People suffering with Depression (or Depression-like) illness should ask one critically important question.

  • Is this really depression or something else?

This post will address that question and provide additional background for thought to help guide decision making in diagnosis and treatment.  

Lets take just a glimpse at the magnitude of the problem.

  • Major depressive disorder affects approximately 15 million American adults (1) and is the leading cause of disability for ages 15-44 (2)
  • People with depression are 4x likely to experience a heart attack compared to those without the illness and are at increased risk of death after a heart attack. (3)
  • About 6 million people are affected by late life depression but only 10% ever receive treatment. (4)
  • As many as 1 in 8 adolescents and 1 in 33 children have depression (5)
  • Depression is the major cause of over 2/3 of the suicides in the US (6)
  • The above becomes even more important when it is recognized that the death rate from suicide (11.3 per 100,000 people) remains higher than the death rate from chronic liver disease, Alzheimer’s, homicide, arteriosclerosis, and hypertension. (7)
  • Links between depression and addiction have also clearly been established (8), a fact that has become much more publicized after Robin William’s recent suicide.
  • In fact, additional studies have shown that  that men with alcohol dependence had rates of depression three times higher than the general population; alcohol dependent women had four times the rates of depression (9)

Standing (or researching) on the other side of the fence, however, are those who feel that a diagnosis of depression is faddish, over diagnosed, and that normal sadness has become “medicalized” 

  • One reason is that current criteria for diagnosing depression fails to take into account the common occurrence of normal sadness. That is, sadness with a clear cause as compared to sadness without an identifiable cause. (10)
  • Earlier researchers postulated that marketing of treatments beyond their true utility were likely to play a role in arriving a such a diagnosis. (11)
  • A more recent study assessing depression found that when assessed for major depressive episodes using a structured interview, only 38.4 percent of adults with clinician-identified depression met the 12-month criteria for depression, despite the majority of participants being prescribed and using psychiatric medications. (12)

As can be seen from the references above, depression can be a confusing and arbitrary diagnosis.  This brings me back to my primary question.  Is this really depression or something else?  

Several conditions are associated with depressive-type symptoms, most of which are correctable if the underlying problem is recognized and properly addressed.  However, it is not uncommon for these to escape detection resulting in ineffective treatment.

The following, although not meant to be an all-encompassing list, are 5 important, but often overlooked, things to consider when suffering depressive type symptoms.

  • Hypothyroidism
  • Adrenal insufficiency
  • Nutrient (vitamin) deficiencies
  • Sex hormone imbalances
  • Disturbances of digestion, absorption, and elimination.

Hypothyroidism is an under diagnosed condition whose symptoms mimic those of depression.  

In fact, Paul Ladenson, MD, professor and director of endocrinology and metabolism at Johns Hopkins Medical Institutions estimates that almost half the people with thyroid dysfunction are not properly diagnosed. (13)  Other authors have pointed out that 10-15% of patients diagnosed with depression actually have an underlying thyroid problem (14) and that 38% of people with low thyroid function exhibit features of depression (15).  These findings were further reinforced by a recent study showing that 63.4% of patients with “sub-clinical” hypothyroidism exhibited depressive symptoms. (16)

The above becomes even more important when it is recognized that subtle hypothyroidism is often missed because many doctors rely only on a test called TSH and fail to order other laboratory studies (such as free T3 and T4 as well as thyroid antibodies) that provide a more in-depth look at thyroid function. (17, 18)

Adrenal gland dysfunction, with either increased or decreased secretion of cortisol, is commonly associated with symptoms of clinical depression. (19,20)

Cushing’s Syndrome (a disorder of excess cortisol either due hyper-secretion or pharmaceutical treatment with steroids) can cause symptoms such as weakness, behavioral disturbances, lethargy, and outright depression.  Conversely, Addison’s Disesase (a disorder of low cortisol output) is also often accompanied by very similar symptoms. (21)

A much more recent study has also shown that cortisol levels alone, even without a diagnosis of Addison’s or Cushing’s disease, are independently related to depression.  This paper found that depression was almost twice as common in those who had either high or low cortisol levels compared with those who had normal levels of the hormone.  Low quality of life was six times more common in the group with low cortisol levels and nearly five times more common among those with high cortisol levels, compared with those who exhibited normal activity in the stress system. (22)

The authors of this study further postulated that persistent stress can lead to an “exhaustion” of the stress system with reduced cortisol levels as a result and that the low cortisol levels, once developed, can contribute to a more chronic state of illness.  This is very similar to what was originally proposed by Dr. Hans Selye, when he first introduced the term “General Adaption Syndrome” in describing the toll taken on our bodies by high levels of chronic stress. (23)

For over 20 years, Dr. James Wilson has researched and written about Adrenal Fatigue.  An excellent questionnaire, to help determine the likelihood of suffering from this disorder can be found HERE.

