Wow. I can't believe how well this fits...
Personal history: Years and years of high chronic stress.
Chronic stress can alter your bodies hypothalamus-pituitary-adrenal function/regulation. Most studies focus on cortisol in the process but aldosterone is also greatly affected in this case.
http://content.karger.com/ProdukteDB/pr ... 323953.pdf
Studies on MS Onset
In the study by Liu et al. [23] , MS patients reported
more negative life events and family problems and less
utilization of social support 3 years before disease diagnosis
than healthy controls. The MS group suffered more
often from negative emotions such as symptoms of depression,
anxiety, obsession, phobia, tense interpersonal
relationship and somatization disorder, all of which were
positively correlated with negative life events and family
problem scores, and negatively with utilization of social
support. Personality did not differ among groups. In a
large retrospective cohort study in the Danish population,
parents who had lost a child younger than 18 years
were at greater risk of MS (hazard ratio, HR: 1.56; 95% CI:
http://www.fatiguesymposium.ca/pdf/Just ... static.pdf
Page 3 of 15 in this document shows graphical illustration of different physiological responses to stress. Prolonged response could lead to chronically elevated aldosterone.
3. Allostatic load model
Allostatic load (AL) represents the ‘wear and tear’ the body
experiences when repeated allostatic responses are activated
during stressful situations (McEwen and Stellar, 1993). Real or
interpreted threats to homeostasis initiate the sympathetic–
adrenal–medullary (SAM) axis release of catecholamines and the
hypothalamic–pituitary–adrenal (HPA) axis secretion of glucocorticoids
that mobilize energy necessary for fight-or-flight responses
(Sapolsky et al., 2000). Coordination of allostasis therefore depends
on the brain’s evaluation of threat (hippocampal, amygdaloid, and
prefrontal cortical regulation); (Herman et al., 2005; McEwen,
2007) and execution of physiological responses. The perception of
threat and mobilization of these allostatic mechanisms are
fundamentally shaped by individual differences in constitutional
(genetics, development, experience), behavioral (coping and
health habits), and historical (trauma/abuse, major life events,
stressful environments) factors that ultimately determine one’s
resiliency to stress (Fig. 1; McEwen, 1998a).
While adaptive acutely, chronic over-activation of SAM- and
HPA-axis products induce a ‘domino effect’ on interconnected
biological systems that overcompensate and eventually collapse
themselves, leaving the organism susceptible to stress-related
diseases (Korte et al., 2005; Lupien et al., 2006; McEwen, 1998b).
Brain changes associated with chronic stress and AL (e.g., synaptic
and dendritic remodeling, suppressed neurogenesis, structural
atrophy/hypertrophy) further diminish the body’s ability to
cognitively process and physiologically respond to stressors
(McEwen, 2000b). These contribute to pathophysiological allostatic
states (Fig. 2) that reflect response patterns in which allostatic
systems are overactivated and/or dysregulated (McEwen, 2003b).
These processes are rooted in biopsychosocial antecedents
integrated within the AL model that postulates a sequential chain
of dysregulation in multiple systemic mediators.
A key feature of allostasis, AL, and ultimately allostatic overload
is that multiple mediators of adaptation are involved and
interconnected in a non-linear network. Each mediator system
produces biphasic effects and is regulated by other mediators,
often in reciprocal fashion, leading to non-linear effects upon many
organ systems of the body (McEwen, 1998a). At first, prolonged
secretion of the stress hormones epinephrine, norepinephrine, and
cortisol (antagonized by dehydroepiandosterone) can falter in
their ability to protect the distressed individual and instead begin
to damage the brain and body (McEwen, 2006a). Stress hormones
and their antagonists, in conjunction with pro- and antiinflammatory
cytokines (e.g., interleukin-6, tumor necrosis factor-
alpha) represent the AL biomarkers referred to as the primary
mediators (McEwen, 2003b). Synergistic effects of these molecules
exert primary effects on cellular activities (enzyme, receptor, ion
channel, genomic) that compromise the physiological integrity of
allostatic mechanisms. Over time, subsidiary biological systems
compensate for the over and/or under production of primary
mediators and in turn shift their own operating ranges to maintain
abated chemical, tissue, and organ functions. This prodromal stage
is referred to as the secondary outcomes, whereby metabolic (e.g.,
insulin, glucose, total cholesterol, high density lipoprotein
cholesterol, triglycerides, visceral fat depositing), cardiovascular
(e.g., systolic and diastolic blood pressure), and immune (e.g.,
fibrinogen, c-reactive protein (CRP)) parameters reach sub-clinical
levels. The final stage of AL progression is allostatic overload,
whereby the culmination of physiological dysregulations leads to
disordered, diseased, and deceased endpoints referred to as tertiary
outcomes.
The AL model proposes that by measuring the multi-systemic
interactions among primary mediators and effects, in conjunction
to sub-clinically relevant biomarkers representing secondary
outcomes, biomedical advances can be made in the detection of
individuals at high risk of tertiary outcomes (McEwen, 2000a;
McEwen and Seeman, 1999). Physicians routinely incorporate
many of these biomarkers already, except attention is largely
placed on values reaching clinically significant levels. By incorporating
and integrating additional biomarkers, identifying preclinical
values, and triangulating methods with various other
measures if feasible (e.g., psychosocial, genotypes, and phenotypes),
greater prediction of pathologies can be achieved. Because
mediators leading to AL and disease susceptibilities interact in a
non-linear manner whereby fluctuations in values induce compensatory
remediation over time (Fig. 3), delineating time-courses
of dysregulation is difficult (McEwen, 2008). Quantifying AL at a
biological level, let alone with respect to the multiplicity of
psychosocial modulators has thus represented a significant
challenge. Nonetheless, advances over the last decade have helped
pave the way to a greater understanding of the winding road to AL.
http://www.sciencedirect.com/science/ar ... ldosterone: A forgotten mediator of the relationship between psychological stress and heart disease
Laura D. Kubzanskya, b, , ,
Gail K. Adlera, b
Abstract
Numerous studies support the notion that cumulative exposure to chronic stress is a risk factor for cardiovascular disease (CVD). Various stress-related hormones have been proposed as potential mediators of the relationship between psychological stress and CVD, including catecholamines and more indirectly, cortisol. Somewhat surprisingly, although aldosterone is also released in response to hypothalamic–pituitary–adrenal (HPA) axis activation, it has not been considered as relevant for this relationship. In the present review we will consider aldosterone as a potentially important mediator of the relationship between negative affective states and CVD. First, we will briefly review the known functions and roles of aldosterone, and then consider its actions in both the brain and the periphery. We will then review the available literature on the role of aldosterone in CVD, and also consider links between aldosterone and various forms of chronic psychological stress. Finally we will present an integrated model of how aldosterone may mediate effects of chronic stress on CVD, recommend new directions for research, and identify important methodological and design issues for this work.
Fig. 1. Effect of ACTH infusion on serum levels of cortisol (μg/dl) (open circles) and aldosterone (ng/dl) (squares). 13 healthy pre-menopausal women on ad lb diets received an intravenous infusion of ACTH at sequential doses of 0.00, 0.00, 0.05, 0.15, 0.50, 1.50 and 5 mIU/kg/30 min. 24 h urinary sodium levels were (156 ± 24 mEquib./24 h). Cortisol data was reported previously (Adler et al., 1999).
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However, I don't want to hyperfocus on ccsvi because I think (this could change after reading his paper) ccsvi is only a component of MS and I am trying to look at a bigger picture. 