How Genetic Variation May Impact Antidepressant Efficacy in Eating Disorder Treatment

DNA Strand of Genetic Variation Impact on Eating Disorder Treatment

Understanding the role of dietary deficiencies and genetic variation impact on the efficacy of medication can be an effective tool when treatment planning with patients and families.

Incorporating information about individualized genetics as part of a larger conversation about medication trials or compliance may be useful for some patients and their treatment allies, including in confronting treatment resistance and limiting time spent pursuing treatment strategies with poor or limited evidence for success.

Also, patients’ belief of themselves as having “treatment-resistant depression” or being “non-responders” to medications may be compassionately challenged if they understand, biologically, why previous trials were not expected to be successful, and that future trials could be.

In concert with nutritional and psychotherapies, many eating disorders patients referred to an inpatient level of care utilize antidepressant medications in an effort to alleviate symptoms.

The majority of antidepressant medications rely on monoamine presence in the brain, either serotonin, as in “selective serotonin reuptake inhibitors” (SSRIs), or serotonin and norepinephrine, as in “serotonin-norepinephrine reuptake inhibitors” (SNRIs), or similar mechanisms.

Norepinephrine action also indicates dopamine reuptake in the prefrontal cortex of the brain, which is the third monoamine action, though not often mentioned in the medication titles. With the best intentions, families and sufferers may seek relief of depression, anxiety and OCD symptoms with these otherwise recommended and effective medications.

Without exception, however, every antidepressant medication trial in malnourished eating disorder patient populations shows these medications are no more effective than placebos. Below are factors that contribute to this phenomenon.

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From here forward, monoamines will refer to serotonin, norepinephrine, and dopamine unless stated individually. Proteins from nutritional intake are processed in the human body through a series of mechanisms that lead to the production of monoamines.

This is a complex process, with many contributing factors, such as folic acid, tryptophan or tyrosine, gonadal steroid levels, and individualized genetic considerations.

It is well established that common eating disorder behaviors, including food restriction, purging, and excessive exercise, impact nutrient availability in the body. Sustained starvation or significant purging would limit both proteins and vitamins, and excessive exercise would drive the body to use those resources for other purposes.

These nutritional deficits lead to a diminished capacity to produce monoamines. For example, excluding proteins rich in tyrosine and tryptophan would limit the basic building blocks for monoamine production.

Folate, which is the naturally occurring form of folic acid found in leafy vegetables, legumes, and fruits, is also an integral part of monoamine synthesis. Cereals and breads are often fortified with synthetic folate (folic acid).

Folate is metabolized by the body into L-methylfolate, which is one of several critical components of neurotransmitter production. If L-methylfolate is deficient, monoamine synthesis is reduced.

Folic Acid & Genetic Variation Impact

Being human involves myriad and mysterious quirks, among them, the genetic variation impact occurrences, termed polymorphisms, in the general population. There are several widespread polymorphisms which can impact an individual’s ability to metabolize folate or folic acid into L-methylfolate naturally.

One particular polymorphism, at MTHFR (methylenetetrahydrofolate reductase), is becoming increasingly well known, accessible for testing and extremely relevant to this discussion.

Man doing eating disorder researchApproximately sixty percent of the general population has at least one polymorphism at this site reducing the synthesis of L-methylfolate, and thirty percent has both polymorphisms at the foci, significantly impacting L-methylfolate synthesis.

Therefore, eating disorders suffers from the MTHFR gene polymorphism can compound their genetic L-methylfolate deficit (and therefore their monoamine deficit) significantly through nutritional restriction.


Clinicians, sufferers and treatment allies may consider whether testing for the common polymorphism is worthwhile and worth the potential expense. L-methylfolate augmentation in sufferers with known MTHFR polymorphyisms may significantly improve medication efficacy in those with a history of “failed” medication trials or family history of poor response to medications if genetic factors limited response.

However, in eating disorder patients, even with recognition and appropriate treatment of the genetic variation impact considerations, it remains clear that nutritional restoration remains the gold standard for optimal response to medications to be possible.


1. Corrina P. Ferguson, et al; Are Serotonin Selective Reuptake Inhibitors Effective in Underweight Anorexia Nervosa; Int J Eat Disord 25: 11-17, 1999.
2. Tanaka, T et al; Genome-wide Association Study of Vitamin B6, Vitamin B12, Folate and Homocysteine Blood Concentrations; The American Journal of Human Genetics 84, 477-482, April 10, 2009; Fava M, et al Folate in Depression: Efficacy, Safety and Differences in Formulations, and Clinical Issues, Journal of Clinical Psychiatry 2009; 70 (suppl 5):12-17; Stahl, S.M., Stahl’s Essential Psychopharmacology; neuroscientific basis and practical application, 4th edition; 2013, p. 347 – 348
3. Stahl, S.M., Stahl’s Essential Psychopharmacology; neuroscientific basis and practical application, 4th edition; 2013, p. 347 – 349

About the Sponsor:

The Laureate Eating Disorders Program offers a full continuum of care for eating disorder recovery, including acute hospitalization, partial hospitalization, residential care, transitional living and outpatient services. A multidisciplinary team of psychiatrists, therapist, dietitians and nurses collaborate daily to meet the individual needs of each patient in a safe, supportive environment.

The combination of our care, our facility and our highly experienced staff creates a program that provides results. By limiting care to 18 adult women and 12 adolescent girls the Laureate Eating Disorders Program maintains a more intimate environment to ensure individualized, patient-centered care. Laureate Psychiatric Clinic & Hospital is a not-for-profit facility and is fully accredited by The Joint Commission as a hospital and behavioral health program. Separate tracks for adult and adolescent patients allows for developmentally-specific treatment.

Call Laureate Eating Disorders Program today to learn more: 866-347-8555

About the Author:

Katherine GodwinKatherine Godwin, M.D., has served as medical director and attending physician of the Laureate adult eating disorders program since 2010. She joined the program as medical director of outpatient services in 2008 and was the medical director of Laureate’s independent living program for outpatient eating disorder care, Magnolia House, from 2007-2010. She has practiced at Laureate since 2005.

Dr. Godwin is board certified by the American Board of Psychiatry and Neurology She received her medical degree from Creighton University in Omaha, Nebraska, and completed her residency in psychiatry at the University of California, San Diego where she served as chief resident.

Katherine Godwin, M.D., shares her expertise locally and nationally about psychopharmacologic considerations with eating disorders. Dr. Godwin is an advocate for patients and their families. She encourages her patients to participate actively in treatment and to work together with their care team for optimal symptom management.

The opinions and views of our guest contributors are shared to provide a broad perspective of eating disorders. These are not necessarily the views of Eating Disorder Hope, but an effort to offer a discussion of various issues by different concerned individuals.

We at Eating Disorder Hope understand that eating disorders result from a combination of environmental and genetic factors. If you or a loved one are suffering from an eating disorder, please know that there is hope for you, and seek immediate professional help.

Published on February 21, 2019.
Reviewed & Approved on February 21, 2019, by Jacquelyn Ekern MS, LPC

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About Baxter Ekern

Baxter is the Vice President of Ekern Enterprises, Inc. He is responsible for the operations of Eating Disorder Hope and ensuring that the website is functioning smoothly.