Phenotype - ADHD and autism comorbidly? / Gene Table & video by Yo Samdy Sam.
Spoiler - autism and ADHD/mood swings are two sections of my Genes Table, phenotype sections and the video by Yo Samdy Sam explains it so much better.
5 signs you have ADHD and autism (Youtube) My Magic Eight Ball says “Yes! Where have you been all my life?”
Nutshell - Sam has a psychology degree and makes Youtube videos about autism, having been diagnosed late in life at age 30. She says the comorbidity of autism and ADHD is common but not mentioned at all in the DSMV and it had been a Never Done thing to diagnose someone with one of the diagnoses if they already had the other.
Her valuable insight - the two issues are different/seem and feel different/ and somewhat balance each other but still make life more difficult to navigate than for a ‘neurotypical’ person. The ADHD side can be chatty and high energy and outgoing at times - but then the autistic side really needs a quiet time out to recover. She suggests getting a sense for who you relate too. She says her chatty ADHD side is too much for a more fully autistic person, while a more fully ADHD person can be overwhelming for her.
Yes, yes, yes. I like stimulation and fun company at times, but really need a time-out desperately at other times.
Housekeeping - I added a lengthy explainer to the zinc post as I had a comment on Telegram that someone didn’t understand it. Zinc Deficiency and elevated IL-6 > mast cell degranulation>histamine excess; also >microbiome dysbiosis. (substack.com) It includes ‘More research is needed’ - because it is. The studies were on mice or human cells taken from either older or younger donors/participants. In the meantime, it helps explain why zinc deficiency can have such a wide range of negative impacts regarding chronic inflammation.
Intro - I include histamine excess with autism, because in my personal experience, the histamine hyperexcitability meltdowns resemble autism meltdowns very closely. Histamine excess is seen in people on the autism spectrum.
Addition - trauma warning, sexual trauma topics are included in one section.
Potential phenotype includes:
Related clinical findings; and medical history of the author.
(A). Autism & Histamine Excess, (B) Neural Tube Defects, (C) Homocystinuria/ Hyperhomocysteinemia, (D) Endocannabinoid deficiency, mood swings, anxiety, (E) Fibromyalgia, (F) Dystonia / POTS, (G) Confounding Variable, Zinc Deficiency. (H) Confounding Variable, ACEs – child & adult trauma, and I) Secondary Hyperparathyroidism - (an addition).
(A) Autism spectrum disorder & Histamine excess.
or alexithymia, (difficulty expressing emotion) which may have hypervigilance to pain as a comorbid condition. (Ikarashi, et al., 2021)
Histamine excess, emotional dysregulation with hyperexcitability episodes.
Gene polymorphisms of the author, associated with autism or histamine excess risks:
The MTHFR/C677T double allele (of the author) has been associated with autism, while the MTHFR/A1298C polymorphism has not. (Li, Y., et al, 2020)
COMT alleles have been associated with alexithymia, (difficulty expressing emotion), and hypervigilance to pain, conditions which have been observed as comorbid. (Ikarashi, et al., 2021)
BHMT dysfunction would reduce cannabinoids needed to inhibit mast cells. (BHMT, genecards) Methylation alleles of MTHFR, (MedlinePlus/MTHFR), MTRR, (MedlinePlus/MTRR), and MTR, (MedlinePlus/MTR), might reduce folate availability and increase histamine accumulation.
The BHMT, MTHFR and MTRR polymorphisms also can increase risk of accumulation of homocysteine and lack of methionine, and BHMT could reduce choline and Dimethylglycine availability.
Medical history regarding autism spectrum and histamine hyperexcitability:
The author sought clinical diagnostic screening and paid for a second opinion and then a full neurological screening with IQ and other tests at which an ADHD diagnosis was confirmed and it was said that while symptoms of autism were present the severity was not clinically significant enough for the diagnosis. A Bipolar Disorder diagnosis was not given at that time, mood symptoms worsened later with menopause and after a brief use of olanzapine which led to akathisia-like withdrawal problems and suicidal urges which turned out to be somewhat controllable with pomegranate seeds, juice, or peel; and significantly improved once histamine foods were removed for the author’s diet.
