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Home > Featured in Experts > Nutrition for Anxiety and Depression: The Role of Genes and Lifestyle (Part 10)

April 24, 2025 By Staci Shacter

Nutrition for Anxiety and Depression: The Role of Genes and Lifestyle (Part 10)

Nutrition and Anxiety Depression - Role of Genes
Nutrition for Anxiety and Depression Series
  • Pt1- Combating Inflammation and Oxidative Stress
  • Pt2- Common Food Sensitivities
  • Pt3- Beyond Histamine and Common Allergies
  • Pt4- Addressing Common Deficiencies
  • Pt5- Tools for Preventing Deficiencies
  • Pt6- Supplements for Deficiencies
  • Pt7- The Gut-Brain Connection
  • Pt8 – Gut Inflammation, Leaky Gut, and Stress.
  • Pt9 – Blood Sugar’s Role
  • Pt10 – Genes & Lifestyle

It used to be that we thought we were bound by our genetics. “My father had it, his father had it — so I’m going to get it anyway. Might as well enjoy life and do whatever I want,” was the mindset. However, advances in genetic research have painted a much more empowering picture.

Turns out, genetics might load the gun, but diet and lifestyle pull the trigger.

Emerging evidence suggests that approximately 90 percent of the factors contributing to most diseases are tied to diet and lifestyle, and less than 10 percent are purely genetic. This is a massive shift in perspective, giving us practical control over our well-being and mental resilience.

Instead of feeling like a prisoner of our DNA, we now understand that our daily choices — what we eat, how we move, how we manage stress — play a critical role in how our genes express themselves. Our genes set the stage, but it’s our lifestyle habits that determine the outcome.

Nutrigenomics: Your Genes and Nutrient Deficiencies

The field of nutrigenomics explores how your genes influence nutrient absorption, metabolism, and overall health — and how your diet and lifestyle can, in turn, influence gene expression. Depending on your specific genetic variants, you may be more prone to certain nutrient deficiencies or imbalances (44), which can impact brain function, mood, and mental health.

Research has identified numerous genes connected to mental health conditions like depression, anxiety, bipolar disorder, schizophrenia, PTSD, ADHD, and autism (29). For individuals with certain predispositions, adopting a nutrient-dense diet rich in vitamins, minerals, and phytonutrients becomes even more essential as a tool to improve mental health outcomes.

Unfortunately, today’s modern diets — heavy in processed foods, refined sugars, and low in micronutrients — often fail to provide the nutritional foundation necessary to compensate for these genetic vulnerabilities. Over time, this imbalance can contribute to nutrient deficiencies that exacerbate mental health struggles.

The good news is, most of us have experienced firsthand how eating well helps us feel better, sharper, and more emotionally balanced. You don’t need a genetic test to know that real, whole foods matter. But it’s fascinating to see how genetic science, which once seemed like a predetermined script, consistently points us back to lifestyle as the key to rewriting the story.

Many genes have been identified as influencing mental health. However, not all of them have been extensively studied in relation to nutritional or lifestyle interventions that can support their optimal function. Below are some genes for which research suggests that lifestyle factors may positively influence their activity, potentially offsetting the effects of less-than-optimal gene variants. It’s important to remember that we all possess these genes, but the specific version you carry can affect how efficiently the gene performs its role. Specialized genetic or nutrigenomic testing can help determine whether you carry versions of these genes where you might benefit from targeted dietary and lifestyle adjustments.

