Yet Again, Brain Inflammation Linked To Depression

[haidut]

This is the first time I see a scientist propose officially that depression be treated with anti-inflammatory drugs. I posted a study showing a human equivalent dosage of 500mg aspirin being a more effective antidepressant (in mice) than Prozac.
I think the more important question is if inflammation in other parts of the organism can cause depression as well. There are several studies on PubMed showing that it can, which explains why people with chronic inflammatory conditions often have depression as well. So, maybe aspirin is an even more versatile drug than we thought.

http://thenational.net/news/new-study-l ... sion/6031/

"...Current treatments do not target inflammation, and treating depression with anti-inflammatories is one avenue for future research. Depression is a complex illness and we know that it takes more than one biological change to tip someone into an episode. But we now believe that inflammation in the brain is one of these changes and that’s an important step forward."

 

[CCD]

Really interested in the lactic acid - serotonin connection in depression. Would be great to be able to simply take sodium bicarb to improve mood. Anything else other than aspirin to counter inflammation? Stuff like nettle and tulsi seem fairly poor anti - inflammations.
The one thing that cured my depression last time was BZP but now this piparizine is illegal

 

[haidut]

Really interested in the lactic acid - serotonin connection in depression. Would be great to be able to simply take sodium bicarb to improve mood. Anything else other than aspirin to counter inflammation? Stuff like nettle and tulsi seem fairly poor anti - inflammations.
The one thing that cured my depression last time was BZP but now this piparizine is illegal

Since ketamine has been shown to quickly reverse treatment-resistant depression, in theory anything that antagonizes NMDA (like ketamine) should be helpful. Magnesium is a powerful NMDA antagonist and has some evidence for helping resistant depression.
http://www.ncbi.nlm.nih.gov/pubmed/16542786

Other NMDA antagonists include theanine and to some degree taurine, and they both have been studied for depression but mostly in animal models.

 

[Such_Saturation]

I have been seeing people complain because scientists are starting to claim it comes from the "gut". To them this is an insensible theory because they have tied their illness to many aspects of their life and they think it is an overly complex matter. This is unfortunate, because at some point with this way of thinking they can even stop having faith in simple lifestyle and dietary changes, leading to a spiral.

 

[CCD]

Really interested in the lactic acid - serotonin connection in depression. Would be great to be able to simply take sodium bicarb to improve mood. Anything else other than aspirin to counter inflammation? Stuff like nettle and tulsi seem fairly poor anti - inflammations.
The one thing that cured my depression last time was BZP but now this piparizine is illegal

Since ketamine has been shown to quickly reverse treatment-resistant depression, in theory anything that antagonizes NMDA (like ketamine) should be helpful. Magnesium is a powerful NMDA antagonist and has some evidence for helping resistant depression.
http://www.ncbi.nlm.nih.gov/pubmed/16542786

Other NMDA antagonists include theanine and to some degree taurine, and they both have been studied for depression but mostly in animal models.

My friend did try k and found a small line in the morning cleared depression for 5 or 6 hrs. Made him go a bit wobbly in the long term though.
I have tried magnsm and taurine and theanine to no great effect. I worry about the diff standard and types of these available. Maybe i took the wrong types...i spend way too much £ on supps!!

 

[mujuro]

I have bipolar disorder and can confirm the potent antidepressant effects of ketamine. However I found that there is a significant subjective difference between racemic ketamine and (s)-ketamine, in both the high and antidepressant after-effect. One can only go so far towards mimicking infusion blood levels. There are currently trials underway in my country for treating depression with ketamine and even though doors would open easily for me, I haven't had any depression in weeks.

My psychiatrist informs me on the happenings in the upper echelons of the psychiatric world, and for a few months now he has told me that it is becoming standard practice to add NAC and ALCAR to normal pharmacotherapy with drugs.

 

[fyo]

if inflammation in other parts of the organism can cause depression as well.

I'm pretty sure I've seen several studies on LPS/endotoxin injections causing depressive behavior in mice and men. I imagine the brain senses this and then itself takes on an inflammatory state, perhaps.

A leaky guy would be like having an endoxin injection. Chronically leaky guy = chronic injection/infection = chronic stress = eventual depression.

