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I have COMT G;G and MAO-A G;G. My childhood was very difficult, enormous temper tantrums. Above average IQ and abnormal intelligence (not savant but similar). Polymorphisms or population variation in a single nucleotide, is unrecognised as disease factor because it never is suspected. While clinicians were unaware of genetic variation or variants combining into disorders, the symptoms presented were labelled a difficult personality, rather than understood as metabolic dysregulation. In case of COMT and MAO-A, the molecules affected are catecholamines, so the ability to tolerate stress may be highly affected. The temper tantrums must be understood as an imbalance, excess of excitability factors (hormones and excitatory neurotransmitters) and lack of calming factors (inhibitory neurotransmitters). The entire autonomous nervous system may be "misswired" because the genes that create its function are mismatched. The child does not know that. The parents and the medical practitioners must recognise that. Psychologists can help but only to a point, because their education does not include genetics and medical conditions, so they won't be able to recognise the clinical signs of metabolic disorder. A disorder is not a disease, so the child won't die, but it will suffer (and so will parents ... More

I have COMT G;G and MAO-A G;G. My childhood was very difficult, enormous temper tantrums. Above average IQ and abnormal intelligence (not savant but similar). Polymorphisms or population variation in a single nucleotide, is unrecognised as disease factor because it never is suspected. While clinicians were unaware of genetic variation or variants combining into disorders, the symptoms presented were labelled a difficult personality, rather than understood as metabolic dysregulation. In case of COMT and MAO-A, the molecules affected are catecholamines, so the ability to tolerate stress may be highly affected. The temper tantrums must be understood as an imbalance, excess of excitability factors (hormones and excitatory neurotransmitters) and lack of calming factors (inhibitory neurotransmitters). The entire autonomous nervous system may be "misswired" because the genes that create its function are mismatched. The child does not know that. The parents and the medical practitioners must recognise that. Psychologists can help but only to a point, because their education does not include genetics and medical conditions, so they won't be able to recognise the clinical signs of metabolic disorder. A disorder is not a disease, so the child won't die, but it will suffer (and so will parents). The causes are always complex (not just COMT, MAO-A), and it is difficult to understand it without a complete profile. It may take minutes to map a complete mismatched genetic profile, but perhaps 10 years to implement the knowledge, and learn to balance the imbalances. Another factor, genetic diseases that were uncovered before were often a consequence of inbreeding. It is my contention that the combinatory metabolic malfunction is result of outbreeding, as that is the only explanation for the incompatibility of genes. Moreover, I believe that this affects not only the genes, but mitochondria (energy production). Everyone on the planet has adapted to certain climate and food conditions, and the genes that survived enabled that adaptation. When people migrate and mix, new adaptations must occur (the fittest surviving again) in order for genes to be efficient in energy production. This is largely unrecognised. My parents came from the same country, but genetically were very different people. My genetic profile is full of inconsistencies, unique to myself. I was not going to survive beyond 35 with my genes, but I did and now I am too frail to write about how I recovered.

It is wrong to label a variant ++ as in "positive for a mutation". Prior to GWAS studies, only the mutations could be responsible for a disease. This model "one gene - one disease" cannot be continued, or it will create an immense confusion. If we inherit a variant of a polymorphism, then we have a variant "NN". In case of rs4680, I have a variant G;G. In case of MAO-A rs6323 I have a variant G;G. All individuals with other variants survive; both variants can contribute to neuroimmunoendocrine dysregulation, possibly having a heterozygous variant of COMT is less problematic. MAO-A affects serotonin metabolism, and it is related to other genes (serotonin transporter gene and transport genes are very important for efficiency), but also the folate and cobalamine metabolism. The modern research is trying to create complex analysis but it is very difficult to make general rules, when individual deviations are high. The reason I commented on this thread is that it touched my heart. That little girl could have been me. Obviously, emotional instability is not a sign of mental maladaption, but of unrecognized incompatibility of molecules that are an essential part of our nerve system. it can vary from a mild malfunction to a life-threatening disease, manifesting as neurologic and psychiatric symptoms.Those symptoms are manifestations of complex deficiencies and imbalances. If we were positive for a single disease or a single mutation, that would manifest differently. Since it is very easy to confuse "I am positive for a NN" with " I have a ++", I prefer to use the letters for the results.

