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23andme & Chronic insomnia and family history of psychiatric/CNS disorders

Discussion in 'Genetic Testing and SNPs' started by xptriado, Feb 12, 2014.

  1. xptriado

    xptriado Senior Member

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    Ok so i have already half my exams prescribed. Next week i will be doing exams again.

    This time i will focus on:
    - liver
    - kidney
    - vitamins 25OHd3 and 1,25 DOH d3, vitamin a and b9,b12,methylb9,methyl/adenosyl b12
    - sam-e, sah, homocisteien, cisteine, taurine, ammonia, sulfites, sulfates, creatine, adenosine, methionine, bh4
    - methylmalonic acid
    - glutatione reduced and oxidizeds well
    - bilirubin,bilirubin conjugated
    - immuno globulins
    - thyroid binding globulin
    - parathyroid hormone
    - calcium, fosfate
    - alkaline phosphatase, phosphorus organic
    - magnesium
    - insulin tolerance test.
     
  2. xptriado

    xptriado Senior Member

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    New tests, still waiting for a few and couln't do many of the ones I wanted like the ones related to methylation as the lab didnt provide them. Already have the new ones to do, which will mostly be to immune system. I can't seem to find anything relevant. I think my problem is related to cortisol so I need to do a proper cortisol test.

    A new symptom has either showed up, or I have only noticed it now (im leaning towards the later). After prolonged fasting, once I eat again I get a itchy scalp.

    09-06-2015

    Eritrocits 5.49 [4.31-6.4]
    Hemoglobin 16 [13.6-18.0]
    Hematocrite 44.9 [39.8-52.0]
    Mean Globular Volume 81.7 [80-97]
    Mean Globular Hemoglobin 29.1 [26-34]
    Mean Globular Hemoglobin Concentration 35.7 [32.0-36.0]

    Red Cell Distribution Width 13.0 [11.5-15]

    Leucocytes 5.18 [4-10]
    Neutrophyls 2.5 [1.5-8.0]
    Eosinophiles 0.2 [0-0.3]
    Basophils 0.0 [0.0-0.3]
    Linphocites 2.1 [0.8-4.0]
    Monocites 0.4 [0.0-1.2]

    Platelets 191 [150-400]
    Mean Platelet Volume 7.5 [6.0-11.1]
    Plateletocrite 0.14 [0.15-0.42]
    Platelet Distribution Width 44.7 [25.0-65.0]

    Folic Acid 10.49 [>5.38]
    Vitamin B12 (cyanocobalamin) 896 [211-911]
    Fasting Glycemia 88 [70-110]
    Glicated Hemoglobin 32.00 [19-44]
    DCCT % 5.00 [3.79-5.8]
    Mean Estimated Glicemia 95mg/dL

    Creatinemia 1.03 [0.5-1.2]
    Calcium 9.1 [8.5-10.1]
    Phosphorus 3.4 [2.5-4.9]
    Magnesium 2.00 [1.7-2.55]
    AST 8 [<38]
    ALT 22 [12-78]
    GGT 17 [15-85]
    AKP 70 [30-120]

    Total Bilirubin 0.84 [0.2-1.00]
    Bilirubin Direct 0.12 [<0.4]
    Bilirubin Indirect 0.72 [0.2-0.8]

    Total proteins 7.3 [6.4-8.2]
    Albumin 4.69 [3.57-5.42]
    Alfa 1-Globuline 0.26 [0.18-0.4]
    Alfa 2-Globuline 0.64 [0.26-0.97]
    Beta 1-Globuline 0.38 [0.3-0.59]
    Beta 2 Globuline 0.3 [0.2-0.53]

    Gama Globulin 1.03 [0.71-1.54]
    Albumin/Globulins Ratio 1.79 [1.20-2.5]

    Vitamin A (waiting)
    Vitamin D3 25OH 24.1 [20-29 indicates insuficiency]
    Vitamin D3 1,25D OH (waiting)

    IgG 1210 [700-1600]
    IgA 142 [70-400]
    IgM 62 [40-230]

    IgE Total 58 [158]

