Cortisol as a Predictor of Clinical Depression


Molecular structure of cortisol. Source: Wiki Commons

Molecular structure of cortisol. Source: Wiki Commons

Major depressive disorder (MDD or MD) is a mental disorder that severely impairs the cognitive well-being of the victim and those around them. Its symptoms include a persistently low mood coupled with a self-reported lack of pleasure in everyday activities (1). Until now, practitioners have relied on subclinical depression symptoms to recognize its onset. As such, there is an increasing need for a measurable biological marker to reliably predict the likelihood of future episodes of MD. Owens et al. (2014) has isolated elevated levels of the hormone cortisol, in conjunction with behavioral symptoms, as a reliable predictor of potential for MD onset.

Cortisol itself is a glucocorticoid, a steroid hormone produced in the adrenal gland, and is released into the body during stressful situations and when glucose levels within the blood become too low (2). While cortisol has a variety of effects, its main functions are to increase blood sugar through gluconeogenesis, suppress the immune system, and aid in metabolism via the breakdown of fats, proteins, and carbohydrates (3). Prior research has shown that dysregulated cortisol levels, specifically elevated morning and evening levels, correlate with symptoms indicative of MD.

Researchers first gathered data from two cohorts of young adults (N = 1,858) within the United Kingdom. They organized this group into four “classes” based on binary representations, high or low, of their morning and evening cortisol levels and the prevalence of depressive symptoms. Class 1 held low cortisol levels and little low depressive symptoms, class 2 held low cortisol and high depressive symptoms, class 3 had high cortisol and low depressive symptoms, and class 4 was high in both categories. General conclusions, drawn from post-hoc access to medical records up to 36 months after the initial testing, indicated that individuals from classes 2-4 were anywhere from 1.6 to 7.1 times more likely to meet criteria for clinical depression than were those in class 1.

Researchers also found a correlation between cortisol levels and likelihood of becoming clinically depressed that was asymmetric across genders. For men, there was a significantly increased probability of developing MD in class 4 as opposed to class 1. For women, individuals in group 3 were more likely to develop MD symptoms, followed by class 4. Given that the only difference between class 3 and class 4 individuals is cortisol levels, it would appear that the hormone paired with depressive symptoms is a predictor primarily in men. For women, the depressive symptoms themselves remained a reliable predictor regardless of cortisol activity.

To dissociate the present results from those of disorders not involving depression, Owens et al. repeated the analysis using non-depressive psychiatric disorders (NDPD). In contrast with results gained by using symptoms of depression, classes 1 and 2 showed no difference in likelihood to report NDPD. Moreover, while classes 3 and 4 were more likely to report than class 1, the two classes differed very little from one another. Furthermore, there was no significant sex-differentiated effect, which was exhibited strongly in the results utilizing depressive symptoms. This single dissociation provides evidence that it is specifically depressive disorders, as opposed to those arising from other psychiatric states, which match with cortisol to predict the onset of MD.

As people with symptoms of depression often fail the overgeneralized memory (OGM) test, this can be used to examine the validity of these findings. As expected, individuals in class 4 showed significantly more OGM responses than classes 1 through 3. However, because it was primarily men that showed MD symptoms in class 4, this behavioral mechanism appears to extend mainly to them. Women showed the largest correlation with MD in class 3.

The above research outlines a positive correlation between the hormone cortisol and the symptoms of major depressive disorder. It also shows that current measurements yield stronger results for men, quantifying the view of differing physiological and behavioral responses to depression for men and women.


1. Djurhuus, C. B., Gravholt, C. H., Nielsen, S., Mengel, A., Christiansen, J. S., Schmitz, O. E., & Møller, N. (2002). Effects of cortisol on lipolysis and regional interstitial glycerol levels in humans. American Journal of Physiology-Endocrinology And Metabolism283(1), E172-E177.

2. K Hoehn, E. M. (2010). Human Anatomy and Physiology. San Francisco: Benjamin Cummings.

3. Owens, M., et al. (2014). Elevated morning cortisol is a stratified population-level biomarker for major depression in boys only with high depressive symptoms. Proceedings of the National Academy of Sciences, 111(9), 3638-3643.


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