344 replies to this topic

[Mr Serendipity]

http://pubmed.ncbi.n...h.gov/28507320/

 

The microbiome regulates amygdala-dependent fear recall

Abstract

The amygdala is a key brain region that is critically involved in the processing and expression of anxiety and fear-related signals. In parallel, a growing number of preclinical and human studies have implicated the microbiome-gut-brain in regulating anxiety and stress-related responses. However, the role of the microbiome in fear-related behaviours is unclear. To this end we investigated the importance of the host microbiome on amygdala-dependent behavioural readouts using the cued fear conditioning paradigm. We also assessed changes in neuronal transcription and post-transcriptional regulation in the amygdala of naive and stimulated germ-free (GF) mice, using a genome-wide transcriptome profiling approach. Our results reveal that GF mice display reduced freezing during the cued memory retention test. Moreover, we demonstrate that under baseline conditions, GF mice display altered transcriptional profile with a marked increase in immediate-early genes (for example, Fos, Egr2, Fosb, Arc) as well as genes implicated in neural activity, synaptic transmission and nervous system development. We also found a predicted interaction between mRNA and specific microRNAs that are differentially regulated in GF mice. Interestingly, colonized GF mice (ex-GF) were behaviourally comparable to conventionally raised (CON) mice. Together, our data demonstrates a unique transcriptional response in GF animals, likely because of already elevated levels of immediate-early gene expression and the potentially underlying neuronal hyperactivity that in turn primes the amygdala for a different transcriptional response. Thus, we demonstrate for what is to our knowledge the first time that the presence of the host microbiome is crucial for the appropriate behavioural response during amygdala-dependent memory retention.

 

[Mr Serendipity]

https://www.research...E_POSSIBILITIES

 

Introduction PROBIOTIC SUPPLEMENTATION IN REDUCING SYMPTOMS OF PTSD -FUTURE POSSIBILITIES

Abstract

Posttraumatic stress disorder (PTSD) is disturbing disorder with a delayed response triggered by the stressful events. That experience is so painful that those people cannot integrate it, nor they can move on. The most significant symptoms are recurrent, involuntary distressing memories, dreams and dissociative reactions (flashbacks), arousal alterations and similar experience. Croatian Homeland War Veterans are due to experiences in The Homeland War often burdened with symptoms of PTSD. 16% of them have PTSD, and even 25% of them have some signs of PTSD. Dysbiosis of the gastrointestinal tract is associated with many systemic diseases and neuropsychiatric disorders, including mood disorders and stress-related disorders (PTSD). This thesis aims to examine how does microbiota affect the course of the disease and does the use of the probiotics ameliorate the severity of discomfort. Methods Investigating existing studies about probiotics interventions on individuals with PTSD. We used relevant scientific papers from psychiatry and internal medicine as well as clinical nutrition findings. Results Gut microbiota consists predominantly of Bacteroidetes, Firmicutes and Proteobacteria phyla but various factors (environment, genetics, diet, antibiotics) can influence its content causing dysbiosis. Gut bacteria influence on the central nervous system via the gut-brain axis. There are several mechanisms including production of short-chain fatty acids (butyrate, acetate) that can activate the sympathetic nervous system and alter the activity of cells located in the blood-brain barrier. Gut microbiota secretes neurotransmitters (serotonin, dopamine) which can affect emotion regulation. Furthermore, chronic stress affects microbiota composition and activates gut-brain axis. It can elevate pro-inflammatory cytokines that increase the permeability of the blood-brain barrier and regulate CNS function and behavior. Several studies showed that supplementation with specific probiotics could have positive effects on the brain and behavior implicating the role of the microbiome in the treatment of PTSD. Preexisting studies are showing promising effects with probiotics supplementation in combat-related PTSD. Studies showed the reduction of anxiety, derealization, panic, widespread infection and headache that represent the major issues in patients with PTSD. Also, supplementation with probiotics has a positive effect on the overall well being through different mechanisms of which the most pronounced are regulation of bacterial homeostasis on the gut level and improved bioavailability of food supplements and medication used to reduce the symptoms of PTSD. Conclusion Promising effects have been observed while also using probiotics in the amelioration of disease symptoms of PTSD. However, additional studies in this challenging therapeutic are needed. TD et al. Growing literature but limited evidence: A systematic review regarding prebiotic and probiotic interventions for those with traumatic brain injury and/or posttraumatic stress disorder. Brain Behav Immun.

 

[Mr Serendipity]

https://www.medicaln...articles/319897

 

PTSD linked to changes in gut bacteria

 

An exploratory study has identified a link between gut bacteria and post-traumatic stress disorder that could bring us closer to fathoming the mechanisms of the complex condition

The researchers, including a team from Stellenbosch University in South Africa, report their findings in the journal Psychosomatic Medicine.

It is not uncommon, at some point in their lives, for people to experience shocking and dangerous events wherein they believe that their lives, or the lives of others, are at risk.

Estimates for the United States suggest that 60 percent of men and 50 percent of women will experience at least one traumatic event during their lifetime.

A small proportion of those who experience trauma develop post-traumatic stress disorder (PTSD), a serious psychiatric disease with a cluster of symptoms. In the U.S., between 7 and 8 percent of the population will have PTSD at some time in their lives.

 

The immune system and inflammation

Previous studies have already pointed to several factors that might determine what makes people either susceptible or resilient to PTSD.

These have highlighted genetic makeup and environmental factors such as living conditions and childhood experiences. Other have suggested that inadequate immune system control and inflammation may raise the risk of PTSD.

Scientists are becoming increasingly aware of the role that the trillions of microbes that live in and on the human body play in health and disease. Many of them live in the gut, where they help to digest food, metabolize drugs, and fight infections.

Gut bacteria also influence the biology and function of the brain through the production of hormones or neurotransmitters, molecules that alter immune function, and toxins.

Bacteria in the gut are also affected by emotional responses. Stress hormones can alter their growth and damage the lining of the gut, allowing both bacteria and their toxins to get into the bloodstream. This can lead to inflammation, which is known to contribute to psychiatric diseases.

Studies have also found that levels of inflammation markers measured in people recently exposed to trauma can predict whether or not they will develop PTSD later.

Examining this research, the team behind the new study highlights some potential common ground between stress and gut microbes — especially in relation to the immune system and inflammation. And yet, they note in their study paper, the link between PTSD and gut microbes “is unknown.”

 

Differences in three types of bacteria

For their investigation, the researchers — including Dr. Stefanie Malan-Müller, a postdoctoral fellow in psychiatry at Stellenbosch University — compared the gut microbes of 18 people diagnosed with PTSD with those of 12 people without PTSD but who had experienced significant trauma (the controls).

Dr. Malan-Müller and her colleagues found that while the overall diversity of the gut microbe population in the PTSD and the trauma-exposed participants was largely similar, there were differences in the abundance of certain classes of bacteria.

“We identified,” explains Dr. Malan-Müller, “a combination of three bacteria (Actinobacteria, Lentisphaerae, and Verrucomicrobia) that were different in people with PTSD.” Those bacteria were less abundant in the PTSD group.

The researchers point out that they were not able to establish whether low levels of these bacteria were a cause or a result of PTSD.

However, they did find that participants who had experienced trauma as children had lower levels of two of the gut bacteria (Actinobacteria and Verrucomicrobia). These two bacteria are known to be important for regulating the immune system.

Dr. Malan-Müller explains that this is an interesting finding because it is already known that people “who experience childhood trauma are at higher risk of developing PTSD later in life.” She suggests that perhaps the altered levels of the bacteria “occurred early in life in response to childhood trauma.”

“We therefore hypothesize that the low levels of those three bacteria may have resulted in immune dysregulation and heightened levels of inflammation in individuals with PTSD, which may have contributed to their disease symptoms.”

Dr. Stefanie Malan-Müller

 

 

Edited by Jesus is King, 15 December 2020 - 11:20 AM.

[Mr Serendipity]

ITF = inulin-type fructans (ITF)

ITF (Synergy 1, namely, inulin/oligofructose 50/50 mix) 

 

https://gut.bmj.com/content/62/8/1112

 

ITF prebiotics induced a significant increase in Firmicutes and Actinobacteria and a decrease in Bacteroidetes (figure 2A).

 

1 = before

2 = after treatment

 

The subjects were assigned to receive either a daily supplement of 16 g (8 g twice a day) of ITF (Synergy 1, namely, inulin/oligofructose 50/50 mix) or placebo (maltodextrin) for 3 months (both products were kindly provided by Orafti, Oreye, Belgium). 

