title: Hyper- and hypocortisolism in bipolar disorder - A beneficial influence of lithium on the HPA-axis?
abstract: A 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.
  
  
  
  This 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.
  
  
  
  Patients 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.
  
  
  
  Cross sectional study design.
  
  
  
  There 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.
authors.affiliation: Division of Psychiatry, Department of Clinical Sciences, Umeå University, SE-901 87 Umeå, Sweden. Electronic address: martin.maripuu@psychiat.umu.se.
authors.forename: Martin
authors.initials: M
authors.lastname: Maripuu
authors.affiliation: Division of Psychiatry, Department of Clinical Sciences, Umeå University, SE-901 87 Umeå, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Wikgren
authors.affiliation: Division of Medicine, Department of Public Health and Clinical Medicine, Umeå University, SE-901 87 Umeå, Sweden.
authors.forename: Pontus
authors.initials: P
authors.lastname: Karling
authors.affiliation: Division of Psychiatry, Department of Clinical Sciences, Umeå University, SE-901 87 Umeå, Sweden.
authors.forename: Rolf
authors.initials: R
authors.lastname: Adolfsson
authors.affiliation: Division of Psychiatry, Department of Clinical Sciences, Umeå University, SE-901 87 Umeå, Sweden.
authors.forename: Karl-Fredrik
authors.initials: KF
authors.lastname: Norrback
mesh_terms: D000328:Adult; D000367:Age Factors; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000503:physiopathology; D003430:Cross-Sectional Studies; D003866:Depressive Disorder / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000503:physiopathology; D008094:Lithium / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000503:physiopathology; D011788:Quality of Life; D012307:Risk Factors
chemical_list: D008094:Lithium; D006854:Hydrocortisone
keywords: Bipolar disorder; Cortisol; Hypercortisolism; Hypocortisolism; Lithium; Stress