Overmethylation and Depression – Walsh Biotypes

TotallyADD, Rick Green, Parker & Galileo
September 21, 2014
Copper Excess and Depression – Walsh Biotypes
October 4, 2014

Overmethylation & Depression Biotypes: 2nd of 5 Subsets

With very few exceptions, these persons report intolerance to SSRI antidepressants and antihistamines. A high percentage are non-competitive persons who complain of chemical and food sensitivities… –  shootings at Columbine High School and Virginia Tech were carried out by students taking SSRIs.1
~ William Walsh

Overmethylation, Folate Deficiency 3 & Treatment Failure

Typical features of overmethylation include excellent socialization skills, many friendships, non-competitiveness, artistic or musical interests, chemical and food sensitivities, and a tendency for high anxiety.
~ William Walsh

Markers Matter Red Can Bouy

Overmethylation – Think: Hot

WD2: Walsh Depression #2 – This is the second in a series [WD1: Undermethylation here] of 5 posts on Dr Bill Walsh's 5 biotypes of depression as described in his book Nutrient Power and listed below. This particular biotype is most important to CorePsych readers because of the 5 subtypes this type of depression also correlates in his data three times more frequently with ADHD and more academic underachievement than the first Undermethylated biotype.

This brief video on this second WD2 – Walsh depression biotype [2 of 5] – will remind you of the fact that depression is more than just an appearance of sadness. Overmethylated depression will prove untreatable if not measured and addressed with some of the laboratory inquiries linked below. Too many fail SSRI treatments with trial after trial of otherwise appropriate medications for the symptoms, not the biologically-based disorder.

From appearances to measurable science – biotype laboratory neurophysiological assessments will change treatment outcomes for depression and a variety of other mind-presentations. Markers matter. Even small markers matter in a sea of navigational guesswork and treatment failure.

Dr William Walsh: CorePsych Critical Thinker

Dr Walsh has presented his research at the American Psychiatric Association, the U.S. Senate, the National Institute of Mental Health, the Society for Neuroscience, and has been a speaker at more than 30 international conferences. He has authored more than 200 scientific articles and reports, and has five patents.

Dr Walsh has researched biomedical details for individuals previously considered as untreatable: from personality disorders to others insufficiently treatable with modern psychopharmacology. He's published research and biomedical evaluations on lost souls from murderers to those more commonplace presentations of untreatable depression and ADHD. Think: new options for treatment failure at any level of mind alteration.

If you're interested in learning more about his groundbreaking work consider attending his Walsh Research Institute meeting in Chicago Oct. 18-22, next month.

Back to WD2 refractory depression: This video and then a brief discussion of overmethylation: 4, 5


Dr Walsh – Whole Blood Histamine as A Marker – 2:16 min


Overmethylation and Depression – 1:44 Min


Symptoms and Traits of Overmethylation

These replicable medical findings clearly encourage more complete assessments – Summarized from Nutrient Power 3 Walsh's most recent book. In Nutrient Power Dr Walsh details of how to both measure and treat this specific, easily identified form of depression.

*Don't let the nutritional title trivialize your response.* Read this book. Measure for methylation imbalances via whole blood histamine.

Important indicators of this overmethylation, low folate depression syndrome include a whole blood histamine level below 40 ng/ml and an elevated SAMe/SAH ratio 7 in combination with key symptoms and traits including OCD tendencies, seasonal allergies and a history of perfectionism.

Treat the underlying overmethylation problem as it looks in your life, your offices. We now measure for these methylation issues at CorePsych.

Overmethylation: Clinical Characteristics

Characteristics of Overmethylation – Incidence: 20% of clinical depression [n – 2800]:


  1. Improvement after folate therapy
  2. High anxiety, panic tendency, talkative
  3. Adverse reaction to SSRIs
  4. Improvement after benzodiazapines
  5. Food and chemical sensitivities
  6. Absence of seasonal allergies
  7. Dry eyes and mouth
  8. Low libido
  9. High artistic abilities and interest
  10. Hirsutism – excess hair (males only)
  11. Nervous legs, pacing
  12. Sleep disorder
  13. Noncompetitive in sports, games
  14. Underachievement in school
  15. Estrogen intolerance [~ estrogen dominance]
  16. Hyperactivity 6

Do you see anything familiar in treatment refractory individuals you know or treat? Did the words adverse reactions to SSRIs and high anxiety catch your attention? Do you think that low libido, sleep disorder, underachievement in school and Executive Function challenges sound familiar as a symptom complex associated with depression?