[Mr Serendipity]

https://www.ncbi.nlm...les/PMC5698696/

 

Microbial Mechanistic Insight into the Role of Inulin in Improving Maternal Health in a Pregnant Sow Model

 

Inulin supplementation increased the relative abundance of Lentisphaerae (P = 0.02), and tended to decrease the relative abundance of Tenericutes (P = 0.09).

 

Moreover, significantly higher abundance of Lentisphaerae due to inulin addition in the present study would also be another possible microbial mechanism underlying the regulatory effects of inulin on host body weight and fat storage.

[Mr Serendipity]

ITFs (OraftiP95, Tienen, Belgium) at 250 mg/mouse/day in the drinking water.

 

https://gut.bmj.com/...ent/67/2/271#F4

 

Targeting the gut microbiota with inulin-type fructans: preclinical demonstration of a novel approach in the management of endothelial dysfunction

 

KO DEF mice presented a lower relative abundance of the Verrucomicrobia phylum compared with WT DEF mice and ITFs were able to restore its abundance (figure 4F).

 

 

Enrichment in Actinobacteria (Bifidobacteriales and Coriobacteriales orders), Enterobacteriaceae and Erysipelotrichaceae characterised ITF-treated mice

 

Accordingly, correlation analysis revealed that Gcg mRNA positively correlates with the abundance of Bifidobacteriaceae and Verrucomicrobiaceae families, both enhanced by ITFs

 

 

 

 

[Mr Serendipity]

https://www.frontier...2018.01832/full

 

Butyrate and Dietary Soluble Fiber Improve Neuroinflammation Associated With Aging in Mice

 

Adult and aged mice were fed either a 1% cellulose (low fiber) or 5% inulin (high fiber) diet for 4 weeks. Findings indicate that mice fed inulin had an altered gut microbiome and increased butyrate, acetate, and total SCFA production.

 

 

Figure 3. Cecal content concentrations of (A) butyrate, (B) acetate, © propionate, and (D) total short-chain fatty acids (SCFAs) in adult and aged mice fed a LF (1% cellulose) or HF (1% cellulose and 5% inulin) diet. Data are presented as mean ± SEM (n = 6–8).

 

 

Edited by Jesus is King, 15 December 2020 - 11:57 AM.

[Mr Serendipity]

So we know people with PTSD have lower levels of Actinobacteria, Lentisphaerae, and Verrucomicrobia.

 

And we also know inulin increases Actinobacteria, Lentisphaerae, and Verrucomicrobia, as well as increasing Butyrate.

 

So this is maybe why I've seen improvement as of late am I'm looking forward to the results over the coming weeks/months.

 

After a while, maybe New Year, as long as I see continued improvement without tickling, I am going to give ticking another go.

 

Go eat your inulin guys!

[Mr Serendipity]

Ok so it was a moment of truth today. Last night I thought screw it, let’s try tickling my amygdalas now instead of waiting. So I did it last night, and before I went to work today. Also to note is I can take much higher doses of inulin without needing to rush to the toilet now. I took my probiotics and 2 teaspoons of inulin this morning.

 

Anyway most of the day is good, I’m doing deliveries with my wife. My mind is a little hyper here and there, I’m a bit more stern/impatient, but I didn’t become manic or experience pressured speech. Wife was in a bit of a funny mood, criticised me a bit, but nothing sent me into a low and I was able to handle it normally and with jest, and I wasn’t even bothered by it. This is huge progress overall, the fact that I didn’t get mania or pressured speech, and whilst my mind was a little hyper, I was stable enough that I couldn’t be sent into a low, an absolute miracle. Praise God!

 

Toward the end of deliveries we’re talking about my mental problems normally, i.e there’s no fighting or negativity, my temples start to really hurt, my throat is hurting too, and then I tell her I feel like I’m about to cry, and let out some crying for about 30 seconds. But the thing to note is this is not the same crying that I was getting on my lows, I wasn’t feeling any negative emotions, I wasn’t feeling down, I wasn’t feeling bad, hurt, emotionally charged or anything. In other words I got that Pseudobulbar affect, which for me seems to occur when my temple areas gets really painful and my throat starts to hurt.

 

So this progress is absolutely amazing. Inulin and probiotics seems to allow me to keep overall control over everything. I don’t become manic or get pressured speech, and I also don’t get triggered into a low I can’t control.

 

It seems like the only thing I’m going to be suffering with when tickling now is the Pseudobulbar affect. So I might end up randomly crying without feeling anything negative or being upset, but at least I will no longer be emotionally volatile/manic/get pressured speech/or get triggered low. 
 

And with what I’ve been through, I’ll take the Pseudobulbar affect over what I was experiencing before every time. With the Pseudobulbar affect I will just look like an idiot who is crying for no reason, but at least I’m in control of my emotions. Whereas before I was highly emotionally charged, and these highly charged emotions had a strong affect on my actions and words, which would cause negative social consequences. So while the Pseudobulbar affect is embarrassing, at the end of the day I’m emotionally stable, I can now pursue amygdala tickling without having to worry about real consequences in my life.

Edited by Jesus is King, 16 December 2020 - 05:03 PM.

[Mr Serendipity]

Just a quick clarification. My inulin seems to be FOS. I take the MyProtein brand which has now been split into a MyVitamins brand. This is the specific product https://www.myvitami...r/11397387.html = Fructo-Oligosaccharide (FOS) (100%).  

 

The Inulin used in that big study on all sorts of bacteria (post #306, 3 posts back) was OraftiP95.

 

From their website, OraftiP95 is 95% Oligofructose powder.

 

It's actually quite hard to determine whether Oligofructose and Fructo-Oligosaccharide (FOS) are the same thing. Some websites say they are, some websites say they aren't. 

 

According to this review: https://pubmed.ncbi....h.gov/19152479/

 

 

Inulin-type prebiotics include fructooligosaccharides (FOS), oligofructose, and inulin - terms that have been used inconsistently in both the scientific literature and in food applications.

 

They seem to acknowledge the inconsistency of the terms being used, but differentiate fructooligosaccharides (FOS) and oligofructose as being 2 separate things. They also both come under the term inulin-type fructans (ITFs).

 

But I think I may have found my answer from this FDA paper: https://www.fda.gov/...116858/download

 

 

Individual fructan products may be distinguished by their source, method of production, or degree of polymerization (DP-the number of fructose or glucose residues in the chain). Inulin is a naturally occurring fructan with a DP ranging from 2 to 60. Inulin can be enzymatically hydrolyzed to produce FOS or oligofructose. FOS generally refers to fructans with a DP < 10. Oligofructose refers to fructans with a DP of < 10 and more specifically with > 25% of the molecules having a DP ~ 5 and < 75% with a DP S 4. 

 

So FOS has a higher degree of polymerization (more than 10) while oligofructose has less than 10.

 

According to that other study I posted which increased the Lentisphaerae bacteria: https://www.ncbi.nlm...les/PMC5698696/

 

The inulin used in the study was obtained from BENEO-Orafti (Orafti GR, Belgium) with purity >90% and average degree of polymerization (DP) = 10–12

 

So I assume this comes under FOS.

 

The ITFs used in the study that showed an increase in Actinobacteria: https://gut.bmj.com/content/62/8/1112

 

ITF (Synergy 1, namely, inulin/oligofructose 50/50 mix) 

 

However from what I can see, there are no oligofructose products on the market bar one: https://www.vitamine...rebiotic-powder (Oligofructose Enriched Inulin (from Chicory Roots, cultivated in Belgium)).

 

And there seems to be no way of determining the DP of inulin & FOS on the market. Also take into account the terms fructooligosaccharides (FOS), oligofructose, and inulin being used incorrectly in a lot of studies, the whole thing becomes a little bit convoluted to say the least. 

 

However we know the smaller the chains as followed: Inulin > FOS > Oligofructose

 

And as inulin is the chemical found in food, I can only assume it won't make much of a difference in feeding the bacteria except the potential increase in rate they may grow with a lower DP in FOS and Oligofructose.

 

And since there is no Oligofructose on the market, and I have no idea if there are any bacteria that won't grow with FOS but will with inulin. I'm going to get hold of some inulin as well and take it as a 50/50 mix, just to cover all bases.

Edited by Jesus is King, 18 December 2020 - 11:30 AM.

[Mr Serendipity]

This will probably be my last update on this for a long time.

 

Because targeting my gut with probiotics & inulin has essentially cured me from the mania, hyped up mind, pressured speech, and extreme lows I use to experience on a regular basis. Also I don't feel major urges to abuse substances anymore (weed or alcohol), and my general interest in life has risen. Temptation is still there for substances when opportunity arises, but with the little bit of extra willpower I have now, I can just say no to these things.

 

As for the pseudobulbar affect, I don't think I have anything to worry about. The only time it might happen is if I tickle my amygdalas a lot that day, but a bit of tickling here and there won't bring it about, except sometimes cause a little grumpiness.

