The Dopamine Breakdown Product, Homocysteine, Is Involved In Working Memory Deficits

[Hans]

This study focuses on the dopamine breakdown product homocysteine, and elevated homocysteine could be due to overmethylation or undermethylation. This study suggests that homocysteine is a dopamine breakdown product caused by hypermethylation...the rapid breakdown of dopamine, as seen in schizophrenia.

Synaptic Effects of Dopamine Breakdown and Their Relation to Schizophrenia-Linked Working Memory Deficits
"In particular, we focus on the dopamine breakdown product homocysteine (HCY), which is consistently elevated in schizophrenia patients. Our previous studies have shown that HCY strongly reduces the desensitization of NMDA currents. Here, we show that HCY likely affects NMDA receptors in brain regions that support working memory; this is because these areas favor dopamine breakdown over transport to clear dopamine from synapses. Finally, within the context of two NMDA-based computational models of working memory, we suggest a mechanism by which HCY could give rise to the working memory deficits observed in schizophrenia patients."

"Dopamine is then methylated by COMT inside the astrocyte, generating HCY that is released back into the extracellular environment."

"We therefore suggest that a previously unappreciated consequence of COMT-mediated synaptic dopamine breakdown is the acute reduction of glycine-dependent NMDAR desensitization by HCY."

Neurotoxicity associated with dual actions of homocysteine at the N-methyl-d-aspartate receptor
"Here we show that homocysteine acts as an agonist at the glutamate binding site of the N-methyl-D-aspartate receptor, but also as a partial antagonist of the glycine coagonist site. With physiological levels of glycine, neurotoxic concentrations of homocysteine are on the order of millimolar. However, under pathological conditions in which glycine levels in the nervous system are elevated, such as stroke and head trauma, homocysteine’s neurotoxic (agonist) attributes at 10–100 μM levels outweigh its neuroprotective (antagonist) activity. Under these conditions neuronal damage derives from excessive Ca2+ influx and reactive oxygen generation. Accordingly, homocysteine neurotoxicity through overstimulation of N-methyl-D-aspartate receptors may contribute to the pathogenesis of both homocystinuria and modest hyperhomocysteinemia."

 

[Goobz]

Just glanced over it as I’m on the run, but looks like a very interesting study, thanks for posting

 

[unsubscribed]

Hey @Hans ,

I have the 'low activity COMT Haplotype' which coincides with:

Poorer response to stress
Higher levels of anxiety-related personality traits, such as neuroticism and irritability
Increased risk of anxiety disorders (such as social phobias and OCD)
Increased pain sensitivity.

I also had high homocysteine which I've since brought down with L-Methylfolate/Adenosylcobalamin but do you have any more insight into the COMT gene, in particularly to those with low activity?

SAMe supplementation
Green Tea (EGCG)

Thanks :)

 

[Jon2547]

Would supplementation with glycine be beneficial to someone with schizophrenia?

 

[Hans]

Hey @Hans ,

I have the 'low activity COMT Haplotype' which coincides with:

Poorer response to stress
Higher levels of anxiety-related personality traits, such as neuroticism and irritability
Increased risk of anxiety disorders (such as social phobias and OCD)
Increased pain sensitivity.

I also had high homocysteine which I've since brought down with L-Methylfolate/Adenosylcobalamin but do you have any more insight into the COMT gene, in particularly to those with low activity?

SAMe supplementation
Green Tea (EGCG)

Thanks :)

Magnesium is a cofactor for COMT, so be sure to consume enough of that. Furthermore, just support the folate cycle with B2, B3, B6, B9 and B12. That should be enough to sort that out. Also, COMT breaks down a lot of other stuff as well, such as histamine, estrogen, etc., so if you have too much of that, then that can also be a problem. Environmental toxins can also clog up COMT, which will cause issues.

 

[Hans]

Would supplementation with glycine be beneficial to someone with schizophrenia?

Yes definitely, it's used as an add-on therapy for schizo (R).
Furthermore, niacin can also be very good for schizo (R).

 

[Beastmode]

@Hans Just seeing this thread and was looking into methylation via possible testing. Are the symptoms enough to confirm methylation issues and/or does this type of gene testing actually come in handy?

There seems to be a few shotgun approaches, like the link below, that seem to go after the common "gene" challenges if one has them.

Methylation

The methylation cycle helps us to operate both physically and mentally. Many core functions in the body use this process including nervous, cardiovascular and immune system activity, as well as energy production, heavy-metal detoxification and hormone balance. Core Methylation helps maintain...

www.mylifeforce.com

Still in the very early stages of investigating this. I've been on a pro-metabolic lifestyle approach consistently since Jan 2017. Always looking to maximize my health.