The Brain and SAD (Stress, Anxiety, Depression)

At Baucom Institute, we focus on the needs of the body to function properly like what we eat and how we supplement what we eat.

Over the next several weeks, we’ll be addressing how the brain, its functions and needsdepressed man sitting in the tunnel, are related to SAD – stress, anxiety and depression.

With the medical community using the prescription pad as the answer to helping patients deal with these issues, it’s time to educate the public about the facts and the options to chemical treatment.

First, let’s address the brain and the areas that are affected by SAD:

Amygdala - Part of the limbic system which controls mood, memory and hormone production and actively assigns negative emotions like fear and anger to our thoughts and perceptions; where negative emotional memories are stored and recalled.

Basil Ganglia - Located under the frontal lobes of the brain, the basal ganglia are connected to the frontal lobe cortex which helps movement, thinking, memories and emotions; studies have shown it atrophies with stress, anxiety and depression.

medical  doctor with brain3d meatl in his hands as conceptPrefrontal Cortex - The front most part of the frontal lobe cerebral cortex helps regulate thinking and reasoning, decision-making, and expression of emotions; stress will cause the prefrontal cortex to shut down and actually shrink as well as lessen metabolism.

Hippocampus - Located under the right and left temporal lobes right behind the amygdala, the hippocampus plays a central role in encoding long-term factual memories, works with the amygdala in creating emotional memories; it will reduce in size with chronic stress, anxiety and depression.

Hypothalamus - The nuclei of the hypothalamus will be altered in chronic stress, anxiety and depression which negatively impacts the pituitary master hormones, affecting the functioning of the entire body and brain.

Next time, we’ll address understanding neuron communication and how stress, anxiety and depression affect neurotransmitters.

Have anything to add? We want to hear from you so post below!

Methylation and Nutrition

We’ve been on a long series about Methylation and how an individual’s nutrition can affect the outcome of their health. Here’s a quick review of MTHFR:

MTHFR-baucom-institute

Once the MTHFR tests shows (+) variants exist, what else can the health provider do to effectively treat the patient?

MTHFR-solutions-baucom-institute

So, what are you doing as a patient to take control of your health in relation to genome testing and restorative care with a physician that understands the impact of these aspects?

As a medical practitioner, are you having your patients tested for this all important genome so that they can be more proactive with their health and prevent disease?

Autism and Impaired Methylation

  • epigenetics-autism-methylation-baucom-instituteAn increased vulnerability to oxidative stress and a decreased capacity for methylation may contribute to the development and clinical manifestation of autism.

  • Children with autism had significantly lower baseline plasma concentrations of methionine, SAM, homocysteine, cystathionine, cysteine, and total glutathione and significantly higher concentrations of SAH, adenosine, and oxidized glutathione.

  • Consistent with impaired capacity for methylation (significantly lower ratio of SAM to SAH) and increased oxidative stress (significantly lower redox ratio of reduced glutathione to oxidized glutathione).

Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with Autism 1 From the Department of Pediatrics, University of Arkansas for Medical Sciences, and the Arkansas Children‘s Hospital Research Institute, Little Rock, AR (SJJ, SM, and SJ); Niagara Falls, NY (PC); Colden, NY (LJ); Gaylor and Associates, LLC, Eureka Springs, AR (DWG); and Edison, NJ (JAN)2 Rep

PMhx – case:autism-methylation-baucom-institute

  • 6 years old
  • HM hx of severe anxiety,
  • unable to perform in class,
  • crying,
  • restless,
  • insomnia,
  • ADD,
  • dyslexia
  • small bumps on cheeks and upper arms mom describes as acne..

The mother of the child took him to the doctor to medicate him for anxiety and for a referral to a special education program. The mother was considering home schooling due to the severity of the child’s anxiety. This testing was done in addition:

  • Labs:  HLA Dq2/ Hla Dq8 negative

  • Food allergy test + gluten, wheat, dairy, honey, yeast, and some other minor antibodies (leaky gut).

  • MTHFR: c677T+/A1298C+

Stay tuned for the results on our next blog.

Xenobiotic Effects on COMT

A xenobiotic is a foreign chemical substance found within an organism that is not normally, naturally produced by or expected to be present within that organism. It can also cover substances which are present in much higher concentrations than are usual.41_SchemaRTS_Eng

  • In humans, 2-Oh and 4-Ohestradiol (catechol estrogens) are rapidly O-methylated to form monomethyl ethers catalyzed by COMT and S-adenosyl-L-methionine.

  • Xenobiotics may strongly inhibit COMT-mediated
    O-methylation of catechol estrogens by xenobiotics and may facilitate the development of estrogen-induced tumors.

  • Xenobiotics may therefore deplete intermediates in the Folate cycle.  Environmental burden of Xenobiotics may create a higher need for methylation support.