 

After this journey of what I would call a type of madness these past 3 and a half years (and most likely longer prior to this), it's nice to finally live a life with more balance, peace, and control. I think my main motivation for amygdala tickling, as well as trying all sorts of supplements, was to find this normality again in my life, as well as feeling enjoyment and interest in life again. Now that I have it, I don't feel the need to keep searching for the answer so to speak.

 

And while I wouldn't consider myself 100% cured in all my issues, it is enough to live a life without worry over any emotional instability I wasn't able to control before, and I can now patiently wait for new cures in the future for my other problems (for example 16 years of anorgasmia). I should also mention that probiotics and inulin were the only things I have been taking the last few weeks, so I was able to rule out all other supplements, and I already knew I would get those aforementioned problems even when I didn't take anything, so I can hone it down to the probiotics and inulin in my case.

 

I will start slowly introducing my other supplements back into my stack to see which ones I want to keep now and which ones I can discard. However because I've found my answer to my major problems and am not looking for it anymore, I have no need or urge to share every detail of my journey anymore. I will only post here now if a major result or euphoric experience occurs (like my first mini pop), or if a question is asked by someone.

 

Until then, God Bless.

 

And all my praise goes to God. Amen.

Edited by Jesus is King, 21 December 2020 - 05:39 PM.

[Mr Serendipity]

I just want to update quickly on this.

 

I was still suffering from mania which I couldn't get full control over. So while improving my gut health definitely helped, it was not the all end cure I was hoping for.

 

However I may have actually found the one best thing for a lot of my problems. Niacin, or specificially niacinamide (the non flush kind of Vitamin B3). Even though it's only been a short while, my insomnia, emotional stability, mania, mental clarity have all improved, and my digestion feels like is has gone up another level. I even tested pizza and tabasco sauce one day, something that is known to trigger madness within me, and I didn't get any reaction to it at all. I even tried drinking a lot of milk one day (I'm lactose intolerant so this is a big no no), but amazingly I had a big reduction of IBS symptoms that lactose usually causes me.

 

Also last week I tested amygdala tickling and I did end up getting a bit of pressured speech and bipolar symptoms, but they was different. For example I'd feel angry but in a controllable way, like the anger was contained. I'd feel irritable but it felt contained. I didn't get an out of control high, low, emotional flashback event. All I can describe it as, is that my emotions while still feeling them, are much more contained and didn't leak out into my behaviours as much.

 

What made me try niacin was actually this study: https://www.ncbi.nlm...les/PMC5852710/

 

Nicotinic Acid Long-Term Effectiveness in a Patient with Bipolar Type II Disorder: A Case of Vitamin Dependency

 

 

 

Nicotinic acid (NA), often called niacin, a form of vitamin B3, is a water-soluble nutrient found in animal and vegetarian foods. Vitamin B3 for healthy people is considered to be needed in doses of less than 20 mg daily. In higher doses, NA has been described to be beneficial in some patients with psychiatric disorders. This report describes a male patient with bipolar type II disorder who for many years had been treated with lithium and other medications applied in affective disorders. These pharmacological drugs had beneficial effects but were at times insufficient. When the patient was prescribed NA, he experienced a comparatively strong effect. Slowly it was discovered that the patient could lower and cease all medications except NA. For over 11 years he has been stable and calm with NA and currently takes 1 g three times daily. When not taking NA, he consistently became anxious and depressed within 2–3 days. The resumption of NA resulted in a normal state usually within 1 day. This finding has been described as a vitamin dependency. The paper discusses possible mechanisms for the effect of NA in this patient. Further studies are needed to investigate the prevalence of vitamin B3 dependency and the biochemical explanations for this phenomenon.

 

This person was able to come off his bipolar meds and take niacin for 11 years while remaining stable and calm. I was worried the non flush version I got might not work, but so far in my short experiment it's working well for me. 

 

So I'll come back in a couple of months again, and update everyone if it's continuing to work for me or not. But I was so sick of my mania/hypomania and pressured speech, that anything that will keep my hyperactive mind calm is very much welcome.

[Mr Serendipity]

The Highs and Lows of Amygdala Reactivity in Bipolar Disorders

 

In this issue of the Journal, Vizueta et al. (1), a research group at the University of California, Los Angeles, led by Lori Altshuler, M.D., present findings from their latest investigation into the neural correlates of mood states in bipolar disorders. Specifically, they provide novel evidence for relatively decreased corticolimbic reactivity and functional connectivity during the perceptual processing of affectively charged stimuli in patients with bipolar II disorder. In and of itself, the study usefully informs our understanding of potential pathophysiologic neural mechanisms in bipolar II disorder, which has received less attention than bipolar I disorder. However, the greater reach of this report is found within the broader context of the investigators' ongoing research seeking to identify the neural correlates of cyclic pathologic mood states as characterized by bipolar disorders.

In the June 2005 issue, Altshuler et al. (2) presented the initial results from this line of research. In that seminal report, the authors discovered relatively increased amygdala reactivity in patients with bipolar I disorder during a manic episode. This pattern is consistent with the role of the amygdala in mediating increases in not only physiologic but also behavioral arousal in response to environmental stimuli. This is accomplished by modulating neuronal populations in the basal forebrain providing cholinergic tone to the neocortex as well as neuromodulatory centers in the brainstem controlling distributed monoaminergic signaling (3). In many ways, such amygdala hyperreactivity in bipolar disorder is consistent with the euphoria, irritability, insomnia, inattention, and distractibility that often define a manic episode. Subsequent to this study of manic bipolar I patients, the research team looked for contrasting decreases in amygdala reactivity in depressed bipolar I patients, who typically exhibit relatively low physiologic and behavioral arousal.

Consistent with their expectations, Altshuler et al. observed relatively decreased amygdala reactivity in depressed bipolar I patients relative to healthy comparison subjects (4). However, this difference failed to reach statistical significance in formal tests. In contrast, statistically significant differences between depressed bipolar I patients and comparison subjects emerged in several prefrontal regions, including decreased activity in lateral aspects of the orbitofrontal cortex (BA 47, also referred to as the ventrolateral prefrontal cortex) and the dorsolateral prefrontal cortex (BA 9) but relatively increased activity in the frontopolar cortex (BA 10). Interestingly, the same BA 47 regions of the orbitofrontal cortex also exhibited a relatively attenuated response during the earlier study of manic bipolar I patients. Moreover, a similar attenuated response in orbitofrontal cortex BA 47 has been reported by this same group in euthymic bipolar I patients (5). Notably, in that study, amygdala reactivity did not significantly differ between euthymic bipolar I patients and healthy comparison subjects. Now, the team again reports relatively decreased activity in orbitofrontal cortex BA 47 in depressed bipolar II patients.

When we look across these prior studies of bipolar I disorder and the Vizueta et al. findings on depressed bipolar II patients, a striking pattern emerges: amygdala reactivity follows a state-dependent course (i.e., increased in manic, decreased in depressed, and unchanged in euthymic states), while prefrontal activation exhibits a state-independent or trait-like course (i.e., decreased in all three states) (Figure 1). Critically, the BA 47 regions of the orbitofrontal cortex exhibiting trait-like hypoactivation across manic, depressed, and euthymic states play an important role in the down-regulation of amygdala reactivity (6–8). In healthy volunteers, BA 47 appears to exert top-down regulatory control over the amygdala (likely through medial prefrontal regions with direct amygdala connections), as indexed by negative functional connectivity between the two regions. Balance in this dynamic functional circuitry is critical for the expression of behavioral and physiologic responses to provocation that are both temporally limited and contextually appropriate (9). The data accrued by Altshuler et al. suggest that during mania, the BA 47 regions of the orbitofrontal cortex may not be adequately capable of regulating amygdala reactivity. In fact, in a follow-up study of their original report on manic bipolar I patients, the research team demonstrated decreased negative functional connectivity between orbitofrontal cortex BA 47 and the amygdala in patients relative to healthy comparison subjects (10).

 

FIGURE 1. Amygdala and Orbitofrontal Cortex Reactivity in Bipolar Disordersa

a The top panel depicts the overlay of bilateral amygdala reactivity onto a single-subject anatomical template in the axial plane. Emerging functional MRI (fMRI) research reveals state-dependent increased amygdala reactivity during mania in bipolar I disorder, decreased reactivity during depression in bipolar I and II disorders, and reactivity equivalent to that seen in comparison subjects during euthymic states in bipolar I disorder. The bottom panel depicts the overlay of bilateral orbitofrontal cortex BA 47 activity onto a single-subject anatomical template in the axial plane. In contrast to the state-dependent patterns of amygdala reactivity, the fMRI research reveals state-independent orbitofrontal cortex BA 47 hypoactivation during manic, depressed, and euthymic episodes in both bipolar I and II disorder. The two horizontal lines in this lower panel indicate that in all three bipolar states, BA 47 activity is unchanging and always less than the activity in a comparison or healthy group. Overlay data are taken from the author's ongoing research using a task similar to that used in the Vizueta et al. study. The time courses for the amygdala and orbitofrontal cortex BA 47 are for illustration purposes and do not represent actual data.

