Mineralocorticoid receptor function and cognition in health and disease

Psychoneuroendocrinology. 2019 Jul:105:25-35. doi: 10.1016/j.psyneuen.2018.09.010. Epub 2018 Sep 15.

Abstract

The steroid hormone cortisol is released in response to stress and exerts its effects in the brain via two different receptors: the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR). This review - dedicated to Dirk Hellhammer - focusses on the role of MR on cognitive and emotional function in healthy individuals and in stress-associated disorders such as major depressive disorder (MDD) or borderline personality disorder (BPD). Animal data and studies from healthy individuals converge such that MR play an important role in the appraisal of new situations and the following response selection. Decision-making and empathy are important determinants of this response selection and both are affected by MR function. Furthermore, MR are crucially involved in visuospatial navigation and memory in young and elderly healthy individuals whereas the exact physiological role of MR in verbal learning and verbal memory needs to be further characterized. In contrast to studies in healthy participants, age played a moderating role on the effects of MR stimulation on cognition in depressed patients. In young depressed patients, MR stimulation exerted beneficial effects on verbal memory and executive function, whereas in elderly depressed patients MR stimulation led to impaired verbal learning and visuospatial memory. Similar to healthy controls, BPD patients showed enhanced emotional empathy but not cognitive empathy after MR stimulation. Accordingly, this make MR an interesting target for potential pharmacological augmentation of psychotherapy in BPD. Given the important role MR play in cognitive and emotional function in health and disease, further studies should examine whether MR modulation can alleviate cognitive and emotional problems in patients with stress-associated disorders.

Keywords: Borderline personality disorder; Cognition; HPA axis; Major depressive disorder; Mental disorders; Mineralocorticoid receptor.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Attention / drug effects
  • Attention / physiology*
  • Borderline Personality Disorder* / metabolism
  • Borderline Personality Disorder* / physiopathology
  • Depressive Disorder, Major* / metabolism
  • Depressive Disorder, Major* / physiopathology
  • Empathy / drug effects
  • Empathy / physiology*
  • Executive Function / drug effects
  • Executive Function / physiology*
  • Humans
  • Hypothalamo-Hypophyseal System* / metabolism
  • Hypothalamo-Hypophyseal System* / physiopathology
  • Learning / physiology*
  • Mineralocorticoid Receptor Antagonists / pharmacology*
  • Receptors, Mineralocorticoid / agonists
  • Receptors, Mineralocorticoid / physiology*
  • Social Perception*

Substances

  • Mineralocorticoid Receptor Antagonists
  • Receptors, Mineralocorticoid