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Relative Hypo-and Hypercortisolism Are Both Associated with Depression and Lower Quality of Life in Bipolar Disorder: A Cross-Sectional Study
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
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2014 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 6, e98682Article in journal (Refereed) Published
Abstract [en]

Background: Depression in unipolar and bipolar disorders is associated with hypothalamic-pituitary-adrenal-axis (HPA-axis) hyperactivity. Also, unipolar disorder has recently been shown to exhibit HPA-axis hypoactivity. We studied for the first time how HPA-axis hypo-and hyperactivity relate to depression and disease burden in bipolar disorder. We were interested in studying hypocortisolism; characterized by increased HPA-axis negative feedback sensitivity and lower basal cortisol levels together with the opposite HPA-axis regulatory pattern of hypercortisolism. Methods: This cross-sectional study includes 145 type 1 and 2 bipolar outpatients and 145 matched controls. A dexamethasone-suppression-test (DST) measures the negative feedback sensitivity and a weight-adjusted very-low-dose DST was employed, which is sensitive in identifying hypocortisolism and hypercortisolism. The 25th and 75th percentiles of control post-DST values were used as cut-offs identifying patients exhibiting relative hypo-, and hypercortisolism. Self-report questionnaires were employed: Beck-Depression-Inventory (BDI), Montgomery-Asberg-Depression-Rating-Scale (MADRS-S), World-Health-Organization-Quality-of-Life-Assessment-100 and Global-Assessment-of-Functioning. Results: Patients exhibiting relative hypocortisolism expectedly exhibited lowered basal cortisol levels (p = 0.046). Patients exhibiting relative hypercortisolism expectedly exhibited elevated basal levels (p<0.001). Patients exhibiting relative hypocortisolism showed 1.9-2.0 (BDI, p = 0.017, MADRS-S, p = 0.37) and 6.0 (p<0.001) times increased frequencies of depression and low overall life quality compared with patients exhibiting mid post-DST values (eucortisolism). Adjusted Odds Ratios (OR:s) for depression ranged from 3.8-4.1 (BDI, p = 0.006, MADRS-S, p = 0.011) and was 23.4 (p<0.001) for life quality. Patients exhibiting relative hypercortisolism showed 1.9-2.4 (BDI, p = 0.017, MADRS-S, p = 0.003) and 4.7 (p<0.001) times higher frequencies of depression and low overall life quality compared with patients exhibiting eucortisolism. Adjusted OR: s for depression ranged from 2.2-2.7 (BDI, p = 0.068, MADRS-S, p = 0.045) and was 6.3 (p = 0.008) for life quality. Limitations: The cross-sectional design and lack of pre-established reference values of the DST employed. Conclusions: Relative hypocortisolism and relative hypercortisolism were associated with depression and lower life quality, providing novel insights into the detrimental role of stress in bipolar disorder.

Place, publisher, year, edition, pages
2014. Vol. 9, no 6, e98682
National Category
URN: urn:nbn:se:umu:diva-91276DOI: 10.1371/journal.pone.0098682ISI: 000337738600011OAI: diva2:735471
Available from: 2014-07-28 Created: 2014-07-28 Last updated: 2015-12-16Bibliographically approved
In thesis
1. Hypocortisolism in recurrent affective disorders
Open this publication in new window or tab >>Hypocortisolism in recurrent affective disorders
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Bipolar disorders and recurrent depressions are two common psychiatric disorders with a life time prevalence of approximately 1% and 8%, respectively. Despite treatment these patients suffer from affective symptoms up to 50% of the time, resulting in lower well-being. The average life length is also reduced with 10-15 years, mainly attributable to suicide and cardiovascular disease. Increased stress is one of many factors that have been shown to be linked to an increased risk for developing affective disorders and some comorbid somatic conditions such as metabolic disturbances and cardiovascular disease. An increased stress level is known to cause hyperactivity of the hypothalamic-pituitary-adrenal-axis (HPA-axis) with increased cortisol secretion. Hyperactivity of the HPA-axis (or hypercortisolism) is one of the most replicated neurobiological finding in depression. In other stress related disorders it has however been shown that prolonged stress over long periods of time can lead to a state of low HPA-axis activity, hypocortisolism. Since persons with recurrent affective disorders such as bipolar disorder and recurrent depression are exposed to a high degree of recurrent and chronic stress it could be expected that in addition to hypercortisolism, a state of hypocortisolism could also develop in these disorders, potentially exerting an influence upon the psychological and somatic wellbeing among these patients.

The major aim of this thesis was to evaluate whether hypocortisolism is related to relevant psychiatric and somatic phenotypes in recurrent affective disorders.

In bipolar disorder, individuals with hypocortisolism exhibited a higher degree of depression and low quality of life compared to patients with normal HPA-axis activity. In recurrent depression, individuals with hypocortisolism exhibited shorter leukocyte telomere length than patients with normal or high HPA-axis activity, which is an indication of an accelerated aging process. In a sample of both bipolar and recurrent depression patients, hypocortisolism was associated with an increased proportion of obesity, dyslipidemia and metabolic syndrome compared with patients with normal or high HPA-axis activity. Patients with recurrent depression showed a higher occurrence of hypocortisolism than the control sample representative of the general population. Patients with bipolar disorder showed a similar occurrence of hypocortisolism as the control sample. Among bipolar disorder patients with a low degree of lifetime with lithium prophylaxis, there was an inverse correlation between age and HPA-axis activity. In contrast, among patients with a higher degree of lifetime with lithium prophylaxis as well as among the controls, there was no correlation between age and HPA-axis activity. Accordingly, hypocortisolism was most common among older patients with a low degree of lifetime with lithium prophylaxis. In conclusion, hypocortisolism in both recurrent depression and bipolar disorder was associated with multiple clinically-relevant phenotypes. Additionally it was shown for bipolar disorder patients that increasing age was a risk factor for hypocortisolism and that prophylactic lithium treatment was a protective factor. It is argued that the protective effect of lithium towards the HPA-axis is attributable to its mood-stabilizing effect, which in turn reduces the chronic stress level. These results provide new insight into the role of hypocortisolism and chronic stress in recurrent affective disorders warranting further studies and hopefully providing clues to improved treatment strategies.

Place, publisher, year, edition, pages
Umeå: Umeå Universitet, 2015. 55 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 1766
Affective disorders, Bipolar disorder, Cortisol, Depression, HPA-axis, Hypercortisolism, Hypocortisolism, Lithium, Metabolic syndrome, Obesity, Quality of life, Recurrent depression, Stress, Telomeres
National Category
urn:nbn:se:umu:diva-112824 (URN)978-91-7601-383-0 (ISBN)
Public defence
2016-01-22, Föreläsningssal A, Psykiatriska kliniken, Byggnad 23, Plan 0, Norrlands universitetssjukhus (NUS), Umeå, 13:00 (Swedish)
Available from: 2015-12-18 Created: 2015-12-15 Last updated: 2016-01-08Bibliographically approved

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