 

[Koveras]

This is the first time I see a scientist propose officially that depression be treated with anti-inflammatory drugs. I posted a study showing a human equivalent dosage of 500mg aspirin being a more effective antidepressant (in mice) than Prozac.
I think the more important question is if inflammation in other parts of the organism can cause depression as well. There are several studies on PubMed showing that it can, which explains why people with chronic inflammatory conditions often have depression as well. So, maybe aspirin is an even more versatile drug than we thought.

http://thenational.net/news/new-study-l ... sion/6031/

"...Current treatments do not target inflammation, and treating depression with anti-inflammatories is one avenue for future research. Depression is a complex illness and we know that it takes more than one biological change to tip someone into an episode. But we now believe that inflammation in the brain is one of these changes and that’s an important step forward."

"The researchers found that a protein called JNK when active, represses the generation of new neurons in the hippocampus, a part of the brain that controls emotions and learning. By inhibiting JNK solely in newly generated nerve cells in the hippocampus, the researchers were able to alleviate anxiety and depressive behaviour in mice. This previously unknown mechanism brings fresh insight on how the brain works to regulate mood and indicates that inhibitors of JNK, such as the one used here, can provide a new avenue for anti-depressant and anxiolytic drug development."

"Promoting adult hippocampal neurogenesis is expected to induce neuroplastic changes that improve mood and alleviate anxiety. However, the underlying mechanisms remain largely unknown and the hypothesis itself is controversial. Here we show that mice lacking Jnk1, or c-Jun N-terminal kinase (JNK) inhibitor-treated mice, display increased neurogenesis in adult hippocampus characterized by enhanced cell proliferation and survival, and increased maturation in the ventral region. Correspondingly, anxiety behaviour is reduced in a battery of tests, except when neurogenesis is prevented by AraC treatment. Using engineered retroviruses, we show that exclusive inhibition of JNK in adult-born granule cells alleviates anxiety and reduces depressive-like behaviour. These data validate the neurogenesis hypothesis of anxiety. Moreover, they establish a causal role for JNK in the hippocampal neurogenic niche and anxiety behaviour, and advocate targeting of JNK as an avenue for novel therapies against affective disorders."

"Inflammatory signals, changes in levels of reactive oxygen species, ultraviolet radiation, protein synthesis inhibitors, and a variety of stress stimuli can activate JNK."

"The exposure of mammalian cells to ultraviolet (UV) irradiation leads to the activation of transcription factors, such as AP-1 and NFkB. We demonstrate that aspirin, a promising cancer chemopreventative agent, inhibited UVC-induced AP-1 activity in JB6 cells. In JB6 cells, UVC stimulated Erks, JNKs and P38 kinase activities; aspirin only inhibited activation of JNKs, but not the other MAP kinases. Since the transcription factor AP-1 is important for the process of tumor promotion, the inhibitory effect of aspirin on AP-1 activation suggests that it can be used as a chemopreventative agent against skin cancer."

https://www.sciencedaily.com/releases/2017/01/170118082644.htm

http://www.nature.com/mp/journal/vaop/ncurrent/full/mp2016203a.html

c-Jun N-terminal kinases - Wikipedia

Inhibition of ultraviolet C irradiation-induced AP-1 activity by aspirin is through inhibition of JNKs but not erks or P38 MAP kinase. - PubMed - NCBI

 

[haidut]

"The researchers found that a protein called JNK when active, represses the generation of new neurons in the hippocampus, a part of the brain that controls emotions and learning. By inhibiting JNK solely in newly generated nerve cells in the hippocampus, the researchers were able to alleviate anxiety and depressive behaviour in mice. This previously unknown mechanism brings fresh insight on how the brain works to regulate mood and indicates that inhibitors of JNK, such as the one used here, can provide a new avenue for anti-depressant and anxiolytic drug development."

"Promoting adult hippocampal neurogenesis is expected to induce neuroplastic changes that improve mood and alleviate anxiety. However, the underlying mechanisms remain largely unknown and the hypothesis itself is controversial. Here we show that mice lacking Jnk1, or c-Jun N-terminal kinase (JNK) inhibitor-treated mice, display increased neurogenesis in adult hippocampus characterized by enhanced cell proliferation and survival, and increased maturation in the ventral region. Correspondingly, anxiety behaviour is reduced in a battery of tests, except when neurogenesis is prevented by AraC treatment. Using engineered retroviruses, we show that exclusive inhibition of JNK in adult-born granule cells alleviates anxiety and reduces depressive-like behaviour. These data validate the neurogenesis hypothesis of anxiety. Moreover, they establish a causal role for JNK in the hippocampal neurogenic niche and anxiety behaviour, and advocate targeting of JNK as an avenue for novel therapies against affective disorders."