Also, people tend to use abbreviations as if they were genetic experts who already know the jargon. We are not, and we must disclose everything of interest, should we learn form shared experience. I have a complex catecholamine deficiency, that consists of symptoms of two (maybe three) different rare genetic diseases. I have symptoms of dopamine beta hydroxylase deficiency, combined with dopamine responsive dystonia, and I have a poorly functioning GCH1 gene, and low BH4, as measured by depleted NO (nitric oxide). In addition, I have numerous other partial diseases. My disorder is therefore unique to me and can never be identified by another similar case. I disclose this, in case someone has the same problem. I treat myself, and it is very difficult. For an average geneticist, who is healthy, my illness is a major challenge. It is like solving complex mathematical problems without computers. In addition, female hormonal cycles affects all the aforementioned. GCH1 expression is affected by estradiol. So even if a well meaning medical expert wanted to help me, he would likely treat me as a male and cause even greater distress. My illness is still affected by those hormones. I have been suffering since age 12, and am not in menopause yet at age 56 (almost but not quite). So if you have problems with COMT, MAO-A, MTRR, MTHFR, BH4, and methylation, you are likely as a woman to suffer without explanation. These problems will not be solved by gynecology, that is mechanistic in its approach, or nutrition knowledge (which helps), or hormonal therapy, because the well intended helpers will ignore your unique genetic and metabolic profile. Only the individual, if surviving to adulthood, can map their own idiosyncratic metabolic profile and learn how to balance the numerous imbalances. What helped me the most, are the glandular extracts, as I cannot tolerate synthetic hormone replacements. So if someone reads this, hormones are the solution, preferably natural, not synthetic. Yet in combinatory disease one can never solve one problem successfully without affecting something else. Self treatments must be exercised with great caution and wisdom. Less

Yes, I do. Struggling with a bunch of cognitive crap right now that probably came from this genetic make-up and Lyme Disease. Still investigating.

hi guys i'm rs4680++ rs4633++ rs6323++ and have a bunch of other heterozygote mutations in methylation pathways... thanks all for posting it's great to know I'm not alone. Has anyone had any success with DEN (Daily Essential Nutrients) or EMP+ (Empower Plus), as I've been involved in a research trial with these products but am a little hesitant to try myself (have just come off psych meds). Also I have the below from a bioinformaticist:

"One interesting feature of MAOA is that the effects of heterozygous variants [in human females] are untestable using current technology. The gene is on the X chromosome, so usually it would be expected that one copy is inactivated. Because this inactivation is random, the variant that is active will be different in different cells in the body, so doing an RNASeq experiment on blood (for example) might have a different outcome than doing an RNASeq experiment on the cells that actually have an influence on behaviour. This means that it's not possible to properly test how MAOA gene variants affect females. It's a gaping hole in the research that doesn't really get discussed."

avoid reishi mushrooms by the way. They didnt help and made my insomnia much worse

Dr Patricia Kane can help. dont hesitate to ask. she is getting me balanced and feeling much better lately. her protocol is very very powerful for neurological issues.

@@CX7129
Wow. Thanks for sharing. Your story sadly reads similarly to my own and its striking to see how our genetic makeup plays into this. I share very similar traits and gene mutations so I mostly understand how it feels.

Things I have found recently that help are avoiding any herbs that are MAO A or B inhibitors. examine.com is useful for checking this. Also take high amounts of B vits along with zinc, magnesium. I am also +/+ for MTRR A66G which means I dont absorb vit b12. I am battling lifelong insomnia - trying to get off Remeron/Mirtazapine at the moment. Feel very well but cant crack the sleep. Also just found that reishi mushrooms help with sedation and california poppy (along with all the others eg valerian, lemon balm, hops etc). Lots of supplements are mao a inhibitors or increase dopamine/serotonin eg quercetin. Good luck

Mental illness runs in my family. I make sure I'm getting enough saturated fat to keep my brain healthy. I'm homo for comt, mao and hetero for a bunch of mthfr. I have found that b6, NAC and glutathione make me extremely irritable. Adeno B12 is the only B I can supplement. I also take molybdenum so I can properly process the b vitamins in my food.
I think the saturated fat thing helped me the most and the 0 fat craze of the 90s is what made my entire family go nutso. A couple were because of drug use, but a few were not. The whole methylation and detox processes are fasinating and everyone is different. But studying it and talking to a naturopath about it has helped me 3000 percent!

Homozygous for two COMT, (Worrier) and Homozygous for MAO-A. Father was chronically suicidal Mom was a narcissist and misogynist. Once I learned about the SNPs everything made a lot of sense. I tend to stay away from methyl donors now, even though I'm also homozygous for MTHFR. I take lithium orotate, tydroxycobalamin, and folicinic acid every day, which seems to help with the moodiness. I'm also receiving EMDR treatment from PTSD stemming from childhood neglect and abuse.

sorry @QY7199 but - you know the story - this is rooted in genetic determinism a la Dawkins. Simple underlying fact; all psych cases have brains starved of lipids.
i advise you contact
http://www.neurolipid.org

@@CX7129, you might check out www.borderlinepersonalitydisorder.com, www.nyp.org/bpdresourcecenter.com & the online test at bpddemystified.com/resources/online-test. It's the least recognized but most prevalent mental illness there is (6-10% of the population), until recently almost always misdiagnosed as bipolar, depression, or GAD. Shame is at the heart of the disorder, but its origins are biological. I don't know how to send private messages and don't want to hijack this thread so I'm afraid all I can say is good luck. I know it's an almost unbearable condition till you find help, but help is out there.

thanks @QY7199 , thats really interesting. any further info would be v helpful. I've always been so up and down, flirting with self destruction and self sabotage , in every way possible. The drug use was always about escaping .

