Written by James L. Wilson, DC, ND, PhD

The World Health Organization lists depression as one of the leading causes of disability worldwide.[i] It is well known that stress can precipitate major depression and influences its incidence, severity and course[ii]. It is also known that many of the features of major depression potentially reflect dysregulation of the stress response of the hypothalamic-pituitary-adrenal (HPA) axis[iii].

There are a number of clinical conditions in which depression and cortisol, a prime adrenal hormone, are associated, but the HPA axis pattern differs from that of major depression. These conditions include but are not limited to:

  • posttraumatic stress disorder[iv]
  • bipolar disorder[v]
  • fibromyalgia
  • chronic fatigue syndrome[vi]
  • functional gastrointestinal disorders[vii]
  • early sexual abuse[viii]
  • Cushing’s syndrome[ix] [x] [xi]
  • Addison’s disease[xii] [xiii]
  • adrenal fatigue[xiv]

This article will focus on HPA axis function in major depression.

Major depression is a heritable disorder that affects approximately 8% of men and 15% of women[xv]. For over 75% of patients, major depression is a recurrent, lifetime illness characterized by repeated remissions and exacerbations[xvi]. Its effects extend beyond psycho-emotional to negatively influence neuroendocrine regulation, autonomic function, and the regulation of sleep, appetite and metabolic activity[xvii] [xviii].

The long-term physiological impact of major depression has serious implications for health, including increased incidence of coronary artery disease[xix] [xx] [xxi], premature osteoporosis[xxii] and the doubling of all-cause mortality at any age[xxiii] [xxiv] [xxv].

The Diagnostic and Statistical Manual of Mental Disorders V (DSM-V)[xxvi], the principal diagnostic instrument used for psychiatric diagnosis in the United States, lists two distinct clinical major depressive syndromes that appear to be the antithesis of one another: melancholic and atypical depression. This distinction is based on their patterns of psychological and behavioral symptoms[xxvii].

Melancholic depression is actually a state of pathological hyperarousal. Its psychological manifestations are intense anxiety; feelings of worthlessness; recollections of past transgressions, failures and helplessness; dread of the future; and feelings of personal deficiency which color thought and affect[xxviii] [xxix].

Severe melancholic depression has long been associated with consistently elevated levels of cortisol[xxx]. Its physiological manifestations include hypercortisol, suppression of growth hormone and the reproductive axes, insomnia (most often early-morning waking) and loss of appetite. The melancholia is greatest early in the morning[xxxi]. Only 25 to 30% of patients with major depression present with pure melancholic features[xxxii].

Atypical depression in many ways is the opposite of melancholic depression. It is associated with a disturbing sense of disconnectedness and emptiness, punctuated by brief emotional reactions to external circumstances. People with atypical depression seem walled off from themselves, and complain of cognitive and mental weariness. They tend to avoid others, often with a sense that contact would be too demanding, tiring and poorly received. They present with lethargy, fatigue, excessive sleepiness, increased food intake, weight gain and depressive symptoms that worsen as the day progresses[xxxiii].

15 to 30% of patients with major depression show pure atypical depression features[xxxiv], about half as frequent as melancholic depression. More recently it has emerged that atypical depression is marked by paradoxically low cortisol levels[xxxv].

The HPA axis functions differently in these two types of major depression. Melancholic depression occurs with an overall hyperactive HPA axis with elevated corticotrophin releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and cortisol. Atypical depression occurs with an overall hypoactive HPA axis with decreased CRH, ACTH and cortisol.

Thus, although both produce major clinical depression, their presenting symptoms and neuroendocrine responses are nearly opposite. It is interesting to note that neither type of major depression shows the same HPA axis patterns as Cushing’s syndrome[xxxvi], Addison’s disease[xxxvii] or adrenal fatigue, which has an HPA axis pattern more closely resembling Addison’s than either of the major depression types[xxxviii].

