Paralimbic and Medial Prefrontal Cortical Involvement in Neuroendocrine Responses to Traumatic Stimuli (original) (raw)
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Psychoneuroendocrinology, 2003
Preclinical studies show that animals with a history of chronic stress exposure have increased hypothalamic-pituitary-adrenal (HPA) axis reactivity following reexposure to stress. Patients with posttraumatic stress disorder (PTSD) have been found to have normal or decreased function of the HPA axis, however no studies have looked at the HPA response to stress in PTSD. The purpose of this study was to assess cortisol responsivity to a stressful cognitive challenge in patients with PTSD related to childhood abuse. Salivary cortisol levels, as well as heart rate and blood pressure, were measured before and after a stressful cognitive challenge in * Corresponding author. Present address: patients with abuse-related PTSD (N = 23) and healthy comparison subjects (N = 18). PTSD patients had 61% higher group mean cortisol levels in the time period leading up to the cognitive challenge, and 46% higher cortisol levels during the time period of the cognitive challenge, compared to controls. Both PTSD patients and controls had a similar 66-68% increase in cortisol levels from their own baseline with the cognitive challenge. Following the cognitive challenge, cortisol levels fell in both groups and were similar in PTSD and control groups. PTSD patients appeared to have an increased cortisol response in anticipation of a cognitive challenge relative to controls. Although cortisol has been found to be low at baseline, there does not appear to be an impairment in cortisol response to stressors in PTSD. Published by Elsevier Science Ltd.
The brain and the stress axis: The neural correlates of cortisol regulation in response to stress
Neuroimage, 2009
The hypothalamic-pituitary-adrenal (HPA) axis is the major endocrine stress axis of the human organism. Cortisol, the final hormone of this axis, affects metabolic, cardiovascular and central nervous systems both acutely and chronically. Recent advances in neuroimaging techniques have led to the investigation of regulatory networks and mechanisms of cortisol regulation in the central nervous system in human populations. In the following review, results from human and animal studies are being presented that investigate the specific role of hippocampus (HC), amygdala (AG), prefrontal cortex (PFC), and brainstem nuclei in cortisol regulation in response to stress. In general, the types of stressors need to be distinguished when discussing the contributions of these structures in regulating the HPA axis. We propose a basic framework on how these structures communicate as a network to regulate cortisol secretion in response to psychological stress. Furthermore, we review critical studies that have substantially contributed to the literature. Possible future research avenues in the field of neuroimaging of cortisol regulation are discussed. In combination with investigations on genetic and environmental factors that influence the development of the HPA axis, this emerging new research will eventually allow the formulation of a more comprehensive framework of functional neuroanatomy of cortisol regulation.
Implications of Hypothalamic-Pituitary-Adrenal Axis Functioning in Posttraumatic Stress Disorder
Journal of the American Psychiatric Nurses Association, 2011
BACkgrounD: Cortisol secretions serve as the barometer of the hypothalamic-pituitary-adrenal (HPA) axis, which regulates and controls responses to stress. Studies of cortisol secretions in patients with posttraumatic stress disorder (PTSD) reveal inconsistent results. PurPoSe: Current research on HPA axis functioning in PTSD is examined to elucidate the neuroendocrine contributions in the disorder, identify current treatment's impact on the HPA axis, and consider implications for nursing care and areas for future research. FInDIngS: There is evidence for HPA dysregulation in PTSD, which contributes to widespread impairment in functions such as memory and stress reactivity and to physical morbidity via processes such as allostatic load. There is limited, but building, evidence that dehydroepiandrosterone (DHEA), which is released simultaneously with cortisol, may provide anti-glucocorticoid and neuroprotective effects. ConCluSIon: Current treatments such as selective serotonin reuptake inhibitors and psychotherapy may have a beneficial impact on the HPA axis in PTSD populations. Somatic approaches to treating PTSD have not yet been studied in relation to their impact on HPA axis parameters in PTSD patients. Treatment studies of DHEA or glucocorticoids have not yet used HPA axis endpoints. PTSD treatment studies that include measures of HPA axis target mechanisms and consider HPA axis regulation as an additional treatment outcome are warranted.
