Neuroendocrine and stress pathways in bipolar disorders

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

1 Citation (Scopus)


Hormones have a crucial part in the progress and manifestation of a wide variety of different behaviors. Of all the neuroendocrine axes, the hypothalamus-pituitary-adrenal (HPA) axis has been the most extensively studied. There is evidence that disturbance in the HPA axis, the primary stress hormone system, could increase treatment resistance and relapse, worsen illness outcome, and cause cognitive deficits in bipolar patients. Glucocorticoids mediate their actions, including feedback regulation of the HPA axis, through two distinct corticosteroid receptor subtypes: mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs). The maintenance of the internal homeostatic state of an individual is proposed to be based on the ability of circulating glucocorticoids to exert negative feedback on the secretion of HPA hormones through binding MRs and GRs limiting the vulnerability to bipolarity. A dissociation between GR and MR function in bipolar patients, was propose to imbalance HPA axis activity and may offer specific biological and clinical information, related to its action at both the GR and the MR. Therefore the relevance of HPA axis dysfunction in affective disorders, may have the ability to distinguish between “true” from “pseudo” treatment resistant. Different psychopathologies underlying bipolar disorders (BDs) are supposed to involve persistent dysfunctions in the expression and role of both MR and GR in the hippocampus. We review, analyze and summarize the evidence related to the correlation between BDs and the consequences and impact of stressful life events on the HPA axis, exploring the importance of these findings in BD and as potential new targets for treatment.

Original languageEnglish
Title of host publicationBiomarkers in Bipolar Disorders
Number of pages18
ISBN (Electronic)9780128213988
ISBN (Print)9780128213995
Publication statusPublished - 1 Jan 2022


  • Corticosteroid receptor
  • Cortisol
  • Glucocorticoid receptors (GRS)
  • Hypothalamus-pituitary-adrenal (HPA) axis
  • Mineralocorticoid receptor
  • Mineralocorticoid receptors (MRS)
  • Prednisolone
  • Prednisolone suppression test


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