Few people are aware of the connection between nutrition and depression, yet individual nutrient inadequacy has been shown to play a key role in the onset, severity, and duration of this disease. (24)

For example, a recent studies have illustrated how low Vitamin D is associated with depressive symptoms in both younger and middle-aged individuals.  Being low in vitamin D may even be predictive of future episodes of depression in those not suffering with current problems.  (25,26)  This becomes especially important since the incidence of Vitamin D deficiency is rising and the vast majority of patients remain undiagnosed (27).  Among many other things, Vitamin D deficiency is also associated with Obesity, Type II diabetes, and Polycystic Ovarian Syndrome each of which carry a higher rate of depression. (28,29)

Depression has also been linked with low Vitamin B status, which when corrected can result in significant changes in mood. (30) This is particularly true for Folate where the initial symptoms of deficiency are usually neuropsychiatric (31) and depressed patients have folate levels 25% lower than non-depressed individuals. (32)

B12 deficiency is estimated to affect up to 25% of the population. The Framingham Offspring Study found that nearly 40% of people aged 26 to 83 years had B12 levels in the “low normal” range—a level at which many begin experiencing neurological and psychological symptoms. This is problematic because B12 deficiency has been severely underplayed in health care and largely ignored in favor of more recognized and more expensive-to-treat diagnoses. This has resulted in both substandard care and malpractice, costing millions of individuals their health and wasting billions of health care dollars. (33)

Beyond what is cited above, numerous other nutrient inadequacies carry an increased risk of depression. Magnesium deficiency, especially common in diabetics, is one such nutrient. (34).  Depression is also more common in individuals with deficiencies of Omega 3 fatty acids (fish oil), Chromium, Selenium, and Zinc. (24).  What is even more interesting is that similar nutrient depletion has been found in abnormal insulin signaling, a precursor to Type II diabetes, Hypothyroidism, and those suffering with Cardio-vascular diseases.

Sex  hormone imbalances have been correlated with depression in both men and women. (35,36)

In women, fluctuations in sex hormones marking female reproductive events have been shown to influence pathways linked to depression.  The gonadal steroids estrogen and progesterone have been shown to affect brain regions known to be involved in the modulation of mood and behavior. (37)  Although it is beyond my expertise, and intent of this post, to provide an exhaustive review of these imbalances; it has become clear that excess adrenaline and cortisol production (due to stress) can lead to estrogen levels that are lower than necessary to preserve normal brain function. (38).  Endocrine disrupting chemicals such (such as pesticides, herbicides, and BPA found in plastics) have also been shown to adversely affect normal sex (and other) hormone balance.  (39,40)

Partial Androgen (Testosterone) Deficiency of the Aging Male (PADM) is characterized by sexual, somatic, and behavioral symptoms, with insidious onset and slow progression. (41) Common symptoms of depression, such as weakness, fatigue, decreased libido and lack of motivation are often associated with this disorder. (42,43,44)  However, the relationship between androgen deficiency and depression is far from exacting as some studies have shown a correlation (45,46) whereas others have not. (47).  Similar to estrogen dynamics in women, a complex web of interactions between testosterone and other hormones exist.  Also similar is how modifiable lifestyle factors such as stress (48), obesity (49), and chronic alcohol use (50) negatively influence male androgen-estrogen hormone balance.

Although testosterone deficiency is most often considered in men, some studies have suggested that low testosterone in females also contributes to a lessening of libido and overall worse sense of well being. (51) A modifiable factor on the positive side is that performing resistance exercises has been shown to induce increased testosterone production in both men and women. (52)

That “gut feeling” you have may be more important that you think as, increasingly, research is showing the link between abnormal digestive-gastrointestinal function and disturbances of mood. (53, 54).

The research has shown that interactions between an individual, and their own internal microbial environment (much of which resides within the gut) plays a key role in maintaining homeostasis and that alterations in gut microbial make-up is associated with marked changes in mood and behavior. (55)  This is felt to be secondary to immune activation leading to the release of inflammatory mediators causing a disruption of brain neurochemical metabolism. (56, 57)

It is also worth noting that a similar degree of immune activation is also seen in the development and maintenance of chronic pain syndromes. (58)

Such discoveries are now opening doors to new ways of treating depression and chronic pain syndromes called “psychobiotics”, where emphasis is placed on probiotic supplementation to restore the normal microbial balance of the GI tract. (59)

Finding and addressing the underlying cause of any disease is the keystone of effective treatment.  This post provides just the “tip of the iceberg” for things to consider in depressive type illnesses prior to embarking on a course of using mood-altering medications.




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