    T3 0.93 [0.6-1.81]
    FT3 4.34 [2.3-4.2]

    T4 8.5 [3.2-12.6]
    FT4 1.24 [0.89-1.76]
    TSH 2.767 [0.35-5.5]
    RT3 (Waiting)

    Androstenedione 4.10 [0.6-3.10]

    11-DesoxiCortisol [waiting]

    Aldosterone 14.00 [1.97-26.0]

    Parathormone Intact (?!) 25.3 [11.1-79.5]
     
  3. xptriado

    xptriado Senior Member

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    If this is high, then normally in men it isnt a problem, except in tissues it would convert to estrogens and this could cause gyno! Which I'm experiencing.

    It is interesting that most of the adrenal products are high. they seem to be overworking to compensate for something.

    I have testosterone RX to try, testogel. I might give it a try. I have T4 to try, i might give it a try...

    Im taking NAC, Glycine, Arginine, Lysine, Citruline, Yucca, Tribulus, B's, Zinc 30mg, copper2mg, manganese sometimes, and my alternative doctor got me someting called trychinoil (?!) she says I have a problem in the Krebs Cycle, as identified in her hair analysis ... whatever, i'll try anything

    i have found relief from insomnia in 25mg trazodone+0.125mg clonazepam. if i wake up during the night I take it again. though, I now this is not my normal sleep, not at all.

    i have the feeling I could benefit a lot from healing my adrenals. My adrenal output seems high, aldosterone is not optimal, and FT3 is over the top, which makes me think its pooling. This occurs with cortisol issues.

    if my 1,25di OH D3 comes back low, I think it could solve my sex steroid issues...and posibly if testosterone rises a bit, cortisol lowers a bit and the thyroid rests a bit more

    on the other hand, tomorrow I will get clonidine and baclofen to try! pharmacies in spain are less regulated and I don't need a RX for those
     
  4. TheChosenOne

    TheChosenOne Senior Member

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    This intrigues me. Do you have leaky gut?
     
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  5. xptriado

    xptriado Senior Member

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    This intrigues me too.

    Can i diagnose leaky gut?
     
  6. TheChosenOne

    TheChosenOne Senior Member

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    It's kind of hard to do. My IgG was out range which was what made me wonder.
    I had a lot of symptoms of a candida infestation.
     
  7. xptriado

    xptriado Senior Member

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    I think it could come from high cortisol.
    I will do a stool exam though..
     
  8. TheChosenOne

    TheChosenOne Senior Member

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    A stool exam is not conclusive. My stool results were negative.
     
    xptriado likes this.
  9. xptriado

    xptriado Senior Member

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    My plan is this:
    Take flax lignans, this will lowrr cortisol and androstenedione. Lowered cortisol will improve temperature and intestinal.permeability. this should reduce candida or whatever i have.
    Flax is a good previotic too. Take glutaminr amd aloe, and do an autoimmune diet.

    The i will check if i still have t3 pooling. If so, i will check if rt3 is high and if so i will do a t3 cycle of 12 weeks to uncouple rt3 from.receptors.

    At thebsame time i need to take digestive enzymes and take care of liver and lower bilirubin. This can be achieved with tudca. As liver heals, i wont have as much aromatization

    I think this will address all my problems including estrigen dominance which seems to come from androstenedione i think.
     
    Last edited: Jun 20, 2015
  10. TheChosenOne

    TheChosenOne Senior Member

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    What you can try is stop eating high sugar foods (like bread, pasta, ...) except for fruits and see if you experience 'die off'.
     
    xptriado likes this.
  11. xptriado

    xptriado Senior Member

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    what is die off?

    i want to do this. i've already started cutting down coffee, sugar, honey and now i will stop bread. i dont like past and i dont like rice.

    where will i get my carbs from?

    so I have a pretty good idea now of what is going on with me. i will post more tomorrow, i discovered a very interesting article which ties my symptoms with adrenals and hypothyroidism. finasteride was just one more nail on my coffin. it is a coincidence though that i have reduced 5ar metabolites. it has nothing to do with finasteride causing genetic changes like they are trying to find in this studies. this condition is to do with busted adrenals and thyroid. in my case it may all come from less dopamine D2 receptors, as I found in promethease.

