A lot of these symptoms could be related to what I have been reading up on lately, The hormone Hepcidin and it's relationship to inflammation and mood. I haven't seen hepcidin mentioned here a lot if at all. It is a hormone that has been called the master regulator of iron homeostasis in the human body. It can cause Hypoferremia in rats when faced with psychological stress as shown in this study.
<h1 class="title">Psychological stress induces hypoferremia through the IL-6-hepcidin axis in rats.</h1>Zhao M
, Chen J
, Wang W
, Wang L
, Ma L
, Shen H
, Li M
Department of Naval Medicine, Second Military Medical University, 800 Xiangxin Road, Shanghai 200433, PR China.
Anemia is a widespread public health problem. The psychological stress decreases serum iron level and inhibits erythropoiesis. However, the molecular mechanisms involved, leading to iron mal-regulation are not well known. We used a communication box paradigm to induce psychological stress and found that serum iron level decreased after 3d while liver iron storage increased after 7d. Moreover, psychological stress up-regulated exp
ressions of interleukin-6 (IL-6) and hepcidin, while down-regulating ferroportin exp
ression after 3d. These changes were blocked by the injection of IL-6 monoclonal antibody. In conclusion, the IL-6-hepcidin axis is up-regulated by psychological stress in rats, resulting in hypoferremia and increase of hepatic iron storage
What is interesting about this is the relationship between the inflammatory cytokine interleukin 6 and hepcidin as the role that this cytokine plays in many diseases is well known. This reaction of the rat made more sense when I read about the link between iron and healthy dopamine levels. It would make sense from an evolutionary point of view for an animal to lower its dopamine production when confronted by a pathogen so as to just settle down and rest while the body fights off the infection. It seems from this study that it took 3 days for this to occur from a psychological stress since it definitely wouldn't be an advantage in an acute psychological stress. The link between IL-6 and hepcidin is well documented now. In my teens through my mid twenties I had brutal Restless leg which along with Adhd has been linked to a problem with low iron even when iron stores seem normal. The next study shows how quickly a pathogen can cause the deterioration in mood of a human. I wonder how much of this is due to upregulation of hepcidin due to interluekin 6?
<h1 class="title">Inflammation causes mood changes through alterations in subgenual cingulate activity and mesolimbic connectivity.</h1>Harrison NA
, Brydon L
, Walker C
, Gray MA
, Steptoe A
, Critchley HD
Wellcome Trust, Centre for Neuroimaging, Institute of Cognitive Neuroscience, UCL, 17 Queen Square, London WC1N 3AR, UK. firstname.lastname@example.org
BACKGROUND: Inflammatory cytokines are implicated in the pathophysiology of depression. In rodents, systemically administered inflammatory cytokines induce depression-like behavior. Similarly in humans, therapeutic interferon-alpha induces clinical depression in a third of patients. Conversely, patients with depression also show elevated pro-inflammatory cytokines. OBJECTIVES: To determine the neural mechanisms underlying inflammation-associated mood change and modulatory effects on circuits involved in mood homeostasis and affective processing. METHODS: In a double-blind, randomized crossover study, 16 healthy male volunteers received typhoid vaccination or saline (placebo) injection in two experimental sessions. Mood questionnaires were completed at baseline and at 2 and 3 hours. Two hours after injection, participants performed an implicit emotional face perception task during functional magnetic resonance imaging. Analyses focused on neurobiological correlates of inflammation-associated mood change and affective processing within regions responsive to emotional exp
ressions and implicated in the etiology of depression. RESULTS: Typhoid but not placebo injection produced an inflammatory response indexed by increased circulating interleukin-6 and significant mood reduction at 3 hours. Inflammation-associated mood deterioration correlated with enhanced activity within subgenual anterior cingulate cortex (sACC) (a region implicated in the etiology of depression) during emotional face processing. Furthermore, inflammation-associated mood change reduced connectivity of sACC to amygdala, medial prefrontal cortex, nucleus accumbens, and superior temporal sulcus, which was modulated by peripheral interleukin-6. CONCLUSIONS: Inflammation-associated mood deterioration is reflected in changes in sACC activity and functional connectivity during evoked responses to emotional stimuli. Peripheral cytokines modulate this mood-dependent sACC connectivity, suggesting a common pathophysiological basis for major depressive disorder and sickness-associated mood change and depression
This is just the tip of the iceberg there is lots of information out there. I find the relationship between inflammation,hepcidin and dopamine very interesting. There are so many things that can cause inflammation out there and combined with the prolonged psychological stress that many people are under it is no wonder so many people are suffering. There has been recent research I believe showing rapid antidepressant effects from a cox2 inhibitor. Any thoughts?