Skip to main content
Article thumbnail
Location of Repository

Can variation in hypothalamic-pituitary-adrenal (HPA)-axis activity explain the relationship between depression and cognition in bipolar patients?

By W.A. Nolen, A. Aleman, E.A. Holthausen, H. Burger, R.F. Riemersma-van der Lek and M.J. van der Werf-Eldering


BACKGROUND: Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is thought to be associated with more mood symptoms and worse cognitive functioning. This study examined whether variation in HPA axis activity underlies the association between mood symptoms and cognitive functioning. METHODOLOGY/PRINCIPAL FINDINGS: In 65 bipolar patients cognitive functioning was measured in domains of psychomotor speed, speed of information processing, attentional switching, verbal memory, visual memory, executive functioning and an overall mean score. Severity of depression was assessed by the Inventory of Depressive Symptomatology-self rating version. Saliva cortisol measurements were performed to calculate HPA axis indicators: cortisol awakening response, diurnal slope, the evening cortisol level and the cortisol suppression on the dexamethasone suppression test. Regression analyses of depressive symptoms and cognitive functioning on each HPA axis indicator were performed. In addition we calculated percentages explanation of the association between depressive symptoms and cognition by HPA axis indicators. Depressive symptoms were associated with dysfunction in psychomotor speed, attentional switching and the mean score, as well as with attenuation in diurnal slope value. No association was found between HPA axis activity and cognitive functioning and HPA axis activity did not explain the associations between depressive symptoms and cognition. CONCLUSIONS/SIGNIFICANCE: As our study is the first one in this field specific for bipolar patients and changes in HPA-axis activity did not seem to explain the association between severity of depressive symptoms and cognitive functioning in bipolar patients, future studies are needed to evaluate other factors that might explain this relationship

Year: 2012
DOI identifier: 10.1371/journal.pone.0037119
OAI identifier:

Suggested articles


  1. (2008). A
  2. (2006). A meta-analysis of cognitive deficits in euthymic patients with bipolar disorder. doi
  3. (2009). A meta-analysis of depression severity and cognitive function. doi
  4. (2009). A meta-analytic investigation of neurocognitive deficits in bipolar illness: Profile and effects of clinical state. doi
  5. (2010). A prospective study of diurnal cortisol and cognitive function in community-dwelling elderly people. doi
  6. (1978). A rating scale for mania: Reliability, validity and sensitivity. doi
  7. (1981). A specific laboratory test for the diagnosis of melancholia. standardization, validation, and clinical utility.
  8. (2011). Abnormal cortisol awakening response predicts worse cognitive function in patients with first-episode psychosis. doi
  9. (2006). Abnormalities of the HPA axis in affective disorders: Clinical subtypes and potential treatments. doi
  10. (2008). Antiglucocorticoid treatments for mood disorders. Cochrane Database Syst Rev. doi
  11. (2009). Associations between sociodemographic, sampling and health factors and various salivary cortisol indicators in a large sample without psychopathology. doi
  12. (2008). Asymptotic and resampling strategies for assessing and comparing indirect effects in multiple mediator models. doi
  13. (1994). Cambridge neuropsychological test automated battery (CANTAB): A factor analytic study of a large sample of normal elderly volunteers. doi
  14. (2010). Cognitive functioning in patients with bipolar disorder: Association with depressive symptoms and alcohol use. doi
  15. (2011). Cooccurring manic symptomatology influences HPA axis alterations in depression. doi
  16. (2005). Cortisol level predicts executive and memory function in depression, symptom level predicts psychomotor speed. doi
  17. (2009). Effects of glucocorticoids on mood, memory, and the hippocampus. treatment and preventive therapy. doi
  18. (2000). Future therapeutic targets in mood disorders: The glucocorticoid receptor. doi
  19. (2009). Glucocorticoid receptor polymorphisms in major depression. focus on glucocorticoid sensitivity and neurocognitive functioning. doi
  20. (2010). Glucocorticoid sensitivity of cognitive and inflammatory processes in depression and posttraumatic stress disorder. doi
  21. (2000). Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders. doi
  22. (1996). Hippocampal atrophy in major depression: A result of depression-induced neurotoxicity?
  23. (1992). Hippocampal formation volume, memory dysfunction, and cortisol levels in patients with cushing’s syndrome. doi
  24. (1999). Hippocampal remodeling and damage by corticosteroids: Implications for mood disorders. doi
  25. (2005). Hypothalamic-pituitary-adrenal axis and bipolar disorder. doi
  26. (2004). Hypothalamic-pituitary-adrenal axis function in patients with bipolar disorder. doi
  27. (2004). Improvement of working but not declarative memory is correlated with HPA normalization during antidepressant treatment. doi
  28. (2011). Location of cerebrovascular and degenerative changes, depressive symptoms and cognitive functioning in later life: The SMART-medea study. doi
  29. (2009). Major depressive disorder and hypothalamic-pituitary-adrenal axis activity: Results from a large cohort study. doi
  30. (1982). National adult reading test (NART) test manual.
  31. (2004). Neuropsychological assessment.
  32. (2007). Neuropsychological functioning in euthymic bipolar disorder: A meta-analysis. Acta Psychiatr Scand suppl 434: doi
  33. (2007). Persistent cognitive impairment in depression: The role of psychopathology and altered hypothalamic-pituitary-adrenocortical (HPA) system regulation. doi
  34. (2009). Psychosocial stress reversibly disrupts prefrontal processing and attentional control. doi
  35. (1994). Salivary cortisol in psychoneuroendocrine research: Recent developments and applications. doi
  36. (2008). Sleep loss affects vigilance: Effects of chronic insomnia and sleep therapy. doi
  37. (2008). Statistical Package for the Social Sciences (SPSS) 1602forWindows doi
  38. (2011). Stress effects on memory: An update and integration. Neurosci Biobehav Rev. doi
  39. (2003). The 16-item quick inventory of depressive symptomatology (QIDS), clinician rating (QIDS-C), and self-report (QIDS-SR): A psychometric evaluation in patients with chronic major depression. doi
  40. (1997). The acute effects of corticosteroids on cognition: Integration of animal and human model studies. doi
  41. (2010). The association between serum cortisol and cognitive decline in older persons.
  42. (1994). The combined dexamethasone/ CRH test: A refined laboratory test for psychiatric disorders. doi
  43. (1995). The contribution of neuropsychology to psychiatry.
  44. (2000). The corticosteroid receptor hypothesis of depression. doi
  45. (2003). The cortisol awakening response in bipolar illness: A pilot study.
  46. (1996). The dexamethasone suppression test in patients with mood disorders. doi
  47. (1996). The inventory of depressive symptomatology (IDS): Psychometric properties. doi
  48. (2004). The inventory of depressive symptomatology, clinician rating (IDS-C) and self-report (IDS-SR), and the quick inventory of depressive symptomatology, clinician Cognition, Depression, HPA-Axis: doi
  49. (1998). The mini-international neuropsychiatric interview (M.I.N.I.): The development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD- doi
  50. (2001). The stanley foundation bipolar treatment outcome network. I. longitudinal methodology.
  51. (2001). The stanley foundation bipolar treatment outcome network. II. demographics and illness characteristics of the first 261 patients.
  52. (2003). Two formulas for computation of the area under the curve represent measures of total hormone concentration versus time-dependent change. doi

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.