The histamine excess / akathisia episodes also included more obvious symptoms of autism: rocking, hand flapping, and repetitive speech, and required a timeout for the author to calm down. The meltdowns were generally taken as ‘anger’ by others and leaving a situation helped more to prevent a worse meltdown than trying to explain. The histamine excess is irrational and over-stimulated, and the dopamine increase during an episode makes it hard to disengage and walk away. Any comment needs to be replied to compulsively; pre-planning a strategy to walk away can help in the heat of a melt-down to just do it – follow the plan, leave. “Autistic meltdown,” “histamine hyperexcitability,” and the mental agitation of “akathisia,” all seem similar and controllable by the same methods – confirmation of that hypothesis by clinical research is needed. [Personal experience of the author.]
(B) Neural tube defects at birth.
Spina bifida or neural tube defects (NTDs) are seen with BHMT alleles, (BHMT, genecards), and with MTTR alleles, though the specific reason why the polymorphisms lead to NTDs is not known. (MedlinePlus/MTRR) Reduced methyl folate availability can be a cause of NTDs. (Obeid, Holzgreve, Pietrzik, 2013)
Methionine deficiency may add to Neural Tube Defect risk prenatally, in addition to methyl folate and cobalamin (B12).
Adequate methionine may be needed prenatally to prevent Neural Tube Defects, in addition to folate and methyl B12. Data from the South Carolina NTD Surveillance, Prevention, and Research Project showed a 30-55% lower NTD risk for women who consumed more methionine than those in the lowest quartile. (Shoob, et al., 2001) The three nutrients may have an interactive effect on DNA methylation rather than just donating a methyl group. A study on Hispanic women found a correlation between dietary methionine intake and NTDs but was limited in number of participants. Some interaction was observed between methionine and B12 intake, particularly at higher levels of intake. (Graham, et al., 2010)
Medical history regarding Neural Tube Defects:
Chiari malformation was identified in an MRI looking for causes of chronic migraine. Slight scoliosis was identified as a child, but was not considered severe enough for a brace. Posture exercises were demonstrated by the doctor and the author did perform the daily posture exercises.
Addition:
“This knowledge should eventually benefit patients, such as those with spinal cord injuries. “Once we better understand the details of proprioception, we’ll be able to optimize the design of neuroprostheses, which take over motor or sensory abilities that have been impaired by an injury,” says Zampieri.
Altered muscle tension causes a crooked spine
He adds that researchers in Israel have recently discovered that properly functioning proprioception is also important for a healthy skeleton. Scoliosis, for instance, is a condition that sometimes develops during growth in childhood and causes the spine to become crooked and twisted. “We suspect this is caused by dysfunctional proprioception, which alters the muscle tension in the back and distorts the spine,” says Zampieri.”
Anke Brodmerkel, ‘The Genes of the Sixth Sense’, Max Delbruck Center, (Press Release No. 54)
Dietrich S, Company C, Song K, et al. Molecular identity of proprioceptor subtypes innervating different muscle groups in mice. Nat Commun. 2022;13(1):6867. doi:10.1038/s41467-022-34589-8 via (technologynetworks.com)
Yes, proprioception impairment is a problem and worsens when tired, hungry, or stressed. An external source of cannabinoids helps normalize a lack of full sensation in the author’s body and it improves coordination. The description of scoliosis as being muscle tension is similar to the torticullis-like skewing to the left she has noticed. The left side is clumsier and gets muscle knots that shorten range of motion of the left arm. Hip dysplasia has also been a problem.
C) Hyper- homocysteinemia, homocystinuria.
See: microRNA, elevated homocysteine and is there a role for excess Retinoic Acid? (substack.com)
D) Endocannabinoid deficiency, Mood swings, ADHD, impulsivity, anxiety, aggression.
The BHMT gene allele can cause lack of most endocannabinoids and excess of a certain type that is broken down by BHMT instead of being produced with the pathway. Clinical endocannabinoid deficiency can increase risk for anxiety, PTSD, depression, and other physical problems that may resemble Ehlers Danlos condition and histamine excess due to less inhibition of mast cells. Lack of choline or dimethylglycine due to BHMT dysfunction may increase impulsivity and add to anxiety.
Methylation pathway alleles of MTHFR, MTRR, and MTR may reduce availability of folate which may increase fatigue from macrocytic anemia and may reduce DNA methylation and have epigenetic effects.