    i took again dexa today, 0.25mg. i was feeling horrible and it changed me to feeling great
     
  12. xptriado

    xptriado Senior Member

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    am currently on the following, since +- one week:

    Everyday:
    1,2G N acetyl Cysteine + 1,5g Glycine -> to reduce glutamate and help liver
    2mg Copper, 30mg Zinc -> to supplement deficiency
    NADH ---> I had a deficiency of this according to my doctor's hair test. This is connected with energy production and I know I have a prob there for sure in that krebs cycle. Read my posts before for more info
    Tribulus 4-6grams a day. ---> we have an imbalance towards 5beta reductase instead of 5alpha reductase. i'm hoping this helps me reset the balance.
    Trazodone 25-50mg ---> for sleep, for erectyle function
    Clonazepam 0.125-0.375mg ---> for sleep, for anxiety
    Creatine Monohydrate 6gr ----> hoping this raises 5ar and DHT for the same reasons as tribulus
    50g of Flax Seed Grounded everyday ---> hoping this lowers cortisol and androstenedione which I think its responsible for estrogen dominance and gyno in me. It should help with gyno and fat loss, and reduce aromatisation in liver. read my previous posts to understand why. i have previously lowered my cholesterol on this, 30 points in 4 weeks. my cholesterol is very high for my age at 220.

    Every 2-3days:
    An homeopathic medicine for a virus that my doctor found. maybe this is BS who knows.
    Manganese ----> necessary from my analysis of my genes
    Activated Vitamin B ---> necessary from my analysis of my genes and for overall absortion
    Glutamin 1g ----> i need this for gut. will increase to 5gr a day
    Arginine+Lysine+Citruline+Yucca ----> yucca to clear ammonia, arginine and citruline to stimulate NOS and KREBS and Arginine+Lysine are necessary to blunt cortisol stress response

    Yesterday I took 0.25mg Dexametashone ---> I wanted to prove a point with this, I had felt better on it before. I think its the lowered androstenedione+increase in cortisol which makes me feel good
    Today I took 0.125mg Dexamethasone ---> the dosage yesterday was too high for it impacted my sleep

    Yesterday I was feeling really bad from not sleeping properly even using traz and clon. I had a very bad feeling I described in the above post.

    Once I took Dexa, and I took it at the same time as tribulus, I started feeling great, a couple hours later.

    During the night, I was sleepy but I woke up after 4 hours of sleep. massive hard on, erection lasted much longer than morning erections the past few days. I had the feeling i had slept a lot. sleep was very deep. but I couldnt fall asleep afterwards. this inability to fall asleep is from dexa, I experienced the same before. Its like cortisol is higher (dexa) and the same amount of trazodone didnt put me to sleep like before, and I had to take a bit more clonazepam. I think I fell asleep at some point. Normally I would have such an hangover, if I didnt sleep the 8 hours, but today I feel great. I do not feel at all the lingering effects of these substances in my body. I used to feel less libido on clonazepam, and if i didnt sleep properly i used to feel really shitty. Its like my metabolism is actually working better!
    When I woke up I took dexa, 0.125mg, and a couple hours later after my lunch I took tribulus and creatine. 4 hours after dexa I am wide awake, enjoying music, chatting, lots of libido, I stare at girls when they pass by me, I'm confident. Don't know exactly what's doing what, I think its Dexa and Tribulus the most important things, but I'm liking this.
     
  13. TheChosenOne

    TheChosenOne Senior Member

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    When candida dies, it releases a bunch of toxins. For me it gives me headaches, makes my liver hurt and most importantly it gives me flu like symptoms. My face feels very warm. These symptoms are very indicative for a candida infestation. Other symptoms include oral thrush, which is a white coating on your tongue.
     
  14. xptriado

    xptriado Senior Member

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    So i used 0.25mg dexametasone in the morning one day, and then the subsequent 3 days i used 0.125mg

    Any idea why I felt normal the first 2 days?i felt like my old self. Its so frustrating that its gone now!

