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DEPRESSION: Methylation Station

Updated: Mar 16, 2023

The best holistic approach to depression considers the mental/emotional as well as the biochemical. Let’s talk for a moment about the biochemical component:

Firstly, there are multiple biochemical components to consider when assessing depression. Specifically, this discussion will focus on the most common biochemical dilemma - the ability to methylate. What exactly is methylation? Methylation is when a ‘methyl group’ gets attached to a molecule in the body. This comes to fruition as DNA production, neurotransmitter production, energy production, histamine metabolism, and mood balancing just to name a few. DNA methylation has been shown to vary between regions of the brain and even possibly between cells in those regions [1].

Depression is a common symptom when the body’s ability to methylate becomes impaired. This occurs when the cells of the body methylate too much or too little. When the body ‘under-methylates’, symptoms may include depression, OCD tendencies, a calm exterior with a ‘tense’ interior, better with a SSRI medication, seasonal allergies, and high libido. The opposite may occur when the body ‘over-methylates’. Symptoms of over-methylation may include depression, high anxiety or panic, sensitivity to certain foods, adverse reaction to SSRI medications, sleep problems, absence of allergies, and low libido.

abstract brain in pink

This is why understanding methylation status is an important component when considering the etiology of depression. A defect in an important gene (the MTHFR gene) can make methylation difficult for many individuals, contributing to a depressed mood. Another common denominator appears to be histamine. In fact, a recent study proposes that histamine might be a missing component when considering depression on a biochemical level [2]. High levels of histamine in the body (as well as low levels) may lead to symptoms of depression.

Through personalized guidance, methylation can be optimized and histamine levels can be brought back into balance. Could methylation or histamine be the reason for putting a damper on your mood? Book an appointment today!

At IVY Integrative, you can work with one practitioner or build your own team of holistic practitioners! Reach your optimum health in-person or online. Check out our Get Started page to learn how to work with us!


  1. Moore LD, Le T, Fan G. DNA methylation and its basic function. Neuropsychopharmacology. 2013 Jan;38(1):23-38. doi: 10.1038/npp.2012.112. Epub 2012 Jul 11. PMID: 22781841; PMCID: PMC3521964.

  2. Hersey M, Hashemi P, Reagan LP. Integrating the monoamine and cytokine hypotheses of depression: Is histamine the missing link? Eur J Neurosci. 2022 May;55(9-10):2895-2911. doi: 10.1111/ejn.15392. Epub 2021 Aug 2. PMID: 34265868.


This information is generalized and intended for educational purposes only. Due to potential individual contraindications, please see your primary care provider before implementing any strategies in these posts.



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