This combination goes along with borderline personality disorder, which my sister & daughter have, as well as my late husband. Please get good psychiatric evaluations. Ask that BPD be ruled out before accepting a bipolar diagnosis. One tip-off is that psychiatric meds don't help -- in fact, often make things worse. Psychotherapy tailored to BPD, like DBT, can work wonders. There is a huge push by NIMH & others to spread awareness of the difference early intervention can make. It's estimated that 40% of opiate users have BPD, and a high percentage of alcoholics. It makes sense; people with the disorder feel so bad they self-medicate.
Sometimes there is early life trauma, sometimes there isn't. People with BPD are exquisitely sensitive -- like burn victims with no skin, as Marsha Linehan said. They live in indescribable pain, but there is hope.

Her pediatrician sent me to 23 and Me 2 years ago after a pattern of sleep troubles. Everything on 23 and Me I have seen allows a "legal authority" over a minor to act on their behalf into the contract of service with them. Had no trouble setting it all up, and now under my account I have both my own and her information on same login and can toggle between the two profiles.

@@GF4105 I'm curious. How are you testing a 3 year old for SNPs? I thought you had to be 18 to test with 23andme. I'd love to test my children but thought it wasn't allowable.

wow, what a story @GF4105 .
Honestly, i would say COMT/MAO snips, combined with some highly unpleasant life experiences have taken me close to the edge.
My real father had huntingtons, and my half brother was in psychosis for 8 years due to child abuse and these SNP's (I'm guessing the second part but watch bruce lipton for clarification on the nature v nurture argument)
i suffered emotional , physical and sexual abuse as a child, so i can't be sure what caused which behavioural patterns, however, i honestly believe that the most extreme effects of said SNP's only kick in if ones life experiences have been sad/violent.
no doubt there will be a predisposition to ups and downs, sadness and emotional fragility , but provided the love and support, and open channels of communications are there, with the right supplements /diet, this can be managed.
I am quite an angry person, but also extremely sensitive and gentle when i feel safe. i am so fragile at times . i can see and feel the positive and negative sides of my situation, plus knowing other MAO a people well, i get a general idea of the likely effects ... More

wow, what a story @GF4105 .
Honestly, i would say COMT/MAO snips, combined with some highly unpleasant life experiences have taken me close to the edge.
My real father had huntingtons, and my half brother was in psychosis for 8 years due to child abuse and these SNP's (I'm guessing the second part but watch bruce lipton for clarification on the nature v nurture argument)
i suffered emotional , physical and sexual abuse as a child, so i can't be sure what caused which behavioural patterns, however, i honestly believe that the most extreme effects of said SNP's only kick in if ones life experiences have been sad/violent.
no doubt there will be a predisposition to ups and downs, sadness and emotional fragility , but provided the love and support, and open channels of communications are there, with the right supplements /diet, this can be managed.
I am quite an angry person, but also extremely sensitive and gentle when i feel safe. i am so fragile at times . i can see and feel the positive and negative sides of my situation, plus knowing other MAO a people well, i get a general idea of the likely effects.
My doc said they had never seen such a collection of SNP's in their whole , very long career. i have 8 +/+ and 71 +/-. many of the inherited, but an equal amount caused in my lifetime. i am now suffering from a severe mould infection (Fumonism which universally infects crops like corn) , my methylation pathways are very broken, so its about damage limitation and trying to make the most of whatever lifecycle there is remaining.

In conclusion , re your daughter, the more love, light and peace she has around her, the more she is nourished well and surrounded by uplifting people, the more it will negate the effects these SNP's. The other alternative is unthinkable.
if you can read about the warrior gene and try to see a BBC horizons program about it. its very interesting.
all the best Less

My 3 year old daughter is homozygous for both COMT and MAO, and we have felt something was just very different from day one, emotionally and neurologically. She has amazed us at her abilities with problem solving as well, and picks up on learning things faster than I have seen any other children her age be able to. But she also has some of the emotional and temperamental struggles (even beyond what an average temperamental 3 year old typically has). I am heterozygous for COMT and homozygous for MAO. Struggle with some of my own emotional and neurological issues as well. Very interested to hear about susceptibility to recreational drug use or addictions. My father suffered addiction issues as well, and I saw it become his demise unfortunately as well. I am sorry that you had so many struggles in your life, but really do appreciate the candid sharing of information for those like myself with a young daughter who I am working to try and understand her tendencies while raising her the best I can. I have been trying to do some research on possible nutritional and holistic type support that may help.

Emotionally up and down, short temper sometimes, impatient (worrier gene) but very good at problem solving, however don't deal with stress well.
have a feeling that either of these SNP's may have been caused by recreational drug use, would like to see more data, in order to be able to pre warn young people .
i took MDMA and Cocaine growing up, over a period of 20 years (never as an addict but often enough to be more than occasional). have a friend who did similar who also has MAO A.
real father , who i spent v little time with was psychopathic woman beater and very dark person. he died fairly young of heart attack.

I have and I agree! Not sure what, if anything, you can do about it though. What's your experience?