 

If amygdala reactivity is a state-dependent phenomenon in bipolar disorders and trait-like hypoactivation of regulatory orbitofrontal regions creates a permissive environment for the translation of amygdala hyperreactivity into manic symptoms, then what could be driving the amygdala hyporeactivity in the depressed state reported in the Vizueta et al. study of bipolar II patients and suggested by the research team's earlier study of bipolar I patients? Again, the relative functioning of prefrontal regions may be key. In the present study of depressed bipolar II patients, Vizueta et al. do not report decreased negative functional connectivity between the amygdala and orbitofrontal cortex BA 47, which can be interpreted as less top-down regulation, as observed in manic bipolar I patients, but rather they report increased positive functional connectivity between these two regions. A similar increase in positive functional connectivity between the amygdala and orbitofrontal cortex BA 47 has been reported by Versace et al. in depressed bipolar I patients (11). Thus, it is possible that the depressed state of bipolar disorders reflects dysfunctional positive connectivity between these two nodes, resulting in inappropriate inhibition of the amygdala. Unfortunately, measures of functional connectivity from blood-oxygen-level-dependent functional MRI data cannot decipher such interactions as being either excitatory or inhibitory in nature. Regardless, these data suggest that it is not simply differences in the activation of brain regions (i.e., orbitofrontal cortex BA 47 is hypoactive across states) but rather alterations in the functional connectivity of distributed regions (i.e., decreased amygdala-orbitofrontal cortex BA 47 connectivity in mania but increased connectivity in depression) that may be particularly important for understanding changes in mood states.

Before one gets too excited about the potential of these data to illuminate a mechanism for cyclic pathologic mood states in bipolar disorders, it is important to note that the literature, particularly with regard to depressed bipolar I disorder, is decidedly mixed at the moment, with some studies finding increased, others decreased, and yet others no significant change in amygdala reactivity (12). There are many likely contributors to this heterogeneity, including studies that 1) collapse patients in manic, depressed, and euthymic states, 2) focus on medicated or nonmedicated patients, and 3) use a variety of experimental paradigms. A notable methodological strength of the research conducted by Altshuler's team is the use of the same functional task paradigm in all of their studies, which has facilitated cross-sectional comparisons across mood states in bipolar I and II disorders. Longitudinal research within a cohort of patients is now necessary to identify the neural basis of the transition between states and the triggers for these transitions. In this context, it will be interesting to establish how observed changes in corticolimbic circuitry map onto specific dimensional aspects of dysfunction, an element missing from the current research.

Altshuler's research team, as well as other groups (13), have begun longitudinal research of bipolar I patients as they move through manic, depressed, and euthymic episodes, and their work should provide further insight into the pathophysiology of cyclic mood states in bipolar disorders. Moreover, the existing research, as well as that under way, usefully informs and encourages a broadening of our appreciation of amygdala reactivity and functional connectivity with prefrontal regions, moving beyond simply negative emotionality to encompass complex and perhaps unexpected influences over behavioral arousal and responsiveness. Moving forward with such a more nuanced approach will hopefully yield a deepening in our understanding of mood states in both health and disease.

 

 

------------------------------------------

 

The study above is the most likely relevance to the experiences I have endured on my amygdala tickling journey these last 3 years since the creation of this thread.

 

These are my own observations, connections, experiences, and conclusions thus far:

 

1. I am bipolar. I have experienced hypomania and pressured speech numerous times, which are exacerbated when tickling my amygdala.

 

2. I believe with all the experiences and observations I have accumulated, that the amygdala can 100% be stimulated through visualization exercises.

 

3. I 100% believe I have been inducing hypomania through the amygdala tickling exercise.

 

4. Even when I don't tickle my amygdalas for a period of time, I suffer from hypomania on a consistent basis, which leads me to believe I have trained my amygdala to react more.

 

5. Lecithin has been shown in a few studies, to help prevent hypomania and mania.

 

6. Around the time of my mini pop of euphoria, I 100% know I was consuming 6 raw egg yolks a day (which of course are high in lecithin). This is my strongest connection for a nutritional component to amygdala tickling and my euphoric experience.

 

7. I believe I will be able experience another euphoria moment with tickling, as long as I am able to find a way to control my hypomania.

 

8. So far my best bet on controlling hypomania is via supplementing lecithin and niacinamide. I also seem to be more of a tranquil mind after having taken anti-histamines for sleeping the day prior. All of which require more self experimentation.

 

9. Lastly while I don't know what may have cured these as I've tried a myriad of things over the years (though I would conjure the guess it was by improving my gut health or self hypnosis). I don't seem to suffer from emotional flashbacks or OCD currently. My biggest issues are hypomania, pressured speech, and irritability. 

 

10. Another note is that I also seem to have cured my lactose intolerance which I've had for more than a decade now. To the point where I am consuming milk daily without IBS.

 

 

If anyone has any experience of controlling mania or hypomania, please feel free to share your experiences.

[zorba990]

My advice would be to drop all stimulants and mind altering substances, weed, lithium, forskolin, excessive caffeine, etc for at least a year. They only interfere with getting root cause.

FIx gut / brain axis with meditation / progressive relation (lots of apps for this I like Relax Melodies), Tributyrin, BPC-157 (NooTroo has the original).

IRT "hypomania and pressured speech" you are missing something there. Childhood PTSD event. Who "pressured" you to speak? What does the term "pressure" mean to you in terms of physical feeling.
Follow the feeling....

[Mr Serendipity]

My advice would be to drop all stimulants and mind altering substances, weed, lithium, forskolin, excessive caffeine, etc for at least a year. They only interfere with getting root cause.

FIx gut / brain axis with meditation / progressive relation (lots of apps for this I like Relax Melodies), Tributyrin, BPC-157 (NooTroo has the original).

IRT "hypomania and pressured speech" you are missing something there. Childhood PTSD event. Who "pressured" you to speak? What does the term "pressure" mean to you in terms of physical feeling.
Follow the feeling....

Pressured speech is a symptom of bipolar and the mania state.

 

Since my last post I have been able to control my hypomania and it’s symptoms with the following combo of supplements:

 

Niacinamide

Forskolin

Lecithin

 

I’ve actually found the combo I’ve been looking for all this time, regardless of how much I tickle I remain in a euthymic state to a large degree.

 

I wouldn’t disregard forskolin completely, I think raising the cAMP in the brain helps, especially trying to increase orbitofrontal cortex activation to a degree. But you also need niacin and lecithin to keep you in normality, testing forskolin on its on previously put me in a great mood but didn’t cure hypomania. So far I’m having quite good success with this combo. I also take two multivitamins and NAC for good measure.

 

I agree with the gut/brain axis hypothesis, and I feel my gut health has improved dramatically since I’ve taken probiotics and inulin since December. I haven’t had an emotional flashback/out of control anger moment since then, even though I only really now take inulin in a oat shake I make every now and then. Hell after more than a decade of lactose intolerance, I am now consuming regular milk and yogurt regularly, which to me is evident of improved gut health; however I also believe niacin has helped me in this regard as well (I seem to tolerate lactose and digestive issues in general much better when I’ve consumed niacinamide).

 

I think for amygdala tickling to be successful (at least in the bipolar person), you have to focus on two things. Improving your gut health and improving your mitochondrial issues. Niacinemide, forskolin, and lecithin all help with the mitchondria. Lecithin also helps with gut health, and of course so does inulin and probiotics.

 

I also believe mania and the frontal lobes pop have similarities, hence why some people feel euphoria in mania. However due to the dysfunctional orbital frontal cortex (the frontal lobes section closest to the amygdala), it just gets a bit out of control (read paper above).

 

Another note is niacinamide can put you into the depressive state if you take too much (for me at least), so 500mg in the morning suffices my needs.

 

I’m actually tickling until kingdom come now, not having to worry about an out of control moment caused by hypomania or emotional flashbacks/PTSD issues or explosive anger. I’m starting to here some clicks again, feel some electricity, have some smiles, and even my dreams have become more clearer and in-depth (it’s hard to explain but there’s a more clear and underlying story to them). As long as I keep my hypomania under control with the supplements aforementioned, I may actually be able to experience another pop by the end of this year after more than a decade since my first (hopefully this isn’t just false optimism). I’m also including in my visualisations the oribitolcortex as well to try and ramp that up.

