Depression and Anxiety: More than Neurotransmitter Deficiencies


How common are depression and anxiety?

We are amidst a public health crisis from an unprecedented decline in mental health.1   Since 2020, worldwide rates of depression and anxiety have doubled in children and adolescents, while adult rates have increased three times.1,2,3 With these increasing rates, it is crucial to identify people at risk and have safe and effective tools available to support their well-being.

What kinds of symptoms do you see with depression and anxiety?

Symptoms of depression in adults are persistent sad mood with feelings of hopelessness, frustration, cognitive issues such as lack of concentration, irritability, poor sleep, and changes in eating patterns.4  People can present with more irritability, agitation, and poor stress tolerance. Psychosomatic complaints such as fatigue, headaches, pain, and digestive issues are common.4 Severe depression and anxiety carry the risk of suicidal thoughts and actions.4 Anxiety often coexists with depression and is persistent or intermittent worry about various issues.

Symptoms of depression in children overlap with adult symptoms but also have unique features. Children tend to have more behavioral issues, such as temper tantrums and irritability, than purely feelings of sadness.5 Problems with school and concentration are common, so children can be labeled with ADHD when depression is the underlying cause. Psychosomatic complaints such as stomach pains and headaches are very common.6  Anxiety issues in children and adolescents commonly overlap with depression and can be part of their behavior issues.

What are the different causes that can lead to depression and anxiety?

Causes of depression are often an interweaving of environmental, social, physical health, and genetic issues. For any age, social support and connections play an integral role in mental and physical health.7  Social isolation is a significant risk factor for depression and anxiety.7 A person’s physical health, in terms of weight management, exercise, sleep, and diet can influence the risk of depression and anxiety.

Decreased physical activity is associated with increased rates of depression.8  Common nutrient deficiencies such as vitamin B6, magnesium, zinc, and omega-3 fatty acids have been associated with depression.9,10,11

Genetics plays a role in depression and anxiety. If one parent or sibling has depression, the incidence of depression will be higher in other family members.12,13,14    Specific single nucleotide polymorphisms (SNP’s) such as methyl tetrahydrofolate reductase (MTHFR) and catechol-o-methyltransferase (COMT) have been associated with increased emotional sensitivity and mental health disorders.15,16    The brain-derived neurotrophic factor (BDNF) gene, which is involved in the neuroplasticity supportive growth factor BDNF levels, can be associated with increased mental health disorders with certain SNP’s.17

Are there any diagnostic tests for depression and anxiety?

Traditional medicine does not have any laboratory tests for diagnosing mental health disorders. It relies on clinical diagnosis and screening tools used by practitioners to aid in diagnosis.

Integrative/Functional medicine looks at underlying causes contributing to mental health disorders. Genetic testing of single nucleotide polymorphisms can aid in supporting different metabolic pathways. For example, identifying MTHFR genes can help practitioners support the methylation pathways with active forms of folate and vitamin B12. Nutritional testing can identify deficiencies where targeted treatment can be helpful. A urine organic acid test is a metabolic test that can determine factors contributing to mental health, including nutritional deficiencies, mitochondrial dysfunction, dysbiosis, and neurotransmitter levels.18

What are natural options for supporting a healthy mood?

Traditional treatment focuses on therapy and prescription medicines, which can be helpful for some but not all people. A natural approach focuses on supporting the underlying physiological functions. It is always important to start with a healthy whole foods organic diet and supporting nutrients. Magnesium and zinc are nutrients that are frequently low in people and can help support healthy mood and cognition.19*  Omega 3 fatty acids are one of the most helpful nutrients for supporting mood stability.20 *  Active B vitamins, including pyridoxine-5-phosphate (P5P), the active form of B6, methylfolate, and methyl B12, are essential for supporting metabolic enzymes.21*

Certain herbs can promote a calming effect and may help support stress, anxiety, depression, and sleep issues.22,23* Herbs often have a synergistic effect, which is why most herbal traditions use targeted herbal combinations. Lavender, lemon balm, and passionflower have good research supporting their ability to promote a healthy mental state.22,23* Adaptogens are particular nutrients such as phosphatidylserine, Ashwagandha, and holy basil that can help support a healthy physiological response to stress, including healthy cortisol levels.24,25,26*

The gut-brain axis

The gut microbiome is now being researched for its role in mood regulation, known as the gut-brain axis. A microbiome that is in a state of dysbiosis may negatively influence mood. Furthermore, research suggests that certain probiotic strains can improve microbial balance in the gut and positively affect mood.27* These strains are commonly referred to as “psychobiotics.” Gut microbes have been shown to influence tryptophan metabolism both directly and indirectly.28* Tryptophan is one of the critical building blocks of serotonin, an important neurotransmitter responsible for controlling mood.


As a growing concern for many patients, the practitioner must find safe and effective ways to support a healthy mental state. A healthy diet, sleep, and exercise are good foundational tools for everyone. Identifying and supporting nutritional deficiencies is vital, along with testing for other conditions that can lead to mood and cognitive issues. Certain herbs, nutrients, and probiotic strains have been shown in research to offer possible support by promoting a calming effect, supporting a healthy physiological response to stress, and supporting the gut-brain axis.*  Because of the potential negative impact stress and mood issues may have on people’s lives and the vast array of causes, it is crucial to have a wide variety of tools to support your patient’s well-being.



