1. Depression and MTHFR
Polymorphism
Joey Gilkey
Presbyterian College

2. Outline
I. Depression
II. Theories and modern research
III. Treatment

3. Depression
I. Estimated 25 percent of American’s will have
a depressive episode at one point in life
(Roman & Bembry, 2011).
II. Ancient Greece- “Melancholia”
III. Early Christianity- result of struggle with sin
(Lawlord, 2012)

4. Modern Theories of Depression
I. Neurotropic hypothesis
II. Autoreceptor Subsenstivity Theory
III. Circadian Rhythm Theory
IV. Monoamine Hypothesis

5. Monoamine Hypothesis
I. What is the Monoamine Hypothesis?
– Most widely supported and accepted theory for
pathology of depression.
– Depletion of monoamine neurotransmitters:
Serotonin, Norepinephrine, and/or Dopamine.
- Mood regulating
- BDNF
– Neural Degeneration in hippocampus and the
prefrontal cortex

6. Figure 1. BDNF Production (Ettinger, 2011).

7. Treatment for Depression
• 20,000 prescriptions per
month
• Tricyclic Antidepressants
• Selective Serotonin
Reuptake Inhibitor (SSRI)
• Serotonin-Norepinephrine
Reuptake Inhibitors (SNRI)
• MAOI’s
• 2/3 of patients treated with
Antidepressants will not
achieve full remission
(Lebano, 2013). Figure 2. SSRI treatment (Priest, 2012).

8. MTHFR
• What is MTHFR?
- Methylenetetrahydrofolate Reductase
- Enzyme that Metabolizes Folate (vitamin
B9) into l-methylfolate.
• Why is MTHFR necessary?
- Blood-Brain Barrier
- Mood regulating neurotransmitter
Production

9. Neurotransmitter Production
Folate/ Folic Acid (inactive) Neurotransmitters
(Reactions)
MTHFR (metabolizes) SAM-e
L-methylfolate (active) Blood-Brain Barrier Methionine
Re-methylation Homocysteine
(Metabolized)

10. MTHFR Polymorphism
• Located on the first chromosome
• 30% of Americans have one mutation and 4-12% have
two
• What is a genetic mutation?
Figure 3. Chromosome Location (Tabke, 2011).

11. Neurotransmitter Production
Folate/ Folic Acid (inactive) Neurotransmitters
(Reactions)
MTHFR (metabolizes) SAM-e
L-methylfolate (active) Blood-Brain Barrier Methionine
Re-methylation Homocysteine
(Metabolized)

12. Effectiveness of Antidepressants
• Prolong existence of neurotransmitters in the
synapse.
• Inhibit enzymatic breakdown
• Ineffective treatment for mutation

13. Deplin
• Generic name:
L-methylfolate
• Medical Food
• 7 mg/ 15 mg tablets
• Not FDA approved Figure 4. Deplin Logo. (“Pamlab,” 2011).

14. Side Effects
• irritability
• insomnia
• sore muscles
• achy joints
• acne
• rash
• severe anxiety
• palpitations
• nausea
• headaches
• Migraines
(Lynch, 2012)

15. Neurotransmitter Production
Folate/ Folic Acid (inactive) Neurotransmitters
(Reactions)
MTHFR (metabolizes) SAM-e
L-methylfolate (active) Blood-Brain Barrier Methionine
Re-methylation Homocysteine
(Metabolized)
Deplin

16. Deplin and Antidepressants
• Deplin Augmented with Antidepressants
found most effective
• 54% of depression participants with MTHFR
polymorphism achieved full remission within
12 months (“Deplin Medical Food,” 2012).
• More Neurotransmitters available along with
inhibited reuptake or breakdown

17. References
• Beck, M. (2012). Giving antidepressants a boost with a vitamin. Wall Street Journal.
Retrieved from http://online.wsj.com/news/articles/SB100014240529702043681
04577136850522166664?mg=reno64-
wsj&url=http%3A%2F%2Fonline.wsj.com%2Farticle%2FSB10001424052970204368
104577136850522166664.html
• Deplin Medical Food Provides Long-Term Benefit for Major Depressive Disorder.
(2012). Monthly Prescribing Reference. Retrieved from
http://www.empr.com/deplin-medical-food-provides-long-term-benefit-for-major-
depressive-disorder/article/240194/
• Elsayed, G. M., Elsayed, S. M., & Ezz-Elarab, S. S. (2014). Maternal MTHFR C677T
genotype and septal defects in offspring with Down syndrome: A pilot study.
Egyptian Journal Of Medical Human Genetics, 15(1), 39-44.
doi:10.1016/j.ejmhg.2013.09.003
• Ettinger, R. H. (2011). Psychopharmacology. New Jersey: Prentice Hall.
• Lawlord, Clark. (2012). From Melancholy to Prozac: A History of Depression. The
Economist. Retrieved from http://www.economist.com/node/21555885
• Lebano, L. (2014). L-Methylfolate: A Promising Therapy for Treatment-Resistant
Depression. PsychCongress Network. Retrieved from
http://www.psychcongress.com/article/l-methylfolate-promising-therapy-
treatment-resistant-depression-11329
• Lynch. (2012). Methylfolate Side Effects. Retrieved from
http://mthfr.net/methylfolate-side-effects/2012/03/01/

18. References
• Lynch. (2012). Methylfolate Side Effects. Retrieved from
http://mthfr.net/methylfolate-side-effects/2012/03/01/
• Miller, A. L. (2008). The methylation, neurotransmitter, and antioxidant
connections between folate and depression. Alternative Medicine Review, 13(3),
216-217. Retrieved from http://www.altmedrev.com/publications/13/3/216.pdf
• NHI. (2011). Genetic Home Reference. Retrieved from
http://ghr.nlm.nih.gov/gene/MTHFR
• “Pamlab, LLC, and Deplin.” (2011). Pamlab, LLc, and Deplin. Retrieved from
http://www.yourhealingretreat.com/june-2011-retreat/sponsors/deplin
• Priest, Alan. (2013). Medication for Depression. Retrieved from
http://www.alanpriest.f2s.com/Depression%20Medication%20p5.htm
• Roman, M. W., & Bembry, F. H. (2011). L-Methylfolate (Deplin®): A New Medical
Food Therapy as Adjunctive Treatment for Depression. Issues In Mental Health
Nursing, 32(2), 142-143. doi:10.3109/01612840.2010.541975
• Tabke, Erica. (2011). Do You Have an MTHFR mutation? Retrieved from
http://www.ivfconnections.com/forums/content.php/859-Do-You-Have-a-MTHFR-
Mutation-Come-Join-Us
• Tarbet, M., York, J., & Liday, C. (2008). L-Methylfolate (Deplin®): A medical food for
depression. Evidence Based Practice, 11(7), 09-10. Retrieved from
http://hdl.handle.net/10355/7342
• Tolmunen, T., Voutilainen, S., Hintikka, J., Rissanen, T., Tanskanen, A., Wiinamakl,
H., Kaplan, G. A., & Salonen, J. T. (2003). Dietary folate and depressive symproms
are associated in middle-aged Finnish men. The Journal of Nutrition,133. Retrieved
from http://jn.nutrition.org/content/133/10/3233.full

19. Questions???