Sensitization of the Hypothalamic-Pituitary-Adrenal Axis in Posttraumatic Stress Disorder
Annals of the New York Academy of Sciences, 1997
Posttraumatic stress disorder (PTSD) is a psychiatric condition that can occur in individuals who have experienced traumatic events. The symptoms of PTSD were initially conceptualized as reflecting a natural process of adaptation to extraordinarily adverse life event~.l-~ However, in recent years prevalence studies have clarified that PTSD only occurs in a percentage of those exposed to trauma."' Furthermore, among trauma survivors who develop this disorder, a substantial proportion appear to show full remission of their symptoms over time.6 This observation demonstrates that chronic PTSD represents a specific type of adaptation to trauma, which may not necessarily reflect typical or even normative stress responsiveness.1°
Frontiers in psychology, 2017
Background: Although depression symptoms are often experienced by individuals who develop posttraumatic stress disorder (PTSD) following trauma exposure, little is know about the biological correlates associated with PTSD and depression co-morbidity vs. those associated with PTSD symptoms alone. Methods: Here we examined salivary cortisol responses to trauma activation in a sample of 60 survivors of the World Trade Center attacks on September 11, 2001. Participants recalled the escape from the attacks 7 months post 9/11. Salivary cortisol levels were measured before and after their recollection of the trauma. PTSD, depression, and somatic symptoms were also assessed. From the behavioral assessment scales, the participants were grouped into three conditions: those with comorbid PTSD and depressive symptoms, PTSD alone symptoms, or no-pathology. Results: Baseline and cortisol response levels differed between the comorbid, PTSD alone, and no-pathology groups. Individuals endorsing co-m...
Psychosomatic Medicine, 2006
The adrenal excretion of cortisol in animals is dependent on the production of corticotropin-releasing factor in the paraventricular nucleus of the hypothalamus. The a priori hypothesis of this study was that hypothalamic regional cerebral blood flow (rCBF) would correlate positively with salivary cortisol levels in patients with social anxiety disorder (SAD) during anxiety provocation. Another objective was to evaluate whether salivary cortisol levels correlated with rCBF in other brain areas. Method: Regional CBF was measured with oxygen-15-labeled water and positron emission tomography during a public speaking task before and after placebo treatment in 12 subjects with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-defined SAD. Cortisol concentrations in saliva were measured 15 minutes after the task. The a priori hypothesis of a salivary cortisol-dependent activation of the hypothalamus was studied with region-of-interest analysis. In addition, the covariation between rCBF and salivary cortisol was studied in the whole brain using the general linear model. Results: The region-of-interest analysis revealed a positive correlation between salivary cortisol and hypothalamic rCBF. In the whole brain analysis, a positive covariation between rCBF and salivary cortisol levels was found in a midbrain cluster encompassing the hypothalamus with its statistical maximum in the mamillary bodies. Negative covariations were observed in the medial prefrontal cortex as well as in the motor and premotor cortices. Conclusion: Like in animals, stress-induced cortisol excretion in humans may be inhibited by activity in the medial prefrontal cortex and enhanced by activity in the hypothalamus. Key words: rCBF, PET, cortisol, symptom provocation, hypothalamus, medial prefrontal cortex.
Fear potentiation is associated with hypothalamic–pituitary–adrenal axis function in PTSD
Psychoneuroendocrinology, 2010
A central problem in posttraumatic stress disorder (PTSD) is the inability to suppress fear under safe conditions. We have previously shown that PTSD patients cannot inhibit conditioned fear. Another relevant finding in PTSD is the hypersensitivity of the hypothalamic-pituitaryadrenal (HPA) axis feedback. Given their common neurobiological pathways, alterations in HPA function in PTSD may be associated with impaired fear inhibition. The present study examined the relationship between HPA axis function and fear-potentiated startle and inhibition of conditioned fear in trauma-exposed individuals. We used a conditional discrimination procedure (AX+/BXÀ), in which one set of shapes (AX+) was paired with aversive airblasts to the throat (danger signal), and the same X shape with a different shape (BXÀ) were presented without airblasts (safety signal). The paradigm also included a transfer of fear inhibition test (AB). In addition to fear-potentiated startle, blood was drawn for neuroendocrine analysis and the dexamethasone suppression test (DEX) was performed; cortisol and ACTH were assessed at baseline and post-DEX. Ninety highly traumatized individuals recruited from Grady Hospital in Atlanta, GA participated in the study. The sample was divided into those who met DSM-IV criteria for PTSD (n = 29) and Non-PTSD controls (n = 61) using the PTSD symptom scale (PSS). Both groups showed significant reduction in cortisol and ACTH levels after DEX. Subjects with PTSD had higher fear-potentiated startle to the safety signal, BXÀ (F(1,88) = 4.44, p < 0.05) and fear inhibition trials, AB (F(1,88) = 5.20, p < 0.05), both indicative of less fear inhibition in the presence of B, compared to control subjects. In addition, fearpotentiated startle to AX+, BXÀ, and AB was positively correlated with baseline and post-DEX ACTH in PTSD subjects. These results suggest that impaired fear inhibition and associated alterations in HPA feedback may reflect amygdala hyperactivity in subjects with PTSD. #
Can the neural–cortisol association be moderated by experience-induced changes in awareness?