Catechol-O-methyl_transferase_baucom-instituteAbstract: COMT genotype, micronutrients in the folate metabolic pathway and breast cancer risk - Goodman JE, Lavigne JA, Wu K, Helzlsouer KJ, Strickland PT, Selhub J, Yager JD; Department of Environmental Health Sciences, Johns Hopkins University, Bloomberg School of Public Health, Baltimore, MD 21205, USA.

  • Catechol-O-methyltransferase (COMT) catalyzes the O-methylation of catechol estrogens (CEs), using S-adenosylmethionine (SAM) as a methyl donor.

  • Several studies have indicated that the val108met COMT polymorphism, which results in a 3-4-fold decrease in activity, is associated with increased breast cancer risk.

  • Folate, whose intake levels have also been associated with breast cancer risk, and other micronutrients in the folate metabolic pathway influence levels of SAM and S-adenosylhomocysteine (SAH), a COMT inhibitor generated by the demethylation of SAM.

  • Because these micronutrients have been shown to alter SAM and SAH levels, we hypothesized that they could also affect COMT-catalyzed CE methylation.

  • Although measurements of SAM and SAH were not initially collected, a secondary analysis of data from two nested case-control studies was performed to examine whether serum levels of folate, vitamin B12 (B12), pyridoxal 5′-phosphate (PLP), cysteine and homocysteine, in conjunction with COMT genotype, were associated with breast cancer risk. COMT(HH) (high activity COMT homozygote) breast cancer cases had statistically significantly lower levels of homocysteine (P = 0.05) and cysteine (P = 0.04) and higher levels of PLP (P = 0.02) than COMT(HH) controls. In contrast, COMT(LL) (low activity COMT homozygote) cases had higher levels of homocysteine than COMT(LL) controls (P = 0.05).

  • No associations were seen between B12, COMT genotype, and breast cancer risk. An increasing number of COMT(L) alleles was significantly associated with increased breast cancer risk in women with below median levels of folate (P(trend) = 0.05) or above median levels of homocysteine (P(trend) = 0.02). These findings are consistent with a role for certain folate pathway micronutrients in mediating the association between COMT genotype and breast cancer risk.

These findings are consistent with a role for certain folate pathway micronutrients in mediating the association between COMT genotype and breast cancer risk.

Case Study: Susan

  • 49 yo CF recent dx of Stage II Breast Ca hormone Rec +,s/p partial mastectomy, body-case-study-baucom-instituteradiation, irregular periods, shingles, intolerant of Fereston due to Headaches, constipated.  Hx of fibroids, heavy periods, fibrocystic breast. G2P2

  • nl vitals,   Estradiol 26.8pg/ml (0-32.2 menopause range)

  • Sed rate 22 (0-20)

  • Cbc, chem, thyroid panel cholesterol wnl

  • Vit D 153 (30-100)

  • GGT 15   Uric Acid 3.2

  • Glutathione 992

  • MTHFR C677+/A1298C+

  • Cytokine: base Il-6++, IL-17+, IL-12–,IFN gamma ++, TNF-a ++, IL-4++, IL-5–, IL-10++, IL-8++, G-CSF++

How would you approach treatment of this patient?

Spectracell-Methylation-Susan-Baucom-Institute

Folate Cycle Nutrients, Homocysteine, and Transsulfuration

  • Transsulfuration is the conversion of Homocysteine with the co-factors B6 and Serine to Cystathionine.

Homocysteine-Damage-Ladd-McNamara

  • Cystathionine is then converted to Cysteine which is one of the three amino acids that compose Glutathione.
  • Polymorphisms in Cysta beta-synthase may affect the rate of conversion of Cystathionine to Cysteine.
  • Cysteine is thought to be the rate limiting step in the formation of Glutathione.

glutathione-structure-baucom-institute (2)

 

What are the Effects of MTHFR?

MTHFR mutational effects include:MTHFR-DNA-Effects-Baucom-Institute

  • chronic low glutathione
  • leaky gut and food allergies
  • chronic viruses
  • high serum B12 levels
  • low serotonin and melatonin
  • high serum ferritin and HFE mutation
  • Thalassemia and hepatorenal failure
  • FSG and renal failure
  • autoimmunity frequency in women
  • chronic dysbiosis/chronic yeast infections
  • estrogen dominant cancers
  • subtype and elevated homocysteine
  • ADD/bipolar/PMS/Chronic Fatigue/Fibromylagia
  • tongue/fingernails/thin hair
  • vericose veins/spider veins
  • hypercoagulopathy/infertility
  • elevated testosterone in men/PCOS in women
  • acne, fibroids, Endometriosis, Menometorrhagia
  • depression when on OCPs
  • exacerbation of menopausal symptoms on BHRT
  • elevated uric acid and elevated ammonia levels
  • gut barrier and dysbiosis
  • CANCER
  • estrogen dominance and obesity (estrogens effects on insulin and the insulin receptor and adiponectin)

 

A1298C Variant

A1298C – a mutation from adenine to cytosine at position 1298 within the gene. These variants lead to amino acid differences in the protein that reduces its ability to function.

