevalent psychiatric diagnosis among veterans and has high comorbidity with other medical and psychiatric conditions. This article reviews the pharmacotherapy recommendations from the 2010 revised Department of Veterans Affairs/Department of Defense Clinical Practice Guideline (CPG) for PTSD and provides practical PTSD treatment recommendations for clinicians. While evidence-based, trauma-focused psychotherapy is the preferred treatment for PTSD, pharmacotherapy is also an important treatment option. First-line pharmacotherapy agents include selective serotonin reuptake inhibitors and the selective serotonin-norepinephrine reuptake inhibitor venlafaxine. Second-line agents have less evidence for their usefulness in PTSD and carry a potentially greater side effect burden. They include nefazodone, mirtazapine, tricyclic antidepressants, and monoamine oxidase inhibitors. Prazosin is beneficial for nightmares. Benzodiazepines and antipsychotics, either as monotherapy or used adjunctively, are not recommended in the treatment of PTSD. Treating co-occurring disorders, such as major depressive disorder, substance use disorders, and traumatic brain injury, is essential in maximizing treatment outcomes in PTSD. The CPG provides evidence-based treatment recommendations for treating PTSD with and without such cooccurring disorders.

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Assessment of HPA-axis function in posttraumatic stress disorder: Pharmacological and non-pharmacological challenge tests, a review

Cited by 428 publications

References 66 publications

SKA2 Methylation is Involved in Cortisol Stress Reactivity and Predicts the Development of Post-Traumatic Stress Disorder (PTSD) After Military Deployment

SKA2 Methylation is Involved in Cortisol Stress Reactivity and Predicts the Development of Post-Traumatic Stress Disorder (PTSD) After Military Deployment

The role of biomarkers and MEG-based imaging markers in the diagnosis of post-traumatic stress disorder and blast-induced mild traumatic brain injury

Pharmacotherapy for posttraumatic stress disorder: Review with clinical applications

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