Browsing by Author "Viljoen, Monet"

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    Anxiety : an overlooked confounder in the characterisation of chronic stress-related conditions?
    (Public Library of Science, 2020-04-16) Viljoen, Monet; Benecke, Rohan M.; Martin, Lindi; Adams, Rozanne C. M.; Seedat, Soraya; Smith, Carine
    Although anxiety disorders are among the most prevalent of psychiatric disorders, childhood trauma-related studies seldom consider anxiety proneness as distinct aetiological contributor. We aimed to distinguish between trauma- and anxiety-associated physiological profiles. South African adolescent volunteers were categorised for trauma exposure (CTQ, mean score 39±11) and anxiety proneness (AP)(CASI, mean score 37±7, STAI-T, mean score 41±8). Circulating hormone and leukocyte glucocorticoid receptor levels, as well as leukocyte functional capacity, were assessed. AP was associated with lower DHEAs (P<0.05) and higher leukocyte GR expression (P<0.05). DHEAs was also negatively correlated with anxiety sensitivity (CASI, P<0.05). In conclusion, AP may have more predictive power than trauma in terms of health profile. Increased glucocorticoid sensitivity previously reported after trauma, may be a unique function of anxiety and not trauma exposure per se. DHEAs concentration was identified as potentially useful marker for monitoring progressive changes in HPA-axis sensitivity and correlated with psychological measures of anxiety.
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    Correlations between stress-associated anxiety and physiological determinants of health in adolescents
    (Stellenbosch : Stellenbosch University, 2016-03) Viljoen, Monet; Smith, Carine; Seedat, Soraya; Stellenbosch University. Faculty of Science. Dept. of Physiological Sciences.
    ENGLISH ABSTRACT: Anxiety disorders are among the most prevalent of psychiatric disorders across age groups, with onset typically in childhood or early adolescence, and risk for developing an anxiety disorder increasing with trauma/childhood maltreatment. Little is known about biomarkers of resilience/vulnerability in relation to subclinical anxiety, especially when trauma-exposed adolescents are implicated. Therefore, better elucidation of the neuro-endocrine and -immunological underpinnings relative to anxiety and trauma, may highlight specific avenues to target with more effective diagnosis, monitoring and/or treatment strategies in the context of youth at risk for later development of anxiety disorders. Thus, our aims were to elucidate the central and peripheral neuroendocrine and immunological profiles in association with anxiety proneness, in comparison to childhood trauma, in older adolescents, and to assess potential outcome modulators. A total of 43 participants, aged 15-18, were selected from an initial cohort of 1149 adolescents. Participants were delineated into four groups based on levels of anxiety proneness and trauma exposure, using questionnaires and a structured diagnostic interview. Blood obtained from each participant was analysed for an HPA-axis hormone profile (cortisol, prolactin, testosterone and dehydroepiandrosterone-sulphate (DHEAs) and immune status (total white blood cell count, leukocyte glucocorticoid receptor (GR) expression and serum cytokine and myeloperoxidase (MPO) levels). Resilience (coping capacity), self-esteem and handedness were assessed via questionnaires. Verbal- and visuospatial working memory, as well as executive neurocognitive function, were assessed by means of the administration of neurocognitive tests. A structural Magnetic Resonance Imaging (MRI) was performed to determine left versus right grey matter volumes of the thalamus, amygdala, hippocampus, and Prefrontal cortex (PFC). Finally, HPA-axis responsivity and concurrent state anxiety to an in vivo Bexamethasone suppression test, in conjunction with as a psychosocial stress test (TSST), were assessed. In terms of neurophysiological maladaptations, main findings included a relatively larger association with anxiety proneness, compared to childhood maltreatment. Specifically, anxiety proneness was associated with poorer neurocognitive function, increased right amygdala volume, lower serum DHEAs levels, lower peripheral leukocyte counts, and increased GR expression. In terms of potential outcome modifying factors (OMFs), resilience and self-esteem were affected by trauma, but not anxiety proneness, while a higher degree of right handedness was associated with poorer neurophysiological outcomes. Furthermore, increased serum IL-12p70 and MPO (suggesting relatively more pro-inflammatory state) were associated with anxiety scales and emotional/physical abuse. Also, better PFC neurocognitive function and larger left PFC volumes were associated with better physiological outcome as indicated by levels of GR expression and DHEAs. In conclusion, this is the first study to have investigated neurophysiological adaptations, as well as psycho-physiological responses to HPA-axis suppression and a psychosocial stress test, in association with anxiety proneness and trauma exposure, in adolescents of low socio-demographic background. Results suggest for the study population, a) chronic hypo-activity and acute hypo-reactivity of the lower HPA-axis, b) neurophysiological perturbations associated relatively closely with anxiety proneness, when compared to trauma exposure, c) central correlates associated with physiological outcome, and d) a higher degree of consistent right handedness to be a potential marker of vulnerability in terms of neurophysiology and anxiety.