Gene Function
Interventions/Improvements
MAOA Breaks down monoamine neurotransmitters; linked to mood regulation and cognitive abilities. It is possible to have over activation of MAOA or under activation of MAOA impacting neurological symptoms. For this reason the focus is on lifestyle interventions (instead of supplements) that have been shown to have positive overall health impacts.
Inhibition by natural metabolites from fruits and vegetables (25); Piperine (from Piper longum) shows antidepressant-like effects (26); lifestyle factors such as daily sunlight/Vitamin D (13-18), stress management (23-24), exercise (19-20), turmeric (7-9), and diets rich in flavonoids (1-6); cold exposure (10-12), quitting smoking (21-22), and possibly a low histamine diet (if MAOA levels are low).
SLC6A4 Encodes the serotonin transporter; critical for serotonin reuptake and implicated in major depressive disorder.
Tryptophan supplementation—efficacy varies based on individual SLC6A4 genotype (30).
COMT Produces an enzyme that clears neurotransmitters (dopamine, epinephrine, norepinephrine) and participates in the methylation process.
Due to the role of COMT in liver detoxification pathways (29), supplementation with SAMe (a methyl donor) (31), magnesium, and B vitamins (B2, B6, B9, B12) (32); consumption of foods that help clear excess estrogen (flaxseeds, cruciferous vegetables (33), bitter herbs); stress reduction techniques (34) may be beneficial.
FKBP5 Expressed in the brain and gastrointestinal tract; associated with major depressive disorders.
Treatment with quercetin has been shown to significantly increase FKBP5 expression (29).
BDNF Brain-derived neurotrophic factor; essential for neuroplasticity, brain function, and resilience.
Dietary leucine supplementation, high protein diet, and exercise increased BDNF in mice (28), nutritional interventions with polyphenols (27) have a positive impact on BDNF concentrations.
MTHFR Methylenetetrahydrofolate reductase; a key enzyme in folate metabolism, converting folate to its active form (5-MTHF) and crucial for proper methylation and homocysteine regulation.
Supplementation with folic acid (the primary methyl donor), vitamins B12, B6, and riboflavin; consumption of folate-rich foods; use of betaine and choline/creatine to spare methylation (since much methylation is used to produce phosphatidylcholine and creatine) (35-43). Glycine buffers methyl groups in the fasted state and harvests them for use when needed so it has been theorized that supplementation of glycine might also be helpful.

How Can You Apply This Knowledge?

At the end of the day, there are two powerful ways to leverage this information:

  1. Use this information as motivation to prioritize a nutrient-dense diet and healthy lifestyle.
    Focus on incorporating plenty of fruits, vegetables, and whole foods into your daily routine, and consider adding a high-quality multivitamin. Throughout this series, we’ve emphasized how crucial a balanced diet is for mental health. Now, you can clearly see one of the key reasons why: it helps you overcome potential obstacles linked to your unique genetic makeup.
  2. Consider getting your own genetic testing.
    If you’re looking to take a more personalized approach to your health, nutrigenomic testing is a tool worth considering. Many reputable companies now offer comprehensive genetic tests that analyze key genes related to nutrient metabolism, mental health, detoxification, and more. These tests don’t just reveal your genetic predispositions — they typically come with tailored nutrition, supplement, and lifestyle recommendations based on your results. Understanding how your unique genetic profile affects factors like vitamin absorption, neurotransmitter activity, or inflammation levels can empower you to make more informed, targeted decisions.

The Bottom Line

Regardless of whether you opt for testing, the takeaway remains the same: a nutrient-dense, whole-foods-based diet, alongside healthy lifestyle habits, is the key to supporting your genes and optimizing your mental health.

The science of genetics doesn’t confine us — it empowers us to make more informed choices, proving once again that what you eat and how you live matters far more than you may have ever realized.

And stay tuned — the next and final article in this series will focus entirely on histamine and mental health. There is so much to explore regarding how genetics, dietary strategies, and specific supplements can influence histamine levels and mental well-being, particularly for certain individuals who may be more affected by histamine imbalances. While it might not be relevant for everyone dealing with mental health challenges, for some, it can be a key piece of the puzzle—making it important enough to warrant an entire article of its own.

REFERENCES

MAOA research

Diet with foods high in flavonoids and MAOA

  1. Chimenti, Franco et al. “Quercetin as the active principle of Hypericum hircinum exerts a selective inhibitory activity against MAO-A: extraction, biological analysis, and computational study.”Journal of natural products  69,6 (2006): 945-9. doi:10.1021/np060015w
  2. Zhang, Zhenxian et al. “Selectivity of Dietary Phenolics for Inhibition of Human Monoamine Oxidases A and B.”BioMed research international  2019 8361858. 23 Jan. 2019, doi:10.1155/2019/8361858
  3. Han, Xiang Hua et al. “Monoamine oxidase inhibitory components from Cayratia japonica.”Archives of pharmacal research  30,1 (2007): 13-7. doi:10.1007/BF02977772
  4. Bandaruk, Yauhen et al. “Evaluation of the inhibitory effects of quercetin-related flavonoids and tea catechins on the monoamine oxidase-A reaction in mouse brain mitochondria.”Journal of agricultural and food chemistry  60,41 (2012): 10270-7. doi:10.1021/jf303055b
  5. Zhao, Xin et al. “Fisetin exerts antihyperalgesic effect in a mouse model of neuropathic pain: engagement of spinal serotonergic system.”Scientific reports  5 9043. 12 Mar. 2015, doi:10.1038/srep09043
  6. Larit, Farida et al. “Inhibition of human monoamine oxidase A and B by flavonoids isolated from two Algerian medicinal plants.”Phytomedicine : international journal of phytotherapy and phytopharmacology  40 (2018): 27-36. doi:10.1016/j.phymed.2017.12.032

