It's maybe an autoimmune reaction, I need some help with reading this articles.

I found very interesting articles about (serotonin, tryptophan, kynurenine, gut, brain and inflammation). Appearently, all of them is related to each other. I tried to read it but couldn't even stand for a five minutes. I couldn't read nor memorize any of the sentences.
Please, may anyone look at these in their free time?

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6160932/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5681735/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6095005/

It may explain my unexplained gut bloating, progressive cognitive deterioration, myoclonic jerks etc. It's an autoimmune reaction either because of serotonin or glucocorticoid receptor imbalance. Fluoxetine messes with both of them.

https://www.imba.oeaw.ac.at/research-highlights/building-block-of-happiness-hormone-is-key-to-controlling-immunity-in-cancer-and-auto-immune-disea/

The effects of kynurenic acid, quinolinic acid and other metabolites of tryptophan on the development of the high pressure neurological syndrome in the rat.
https://www.ncbi.nlm.nih.gov/pubmed/2927579
The effects of some biologically active metabolites of tryptophan on the high pressure neurological syndrome (HPNS) were studied. Kynurenic acid, quinolinic acid, 5-hydroxytryptophan, kynurenine and 3-hydroxyanthranilic acid, at doses within the physiological range, were administered exogenously to rats prior to exposure to increased pressure and any effects on the tremor, myoclonus and convulsion end points of the high pressure neurological syndrome were observed. Quinolinic acid (25 and 50 mg/kg) and kynurenine (50 mg/kg) reduced the onset pressure for tremor, but not myoclonus or convulsions. Kynurenic acid (100 mg/kg) increased tremor onset pressure; 5-hydroxytryptophan (20 mg/kg) slightly increased onset pressure for tremor but decreased that for myoclonus. 3-Hydroxyanthranilic acid (20 mg/kg) had no significant effect on any of the motor signs of the syndrome. These data provide further support for the idea that the motor events seen in the high pressure neurological syndrome are not produced by a single mechanism. Differences between the responses to related metabolites suggest that the precise balance between compounds such as kynurenic acid and quinolinic acid may be important in the appearance of the high pressure neurological syndrome.

The ACMSD gene, involved in tryptophan metabolism, is mutated in a family with cortical myoclonus, epilepsy, and parkinsonism.
https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23955123/
Familial cortical myoclonic tremor and epilepsy is a phenotypically and genetically heterogeneous autosomal dominant disorder characterized by the presence of cortical myoclonic tremor and epilepsy that is often accompanied by additional neurological features. Despite the numerous familial studies performed and the number of loci identified, there is no gene associated with this syndrome. It is expected that through the application of novel genomic technologies, such as whole exome sequencing and whole genome sequencing, a substantial number of novel genes will come to light in the coming years. In this study, we describe the identification of two disease-segregating mutations in a large family featuring cortical myoclonic tremor with epilepsy and parkinsonism. Due to the previous association of ACMSD deficiency with the development of epileptic seizures, we concluded that the identified nonsense mutation in the ACMSD gene, which encodes for a critical enzyme of the kynurenine pathway of the tryptophan metabolism, is the disease-segregating mutation most likely to be responsible for the phenotype described in our family. This finding not only reveals the identification of the first gene associated with familial cortical myoclonic tremor and epilepsy but also discloses the kynurenine pathway as a potential therapeutic target for the treatment of this devastating syndrome.
KEY MESSAGE:
ACMSD is mutated in a family with cortical myoclonus, epilepsy, and parkinsonism. ACMSD mutation contributes to the development of FCMTE QA accumulation is likely to play an important role in the pathogenesis of FCMTE. The kynurenine pathway as a potential drug target for the treatment of epilepsy.

Found this,
the first old study shows that kynurenine-> quinolinic pathway leads to more tremors, but 5-htp reduces threshold for the myoclonus.

I read first link from you fully and I'm aware of most parts of it. I think omega 3 ratio increasing is def. a way to go
https://www.ncbi.nlm.nih.gov/pubmed/12449068

I am actually became quite interested with movement disorders theory.

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 [101]."

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 [269]; 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 [1]. 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 [252], 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) [252]. 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 [289], progressively increasing 5-HT levels, also in the circulation [290, 291], and influencing the immune response in a dose-dependent manner [252]. 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 [35]. Thus, drug-mediated enhancement of 5-HT activity exerts immunostimulatory effects on Th1 cytokines [32], 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 [27], thus restoring negative feedback by cortisol on the HPA axis [297-299]. "

I have read this article in the beginning of 2016. I was looking for that table where drugs increase il-6 which is certainly prodepressive. 5-ht2a are probably low in rheumatoid arthritis. They were found to lower tnf-alpha.
I introduced the topic of orexin slightly on pssdforum. I think that could be relevant to your loss of anxiety and sleepiness.

Adiponectin should be relevant to what you described
https://www.ncbi.nlm.nih.gov/pubmed/21355722
Interestingly orexin may stimulate it
https://www.ncbi.nlm.nih.gov/pubmed/21505958
https://www.ncbi.nlm.nih.gov/pubmed/28755843
So if you gained weight it could be lower orexin, if you lost it then you can have higher orexin, anxiety (overvigilance) and may be changes in 2 its receptors are involved.

I didn't gained much weight. Still under 65. I have more fat tissue on my stomach area and adipose, but I don't think it's relatable. I had tried progesterone and saw palmetto, and they caused the boob growing(I had pain in my armpits for a month) with along increased fat tissue. Probably because of short-term estrogen domination. I don't have much problem with that though.

Kpavel, I didn't talked about that before, but I'm sneezing one or two times usually after eat something. I said that I suspect from th2->th1 switch but there seems I have alergic reaction to some foods too.

I have probably metabolic syndrome as you said. Adipose tissue fat growth maybe not related to SP or progesterone at all. I was a very lean guy, I don't know why I got fat on my stomach suddenly.

Also you know that I'm getting hungry much quicker than before.

I probably get some (6 pills) naltrexone. I hope it can help.

What do you think about bupropion? It mediates th2 shift, maybe could help? I'm plaaning to try it in daily dosage (150 mg).

Ciprofloxacin wrote:Kpavel, I didn't talked about that before, but I'm sneezing one or two times usually after eat something. I said that I suspect from th2->th1 switch but there seems I have alergic reaction to some foods too.

I have probably metabolic syndrome as you said. Adipose tissue fat growth maybe not related to SP or progesterone at all. I was a very lean guy, I don't know why I got fat on my stomach suddenly.

Also you know that I'm getting hungry much quicker than before.

I had a new sneezing sensitivity to air pollutants and that was for a pair of years after last 5-htp dose. Appetite was only anxiety stimulated. Now I have pleasure from food returned. Raising adiponectin may help reduce inflammation, fat in wrong places. I don't know much about bupropion, some guys on pssdforum used it.
Offtopic, bupropion disappeared from sale here and recently there was a scandal arrest of a girl who ordered it from abroad (we have crazy policies on 'narcotic drugs').

Naltrexone may have effect on your motor symptoms.

Cold shower not working so much, kpavel. Do you know something I can use now? Have you read my last post on pssdforum? I did found prader-willi syndrome so interesting.

I searched really much but couldn't found any significant and available way to fix 5-ht2c. At least, even if it's not the culprit, I would like to temporary see what changes it makes in my body(2c upregulation)

Don't drop this that easy, I wouldn't offer you this if I didn't feel the potential.