Overmethylation Treatment Response Time 4

Increased anxiety for the first 2-3 weeks, followed  by sharp improvement in 4-8 weeks and significant effectiveness in 3-4 months.


Four More Depression Biotypes

Soon: the additional four Walsh depression biotypes, 3 and incidence in his research.


  1. Undermethylated – decreased serotonin and dopamine – 38%
  2. Copper Overload – elevated norepinephrine – 17%
  3. Pyrrole Disorder – reduced serotonin, GABA – 15%
  4. Toxic Overload – lead, mercury, cadmium or arsenic – 5%


Download Overview Of Walsh CorePsych Testing:


Walsh Resources and References


+ 2 Video Playlists on Epigenetics: 1. Public, 2. Professionals, & one program by

Dr Walsh on Epigenetics and Methylation


PS: Don't Forget This TotallyADD Recording

Register for, and make sure you go back to watch, our Rick Green/Parker Webinars as we discuss Why [Dig Deeper], How [Brain Function] and, in the third TotallyADD Webinar, What [To Explore] series. Topics: psychiatric diagnosis and treatment for ADHD/Executive Function. Mind science is slowly but inexorably changing. Watch the first two meetings to prepare for our anticipated discussion about Dr Walsh's laboratory measurements and nutrient interventions in the third webinar. Details matter.

NB: The first Why Webinar is now recorded and ready for review. Prepare for How coming on Oct. 19, available here:


Do subscribe below for future CorePsych updates, and please forward these important new data-tools to your colleagues.

Dr Charles Parker
Connect & Subscribe To CorePsych News: This Link
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Complimentary & New: 23 pg Special Report: Predictable Solutions For ADHD Medications
Book: New ADHD Med Rules: http://amzn.to/1zeDMga


1 Larkin RW. (2007). Comprehending Columbine. Temple University Press: Philadelphia. Reported by Dr Walsh at the Amer. Psychiatric Assoc meeting in '14
2 Walsh, WJ, Nutrient Power – Heal Your Biochemistry and Heal Your Brain, Skyhorse Publishing 2012.
3 Ibid., p 77.
4 Ibid., p 150.
5 Walsh WJ, Rehman F. (1997). Methylation syndromes in mental illness. Abstracts: Society for Neuroscience 27th Annual Meeting (pt 2). New Orleans, LA, October 25-29.
6 Walsh, Dr. William J. (2014-05-06). Nutrient Power: Heal Your Biochemistry and Heal Your Brain (Kindle Locations 1483-1488). Skyhorse Publishing. Kindle Edition.
7 http://hmg.oxfordjournals.org/content/14/suppl_1/R139.long


  1. Kelly says:

    Hi Dr. Parker,

    I have been reading your articles on over-methylation, and I see many of the characteristics in myself. I respond negatively to antihistamines and SSRIs, for example. I also have no seasonal allergies, but I do have chemical and food sensitivities. I have taken Adderall for quite some time with positive results for several years. (I do feel like I burn through it very quickly, though–don’t know if that is associated with over-methylation.) Recently, I have not been noticing the some positive results, and I’m trying to figure out what could be going on. After reading about over-methylation, I decided to try folic acid. Within days, I felt noticeably better. I’m really confused, though, because I felt sure that I had low dopamine levels. If I’m understanding correctly, over-methylation typically results in high levels of dopamine (in addition to serotonin)? I’m just wondering, is there any way I could have low dopamine and also be over-methylated? (My apologies if I’m not wording these terms correctly.)

    • Kelly,
      Your question is quite typical, and one of the main reasons I strongly support Walsh’s work, as I worked from the same misunderstandings for years with dopamine levels. Measurement matters, and will tell the tale.

      Key Issue: Overmethylation can look like undermethylation clinically and, if not measured, can create unpredictable outcomes for years. Usually, however, the signs of OM are associated with *marked sensitivity* to any meds, stimulants or antidepressants – they just can’t take them. More often than not these confusing clinical pictures arise from the underlying complexity of challenges, often with more than one of these Walsh imbalances present simultaneously – for example: undermethylation with copper or pyrrole issue associated.

