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J Affect Disord. 2016 Nov 1;204:187-96. doi: 10.1016/j.jad.2016.06.024. Epub 2016 Jun 21.

Relative hypocortisolism is associated with obesity and the metabolic syndrome in recurrent affective disorders.

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Division of Psychiatry, Department of Clinical Sciences, Umeå University, Umeå, Sweden. Electronic address:
Division of Psychiatry, Department of Clinical Sciences, Umeå University, Umeå, Sweden.
Division of Medicine, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.



Cardiovascular disease (CVD) is one of the main causes of excess deaths in affective disorders. Affective disorders are associated with increased frequencies of CVD risk-factors such as obesity, dyslipidemia, and metabolic syndrome. Stress-induced chronic cortisol excess has been suggested to promote obesity and metabolic syndrome. Chronic stress with frequent or persisting hypothalamic-pituitary-adrenal-axis (HPA-axis) hyperactivity may, over time, lead to a state of low HPA-axis activity, also denoted hypocortisolism. A low-dose weight-adjusted dexamethasone-suppression-test (DST) is considered to be a sensitive measure of hypocortisolism.


245 patients with recurrent depression or bipolar disorder and 258 controls participated in a low-dose DST and were also examined with regard to metabolic status.


Patients with hypocortisolism (low post-DST cortisol) compared with patients without hypocortisolism (normal or high post-DST cortisol) exhibited increased odds ratios (OR) for obesity (OR=4.0), overweight (OR=4.0), large waist (OR=2.7), high LDL (OR=4.2), low HDL (OR=2.4), high LDL/HDL ratio (OR=3.3), high TC/HDL ratio (OR=3.4) and metabolic syndrome (OR=2.0). A similar pattern but less pronounced was also found in the control sample.


The cross sectional study design and absence of analyses addressing lifestyle factors.


Our findings suggest that a substantial portion of the metabolic disorders and cardiovascular risk factors seen in recurrent affective disorders are found among individuals exhibiting hypocortisolism. This might indicate that long-term stress is a central contributor to metabolic abnormalities and CVD mortality in recurrent affective disorders.


Affective disorder; Cortisol; Dyslipidemia; Hypocortisolism; Metabolic syndrome; Obesity

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