 

Regardless there’s been a hell of a lot of progress in a short time since December when I started focusing on my gut health . And I cannot comment right now whether tackling past traumas is even necessary to overcome neurosis. But then again I could probably never comment on this as I’ve delved into self hypnosis for various on the top layer things (nothing deep like regression to specific traumas). But I hypothesise it may be possible to heal and pop without ever visiting the past, but I reserve judgement on the matter.

 

Anyway the future possibilities are the brightest they’ve ever been so far in my journey. So let’s wait and see what happens with my supplement combo and lots of tickling.

Edited by Jesus is King, 12 March 2021 - 10:18 PM.

[Mr Serendipity]

https://www.ncbi.nlm...les/PMC2838627/

 

DHA Deficiency and Prefrontal Cortex Neuropathology in Recurrent Affective Disorders1–3

Robert K. McNamara

Additional article information

Abstract

Increasing evidence suggests that docosahexaenoic acid [DHA, 22:6(n-3)], the principal (n-3) fatty acid in brain gray matter, has neurotrophic and neuroprotective properties. Preliminary clinical evidence also suggests that the perinatal accrual, and the subsequent dietary maintenance of, cortical DHA is positively associated with cortical gray matter volumes. The pathophysiology of recurrent affective disorders, including unipolar and bipolar depression, is associated with (n-3) fatty acid deficiency, DHA deficits, impaired astrocyte mediated vascular coupling, neuronal shrinkage, and reductions in gray matter volume in the prefrontal cortex (PFC). Preclinical studies have also observed neuronal shrinkage and indices of astrocyte pathology in the DHA-deficient rat brain. Together, this body of evidence supports the proposition that DHA deficiency increases vulnerability to neuronal atrophy in the PFC of patients with affective disorders. Because projections from the PFC modulate multiple limbic structures involved in affective regulation, this represents one plausible mechanism by which (n-3) fatty acid deficiency may increase vulnerability to recurrent affective disorders.

———

This is interesting to me because there was once a time I use to megadose fish oil, 30g a day (yes crazy doses). Though I cannot tell whether it was during university, though I think it could have been around that time. So I might have to look into increasing my cod liver oil (I understand the risk of vitamin a toxicity) or DHA some other way to see if it has any effect.

 

[Mr Serendipity]

Ok I think I've finally found my cure, which no amount of hypnotherapy or other supplements helped.

 

Basically I've been hypomanic for many years now, along with agitation/anger problems. Amygdala tickling exacerbated my hypomania and also caused emotional flashbacks, hence why I stopped the practice. However I continued to be hypomanic everyday without this practice.

 

After having tried everything, I forgot to experiment with higher doses of niacinamide. So since I've started experimenting with higher doses 1.5-3g a day, my hypomania and emotional agitation/anger problems have been completely cured. I've even started tickling again without any issue.

 

So I guess I prescribe to the theory of Dr Hoffer that some people are niacin dependent vs niacin deficient. I don't know whether this is because it soaks up extra methyl groups and prevents noradrenaline converting to adrenaline, though whenever I went manic, or crazy on alcohol, it feels like my brain is pumping full of adrenaline. Or could be because it acts like a benzo. Or whatever else is does. All I know is that is works amazingly well, better than anything I've tried. And this is from someone who goes hypomanic daily.

 

Other things are clearer vision and thinking.

 

I'm going to continue experimenting with these high doses, finding the right dose and time to split and take them. And I still take my main stack in the morning to cover all other bases. 

[Mr Serendipity]

BOOM! Thank you Jesus!

 

Finally I have found a cure to my problems. The GABAgenic system.

 

Since I've added (all Now Foods brands except citrulline):

 

2 x GABA [500mg]

2 x Kava Kava

2 x DHA-500

1 x Gotu Kola

1 x tsp of Citrulline (to help GABA BBB permeability)

 

I've stopped becoming hypomanic.

I've stopped getting agitation/irritability/anger problems.

I've stopped getting any negative reactions to amygdala tickling.

I've stopped going hypomanic/crazy on a little bit of alcohol (6 small beers or 3 big ones), acting normally, not seeking out more, stopping when I've had enough, and all if I decide to drink that is.

My clarity of thought and calmness is through the roof.

And most of all, I fall asleep so easily, and the sleep quality is so goooood and refreshing.

 

Sleep and insomnia are the biggest improvements. Even when I wasn't taking or consuming anything, I had major issues with hypomania, falling asleep, and getting a good sleep quality. And when I did decide to take supplements, a myriad of supplements would worsen my insomnia ten fold, I was always super sensitive, even taking too much vitamin c would do this to me, or eating cereal with added vitamins.

 

But now! I can take a whole load of supplements in the morning. Selenium, benfotiamine, Maca, drink Cocoa etc... and I'll still sleep so well at night. In fact I've just been taking more and more variety of supplements in the morning, many of which I had to put aside because of the insomnia issue.

 

I don't know whether GABA can cross the BBB or not, I know there's a lot of debate. Or whether I'm just benefiting because of GABA in the rest of my body. But with the aforementioned supplements in my stack now, I've made the biggest and most consistent progress to date.

 

I also did some quick googling, and found some things which may be relevant to my issues:

 

GABA and mood disorders: a brief review and hypothesis  

 

Low GABA levels are found in brain, cerebrospinal fluid and plasma of patients with depression and in plasma of patients with mania.

 

Cortical Gamma-Aminobutyric Acid and Glutamate in Posttraumatic Stress Disorder and Their Relationships to Self-Reported Sleep Quality

 

Conclusions: Low brain gamma-aminobutyric acid (GABA) concentration in posttraumatic stress disorder (PTSD) is consistent with most findings in panic and social anxiety disorders. Low GABA associated with poor sleep quality is consistent with the hyperarousal theory of both primary insomnia and PTSD. Our data demonstrate that poor sleep quality mediates low parieto-occipital GABA in PTSD. The findings have implications for PTSD treatment approaches.

 

 

And there are some more studies around PTSD, bipolar, and GABA. But I'm sure you can find studies for nearly any disorder with specific supplements/drugs/neuro-chemicals that affirm or contradict the benefits, so I'm not giving a blanket statement on anything, each person and their biological/supplement needs are unique.

 

All I'm saying is targeting the GABA system for me is what I really needed all of this time, and I feel calmly great and refreshed!

 

Never give up!

Edited by Jesus is King, 20 May 2021 - 05:33 AM.

[Mr Serendipity]

I need to update this.

 

So I haven't been taking my stack regularly, it doesn't seem to make much of a difference to my hypomania and pressured speech which I experience daily, so I've just been taking benfotiamine in recent weeks because it helps with digestive issues.

 

But here is what I learnt today.

 

I only took benfotiamine (150mg) and niacinamide (500mg) today, and for the first time in a long time, I didn't experience any hypomania. This was definitely due to adding niacinamide, because I had been only taking benfotiamine for weeks prior. I'm not sure how it works exactly, whether the niacinamide is lowering my methylation which is helping, or just helping cellular metabolism, but I haven't experienced hypomania at all today.

 

The other thing I've been experimenting with the last few months is taurine. It's interesting NAC completely eradicates my OCD, I use to think it was because it increased my glutathione in the brain, but I learnt cysteine also makes taurine. The observable effects with taurine were a major libido increase, better visual clarity, better digestion, and better cognition and memory. But the most interesting observation, is I think taurine seems to better my digestion/microbiome, even more so than probiotics.

 

The last observation was nicotine. I've been a regular smoker for awhile. I recently tried to quit with vaping. One thing I noticed, is when I vape with nicotine, I can go into a deep depression soon after, and I've repeated this experiment a few times and it always happens. So nicotine all this time, has definitely not been a helping to my mental health at all. But I also noted I become my most hypomanic when I haven't had nicotine for awhile, so I feel it works as a crutch of a mood stabiliser.

 

As for amygdala tickling, I'm not pursuing it at this point in time because every time I do it, it always exacerbates my hypomania like clockwork. But even without tickling I experience hypomania daily. Maybe if I show no signs of hypomania for a month I may pursue it again.

 

That's it. I'm gonna rebuild my stack around benfotiamine and nicotiamide, as controlling my hypomania is paramount to me.

 

[Mr Serendipity]

New Theory, New Hope

 

So I recently came down with the cold or flu, it's hard for me to tell. But when I get hit, it seems to hit me harder than anything. Just like when I got COVID last year, I got hit pretty bad, and I took the longest to recover out of all my family members (and I'm the one who takes supplements). So I feel I may have some underlying health condition that could be connected to all my issues, including my bipolar.