    I seem to have retained better sleepm today i slept unassisted.

    My doctor was so worried that i was doing that. She said i can get cushings from it. Even from licorice root...
    I was very worried.

    I felt like my old self.
     
  15. xptriado

    xptriado Senior Member

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    So I came to a conclusion.

    I have lots of mutations for Chron's and Dopamine related issues (parkinson's, adhd, etc).

    I have particularly a mutation for D2DR which has 4% frequency, and is linked to less D2 receptor density. So, I think I can assume I have this ongoing since:
    - Metoclopramide (D2 blocker) gave me seizures.
    - always felt some sort of melancholy in the past.i have spasms at night.
    - I woke up with moving arms in the past
    - I git seriously worse on amytriptyline, mirtazapine, doxepin, etc, they all cause rythmic involuntary movements of members, but especially fingers.
    - I havr low desire, low mood.
    - Prolactin is top of range.
    - I sleep better when i enter periods of sexual abstinence.
    - I lost morning erections, yet I have nocturnals and all my hormones look fine. Morning erections are dopamine related.
    - Dexametasone increases free plasma dopamine levels and D2 receptor expression, and I did feel more libido, music sounded good again and I felt more alive, like before. I also felt like something in my metabolism clicked. Right now my baseline after dexa seems better than before.

    I am getting on TUDCA and Uridine, this will take care of rT3 and dopamine. I'll let you know what happens.

    I take flax seed nowadays as I have hopes it will lower androstenedione. I sleep better. I think my gyno has been reduced too.

    Im on NAC and Glycine, and some other supplements. More good days than bad lately and today I woke up in the early morning but managed to fall asleep again.

    I am refusing the anti depressives until I exausted all the other options. Once in a while I take trazodone and clonazepam, that's it.
     
    heyitisjustin likes this.
  16. xptriado

    xptriado Senior Member

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    hi everyone, i think i have finally found out my problem. its a pathogenic alelle called TaqI A1, it leads to Aromatic Amino Acid Decarboxylase enzyme overexpression, which makes me have less Dopamine type 2 receptors (autoreceptors?) in the striatum.

    i dont know if the insomnia is connected to this yet, but it explains the bad experience with dopamine pathway blockers (neuroleptics, serotonin enhancers). I will make a very detailed post soon. It also explains why I felt good on dexamethasone. today i will go to the neurologist and i hope he understands what i have to tell me (especially because it will cost a butload of money)
     
  17. Valentijn

    Valentijn Senior Member

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    Which gene? DDC, DRD2/ANKK1? And which mutation?

    If it's rs1800497 on DRD2/ANKK1, it's not really causing disease. It's just been inconsistently associated with tendency toward addiction. If that is the one, it's not on DRD2 at all, and it's also a very common variation.
     
  18. xptriado

    xptriado Senior Member

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    Exactly that one and you are wrong about it being only inconsistently associated with a tendecy towards addiction.

    My symptoms are pretty common too, i dont have anything out of the box except for one or two issues related to movement disorders.

    It just isnt true that you need a super rare mutation to feel like i feel. It can be a set of common mutations.

    I will post later when i finish writing about it
     
    Last edited: Dec 2, 2015
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  19. Hip

    Hip Senior Member

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    Could you provide a link to where you read that.

    If you want to boost dopamine D2 receptor activation, then very low dose amisulpride can do that job without any long term tolerance building up. See this thread: Amisulpride — A Multipurpose Drug for ME/CFS


    Amantadine might also be useful, as this drug increases the density of dopamine D2 binding sites. Ref: 1 It also can be generally helpful for ME/CFS.

    Citalopram (an SSRI) increases dopamine D2 receptor expression in the rat brain striatum. 1

    Cabergoline and bromocriptine are potent D2 agonists.
     