      Because the appearances often do prove confusing we strongly encourage measurement to move forward with resolving those several underlying possibilities. The food sensitivities issue is but another confounding challenge. If you have significant IgG issues they will corrupt outcomes whatever you do until they are first corrected – with supplements or meds either one or both. Cytokines from IgG reactions corrupt the system and it therefore remains unbalanced whatever you do.

      The order of these tests with more videos and explanations are listed in clinical importance here: http://corepsych.com/tests. – Hope this helps,

  2. Jimmy says:

    Hi Dr,

    I am keep on having thoughts of suicide but I do not know if I should start Venlafaxine treatment as my Dr has advised or wait for my histamine test to come back – isnt there a danger that if I am overmethylated that Venlafaxine could make me worse?

    • Jimmy,
      Sounds like you have a well informed doctor, more well informed than average. Please ask him this question as he is much more on top of your situation than I could ever be from this distance.

      My experience, with patients I’ve seen: I’ve given Venlafaxine for many, many years without knowing about overmethylation, and with watchful care have not had a problem. Further, my experience now that I know about overmethylation: reactions can occur quite quickly if overmethylation is a problem – so appropriate response can take place quickly.

      For your consideration Monday when you speak to him: watchful trial of meds, careful follow up until testing is back – and knowing that you can become worse puts you on full alert to prevent destructive actions. Do leave it up to your doctor, and hang strong… the results come in quickly, about 2-3 weeks.

  3. […] Overmethylation and Depression – Walsh Biotypes […]

  4. […] Walsh Depression #5 – This is the last in a series [WD1: Undermethylation here, | WD2: Overmethylation here | WD3: Copper Excess here | WD4: Pyrrole Disorder here] of 5 posts on Dr Bill Walsh’s 5 […]

  5. Pamela says:

    Thanks Dr. Parker – you are helping me and our son’s integrative psychiatrist understand this. Just to clarify- for over-methylators – do not give methylated forms of folic acid or Vitamin B12, to further add to methyl status. So use folic acid or folinic acid, Vitamin B12 as cyanocobalamin, and Niacinamide (Vit B3) as correct supplement forms. This combination should soak up extra methyl groups and eventually bring down excessively high dopamine levels, resulting in much better symptom control (extreme impulsivity, hyperactive, borderline paranoia and obsessions).

    I think the key that you keep reminding us, is to always go back to what’s happening with the neurotransmitters. There are so many people (at least on the web!) who are getting genetic testing, and then jumping on the MTHFR and other SNP mutation bandwagons. That’s what happened to us – and we ended up giving our son exactly the Wrong supplements, when overall, his completely bioindividual makeup shows he is an overmethylator.

    One other interesting statement from Dr. Walsh’s work (page 24): Folate does increase methylation. However, folate generates acetylase enzymes that alter histones, promoting expression of SERT and DAT transporter proteins.

    This is how folate reduces dopamine activity in the synapse, even while increasing dopamine production via the methylation cycle. Overall, folate works to enhance the reuptake of dopamine to combat excess.

    • Pamela,
      Outstanding, so well said in so few words! I was just listening to a Bulletproof podcast with Ben Lynch the MTHFR guy and quite honestly the points you are making here are points I do think they were confused on during the podcast. I do have to re-listen, but you are quite accurate here in what I’ve seen in my office and why I’m so pleased to be working w the Walsh protocols.

      Thanks for weighing in!
      Quick PS: See this page on Epigenetics if you haven’t – I’ve pulled together a number of training vids to make that part of it more understandable. http://corepsych.com/walsh-resources

  6. Pamela says:

    I still can’t get my head around this correctly. Everything I have read about methylfolate is that a deficiency of methylfolate can cause low levels of serotonin and dopamine to be produced.

    Yet Dr. Walsh says that folate deficiency should be treated with methylfolate, to reduce high dopamine/serotonin. So why would we give methylfolate to people that have excessively high levels of dopamine?? Please explain

    • Pamela,
      Good question: this is a quote from his book Nutrient Power


      “It’s interesting to note that high oxidative stress can cause undermethylation and also that undermethylation can cause excessive oxidative stress. The presence of either imbalance can cause the other. Recycling of Hcy [Homocystine] to methionine can be achieved by reactions with 5-methyltetrahydrofolate (5-MeTHF) and vitamin B-12. The 5-MeTHF supplies a methyl group to form methyl-B-12, which then reacts with Hcy to produce recycled methionine. This reaction is enabled by the methionine synthase enzyme. Hcy can also convert to methionine by direct reaction with trimethylglycine (TMG), a molecule that transfers a methyl group to Hcy to form methionine and dimethylglycine (DMG).”