 

Now I have Beta Thalassemia Minor/Trait, which is a genetic blood disorder where I make less haemoglobin. Because it's the minor/trait, I've always been told there's no medical treatment necessary because it's asymptomatic. However because I make less haemoglobin, my iron requirements are lower than a normal persons.

 

This brought me to the iron overload theory. If the theory of iron overload affects normal people without blood disorders, how much more could it be effecting me, who's iron level requirements need to be even lower than the normal population?

 

So I searched to see if there was any connection between iron overload and bipolar, and I found a case report and study.

 

 

Hemochromatosis-induced bipolar disorder: a case report

Abstract

Objective: A patient presenting with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, bipolar disorder was found to be affected by high iron hemochromatosis. This prompted us to explore the relation between bipolar disorder and iron overload.

Method: We report the case and review the peer-reviewed literature focusing on mood symptoms in patients with hemochromatosis or iron overload. Animal studies of brain effects of iron overload are summarized. High iron hemochromatosis was confirmed by genetic testing, and treatment was instituted to address iron overload.

Results: Patient's bipolar symptoms completely subsided after phlebotomic reduction of iron overload.

Conclusion: Clinicians should explore the possibility of iron overload and seek genetic confirmation of hemochromatosis in resistant bipolar disorder to avoid unnecessary medication.

 

 

Iron overload among a psychiatric outpatient population

Abstract

Background: Iron overload has been suggested to be an unrecognized cause of psychiatric morbidity. This study sought to estimate the prevalence of iron overload in a large outpatient psychiatric clinic.

Method: A retrospective review of screening blood chemistries was conducted on 661 active outpatients at a large, university outpatient psychiatric clinic to identify elevated iron status results (plasma iron, percentage of iron saturation) suggestive of iron overload. Patients with positive profiles were asked to undergo a subsequent blood chemistry to confirm positive results (plasma iron, percentage of iron saturation, plus plasma ferritin). Patients with positive repeated iron chemistry results were considered likely candidates for iron overload.

Results: Twenty-one patients (3.2%) were identified as meeting one of the criteria suggestive of iron overload on initial screening reports. Thirty-one percent of those who underwent subsequent, confirmatory testing (5/16) continued to meet one of the criteria. On the basis of these results, we estimated a 1% (3.2 x 0.31) prevalence rate of likely candidates for iron overload. A review of these patients' charts indicated that they carried an unexpectedly high rate of bipolar affective disorder (80%) as a diagnosis and were, without exception, atypical in that they were resistant to conventional psychiatric treatment and lacked a family history for this disorder. The prevalence of positive iron overload profiles on a routine blood chemistry was similar to the prevalence of positive thyroid abnormalities based on TSH results in this population.

Conclusion: Blood chemistry profiles suggestive of iron overload may be associated with a small portion of treatment-resistant psychiatric patients. Routine screening for iron abnormalities, especially in treatment-resistant patients, should be considered. Further studies are required to determine the causal association, if any, between iron excess and primary psychiatric illnesses.

 

 

This study and case report shows an incredible link between iron overload and bipolar. In my case this might be the strongest link yet, as my iron requirements are even lower than the average person because of my beta thalassemia minor blood disorder.

 

It's a nice new theory, and something I'm going to explore. I've ordered IP6 for the first time in my life, and will be experimenting with that and aspirin to see if I feel any different at all.

[Mr Serendipity]

Iron overload in beta-thalassaemia minor. A family study

 

Abstract

 

23 descendents of a 74--year-old Englishman who had beta-thalassaemia trait, and died of hepatoma, were studied to discover whether thalassaemia minor alone could predispose to iron overload. Serum ferritin and HLA antigens were assessed in all members, and adults underwent radioiron investigations and liver biopsy. 2 members of the second generation and 1 of the third generation, all of whom had thalassaemia trait, had elevated liver iron concentration, indicating preclinical iron overload. This was not associated with any HLA type. None of the subjects had been treated with exogenous iron. The one member of the second generation who had thalassaemia minor but not iron overload was female, and the 5 members of the third generation with the trait, but with normal serum ferritin levels, were all under the age of 15 years. Members of the family without beta-thalassaemia minor had normal iron metabolism. It is possible that the development of iron overload in 4 members of this family was related to the presence of thalassaemia minor, and not to the inheritance of another abnormal gene causing idiopathic haemochromatosis.

 

This study shows a possible link to iron overload related to beta-thalassaemia minor, which is what I have. And as the previous post shows, iron overload can cause bipolar symptoms.

 

I will say the last 3 days I've been taking IP6, Aspirin, and NAC, and avoiding iron fortified foods, and becoming a vegetarian, I have felt much calmer. But at the same time I am also showing symptoms of a lack of focus, slight euphoria, lower back pain, joint pain, and headaches (I don't suffer with any of these symptoms usually). I notice each of the symptoms occasionally, except for the lack of focus, which seems to be continuous (for example typing this right now, it's hard to concentrate).

 

So I think the chelating stack is working very well, to the point of making me anaemic, so there seems to be very fine line for me. It will require more experimentation, but it's interesting how calm I'm feeling since chelating my iron the last 3 days. Currently I'm taking 4 IP6 capsules which makes 2g, 2 aspirin which makes 150mg, and 1 NAC at 500mg. I think tomorrow I'm going to have to experiment with lower IP6 doses, in this case just 1 capsule at 500mg, and see if I can get that balance of chelating iron but not going anaemic.

 

But my focus is bad right now, I've had to go back and correct several things, and there's only a few sentences.

[Mr Serendipity]

Underestimation of the coexistence of iron deficiencies and thalassemia minors: a single institution experience in Taiwan

 

Abstract

 

Some physicians neglect the possible coexistence of an iron deficiency with a thalassemia minor and do not treat the iron deficiency accordingly. This motivated us to conduct this study. We retrospectively reviewed the records of 3892 patients who visited our clinics and had hemoglobin (Hb) electrophoreses performed in our hematologic laboratory from August 1, 2007 to December 31, 2012. The thalassemia minors were identified by characteristic complete blood count (CBC) parameters obtained from an autoanalyzer and Hb electrophoresis, and some cases were confirmed with molecular tests. Then, we checked iron studies [ferritin and/or serum iron with total iron-binding capacity (TIBC)] to determine the coexistence of an iron deficiency with a thalassemia minor and a response to iron, if such treatments were given. We found 792 cases with thalassemia minors, and excluded those without iron studies, with 661 cases as our sample. A total of 202/661 cases (31%) also had iron deficiencies. They had lower red blood cell (RBC) counts, Hb, and ferritin levels as compared to those thalassemia minor cases without coexistence of iron deficiencies. We concluded that the thalassemia minor patients did not have iron overload complications in our population. On the contrary, iron deficiencies commonly coexist in the clinical visits. We propose that if Hb < 11.5 g/dL in a case of thalassemia minor, one should screen for iron deficiency simultaneously. The sensitivity is 79.8% and the specificity is 82.6%. Therefore, physicians should be aware of this coexisting condition, and know how to recognize and treat it accordingly.

 

Here we have the flip side, where iron deficiencies were more associated with thalassemia minor rather than iron overload. Which would mirror my current experience of anaemic symptoms since integrating IP6 for chelation and avoiding iron rich foods on purpose.

[Mr Serendipity]

The anaemic theory as the cause of my mental issues may be a very real possibility.

 

1. So far chelating iron from the blood using my chelating stack which includes IP6 sends me into anaemia. Shortness of breath, lower back pain, and loss of concentration all become significantly observable after taking it.

 

2. There's a theory by some that lowering iron can help retain youthful looks and increase lifespan due to lower oxidative stress, and one can do this through bloodletting and chelating. As someone who is 33, I do look much younger for my age, such as 18-20. Going by this theory, I may have been low on iron for a long time, maybe through poor absorption.

 

3. There is a link between bipolar symptoms occurring through anaemia as well as iron overload.

 

4. Due to my blood disorder, beta-thalassemia trait/minor/carrier, I already make less haemoglobin, and we're know to already be mildly anaemic, but require no treatment. However iron deficiency anaemia can co-exist at the same time, but is also harder to diagnose and distinguish because of the beta thalassemia.

 

5. Smoking. Relearning the basics of how smoking damages health, one way is how carbon monoxide displaces haemoglobin in the blood. I've been smoking for the past 17 years, with some periods of being able to quit and abstain. Since I already create less haemoglobin, displacing more with smoking could have been contributing to a long term anaemia. What's also interesting, is the time I had that mini pop, was the year at university I didn't smoke (2010-2011), and since then have smoked and not gotten the same results, but suffered bipolar and strong emotional symptoms.