Scientific Reports, 2015
Cortisol homeostasis is important for cognitive and affective functions that depend on cortisolsensitive brain regions including the hippocampus and prefrontal cortex. Recent studies have shown that training induces changes in the brain. We report the findings of a longitudinal study that verified the moderation effect of experience-induced changes in awareness on the neural-cortisol association in cortisol-sensitive brain regions. These findings provide the first piece of evidence that planned behavioral experience can moderate the neural-cortisol association. A range of changes in awareness was achieved in a sample of 21 Chinese participants, divided into two groups: Awarenessbased compassion meditation (ABCM) (n = 10) and relaxation (n = 11). We observed that changes in awareness were significant moderators of hippocampal-cortisol changes. Furthermore, a significant negative association between changes in plasma cortisol level and the resting-state synchrony of the right hippocampal and insular-frontal-operculum regions was observed. These novel findings shed light on the interrelationships between changes in hippocampal-cortisol levels and changes in awareness and preliminarily identify the neural underpinnings of interventions for cortisol-related abnormal functioning for further study. Neuroplasticity underlies changes in neural pathways and synapses of the human neural system, and it plays an important role in the modification of neural communication with the endocrine system to produce adaptive responses to life changes 1,2. In fact, the nervous and endocrine systems contribute to a large proportion of human bodily functions, and these two systems are interrelated via different pathways. One of the well-studied pathways is the hypothalamus-pituitary-adrenal (HPA) axis, which regulates peripheral cortisol levels. Disruption of cortisol homeostasis is associated with various cognitive and affective dysfunctions. For example, elevated plasma cortisol levels are associated with major depressive disorder 3 , and lower plasma cortisol levels may be associated with emotional numbing symptomatology in people with posttraumatic stress disorder 4. Cortisol also plays a role in neuroplasticity. The effect of peripheral cortisol levels on neuroplastic changes involves brain regions that express glucocorticoid receptors, such as the hippocampus 5. A recent study demonstrated that changes in peripheral cortisol levels under stress conditions have important implications on the functioning of neural structures of the default-mode network (DMN), including the hippocampus, which likely actively retrieves past experiences, anticipates future events 6 , and regulates our mind-wandering activity 7. Furthermore, the intake of hydrocortisone may affect resting-state functional coupling of neural substrates that are important
Role of Prefrontal Cortex Glucocorticoid Receptors in Stress and Emotion
Biological Psychiatry, 2013
Background-Stress-related disorders (e.g., depression) are associated with hypothalamicpituitary-adrenocortical axis dysregulation and prefrontal cortex (PFC) dysfunction, suggesting a functional link between aberrant prefrontal corticosteroid signaling and mood regulation.
Psychoneuroendocrinology, 2012
Whether glucocorticoids mediate medial prefrontal cortex (mPFC) regulation of the amygdala in humans remains unclear. In the current study we investigated whether cortisol levels under relatively stress-free circumstances are related to amygdala resting-state functional connectivity with the mPFC. Resting-state fMRI data were acquired from 20 healthy male participants. Salivary cortisol was sampled at multiple times throughout the experiment. The cortisol area under the curve increase (AUCi) was calculated as a measure of cortisol dynamics. Next, seed based correlations were employed on the resting-state fMRI data to reveal regions of amygdala functional connectivity related to variations in cortisol AUCi. The resulting statistical maps were corrected for multiple comparisons using cluster based thresholding (Z > 2.3, p < .05). Two regions in the mPFC showed decreasing negative functional connectivity with the amygdala when a lesser decrease in cortisol AUCi was observed: the perigenual anterior cingulate cortex and medial frontal pole (BA10). Although we initially showed a relation with cortisol AUCi, it seemed that the baseline cortisol levels were actually driving this effect: higher baseline cortisol levels related to stronger negative functional connectivity with the mPFC. Endogenous cortisol levels may modulate amygdala functional connectivity with specific regions in the mPFC, even under relatively stress-free circumstances. Our results corroborate previous findings from both animal and human studies, suggesting cortisol-mediated regulation of the amygdala by the mPFC. We propose that through this feedback mechanism the stress response might be adjusted, pointing to the putative role of cortisol in modulating stress-and, more generally, emotional responses. #