Turmeric and MAOA

  1. Silva de Sá, Igor et al. “In vitro and in vivo evaluation of enzymatic and antioxidant activity, cytotoxicity and genotoxicity of curcumin-loaded solid dispersions.”Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association  125 (2019): 29-37. doi:10.1016/j.fct.2018.12.037
  2. Nath, Chandrani et al. “Curcumin-based pyrazoline analogues as selective inhibitors of human monoamine oxidase A.”MedChemComm  9,7 1164-1171. 8 Jun. 2018, doi:10.1039/c8md00196k
  3. Khatri, Dharmendra Kumar, and Archana Ramesh Juvekar. “Kinetics of Inhibition of Monoamine Oxidase Using Curcumin and Ellagic Acid.”Pharmacognosy magazine 12,Suppl 2 (2016): S116-20. doi:10.4103/0973-1296.182168

Cold Exposure and MAOA

  1. Gorshinskaia, I A et al. “Aktivnost’ monoaminoksidaz mozga pri kholodovoĭ adaptatsii i sovmestnom deĭstvii kholoda i giperbarooksigenatsii” [Monoamine oxidase activity in the brain during adaptation to cold and simultaneous exposure to cold and hyperbaric oxygenation].Fiziologicheskii zhurnal SSSR imeni I. M. Sechenova  67,11 (1981): 1611-6.
  2. Molodtsova, G F. “Vliianie dlitel’nogo vozdeĭstviia kholoda na aktivnost’ i kinetiku monoaminoksidazy i obmen serotonina v mozge krys” [Effect of prolonged cold exposure on monoamine oxidase activity and kinetics and on serotonin metabolism in the rat brain].Biulleten’ eksperimental’noi biologii i meditsiny 96,9 (1983): 16-8.

Cold increased serotonin and dopamine in the brain

  1. Ishiwata, Takayuki, and Benjamin N Greenwood. “Changes in thermoregulation and monoamine release in freely moving rats during cold exposure and inhibition of the ventromedial, dorsomedial, or posterior hypothalamus.”Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology  188,3 (2018): 541-551. doi:10.1007/s00360-017-1130-5

Sunlight exposure and increased serotonin and melatonin, dopamine

  1. Gambichler, Thilo et al. “Impact of UVA exposure on psychological parameters and circulating serotonin and melatonin.”BMC dermatology  2 6. 12 Apr. 2002, doi:10.1186/1471-5945-2-6
  2. Dong, C J, and J S McReynolds. “The relationship between light, dopamine release and horizontal cell coupling in the mudpuppy retina.”The Journal of physiology  440 (1991): 291-309. doi:10.1113/jphysiol.1991.sp018709
  3. Cawley, Elizabeth I et al. “Dopamine and light: dissecting effects on mood and motivational states in women with subsyndromal seasonal affective disorder.”Journal of psychiatry & neuroscience : JPN  38,6 (2013): 388-97. doi:10.1503/jpn.120181

Vitamin D and MAOA activity

  1. Sabir, Marya S et al. “Optimal vitamin D spurs serotonin: 1,25-dihydroxyvitamin D represses serotonin reuptake transport (SERT) and degradation (MAO-A) gene expression in cultured rat serotonergic neuronal cell lines.”Genes & nutrition 13 19. 11 Jul. 2018, doi:10.1186/s12263-018-0605-7
  2. Pertile, Renata A N et al. “Vitamin D signaling and the differentiation of developing dopamine systems.”Neuroscience 333 (2016): 193-203. doi:10.1016/j.neuroscience.2016.07.020
  3. Sturza, Adrian et al. “Vitamin D improves vascular function and decreases monoamine oxidase A expression in experimental diabetes.”Molecular and cellular biochemistry 453,1-2 (2019): 33-40. doi:10.1007/s11010-018-3429-2