 

6. The palm of my hands have always been pale/yellowy, but I always assumed that was due to just having beta thalassemia trait, rather than a co-existing iron deficiency anaemia.

 

 

So the anaemic theory may be a real possibility. A lot of my emotional issues in recent years could simply have been because my brain has been starved of oxygen due to long term anaemia which may be the result of a combination of my blood disorder (which makes less haemoglobin), smoking (which displaces haemoglobin), and possible B9, B12, or Iron deficiencies (iron being the most possible because of the aforementioned anaemia induced effects chelating has on me).

 

This could also mean amygdala tickling raises my oxygen needs in the brain, which my body can't supply, and thus I experience bipolar symptoms.

 

Regardless of what is it, I've now started taking B9 and B12 in their methyl forms. I've also quit smoking, which while I've struggled to do before, I've never had a stronger reason to quit until now, after relearning that I already genetically create less haemoglobin, and how smoking displaces more haemoglobin in the body via carbon monoxide. So I'm hoping I've quit for good this time.

 

Lastly I've requested a ferritin test from my local surgery. I don't want to supplement iron until I see what my results are, so I'll stick with the B9/B12 and smoking cessation until then. My blood test is booked in for the 12th November, but I honestly have no idea what the blood test will be, since it's on the NHS, and they usually do what they want and ignore requests, but I'm hoping the test will include ferritin.

 

So now it's a point of waiting for my blood results and observe how smoking cessation and adding B9/B12 effect me. 

Edited by Mr Serendipity, 25 October 2021 - 12:15 AM.

[Mr Serendipity]

So the new hope new theory seems to be looking positive.

 

Earlier this week I had severe hypomania and pressured speech, whereas yesterday it was significantly less, and today it feels non existent. This is around a week of supplementing b9 and b12 in their methyl forms.

 

I have however developed the side effect of insomnia, which from what I've read, may be due to increased potassium requirements from the b9 & b12. So I'm trying to consume more potatoes to see if I can offset this side effect. 

 

I googled keywords "b12" and "b9" with "bipolar" and "hypomania", and a few studies came up linking them and their symptoms.

 

I have also noticed an increase in pinkness in the palms of my hands. I still think I may need to supplement iron, but I'm still waiting on my blood test, which is 3 weeks away.

 

One interesting hindsight, is cardio exercise would also cause me to become hypomanic afterward. If I was indeed somewhat anaemic due to deficiencies to start with, cardio exercise would have exacerbated this anaemia due to increase oxygen needs from red blood cells during exercise, thus causing me to become hypomanic afterward. So theory goes.

 

Anyway it's all rather interesting, let's wait and see how my results are in the coming weeks.

[Mr Serendipity]

Well my turn around has been remarkable. As this thread can attest to my insanity over the past few years, it seems to be a simple case of either B9 or B12 deficiency.

 

Here's a case report from 2003: 

 

 

[Psychiatric manifestations of vitamin B12 deficiency: a case report]

 

Abstract

 

Psychiatric manifestations are frequently associated with pernicious anemia including depression, mania, psychosis, dementia. We report a case of a patient with vitamin B12 deficiency, who has presented severe depression with delusion and Capgras' syndrome, delusion with lability of mood and hypomania successively, during a period of two Months. Case report - Mme V., a 64-Year-old woman, was admitted to the hospital because of confusion. She had no history of psychiatric problems. She had history of diabetes, hypertension and femoral prosthesis. The red blood count revealed a normocytosis with anemia (hemoglobin=11,4 g/dl). At admission she was uncooperative, disoriented in time and presented memory and attention impairment and sleep disorders. She seemed sad and older than her real age. Facial expression and spontaneous movements were reduced, her speech and movements were very slow. She had depressed mood, guilt complex, incurability and devaluation impressions. She had a Capgras' syndrome and delusion of persecution. Her neurologic examination, cerebral scanner and EEG were postponed because of uncooperation. Further investigations confirmed anemia (hemoglobin=11,4 g/dl) and revealed vitamin B12 deficiency (52 pmol/l) and normal folate level. Antibodies to parietal cells were positive in the serum and antibodies to intrinsic factor were negative. An iron deficiency was associated (serum iron=7 micromol/l; serum ferritin concentration=24 mg/l; serum transferrin concentration=3,16 g/l). This association explained normocytocis anemia. Thyroid function, hepatic and renal tests, glycemia, TP, TCA, VS, VDRL-TPHA were normal. Vitamin B12 replacement therapy was started with hydroxycobalamin 1 000 ng/day im for 10 days and iron replacement therapy. Her mental state improved dramatically within a few days. After one week of treatment the only remaining symptoms were lability of mood, delusion of persecution, Capgras' syndrome but disappeared totally 9 days after the beginning of the treatment. A neurologic examination was possible because of cooperation. All the tendon reflexes of inferior members were absent. The plantars were in flexion and there was a left inferior member hypoesthesia. The cerebral scan and EEG were normal. Fundic biopsy, realized by fibroscopy, revealed fundic atrophia and intestinal metaplasia compatible with Biermers' disease. The iron deficiency exploration concluded diet deficiency. Mme V. appeared euphoric, her speech was very rapid with play on words and overactivity. This hypomania state totally disappeared 3 days after. Six Months after her hospitalisation, she presented an hypothyroidism (TSH=3,780; T3=1,35; T4=1,08). A thyroid hormones replacement was started and she continued to receive Monthly B12 replacement. Discussion - This case report illustrates psychiatric manifestations of Biermers' disease. The clinical arguments in favour are: white woman, more than 60 Years old, no history of psychiatric problems, atypical symptoms (confusional state with psychiatric symptoms), fluctuation of symptoms (severe depression with confusional state, delusion of persecution and Capgras' syndrome; delusion with lability of mood and hypomania), dramatic improvement after 9 days of vitamin B12 replacement therapy. The biological arguments are: anemia, vitamin B12 deficiency, normal folate level, atrophia and fundic metaplasia, positive antibodies to parietal cells in the serum, association between Biermers' disease and autoimmune disease (Haschimoto thyroidite). Psychiatric manifestations can occur in the presence of low serum B12 levels but in the absence of the other well recognized neurological and haematological abnormalities of pernicious anemia. Mental or psychological changes may precede haematological signs by Months or Years. They can be the initial symptoms or the only ones. Verbank et al. described the case of a patient with vitamin B12 deficiency in whom hypomania, paranoia and depression had been successively presented during a period of 5 Years before anemia have been developed. The case of Mme V. is similar in the succession of severe depression with delusion of persecution and Capgras' syndrome, delusion with lability of mood and hypomania, during a period of two Months. This report seems to be the first one of a sequence of several psychiatric states with pernicious anemia during a period of two Months with normocytosis anemia. To illustrate this illness we reviewed the literature regarding psychopathology associated with B12 deficiency. The most common psychiatric symptoms were depression, mania, psychotic symptoms, cognitive impairment and obsessive compulsive disorder. The neuropsychiatric severity by vitamin B12 deficiency and the therapeutic efficacy depends on the duration of signs and symptoms. Conclusion - We recommend consideration of B12 deficiency and serum B12 determinations in all the patients with organic mental disorders, atypical psychiatric symptoms and fluctuation of symptomatology. B12 levels should be evaluated with treatment resistant depressive disorders, dementia, psychosis or risk factors for malnutrition such as alcoholism or advancing age associated with neurological symptoms, anemia, malabsorption, gastrointestinal surgery, parasite infestation or strict vegetarian diet. In first intention, B12 deficiency should be researched by serum B12 determination (normal 200-950 pg/ml). Studies of methylmalonic acid and homocysteine showed that they are very sensitive functional indicators of cobalamin status especially when other evidence of cobalamin (B12) deficiency was equivocal. Measurement of methylmalonic acid (normal 73-271 nmol/l) and homocysteine (normal 5,4-13,9 micromol/l) should not replace the measurement of serum cobalamin.

 

This case study reflects my quick turn around from hypomania after only a week and a half of B9 & B12 supplementation.

 

Here's another case report from 2007:

 

 

Vitamin B12 Deficiency Manifested as Mania: A Case Report

 

Sir: Multiple psychiatric symptoms may precede pernicious anemia. Only 1 case of full manic syndrome secondary to B12 deficiency has been reported.1

 

Case report. Ms. A was a 35-year-old woman with no personal or family history of psychiatric disorders, who was admitted to the hospital in February of 2005 with a 3-week history of episodes of manic symptoms of several hours' duration, including grandiosity, hyperactivity, sexual indiscretion, hyperphagia, irritable mood, reckless behavior, flight of ideas, and overbearing manner. These episodes had a sudden onset and conclusion, and the patient was able to remember them. No hallucinations were reported at any time.

