Selective attention to emotional stimuli and emotion recognition in patients with major depression: The role of mineralocorticoid and glutamatergic NMDA receptors

J Psychopharmacol. 2021 Aug;35(8):1017-1023. doi: 10.1177/02698811211009797. Epub 2021 Apr 28.

Abstract

Background: Mineralocorticoid receptors (MR) are highly expressed in limbic brain areas and prefrontal cortex, which are closely related to selective attention to emotional stimuli and emotion recognition. Patients with major depressive disorder (MDD) show alterations in MR functioning and both cognitive processes. MR stimulation improves cognitive processes in MDD and leads to glutamate release that binds upon N-methyl-D-aspartate receptors (NMDA-R).

Aims: We examined (1) whether MR stimulation has beneficial effects on selective attention to emotional stimuli and on emotion recognition and (2) whether these advantageous effects can be improved by simultaneous NMDA-R stimulation.

Methods: We examined 116 MDD patients and 116 healthy controls matched for age (M = 34 years), sex (78% women), and education in the following conditions: no pharmacological stimulation (placebo), MR stimulation (0.4 mg fludrocortisone + placebo), NMDA-R stimulation (placebo + 250 mg D-cycloserine (DCS)), MR + NMDA-R stimulation (fludrocortisone + DCS). An emotional dot probe task and a facial emotion recognition task were used to measure selective attention to emotional stimuli and emotion recognition.

Results: Patients with MDD and healthy individuals did not differ in task performance. MR stimulation had no effect on both cognitive processes in both groups. Across groups, NMDA-R stimulation had no effect on selective attention but showed a small effect on emotion recognition by increasing accuracy to recognize angry faces.

Conclusions: Relatively young unmedicated MDD patients showed no depression-related cognitive deficits compared with healthy controls. Separate MR and simultaneous MR and NMDA-R stimulation revealed no advantageous effects on cognition, but NMDA-R might be involved in emotion recognition.

Keywords: Mineralocorticoid receptor; NMDA receptor; depression; emotion recognition; selective attention.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Case-Control Studies
  • Cognition / drug effects
  • Cognition / physiology*
  • Cycloserine / pharmacology
  • Depressive Disorder, Major / physiopathology*
  • Emotions / drug effects
  • Emotions / physiology
  • Facial Recognition / drug effects
  • Facial Recognition / physiology
  • Female
  • Fludrocortisone / pharmacology
  • Humans
  • Male
  • Middle Aged
  • Receptors, Mineralocorticoid / drug effects
  • Receptors, Mineralocorticoid / metabolism*
  • Receptors, N-Methyl-D-Aspartate / agonists
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Young Adult

Substances

  • NR3C2 protein, human
  • Receptors, Mineralocorticoid
  • Receptors, N-Methyl-D-Aspartate
  • Cycloserine
  • Fludrocortisone