Exercise and MAOA activity

  1. Hattori, S et al. “Striatal dopamine turnover during treadmill running in the rat: relation to the speed of running.”Brain research bulletin  35,1 (1994): 41-9. doi:10.1016/0361-9230(94)90214-3
  2. Morishima, Masaki et al. “Monoamine oxidase A activity and norepinephrine level in hippocampus determine hyperwheel running in SPORTS rats.”Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 31,12 (2006): 2627-38. doi:10.1038/sj.npp.1301028

Smoking and MAOA

  1. Hogg, Ron C. “Contribution of Monoamine Oxidase Inhibition to Tobacco Dependence: A Review of the Evidence.”Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco  18,5 (2016): 509-23. doi:10.1093/ntr/ntv245
  2. Smith, Tracy T et al. “Effects of Monoamine Oxidase Inhibition on the Reinforcing Properties of Low-Dose Nicotine.”Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology  41,9 (2016): 2335-43. doi:10.1038/npp.2016.36

Stress Management and MAOA activity

  1. Soliman, Alexandra et al. “Convergent effects of acute stress and glucocorticoid exposure upon MAO-A in humans.”The Journal of neuroscience : the official journal of the Society for Neuroscience 32,48 (2012): 17120-7. doi:10.1523/JNEUROSCI.2091-12.2012
  2. Tseilikman, Vadim et al. “Role of glucocorticoid- and monoamine-metabolizing enzymes in stress-related psychopathological processes.”Stress (Amsterdam, Netherlands) 23,1 (2020): 1-12. doi:10.1080/10253890.2019.1641080

Fruit and Vegetable intake and MAOA

  1. Marzo CM, Gambini S, Poletti S, Munari F, Assfalg M, Guzzo F. Inhibition of human monoamine oxidases A and B by specialized metabolites present in fresh common fruits and vegetables. Plants. 2022;11:346. doi: 10.3390/plants11030346.

Piperine and MAOA

  1. Lee SA, Hong SS, Han XH, Hwang JS, Oh GJ, Lee KS, et al. Piperine from the fruits of Piper longum with inhibitory effect on monoamine oxidase and antidepressant-like activity. Chem Pharm Bull. 2005;53:832–835. doi: 10.1248/cpb.53.832.

BDNF research

A systemic review: polyphenols significantly positively impacted BDNF levels.

  1. Gravesteijn, Elske et al. “Effects of nutritional interventions on BDNF concentrations in humans: a systematic review.”Nutritional neuroscience  25,7 (2022): 1425-1436. doi:10.1080/1028415X.2020.1865758
  2. Zeeni N, Haidar EA, Azar A, Ghanem A, Bassil K, Bassil M, et al. The combinatory effects of diet and exercise on BDNF gene expression. FASEB J. 2017;31:150. doi: 10.1096/fasebj.31.1_supplement.150.8.

Quercetin and FKBP5

  1. Birla M, Choudhary C, Singh G, Gupta S, Bhawana, Vavilala P. The Advent of Nutrigenomics: A Narrative Review with an Emphasis on Psychological Disorders. Prev Nutr Food Sci. 2022 Jun 30;27(2):150-164. doi: 10.3746/pnf.2022.27.2.150. PMID: 35919568; PMCID: PMC9309077.

Tryptophan and SLC6A4

  1. Ugartemendia, Lierni et al. “SLC6A4 polymorphisms modulate the efficacy of a tryptophan-enriched diet on age-related depression and social cognition.”Clinical nutrition (Edinburgh, Scotland)  40,4 (2021): 1487-1494. doi:10.1016/j.clnu.2021.02.023

COMT

SAMe and COMT

  1. Sharma, Anup et al. “S-Adenosylmethionine (SAMe) for Neuropsychiatric Disorders: A Clinician-Oriented Review of Research.” The Journal of clinical psychiatry 78,6 (2017): e656-e667. doi:10.4088/JCP.16r11113

B vitamins secondary to impact on Homocysteine of COMT

  1. Gellekink, Henkjan et al. “Catechol-O-methyltransferase genotype is associated with plasma total homocysteine levels and may increase venous thrombosis risk.” Thrombosis and haemostasis 98,6 (2007): 1226-31.

