title: Mineralocorticoid receptor stimulation improves cognitive function and decreases cortisol secretion in depressed patients and healthy individuals.
abstract: Memory and executive function are often impaired in patients with major depression, while cortisol secretion is increased. Mineralocorticoid receptors (MR) are abundantly expressed in the hippocampus and in the prefrontal cortex, brain areas critical for memory, executive function, and cortisol inhibition. Here, we investigated whether MR stimulation with fludrocortisone (1) improves memory and executive function and (2) decreases cortisol secretion in depressed patients and healthy individuals. Twenty-four depressed patients without medication and 24 age-, sex-, and education-matched healthy participants received fludrocortisone (0.4 mg) or placebo in a randomized, double-blind, within-subject cross-over design. We measured verbal memory, visuospatial memory, executive function, psychomotor speed, and salivary cortisol secretion during cognitive testing between 1400 and 1700 hours. For verbal memory and executive function, we found better performance after fludrocortisone compared with placebo across groups. No treatment effect on other cognitive domains emerged. Depressed patients performed worse than healthy individuals in psychomotor speed and executive function. No group effect or group × treatment interaction emerged on other cognitive domains. Fludrocortisone decreased cortisol secretion across groups and there was a significant correlation between cortisol inhibition and verbal memory performance. Our data suggest a crucial role of MR in verbal memory and executive function and demonstrate the possibility to improve cognition in depressed patients and healthy individuals through MR stimulation.
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité University Medical Center, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Otte
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité University Medical Center, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Wingenfeld
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité University Medical Center, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: Linn K
authors.initials: LK
authors.lastname: Kuehl
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité University Medical Center, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Kaczmarczyk
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité University Medical Center, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Richter
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité University Medical Center, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: Arnim
authors.initials: A
authors.lastname: Quante
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité University Medical Center, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: Francesca
authors.initials: F
authors.lastname: Regen
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité University Medical Center, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: Malek
authors.initials: M
authors.lastname: Bajbouj
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité University Medical Center, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Zimmermann-Viehoff
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Wiedemann
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité University Medical Center, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: Kim
authors.initials: K
authors.lastname: Hinkelmann
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D003071:Cognition / Q000187:drug effects* / Q000502:physiology; D018592:Cross-Over Studies; D003866:Depressive Disorder / Q000188:drug therapy; D004311:Double-Blind Method; D056344:Executive Function / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005438:Fludrocortisone / Q000627:therapeutic use*; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology; D009483:Neuropsychological Tests; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D011619:Psychotropic Drugs / Q000627:therapeutic use*; D018161:Receptors, Mineralocorticoid / Q000378:metabolism; D012463:Saliva / Q000378:metabolism
chemical_list: D011619:Psychotropic Drugs; D018161:Receptors, Mineralocorticoid; D005438:Fludrocortisone; D006854:Hydrocortisone