Evidence for an association between mineralocorticoid receptor gene haplotypes and psychobiological measures of atypical depression

Kumsta, Robert; Kliegel, David; Kloet, E. R. de; Rijk, R. H. De; Hellhammer, Dirk H.

doi:10.1016/j.psyneuen.2015.07.426

Cited by 2 publications

(1 citation statement)

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“…Furthermore, two copies of haplotype 1 were related to a higher number of Patient Health Questionnaire screening diagnoses and also to a higher number of diagnoses across International Statistical Classification of Diseases and Related Health Problems (ICD‐10) diagnostic categories. These data suggest that MR gene haplotypes might serve as valuable biomarkers for a subgroup of atypical depression .…”

Section: Mr Gene Variantsmentioning

confidence: 99%

Stress and Depression: a Crucial Role of the Mineralocorticoid Receptor

Kloet

Otte

Kumsta

et al. 2016

J Neuroendocrinology

143

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Cortisol and corticosterone act on the appraisal process, which comprises the selection of an appropriate coping style and the encoding of the experience for storage in the memory. This action exerted by the stress hormones is mediated by mineralocorticoid receptors (MRs), which are expressed abundantly in the limbic circuitry, particularly in the hippocampus. Limbic MR is down-regulated by chronic stress and during depression but induced by antidepressants. Increased MR activity inhibits hypothalamic-pituitary-adrenal axis activity, promotes slow wave sleep, reduces anxiety and switches circuit connectivity to support coping. Cortisol and emotioncognition are affected by MR gene haplotypes based on rs5522 and rs2070951. Haplotype 1 (GA) moderates the effects of (early) life stressors, reproductive cycle and oral contraceptives. MR haplotype 2 (CA) is a gain of function variant that protects females against depression by association with an optimistic, resilient phenotype. Activation of MR therefore may offer a target for alleviating depression and cognitive dysfunction. Accordingly, the MR agonist fludrocortisone was found to enhance the efficacy of antidepressants and to improve memory and executive functions in young depressed patients. In conclusion, CORT coordinates via MR the networks underlying how an individual copes with stress, and this action is complemented by the widely distributed lower affinity glucocorticoid receptor (GR) involved in the subsequent management of stress adaptation. In this MR:GR regulation, the MR is an important target for promoting resilience.

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Section: Mr Gene Variantsmentioning

confidence: 99%