Psychoneuroendocrinology
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Psychoneuroendocrinology · Jul 2012
Randomized Controlled TrialSocial subordination produces distinct stress-related phenotypes in female rhesus monkeys.
Social subordination in female macaques is imposed by harassment and the threat of aggression and produces reduced control over one's social and physical environment and a dysregulation of the limbic-hypothalamic-pituitary-adrenal axis resembling that observed in people suffering from psychopathologies. These effects support the contention that this particular animal model is an ethologically relevant paradigm in which to investigate the etiology of stress-induced psychological illness related to women. Here, we sought to expand this model by performing a discriminate analysis (DA) on 33 variables within three domains; behavioral, metabolic/anthropomorphic, and neuroendocrine, collected from socially housed female rhesus monkeys in order to assess whether exposure to social subordination produces a distinct phenotype. ⋯ Serum oxytocin, CSF DOPAC and serum PACAP were all significantly higher in dominant females. ROC curve analysis accurately predicted social status in all three domains. Results suggest that socially house rhesus monkeys represent a cogent animal model in which to study the physiology and behavioral consequences of chronic psychosocial stress in humans.
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The role of cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) signaling in the molecular pathways involved in fear and memory is well established. Prior studies in our lab reported that transgenic mice with an inactivating mutation in Prkar1a gene (codes for the 1-alpha regulatory subunit (R1α) of PKA) exhibited behavioral abnormalities including anxiety and depression. In the present study, we examined the role of altered PKA signaling on anxiety-like behaviors in Prkar1a(+/-) mice compared to wild-type (WT) littermates. ⋯ Results of hotplate testing showed no genotype effect however; the expected sex difference was noted. Analysis of PKA activity showed the loss of one Prkar1a allele led to an increase in basal and cAMP-stimulated kinase activity in both the basolateral and central amygdala. These results suggest that the alteration in PKA signaling in Prkar1a(+/-) mice is not a ubiquitous effect; and supports the importance of cAMP/PKA pathway in neurobiological processes involved in anxiety and fear sensitization.
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Psychoneuroendocrinology · May 2012
Evidence for an association between an enhanced reactivity of interleukin-6 levels and reduced glucocorticoid sensitivity in patients with fibromyalgia.
Pain and fatigue have been identified as core symptoms of fibromyalgia syndrome (FMS). Since both symptoms are also characteristic of hypocortisolemic disorders, reduced cortisol levels have been thought to promote an exacerbation of these FMS core symptoms by an enhanced reactivity of interleukin-6 (IL-6) levels. The aim of the current study was to investigate the pathophysiologic relevance of reduced cortisol levels for manifestation of FMS core symptoms. ⋯ PPT measurement did induce three times higher cortisol and four times higher IL-6 levels in FMS patients, but no change in their ACTH levels. The enhanced IL-6 reactivity after PPT measurement was accompanied by an increase in the severity of FMS patients' pain and fatigue ratings. The findings of the present study provide evidence for the pathophysiologic relevance of a disturbed glucocorticoid receptor (GR) function, rather than reduced cortisol levels for the maintenance of FMS core symptoms.
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Psychoneuroendocrinology · Apr 2012
Comparative StudyCortisol levels in response to starting school in children at increased risk for social phobia.
Research on depression has identified hyperactivity of the HPA axis as a potential contributory factor to the intergenerational transmission of affective symptoms. This has not yet been examined in the context of social phobia. The current study compared HPA axis activity in response to a universal social stressor (starting school) in children of 2 groups of women: one with social phobia and one with no history of anxiety (comparison group). To determine specificity of effects of maternal social phobia, a third group of children were also examined whose mothers had generalised anxiety disorder (GAD). ⋯ A persistent stress response to school in the morning and afternoon is typical for all children, but children of mothers with social phobia also display atypical elevations in evening cortisol levels when at school--signalling longer-term disruption of the circadian rhythm in HPA axis activity. This is the first study to report HPA axis disruption in children at increased risk of developing social phobia. Future research should determine whether this represents a pathway for symptom development, taking early temperament into account.
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Psychoneuroendocrinology · Mar 2012
Neuroendocrine response to CRF stimulation in veterans with and without PTSD in consideration of war zone era.
Alterations in hypothalamic-pituitary-adrenal (HPA) axis activity have been observed in Gulf War veterans with posttraumatic stress disorder (PTSD) which differ from those observed in other veteran groups, raising the possibility that there is a unique neuroendocrine profile in this group of veterans. This study seeks to further characterize the effects of PTSD, military cohort (Vietnam, 1991 Gulf War, Operations Enduring Freedom/Iraqi Freedom (OEF/OIF)), and their interaction on the neuroendocrine response to synthetic corticotrophin-releasing factor (CRF) stimulation. ⋯ A uniform pattern of PTSD-related alterations in the response to intravenous CRF was not found. Rather, PTSD-related alterations were found only in veterans of the 1991 Gulf War, and were characterized by an enhanced pituitary response to CRF which may reflect increased sensitivity of pituitary corticotrophs or CRF hyposecretion. Together with previous neuroendocrine findings, the data suggest the HPA axis is dysregulated in Gulf War veterans in unique ways which may reflect the long-term effects of environmental exposures in addition to disease effects. Further work is needed to characterize these effects and their impact on long-term psychological and medical outcomes.