      Walsh, Dr. William J. (2014-05-06). Nutrient Power: Heal Your Biochemistry and Heal Your Brain (Kindle Locations 3858-3862). Skyhorse Publishing. Kindle Edition.

      —- And further on methylfolate

      “Part of the homocysteine is recycled to methionine, with the remainder converted to cystathionine. Both of these pathways are essential to good health: (a) recycling to methionine assists in maintenance of SAMe levels, and (b) the cystathionine pathway is a primary source of cysteine, glutathione, and other valuable antioxidants.”

      Walsh, Dr. William J. (2014-05-06). Nutrient Power: Heal Your Biochemistry and Heal Your Brain (Kindle Locations 3855-3857). Skyhorse Publishing. Kindle Edition.


      For folate deficiency, overmethylation, he only recommends folate not methylfolate.

  7. […] Walsh Depression #4 – This is the fourth in a series [WD1: Undermethylation here, | WD2: Overmethylation here | WD3: Copper Excess here] of 5 posts on Dr Bill Walsh’s 5 biotypes of depression as […]

  8. […] Overmethylation and Depression – Walsh Biotypes […]

  9. […] Walsh Depression #3 – This is the third in a series [WD1: Undermethylation here, | WD2: Overmethylation here] of 5 posts on Dr Bill Walsh’s 5 biotypes of depression as described in his book Nutrient […]

  10. Pamela says:

    Hi Dr. Parker- Am very confused. Read Dr. Walsh’s excellent book. Please explain for me: If a person has a high dopamine level but a low serotonin level, how do you handle over/under methylation issues? I believe folate & B12 helps increase methylation to make more of both serotonin and dopamine, while niacin etc reduces methylation to drop both serotonin and dopamine.

    What is the best approach for divergent neurotransmitter levels??
    thanks for all you do.

    • Pamela,
      Excellent question, thanks for asking. Specificity is the key to those next steps. This is a protocol I use in my office – in sequence as DA is more problematic often than 5-HT [serotonin].
      1. “About 29.5% of the BD subjects exhibited depressed blood histamine, which is a biomarker for overmethylation, an elevated methyl/ folate ratio, and elevated levels of dopamine and norepinephrine. This imbalance is associated with anxiety, paranoia, and depression and was treated using folic acid, vitamins B-3 and B-12, and augmenting nutrients.” These interventions help most w DA. Start w DA, then, after some symptomatic changes take place move to 2.
      Walsh, Dr. William J. (2014-05-06). Nutrient Power: Heal Your Biochemistry and Heal Your Brain (Kindle Locations 2438-2440). Skyhorse Publishing. Kindle Edition.

      1a: “Copper has special significance in mental health due to its role in metabolism of dopamine and synthesis of norepinephrine’
      Walsh, Dr. William J. (2014-05-06). Nutrient Power: Heal Your Biochemistry and Heal Your Brain (Kindle Locations 2829-2830). Skyhorse Publishing. Kindle Edition.

      2. Then, after 1: SAMe, L-tryptophane and 5-HTP to encourage, support serotonin levels following the direct intervention on DA.
      “Methionine, SAMe, 5-HTP, tryptophan, inositol, Ca, Mg, vitamins B-2, B-6, D all increase 5-HT.”
      Walsh, Dr. William J. (2014-05-06). Nutrient Power: Heal Your Biochemistry and Heal Your Brain (Kindle Locations 2864-2865). Skyhorse Publishing. Kindle Edition.

      If you were tested by Neuroscience they often recommend covering both imbalances at the same time – but if the patient is more refractory to treatment the Overmethylation is the one to deal with first. Without first covering overmethylation it’s quite impossible to give any supplements or medications that don’t build up and create a toxic reaction.

  11. […] changes that absolutely improve ADHD treatment outcome on a sub-cellular level with more at this Dr William Walsh Series of Postings on Nutrient Biotypes at […]

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