 

At admission, she was oriented in all spheres, but was easily distractible. Full manic syndrome (DSM-IV criteria) was present and there was no coexisting delirium. All these psychiatric symptoms disappeared after 1 hour, without any medical intervention.

 

An examination revealed the presence of a left Babinski's reflex and ataxia, as well as a bilateral loss of proprioception, vibration, and sensation of light touch and pain in the lower extremities. Strength and reflex in the lower extremities were diminished.

 

The results of general blood chemistries, a thyroid function test, and a comprehensive drug screen were within normal limits. Although the results of electroencephalogram (EEG) and brain magnetic resonance imaging were normal, the duration, as well as the sudden onset and conclusion of episodes, suggested an epileptic cause for this patient's mania.2 Ms. A was treated with valproic acid for 3 weeks with no improvement.

 

Serum vitamin B12 level was measured and was found to be markedly diminished––less than 60 pg/mL. Vitamin B12 (1000 µg/day) was administered intravenously for 1 week. After the third day of B12 replacement therapy, our patient did not experience new manic episodes. Therapy was continued with 1000 µg intramuscular injections weekly for 1 month and then with monthly intramuscular injections as maintenance treatment. Within 1 month, neurologic symptoms had improved. One year after B12 vitamin replacement started, her mental status was still normal.

 

Although many psychiatric symptoms have been considered to be related to B12 deficiency,3,4 this is the first report of short duration episodes of manic symptoms secondary to B12 deficiency. The absence of previous psychiatric or medical disorders, coupled with her continued clinical remission while she was receiving B12 alone, argues that B12 deficiency was the most likely cause of her psychiatric disorder.

 

Our case could also raise the hypothesis of different neuro-biological mechanisms underlying mood disorders and the importance of B12 and folate in their genesis.5

 

Another quick turn around from mania symptoms after the 3rd day.

 

There's not much information regarding folate and mania, from the studies I've come across there's a lack of evidence, and can even increase agitation. I also know taking folate can hide a B12 deficiency in blood tests.

 

So it could be a simple case of B12 deficiency for myself. A decade ago I've taken Methyl B12 with no side effects, but haven't taken it regularly at all in recent years. Since taking methyl B9 & B12 my symptoms have improved, however I've developed the side effect of insomnia, you feel tired, but can't go to sleep. Since I didn't experience this side effect a decade ago with Methyl B12, I assume it might be due to the methyl folate.

 

So here's me hoping I can drop the methyl folate and stop the insomnia side effect, and just stick with the methyl b12 instead and continue to see improvement from hypomania and pressured. So that's what I'll be experimenting with, but will keep the methyl folate on hand just in case.

[Mr Serendipity]

My hypomania and pressured speech returned. I had dropped the methyl-folate (b9) because of its insomnia side effect, and instead just kept taking the methyl-cobalamin (b12). However going by the reemergence of my symptoms, my improvement from hypomania may have come more from the b9 than the b12. There’s some literature linking mania to folate deficiency as well. And some literature linking homocysteine levels to mania also.

Edited by Mr Serendipity, 09 November 2021 - 12:34 AM.

[Mr Serendipity]

Okay I may have possibly found the connection to all of this, which is Vitamin K2 MK-4, as well as a calcium deficiency.

 

Quick recap:

 

1. My mini euphoria experience occurred during university. At that time I was consuming around 6 raw egg yolks everyday. Egg yolks are high in vitamin K2 MK4.

2. I’m lactose intolerant, so have been avoiding most milk dairy the last decade, thus possibly creating a vitamin d deficiency, and definitely creating a calcium deficiency.

 

3. Experimenting with vitamin k2 mk4 a couple of years ago would make me light headed and lack concentration, this I can only conclude was due to the lack of calcium in my diet, and I shelved the supplement.

 

4. I created a thread on here about on milk being a nootropic, which may have been due to the increased calcium rather than b12. https://www.longecit...as-a-nootropic/

 

5. I recently experimented with megadosing vitamin d to get my levels up (300,000 IU in a single dose twice in the space of a couple of weeks). Low vitamin d levels were part of my problem (though my levels were never tested) as it cured a long term indigestion problem I suffered with. However I’ve been suffering from hypercalcemia symptoms (tiredness, sleeping for a long time, muscle weakness, bone pain, and nausea). 

 

6. Then last night I took 10mg Vitamin k2 mk4 with a yogurt, and this morning took emu oil (apparently the highest food source of k2 mk4) with a yogurt.

 

My brain calmness and clarity of thought shot up, very noticeable, very tranquil, no OCD thoughts.

Vitamin k2 mk-4 helps build myelin. I think the connection lies there somewhere. I found a study looking for a correlation between BD and MS.

 

Also high PTH (parathyroid hormone) and low vitamin d is implicated in bipolar. Now I’ve raised my vitamin d and have experienced hypercalcemia, I think I can assume my PTH is low now, and any vitamin d deficiency has been corrected,

 

So my focus is on experimenting with vitamin k2, calcium, to see if my mental issues improve, using a mix of supplementation, and consuming dairy and emu oil.

 

The other hypothesis is the other components in emu oil such as the fatty acids gave me the increase in clarity and improved mental calmness.

 

[Mr Serendipity]

Ketosis.

 

Ketosis may be the answer to all my problems. My problems may be a result of metabolic dysfunction in the brain causing my bipolar symptoms that all the supplements and drugs in the world can’t fix. I’ve had experience with my snoring in the past being fixed by ketosis, where all the supplements and methods I used couldn’t fix my snoring, so I think my snoring is related too.

 

Also lecithin/increasing acetylcholine helps with hypomania.

 

I’ll stick to it for 30 days and report back. Should be easy to observe a positive change because my hypomania has been very prominent as of late.

[zorba990]

Ketosis.

Ketosis may be the answer to all my problems. My problems may be a result of metabolic dysfunction in the brain causing my bipolar symptoms that all the supplements and drugs in the world can’t fix. I’ve had experience with my snoring in the past being fixed by ketosis, where all the supplements and methods I used couldn’t fix my snoring, so I think my snoring is related too.

Also lecithin/increasing acetylcholine helps with hypomania.

I’ll stick to it for 30 days and report back. Should be easy to observe a positive change because my hypomania has been very prominent as of late.

Remember Ketosis alters gut flora, so the root change may be due to that:

https://www.ucsf.edu...ome-humans-mice

https://www.ncbi.nlm...les/PMC5923270/
"Neurovascular integrity, including cerebral blood flow (CBF) and blood-brain barrier (BBB) function, plays a major role in determining cognitive capability. Recent studies suggest that neurovascular integrity could be regulated by the gut microbiome. The purpose of the study was to identify if ketogenic diet (KD) intervention would alter gut microbiome and enhance neurovascular functions, and thus reduce risk for neurodegeneration in young healthy mice (12–14 weeks old). Here we show that with 16 weeks of KD, mice had significant increases in CBF and P-glycoprotein transports on BBB to facilitate clearance of amyloid-beta, a hallmark of Alzheimer’s disease (AD). These neurovascular enhancements were associated with reduced mechanistic target of rapamycin (mTOR) and increased endothelial nitric oxide synthase (eNOS) protein expressions. KD also increased the relative abundance of putatively beneficial gut microbiota (Akkermansia muciniphila and Lactobacillus), and reduced that of putatively pro-inflammatory taxa (Desulfovibrio and Turicibacter). We also observed that KD reduced blood glucose levels and body weight, and increased blood ketone levels, which might be associated with gut microbiome alteration. Our findings suggest that KD intervention started in the early stage may enhance brain vascular function, increase beneficial gut microbiota, improve metabolic profile, and reduce risk for AD."

[Mr Serendipity]

Quick update, I haven’t felt much from ketosis yet these past few days.

 

But this evening was the first time I ate 25% fat beef mince cooked with coconut oil. I then had a 2 hour nap, and I’ve woken up so refreshed and generally uplifted, a noticeable change from my usual. Since this didn’t happen from being on a keto diet until this meal, I suspect it has to do with the MCT’s in the coconut oil. So I’m going to make sure I try and consume some coconut oil through my cooking.

 

To be honest I’ve always wanted to make coconut oil a part of my intake, but the wife always cooks and always refuses to use coconut oil (likes olive oil instead). But now I’m following keto I’m cooking my own meals so I stick to it, and am just creating basic meals for convenience, such as cheese omelettes in my omelette maker, or mince with spices.

 

 

Remember Ketosis alters gut flora, so the root change may be due to that:

 

Could be. I haven’t done ketosis long enough to notice any long term changes yet, I only have todays positive experience of ketosis to go on in recent memory. But if this works long term, I’ll be interested with why it works so well.

Edited by Mr Serendipity, 31 March 2022 - 01:09 AM.