"Inflammatory signals, changes in levels of reactive oxygen species, ultraviolet radiation, protein synthesis inhibitors, and a variety of stress stimuli can activate JNK."

"The exposure of mammalian cells to ultraviolet (UV) irradiation leads to the activation of transcription factors, such as AP-1 and NFkB. We demonstrate that aspirin, a promising cancer chemopreventative agent, inhibited UVC-induced AP-1 activity in JB6 cells. In JB6 cells, UVC stimulated Erks, JNKs and P38 kinase activities; aspirin only inhibited activation of JNKs, but not the other MAP kinases. Since the transcription factor AP-1 is important for the process of tumor promotion, the inhibitory effect of aspirin on AP-1 activation suggests that it can be used as a chemopreventative agent against skin cancer."

https://www.sciencedaily.com/releases/2017/01/170118082644.htm

Molecular Psychiatry - JNK1 controls adult hippocampal neurogenesis and imposes cell-autonomous control of anxiety behaviour from the neurogenic niche

c-Jun N-terminal kinases - Wikipedia

Inhibition of ultraviolet C irradiation-induced AP-1 activity by aspirin is through inhibition of JNKs but not erks or P38 MAP kinase. - PubMed - NCBI

Yep, thanks. I posted something similar in another thread.
Aspirin Is A Janus Kinase (JK) Inhibitor

 

[Koveras]

Yep, thanks. I posted something similar in another thread.
Aspirin Is A Janus Kinase (JK) Inhibitor

Separate but interrelated pathways!

 

[johnsmith]

Supposedly near infrared light therapy, when shone on the head, is a great anti-inflammatory for the brain as well. I've been looking into how to do this and thinking of getting a better device than my 250 watt infrared bulb. If anyone has tips it would be much appreciated.

 

[Amazoniac]

Nutrition and Lifestyle Intervention on Mood and Neurological Disorders
Gary of the Nulls was involved.

"This group study explored how an intervention of diet and lifestyle, including a vegan diet, fruit and vegetable juicing, nutritional supplements, regular exercise, and destressing techniques, would affect 27 subjects with anxiety, depression, poor memory, dementia, Alzheimer’s disease, Parkinson’s disease, history of stroke, or multiple sclerosis. Several subjects had overlapping conditions. Videotaped testimonials were obtained describing subjective results. Testimonials stated multiple benefits across all conditions addressed by the study, with subjects often reporting substantial benefits. These results demonstrate that an intervention of diet, juicing, supplements, exercise, and lifestyle may provide considerable benefits for all conditions addressed."

 

[Suikerbuik]

Thank you for posting that study @Amazoniac, do you think the benefits could be even more pronounced if some aspects of the diet were changed?

 

[InChristAlone]

Be careful not to think a vegan diet cures depression. Many vegan YouTuber's still depressed (at least one said she decided to go on antidepressants it was that bad). In my opinion after following the vegan community (and more specifically raw vegan and fruitarian) for 9 yrs there may even be more mental illness among them.

 

[Amazoniac]

Thank you for posting that study @Amazoniac, do you think the benefits could be even more pronounced if some aspects of the diet were changed?

Ach ja, various ways. It was a standard protocol for everyone, this alone is an issue. Another example of standarization is the 50 B-complex, the idea of fixing all them to 50 mg is silly. I mean, I know that the body only accepts rounded numbers, but why 50 for all them?

Regarding the model above, people often underestimate issues with protein, from digestion to metabolism. Gluten and dairy are two foods that tend to inflamme many and people adapt to such state to the point of barely noticing. The easiest way to know is to test, and a temporary vegan diet can be useful for that purpose. Most therapeutic diets exclude animal proteid for a while.

 

[johnsmith]

Ach ja, various ways. It was a standard protocol for everyone, this alone is an issue. Another example of standarization is the 50 B-complex, the idea of fixing all them to 50 mg is silly. I mean, I know that the body only accepts rounded numbers, but why 50 for all them?

Regarding the model above, people often underestimate issues with protein, from digestion to metabolism. Gluten and dairy are two foods that tend to inflamme many and people adapt to such state to the point of barely noticing. The easiest way to know is to test, and a temporary vegan diet can be useful for that purpose.

I feel much better after taking some measures to lower glutamate. Cutting out dairy was one of them. I will soon try to reintroduce some dairy to see if it was more so due to the glutamate/gaba balancing supplements I started. I did what Chris Masterjohn recommends for glutamate sensitivity, b6, 3g glycine with each meal, and magnesium-glycinate. I also started consistently taking 2 aspirin each morning.