  1. Magson NR. Et al. Risk and Protective Factors for Prospective Changes in Adolescent Mental Health during the COVID-19 Pandemic. J Youth Adolesc. 2021 Jan;50(1):44-57.
  2. Racine N. Et al. Global Prevalence of Depressive and Anxiety Symptoms in Children and Adolescents During COVID-19: A Meta-analysis. JAMA Pediatr. 2021 Nov 1;175(11):1142-1150.
  3. Ettman CK. Et al. Prevalence of Depression Symptoms in US Adults Before and During the COVID-19 Pandemic. JAMA Netw Open. 2020 Sep 1;3(9):e2019686.
  5. Weiss B, Garber J. Developmental differences in the phenomenology of depression. Dev Psychopathol 2003;15(2):403–30.
  6. Charles J, Fazeli M. Depression in children. Aust Fam Physician. 2017 Dec;46(12):901-907. PMID: 29464226.
  7. Matthews T. Et al. Social isolation, loneliness and depression in young adulthood: a behavioural genetic analysis. Soc Psychiatry Psychiatr Epidemiol. 2016 Mar;51(3):339-48.
  8. Korczak DJ. Et al. Children’s Physical Activity and Depression: A Meta-analysis. 2017 Apr;139(4):e20162266.
  9. Mikkelsen K. Et al. The Effects of Vitamin B in Depression. Curr Med Chem. 2016;23(38):4317-4337.
  10. Noah L. Et al. Effect of magnesium and vitamin B6 supplementation on mental health and quality of life in stressed healthy adults: Post-hoc analysis of a randomized controlled trial. Stress Health. 2021 Dec;37(5):1000-1009.
  11. Sanhueza C. Et al. Diet and the risk of unipolar depression in adults: systematic review of cohort studies. J Hum Nutr Diet. 2013;26:56-70.
  12. Weissman M. Et al. Offspring of depressed parents: 20 years later. Am J Psychiatry. 2006;163(6):1001–1008.
  13. Lewis G. Et al. Investigating environmental links between parent depression and child depressive/anxiety symptoms using an assisted conception design. J Am Acad Child Adolesc Psychiatry. 2011 May;50(5):451-459.e1.
  14. Subbarao A. Et al. Common genetic and environmental influences on major depressive disorder and conduct disorder. J Abnorm Child Psychol. 2008 Apr;36(3):433-44.
  15. Wu YL, Et al. Association between MTHFR C677T polymorphism and depression: an updated meta-analysis of 26 studies.  Neuropsychopharmacol. Biol. Psychiatry. 2013;46:78–85.
  16. Antypa N. Et al. The role of COMT gene variants in depression: Bridging neuropsychological, behavioral and clinical phenotypes. Neurosci Biobehav Rev. 2013 Sep;37(8):1597-610.
  17. Lee Y. Et al. Association between the BDNF Val66Met Polymorphism and Chronicity of Depression. Psychiatry Investig. 2013 Mar;10(1):56-61.
  18. Kałużna-Czaplińska J. Noninvasive urinary organic acids test to assess biochemical and nutritional individuality in autistic children. Clin Biochem. 2011 Jun;44(8-9):686-91.
  19. Kris-Etherton PM. Et al. Nutrition and behavioral health disorders: depression and anxiety. Nutr Rev. 2021 Feb 11;79(3):247-260.
  20. Deacon G. Et al. Omega 3 polyunsaturated fatty acids and the treatment of depression. Crit Rev Food Sci Nutr. 2017 Jan 2;57(1):212-223.
  21. Mitchell ES. Et al. B vitamin polymorphisms and behavior: evidence of associations with neurodevelopment, depression, schizophrenia, bipolar disorder and cognitive decline. Neurosci Biobehav Rev. 2014 Nov;47:307-20.
  22. Ghazizadeh J. Et al. The effects of lemon balm (Melissa officinalis L.) on depression and anxiety in clinical trials: A systematic review and meta-analysis. Phytother Res. 2021 Dec;35(12):6690-6705.
  23. Yeung KS. Et al. Herbal medicine for depression and anxiety: A systematic review with assessment of potential psycho-oncologic relevance. Phytother Res. 2018 May;32(5):865-891.
  24. Lopresti AL. Et al. An investigation into the stress-relieving and pharmacological actions of an ashwagandha (Withania somnifera) extract: A randomized, double-blind, placebo-controlled study. Medicine (Baltimore). 2019;98(37):e17186.
  25. Baumeister et al. Influence of phosphatidylserine on cognitive performance and cortical activity after induced stress. Nutr Neuroscience. 2008 Jun;11(3):103-10.
  26. Bhattacharyya D. Et al. Controlled programmed trial of Ocimum sanctum leaf on generalized anxiety disorders. Nepal Med Coll J. 2008 Sep;10(3):176-9.
  27. Huang R. Et al. Effect of Probiotics on Depression: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Nutrients. 2016 Aug 6;8(8):483.
  28. Roth W, Zadeh K, Vekariya R, Ge Y, Mohamadzadeh M. Tryptophan Metabolism and Gut-Brain Homeostasis. Int J Mol Sci. 2021 Mar 15;22(6):2973.