Choline supplements may also be needed with folate enzyme dysfunction for phosphatidylcholine production as it is used more for betaine production. Gene polymorphisms that may affect choline needs include MTR, rs1805087 [wild-type (WT)]; MTRR, rs1801394; MTHFR, rs1801133; and MTHFD1, rs2236225. (Ganz, et al., 2016)
MAO-A T alleles are linked to anxiety, aggression, and impulsivity.
COMT alleles are linked to fibromyalgia, schizophrenia, opioid and alcohol addictions.
COMT and MAO-A alleles may have a gender related bias in risk for ADHD, preliminary findings. SLC6A2 and 4 were also assessed. COMT and SLC6A4 alleles were more of an ADHD risk for males and MAO A and SLC6A2 for females. (Biederman, et al., 2008)
VDR/Fok 1 alleles are linked to mood swings.
Medical history regarding endocannabinoid deficiency, impulsivity, and mood swings:
The author has a diagnosis of Bipolar Disorder Type 1, that occurred with perimenopausal changes. Earlier in her adult life ADHD and Generalized Anxiety Disorder were diagnosed. Currently the author is stable with the use of pomegranate products and other supplements including medical marijuana and nicotine lozenges; and is not on a prescription medication. Clinical Endocannabinoid Deficiency conditions that have been experienced by the author include chronic migraines, PTSD, phantom nerve symptoms, depression, anxiety, Bipolar Disorder, and Irritable Bowel Syndrome. (Russo, 2016) [Personal experience of the author.]
E) Fibromyalgia – potentially the phenotype of a heterogenic genotype.
A review by Janssen, et al., 2021, of polymorphisms identified in patients with fibromyalgia found three of the genes, COMT, MAOA and MTHFR, with alleles for the author; and also, ACE I/D, ADRA1A, ADRB2, ADRB3, BDNF, CNR1, DRD3, EDN1, GCH1, GRIA4, HLA-DRB1, HTR3A, HTR3B, HTR2A, IL-4, NRXN3, MEFV, RGS4, MYT1L, OPRM1, SCN9A, SERPINA 1 or A1AT, SLC6A4, TAAR1, TACR1, TRPV3, and TSPO. (Janssen, et al., 2021)
Two of the COMT SNPs of the author, rs4680 and rs4633, were seen more frequently in patients with fibromyalgia compared to the control group; and also rs4818, and rs6269 were more frequent in the fibromyalgia cohort. (Lee, et al., 2018)
Medical history regarding fibromyalgia-like symptoms:
The author experienced symptoms similar to Chronic Fatigue Syndrome and fibromyalgia following an infection with mononucleosis/EBV during high school. The diagnoses were new at the time and were not an exact match for the author’s pain points. White potatoes increased symptoms and learning what to avoid was similar to learning what to avoid for migraine triggers. The author got better or maintained instead of worsening enough for a diagnosis for either condition. Both Retinoid Toxicity (Vitamin A and carotenoids) and histamine foods are dietary triggers for the symptoms.
F) Dystonia / POTS, epigenetic risks.
See: POTS - Postural Orthostatic Tachycardia Syndrome, can be epigenetic & therefore may be reversible. (substack.com)
G) Confounding Variable – Zinc deficiency as a comorbid condition
…would exacerbate the risk of elevated homocysteine due to the role of zinc ion binding for the BHMT, SHMT, and MTR proteins, and lead to elevated IL-6 due to epigenetic changes; IL-6 degranulates mast cells, adding to histamine excess.
See: Zinc Deficiency and elevated IL-6 > mast cell degranulation>histamine excess; also >microbiome dysbiosis. (substack.com)
H) Confounding variable – ACEs, child or adult sexual trauma.
Hypermethylation can occur, more frequently in females, after childhood or adult trauma, or sex trauma, penetrative leaving a worse risk. Women methylate more than men, after adjustments for some variables it remained the same. Women who experienced sexual abuse methylate even more and MAO A gene alleles showed the same gender pattern – women methylate more than men. (Checknita, Tiihonen, Hodgins, Nilsson, 2021)
Hypermethylation tends to silence genes and sometimes permanently and the change may be passed to the next generation, (Ehrlich, 2019), via changes in sperm. (Jiang, et al., 2019) (An ovum is formed during fetal development and would be affected by the mother’s diet and her adequacy of zinc, choline, riboflavin, and methyl Bs, etcetera.)
