title: Relative hypo- and hypercortisolism are both associated with depression and lower quality of life in bipolar disorder: a cross-sectional study.
abstract: 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-Åsberg-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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Psychiatry, Department of Clinical Sciences, Umeå University, Umeå, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Maripuu
authors.affiliation: Division of Psychiatry, Department of Clinical Sciences, Umeå University, 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, Umeå, Sweden.
authors.forename: Pontus
authors.initials: P
authors.lastname: Karling
authors.affiliation: Division of Psychiatry, Department of Clinical Sciences, Umeå University, Umeå, Sweden.
authors.forename: Rolf
authors.initials: R
authors.lastname: Adolfsson
authors.affiliation: Division of Psychiatry, Department of Clinical Sciences, Umeå University, Umeå, Sweden.
authors.forename: Karl-Fredrik
authors.initials: KF
authors.lastname: Norrback
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000378:metabolism / Q000523:psychology*; D003430:Cross-Sectional Studies; D003863:Depression / Q000378:metabolism*; D003907:Dexamethasone / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010913:Pituitary-Adrenal System; D011569:Psychiatric Status Rating Scales; D011788:Quality of Life
chemical_list: D003907:Dexamethasone; D006854:Hydrocortisone