Although most patients with major depression can be classified as either melancholic or atypical, not all cases within a classification resemble one another[xxxix]. The majority of patients with major depression present with a mixture of cognitive, affective and physiological features (referred to as a mixed neurovegetative type) and do not show clearly hyper or hypo HPA axis function[xl] [xli].

However, those who do show a clear melancholic or atypical presentation and HPA axis pattern have a much poorer outcome[xlii]. In other words: those suffering from major clinical depression where the HPA axis is clearly disturbed, in either an overactive or suppressed pattern, have a poorer prognosis.

In summary, depression is one of the most common health problems occurring worldwide. Cortisol, both high and low, has been closely associated with major depression in which two distinct clinical sub-types can be separated out; melancholic and atypical. Melancholic depression is more frequent and shows an overall elevated HPA axis pattern with high cortisol as an end-point, whereas atypical depression shows an overall hyporeactivity of the HPA axis manifesting as low cortisol.

Neither pattern is identical to the HPA axis responses seen in Cushing’s syndrome, Addison’s disease or adrenal fatigue. Thus, there appear to be several response patterns associated with depression and cortisol. Therefore, once depression is diagnosed, the astute clinician should investigate HPA function further to gain important information that will lead to a more accurate diagnosis and a more effective therapeutic outcome.

The original blog can be found here.

 

Dr James Wilson

James L. Wilson, DC, ND, PhD, received his Ph.D. in Human Nutrition from the University of Arizona, with minors in Immunology, Microbiology, Pharmacology and Toxicology, and research in Cellular Immunology. His doctorates in Chiropractic Medicine and Naturopathic Medicine are from the Canadian Memorial Chiropractic College and the Ontario College of Naturopathic Medicine (CCNM).

As one of the 14 founding members of CCNM, now the largest Naturopathic College in the world, Dr. Wilson has long been on the forefront of alternative medicine. For over twenty-five years, he was in private practice in Canada and the United States. In 1998, Dr. Wilson coined the term ‘adrenal fatigue’ to identify below optimal adrenal function resulting from stress and distinguish it from Addison’s disease.

With a researcher’s grasp of science and a clinician’s understanding of its human impact, Dr. Wilson has helped many physicians understand the physiology behind and treatment of various health conditions. He is acknowledged as an expert on alternative medicine, especially in the area of stress and adrenal function. Dr. Wilson is a respected and sought after lecturer and consultant in the medical and alternative healthcare communities in the United States and abroad.

Watch this short video to see why Power2Practice is an essential tool for Integrative and Functional Medicine!

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Frank E & Thase ME. Natural history and preventive treatment of recurrent mood disorders. Amer. Rev. Med. 1999. 50: 453-68.

Gold PW & Chrousos GP. Organization of the stress system and its dysregulation in melancholic and atypical depression: High versus low CRH/NE states. Molecular Psychiatry. 2002: 7; 254-275.

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[xxiv] Barefoot JC & Schroll M. Symptoms of depression, acute myocardial infarction, and total mortality in a community sample. Circulation. 1996; 93: 1976-1980.

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[xxxiv] Gold PW & Chrousos GP. Organization of the stress system and its dysregulation in melancholic and atypical depression: High versus low CRH/NE states. Molecular Psychiatry. 2002:7; 254-275

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[xxxix] Gold PW & Chrousos GP. Organization of the stress system and its dysregulation in melancholic and atypical depression: High versus low CRH/NE states. Molecular Psychiatry. 2002: 7; 254-275.

[xl] Gold PW & Chrousos GP. Organization of the stress system and its dysregulation in melancholic and atypical depression: High versus low CRH/NE states. Molecular Psychiatry. 2002: 7; 254-275.

[xli] Levitan R, Lesage A, Parikh S, Goering P, Kennedy S. Reversed neurovegetative symptoms of depression: A community study. Am. J. Psychiatry 1997; 154: 934-940.

[xlii] Gold PW & Chrousos GP. Organization of the stress system and its dysregulation in melancholic and atypical depression: High versus low CRH/NE states. Molecular Psychiatry. 2002: 7; 254- 275.