Childhood trauma has been linked to an increased risk for anxiety, depression, posttraumatic stress disorder (PTSD), bipolar disorder, diabetes, and cardiovascular disease. The genes that are hypermethylated during childhood trauma/sex trauma tend to cause dysfunction in the stress response and the function of the hypothalamic-pituitary-adrenal (HPA) axis. (Jiang, et al., 2019, Figure 1)
“Labonte and colleagues reported that in hippocampal tissues derived from those who had died by suicide, comparing those with and without a history of childhood abuse, there were 362 differentially methylated promoter sites. Among these, 248 sites were hypermethylated and 114 were hypomethylated (102). Similarly, there was a bidirectional regulation of methylation in the cingulate cortex of those with/without childhood trauma who has had depression and died by suicide, with the highest differential methylation occurring in genes that related to myelin (103).” (CC-BY the authors: Jiang, et al., 2019)
Gene polymorphisms of the MAO A or epigenetic hypomethylation of the MAO B gene have been linked to negative health effects following child trauma/sex trauma. COMT and IL-6 gene polymorphisms may also be risk factors. Dopamine, serotonin and endocannbinoid interactions seems to be involved in mood regulation and stress coping. (Jiang, et al., 2019)
Medical history regarding ACES, child and adult trauma/sexual trauma: Yes. ACEs score 5/10. (americanspcc.org/take-the-aces-quiz) Child and adult sexual and physical trauma and an emotionally unstable childhood home with some binge drinking by the father and verbal abuse or scary behavior by both parents occasionally. Physical and other trauma by an older male sibling. Dissociative episodes since a toddler experience that became a recurring nightmare until EMDR therapy helped address it.
I) Secondary Hyperparathyroidism - (addition).
VDR gene alleles may affect risk of secondary hyperparathyroidism. (Nagaba, et al., 1998) Fok-1 has been linked to parathyroid hormone levels in postmenopausal women. (Žofková, Zajíčková, Hill, 2003) Polymorphisms in the parathyroid hormone gene has also been associated with hyperparathyroidism in renal dialysis patients. (Gohda, et al., 2002)
*The blood screening designed for autism did not include the parathyroid hormone gene. (PTH Single Nucleotide Polymorphisms - SNPs (ncbi.nlm.nih.gov/snp/?term=PTH)
Medical history regarding fibromyalgia-like symptoms:
Secondary hyperparathyroidism is a condition the author experienced undiagnosed for many years. It causes significant odd mental and physical symptoms that were called “crazy” for far longer than necessary as all that was needed for treatment was to take more calcium (but not too much more. The author uses 250 mg per day as a supplement - not the often-recommended 1000 mg.) The odd symptoms of internal pressure and jitteriness, like a fidgety body and brain, can return if the extra calcium is missed too often.
If the symptoms worsen too much, self-harm urges can occur from a feeling of the internal pressure. There is an urge odd to ‘pop’ the eyes or body, with sharp things, like to relieve an overfull balloon. The ‘stabby’ feeling is about the internal pressure, rather than any feeling of shame or worthlessness. Eye gouging is in the literature for an autism case and providing calcium helped but that case didn’t include a connection to secondary hyperparathyroidism. Either low vitamin D or low calcium can be a cause. It was a very disturbing feeling and a strong urge, hard to resist even as an educated person. Before the reason was discovered it had helped the author to at least label the odd feeling ‘stabby’, as it helped put some sense of control over a scary situation. “Oh, that is just my stabby feelings, well, don’t do that.”
See this post: Self injurious behavior in autism patients with low calcium levels, (transcendingsquare.com).
The author doesn’t use any dairy products due to it causing congestion within ~ 45 minutes of eating, but the seeds and nuts and green vegetables in her vegan plus other restrictions diet, add quite a bit of calcium. Too much calcium increases her fibromyalgia-like muscle cramps and irritability symptoms. The secondary hyperparathyroidism symptoms started after she had stopped using a higher dose calcium supplement and focused more on magnesium to reduce muscle cramps and anxiety. Note: We need both calcium and magnesium in balance.
