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Arch Gen Psychiatry. 2009 Jun;66(6):617-26
Authors: Vreeburg SA, Hoogendijk WJ, van Pelt J, Derijk RH, Verhagen JC, van Dyck R, Smit JH, Zitman FG, Penninx BW
CONTEXT: There is a central belief that depression is associated with hyperactivity of the hypothalamic-pituitary-adrenal axis, resulting in higher cortisol levels. However, results are inconsistent.
OBJECTIVE: To examine whether there is an association between depression and various cortisol indicators in a large cohort study. Design, Setting, and
PARTICIPANTS: Data are from 1588 participants of the Netherlands Study of Depression and Anxiety who were recruited from the community, general practice care, and specialized mental health care. Three groups were compared: 308 control subjects without psychiatric disorders, 579 persons with remitted (no current) major depressive disorder (MDD), and 701 persons with a current MDD diagnosis, as assessed using the DSM-IV Composite International Diagnostic Interview.
MAIN OUTCOME MEASURES: Cortisol levels were measured in 7 saliva samples to determine the 1-hour cortisol awakening response, evening cortisol levels, and cortisol suppression after a 0.5-mg dexamethasone suppression test.
RESULTS: Both the remitted and current MDD groups showed a significantly higher cortisol awakening response compared with control subjects (effect size [Cohen d] range, 0.15-0.25). Evening cortisol levels were higher among the current MDD group at 10 pm but not at 11 pm. The postdexamethasone cortisol level did not differ between the MDD groups. Most depression characteristics (severity, chronicity, symptom profile, prior childhood trauma) were not associated with hypothalamic-pituitary-adrenal axis activity except for comorbid anxiety, which tended to be associated with a higher cortisol awakening response. The use of psychoactive medication was generally associated with lower cortisol levels and less cortisol suppression after dexamethasone ingestion.
CONCLUSIONS: This large cohort study shows significant, although modest, associations between MDD and specific hypothalamic-pituitary-adrenal axis indicators. Because a higher cortisol awakening response was observed among both subjects with current MDD and subjects with remitted MDD, this may be indicative of an increased biological vulnerability for depression.
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This is an interesting study because it uses salivary cortisol as a measure of adrenal function.
The study shows that cortisol levels are elevated in patients with both remitted and current major depressive disorder compared to controls. This is in line with current textbook information.
The problem I have is that I hardly high cortisol levels this in real life. I estimate that I see elevated cortisol levels in less than 1 in 1000 patients with major depressive disorder. The vast majority have low to very low cortisol levels.
The answer to this discrepancy lies in examining the demographic characteristics of the patients in this study:
1. The majority of the patients are working.
2. Greater than 93% of them are Northern European White. They are all from the Netherlands.
3. The vast majority of the patients were high school graduates with many of them having a college education.
4. The patients were physically active.
5. At least 2/3 or more of the patients with depression or remitted depression were able to sleep > 6 hours a night.
The Netherlands is ranked 1st among countries in chid well-being. It has the lowest rate of unemployment among the European Union member states. Life expectancy is high in the Netherlands (82 years for newborn girls and 77 for boys). The country has a universal social medical system – everyone has health insurance. The state provides regular check ups for children. Parents receive government quarterly payments to help raise their children, including money for school books. The government reimburses 70% of the cost of daycare (which costs about $14,000 a year). By law, employers have to give you 8% of your income on top of what you already earn for vacation money. And by law, employers have to give you at least 4 weeks vacation per year. If you are unemployed, the government gives you money so you can take a vacation. The Netherlands has a non-profit public housing system where 1/3 of the dwellings in the country are for social housing. Qualified individuals received below-market rents. There is less stigma for living in public housing in the Netherlands than exists in the U.S.
The social services available in the Netherlands for housing, medical care, and income are far superior what is available in the U.S. – where the stress of living is far harsher. For example, homelessness is a huge stress that my patients face. Some have to live on the streets. Homelessness as a stress is practically non-existent in the Netherlands. Poverty with zero income is common among my patients. Malnutrition is common. When one has litttle money, one has little choice in what to eat – generally cheap, fattening, and inflammatory processed carbohydrates. Patients in the Netherlands automatically have income from the government – something we have to fight for in the U.S. for our patients. A large number of patients have no health insurance in the U.S. Many of these patients only seek help when they are direly ill and have to go to the emergency room. This situation is not faced by patients in the Netherlands. They can get treated at a much earlier and lower level of illness due to having universal health care.
The advantages patients have in the Netherlands compared to the U.S. patients increases the likelihood that patients with major depression in the Netherlands are much healthier and much higher functioning than in the U.S. This accounts for the high cortisol levels seen in patients with major depressive disorder. When graphed, there is little visual difference between the cortisol levels of control patients and patients with active major depressive disorder. In the U.S., by the time a patient sees me, they may often be a train-wreck with multiple serious physical illnesses. Inflammatory conditions are frequent. Heart disease, diabetes, hypertension, allergies, asthma, dyslipidemia, etc. etc. are common. The high cortisol levels seen in the Netherlands may indicate that inflammatory conditions are less likely to be present. The patients’ bodies are healthy enough to be capable of controlling inflammation despite having major depressive disorder.
Despite the large number of patients involved (n = 701 for current MDD, n = 579 for remitted MDD), this is a high functioning group of patients who are not as severely ill as the patients I see. I would estimate that the average GAF score for the patients in this study with current MDD would be between 60-80. This compares to the average 30-50 GAF range for the patients I see.