1298:genes_MTHFR_baucom_institute

  • AA-normal homozygous
  • AC or CC – one or two variant copies
  • about 30% of the population
  • not associated with increased risk
  • associated with increased risk if found together with a 677 variant

Severe MTHFR deficiency:

  • Severe MTHFR deficiency is rare (about 50 cases worldwide) and caused by mutations resulting in 0-20% residual enzyme activity.
  • Characterization of six novel mutations in the methylenetetrahydrofolate reductase (MTHFR) gene in patients with homocystinuria. Hum Mutat 15 (3): 280-7
  • These patients exhibit:
  1. developmental delay,
  2. motor and gait dysfunction,
  3. seizures,
  4. neurological impairment and
  5. have extremely high levels of homocysteine in their plasma and urine as well as low to normal plasma methionine levels.

Epigenetic_mechanisms_MTHFR_methylationBottom line:  If one leads a lifestyle which is unhealthy (smoking, high stress, toxic exposures) and consumes an unhealthy diet (refined carbs, processed meats, saturated fats), having a heterozygous A1298C mutation may contribute to cardiovascular disease, depression, fibromyalgia and others.

Possible symptoms associated with A1298C MTHFR mutations:

  • hypertension
  • delayed speech
  • muscle pain
  • insomnia
  • irritable bowel syndrome
  • fibromyalgia
  • chronic fatigue syndrome
  • hand tremor
  • memory loss
  • headaches
  • brain fog

Possible signs associated with A1298C MTHFR Mutations:

  • elevated ammonia levels
  • decreased dopamine
  • decrease serotonin
  • decreased epinephrine and norepinephrine
  • decreased nitric oxide
  • elevated blood pressure
  • muscle tenderness
  • ulcers
  • pre-eclampsia

Possible conditions associated with A1298C MTHFR mutations:

  • fibromyalgia
  • chronic fatigue syndrome
  • autism
  • depression
  • insomnia
  • ADD/ADHD
  • irritable bowel syndrome
  • inflammatory bowel syndrome
  • erectile dysfunction
  • migraine
  • Raynaud’s
  • cancer
  • Alzheimer’s
  • Parkinson’s
  • recurrent miscarriages

Frequency of MTHFR Polymorphisms

30-40% of Americans are found to have either a single or double polymorphism of either C677T or A1298C.

  • There is ethnic variability in the frequency of the T allel-frequency in Mediterranean/Hispanics>Caucasians>Africans/African-Americans (Worldwide distribution of a common methylenetetrahydrofolate reductase mutation. Am J Hum Genet 62 (5): 1258-60)
  • Higher frequency in chronic disease: Autoimmune diseases, diseases of the gut, Fibromyalgia, Chronic Fatigue, Chronic Retroviruses, Cancer, Hormone dysregulation, Mood issues, Cardiometabolic patients.

C667Tpolymorphtandem-baucom-institute

  • There is a mutation from cytosine to adenine at position 677 within the gene.
  • Possible genotypes?
  • 677-CC, CT, or TT
  • CC-homozygous normal
  • About 45% of the population
  • No increased risk associate
  • CT-on variant copy
  • About 45% of the population
  • Some reduced enzymatic activity, alone not associated with increased risk
  • TT-two variant copies
  • About 10% of the population
  • Increased risk for elevated homocysteine level and associated complications

Homocysteine & Vascular Disease

Pathophysiology of Homocysteine:

1. Interference with normal thrombolysisHomocysteine-Damage-Ladd-McNamara

  • decreased antithrombin III activity
  • Activation of factor V or XII
  • Inactivation of protein C
  • Promote binding of Lp(a) to fibrin
  • Platelet inhibition (interaction with nitric oxide)

2. Promote SMC proliferation

3. Promote LDL oxidation

4. Direct toxicity to endothelium

Genetic and Dietary Determinants of Serum Homocysteine Concentrations:

Genetic -

  • Cystathionine-beta-synthase deficiency
  • Methionine synthase deficiency
  • MTHFR deficiency
  • Defective absorption of B12 or folate
  • Prevalence – 30% Female V. 25% Male

lowering-homocysteine-levels-naturally-baucom-instituteNutritional -

  • Vitamin B6
  • Vitamin B12
  • Folate

Risks Associated with MTHFR Variants/High Homocysteine:

  • Cardiovascular Disease
  • Cerebral Vascular Disease (stroke)
  • Venous and Arterial Thrombosis
  • Methotrexate Toxicity for Cancer Therapy