Cruciferous vegetables impact on COMT

  1. Wu, Qian et al. “Estrogen down regulates COMT transcription via promoter DNA methylation in human breast cancer cells.” Toxicology and applied pharmacology 367 (2019): 12-22. doi:10.1016/j.taap.2019.01.016

Stress and COMT

  1. Armbruster D, Mueller A, Strobel A, Lesch KP, Brocke B, Kirschbaum C. Children under stress – COMT genotype and stressful life events predict cortisol increase in an acute social stress paradigm. Int J Neuropsychopharmacol. 2012 Oct;15(9):1229-39. doi: 10.1017/S1461145711001763. Epub 2011 Dec 12. PMID: 22152146.

MTHFR

  1. Chmurzynska, A., et al. Associations between folate and choline intake, homocysteine metabolism, and genetic polymorphism of MTHFR, BHMT and PEMT in healthy pregnant Polish women. Nutrition & Dietetics. 2019. https://onlinelibrary.wiley.com/doi/abs/10.1111/1747-0080.12549
  2. Chew, T., et al. Folate Intake, Mthfr Genotype, and Sex Modulate Choline Metabolism in Mice. 2011. The Journal of Nutrition. 141(8): 1475-1481. https://academic.oup.com/jn/article/141/8/1475/4630515
  3. Shin, W., et al. Choline Intake Exceeding Current Dietary Recommendations Preserves Markers of Cellular Methylation in a Genetic Subgroup of Folate-Compromised Men. J Nutr. 2010 May; 140(5): 975–980. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2855263/
  4. Garcia-Martin, E., et al., Histamine pharmacogenomics. Pharmacogenomics, 2009. 10(5): 867-83. https://www.ncbi.nlm.nih.gov/pubmed/19450133
  5. Gervasini, G., et al., Variability of the L-Histidine decarboxylase gene in allergic rhinitis. 2010. Allergy. 65(12): p. 1576-84. https://www.ncbi.nlm.nih.gov/pubmed/20608921
  6. Allen PJ. Creatine metabolism and psychiatric disorders: Does creatine supplementation have therapeutic value?. Neurosci Biobehav Rev. 2012;36(5):1442-1462. doi:10.1016/j.neubiorev.2012.03.005
  7. Stead LM, Brosnan JT, Brosnan ME, Vance DE, Jacobs RL. Is it time to reevaluate methyl balance in humans?. Am J Clin Nutr. 2006;83(1):5-10. doi:10.1093/ajcn/83.1.5
  8. Hustad S, Schneede J, Ueland PM. Riboflavin and Methylenetetrahydrofolate Reductase. In: Madame Curie Bioscience Database [Internet]. Austin (TX): Landes Bioscience; 2000-2013. Available from: https://www.ncbi.nlm.nih.gov/books/NBK6145/#
  9. Ganz AB, Shields K, Fomin VG, et al. Genetic impairments in folate enzymes increase dependence on dietary choline for phosphatidylcholine production at the expense of betaine synthesis. FASEB J. 2016;30(10):3321-3333. doi:10.1096/fj.201500138RR

Nutrigenomics and Nutrient Deficiencies

  1. Micheletti C, Madeo G, Macchia A, Donato K, Cristoni S, Ceccarini MR, Beccari T, Iaconelli A, Aquilanti B, Matera G, Herbst KL, Bertelli M. Nutrigenomics: SNPs correlated to vitamins’ deficiencies. Clin Ter. 2023 Nov-Dec;174(Suppl 2(6)):173-182. doi: 10.7417/CT.2023.2485. PMID: 37994762.
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Filed Under: Featured in Experts, Experience Blog, Expert Columns

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About Staci Shacter

Staci Shacter, MS, RD, LDN, is a registered dietitian, specializing in integrative nutrition and lifestyle strategies to support mental health, recovery, and digestive health, and has worked with FHE Health since 2018. A highly regarded expert in her field, Staci also serves as a columnist for FHE Health, offering practical, evidence-based insights on a wide range of topics related to diet, lifestyle, and mental well-being. Passionate about education, she loves empowering both the public and healthcare professionals with science-backed approaches to optimize immune function, digestive health, and mental wellness. She also provides continuing education to pharmacists through Nova Southeastern University, helping them integrate functional medicine nutrition principles in their clinical practice for more holistic patient care.

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