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    An integrative approach to the effect of interleukin-6 on adaptation to restraint stress in rats
    (Stellenbosch : University of Stellenbosch, 2009-12) Viljoen, Monet; Smith, Carine; University of Stellenbosch. Faculty of Science. Dept. of Physiological Sciences.
    ENGLISH ABSTRACT: Bi-directional communication exists between HPA-axis activation and interleukin-6 (IL-6). However, the relative contribution of centrally versus peripherally secreted IL- 6 remains unclear, especially under psychological stress conditions. We hypothesised that the HPA response to mild psychological stress is dependent on IL- 6, both centrally and peripherally. 120 male Wistar rats were divided into four groups, depending on whether they received an anti-IL-6 antibody (Ab) (2μg/ml/kg body weight) or a placebo (sterile saline) injection and whether or not they were subjected to 1 hour of restraint stress for 1, 2 or 3 days. Rats were euthanized 24 hours after stress exposure. Plasma corticosteroid (GC) levels remained significantly increased 24 hours after a single stress exposure (control placebo (CP) versus stress placebo (SP): p < 0.05). The undetectable plasma IL-6 levels evident across all groups may be explained by the short half-life of IL-6. Plasma IL-1β levels decreased when IL-6 was blocked in unstressed animals (CP versus CAb: p < 0.05), suggesting a role for IL-6 in the maintenance of IL-1β levels under tonic physiological conditions. At tissue level, pituitary gland mass increased significantly at time point 2, independently of stress when blocking IL-6 (CAb: p < 0.05). This suggests that when normal homeostasis is threatened, immediate adaption or at least compensation may occur. It was observed that GR, IL-1β, IL-1βR, IL-6, IL-6R and GABAARα1 showed no response to stress alone in the pituitary. It is therefore more likely that resistance to adaptation exists centrally. IL-1β and IL-1βR (p < 0.05) and GABAARα1 (p < 0.005) expression increased in the CAb group in the pituitary, again suggesting a role for IL-6 under control conditions. In terms of the adrenal, blocking IL-6 resulted in decreased glandular mass at time point 1, independent of stress (CAb and SAb: p < 0.005). The up-regulation in GR expression seen in CAb and SAb (p < 0.05) may be the effect of a compensatory mechanism to increase IL-6 dependent bioactivity of GCs. The fact that expression of IL-6, IL-6R, IL-1β and IL- 1βR consistently increased in the Ab groups, and mostly in the zona fasciculata and zona reticularis, suggests that lack of local direct negative cytokine feedback occurred in response to very low plasma IL-6 levels and that this contributes more than GCs in the down-regulation of inflammatory cytokine release. In conclusion, consistent effects of the Ab were apparent in the tissues investigated, even in control conditions, suggesting that IL-6 plays a role in the maintenance of basal homeostasis, including its regulation of the response to psychological stress. We found differential regulation in terms of cytokines and GCs when comparing peripheral versus central effects of stress and Ab, as well as the levels of cytokines in the blood compartment, compared to within tissues.