    Last edited: Dec 2, 2015
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  20. xptriado

    xptriado Senior Member

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    @Hip , I . Have met with the doctor and he gave me 1) methylfenilate in the morning, 2) ropinole in the night. I think the methylfenilate in the morning is overkill and opposite to what I need (maybe this is similar to Amantadine ?). I think the ropinole could be helpful as it is a d2 agonist. I tried asking for tianeptine but he didnt listen. I will go to another neuro/psychiatrist. Amilsupride seems great and I have it here at home but I chickened out when I saw it rraises prolactin 8x and mine tested many times on the limit.
    I think the study you want is PMID 15900211.

    Thanks for the suggestions. I will add Amantadine to my "to try" list :))

    I have gathered the following from studies i read, and came up with this text. I think I can't say that this SNP is surely not linked to my problem. It probably pays a big role. It has even been patented as a marker for antidepressive/antypsychotic responsiveness (see NOTE at the end). I am also doubtful I had epileptic fits. They were probably extrapyramidal reactions (accute dystonic storm/seizures) to metoclopramide. I was drugged 2 years on phenobarbital for possibly no good reason.


    Dystonia is a movement disorder characterized by involuntary, sustained muscle contractions that result in twisting and repetitive movements or abnormal postures [PMID 16914406]. Dystonia can be classified by the age of onset, body distribution, and etiology. Classification by etiology separates the spectrum of dystonia into primary and secondary categories. Secondary dystonia is associated with a known acquired causes or additional neurologic signs, such as muscle weakness, spasticity, ataxia, ocular motility abnormalities, retinal abnormalities, cognitive impairment, or seizures. Secondary dystonia typically arises from a specific underlying condition, such as exposure to dopamine receptor-blocking drugs [PMID 14509661].

    The rs1800497 SNP, or Taq1A, C>T,was considered a silent mutation located 10 kb from DRD2 gene, in the 3’ untranslated region. However recently the identification of a novel gene in the neighboring forward-strand region of DRD2 gene, named ANKK1 gene, showed that the rs1800497 SNP is located in exon 8 of the ANKK1 gene [PMID 15146457].
    The rs1800497 Taq1A, alelle A1, (TT) , is associated with a reduced number of dopamine binding sites in the brain [PMID 9672901], up to 30% less [PMID 22848508], which is the result of an increased activity of striatal Aromatic Amino Acid Decarboxylase enzyme [2005, PMID 15900211]

    Aromatic Amino Acid Decarboxylase enzyme catalyzes several different decarboxylation reactions:[http://www.hmdb.ca/proteins/HMDBP00278]
    L-DOPA to dopamine - a neurotransmitter
    5-HTP to serotonin (5-HT) - a neurotransmitter
    L-histidine to histamine - a neurotransmitter
    phenylalanine to phenethylamine - trace amine neurotransmitter
    L-tyrosine to tyramine - trace amine neurotransmitter
    tryptophan to tryptamine - trace amine neurotransmitter

    It is known that extrapyramidal adverse effects are associated with increased drug occupancy of the dopamine 2 receptors (DRD2). The
    A1 allele of the DRD2/ANKK1, rs1800497, is associated with decreased striatal DRD2 density. Results strongly suggested that A1+ variants of the DRD2/ANKK1 Taq1A allele do confer an associated risk for akathisia in patients who were treated with SGAs [2013, DRD2/ANKK1 Taq1A (rs 1800497 C>T)
    genotypes are associated with susceptibility to second generation antipsychotic-induced akathisia]. It has thus been suggested that DRD2 polymorphisms can be usedas a pretreatment marker for response to DRD2antagonists at therapeutic doses, and that A1 (+) or Del(-) subjects are highly sensitive to DRD2 antagonists, expressed as either treatment responders or non-responders vulnerable to extrapyramidal symptoms.[2007, PMID 17362435]

    In one study of 64 cases, the risk of ExtraPyramidal Symptoms with SSRIs, seems to be associated, with the presence of the A1 allele of DRD2 Taq1A polymorphism. [PMID 16633151]

    DRD2 TaqIA polymorphism has been reported to be associated with an increased risk for developing motor fluctuations but not hallucinations in Parkinson's disease. [PMID 11425949][PMID 14732464]


    Metoclopramide is a dopamine-2 receptor antagonist used for various gastrointestinal disorders. The anti-emetic action of metoclopramide is the result of its antagonist activity at D2 receptors in the chemoreceptor trigger zone in the central nervous system; this action prevents the nausea and vomiting triggered by most stimuli [Rang HP, Dale MM, Ritter JM, et al. Pharmacology. 5th ed. Edinburgh: Churchill Livingstone; 2003.].

