Research paperHyper- and hypocortisolism in bipolar disorder - A beneficial influence of lithium on the HPA-axis?

- There was a negative association between age and HPA-axis activity in BD.
- Hypercortisolism was characterized by young age and female gender.
- Hypocortisolism was characterized by long disease duration without lithium prophylaxis.
- Lithium prophylaxis seemed to prevent the development of hypocortisolism.
- Development from hyper- to hypocortisolism may be associated with disease progression.

BackgroundA hyperactive hypothalamic-pituitary-adrenal axis (HPA-axis) is a well-known phenomenon in bipolar disorder (BD). However, hypocortisolism has also been described and found associated with depression, low quality of life and cardiovascular risk factors in BD patients. Although the pathophysiology related to hypocortisolism in BD is largely unknown, hypocortisolism is associated with chronic stress exposure and after inducing an initial rise in cortisol long-term stress may result in a transition to hypocortisolism. BD patients are throughout life often exposed to chronic stress. We therefore hypothesized that higher age would be associated with lower HPA-axis activity especially among patients without previous mood stabilizing treatment.MethodsThis cross-sectional study consisted of 159 bipolar outpatients and 258 controls. A low-dose-dexamethasone-suppression-test (DST) was used to measure HPA-axis activity.ResultsPatients with BD showed a negative association between post DST cortisol and age (−3.0 nmol/l per year; p=0.007). This association gradually increased in subgroups that were naïve to lithium (−7.7 nmol/l per year; p=0.001) and “all mood stabilizers” (−11.4 nmol/l per year; p=0.004). Patients exhibiting hypercortisolism were characterized by younger age and female gender, whereas patients exhibiting hypocortisolism were characterized by long disease duration without prophylactic lithium treatment as well as absence of current lithium medication.LimitationsCross sectional study design.ConclusionsThere was a negative association between HPA-axis activity and age in BD, rendering BD patients at risk for developing hypocortisolism. This association was most pronounced among patients without previous or current lithium prophylaxis.