3 replies to this topic

[jack black]

this is completely news for me, but there is an arachidonic acid hypothesis of bipolar and depression:

Mood-Stabilizers Target the Brain Arachidonic Acid Cascade

 

Bipolar disorder (BD) is a severe psychiatric illness characterized by recurrent manic and depressive episodes, without a characteristic neuropathology or clear etiology. Drugs effective in BD target many key signaling pathways in animal and cell studies. However, their mode of action in the BD brain remains elusive. In the rat brain, some of the mood stabilizers effective in treating mania (lithium, carbamazepine, valproate) or depression (lamotrigine) in BD are reported to decrease transcription of cytosolic phospholipase A₂ and cyclooxygenase-2 and to reduce levels of AP-2 and NF-κB, transcription factors of the two enzymes. The anti-manic drugs also decrease arachidonic acid (AA) turnover in brain phospholipids when given chronically to rats. Thus, drugs effective in BD commonly target AA cascade kinetics as well as AA cascade enzymes and their transcription factors in the rat brain. These studies suggest that BD is associated with increased AA signaling in the brain. Developing therapeutic agents that suppress brain AA signaling could lead to additional treatments for BD. In this review, we discuss the mechanisms of action of mood stabilizers and the effects of docosahexaenoic acid on AA cascade enzymes in relation to BD.

https://www.ncbi.nlm...les/PMC2825027/

 

 

furthermore:

NSAID induced hypomania in stable bipolar disorder

 

Some case reports have proposed the antidepressant role of the non-steroidal anti- inflammatory drugs. These effects might reflect the activation syndrome[1] induced by these agents.

We describe three patients of bipolar mood disorder currently in remission as per the DSM-IV criterion who were on treatment with mood stabilizers (lithium carbonate/sodium valproate). Patients experienced pain due to neuromuscular conditions and were advised treatment with NSAIDs (nimesulide/etoricoxib/celecoxib). While on treatment, they developed symptoms of hypomania. The symptoms were seen within 3 days of the administration of the agent and remitted when the NSAIDs were stopped. Symptoms reappeared with the drug rechallenge and disappeared within 2 days of drug discontinuation. All patients stabilized after that and did not restart the NSAID.

https://www.ncbi.nlm...les/PMC3512378/

 

 

amazingly, even low dose aspirin is effective:

 

 

The AA hypothesis for mood stabilizer action is consistent with reports that low-dose aspirin reduced morbidity in patients taking lithium, and that high n-3 and/or low n-6 polyunsaturated fatty acid diets, which in rats reduce brain AA metabolism, were effective in BD and migraine patients.

https://www.ncbi.nlm...pubmed/24786695

 

 

I personally never noticed any effects from aspirin or NSAIDs, but benefited from low dose Li. Now I know Li is COX2 inhibitor!

[jack black]

No takers?

This hypothesis potentially explains why allopurinol, a common anti-gout medication, is effective in treatment of mania, something that is not well explained, but well accepted.

 

turns out

"In vitro and in vivo arachidonic acid conversions into biologically active derivatives are enhanced by uric acid"

https://www.scienced...006295281900940

[Mind_Paralysis]

Fascinating stuff... this seems to mirror the Kynurenic Acid hypothesis of Schizophrenia - and since there have been multiple similarities, on the genetic level, between Bipolars and Schizophrenics, then this is certainly intriguing.

 

Would be interesting to see what would happen if Bipolars were given Arachidonic Acid fat-supplements in a pilot-study? Because there are multiple Bipolars whom claim that Omega-3, the OTHER primary constituent of the central nervous system, improves their symptoms. What's the relationship between the two? Could it, in fact, actually be about the BALANCE between these two fatty acids, and their metabolism? I mean, logically, they should be getting better from eating BUTTER, not FISH - but fish it is... Why?

 

A big difference between Bipolars and Schizo's, even though there is comorbidity, is of course that the NMDA-antagonist MEMANTINE, which is also a weak D2-agonist, actually seems to be mood-stabilizing, and there are a few pilot-studies showing efficacy in Rapid Cycling - however, people with Schizophrenia whom take it, have very mixed results - most point towards worsening of symptoms, yet one or two studies show improvements. A direct worsening of symptoms make sense, since D2 and NMDA are both believed to be the key cornerstones in Schizophrenia -treatments - NMDA-agonism is coming up as a potential treatment-method, becuase

 

 

I do wonder... what effect does NSAID's have on Kynurenic Acid? Do they increase production? If so, I guess Schizophrenics would have to stay away from NSAID's.

 

 

As a final side-note, I haven't noticed any improvement with NSAID's, to my knowledge - I seem to feel better when I use Paracetamol though, which obviously work from a very different mechanism, namely the cannabinoid receptors. In theory, since CB is known to trigger mania and psychosis in those with bipolar, they might need to stay away from Paracetamol. (well, high-dose paracet, that is)

 

 

References:

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

The NMDA Receptor and Schizophrenia: From Pathophysiology to Treatment

https://www.ncbi.nlm...les/PMC5518924/

 

Memantine: New prospective in bipolar disorder treatment

https://www.ncbi.nlm...les/PMC4274590/

[jack black]

As a final side-note, I haven't noticed any improvement with NSAID's, to my knowledge

 

same here, i guess we don't have bipolar, or at least the one mediated by AA. but, i have no illusion that this is the only mechanism for bipolar, just like Kynurenic Acid may not be responsible for all Schizophrenia.

 

BTW, thanks for replying. i hate monologues and they are common here.