    Metoclopramide can cause or worsen extrapyramidal symptoms (EPS)/drug-induced movement disorders (DIMD). Tardive dyskinesia and Parkinsonism is generally seen after long-term use,whereas dystonia and akathisia can occur after a single dose of metoclopramide.[PMID 18926476]. Metoclopramide's extrapyramidal symptoms generally manifest as acute dystonic reactions within the initial 24–48 hours of use. The risk of these reactions is increased at higher doses and in pediatric patients and adults <30 years of age. [http://www.nejm.org/doi/full/10.1056/NEJMicm1412207], [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4261495/]

    Acute dystonic reactions, the most common type of extrapyramidal symptom associated with metoclopramide, occur in approximately 0.2% of patients (1 in 500) treated with 30 to 40 mg of metoclopramide per day [PMID 1298936]. Symptoms include involuntary limb movements, facial grimacing, torticollis, oculogyric crisis, rhythmic protrusion of the tongue, bulbar type of speech, trismus, opisthotonus (tetanus-like reactions), and, rarely, stridor and dyspnea, which possibly result from laryngospasm. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4261495/]

    The most rapid treatment of an acute dystonic reaction caused by metoclopramide is the intravenous or intramuscular administration of anticholinergics.[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4261495/]

    Metoclopramide-induced acutedystonic reaction, may occur in patients carrying a CYP2D6 genetic polymorphism. [PMID 16702617] Author's of a previous study felt that if there is a case of dystonic reaction to metoclopramide, this drug should not be administered to other members of the family. [PMID 1298936]

    Dexamethasone is one of the few CYP2D6 inducers and at the same time it significantly increases D2 receptor binding in the limbic system of rats [PMID 15520493]

    The common link between all these meds is that they were all neuroleptics in one way or another, some by inducing serotonergic pathways,others by directly blocking dopamine. This has led to Extrapyramidal symptoms/drug induced movement disorders, be it accute dystonic reactions to metoclopramide or sleep myoclonus, dystonic reactions, from other neuroleptics. All of the medications to which I had adverse side effects are heavily metabolised by CYP2D6, which I also have polymorphisms for. The one medication which made me feel great, Dexamethasone, is a CYP2D6 inducer, one of the few known, and is known to increase D2 receptor density in rats. I have found a few people who felt good on dexamethasone, which they tried for some reason unrelated to fatigue, and they were put on a prodopaminergic and felt great, when before all the ADs had failed (of course this is all anectodal...)

    What the neurologists told me at the time about having epileptic convulsions, which happened after metoclopramide, was severely wrong, in fact they were not epileptic patterns but rather Drug Induced Movement Disorders.

    The likely culprits for my Extrapyramidal issues with these medications have been an impaired metabolism of the drugs used coupled with a problem in the dopaminergic pathway (maybe underactivation, maybe in the mesolimbic pathway), resulting of CYP2D6 and Taq1A A1, respectively.



    Note: interesting related patent

    http://www.google.com/patents/US20070026402
    Genetic marker of response to atypical antipsychotics and antidepressants methods

    The invention provides methods of identifying candidate psychiatric patients, or patients with movement disorder, for treatment with receptor site or increases density of D2 dopamine receptors. The method comprises determining a patient's DRD2 genotype. Patients having the Taq1A (A1) allele (A1+ allelic status) are candidates for treatment with high dose, high binding antipsychotics and/or SSRIs that influence D2 receptor density. Patients lacking the Taq1A allele (A1− allelic status) are candidates for treatment with low dose, low binding atypical antipsychotics, and are not likely to respond well to these SSRIs.
     
    Last edited: Dec 3, 2015

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