Kpavel, I have found. I'm glad that's only study is what I have read with my last brain cells left there.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3386509/
I have read the whole page. And that's the simple explanation of the situation:
I had been an extremely anxious person ---> desenstization of glucocrticoid receptors and loss of negative feedback ---> chronic stress shifted my immune system to the th2 also all my body homeostasized properly to compensate chronic stress ---> I took a few dose of fluoxetine ---> that bombarded everything in my body including glucocorticoid receptors ---> I left with hypocortisol/hypostress state and the immune system shifted to th1 ---> progressive brain damage, diabete(I have pretty much diabete symptoms, you know?), CFS, etc.
Also regarding to kynurenine metabolism, glucocorticoids are responsible of inducing the TDO enzyme. It's the enzyme responsible of degrading %95 of tryptophan.
Less TDO ---> more free tryptophan --> more serotonin --> more melatonin etc..
You understand? If you don't have the time to read the page, I have some quotes here.
"Components of the stress system such as norepinephrine (NE) and glucocorticoids appear to mediate a Th2 shift, while serotonin (5-HT) and melatonin might mediate a Th1 shift."
"Interestingly, some studies show that a hypoactive stress system may facilitate or sustain the Th1 shift in Th1-mediated diseases, such as rheumatoid arthritis "
"In summary, several immune-mediated diseases seem to be characterized by a multistep process resulting from complex interaction between predisposing genetic traits, infections, episodic and chronic activation of the neuroendocrine stress system and fluctuations in the Th1-Th2 system."
"Episodic or chronic activation of the neuroendocrine stress system due to several causes, including stressful events and intercurrent infections together with genetic polymorphisms and epigenetic factors, affects the Th2 response, while the Th2-to-Th1 switch has been in some cases linked to a hypoactive stress system."
"Chronic activation of the Th2-related stress system seems to lead to a Th1 switch with elevation of both Th1 and Th2 inflammatory cytokines that result in chronic systemic inflammation associated with a cluster of metabolic disturbances named metabolic syndrome, including arterial hypertension, dyslipidemia and obesity (specifically the visceral type), insulin resistance and/or diabetes type 2, in addition to endothelial inflammation and hypercoagulability of the blood ."
Dyslipidemia ---> I don't remember if I said before, but I have been reacting to "turkish coffee" pretty bad. I makes all my sympoms worse, plus gives me jitters. I don't get the same effects from even 6 cups of filter coffee a day. That's clearly a problem about cholesterol.
"So, depressive and anxiety syndromes seem to be mainly characterized by chronic hyposerotonergic state, HPA axis hyperactivation and Th2 shift. Nevertheless, other studies suggest an imbalance Th1/Th2 shifted towards Th1 in depression [267, 268]. In this regard, a dimensional approach could lead to further insight of the issue. In melancholic depression, condition in which patients have anxiety, insomnia, anorexia and circadian variation with worsening in the morning, appears to be associated with significantly higher CSF NE and plasma cortisol levels that are increased around the clock, with inappropriately high plasma ACTH and CSF CRH levels considering the degree of their hypercortisolism. These data suggest a central hyper-noradrenergic state in association to hyperfunction of central CRH pathway ; furthermore, the chronic hyper-noradrenergic state may drive the increase in systemic IL-6 levels, since NE up-regulates IL-6 production, and, theoretically, to a Th2 shift . On the other hand, atypical depression, condition in which patients have hypersomnia, hyperphagia and fatigue, appears to be associated with a central hypo-noradrenergic state in association to hypofunction of central CRH pathway [270, 271] and so, hypothetically, to a Th1 shift. It is noteworthy that atypical depression, ideally characterized by Th1 shift,"
Before fluoxetine --> Insomnia, melancholic depression, anxiety etc.
After fluoxetine --> Hypersomnia, emotional numbness, zero anxiety.
"Selective Serotonin Reuptake Inhibitors (SSRIs)
In rigorous and long term clinical study, SSRIs seem to increase Th1 cytokines, such as IL-1β, IL-2 and IFN-γ, and decrease Th2 cytokines, such as IL-4, IL-10 and IL-13, and cortisol levels after 52 weeks treatment in depressed patients , although other in vitro and short term ex-vivo studies reported conflicting results, showing decrease in IL-1β, IL-6, IL-10, IFN-γ and TNF-α after SSRI treatment in a dose dependent manner [284-288]. In that study, administration of SSRI in MDD patients, confirming baseline high levels of cortisol, IL-4, IL-13 and IL-10 (Th2) compared with healthy volunteers, induced clinical remission at week 20 of treatment, concomitantly with an increase in IL-2 and IL-1β levels (Th1) without changes in cortisol level. At week 52 of treatment, SSRI administration induced an increase in IL-1β and IFN-γ levels (Th1), together with a reduction in IL-4, IL-13 and IL-10 levels (Th2) and in cortisol levels (a 30% diminution compared to baseline) . Variations in these parameters could be caused by SSRI effects both on 5-HT and glucocorticoid receptors, as a result of chronic intake of these drugs. SSRIs exert a relatively selective blockade of 5-HT transporter , progressively increasing 5-HT levels, also in the circulation [290, 291], and influencing the immune response in a dose-dependent manner . As a consequence, long-term SSRI treatment desensitizes the inhibitory somatodendritic 5-HT1A autoreceptors in the dorsal and medial raphe, and 5-HT neurotransmission is enhanced [292-294]. Furthermore, a desensitization of 5-HT2A and 5-HT2C receptors occurs as a consequence of prolonged exposure to elevate levels of 5-HT [295, 296]. Finally, since 5-HT neurons exert a tonic inhibitory effect on locus coeruleus neurons, it appears that enhancing 5-HT neurotransmission by sustained SSRI administration leads to a reduction in the firing rate of noradrenergic neurons . Thus, drug-mediated enhancement of 5-HT activity exerts immunostimulatory effects on Th1 cytokines , possibly acting on 5-HT1A receptors, and concomitant immunoinhibitory effects on Th2 cytokines. Furthermore, it has been proposed that long term SSRI treatment in depressed patients causes a decrease in circulating cortisol levels by reestablishing the down-regulated glucocorticoid receptor sensitivity , thus restoring negative feedback by cortisol on the HPA axis [297-299]. "