Anxiety & the Stress Response: Traditional vs. Functional Medicine
Anxiety disorders affect 18.1% of adults in the United States (approximately 40 million adults between the ages of 18 to 54), according to the National Institute of Mental Health (NIMH).
The traditional western medical approach to treat patients with anxiety disorders centers around manipulation of the serotonergic and gabaminergic systems, which includes prescriptions for medications like Lexapro, Prozac, Zoloft (serotonin-focused) and/or benzodiazepine-based medications such as Xanax, Valium, and Ativan (GABA-receptor focused).
The functional medicine/psychiatry based approach relentlessly attempts to uncover and then treat the root cause of EACH patient’s anxiety disorder. These causes may include hormonal imbalances, inflammatory cytokine elevations, dietary sources of neuroinflammation, blood sugar dysregulation, trauma or abuse history, nutritional deficits that lead to pyroluria, homocysteinemia or low amino acid status, and can extend to toxic tissue burden and inherited genomic impairments such as MTHFR gene defects.
Chronic Anxiety and the HPA Axis
At the core of chronic anxiety, and where all roads (i.e., root causes) lead, is the dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, essentially your body’s stress response system. The true diagnosis from a biological psychiatry perspective then becomes “HPA axis dysfunction”. The tail end of the HPA axis controls the production of stress hormones such as cortisol and DHEA, as well as catecholamines like epinephrine and norepinephrine. Chronic activation of the HPA axis from chronic stress, triggers and leads to the dysregulation of the HPA axis and subsequent imbalances in stress hormone levels, of which a critical feature is abnormal production of cortisol.
Chronic activation of the stress response can be caused by:
- metabolic stress
- hormonal imbalances
- sleep cycle disruption
- pain and overt inflammation
Chronic stress is akin to the wear and tear on the tread of a tire. It takes its toll. As the tread on a tire wears with chronic stress/use, the performance of the tire goes down as well, and so does the performance of the homeostatic, self-regulating, self-healing powers of the body as it manages the incoming feedback and perception of stress. The result: poor stress tolerance and increasing stress-related symptoms such as anxiety.
Cortisol: the ‘Just Right’ Hormone
Cortisol can be a tricky hormone. While a certain amount of cortisol is necessary for optimal health, too much or too little can be disruptive and lead to symptoms that may not necessarily rise to the level of a diagnosable adrenal disease like Addison’s or Cushing’s disease. The term “adrenal fatigue” is used often by patients (and some practitioners), but is misleading and not understood nor recognized by traditional medical doctors. Better, more accurate terms might be “hypocortisolism”, “hypercortisolism”, and “adrenal dysfunction or dysregulation”.
During acute episodes of stress, more cortisol is released to help the body cope with physical or psychological stressors (1). Depending on diet, exercise, stress, and time of day, levels of cortisol will vary. During healthy conditions, cortisol levels peak in the early morning hours (usually around 8AM) and dip to their lowest after midnight. In the face of chronic psychological stress, the adrenal glands excrete an abnormal amount of cortisol in an abnormal rhythm. Receptors for cortisol reside throughout the body, including in the brain, and can therefore disrupt many seemingly separate bodily systems (1-3), producing wide-ranging effects and symptoms.
Regaining Control: Neurotransmitter Testing
To alleviate cortisol dysregulation and the anxiety it can induce, controlling the stress response is a crucial aspect of treatment. Research has clearly linked excessive stress and reduced stress tolerance to an increased incidence of anxiety (4-5).
Proper treatment of individual patients presenting with anxiety must include assessment of HPA axis function, in addition to patient-specific biomarkers that can become more clear via a thorough medical history. Assessment is straight-forward with the availability of urinary neurotransmitter measurements along with salivary cortisol and DHEA from waking through bedtime.
In our practice in Atlanta we typically assess over 175 biomarkers, including HPA axis data points, and taken together, a picture of a previously cloudy, distorted puzzle begins to emerge that allows for treatment of the individual and his/her specific causes along the metabolic, hormonal, nutritional, genomic and lifestyle continuum.
It is crucial to understand that treatment of one anxiety patient may differ significantly from another anxiety patient, and the reasons for this difference. Biochemical and genetic individuality must be factored into the treatment plan for every patient and extend to an individualized dietary regimen, nutraceutical plan, stress management and resilience building program such as mindfulness training (6) and/or cognitive therapy (7), exercise prescription and the like. At the core of any successful treatment plan for the patient with anxiety will be assessment and correction of HPA axis dysfunction.
- Endocr Rev. 2004 Oct;25(5):831-66. 11beta-hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid response. Tomlinson JW1, Walker EA, Bujalska IJ, Draper N, Lavery GG, Cooper MS, Hewison M, Stewart PM.
- Intensive Care Med. 2001 Oct;27(10):1584-91. Patterns of corticosteroid-binding globulin and the free cortisol index during septic shock and multitrauma. Beishuizen A1, Thijs LG, Vermes I.
- Early Hum Dev. 2003 Aug;73(1-2):39-52. Development of cortisol circadian rhythm in infancy. de Weerth C1, Zijl RH, Buitelaar JK.
- 2003 Nov;36 Suppl 3:S207-14. Stress responsive neurohormones in depression and anxiety. Ströhle A1, Holsboer F.
- Mol Psychiatry. 2010 Jun;15(6):574-88. doi: 10.1038/mp.2009.141. Epub 2009 Dec 15. The CRF system, stress, depression and anxiety-insights from human genetic studies. Binder EB1, Nemeroff CB.
- J Clin Psychiatry. 2013 Aug;74(8):786-92. doi: 10.4088/JCP.12m08083. Randomized controlled trial of mindfulness meditation for generalized anxiety disorder: effects on anxiety and stress reactivity. Hoge EA1, Bui E, Marques L, Metcalf CA, Morris LK, Robinaugh DJ, Worthington JJ, Pollack MH, Simon NM.
- Cogn Affect Behav Neurosci. 2005 Mar;5(1):37-40. Regulation of hypothalamic-pituitary-adrenal activity in response to cognitive therapy in patients with generalized anxiety disorder. Tafet GE1, Feder DJ, Abulafia DP, Roffman SS.