Steroid hormone secretion after stimulation of mineralocorticoid and NMDA receptors and cardiovascular risk in patients with depression

Nowacki, Jan; Wingenfeld, Katja; Kaczmarczyk, Michael; Chae, Woo Ri; Salchow, Paula; Abu-Tir, Ikram; Piber, Dominique; Hellmann-Regen, Julian; Otte, Christian

doi:10.1038/s41398-020-0789-7

Cited by 21 publications

(13 citation statements)

References 88 publications

(117 reference statements)

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“…In line with studies by others that reported increased levels of cortisol in cerebrospinal fluid (CSF) and plasma of MDD patients, we found elevated cortisol levels in the MDD group pre- as well as post-fasting, indicating an increase in HPA axis activity 27 . Finally, aldosterone levels were comparable in the MDD and Ctrl group, which contrasts previous findings that mainly reported increased levels in the context of MDD 26 , 36 , 37 , although also decreased levels in suicide victims with MDD were described 38 . In line with previous studies in mentally healthy individuals 21 , 31 , fasting significantly increased all analyzed stress parameters and albeit cortisol levels remained elevated in the MDD group post-fasting, the induction was comparable in the Ctrl and MDD group, indicating a similar response to metabolic stress in the context of MDD.…”

Section: Discussioncontrasting

confidence: 99%

Impact of fasting on stress systems and depressive symptoms in patients with major depressive disorder: a cross-sectional study

Stapel

Fraccarollo

Westhoff-Bleck

et al. 2022

Sci Rep

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Major depressive disorder (MDD) is frequently associated with poor response to treatment. Common antidepressants target neurotransmission and neuronal plasticity, which require adequate energy supply. As imaging studies indicate disturbances in central energy metabolism, and caloric restriction improves neuroplasticity and impacts mood and cognition, correction of energy status might increase the effectiveness of antidepressant treatments and reduce the psychopathological symptoms of depression. Metabolic parameters, stress hormones, and brain-derived neurotrophic factor (BDNF) levels were assessed in serum of depressed inpatients (MDD, N = 21) and healthy volunteers (Ctrl, N = 28) before and after a 72 h fasting period during which only water was consumed. Depression severity was assessed by Beck’s Depression Inventory (BDI)-2 sum-score and cognitive-affective and somatic sub-scores. Fasting similarly impacted metabolic parameters and stress systems in both groups. Fasting elevated BDI-2 sum-scores and somatic sub-scores in Ctrl. In MDD, fasting increased somatic-, but decreased cognitive-affective symptoms. Sub-group analyses based on BDI-2 sum-scores pre-fasting showed that cognitive-affective symptoms decreased in patients with moderate/severe but not in those with mild symptoms. This was associated with differential changes in BDNF levels. In conclusion, fasting improved cognitive-affective sub-scores in MDD patients with moderate/severe symptoms that had not responded to prior therapy. Interventions that modulate energy metabolism might directly improve cognitive-affective symptoms and/or augment therapeutic efficacy in moderate-to-severely depressed patients.

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Section: Discussioncontrasting

confidence: 99%

Impact of fasting on stress systems and depressive symptoms in patients with major depressive disorder: a cross-sectional study

Stapel

Fraccarollo

Westhoff-Bleck

et al. 2022

Sci Rep

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“…Experiment starting time was 11:30 h for all participants. First and second medication intake was at 12:05 and 13:05 h, respectively, and the emotional dot probe and the facial emotion recognition task were conducted between 16:00 and 17:00 h. We also assessed blood pressure, heart rate, and steroid hormone concentrations (cortisol, aldosterone, and DHEA-S) hourly between 12:00 and 18:00 h, as described elsewhere (Nowacki et al, 2020).…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2021

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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.

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“…We measured steroid hormone concentrations (cortisol, aldosterone, and DHEA-S), as well as blood pressure and heart rate every hour from 1200 to 1800 h. The effect of the treatment conditions on the cortisol response can be summarized as follows: cortisol concentrations decreased in both fludrocortisone conditions (fludrocortisone and fludrocortisone + DCS) across groups, whereas DCS had no effect on steroid hormone concentrations as described elsewhere [ 38 ].…”

Section: Methodsmentioning

confidence: 99%

Cognitive and emotional empathy after stimulation of brain mineralocorticoid and NMDA receptors in patients with major depression and healthy controls

Nowacki

Wingenfeld

Kaczmarczyk

et al. 2020

Neuropsychopharmacol.

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Mineralocorticoid receptors (MR) are predominantly expressed in the hippocampus and prefrontal cortex. Both brain areas are associated with social cognition, which includes cognitive empathy (ability to understand others’ emotions) and emotional empathy (ability to empathize with another person). MR stimulation improves memory and executive functioning in patients with major depressive disorder (MDD) and healthy controls, and leads to glutamate-mediated N-methyl-D-aspartate receptor (NMDA-R) signaling. We examined whether the beneficial effects of MR stimulation can be extended to social cognition (empathy), and whether DCS would have additional beneficial effects. In this double-blind placebo-controlled single-dose study, we randomized 116 unmedicated MDD patients (mean age 34 years, 78% women) and 116 age-, sex-, and education years-matched healthy controls to four conditions: MR stimulation (fludrocortisone (0.4 mg) + placebo), NMDA-R stimulation (placebo + D-cycloserine (250 mg)), MR and NMDA-R stimulation (both drugs), or placebo. Cognitive and emotional empathy were assessed by the Multifaceted Empathy Test. The study was registered on clinicaltrials.gov (NCT03062150). MR stimulation increased cognitive empathy across groups, whereas NMDA-R stimulation decreased cognitive empathy in MDD patients only. Independent of receptor stimulation, cognitive empathy did not differ between groups. Emotional empathy was not affected by MR or NMDA-R stimulation. However, MDD patients showed decreased emotional empathy compared with controls but, according to exploratory analyses, only for positive emotions. We conclude that MR stimulation has beneficial effects on cognitive empathy in MDD patients and healthy controls, whereas NMDA-R stimulation decreased cognitive empathy in MDD patients. It appears that MR rather than NMDA-R are potential treatment targets to modulate cognitive empathy in MDD.

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Steroid hormone secretion after stimulation of mineralocorticoid and NMDA receptors and cardiovascular risk in patients with depression

Cited by 21 publications

References 88 publications

Impact of fasting on stress systems and depressive symptoms in patients with major depressive disorder: a cross-sectional study

Impact of fasting on stress systems and depressive symptoms in patients with major depressive disorder: a cross-sectional study

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

Cognitive and emotional empathy after stimulation of brain mineralocorticoid and NMDA receptors in patients with major depression and healthy controls

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