~~~
The author likes health too much to leave her health in the hands of the current medical system.
*Writing in third person is kind of fun. I will stop now.
When medical advice is not helpful, and is stigmatizing, mislabeling, and disempowering - consider not seeking advice from those sources - and do your own research which means listening to your body, not just reading complex material. We often know what is hurting us. It may have been fine when we were young but is no longer fine now. Face it, grieve it, and give it up.
“We don’t know the cause,” is not an answer, it is a challenge to find the cause. Too many in the medical industry are focused on finding patentable ‘answers’ that may be profitable, rather than on finding helpful guidance for preserving or restoring function. We need to start over with a system that is not for profit, or one in which the health professional only gets paid when the patient is healthy as was a norm in ancient China (I think). When sickness generates profit, there is no motivation to support health.
I am fortunate to have done as well as I did, given the difficult health issues I have faced. I did seek specialists at times and did learn from their guidance, but also didn’t follow some of it as I knew by that time, that certain standard recommendations would not help my individual needs (like high dose vitamin D and 1000 mg of calcium).
A treatment section seems like it might be helpful and would be part of a SOAPIE note Plan/Intervention - what did I do more precisely and still do to maintain health?
*Subjective (person’s own feelings or opinions), Objective (data, like physical measurements or observation of visual symptoms), Assessment, Plan, Intervention, Evaluation.
Disclaimer: This information is being shared for educational purposes within the guidelines of Fair Use and is not intended to provide individual health guidance.
Reference List
(Checknita, Tiihonen, Hodgins, Nilsson, 2021) Checknita, D., Tiihonen, J., Hodgins, S., Nilsson, K.W., (2021). Associations of age, sex, sexual abuse, and genotype with monoamine oxidase a gene methylation. J Neural Transm (Vienna). Nov;128(11):1721-1739. doi: 10.1007/s00702-021-02403-2. Epub 2021 Aug 23. PMID: 34424394; PMCID: PMC8536631. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8536631/
(Ehrlich, 2019) Ehrlich M. DNA hypermethylation in disease: mechanisms and clinical relevance. Epigenetics. 2019 Dec;14(12):1141-1163. doi: 10.1080/15592294.2019.1638701. Epub 2019 Jul 8. PMID: 31284823; PMCID: PMC6791695. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6791695/
(Gohda, et al., 2002) Gohda, T., Shou, I., Fukui, M., Funabiki, K., Horikoshi, S., Shirato, I., Tomino, Y., (2002). Parathyroid hormone gene polymorphism and secondary hyperparathyroidism in hemodialysis patients, Am J Kidney Dis. 39(6):1255-1260, ISSN 0272-6386, https://doi.org/10.1053/ajkd.2002.33399. https://www.sciencedirect.com/science/article/pii/S0272638602766791
(Jiang, et al., 2019) Jiang, S., Postovit, L., Cattaneo, A., Binder, E.B., Aitchison, K.J., (2019). Epigenetic Modifications in Stress Response Genes Associated With Childhood Trauma. Front Psychiatry. Nov 8;10:808. doi: 10.3389/fpsyt.2019.00808. PMID: 31780969; PMCID: PMC6857662. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6857662/ (Figure 1)
(Nagaba, et al., 1998) Nagaba, Y., Heishi, M., Tazawa, H., Tsukamoto, Y., Kobayashi, Y., (1998). Vitamin D receptor gene polymorphisms affect secondary hyperparathyroidism in hemodialyzed patients. Am J Kidney Dis. Sep;32(3):464-9. doi: 10.1053/ajkd.1998.v32.pm9740163. PMID: 9740163. https://www.ajkd.org/article/S0272-6386(98)00251-0/fulltext
(Žofková, Zajíčková, Hill, 2003) Žofková, I., Zajíčková, K., Hill, M., Serum parathyroid hormone levels are associated with FokI polymorphism of the vitamin D receptor gene in untreated postmenopausal women, (2003). Eur J Internal Medicine, (14)4:232-236, ISSN 0953-6205, https://doi.org/10.1016/S0953-6205(03)00065-7. https://www.sciencedirect.com/science/article/pii/S0953620503000657